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Accurate prediction of anticancer peptides using a stacking ensemble of convolutional and transformer models with conjoint sequence representations 使用卷积和变压器模型的叠加集合与联合序列表示精确预测抗癌肽
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-14 DOI: 10.1016/j.compbiomed.2026.111463
Huynh Anh Duy , Phurinut Khampasri , Pimmada Janthanet , Patlissa Pattiyamongkhonkul , Tarapong Srisongkram
We present a high-performance predictive framework for anticancer peptide (ACP) identification, based on a stacking ensemble learning approach that synergistically combines convolutional neural networks and transformer models using a random forest as a meta-classifier. This architecture is driven by conjoint sequence representations that integrate both one-hot encoding and pre-trained evolutionary scale modeling embeddings, enabling the extraction of complementary local and global features from peptide sequences. Our proposed model achieved a robust accuracy of 88.9% on the primary ACP data set, while maintaining competitive or superior performance across multiple external benchmark data sets, with accuracies ranging from 83.2% to 95.2%, highlighting its strong generalization capability on par with the state-of-the-art models. To demonstrate translational relevance, the model was applied to a curated set of clinically approved and candidate ACPs, producing probabilistic scores to support experimental prioritization. To further enhance model interpretability, SHapley Additive exPlanations analysis was employed, revealing lysine as a consistently influential residue, alongside other positively charged and hydrophobic amino acids. These findings not only corroborate known mechanistic insights into ACP-membrane interactions but also highlight the utility of model-derived feature importance in guiding peptide design. Taken together, this work introduces a robust, interpretable, and generalizable approach for computational ACP prediction, offering valuable implications for peptide-based anticancer drug discovery. To enhance the accessibility and translational potential of our model, we developed an interactive web-based prediction tool, named ACPredictor, for the identification of ACPs. This platform is freely available at https://acpredictor.streamlit.app/.
我们提出了一种用于抗癌肽(ACP)识别的高性能预测框架,该框架基于堆叠集成学习方法,该方法将卷积神经网络和变压器模型协同结合,使用随机森林作为元分类器。该结构由整合了单热编码和预训练进化尺度建模嵌入的联合序列表示驱动,能够从肽序列中提取互补的局部和全局特征。我们提出的模型在主要ACP数据集上实现了88.9%的鲁棒准确率,同时在多个外部基准数据集上保持了竞争或优越的性能,准确率范围从83.2%到95.2%,突出了其与最先进模型相当的强大泛化能力。为了证明翻译相关性,该模型被应用于一组经过筛选的临床批准和候选acp,产生概率分数以支持实验优先级。为了进一步提高模型的可解释性,采用了SHapley加性解释分析,揭示赖氨酸与其他带正电和疏水的氨基酸一起始终是有影响的残基。这些发现不仅证实了acp -膜相互作用的已知机制见解,而且强调了模型衍生特征在指导肽设计中的重要性。综上所述,这项工作为计算ACP预测引入了一种强大的、可解释的和可推广的方法,为基于肽的抗癌药物的发现提供了有价值的意义。为了提高我们模型的可及性和转化潜力,我们开发了一个交互式的基于网络的预测工具,名为ACPredictor,用于识别acp。该平台可在https://acpredictor.streamlit.app/免费获得。
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引用次数: 0
Mechano-electric feedback reduces the occurrence of delayed-afterdepolarization-driven focal activity 机电反馈减少了延迟后去极化驱动的焦点活动的发生。
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.compbiomed.2025.111436
Navneet Roshan, Rahul Pandit
Delayed afterdepolarizations (DADs), which occur during the diastolic phase of a cardiomyocyte action potential (AP), are frequently observed under specific pathophysiological conditions. The synchronization of DAD-capable myocytes can effectively overcome the inherent source-sink mismatch with adjacent normal myocytes, so it is an important mechanism for the genesis of premature ventricular contractions (PVCs). Our study elucidates the role of mechano-electrical feedback in modulating this critical source-sink requirement and its interplay with diffusional anisotropy in cardiac tissue. We combine the ten Tusscher-Panfilov 06 (TP06) electrophysiological model for human ventricular myocytes with cardiac-tissue-mechanics models and account for spontaneous calcium releases (SCRs) and the randomness associated with these and with the disordered arrangement of DAD myocytes in a clump. Our work leads to a quantification of the time dependence of the intracellular cytosolic calcium transient Cai and the active-contraction ratio λo, without and with SCRs and shows explicitly how the parameter gspon, which controls the strength of the SCRs, affects DADs and λo. We then illustrate the spatiotemporal evolution of the PVCs in the presence of domain deformation and a clump of DAD-capable myocytes. In a cable-type domain we demonstrate how contraction and elongation of the domain, the coupling interval of the DADs with the previous AP, and the width of the probability distribution function (PDF) of the coupling interval influence the source-size requirement for the formation of PVCs. We then extend our cable results to two dimensions (2D) by calculating the effect of the mechano-electric feedback on the origin and evolution of DAD-induced PVCs in 2D tissue. Our work leads to the following insights on the interplay of mechanical deformation and electrophysiology in DAD-induced PVCs: (1): mechano-electrical feedback markedly reduces the source requirement, which we quantify by the size of a clump of DAD-myocytes; (2): an extended coupling interval of DADs, relative to the preceding AP, reduces the source requirement; (3): sparse distribution of DAD-myocytes in a clump and the distribution in their coupling intervals, along with mechano-electric feedback, reduces the chances of the DAD-induced PVCs; (4): this suppression of PVCs is more pronounced in 2D than in 1D domains.
