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Exploring thermodynamic processes through CFD of free convection of Bingham fluids in innovative hexagonal enclosure (Papanastasiou model) 利用CFD研究Bingham流体在创新六角形壳体(Papanastasiou模型)中自由对流的热力学过程
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-04 DOI: 10.1016/j.jrras.2026.102161
Benhanifia Kada , Mebarki Brahim , Ahmed Remlaoui , Keddar Mohammed , Syed M. Hussain , Hijaz Ahmad , Neissrien Alhubieshi , Assmaa Abd-Elmonem , Bandar M. Fadhl , Basim M. Makhdoum
This research presents a unique enclosure geometry, namely, a hexagonal finned cavity, for the analysis of Bingham–Papanastasiou fluid natural convection, which is examined numerically through COMSOL Multiphysics. The momentum and energy equations that govern the phenomena are solved via the Galerkin approach. The external walls have been assumed to be cold, while the inner wall has been taken as hot. A thorough investigation of the thermo-hydrodynamic flow is carried out considering the nominal value of the Rayleigh number (Ra), the range of plasticity Bn (1–50), and the obstacle lengths L (0.1, 0.4). The findings demonstrate that the rate of heat transfer (Nu) is positively correlated with the buoyancy parameter (Ra) while it is inversely related to the plasticity parameter (Bn), with larger values of the latter resulting in lesser heat transfer. This reduction seems to occur due to lame yield stress at a bigger Bn, damping the fluid flow inside the enclosure. The streamline patterns further confirm this trend, showing a significant weakening of circulation at high plasticity levels, particularly for Bn = 50. The effect of obstacle length can be seen on the streamline and isotherm contours, which may indicate the intermediate fin length (L = 0.2) for Rayleigh Number (Ra) as the best, as it increases vortex creation and supports good circulation in the cavity, thus enhancing the heat transfer performance.
本研究提出了一种独特的封闭几何形状,即六角形翅片腔,用于分析Bingham-Papanastasiou流体自然对流,并通过COMSOL Multiphysics进行了数值研究。控制这些现象的动量和能量方程通过伽辽金方法求解。外墙被假定为冷的,而内墙被假定为热的。考虑瑞利数(Ra)的标称值、塑性范围Bn(1-50)和障碍物长度L(0.1, 0.4),对热流体动力流动进行了深入的研究。结果表明:换热速率Nu与浮力参数Ra成正相关,与塑性参数Bn成负相关,后者值越大换热越小。这种减少似乎是由于较大Bn时的屈服应力减弱,从而抑制了外壳内的流体流动。流线模式进一步证实了这一趋势,表明在高塑性水平下环流明显减弱,特别是Bn = 50时。障碍物长度对流线和等温线的影响可以看出,对于瑞利数(Ra),中间翅片长度(L = 0.2)是最好的,它增加了涡流的产生,支持了腔内良好的循环,从而提高了换热性能。
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引用次数: 0
Artificial intelligence in MRI clinical practice: From historical innovation to emerging trends 人工智能在MRI临床实践中的应用:从历史创新到新兴趋势
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-03 DOI: 10.1016/j.jrras.2026.102158
Shrooq T. Aldahery
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引用次数: 0
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-01
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引用次数: 0
A machine learning-based gene signature reveals radiotherapy-induced remodeling of the immune microenvironment in esophageal cancer 一项基于机器学习的基因标记揭示了食管癌中放疗诱导的免疫微环境重塑
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-01 DOI: 10.1016/j.jrras.2025.102129
Xiaoyu He , Zhuo Li , Yao Liu , Junsheng Chen , Zihao Yuan , Lina Huang , Ting Wang

Objective

This study aimed to develop a machine learning-based signature using radiotherapy-responsive genes to characterize immune infiltration dynamics and evaluate drug sensitivity in esophageal cancer (EC) before and after radiotherapy.

Methods

Based on the GSE137867 dataset from GEO, which includes 4 pre-radiotherapy and 4 post-radiotherapy esophageal cancer samples, we identified significantly differentially expressed genes (DEGs) through differential analysis. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were performed based on the DEGs. Signature genes were screened using Lasso and SVM machine learning algorithms. These signature genes underwent CIBERSORT immune infiltration analysis, ssGSEA, ESTIMATE immune scoring, drug sensitivity analysis, and ceRNA network analysis. To validate the expression profiles of the target genes, we cultured the esophageal cancer OE19 cell line and performed Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR).

