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Concentration dependent gamma degradation of inulin in aqueous phase and its impact on antioxidant capacity and probiotic fermentability 菊粉在水相中浓度依赖性γ降解及其对抗氧化能力和益生菌发酵能力的影响
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-20 DOI: 10.1016/j.jrras.2025.102131
Sudesh , Sahayog N. Jamdar
Inulin is a water soluble, non-digestible polysaccharide with diverse food and clinical applications depending on its degree of polymerization. This study investigated the effect of inulin concentration on its gamma-induced depolymerization in aqueous phase by analysing changes in relative viscosity (ηr), solubility (%), total reducing sugar (TRS), free fructose (Ff) content, and •OH radical scavenging activity. The extent of inulin degradation in aqueous solution was influenced by both irradiation dose and sample concentration. Degradation increased with irradiation dose, while concentration and degree of degradation were in inverse relationship. The level of degradation as a result of molecular fragmentation was confirmed by thin layer chromatography (TLC) and gel permeation chromatography (GPC). FT-IR spectral characterization of unirradiated and irradiated samples revealed no significant changes in peak profiles. Furthermore, concentration-dependent degradation was evaluated for its impact on antioxidant capacity and probiotic fermentability. Inulin irradiated at lower concentrations exhibited significantly higher (p < 0.05) ABTS and DPPH radical scavenging activity and probiotic fermentability than samples irradiated at higher concentrations; specifically, at 25 kGy, inulin irradiated in a 5 % (w/v) aqueous system showed ∼3.5-fold higher antioxidant activity and a ∼2.5-log increase in probiotic fermentability compared to the 60 % (w/v) system.
菊粉是一种水溶性、不可消化的多糖,其聚合程度决定了其在食品和临床中的应用。本研究通过分析菊粉相对粘度(ηr)、溶解度(%)、总还原糖(TRS)、游离果糖(Ff)含量和•OH自由基清除活性的变化,研究了菊粉浓度对其在水相中γ -诱导解聚的影响。菊粉在水溶液中的降解程度受辐照剂量和样品浓度的影响。降解程度随辐照剂量增加而增加,辐照浓度与降解程度呈反比关系。通过薄层色谱(TLC)和凝胶渗透色谱(GPC)证实了分子破碎导致的降解程度。未辐照和辐照样品的FT-IR光谱表征显示峰谱没有显著变化。此外,还评估了浓度依赖性降解对益生菌抗氧化能力和发酵能力的影响。低浓度菊粉对ABTS和DPPH自由基的清除能力和益生菌的发酵能力显著高于高浓度菊粉;具体来说,在25 kGy时,与60% (w/v)的水体系相比,5% (w/v)的菊粉的抗氧化活性提高了约3.5倍,益生菌的发酵能力提高了约2.5倍。
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引用次数: 0
Engineering software-based evaluation of pelvic floor muscle defects in anterior vaginal wall prolapse 基于工程软件的阴道前壁脱垂盆底肌肉缺损的评价
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-20 DOI: 10.1016/j.jrras.2025.102119
Lifan Shen , Huijun Bai

Objective

To assess the relationship between pelvic floor muscle morphology and anterior vaginal wall prolapse using MRI 3D reconstruction and engineering software.

Methods

This study conducted a retrospective analysis involving 68 patients diagnosed with anterior vaginal wall prolapse. Magnetic resonance images (MRI) of the relevant pelvic floor muscles from these patients were utilized for three-dimensional reconstruction using Mimics. Subsequently, the IGS models generated by Geomagic Wrap were employed for material property assignment and analysis within SolidWorks. The muscle models were then transformed into visual simulation entities, facilitating the derivation of metrics such as, volume, and surface area of the muscles associated with anterior vaginal wall prolapse. This methodology allowed for a direct assessment of muscle tissue defects and symmetry.

Results

In patients with anterior vaginal wall prolapse, statistically significant differences (P < 0.05) were observed in the volume, and maximum thickness of the bulbocavernosus muscle relative to the POP-Q grading of anterior vaginal wall prolapse. Whether there was damage to the obturator internus, ischiocavernosus, levator ani muscle, external urethral sphincter, and external anal sphincter muscles was statistically significant in relation to anterior vaginal wall prolapse (P < 0.05). Symmetry of the ischiocavernosus and levator ani muscle also showed statistical significance concerning anterior vaginal wall prolapse (P < 0.05). Factors related to the level of anterior vaginal wall prolapse included the maximum thickness of the bulbocavernosus muscle (OR = 0.005719), damage to the ischiocavernosus muscle (OR = 0.084754), damage to the levator ani muscle (OR = 0.083995), damage to the external urethral sphincter (OR = 0.005917), and damage to the external anal sphincter (OR = 0.004091) (P < 0.05).

