Short-term respiratory cadmium exposure partially activates pulmonary NLRP3 inflammasome by inducing ferroptosis in mice.

Cadmium (Cd) is a common environmental metal. Previous studies indicated that long-term respiratory Cd exposure caused lung injury and airway inflammation. The purpose of this study was to evaluate whether short-term respiratory Cd exposure induces pulmonary ferroptosis and NLRP3 inflammasome activation. Adult C57BL/6J mice were exposed to Cd by inhaling CdCl2 aerosol (0, 10, or 100 ppm) for 5 days. Serum and lung Fe2+ contents were elevated in Cd-exposed mice. Oxidized AA metabolites, the major oxidized lipids during ferroptosis, were upregulated in Cd-exposed mouse lungs. Pulmonary MDA content and 4-HNE-positive cells were increased in Cd-exposed mice. ACSL4 and COX-2, two lipoxygenases, were upregulated in Cd-exposed mouse lungs. Further analyses found that phosphorylated NF-kB p65 was elevated in Cd-exposed mouse lungs. Innate immune receptor protein NLRP3 and adapter protein ASC were upregulated in Cd-exposed mouse lungs. Caspase-1 was activated and IL-1ß and IL-18 were upregulated in Cd-exposed mouse lungs. Fer-1, a specific inhibitor of ferroptosis, attenuated Cd-induced elevation of pulmonary NLRP3 and ASC, caspase-1 activation, and IL-1ß and IL-18 upregulation. Finally, mitoquinone (MitoQ), a mitochondria-target antioxidant, suppressed Cd-caused ferroptosis and NLRP3 inflammasome activation. Our results demonstrate that ferroptosis might partially mediate Cd-evoked activation of NLRP3 inflammasome in the lungs.

Delta magnetic resonance imaging radiomics features­based nomogram predicts long­term efficacy after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To establish and validate a delta-radiomics-based model for predicting progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) following induction chemotherapy (IC). METHODS AND MATERIALS: A total of 250 LA-NPC patients (training cohort: n = 145; validation cohort: n = 105) were enrolled. Radiomic features were extracted from MRI scans taken before and after IC, and changes in these features were calculated. Following feature selection, a delta-radiomics signature was constructed using LASSO-Cox regression analysis. A prognostic nomogram incorporating independent clinical indicators and the delta-radiomics signature was developed and assessed for calibration and discrimination. Risk stratification by the nomogram was evaluated using Kaplan-Meier methods. RESULTS: The delta-radiomics signature, consisting of 12 features, was independently associated with prognosis. The nomogram, integrating the delta-radiomics signature and clinical factors demonstrated excellent calibration and discrimination. The model achieved a Harrell's concordance index (C-index) of 0.848 in the training cohort and 0.820 in the validation cohort. Risk stratification identified two groups with significantly different PFS rates. The three-year PFS for high-risk patients who received concurrent chemoradiotherapy (CCRT) or radiotherapy plus adjuvant chemotherapy (RT+AC) after IC was significantly higher than for those who received RT alone, reaching statistical significance. In contrast, for low-risk patients, the three-year PFS after IC was slightly higher for those who received CCRT or RT+AC compared to those who received RT alone; however, this difference did not reach statistical significance. CONCLUSIONS: Our delta MRI-based radiomics model could be useful for predicting PFS and may guide subsequent treatment decisions after IC in LA-NPC.

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

CRISPR-Cas13d screens identify KILR, a breast cancer risk-associated lncRNA that regulates DNA replication and repair.

BACKGROUND: Long noncoding RNAs (lncRNAs) have surpassed the number of protein-coding genes, yet the majority have no known function. We previously discovered 844 lncRNAs that were genetically linked to breast cancer through genome-wide association studies (GWAS). Here, we show that a subset of these lncRNAs alter breast cancer risk by modulating cell proliferation, and provide evidence that a reduced expression on one lncRNA increases breast cancer risk through aberrant DNA replication and repair. METHODS: We performed pooled CRISPR-Cas13d-based knockdown screens in breast cells to identify which of the 844 breast cancer-associated lncRNAs alter cell proliferation. We selected one of the lncRNAs that increased cell proliferation, KILR, for follow-up functional studies. KILR pull-down followed by mass spectrometry was used to identify binding proteins. Knockdown and overexpression studies were performed to assess the mechanism by which KILR regulates proliferation. RESULTS: We show that KILR functions as a tumor suppressor, safeguarding breast cells against uncontrolled proliferation. The half-life of KILR is significantly reduced by the risk haplotype, revealing an alternative mechanism by which variants alter cancer risk. Mechanistically, KILR sequesters RPA1, a subunit of the RPA complex required for DNA replication and repair. Reduced KILR expression promotes breast cancer cell proliferation by increasing the available pool of RPA1 and speed of DNA replication. Conversely, KILR overexpression promotes apoptosis in breast cancer cells, but not normal breast cells. CONCLUSIONS: Our results confirm lncRNAs as mediators of breast cancer risk, emphasize the need to annotate noncoding transcripts in relevant cell types when investigating GWAS variants and provide a scalable platform for mapping phenotypes associated with lncRNAs.