Results

After identifying 28 DEGs, GO and GSEA analysis revealed that these DEGs were enriched in regulation of memory/regulatory T cell differentiation, chemokine activity and cytokine-cytokine receptor interaction pathways. Through Lasso and SVM, three signature genes were identified: ZDHHC11B, CD46, and PFKFB3. CIBERSORT analysis showed a marked elevation in CD8+ T cells after radiotherapy. Drug sensitivity analysis revealed that CD46 was negatively correlated with cisplatin, positively correlated with sapitinib, while PFKFB3 showed a negative correlation with linsitinib. The ceRNA network included 21 miRNAs, 3 mRNAs, and 18 lncRNAs. Specifically, 21 miRNA-mRNA regulatory pairs and 18 lncRNA-mRNA regulatory pairs were identified. RT-qPCR showed that compared with the control group, ZDHHC11B decreased significantly in the post-radiotherapy group, while CD46 and PFKFB3 increased significantly.

Conclusion

This study comprehensively investigated the immune landscape of EC pre- and post-radiotherapy and analyzed drug sensitivity of these signature genes, thereby elucidating alterations in the immune microenvironment of EC and nominating ZDHHC11, CD46, and PFKFB3 as potential biomarkers for predicting immune status and therapeutic sensitivity.
目的利用放射反应基因建立基于机器学习的特征,表征食管癌放疗前后的免疫浸润动力学和药物敏感性。方法基于GEO的GSE137867数据集,包括4个放疗前和放疗后食管癌样本,通过差异分析鉴定出显著差异表达基因(DEGs)。基于DEGs进行基因本体(GO)分析和基因集富集分析(GSEA)。使用Lasso和SVM机器学习算法筛选特征基因。对这些特征基因进行了CIBERSORT免疫浸润分析、ssGSEA、ESTIMATE免疫评分、药物敏感性分析和ceRNA网络分析。为了验证靶基因的表达谱,我们培养了食管癌OE19细胞系,并进行了逆转录定量实时聚合酶链反应(RT-qPCR)。结果鉴定出28个DEGs后,GO和GSEA分析显示,这些DEGs富集于调节记忆/调节性T细胞分化、趋化因子活性和细胞因子-细胞因子受体相互作用途径。通过Lasso和SVM分别鉴定出ZDHHC11B、CD46和PFKFB3三个特征基因。CIBERSORT分析显示放疗后CD8+ T细胞明显升高。药敏分析显示CD46与顺铂呈负相关,与沙匹替尼呈正相关,而PFKFB3与利西替尼呈负相关。ceRNA网络包括21个mirna, 3个mrna和18个lncrna。具体来说,鉴定了21对miRNA-mRNA调控对和18对lncRNA-mRNA调控对。RT-qPCR结果显示,与对照组相比,放疗后组患者ZDHHC11B水平明显降低,CD46、PFKFB3水平明显升高。结论本研究全面研究了EC放疗前后的免疫景观,分析了这些特征基因的药物敏感性,从而阐明了EC免疫微环境的变化,并提名ZDHHC11、CD46和PFKFB3作为预测免疫状态和治疗敏感性的潜在生物标志物。
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引用次数: 0
Integrated RP-HPLC degradation profiling and Monte Carlo modeling for evaluating gamma-ray radiosterilization suitability of imidazole antifungals 综合RP-HPLC降解谱和蒙特卡罗模型评价咪唑类抗真菌药物的γ射线灭菌适宜性
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102132
Abdelmoneim Saleh , Zehra Üstün , Ümit Kara
This study introduces an integrated approach combining forced degradation analysis and Monte Carlo gamma modeling to assess the radiosterilization suitability of pharmaceutical compounds. Three imidazole antifungals were subjected to controlled UV (365 nm) and oxidative (3 % H2O2) stress conditions, and their degradation behavior was quantitatively assessed using validated reversed phase high performance liquid chromatography (RP-HPLC), yielding percentage degradation, rate constants, and half-life values. UV degradation after 3h was highest for lanoconazole (70.97 %), followed by bifonazole (50.80 %) and butoconazole (15.44 %), confirming greater photostability for butoconazole. Under oxidative stress, bifonazole showed the highest resistance, while lanoconazole fully degraded within 12h. MCNPX Monte Carlo simulations revealed enhanced gamma attenuation and localized energy deposition for bifonazole, consistent with its experimental degradation resistance. Kerma and dose-rate analyses supported a balanced energy deposition profile for bifonazole, correlating with its experimental stability. The integration of chemical degradation profiling via RP-HPLC with physical interaction modeling via Monte Carlo simulations offers a predictive, quantitative framework for assessing radiosterilization tolerance. This approach reduces reliance on empirical irradiation trials, enables early identification of the most stable active pharmaceutical ingredients, and supports the optimization of sterilization protocols in pharmaceutical development. This framework enables early identification of radiation-stable APIs, minimizing empirical trials and supporting optimized sterilization strategies without compromising drug efficacy.
本研究引入了一种结合强制降解分析和蒙特卡罗伽马模型的综合方法来评估药物化合物的放射性灭菌适用性。在可控紫外(365 nm)和氧化(3% H2O2)胁迫条件下,对3种咪唑类抗真菌药物的降解行为进行了定量评价,并采用反相高效液相色谱法(RP-HPLC)对其降解率、速率常数和半衰期进行了定量评价。紫外降解率最高的是硝康唑(70.97%),其次是联苯唑(50.80%)和丁康唑(15.44%),说明丁康唑具有较好的光稳定性。在氧化应激下,苯苯唑表现出最高的抗性,而硝康唑在12h内完全降解。MCNPX蒙特卡罗模拟显示,联苯唑的伽马衰减和局部能量沉积增强,与实验中抗降解性一致。Kerma和剂量率分析支持了联苯唑的平衡能量沉积谱,这与它的实验稳定性有关。通过RP-HPLC进行的化学降解分析与通过蒙特卡罗模拟进行的物理相互作用建模相结合,为评估放射性灭菌耐受性提供了预测的定量框架。这种方法减少了对经验性辐照试验的依赖,能够早期识别最稳定的活性药物成分,并支持药物开发中灭菌方案的优化。该框架能够早期识别辐射稳定的原料药,最大限度地减少经验性试验,并在不影响药物功效的情况下支持优化的灭菌策略。
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引用次数: 0
Network pharmacology, molecular dynamics simulation, and experiments uncover icariin's role in ferroptosis during postmenopausal osteoporosis 网络药理学,分子动力学模拟和实验揭示淫羊藿苷在绝经后骨质疏松症中铁下垂的作用
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102147
Feng Chen , Yueping Chen , Xiaoyun Zhang

