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Medical and radiation science analysis using a probability U-Net with a GRU model 使用带有GRU模型的概率U-Net进行医学和辐射科学分析
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-19 DOI: 10.1016/j.jrras.2025.102134
Ahmed I. Taloba, Rayan Alanazi
Accurate and interpretable segmentation of CT images of the lungs is critical for early diagnosis and treatment planning in pulmonary diseases. The current deep learning (DL) models tend to lack uncertainty quantification, lack consistency over time, and do not extrapolate into ambiguous areas. To solve these problems, this study suggests a hybrid DL model that combines U-Net with Gated Recurrent Units (GRUs) and a probabilistic latent space to segment based on uncertainty. The encoder learns both spatial and temporal features using GRU-enhanced convolutional blocks, and the probabilistic module of the bottleneck addresses aleatory and epistemic uncertainty via Monte Carlo sampling. This joint temporal modeling and probabilistic representation allows the system to perform temporally consistent segmentation with only one lightweight architecture. The experiments on the IQ-OTH/NCCD lung CT dataset (1295 annotated images) demonstrate that the proposed model achieves 98.9 % accuracy and a 91.5 % Dice coefficient, which is 7–15 % higher than state-of-the-art models, including ResNet18 with MC Dropout and SkinSAM. The model also achieves an Expected Calibration Error of just 2.8 % which justifies its validity in the clinic. Uncertainty maps can also aid decision-making regarding tumor boundaries. Compared with previous applications such as Probabilistic U-Net and GRU-Net, which operate independently, the suggested U-Net-GRU-Probabilistic framework offers an integrated, confident, and understandable method for segmenting lung CT. Demonstrates potential for real-time diagnostic deployment.
肺部CT图像的准确和可解释的分割对于肺部疾病的早期诊断和治疗计划至关重要。当前的深度学习(DL)模型往往缺乏不确定性量化,缺乏随时间推移的一致性,并且不能推断到模糊的领域。为了解决这些问题,本研究提出了一种混合深度学习模型,该模型将U-Net与门控循环单元(gru)和基于不确定性的概率潜在空间相结合。编码器使用gru增强的卷积块学习空间和时间特征,瓶颈的概率模块通过蒙特卡罗采样解决了选择性和认知不确定性。这种联合时间建模和概率表示允许系统仅使用一个轻量级架构执行时间一致的分割。在IQ-OTH/NCCD肺CT数据集(1295张带注释的图像)上的实验表明,该模型达到了98.9%的准确率和91.5%的Dice系数,比目前最先进的模型(包括带有MC Dropout和SkinSAM的ResNet18)高出7 - 15%。该模型的预期校准误差仅为2.8%,证明了其在临床中的有效性。不确定性图也可以帮助决定肿瘤的边界。与之前独立运行的Probabilistic U-Net和GRU-Net相比,我们提出的U-Net- gru -Probabilistic框架为肺CT分割提供了一种完整、可靠且易于理解的方法。演示实时诊断部署的潜力。
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引用次数: 0
ARHGAP11A promotes proliferation and invasion through RhoA/RAC1 in LUAD ARHGAP11A通过RhoA/RAC1在LUAD中促进增殖和侵袭
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102123
Xinyu Liu , Xuesong Zhao , Haifeng Hu , Tianyu Zhang , Yi Qi , Bo Liu , Bing Lan , Bin Li

Background

Lung adenocarcinoma (LUAD) ranks among the most common subtypes of lung cancer, characterized by a poor prognosis due to the scarcity of effective treatment options. Functional role and underlying mechanisms of Rho GTPase-activating protein 11A (ARHGAP11A) in LUAD remain insufficiently characterized. The study aims to explore it, with the hypothesis that ARHGAP11A is a pivotal driver of tumor progression and a potential therapeutic target.

Methods

The research employed bioinformatics analysis to identify ARHGAP11A's overexpression in LUAD and its correlation with poor prognosis. To evaluate how reducing ARHGAP11A affects LUAD cell movement and invasion, various functional tests such as cell scratch and transwell cell invasion assays were conducted. Additionally, the study investigated ARHGAP11A's involvement in LUAD epithelial-mesenchymal transition and its regulation through the RhoA/RAC1 pathway using RAC1-specific inhibitor EHT-1864. In vivo tumor growth was assessed following ARHGAP11A knockdown, and the efficacy of the RAC1-specific inhibitor EHT-1864 in reducing tumor growth was tested.

Results

The bioinformatics investigation indicated that ARHGAP11A is upregulated in LUAD and correlates with unfavorable outcomes. Cell migration and invasion were inhibited after ARHGAP11A knockdown. The study also implicated ARHGAP11A in LUAD epithelial-mesenchymal transition and demonstrated its regulation through the RhoA/RAC1 pathway using a RAC1-specific inhibitor. In vivo tumor growth was significantly inhibited by ARHGAP11A knockdown, and treatment with EHT-1864 reduced tumor growth, indicating a potential therapeutic strategy.