Conclusion

Utilizing engineering software and 3D reconstruction to create muscle models offers an impartial and three-dimensional depiction of the morphological alterations in pelvic floor muscles, along with their connection to anterior vaginal wall prolapse. This can help predict and manage the potential impacts on patients.
目的应用MRI三维重建和工程软件研究盆底肌肉形态与阴道前壁脱垂的关系。方法回顾性分析68例阴道前壁脱垂患者的临床资料。这些患者的相关盆底肌肉的磁共振图像(MRI)被利用Mimics进行三维重建。随后,利用Geomagic Wrap生成的IGS模型在SolidWorks中进行材料属性分配和分析。然后将肌肉模型转换为视觉模拟实体,方便推导与阴道前壁脱垂相关的肌肉的体积和表面积等指标。这种方法允许直接评估肌肉组织缺陷和对称性。结果阴道前壁脱垂患者的球海绵体肌体积、最大厚度相对于阴道前壁脱垂的POP-Q分级,差异有统计学意义(P < 0.05)。是否有闭孔内肌、坐骨海威肌、提肛肌、尿道外括约肌、肛门外括约肌受损与阴道前壁脱垂有统计学意义(P < 0.05)。坐骨海绵体和肛提肌的对称性在阴道前壁脱垂方面也有统计学意义(P < 0.05)。影响阴道前壁脱垂程度的因素包括球海绵体肌最大厚度(OR = 0.005719)、坐骨海绵体肌损伤(OR = 0.084754)、提肛肌损伤(OR = 0.083995)、尿道外括约肌损伤(OR = 0.005917)、肛门外括约肌损伤(OR = 0.004091) (P < 0.05)。结论利用工程软件和三维重建技术创建的肌肉模型可以公正、三维地描述骨盆底肌肉的形态学改变,以及它们与阴道前壁脱垂的联系。这有助于预测和管理对患者的潜在影响。
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引用次数: 0
CT and MRI measurement of the femoral anterior tangent for the rotational reference axis of femoral prostheses 股骨假体旋转参考轴的股骨前切线的CT和MRI测量
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-20 DOI: 10.1016/j.jrras.2025.102130
Haibo Liang, Haiquan Deng, Jianchao Sun, Kaitian Wu, Shuzhen Li

Background

This study aims to evaluate the value of the femoral anterior tangent (FAT) as a reference axis for the rotation of femoral prostheses on computed tomography (CT) and magnetic resonance imaging (MRI).

Methods

We retrospectively included 66 patients (83 knees) with primary knee osteoarthritis. FAT, clinical transepicondylar axis (cTEA), surgical transepicondylar axis (sTEA), anterior-posterior axis (APA), perpendicular axis to the posterior-anterior axis of the femoral condyles (pAPA), and posterior condylar axis (PCA) were measured on CT and MRI. The rotation angles of FAT, pAPA, and PCA relative to cTEA and sTEA were measured on the same layer. Patients were further subgrouped based on Kellgren-Lawrence (K-L) grade and gender to assess the variance of different rotational reference axes.

Results

The mean values of FAT/cTEA, FAT/sTEA, and pAPA/cTEA measured on CT were significantly lower, indicating greater internal rotation, than those measured on MRI (P < 0.05). There were no statistical differences between FAT/sTEA, FAT/cTEA, pAPA/cTEA, and PCA/cTEA among genders (P > 0.05). The CT measurement of pAPA/cTEA in K-L grade 3 knees was −1.1° ± 3.7°, significantly higher than in K-L grade 4 knees (P = 0.036). FAT/cTEA, FAT/sTEA, and PCA/cTEA demonstrated higher stability in various subgroups of knee osteoarthritis.