Background

Icariin (ICA) shows therapeutic potential for postmenopausal osteoporosis (PMO), yet its mechanism in regulating osteoblast ferroptosis remains unclear. We combined network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation to elucidate ICA-mediated anti-ferroptotic effects in PMO.

Methods

Potential ICA targets were obtained from PubChem, the Comparative Toxicogenomics Database, SwissTargetPrediction, and the Similarity Ensemble Approach, while PMO-associated genes were identified through GeneCards, OMIM, DrugBank, and the Therapeutic Target Database. Ferroptosis-related genes were extracted from FerrDb. Intersecting targets were used to construct drug–target and protein–protein interaction (PPI) networks, and key nodes were identified by topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional enrichment. Molecular docking assessed ICA affinity toward candidate proteins, and molecular dynamics simulations evaluated complex stability. Reactive oxygen species (ROS), apoptosis, and the expression of markers linked to ferroptosis, antioxidants, and osteogenesis were measured using osteoblasts in vitro using quantitative RT-PCR and western blotting.

Results

Eight key targets were identified through PPI network analysis. GO and KEGG enrichment analyses highlighted pathways associated with redox regulation and ferroptosis. Docking studies revealed the strongest binding affinity between ICA and Nrf2 (Nuclear Factor Erythroid 2–Related Factor 2), further confirmed by stable interactions in molecular dynamics simulations. Experimentally, ICA promoted osteoblast proliferation, reduced intracellular ROS levels and apoptosis, and upregulated antioxidant, osteogenic, and ferroptosis-related proteins, including Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), alkaline phosphatase (ALP), and runt-related transcription factor-2 (RUNX2), while suppressing caspase-3 activation.