Conclusion

The study's findings establish ARHGAP11A as a key factor in LUAD progression, enhancing cell proliferation and invasion. These results warrant further exploration of ARHGAP11A's mechanisms and clinical applications, potentially leading to new therapeutic strategies for LUAD treatment.
肺腺癌(LUAD)是最常见的肺癌亚型之一,由于缺乏有效的治疗方案,其预后较差。Rho gtpase激活蛋白11A (ARHGAP11A)在LUAD中的功能作用和潜在机制尚未得到充分的研究。本研究旨在对此进行探索,并假设ARHGAP11A是肿瘤进展的关键驱动因素和潜在的治疗靶点。方法采用生物信息学分析方法鉴定ARHGAP11A在LUAD中的过表达及其与不良预后的相关性。为了评估降低ARHGAP11A对LUAD细胞运动和侵袭的影响,我们进行了各种功能测试,如细胞划痕和transwell细胞侵袭试验。此外,本研究利用RAC1特异性抑制剂EHT-1864研究了ARHGAP11A参与LUAD上皮-间质转化及其通过RhoA/RAC1通路的调控。在ARHGAP11A基因敲除后评估体内肿瘤生长情况,并检测rac1特异性抑制剂EHT-1864抑制肿瘤生长的效果。结果生物信息学研究表明,ARHGAP11A在LUAD中表达上调,并与不良预后相关。敲低ARHGAP11A后,细胞迁移和侵袭受到抑制。该研究还发现ARHGAP11A参与LUAD的上皮-间质转化,并通过RAC1特异性抑制剂通过RhoA/RAC1通路进行调控。体内肿瘤生长被ARHGAP11A敲低显著抑制,用EHT-1864治疗可降低肿瘤生长,提示一种潜在的治疗策略。结论本研究结果证实ARHGAP11A在LUAD进展中起关键作用,可促进细胞增殖和侵袭。这些结果为进一步探索ARHGAP11A的作用机制和临床应用提供了依据,有可能为LUAD治疗提供新的治疗策略。
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引用次数: 0
Predicting cognitive decline in Parkinson's disease using multimodal MRI features and serum inflammatory markers 利用多模态MRI特征和血清炎症标志物预测帕金森病的认知能力下降
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102124
Ren Dong , Haiqing Shen , Qianning Li

Purpose

Cognitive decline is a significant concern in Parkinson's disease, affecting patient quality of life and increasing healthcare burden. This study aims to construct and validate a risk prediction model for cognitive decline in Parkinson's disease patients using multimodal MRI features and serum inflammatory markers.

Methods

A retrospective case-control study was conducted involving 413 Parkinson's disease patients with normal cognition at baseline. These patients were divided into a primary cohort (n = 321) and an external validation cohort (n = 92). Patients were followed for 1–4 years, and patients with disease progression were compared with those without progression. Multimodal MRI scans and serum inflammatory marker assessments were performed. Univariate, multivariate logistic regression, and receiver operator characteristic (ROC) analyses were used to identify predictors of cognitive decline.

Results

Compared with the non-progression group, the progression group showed significant differences in T1 characteristics, including cortical thickness of the left hemisphere (LH) postcentral gyrus (P = 0.008), left hippocampal volume (P = 0.005), and right hippocampal volume (P = 0.004). The progression group showed significant differences in Susceptibility-Weighted Imaging (SWI) characteristics. Symptoms on the opposite side of Substantia Nigra pars compacta (SNc) were more pronounced in the non-progression group compared to the progression group (P = 0.006). Similarly, for symptoms on the same side of SNc, the non-progression group showed more prominent findings than the progression group (P < 0.001). Serum inflammatory marker analysis indicated that the progression group also showed significant differences in lymphocyte count (P = 0.023), neutrophil-to-lymphocyte ratio (NLR) (P = 0.002), lymphocyte-to-monocyte ratio (LMR) (P = 0.003), and albumin-to-fibrinogen ratio (AFR) (P = 0.004). The combined prediction model demonstrated high diagnostic accuracy, with an area under the curve (AUC) of 0.809 in the primary cohort and 0.812 in the external validation cohort.