Conclusion

The rotational angles of femoral prostheses measured by CT for FAT and other reference axes show increased internal rotation compared to MRI measurements. Both measurement methods provide relatively stable values for FAT measurements. Clinicians should be cautious of the numerical differences between MRI and CT measurements in clinical applications and should consider modality-specificreference values for pre-operative planning.
本研究旨在评估股骨前切线(FAT)在计算机断层扫描(CT)和磁共振成像(MRI)上作为股骨假体旋转参考轴的价值。方法回顾性分析66例原发性膝骨关节炎患者(83个膝关节)。在CT和MRI上测量FAT、临床经髁突轴(cTEA)、手术经髁突轴(sTEA)、前后轴(APA)、股髁前后轴垂直轴(pAPA)和后髁轴(PCA)。在同一层上测量FAT、pAPA和PCA相对于cTEA和sTEA的旋转角度。进一步根据Kellgren-Lawrence (K-L)分级和性别对患者进行亚组,以评估不同旋转参考轴的方差。结果CT测量的FAT/cTEA、FAT/sTEA、pAPA/cTEA均值较MRI测量值明显降低,内旋较大(P < 0.05)。FAT/sTEA、FAT/cTEA、pAPA/cTEA、PCA/cTEA在性别间差异无统计学意义(P > 0.05)。K-L 3级膝关节的CT测量pAPA/cTEA为- 1.1°±3.7°,显著高于K-L 4级膝关节(P = 0.036)。FAT/cTEA、FAT/sTEA和PCA/cTEA在膝关节骨关节炎的各个亚组中表现出更高的稳定性。结论通过CT测量股骨假体的FAT和其他参考轴的旋转角度,与MRI测量结果相比,内旋增加。两种测量方法都为FAT测量提供了相对稳定的值。临床医生在临床应用中应注意MRI和CT测量值之间的数值差异,并应考虑特定模式的术前计划参考值。
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引用次数: 0
Radiological safety assessment of packaged bottle drinking water in India – Age dependent analysis 印度包装瓶装饮用水的放射性安全评价——年龄相关分析
IF 2.5 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES Pub Date : 2025-12-19 DOI: 10.1016/j.jrras.2025.102128
Mahasin Gazi , Arindam Kumar Naskar , Argha Deb
Radioactive radon (222Rn) concentrations in 121 different brands of packaged bottle drinking water (PBDW) samples from different states of India have been assessed in the present study using a potable AlphaGUARD radon monitor along with AlphaGUARD aqua kit. Among the collected samples, the production sites of 72 number of PBDW samples are different places of West Bengal and the remaining 49 samples are different places of other different states of India. Thus, assessing the radon levels in different brands of packaged drinking water that are accessed from most parts of India gives a general picture of the 222Rn concentrations in packaged bottled drinking water throughout India.
Measured radon concentration levels vary between 0.19 and 5.81 Bq/l with an average value of 1.36 Bq/l. Radon concentration of no sample has exceeded the WHO, IAEA and EU Commission prescribed reference level of 100 Bq/l or even USEPA's proposed MCL (11.11 Bq/l).
The measured radon concentrations of the collected samples manifest no significant correlation with either Total Dissolved Solids (TDS) or pH values of the samples.
Annual effective dose (AED) due to radon from these bottled drinking water for three age groups namely infants, children and adults are found to vary between 0.66 and 20.00 μSv/y with a mean of 4.68 ± 0.29 μSv/y, 0.82–25.00 μSv/y with a mean of 5.84 ± 0.36 μSv/y and 0.73–22.30 μSv/y with a mean of 5.21 ± 0.32 μSv/y respectively. Assessment of dose shows that total annual effective dose to the children is the highest among the age groups. No sample has exceeded the WHO, ICRP and the EU commission proposed reference dose limit of 100 μSv/y.
本研究使用便携式AlphaGUARD氡监测仪和AlphaGUARD aqua试剂盒对来自印度不同邦的121种不同品牌包装瓶装饮用水(PBDW)样品中的放射性氡(222Rn)浓度进行了评估。在收集到的样品中,72个PBDW样品的生产地点位于西孟加拉邦的不同地方,其余49个样品位于印度其他不同邦的不同地方。因此,对从印度大部分地区获取的不同品牌包装饮用水中的氡水平进行评估,可以大致了解印度各地包装瓶装饮用水中222Rn的浓度。测得的氡浓度水平在0.19至5.81 Bq/l之间,平均值为1.36 Bq/l。没有样品的氡浓度超过世界卫生组织、国际原子能机构和欧盟委员会规定的100 Bq/l的参考水平,甚至超过美国环保署提出的MCL (11.11 Bq/l)。所采集样品的氡浓度与样品的总溶解固形物(TDS)或pH值均无显著相关性。对婴幼儿、儿童和成人3个年龄组的氡年有效剂量分别为0.66 ~ 20.00 μSv/y,平均值为4.68±0.29 μSv/y, 0.82 ~ 25.00 μSv/y,平均值为5.84±0.36 μSv/y, 0.73 ~ 22.30 μSv/y,平均值为5.21±0.32 μSv/y。剂量评估表明,儿童的年总有效剂量在各年龄组中最高。没有样品超过世界卫生组织、ICRP和欧盟委员会提出的100 μSv/y的参考剂量限值。
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引用次数: 0
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。
{"title":"Isocitrate dehydrogenase 2 promotes tumor progression and glycolysis in cervical squamous cell carcinoma by activating the HIF1A signaling pathway","authors":"Xiaojuan Liu ,&nbsp;Lisha Shu ,&nbsp;Huiying Zhang","doi":"10.1016/j.jrras.2025.102113","DOIUrl":"10.1016/j.jrras.2025.102113","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":16920,"journal":{"name":"Journal of Radiation Research and Applied Sciences","volume":"19 1","pages":"Article 102113"},"PeriodicalIF":2.5,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145787134","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
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Journal of Radiation Research and Applied Sciences
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