Conclusion

ICA activates the Nrf2/HO-1 pathway to suppress ferroptosis and oxidative stress, reduce apoptosis, and promote osteogenic activity, thereby alleviating PMO-related osteoblast dysfunction. These findings provide mechanistic support for ICA as a multi-target candidate for PMO management.
背景:dicariin (ICA)显示出治疗绝经后骨质疏松症(PMO)的潜力,但其调节成骨细胞铁下垂的机制尚不清楚。我们结合网络药理学、分子对接、分子动力学模拟和体外验证等方法,阐明了ica介导的PMO抗铁衰作用。方法通过PubChem、Comparative Toxicogenomics Database、SwissTargetPrediction和Similarity Ensemble Approach获得潜在的ICA靶点,通过GeneCards、OMIM、DrugBank和Therapeutic Target Database鉴定pmo相关基因。从ferdb中提取了嗜铁相关基因。利用交叉靶点构建药物-靶点-蛋白相互作用(PPI)网络,通过拓扑分析确定关键节点。使用基因本体(GO)和京都基因与基因组百科全书(KEGG)分析进行功能富集。分子对接评估了ICA对候选蛋白的亲和力,分子动力学模拟评估了复合物的稳定性。利用体外成骨细胞,采用定量RT-PCR和western blotting技术,测量了活性氧(ROS)、细胞凋亡以及与铁凋亡、抗氧化剂和成骨相关的标志物的表达。结果通过PPI网络分析,确定了8个关键靶点。GO和KEGG富集分析强调了与氧化还原调节和铁下垂相关的途径。对接研究发现ICA与Nrf2 (Nuclear Factor Erythroid 2 - related Factor 2)的结合亲和性最强,分子动力学模拟进一步证实了这一点。实验结果表明,ICA可促进成骨细胞增殖,降低细胞内ROS水平和细胞凋亡,上调抗氧化、成骨和凋亡相关蛋白,包括Nrf2、血红素加氧酶-1 (HO-1)、谷胱甘肽过氧化物酶-4 (GPX4)、溶质载体家族7成员11 (SLC7A11)、碱性磷酸酶(ALP)和矮子相关转录因子-2 (RUNX2),同时抑制caspase-3的激活。结论ica激活Nrf2/HO-1通路,抑制铁凋亡和氧化应激,减少细胞凋亡,促进成骨活性,从而减轻pmo相关成骨细胞功能障碍。这些发现为ICA作为PMO管理的多靶点候选提供了机制支持。
{"title":"Network pharmacology, molecular dynamics simulation, and experiments uncover icariin's role in ferroptosis during postmenopausal osteoporosis","authors":"Feng Chen ,&nbsp;Yueping Chen ,&nbsp;Xiaoyun Zhang","doi":"10.1016/j.jrras.2025.102147","DOIUrl":"10.1016/j.jrras.2025.102147","url":null,"abstract":"<div><h3>Background</h3><div>Icariin (ICA) shows therapeutic potential for postmenopausal osteoporosis (PMO), yet its mechanism in regulating osteoblast ferroptosis remains unclear. We combined network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation to elucidate ICA-mediated anti-ferroptotic effects in PMO.</div></div><div><h3>Methods</h3><div>Potential ICA targets were obtained from PubChem, the Comparative Toxicogenomics Database, SwissTargetPrediction, and the Similarity Ensemble Approach, while PMO-associated genes were identified through GeneCards, OMIM, DrugBank, and the Therapeutic Target Database. Ferroptosis-related genes were extracted from FerrDb. Intersecting targets were used to construct drug–target and protein–protein interaction (PPI) networks, and key nodes were identified by topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional enrichment. Molecular docking assessed ICA affinity toward candidate proteins, and molecular dynamics simulations evaluated complex stability. Reactive oxygen species (ROS), apoptosis, and the expression of markers linked to ferroptosis, antioxidants, and osteogenesis were measured using osteoblasts in vitro using quantitative RT-PCR and western blotting.</div></div><div><h3>Results</h3><div>Eight key targets were identified through PPI network analysis. GO and KEGG enrichment analyses highlighted pathways associated with redox regulation and ferroptosis. Docking studies revealed the strongest binding affinity between ICA and Nrf2 (Nuclear Factor Erythroid 2–Related Factor 2), further confirmed by stable interactions in molecular dynamics simulations. Experimentally, ICA promoted osteoblast proliferation, reduced intracellular ROS levels and apoptosis, and upregulated antioxidant, osteogenic, and ferroptosis-related proteins, including Nrf2, heme oxygenase-1 (HO-1), glutathione peroxidase-4 (GPX4), solute carrier family 7 member 11 (SLC7A11), alkaline phosphatase (ALP), and runt-related transcription factor-2 (RUNX2), while suppressing caspase-3 activation.</div></div><div><h3>Conclusion</h3><div>ICA activates the Nrf2/HO-1 pathway to suppress ferroptosis and oxidative stress, reduce apoptosis, and promote osteogenic activity, thereby alleviating PMO-related osteoblast dysfunction. These findings provide mechanistic support for ICA as a multi-target candidate for PMO management.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102147"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Integrated functional and metabolomic profiling reveals coordinated roles of CDK1 and FUT2 in lung adenocarcinoma progression 综合功能和代谢组学分析揭示了CDK1和FUT2在肺腺癌进展中的协调作用
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102157
Yongjian Tian , Wenfeng Zhang , Xue Li , Shunshun Cui , Hao Wu , Pengjuan Liu , Wei Wang

Background

Lung adenocarcinoma (LUAD) exhibits uncontrolled proliferation and metabolic reprogramming. Cyclin-dependent kinase 1 (CDK1) drives the G2/M transition, while fucosyltransferase 2 (FUT2) catalyzes α1,2-fucosylation, which broadly influences receptor signaling and stress responses. The mechanism by which these two proteins interact to shape LUAD metabolism remains unclear.