Conclusion

The developed model combining multimodal MRI features and serum inflammatory markers effectively identifies key factors influencing cognitive decline in Parkinson's disease, offering high diagnostic accuracy and valuable clinical insights for early detection and personalized treatment.
目的认知能力下降是帕金森病的一个重要问题,影响患者的生活质量,增加医疗负担。本研究旨在利用多模态MRI特征和血清炎症标志物构建并验证帕金森病患者认知能力下降的风险预测模型。方法对413例基线认知正常的帕金森病患者进行回顾性病例对照研究。这些患者被分为初级队列(n = 321)和外部验证队列(n = 92)。患者随访1-4年,将疾病进展患者与无进展患者进行比较。进行多模态MRI扫描和血清炎症标志物评估。采用单因素、多因素逻辑回归和受试者操作特征(ROC)分析来确定认知能力下降的预测因素。结果与非进展组相比,进展组T1特征包括左半球(LH)中央后回皮质厚度(P = 0.008)、左海马体积(P = 0.005)、右海马体积(P = 0.004)均有显著差异。进展组在敏感性加权成像(SWI)特征上有显著差异。与进展组相比,非进展组黑质致密部(SNc)对侧症状更为明显(P = 0.006)。同样,对于SNc同侧的症状,非进展组比进展组表现出更突出的发现(P < 0.001)。血清炎症标志物分析显示,进展组淋巴细胞计数(P = 0.023)、中性粒细胞与淋巴细胞比值(NLR) (P = 0.002)、淋巴细胞与单核细胞比值(LMR) (P = 0.003)、白蛋白与纤维蛋白原比值(AFR) (P = 0.004)也有显著差异。联合预测模型具有较高的诊断准确率,主要队列的曲线下面积(AUC)为0.809,外部验证队列的AUC为0.812。结论建立的多模态MRI特征与血清炎症标志物相结合的模型能有效识别影响帕金森病认知能力下降的关键因素,诊断准确率高,为早期发现和个性化治疗提供了有价值的临床见解。
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引用次数: 0
SF3B3-mediated alternative splicing of ATP2B4 via exon 21 skipping contributes to the progression of bladder cancer sf3b3介导的ATP2B4通过外显子21跳变的选择性剪接有助于膀胱癌的进展
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102121
Cong Cheng , Tao Yang , Li Wang, Youji Yan, Yixiang Liao

Background

While alternative splicing is increasingly recognized in cancer, its specific regulators and functional consequences in bladder cancer remain largely uncharted. This study aims to investigate the role of abnormal alternative splicing of ATP2B4 in the progression of bladder cancer.

Methods

Exon sequencing data from The Cancer Genome Atlas were analyzed using bioinformatics algorithms, revealing significant exon skipping events in bladder cancer. Then, confirm the dysregulated expression of specific transcripts in bladder cancer tissues. Additionally, ATP2B4 was overexpressed or knocked down in tumor cells for in vitro functional experiments.

Results

Experimental results show that ATP2B4 produces two transcripts: the full-length transcript (ATP2B4-V1) and the spliced transcript (ATP2B4-V2), where the spliced transcript skips exon 21. ATP2B4-v2 is highly expressed in bladder cancer tissues, while ATP2B4-v1 is mainly expressed in non-cancerous tissues and normal bladder epithelium. Moreover, a higher PSI (Percent Spliced In) value for exon 21, indicative of greater ATP2B4-V1 expression, was correlated with improved survival in bladder cancer patients. In vitro functional assays demonstrated that the ATP2B4 splicing variant (ATP2B4-V2) enhanced the proliferation, migration, and invasion of bladder cancer cells, whereas the full-length transcript (ATP2B4-V1) exerted an opposing effect. We also identified a group of splicing factors, among which the splicing factor SF3B3 (Splicing Factor 3b Subunit 3) was found to promote the skipping of exon 21 of ATP2B4, and explored their role in regulating ATP2B4 precursor mRNA. The results showed that SF3B3 could promote the skipping of exon 21 of ATP2B4, resulting in an increased proportion of bladder cancer cells and enhanced carcinogenicity.