A comprehensive review on the heterotrophic production of bioactive compounds by microalgae.

Bioactive compounds derived from microalgae have garnered considerable attention as valuable resources for drugs, functional foods, and cosmetics. Among these compounds, photosynthetic pigments and polyunsaturated fatty acids (PUFAs) have gained increasing interest due to their numerous beneficial properties, including anti-oxidant, anti-viral, anti-bacterial, anti-fungal, anti-inflammatory, and anti-tumor effects. Several microalgae species have been identified as rich sources of bioactive compounds, including the Chlorophyceae Dunaliella and Haematococcus, the Bacillariophyta Phaeodactylum and Nitzschia, and the dinoflagellate Crypthecodinium cohnii. However, most of the reported microalgae species primarily grow through autotrophic mechanisms, resulting in low yields and high production costs of bioactive compounds. Consequently, the utilization of heterotrophic microalgae, such as Chromochloris zofingiensis and Nitzschia laevis, has shown significant advantages in the production of astaxanthin and eicosapentaenoic acid (EPA), respectively. These heterotrophic microalgae exhibit superior capabilities in synthesizing target compounds. This comprehensive review provides a thorough examination of the heterotrophic production of bioactive compounds by microalgae. It covers key aspects, including the metabolic pathways involved, the impact of cultivation conditions, and the practical applications of these compounds. The review discusses how heterotrophic cultivation strategies can be optimized to enhance bioactive compound yields, shedding light on the potential of microalgae as a valuable resource for high-value product development.

Asprosin contributes to vascular remodeling in hypertensive rats via superoxide signaling.

OBJECTIVE: Proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to vascular remodeling. Asprosin, a newly discovered protein hormone, is involved in metabolic diseases. Little is known about the roles of asprosin in cardiovascular diseases. This study focused on the role and mechanism of asprosin on VSMC proliferation and migration, and vascular remodeling in a rat model of hypertension. METHODS AND RESULTS: VSMCs were obtained from the aortic media of 8-week-old male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Asprosin was upregulated in the VSMCs of SHR. For in vitro studies, asprosin promoted VSMC proliferation and migration of WKY and SHR, and increased Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, NOX1/2/4 protein expressions and superoxide production. Knockdown of asprosin inhibited the proliferation, migration, NOX activity, NOX1/2 expressions and superoxide production in the VSMCs of SHR. The roles of asprosin in promoting VSMC proliferation and migration were not affected by hydrogen peroxide scavenger, but attenuated by superoxide scavenger, selective NOX1 or NOX2 inhibitor. Toll-like receptor 4 (TLR4) was upregulated in SHR, TLR4 knockdown inhibited asprosin overexpression-induced proliferation, migration and oxidative stress in VSMCs of WKY and SHR. Asprosin was upregulated in arteries of SHR, and knockdown of asprosin in vivo not only attenuated oxidative stress and vascular remodeling in aorta and mesentery artery, but also caused a subsequent persistent antihypertensive effect in SHR. CONCLUSIONS: Asprosin promotes VSMC proliferation and migration via NOX-mediated superoxide production. Inhibition of endogenous asprosin expression attenuates VSMC proliferation and migration, and vascular remodeling of SHR.

Fluorinated Organic Polymers for Cancer Drug Delivery.

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.

Effect of in vivo culture conditions on the proliferation and differentiation of rat adipose-derived stromal cells.