延迟去极化(DADs)发生在心肌细胞动作电位(AP)舒张期,在特定的病理生理条件下经常观察到。具有dad能力的肌细胞的同步化可以有效地克服与相邻正常肌细胞固有的源池失配,是室性早搏发生的重要机制。我们的研究阐明了机电反馈在调节这一关键源库需求中的作用及其与心脏组织扩散各向异性的相互作用。我们将人类心室肌细胞的十个Tusscher-Panfilov 06 (TP06)电生理模型与心脏组织力学模型相结合,并解释了自发钙释放(SCRs)以及与这些和DAD肌细胞在团块中无序排列相关的随机性。我们的工作导致了细胞内胞质钙瞬态Cai和主动收缩比λo的时间依赖性的量化,没有和有SCRs,并明确显示了参数gspon,控制SCRs的强度,如何影响DADs和λo。然后,我们说明了在结构域变形和一团具有dad能力的肌细胞的存在下,室性早搏的时空演变。在电缆型结构域中,我们展示了结构域的收缩和伸长、dad与前一个AP的耦合间隔以及耦合间隔的概率分布函数(PDF)的宽度如何影响pvc形成的源尺寸要求。然后,我们通过计算机电反馈对二维组织中dad诱导的室性早搏的起源和演变的影响,将我们的电缆结果扩展到二维(2D)。我们的工作导致了以下关于机械变形和电生理在dad诱导的室性早搏中的相互作用的见解:(1):机电反馈显着降低了源需求,我们通过dad肌细胞团的大小来量化;(2):相对于之前的AP,延长了dad的耦合间隔,减少了对源的需求;(3): dad -肌细胞的稀疏分布及其耦合间隔的分布,以及机电反馈,减少了dad -肌细胞诱发早搏的机会;(4):这种对室性早搏的抑制在二维结构域中比在一维结构域中更为明显。
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引用次数: 0
Unraveling the link between beta cell dysfunction, insulin imbalance, and neurodegeneration in Alzheimer’s disease 揭示阿尔茨海默病中β细胞功能障碍、胰岛素失衡和神经变性之间的联系。
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-05 DOI: 10.1016/j.compbiomed.2025.111402
Sevak Ram Sahu , Parimita Roy , Ranjit Kumar Upadhyay
The onset and progression of Alzheimer’s disease (AD) have long been strongly associated with obesity and diabetes caused by hyperglycemia, which leads to beta-cell dysfunction and insulin imbalance. This imbalance promotes the release of cytokines and activation of microglia, which play a crucial role in the production of amyloid-beta and neurofibrillary tangles. In this context, we formulate a delayed reaction-diffusion model of obesity induced AD to examine the dynamical behavior of the above biological hypothesis. We investigate the existence and uniqueness of solutions, stability of equilibria (local and global), sensitivity analysis as well as the occurrence of Hopf bifurcation and Turing instability. The findings highlight the importance of insulin diffusion rate, insulin secretion delay, glucose, and beta cell in developing AD and its effective control strategies. Spatiotemporal dynamics such as patchy patterns exhibit how Aβ accumulates and spreads in the brain. A higher growth rate of beta cell supports sufficient insulin secretion, which can delay the progression of AD. In contrast, when beta cell growth is impaired, even a slight delay in secretion can accelerate disease progression. This study reveals that maintaining high-calorie food to support sufficient growth of beta cell and insulin for a long-term healthy lifestyle along with targeted anti-amyloid approaches can remarkably delay Alzheimer’s progression.