Methods

We employed structural modeling, transcriptomics, functional assays, and untargeted metabolomics to elucidate the roles of CDK1 and FUT2 in LUAD. A549 cells, a well-characterized lung adenocarcinoma model commonly used for studies of proliferation and metabolic rewiring, were selected for functional assays and untargeted metabolomics.

Results

Overexpressing CDK1 or FUT2 in A549 cells significantly altered cell viability and induced distinct metabolic shifts. CDK1 overexpression was associated with enrichment of oxidative phosphorylation and AMPK signaling pathways, thereby elevating key metabolites such as NAD+ and taurocholic acid. FUT2 overexpression perturbed tryptophan metabolism and Wnt signaling, resulting in increased levels of L-kynurenine, pyridoxine, and xanthurenic acid. Functionally, CDK1 inhibition using RO-3306 suppressed A549 cell proliferation and disrupted energy metabolism, whereas FUT2 promoted proliferation, potentially through antioxidant defense and lipid biosynthesis pathways.

Conclusions

CDK1 and FUT2 regulate complementary metabolic programs in LUAD, linking cell-cycle control and glycosylation to metabolic adaptation. These results provide a rationale for combined targeting of CDK1- and FUT2-linked pathways and support further preclinical evaluation of combination regimens.
肺腺癌(LUAD)表现出不受控制的增殖和代谢重编程。细胞周期蛋白依赖性激酶1 (CDK1)驱动G2/M转变,而聚焦转移酶2 (FUT2)催化α1,2-聚焦化,广泛影响受体信号传导和应激反应。这两种蛋白相互作用形成LUAD代谢的机制尚不清楚。方法采用结构建模、转录组学、功能分析和非靶向代谢组学来阐明CDK1和FUT2在LUAD中的作用。A549细胞是一种特征良好的肺腺癌模型,通常用于研究增殖和代谢重新布线,我们选择A549细胞进行功能分析和非靶向代谢组学。结果在A549细胞中过表达CDK1或FUT2可显著改变细胞活力并诱导明显的代谢变化。CDK1过表达与氧化磷酸化和AMPK信号通路的富集有关,从而升高NAD+和牛磺胆酸等关键代谢物。FUT2过表达扰乱色氨酸代谢和Wnt信号,导致l -犬尿氨酸、吡哆醇和黄嘌呤酸水平升高。在功能上,使用RO-3306抑制CDK1抑制A549细胞增殖并破坏能量代谢,而FUT2可能通过抗氧化防御和脂质生物合成途径促进增殖。结论scdk1和FUT2调节LUAD中互补的代谢程序,将细胞周期控制和糖基化与代谢适应联系起来。这些结果为联合靶向CDK1-和fut2相关途径提供了理论依据,并支持进一步对联合方案进行临床前评估。
{"title":"Integrated functional and metabolomic profiling reveals coordinated roles of CDK1 and FUT2 in lung adenocarcinoma progression","authors":"Yongjian Tian ,&nbsp;Wenfeng Zhang ,&nbsp;Xue Li ,&nbsp;Shunshun Cui ,&nbsp;Hao Wu ,&nbsp;Pengjuan Liu ,&nbsp;Wei Wang","doi":"10.1016/j.jrras.2025.102157","DOIUrl":"10.1016/j.jrras.2025.102157","url":null,"abstract":"<div><h3>Background</h3><div>Lung adenocarcinoma (LUAD) exhibits uncontrolled proliferation and metabolic reprogramming. Cyclin-dependent kinase 1 (CDK1) drives the G2/M transition, while fucosyltransferase 2 (FUT2) catalyzes α1,2-fucosylation, which broadly influences receptor signaling and stress responses. The mechanism by which these two proteins interact to shape LUAD metabolism remains unclear.</div></div><div><h3>Methods</h3><div>We employed structural modeling, transcriptomics, functional assays, and untargeted metabolomics to elucidate the roles of CDK1 and FUT2 in LUAD. A549 cells, a well-characterized lung adenocarcinoma model commonly used for studies of proliferation and metabolic rewiring, were selected for functional assays and untargeted metabolomics.</div></div><div><h3>Results</h3><div>Overexpressing CDK1 or FUT2 in A549 cells significantly altered cell viability and induced distinct metabolic shifts. CDK1 overexpression was associated with enrichment of oxidative phosphorylation and AMPK signaling pathways, thereby elevating key metabolites such as NAD<sup>+</sup> and taurocholic acid. FUT2 overexpression perturbed tryptophan metabolism and Wnt signaling, resulting in increased levels of L-kynurenine, pyridoxine, and xanthurenic acid. Functionally, CDK1 inhibition using RO-3306 suppressed A549 cell proliferation and disrupted energy metabolism, whereas FUT2 promoted proliferation, potentially through antioxidant defense and lipid biosynthesis pathways.</div></div><div><h3>Conclusions</h3><div>CDK1 and FUT2 regulate complementary metabolic programs in LUAD, linking cell-cycle control and glycosylation to metabolic adaptation. These results provide a rationale for combined targeting of CDK1- and FUT2-linked pathways and support further preclinical evaluation of combination regimens.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102157"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Silencing IFI6 enhances radiation sensitivity of triple-negative breast cancer via ER stress-driven immunogenic cell death 沉默IFI6通过内质网应激驱动的免疫原性细胞死亡增强三阴性乳腺癌的辐射敏感性
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102144
Yanyan Liu , Haifeng Jia , Wanpeng Wang , Junxiang Liu , Fuyang Xie , Xin Xu , Juan Pu