Conclusion

SF3B3 promotes the skipping of ATP2B4 exon 21, leading to the preferential expression of an oncogenic isoform (ATP2B4-V2) which promotes the malignant phenotype of bladder cancer cells, suggesting that targeting alternative splicing regulation may represent a promising therapeutic strategy.
虽然选择性剪接在癌症中的作用越来越被认识到,但其在膀胱癌中的特定调节因子和功能后果在很大程度上仍是未知的。本研究旨在探讨ATP2B4异常选择性剪接在膀胱癌进展中的作用。方法利用生物信息学算法分析来自Cancer Genome Atlas的sexon测序数据,揭示膀胱癌中显著的外显子跳变事件。然后,确认特定转录本在膀胱癌组织中的表达失调。此外,ATP2B4在肿瘤细胞中过表达或敲低进行体外功能实验。结果ATP2B4产生两个转录本:全长转录本(ATP2B4- v1)和剪接转录本(ATP2B4- v2),其中剪接转录本跳过21外显子。ATP2B4-v2在膀胱癌组织中高表达,而ATP2B4-v1主要在非癌组织和正常膀胱上皮中表达。此外,外显子21较高的PSI (Percent Spliced In)值,表明ATP2B4-V1表达较高,与膀胱癌患者的生存率提高相关。体外功能分析表明,ATP2B4剪接变体(ATP2B4- v2)增强膀胱癌细胞的增殖、迁移和侵袭,而全长转录本(ATP2B4- v1)则发挥相反的作用。我们还发现了一组剪接因子,其中剪接因子SF3B3 (splicing factor 3b Subunit 3)促进了ATP2B4外显子21的跳变,并探讨了它们在调节ATP2B4前体mRNA中的作用。结果表明,SF3B3可以促进ATP2B4外显子21的跳变,导致膀胱癌细胞比例增加,致癌性增强。结论sf3b3可促进ATP2B4外显子21的跳变,导致致癌亚型(ATP2B4- v2)的优先表达,从而促进膀胱癌细胞的恶性表型,提示靶向选择性剪接调控可能是一种很有前景的治疗策略。
{"title":"SF3B3-mediated alternative splicing of ATP2B4 via exon 21 skipping contributes to the progression of bladder cancer","authors":"Cong Cheng ,&nbsp;Tao Yang ,&nbsp;Li Wang,&nbsp;Youji Yan,&nbsp;Yixiang Liao","doi":"10.1016/j.jrras.2025.102121","DOIUrl":"10.1016/j.jrras.2025.102121","url":null,"abstract":"<div><h3>Background</h3><div>While alternative splicing is increasingly recognized in cancer, its specific regulators and functional consequences in bladder cancer remain largely uncharted. This study aims to investigate the role of abnormal alternative splicing of ATP2B4 in the progression of bladder cancer.</div></div><div><h3>Methods</h3><div>Exon sequencing data from The Cancer Genome Atlas were analyzed using bioinformatics algorithms, revealing significant exon skipping events in bladder cancer. Then, confirm the dysregulated expression of specific transcripts in bladder cancer tissues. Additionally, ATP2B4 was overexpressed or knocked down in tumor cells for in vitro functional experiments.</div></div><div><h3>Results</h3><div>Experimental results show that ATP2B4 produces two transcripts: the full-length transcript (ATP2B4-V1) and the spliced transcript (ATP2B4-V2), where the spliced transcript skips exon 21. ATP2B4-v2 is highly expressed in bladder cancer tissues, while ATP2B4-v1 is mainly expressed in non-cancerous tissues and normal bladder epithelium. Moreover, a higher PSI (Percent Spliced In) value for exon 21, indicative of greater ATP2B4-V1 expression, was correlated with improved survival in bladder cancer patients. In vitro functional assays demonstrated that the ATP2B4 splicing variant (ATP2B4-V2) enhanced the proliferation, migration, and invasion of bladder cancer cells, whereas the full-length transcript (ATP2B4-V1) exerted an opposing effect. We also identified a group of splicing factors, among which the splicing factor SF3B3 (Splicing Factor 3b Subunit 3) was found to promote the skipping of exon 21 of ATP2B4, and explored their role in regulating ATP2B4 precursor mRNA. The results showed that SF3B3 could promote the skipping of exon 21 of ATP2B4, resulting in an increased proportion of bladder cancer cells and enhanced carcinogenicity.</div></div><div><h3>Conclusion</h3><div>SF3B3 promotes the skipping of ATP2B4 exon 21, leading to the preferential expression of an oncogenic isoform (ATP2B4-V2) which promotes the malignant phenotype of bladder cancer cells, suggesting that targeting alternative splicing regulation may represent a promising therapeutic strategy.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102121"},"PeriodicalIF":2.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787195","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
The effects of acute and chronic exposure of 2100 MHz radiofrequency radiation on rat mismatch negativity 2100 MHz射频辐射急性和慢性照射对大鼠失配负性的影响
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102126
Hakan Er , Enis Hidisoglu , Deniz Kantar , Alev Duygu Acun , Gokhan Akkoyunlu , Sukru Ozen , Piraye Yargicoglu
Cell phones operate by emitting radiofrequency radiation (RFR), a form of electromagnetic radiation (EMR). Consequently, ongoing researches target to determine whether it poses potential risks to human health. One of these risks is related with brain and auditory system. This study aims to examine the impact of acute and chronic exposure to 2100 MHz radiofrequency radiation on mismatch negativity (MMN) in rats.
In this study, we established 1-week (RFR1) and 10-week (RFR10) RFR groups from rats, which were subjected to 2100 MHz RFR exposure. Cage control groups (CC1, CC10) and sham groups (S1, S10) that were not subjected to RFR for equivalent durations were also established. Following auditory event-related potential (AERP) recordings, MMN waves were computed and analyzed. Additionally, brain samples were collected and biochemical and histological analyses were performed.
The RFR1 group exhibited a reduction in AMPAR GluR2 subunit protein levels relative to the CC1 and S1 groups, although GFAP protein levels increased. Conversely, the opposite was observed in the chronic groups. Edema of astrocytic endfeet, mitochondrial damage, and lysosomal vesicles were identified in the RFR1 group. The MMN amplitude was found to be reduced in the RFR1 group relative to the CC1 group. The RFR1 group exhibited a reduction in delta and theta power relative to the S1/CC1 groups. Alpha coherence diminished in the RFR1 group relative to the S1 group, however it augmented in the RFR10 group compared to the S10 group.
The assessment of event-related potentials indicated that 2100 MHz RFR led to a decrease in MMN amplitude, power spectrum, and coherence values in the RFR1 group relative to the S1 and CC1 groups, but an increase was observed in the RFR10 group compared to the S10 group. Consequently, in the acute period, 2100 MHz RFR may have adverse effects on auditory sensory memory.
手机通过发射射频辐射(RFR)来工作,这是一种电磁辐射(EMR)。因此,正在进行的研究旨在确定它是否对人类健康构成潜在风险。其中一种风险与大脑和听觉系统有关。本研究旨在探讨急性和慢性暴露于2100 MHz射频辐射对大鼠失配负性(MMN)的影响。在本研究中,我们建立了2100 MHz RFR暴露大鼠1周(RFR1)和10周(RFR10) RFR组。同样建立不进行RFR治疗相同时间的笼子对照组(CC1、CC10)和假手术组(S1、S10)。在听事件相关电位(AERP)记录后,计算并分析MMN波。此外,收集脑样本并进行生化和组织学分析。与CC1和S1组相比,RFR1组AMPAR GluR2亚基蛋白水平降低,尽管GFAP蛋白水平升高。相反,在慢性组中观察到的情况正好相反。RFR1组出现星形细胞终足水肿、线粒体损伤和溶酶体囊泡。与CC1组相比,RFR1组的MMN振幅减小。与S1/CC1组相比,RFR1组表现出δ和θ功率的降低。与S1组相比,RFR1组的α相干性减弱,而与S10组相比,RFR10组的α相干性增强。事件相关电位评估表明,2100 MHz RFR导致RFR1组相对于S1和CC1组MMN振幅、功率谱和相干值降低,但RFR10组相对于S10组增加。因此,在急性期,2100 MHz RFR可能对听觉感觉记忆产生不利影响。
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引用次数: 0
Isocitrate dehydrogenase 2 promotes tumor progression and glycolysis in cervical squamous cell carcinoma by activating the HIF1A signaling pathway 异柠檬酸脱氢酶2通过激活HIF1A信号通路促进宫颈鳞状细胞癌的肿瘤进展和糖酵解
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102113
Xiaojuan Liu , Lisha Shu , Huiying Zhang