Adipose-derived stromal cells (ADSCs) are promising stem cell sources for tissue engineering and cell-based therapy. However, long-term in vitro expansion of ADSCs impedes stemness maintenance, which is partly attributed to deprivation of their original microenvironment. Incompetent cells limit the therapeutic effects of ADSC-based clinical strategies. Therefore, reconstructing a more physiologically and physically relevant niche is an ideal strategy to address this issue and therefore facilitates the extensive application of ADSCs. Here, we transplanted separated ADSCs into local subcutaneous adipose tissues of nude mice as an in vivo cell culture model. We found that transplanted ADSCs maintained their primitive morphology and showed improved proliferation and delayed senescence compared to those of cells cultured in an incubator. Significantly increased expression of stemness-related markers and multilineage differentiation abilities were further observed in in vivo cultured ADSCs. Finally, sequencing revealed that genes whose expression differed between ADSCs obtained under in vivo and in vitro conditions were mainly located in the extracellular matrix and extracellular space and that these genes participate in regulating transcription and protein synthesis. Moreover, we found that an Egr1 signaling pathway might exert a crucial impact on controlling stemness properties. Our findings might collectively pave the way for ADSC-based applications.

Establishment of a mouse allergy model for Culicoides (Diptera: Ceratopogonidae).

BACKGROUND: Culicoides is a genus of ubiquitous biting midges (Ceratopogonidae). Female midges have blood-sucking habit. They not only bite and harass humans and animals but also may be an important vector of disease transmission. Therefore, building an animal allergy model caused by Culicoides biting is very beneficial for studying its pathogenesis and exploring the therapeutic methods. MATERIAL AND METHOD: Kunming mice were used in this study to build the model and sensitised by two-step injection of midge extracts. Scratching behaviour and histological examination were used to check the immediate and delayed responses. Immunoglobulin E (IgE) and Immunoglobulin G (IgG) were detected using indirect enzyme-linked immunosorbent assay (ELISA) assay. Splenic cell proliferation and cytokine production were determined using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and ELISA assays. The response of cytokine gene expression to midge stimulation was analysed through quantitative real-time polymerase chain reaction (qPCR). RESULTS: Behavioural results revealed a significant increase in scratching frequency among the midge-sensitised animals (p < 0.05). Histological examination showed more inflammatory cytokine infiltration at the injection site of midge-sensitised mice comparing to the ones in the control group. The serum levels of IgE and IgG1 antibodies in the midge-sensitised group were significantly elevated (p < 0.05). After splenocytes were stimulated in vitro with midge extracts, the midge-sensitised group's splenocyte count significantly increased in comparison to the control group. The midge-sensitised group's qPCR data revealed a down-regulation of tumor necrosis factor alpha (TNF-α) expression and an increase in the expression of interleukin (IL)-4, IL-5, IL-10 and IL-13 but not in the control group (p < 0.05). CONCLUSIONS: In this study, an animal model of Culicoides-mouse sensitisation was successfully constructed using a two-step method. The mode of administration of the model was in good agreement with the natural immune pathway, and the immune response induced by the sensitisation of the model was similar to that produced by the bite of a midge.

Ultrafine Pt Nanoparticles on Defective Tungsten Oxide for Photocatalytic Ethylene Synthesis.

The selective conversion of ethane (C2H6) to ethylene (C2H4) under mild conditions is highly wanted, yet very challenging. Herein, it is demonstrated that a Pt/WO3-x catalyst, constructed by supporting ultrafine Pt nanoparticles on the surface of oxygen-deficient tungsten oxide (WO3-x) nanoplates, is efficient and reusable for photocatalytic C2H6 dehydrogenation to produce C2H4 with high selectivity. Specifically, under pure light irradiation, the optimized Pt/WO3-x photocatalyst exhibits C2H4 and H2 yield rates of 291.8 and 373.4 µmol g-1 h-1, respectively, coupled with a small formation of CO (85.2 µmol g-1 h-1) and CH4 (19.0 µmol g-1 h-1), corresponding to a high C2H4 selectivity of 84.9%. Experimental and theoretical studies reveal that the vacancy-rich WO3-x catalyst enables broad optical harvesting to generate charge carriers by light for working the redox reactions. Meanwhile, the Pt cocatalyst reinforces adsorption of C2H6, desorption of key reaction species, and separation and migration of light-induced charges to promote the dehydrogenation reaction with high productivity and selectivity. In situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory calculation expose the key intermediates formed on the Pt/WO3-x catalyst during the reaction, which permits the construction of the possible C2H6 dehydrogenation mechanism.