长期以来,阿尔茨海默病(AD)的发生和发展与高血糖引起的肥胖和糖尿病密切相关,高血糖导致β细胞功能障碍和胰岛素失衡。这种不平衡促进了细胞因子的释放和小胶质细胞的激活,它们在淀粉样蛋白和神经原纤维缠结的产生中起着至关重要的作用。在此背景下,我们建立了肥胖诱导AD的延迟反应-扩散模型来检验上述生物学假设的动力学行为。我们研究了解的存在唯一性、平衡点(局部和全局)的稳定性、灵敏度分析以及Hopf分岔和图灵不稳定性的发生。这些发现强调了胰岛素扩散速率、胰岛素分泌延迟、葡萄糖和β细胞在AD发生及其有效控制策略中的重要性。时空动态,如斑块模式,展示了Aβ如何在大脑中积累和扩散。较高的β细胞生长速率支持足够的胰岛素分泌,从而延缓AD的进展。相反,当β细胞生长受损时,即使分泌的轻微延迟也会加速疾病的进展。这项研究表明,维持高热量食物来支持β细胞和胰岛素的足够生长,长期健康的生活方式,以及有针对性的抗淀粉样蛋白方法可以显著延缓阿尔茨海默氏症的进展。
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引用次数: 0
Unravelling the structural impact of progesterone receptor mutations in myoma and progesterone intolerance through computational modeling 通过计算模型揭示肌瘤和黄体酮不耐受中黄体酮受体突变的结构影响
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-15 DOI: 10.1016/j.compbiomed.2026.111476
F. Saritha , R. Aswath Kumar , K.V. Dileep
Progesterone (P4) is a steroid hormone involved in the regulation of female reproductive functions. The endogenous progesterone receptor (PR), a member of the nuclear receptor family of ligand-dependent transcription regulators responsible for P4 action in the body through the ‘ligand binding domain’ (LBD). PR isoforms, PR-A and PR-B, are encoded by a single gene, PGR and variations in this gene can disrupt cellular signaling. In the current study, putative disease-causing mutations on PR has been identified through computationally and its mechanistic effects were explored using structural bioinformatics tools. Studies suggested that 11 of 66 missense variants (within the LBD) induce structural destabilization and were identified as potentially deleterious. Our ensemble docking suggested that these variations have a limited impact on P4 binding, however they significantly disrupt the binding of co-activators as evident by the protein-peptide docking. The binding of co-activators to the PR is the determining factor for the P4 signaling. Finally, based on the free energy of binding, we proposed two variations such as R869H and C798Y could cause myoma and progesterone tolerance conditions respectively. These findings were further validated through the use of allostery predictions. Our results reveal distinct mechanisms by which PR mutations modulate receptor function, laying the framework for future mechanistic studies and therapeutic development for PR-associated reproductive disorders.
黄体酮(P4)是一种类固醇激素,参与调节女性生殖功能。内源性孕激素受体(PR)是核受体家族的一员,是配体依赖性转录调节因子,通过“配体结合域”(LBD)在体内负责P4的作用。PR亚型PR- a和PR- b由单个基因PGR编码,该基因的变异可以破坏细胞信号传导。在目前的研究中,通过计算确定了PR上可能的致病突变,并利用结构生物信息学工具探索了其机制作用。研究表明,66个错义变异中有11个(在LBD内)诱导结构不稳定,并被确定为潜在的有害变异。我们的集合对接表明,这些变异对P4结合的影响有限,但它们显著破坏了共激活物的结合,这一点从蛋白-肽对接中可以看出。共激活剂与PR的结合是P4信号转导的决定因素。最后,基于结合自由能,我们提出了R869H和C798Y两种变异分别可引起肌瘤和黄体酮耐受条件。这些发现通过使用变构预测得到进一步验证。我们的研究结果揭示了PR突变调节受体功能的独特机制,为PR相关生殖疾病的未来机制研究和治疗开发奠定了框架。
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引用次数: 0
Reliable leukemia detection via transfer-enhanced Bayesian CNNs 可靠的白血病检测传输增强贝叶斯cnn
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-03 DOI: 10.1016/j.compbiomed.2025.111419
Xhesina Hita , Farrukh Javed , Stefano Lodi
Accurate and early detection of Acute Lymphoblastic Leukemia (ALL) is critical for timely intervention and improved patient outcomes. However, the development of reliable deep learning models for hematological image analysis is challenged by limited data availability, dataset bias, and the need for trustworthy predictions in clinical settings. In this study, we propose a Bayesian deep learning framework that integrates transfer learning, data augmentation, and uncertainty quantification for robust classification of leukemic and healthy lymphocytes from peripheral blood smear images. Three widely used convolutional neural network architectures, InceptionV3, VGG16, and