Background

Isocitrate dehydrogenase 2 (IDH2), a mitochondrial enzyme central to metabolic processes, has been associated with tumorigenesis in multiple cancers; however, its functional significance in cervical squamous cell carcinoma (CSCC) remains unclear.

Methods

We assessed IDH2 expression in clinical CSCC samples and established cell lines. Functional analyses, including IDH2 knockdown in CaSki cells, were performed to evaluate its impact on cellular proliferation, migratory capacity, and glycolytic metabolism. To uncover the molecular mechanism, we investigated the interplay between IDH2 and hypoxia-inducible factor 1-alpha (HIF1α), along with the expression of downstream glycolytic targets such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). The in vivo role of IDH2 was further examined using xenograft models in nude mice, monitoring tumor growth and the levels of HIF1α, Ki67, and glycolytic indicators.

Results

IDH2 was markedly overexpressed in both CSCC tissues and cell lines, with elevated levels correlating with with elevated levels associated with enhanced malignant potential in functional assays. Depletion of IDH2 inhibited cell proliferation, migration, and glycolytic activity in CaSki cells. Mechanistically, IDH2 was shown to upregulate HIF1α, thereby enhancing the transcription of glycolytic enzymes HK2 and LDHA. Notably, the oncogenic and metabolic effects induced by IDH2 were reversed upon HIF1α silencing, confirming its essential mediating role. In mouse models, IDH2 knockdown significantly suppressed tumor growth and downregulated HIF1α, Ki67, and key glycolytic markers. Notably, the oncogenic and metabolic effects induced by IDH2 were reversed upon HIF1α silencing, confirming its essential mediating role.