The Segmentation of Multiple Types of Uterine Lesions in Magnetic Resonance Images Using a Sequential Deep Learning Method with Image-Level Annotations.

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods.

Gene signatures to therapeutics: Assessing the potential of ivermectin against t(4;14) multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS: The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, GSE16558 and GSE116294, which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein-protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS: In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes (cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb. Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION: Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

Myocardial hypertrophy with aortic dysplasia: a rare case of Noonan syndrome.

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Effects of cyclophosphamide and mitomycin C on radiation-induced transcriptional biomarkers in human lymphoblastoid cells.

PURPOSE: Ionizing radiation (IR)-induced transcriptional changes are considered a potential biodosimetry for dose evaluation and health risk monitoring of acute or chronic radiation exposure. It is crucial to understand the impact of confounding factors on the radiation-responsive gene expressions for accurate and reproducible dose assessment. This study aims to explore the potential influence of exposures to chemotherapeutic agents such as cyclophosphamide (CP) and mitomycin C (MMC) on IR-induced transcriptional biomarkers. METHODS: The human B lymphoblastoid cells (AHH-1) were exposed to 0, 20, 50, 100, 200 and 500 µg/ml CP or 0, 0.025, 0.05, 0.1 and 1 µg/ml MMC, respectively. The appropriate concentrations of CP and MMC were added for 1 h before irradiation with 0, 2, 4 and 6 Gy of 60Co γ-rays at a dose rate of 1 Gy/min. Cell viability was evaluated by CCK-8 assay. The gene expression responses of 18 radiation-induced transcriptional biomarkers were examined at 24 h after exposures to CP and MMC, respectively. The expression levels of five crucial DNA interstrand crosslinks (ICLs) repair genes were also evaluated. The biodosimetry models were established based on the specific radiation-responsive gene combinations. RESULTS: The baseline transcriptional levels of the 18 selected genes were slightly affected by CP treatment in the absence of IR, while the transcript responses to IR could be inhibited as the concentration of CP up to 50 µg/ml. MMC treatment up-regulated the background levels in most radiation-responsive gene expressions. Of 18 genes, only the relative mRNA expression levels of CDKN1A and BBC3 were repressed after treatment with IR and MMC in combination. The relative mRNA level of RAD51 was significantly up-regulated after exposure to CP, while the expression of FANCD2, RAD51 and BLM showed an overall increase in response to MMC treatment. After irradiation, the relative mRNA expression levels of FANCD2, BRCA2 and RAD51 exhibited dose-dependent increases in IR alone and MMC treatment groups. In addition, the biodosimetry models were established using 2-4 radiation-responsive genes based on different radiation exposure scenarios. CONCLUSION: Our findings suggested that IR-induced gene expression changes were slightly affected after exposure to a relatively low concentration of CP and MMC. Gene expression combinations might improve the broad applicability of transcriptional biodosimetry across diverse radiation exposures.

Diagnostic performance of radiomics model for preoperative risk categorization in thymic epithelial tumors: a systematic review and meta-analysis.

BACKGROUND: Incidental thymus region masses during thoracic examinations are not uncommon. The clinician's decision-making for treatment largely depends on imaging findings. Due to the lack of specific indicators, it may be of great value to explore the role of radiomics in risk categorization of the thymic epithelial tumors (TETs). METHODS: Four databases (PubMed, Web of Science, EMBASE and the Cochrane Library) were screened to identify eligible articles reporting radiomics models of diagnostic performance for risk categorization in TETs patients. The quality assessment of diagnostic accuracy studies 2 (QUADAS-2) and radiomics quality score (RQS) were used for methodological quality assessment. The pooled area under the receiver operating characteristic curve (AUC), sensitivity and specificity with their 95% confidence intervals were calculated. RESULTS: A total of 2134 patients in 13 studies were included in this meta-analysis. The pooled AUC of 11 studies reporting high/low-risk histologic subtypes was 0.855 (95% CI, 0.817-0.893), while the pooled AUC of 4 studies differentiating stage classification was 0.826 (95% CI, 0.817-0.893). Meta-regression revealed no source of significant heterogeneity. Subgroup analysis demonstrated that the best diagnostic imaging was contrast enhanced computer tomography (CECT) with largest pooled AUC (0.873, 95% CI 0.832-0.914). Publication bias was found to be no significance by Deeks' funnel plot. CONCLUSIONS: This present study shows promise for preoperative selection of high-risk TETs patients based on radiomics signatures with current available evidence. However, methodological quality in further studies still needs to be improved for feasibility confirmation and clinical application of radiomics-based models in predicting risk categorization of the thymic epithelial tumors.