Background/objective

Interferon-γ-inducible protein 6 (IFI6) has been implicated in tumour progression and resistance to ionizing radiation; nevertheless, its functional relevance and mechanistic underpinnings in triple-negative breast cancer (TNBC) radioresistance remain inadequately characterised. Here, we interrogated the contribution of IFI6 to the radiosensitivity of TNBC cells and dissected the associated regulatory circuitry.

Materials and methods

An isogenic radioresistant MDA-MB-231 sub-line (MDA-MB-231/IR) was generated by fractionated irradiation, and IFI6 expression was quantified by quantitative RT-PCR and immunoblot analyses, revealing pronounced up-regulation in radioresistant cells. Loss-of-function studies employing lentiviral short-hairpin RNA (shRNA)-mediated silencing were conducted to investigate the functional role of IFI6 and underlying molecular mechanisms.

Results

It was demonstrated that IFI6 depletion markedly sensitized MDA-MB-231/IR cells to irradiation, as evidenced by enhanced apoptotic index and induction of immunogenic cell death (ICD). Mechanistically, IFI6 knock-down triggered endoplasmic-reticulum stress (ERS) and consequent reactive oxygen species (ROS) accumulation, thereby amplifying the cytotoxic effects of radiation. Rescue experiments with the ERS inhibitor 4-phenylbutyric acid (4-PBA) corroborated this causal axis: 4-PBA attenuated ROS generation and partially reversed the radiosensitising effect elicited by IFI6 silencing.