Conclusion

Our study identifies an IDH2-HIF1α-glycolysis signaling cascade that promotes CSCC progression. These findings establish IDH2 as a key driver of metabolic reprogramming in cervical cancer and support its potential as a target for therapeutic strategies, potentially involving the repurposing of existing IDH2 inhibitors, aimed at disrupting cancer metabolism in CSCC.
二枸橼酸脱氢酶2 (IDH2)是代谢过程的核心线粒体酶,与多种癌症的肿瘤发生有关;然而,其在宫颈鳞癌(CSCC)中的功能意义尚不清楚。方法在临床CSCC样品和建立细胞系中检测IDH2的表达。功能分析,包括CaSki细胞中IDH2敲低,评估其对细胞增殖、迁移能力和糖酵解代谢的影响。为了揭示其分子机制,我们研究了IDH2与缺氧诱导因子1- α (HIF1α)之间的相互作用,以及下游糖酵解靶点如己糖激酶2 (HK2)和乳酸脱氢酶A (LDHA)的表达。通过裸鼠异种移植模型进一步检测IDH2的体内作用,监测肿瘤生长和HIF1α、Ki67和糖酵解指标的水平。结果在CSCC组织和细胞系中,sidh2均显著过表达,功能分析显示,sidh2水平升高与恶性潜能增强相关。IDH2的缺失抑制了CaSki细胞的增殖、迁移和糖酵解活性。在机制上,IDH2被证明上调HIF1α,从而增强糖酵解酶HK2和LDHA的转录。值得注意的是,IDH2诱导的致癌和代谢效应在HIF1α沉默后被逆转,证实了其重要的介导作用。在小鼠模型中,IDH2敲低可显著抑制肿瘤生长,下调HIF1α、Ki67和关键糖酵解标志物。值得注意的是,IDH2诱导的致癌和代谢效应在HIF1α沉默后被逆转,证实了其重要的介导作用。结论本研究确定了idh2 - hif1 α-糖酵解信号级联促进CSCC进展。这些发现表明IDH2是宫颈癌代谢重编程的关键驱动因素,并支持其作为治疗策略靶点的潜力,可能涉及现有IDH2抑制剂的重新用途,旨在破坏CSCC中的癌症代谢。
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引用次数: 0
Hypoxia-immune ceRNA network identifies novel diagnostic biomarkers and therapeutic targets in pulpitis 缺氧免疫ceRNA网络确定了牙髓炎新的诊断生物标志物和治疗靶点
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-18 DOI: 10.1016/j.jrras.2025.102122
Simin Li , Jingwen Ding , Linxin Jiang , Daniel R. Reissmann , Deborah Kreher , Gerhard Schmalz , Wei Shang , Xianda Hu

Background

Pulpitis is a common inflammatory condition of dental pulp tissue, but the underlying molecular mechanisms remain poorly understood. This study applied a novel hypoxia-immune integrated competing endogenous RNA (ceRNA) network approach to identify key regulatory mechanisms in pulpitis pathogenesis.

Methods

RNA sequencing was performed on pulp tissues from 6 pulpitis patients and 6 healthy controls using the BGISEQ platform. Differential expression analysis identified dysregulated mRNAs, miRNAs, and lncRNAs. Hypoxia- and immune-related genes were obtained from pre-defined gene sets in the MSigDB, ImmPort, and InnateDB databases. A ceRNA network was constructed using TargetScan, miRcode, and miRDB databases, followed by identification of key regulatory axes through correlation analysis. Immune infiltration and drug target prediction analyses were performed. External validation was conducted using the GSE77459 dataset.

Results

We identified 3347 differentially expressed mRNAs, 155 miRNAs, and 2286 lncRNAs. Among these, 557 mRNAs were related to hypoxia-immune pathways. Two key regulatory axes were identified: BCYRN1-hsa-miR-25-5p-EDIL3 and BCYRN1/PCA3-hsa-miR-425-5p-MAP2K6. The regulatory factors showed significant correlations with immune checkpoints and NK cell infiltration, with hsa-miR-425-5p exhibiting positive correlations with immune checkpoints but negative correlation with NK cell infiltration, while BCYRN1 and MAP2K6 showed opposite patterns. MAP2K6 was predicted as a target for Fostamatinib. External validation confirmed the differential expression patterns, with both MAP2K6 and EDIL3 achieving perfect diagnostic performance (AUC = 1.00).