Prognostic value of circulating Epstein-Barr virus DNA level post-induction chemotherapy for patients with nasopharyngeal carcinoma: A recursive partitioning risk stratification analysis.

BACKGROUND: To evaluate the prognostic value of plasma Epstein-Barr virus (EBV) DNA level post-induction chemotherapy (IC) for patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 893 newly diagnosed NPC patients treated with IC were retrospectively reviewed. The recursive partitioning analysis (RPA) was performed to construct a risk stratification model. The receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off value of post-IC EBV DNA. RESULTS: Post-IC EBV DNA levels and overall stage were independent predictors for distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). The RPA model base on post-IC EBV DNA and overall stage categorized the patients into three distinct risk groups: RPA I (low-risk: stage II-III and post-IC EBV DNA < 200 copies/mL), RPA II (median-risk: stage II-III and post-IC EBV DNA ≥ 200 copies/mL, or stage IVA and post-IC EBV DNA < 200 copies/mL), and RPA III (high-risk: stage IVA and post-IC EBV DNA ≥ 200 copies/mL), with 3-year PFS of 91.1%, 82.6%, and 60.2%, respectively (p < 0.001). The DMFS and OS rates in different RPA groups were also distinct. The RPA model showed better risk discrimination than either the overall stage or post-RT EBV DNA alone. CONCLUSIONS: Plasma EBV DNA level post-IC was a robust prognostic biomarker for NPC. We developed an RPA model that provides improved risk discrimination over the 8th edition of the TNM staging system by integrating the post-IC EBV DNA level and the overall stage.

Low-dose ionizing radiation: Effects on the proliferation and migration of lens epithelial cells via activation of the Wnt/ß-catenin pathway.

Eye lens opacification (cataract) induced by ionizing radiation is an important concern for radiation protection. Human lens epithelial cells (HLE-B3) were irradiated with γ-rays and radiation effects, including cell proliferation, cell migration, cell cycle distribution, and other changes related to the ß-catenin pathway, were determined after 8-72 h and 7 d. In an in vivo model, mice were irradiated; DNA damage (γH2AX foci) in the cell nucleus of the anterior capsule of the lens was detected within 1 h, and radiation effects on the anterior and posterior lens capsules were observed after 3 months. Low-dose ionizing radiation promoted cell proliferation and migration. The expression levels of ß-catenin, cyclin D1, and c-Myc were significantly increased in HLE-B3 cells after irradiation and ß-catenin was translocated into the cell nucleus (activation of the Wnt/ß-catenin pathway). In C57BL/6 J mouse lens, even a very low irradiation dose (0.05 Gy) induced the formation of γH2AX foci, 1 h after irradiation. At 3 months, migratory cells were found in the posterior capsule; expression of ß-catenin was increased and it was clustered at the nucleus in the epithelial cells of the lens anterior capsule. The Wnt/ß-catenin signaling pathway may an important role in promoting abnormal proliferation and migration of lens epithelial cells after low-dose irradiation.

[Omics Analysis of Ferroptosis and Establishment of Prognostic Model for multiple myeloma Patients].

OBJECTIVE: To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients. METHODS: Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM. RESULTS: 36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients. CONCLUSION: Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.

[Clinical Research Advances of Duodenal-Type Follicular Lymphoma--Review].

Duodenal-type follicular lymphoma (DFL) is a unique subtype of follicular lymphoma (FL), which often involves the second portion of duodenum (descending part of duodenum). Due to its specific pathological features, such as lack of follicular dendritic cells meshwork and disappearance of activation-induced cytidine deaminase expression, DFL presents an inert clinical course and is often confined to the intestinal tract. Inflammation-related biomarkers suggest that the microenvironment may play a likely role in the pathogenesis and favorable prognosis of DFL. Since patients generally have no obvious clinical symptoms and low progression rate, the treatment regimen for DFL is mainly observation and waiting (W&W) strategy. This study will review the latest research progress of epidemiology, diagnosis, treatment and prognosis of DFL in recent years.