Conclusion

Collectively, our data establish IFI6 as a critical molecular determinant of TNBC radioresistance and unveil that its targeted suppression can overcome radioresistance by converting a sub-lethal stress into a potent ERS-dependent ICD pathway.
背景/目的干扰素-γ诱导蛋白6 (IFI6)与肿瘤进展和对电离辐射的抵抗有关;然而,其在三阴性乳腺癌(TNBC)放射耐药中的功能相关性和机制基础仍未充分表征。在这里,我们研究了IFI6对TNBC细胞放射敏感性的贡献,并剖析了相关的调节回路。材料与方法通过分级辐照产生等基因的耐辐射MDA-MB-231亚系(MDA-MB-231/IR),并通过定量RT-PCR和免疫印迹分析对IFI6的表达进行定量分析,发现在耐辐射细胞中IFI6的表达明显上调。利用慢病毒短发夹RNA (shRNA)介导的沉默进行功能丧失研究,以研究IFI6的功能作用及其潜在的分子机制。结果IFI6耗损使MDA-MB-231/IR细胞对辐照显着增敏,凋亡指数升高,免疫原性细胞死亡(ICD)诱导。在机制上,IFI6敲除触发内质网应激(ERS)和随之而来的活性氧(ROS)积累,从而放大辐射的细胞毒性作用。用ERS抑制剂4-苯基丁酸(4-PBA)进行的救援实验证实了这一因果轴:4-PBA减弱了ROS的产生,部分逆转了IFI6沉默引起的放射致敏效应。总之,我们的数据证实IFI6是TNBC辐射耐药的关键分子决定因素,并揭示其靶向抑制可以通过将亚致死应激转化为有效的ers依赖性ICD途径来克服辐射耐药。
{"title":"Silencing IFI6 enhances radiation sensitivity of triple-negative breast cancer via ER stress-driven immunogenic cell death","authors":"Yanyan Liu ,&nbsp;Haifeng Jia ,&nbsp;Wanpeng Wang ,&nbsp;Junxiang Liu ,&nbsp;Fuyang Xie ,&nbsp;Xin Xu ,&nbsp;Juan Pu","doi":"10.1016/j.jrras.2025.102144","DOIUrl":"10.1016/j.jrras.2025.102144","url":null,"abstract":"<div><h3>Background/objective</h3><div>Interferon-γ-inducible protein 6 (IFI6) has been implicated in tumour progression and resistance to ionizing radiation; nevertheless, its functional relevance and mechanistic underpinnings in triple-negative breast cancer (TNBC) radioresistance remain inadequately characterised. Here, we interrogated the contribution of IFI6 to the radiosensitivity of TNBC cells and dissected the associated regulatory circuitry.</div></div><div><h3>Materials and methods</h3><div>An isogenic radioresistant MDA-MB-231 sub-line (MDA-MB-231/IR) was generated by fractionated irradiation, and IFI6 expression was quantified by quantitative RT-PCR and immunoblot analyses, revealing pronounced up-regulation in radioresistant cells. Loss-of-function studies employing lentiviral short-hairpin RNA (shRNA)-mediated silencing were conducted to investigate the functional role of IFI6 and underlying molecular mechanisms.</div></div><div><h3>Results</h3><div>It was demonstrated that IFI6 depletion markedly sensitized MDA-MB-231/IR cells to irradiation, as evidenced by enhanced apoptotic index and induction of immunogenic cell death (ICD). Mechanistically, IFI6 knock-down triggered endoplasmic-reticulum stress (ERS) and consequent reactive oxygen species (ROS) accumulation, thereby amplifying the cytotoxic effects of radiation. Rescue experiments with the ERS inhibitor 4-phenylbutyric acid (4-PBA) corroborated this causal axis: 4-PBA attenuated ROS generation and partially reversed the radiosensitising effect elicited by IFI6 silencing.</div></div><div><h3>Conclusion</h3><div>Collectively, our data establish IFI6 as a critical molecular determinant of TNBC radioresistance and unveil that its targeted suppression can overcome radioresistance by converting a sub-lethal stress into a potent ERS-dependent ICD pathway.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102144"},"PeriodicalIF":2.5,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Flexible lead-free gamma-ray radiation shielding using La(OH)3-enhanced natural rubber composites 采用La(OH)3增强天然橡胶复合材料的柔性无铅伽马射线辐射屏蔽
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-31 DOI: 10.1016/j.jrras.2025.102150
Adel Fisli , Asron Ferdian Falaah , Deni Mustika , Sulistioso Giat Sukaryo , Sairun , Nadya Nurdini , Saeful Yusuf , Th. Rina Mulyaningsih , Agus Salim Afrozi , Auring Rachminisari , Agus Taufiq , Agus Sunardi , Syukri Arief , Henry Prastanto , Mohamad Irfan Fathurrohman , Ridwan
Ionizing radiation is widely applied in medicine, industry, and agriculture; however, it presents health risks to workers. This study aimed to develop lead-free, flexible gamma-ray shielding composites by incorporating lanthanum hydroxide [La(OH)3] into natural rubber (NR). Composites with varying La(OH)3 contents (0–250 phr) were prepared using an open two-roll mill and compression molding. Microstructure, mechanical properties, and gamma attenuation were characterized, and the results were compared with XCOM simulations. Gamma shielding was tested at 81–1332 keV using Ba-133, Cs-137, and Co-60 sources. SEM/EDS confirmed uniform La(OH)3 dispersion in the NR matrix. Density increased from 0.975 g/cm3 (NR) to 2.156 g/cm3 (La250/NR), and hardness increased from 27 % to 53 %. Tensile strength decreased from 13.1 MPa to 5.8 MPa, while elongation at break declined from 440 % to 320 %. At 81 keV, the mass attenuation coefficient increased from 0.161 to 2.029 cm2/g, and the half-value layer was reduced from 4.41 cm to 0.16 cm (∼96 % reduction). Compared to pure Pb, the HVL ratio of LaOH-natural rubber composite at 81 keV is 5.3, meaning the composite needs about five times greater thickness for equivalent shielding; at 1332 keV, the ratio is 6.04. Experimental results agreed with XCOM within 20 %. The developed LaOH-natural rubber composites demonstrate strong, flexible, and environmentally friendly alternatives for gamma shielding, especially in applications requiring lightweight and wearable protection.
电离辐射广泛应用于医药、工业和农业;然而,它给工人带来了健康风险。本研究旨在将氢氧化镧[La(OH)3]掺入天然橡胶(NR)中,开发无铅、柔性γ射线屏蔽复合材料。采用双辊开轧机压缩成型工艺制备了不同La(OH)3含量(0 ~ 250 phr)的复合材料。对其微观结构、力学性能和γ衰减特性进行了表征,并与XCOM模拟结果进行了比较。使用Ba-133, Cs-137和Co-60源测试了81-1332 keV的伽马屏蔽。SEM/EDS证实了La(OH)3在NR基体中的均匀分散。密度由0.975 g/cm3 (NR)提高到2.156 g/cm3 (La250/NR),硬度由27%提高到53%。拉伸强度由13.1 MPa降至5.8 MPa,断裂伸长率由440%降至320%。在81 keV下,质量衰减系数从0.161增加到2.029 cm2/g,半值层从4.41 cm减少到0.16 cm(减少约96%)。与纯Pb相比,在81 keV下,lah -天然橡胶复合材料的HVL比为5.3,这意味着复合材料需要的等效屏蔽厚度约为5倍;在1332 keV时,比值为6.04。实验结果与XCOM的一致性在20%以内。开发的lah -天然橡胶复合材料展示了强大,灵活和环保的伽马屏蔽替代品,特别是在需要轻质和可穿戴保护的应用中。
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引用次数: 0
Dose-effect analysis of 60Co-γ radiation on Astragalus membranaceus across life cycle and creation of high-flavonoid/super-biomass germplasm 60Co-γ辐射对黄芪全生命周期及高黄酮/超生物量种质形成的剂量效应分析
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-30 DOI: 10.1016/j.jrras.2025.102149
Ming Jiang , Zun Lv , Jiajia Chen , Yue Pan , Ying Yu , Kanchao Yu , Lijuan Xia , Jicheng Liu , Hui Li , Keyong Zhang