Conclusions

This study reveals novel ceRNA regulatory mechanisms in pulpitis and identifies potential biomarkers and therapeutic targets, providing new insights into pulpitis pathogenesis and clinical management strategies.
牙髓炎是一种常见的牙髓组织炎症,但其潜在的分子机制尚不清楚。本研究采用一种新的缺氧免疫整合竞争内源性RNA (ceRNA)网络方法来确定牙髓炎发病机制的关键调控机制。方法采用BGISEQ平台对6例牙髓炎患者和6例正常人的牙髓组织进行srna测序。差异表达分析确定了失调的mrna、mirna和lncrna。缺氧和免疫相关基因从MSigDB、import和InnateDB数据库中的预定义基因集中获得。利用TargetScan、miRcode和miRDB数据库构建ceRNA网络,通过相关分析确定关键调控轴。进行免疫浸润和药物靶标预测分析。外部验证使用GSE77459数据集进行。结果共鉴定出3347个差异表达mrna、155个mirna和2286个lncrna。其中,557个mrna与缺氧免疫途径相关。鉴定出两个关键调控轴:BCYRN1-hsa- mir -25-5p- edil3和BCYRN1/PCA3-hsa-miR-425-5p-MAP2K6。调节因子与免疫检查点和NK细胞浸润呈显著相关,其中hsa-miR-425-5p与免疫检查点呈正相关,与NK细胞浸润呈负相关,而BCYRN1和MAP2K6则相反。MAP2K6被预测为Fostamatinib的靶点。外部验证证实了差异表达模式,MAP2K6和EDIL3均获得完美的诊断性能(AUC = 1.00)。结论本研究揭示了新的ceRNA在牙髓炎中的调控机制,确定了潜在的生物标志物和治疗靶点,为牙髓炎的发病机制和临床治疗策略提供了新的见解。
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引用次数: 0
Effect of MgO on the structural, optical, and radiation shielding behavior of multi-component borate glass MgO对多组分硼酸盐玻璃结构、光学和辐射屏蔽性能的影响
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.jrras.2025.102110
Samar Al-Shehri , Nawal K. Almaymoni , Nuha Al-Harbi , Mona Mahmoud , Kottakkaran Sooppy Nisar , Wedad R. Alharbi , Hosam M.G. Al-Qatlawi , Sarah M. Kamil , Ahmad S. Abu-Khadra , A.M. Abdel-Ghany
This study investigates the influence of the replacement of B2O3 with MgO on the structural, optical, and radiation shielding properties of borate-based glasses. Three samples were prepared based on the chemical formula (77.5 – x) mol% B2O3 + 2.5 mol% V2O5 + 2.5 mol% CeO2 + 10 mol% PbO + 7.5 mol% Na2O + x mol% MgO (x = 0, 1.25, and 2.5). As the content of MgO increased, it was observed an enhancement in glass transparency and improved surface uniformity. Based on the Fourier transform inferred, FTIR, spectral analysis the network polymerization has been confirmed. Also, a conversion of BO3 to BO4 has been observed. Optical sherardization has been achieved using the UV–Vis spectra measurements. The results showed a reduction in both transmittance and optical energy gap as the MgO content increased. While the value experimental measured density increased from 1.78 to 2.16 g/cm3. Also, the glass packing efficiency increased from 54 % to >65 %, which confirmed improved structural compactness. Radiation shielding parameters, calculated using XCOM at 0.662, 1.173, and 1.333 MeV, showed enhanced LAC and reduced HVL. It was found that, the sample with 2.5 mol% MgO exhibited the best shielding performance. In general, while these glasses do not surpass lead or commercial high-density glasses in shielding efficiency, they significantly outperform concrete. based on the findings, the prepared samples show competitive performance relative to some polymer-based shields. This supports the MgO-containing borate glasses for use in optical, radiation shielding, and biomedical applications.
本文研究了MgO取代B2O3对硼酸盐基玻璃的结构、光学和辐射屏蔽性能的影响。根据化学式(77.5 - x) mol% B2O3 + 2.5 mol% V2O5 + 2.5 mol% CeO2 + 10 mol% PbO + 7.5 mol% Na2O + x mol% MgO (x = 0,1.25和2.5)制备了3种样品。随着MgO含量的增加,玻璃透明度增强,表面均匀性改善。基于傅里叶变换推断,FTIR,光谱分析证实了网络聚合。此外,还观察到BO3向BO4的转化。利用紫外可见光谱测量实现了光学渗矿化。结果表明,随着MgO含量的增加,透光率和光能隙均降低。而实验测得的密度值由1.78 g/cm3增加到2.16 g/cm3。此外,玻璃填充效率从54%提高到65%,这证实了结构致密性的改善。在0.662、1.173和1.333 MeV下使用XCOM计算的辐射屏蔽参数显示LAC增强,HVL降低。结果表明,添加2.5 mol% MgO的样品具有最佳的屏蔽性能。一般来说,虽然这些玻璃的屏蔽效率不超过铅或商用高密度玻璃,但它们的性能明显优于混凝土。根据研究结果,制备的样品相对于一些聚合物基屏蔽物表现出竞争性的性能。这支持含镁硼酸盐玻璃用于光学,辐射屏蔽和生物医学应用。
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引用次数: 0
On the exponent power sine Lomax distribution with applications in the music education and radiation fields 指数幂正弦Lomax分布及其在音乐教育和辐射领域的应用
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.jrras.2025.102109
Yuwei Zhang , Qimeng Mao , Jun Xu , Hassan M. Aljohani , Bassant Elkalzah , Ghareeb A. Marei
Considering the decisive role of probability distributions in applied fields, we consider and implement a new probability distribution. The proposed distribution is a sine-oriented modification of the Lomax distribution by modifying the power Lomax distribution, and is called the exponent sine power Lomax (ESP-Lomax) distribution. We go into the computation of the mathematical properties and analytical studies based on these properties of the ESP-Lomax distribution. In addition, this paper also provides the mathematical derivation of the heavy-tailed characteristics of the ESP-Lomax distribution. The mathematical computation of maximum likelihood estimators and simulation studies under various parameter settings based on the ESP-Lomax distribution is also provided. In comparison with other distributions, we check and establish the practical superiority of the ESP-Lomax distribution using two practical data sets, which are sourced from two different applied sectors. By employing several key tools, we empirically demonstrated that the ESP-Lomax distribution can fit real-world events well across various domains.
考虑到概率分布在应用领域中的决定性作用,我们考虑并实现了一种新的概率分布。所提出的分布是通过修正幂Lomax分布对Lomax分布进行的一种面向正弦的修正,称为指数正弦幂Lomax (ESP-Lomax)分布。我们将根据ESP-Lomax分布的这些性质进行数学性质的计算和分析研究。此外,本文还给出了ESP-Lomax分布重尾特性的数学推导。给出了基于ESP-Lomax分布的极大似然估计的数学计算和各种参数设置下的仿真研究。与其他分布相比,我们使用来自两个不同应用部门的两个实际数据集来检验并建立ESP-Lomax分布的实际优势。通过使用几个关键工具,我们从经验上证明了ESP-Lomax分布可以很好地适应不同领域的真实事件。
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引用次数: 0
Screening and mechanistic investigation of key radioresistance genes in oral squamous cell carcinoma 口腔鳞状细胞癌关键放射耐药基因的筛选及机制研究
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-17 DOI: 10.1016/j.jrras.2025.102112
Haifeng Zhou , Lijuan Liu , Simin Li , Linxin Jiang , Xinying Han