Objectives

This study aimed to systematically investigate the dose-dependent effects of 60Co-γ radiation on the entire growth cycle of Astragalus membranaceus, using a dose gradient ranging from 50 to 400 Gy. The specific objectives were to evaluate its impacts on seed germination, seedling physiology, agronomic traits of one-year-old plants, and the accumulation of medicinal components.

Methods

A radiation dose gradient of 50–400 Gy was applied to Astragalus membranaceus seeds. Assessments included seed germination and seedling emergence rates, physiological and biochemical markers (e.g., antioxidant enzyme activities and secondary metabolites), agronomic traits, and medicinal compound accumulation. The median lethal dose (LD50) was calculated, and a multi-trait weighted index (I) was used to screen superior germplasm lines.

Results

Low-dose radiation (50–100 Gy) significantly improved seed germination and emergence rates, while high doses (≥200 Gy) were inhibitory, with an LD50 of 201.95 Gy. At 50 Gy, antioxidant defense mechanisms were activated, indicated by increased CAT and APX activities, and flavonoid content rose by 48.2 %. Doses≥300 Gy caused severe damage, including a 57.8 % reduction in thylakoid density. In one-year-old plants, 50 Gy synergistically improved biomass and active compound content. Doses of 100–300 Gy induced transgressive segregation: one line (300 Gy-2) showed a root dry weight 4.63 times that of the control. Using a multi-trait index, seven superior lines were selected. Line 100 Gy-8 exhibited a 1.54-fold increase in total flavonoids (93.03 mg/g), while line 400 Gy-12 showed a threefold enhancement.

Conclusion

The results indicate that 50 Gy is an optimal dose for simultaneously improving yield and quality in Astragalus membranaceus, whereas the 100–300 Gy range serves as a promising mutagenic window for generating high-flavonoid or high-biomass variants. This study provides theoretical support and core germplasm resources for targeted breeding strategies.
目的采用50 ~ 400 Gy剂量梯度,系统研究60Co-γ辐射对黄芪整个生长周期的剂量依赖性。具体目的是评价其对一年生植物种子萌发、幼苗生理、农艺性状和药用成分积累的影响。方法对黄芪种子进行50 ~ 400 Gy剂量梯度辐射。评估包括种子发芽和出苗率、生理生化指标(如抗氧化酶活性和次生代谢物)、农艺性状和药用化合物积累。计算中位致死量(LD50),采用多性状加权指数(I)筛选优良种质系。结果低剂量辐射(50 ~ 100 Gy)显著提高种子萌发率和出苗率,高剂量辐射(≥200 Gy)抑制种子萌发,LD50为201.95 Gy。在50 Gy下,抗氧化防御机制被激活,表现为CAT和APX活性升高,类黄酮含量升高48.2%。剂量≥300 Gy造成严重损害,包括类囊体密度降低57.8%。在一年生植株中,50 Gy可协同提高生物量和活性化合物含量。100-300 Gy的剂量诱导了越界分离:一条线(300 Gy-2)的根干重是对照的4.63倍。利用多性状指数筛选7个优良品系。总黄酮含量增加了1.54倍(93.03 mg/g), 400 Gy-12增加了3倍。结论50 Gy是同时提高黄芪产量和品质的最佳剂量,而100-300 Gy是产生高黄酮或高生物量变异的理想诱变窗口。该研究为有针对性的育种策略提供了理论支持和核心种质资源。
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Journal of Radiation Research and Applied Sciences
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