Objectives

To identify key candidate genes associated with radioresistance in oral squamous cell carcinoma (OSCC), elucidate their regulatory mechanisms and molecular pathways.

Methods

This study integrated bulk transcriptomic data from TCGA-OSCC and GEO databases with single-cell RNA sequencing (scRNA-seq) data. Key prognostic genes were identified through differential expression analysis, protein-protein interaction (PPI) network analysis, and Cox and Lasso regression modeling. Single-cell analysis was performed to validate gene expression patterns and cellular mechanisms. The expression levels of the selected genes were subsequently verified by RT-qPCR and Western blot (WB) analyses.

Results

From the intersection of 7695 OSCC-related and 66 radiotherapy-related differentially expressed genes, we identified 39 radioresistance-associated candidate genes. Subsequent Cox and Lasso regression analyses revealed two key prognostic genes: TNFRSF19 (protective factor, HR < 1) and CCNA1 (risk factor, HR > 1). The risk prediction model demonstrated moderate but significant predictive performance, with AUCs of 0.62, 0.64, and 0.64 for 1-year, 3-year, and 5-year survival, respectively. Single-cell analysis revealed that macrophages represent a pivotal cell type mediating radioresistance. Pseudotime trajectory analysis showed that TNFRSF19 expression increased during macrophage maturation, promoting anti-tumor polarization, while CCNA1 expression decreased, facilitating functional differentiation. RT-qPCR revealed a dose-dependent increase in TNFRSF19 mRNA and a concomitant decrease in CCNA1 mRNA with escalating radiation, which was corroborated at the protein level by Western blotting.

Conclusion

TNFRSF19 and CCNA1 serve as critical regulators of radioresistance in OSCC, exerting their effects through modulation of macrophage differentiation and function. These findings provide novel biomarkers for predicting radiotherapy response and potential therapeutic targets for synergistic radiosensitization strategies.
目的寻找口腔鳞状细胞癌(OSCC)放射耐药相关的关键候选基因,阐明其调控机制和分子通路。方法本研究将TCGA-OSCC和GEO数据库的大量转录组学数据与单细胞RNA测序(scRNA-seq)数据相结合。通过差异表达分析、蛋白相互作用(PPI)网络分析和Cox和Lasso回归模型确定关键预后基因。进行单细胞分析以验证基因表达模式和细胞机制。随后通过RT-qPCR和Western blot (WB)分析验证所选基因的表达水平。结果从7695个oscc相关基因和66个放疗相关差异表达基因的交集中,我们鉴定出39个放射耐药相关候选基因。随后的Cox和Lasso回归分析揭示了两个关键的预后基因:TNFRSF19(保护因素,HR < 1)和CCNA1(危险因素,HR < 1)。该风险预测模型表现出中等但显著的预测效果,1年、3年和5年生存率的auc分别为0.62、0.64和0.64。单细胞分析显示巨噬细胞是介导辐射抗性的关键细胞类型。伪时间轨迹分析显示,在巨噬细胞成熟过程中,TNFRSF19表达增加,促进抗肿瘤极化,而CCNA1表达减少,促进功能分化。RT-qPCR显示,随着辐射的增加,TNFRSF19 mRNA呈剂量依赖性增加,CCNA1 mRNA随之减少,Western blotting在蛋白水平上证实了这一点。结论tnfrsf19和CCNA1通过调节巨噬细胞的分化和功能,在OSCC中发挥重要的辐射耐药调节作用。这些发现为预测放射治疗反应和协同放射增敏策略的潜在治疗靶点提供了新的生物标志物。
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引用次数: 0
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Journal of Radiation Research and Applied Sciences
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