ResNet50, pretrained on ImageNet are fine-tuned on the ALL-IDB2 dataset and extended with Monte Carlo dropout to enable Bayesian inference. Model performance is evaluated using 10-fold cross-validation on both original and augmented datasets, with accuracy, sensitivity, specificity, Youden’s index, and Brier score used as evaluation metrics. Among the evaluated models, VGG16 demonstrates the most consistent improvements under data augmentation, achieving the highest accuracy (98.65%±0.09), Youden’s index (0.97±0.001) and Brier score (0.035±0.010), while ResNet50 shows strong but more moderate gains. In contrast, InceptionV3 exhibits limited sensitivity to augmentation and comparatively lower robustness. Beyond average predictive performance, Bayesian uncertainty analysis reveals that misclassifications and borderline predictions are consistently associated with elevated predictive entropy and mutual information. Saliency map inspection further indicates that high-uncertainty cases correspond to diffuse or non-localized attention patterns, suggesting reliance on spurious contextual features rather than stable morphological cues. These findings highlight the importance of uncertainty-aware predictions for identifying cases that may require expert pathological review. Overall, the proposed framework combines strong diagnostic performance with interpretable uncertainty estimates, supporting its role as a transparent and clinically trustworthy tool for AI-assisted leukemia screening.
准确和早期发现急性淋巴细胞白血病(ALL)对于及时干预和改善患者预后至关重要。然而,开发用于血液学图像分析的可靠深度学习模型受到数据可用性有限、数据集偏差以及临床环境中对可信预测的需求的挑战。在这项研究中,我们提出了一个贝叶斯深度学习框架,该框架集成了迁移学习、数据增强和不确定性量化,用于从外周血涂片图像中稳健地分类白血病和健康淋巴细胞。三种广泛使用的卷积神经网络架构,InceptionV3, VGG16和ResNet50,在ImageNet上进行预训练,在ALL-IDB2数据集上进行微调,并使用蒙特卡罗dropout进行扩展,以实现贝叶斯推理。对原始数据集和增强数据集使用10倍交叉验证来评估模型的性能,以准确性、灵敏度、特异性、约登指数和Brier评分作为评估指标。在评估的模型中,VGG16在数据增强下表现出最一致的改进,达到最高的准确率(98.65%±0.09),约登指数(0.97±0.001)和Brier评分(0.035±0.010),而ResNet50表现出强劲但较为温和的增长。相反,InceptionV3对增强的敏感性有限,鲁棒性相对较低。除了平均预测性能之外,贝叶斯不确定性分析表明,错误分类和边缘预测始终与预测熵和互信息的升高有关。显著性图检查进一步表明,高不确定性案例对应于分散或非局部的注意模式,表明依赖于虚假的上下文特征,而不是稳定的形态线索。这些发现强调了不确定性预测对于识别可能需要专家病理检查的病例的重要性。总体而言,所提出的框架结合了强大的诊断性能和可解释的不确定性估计,支持其作为人工智能辅助白血病筛查的透明和临床可靠工具的作用。
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引用次数: 0
In-silico and In-vitro role of chimeric peptide on the impact of nsSNPs in human Cannabinoid receptors 1 and 2 嵌合肽对人大麻素受体1和2中非单核苷酸多态性影响的实验和体外研究
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-07 DOI: 10.1016/j.compbiomed.2026.111451
Jerine Peter Simon , Huiming Bao , Zhanyu Niu , Hongyang Man , Shouliang Dong
Cannabinoid receptors 1 and 2 (CNR1 and CNR2) play an important role in the endocannabinoid system and intracellular pathways. Their beneficial effects became destroyed in the event of some mutation. Identifying protective drugs for mutation is highly necessary to eliminate its destruction. The research aims to understand the role of chimeric peptides in CNR1 and CNR2 nsSNPs. The research objectives are to find destructive nsSNPs through in-silico prediction and protein-only state molecular dynamics simulation. To understand the role of chimeric peptides on interaction with nsSNPs through docking analysis and protein-ligand state molecular dynamics simulation. To validate in-silico findings through in-vitro cell expression experiments. The research methods involved 36 in-silico online prediction tools, simulation for 100 ns, 29 trajectory analysis modules, three docking programs, and western blotting techniques. Four CNR1 and six CNR2 nsSNPs were shortlisted as destructive nsSNPs using in-silico tools. Further, CNR1 N134T and CNR2 I298N nsSNPs were shortlisted as highly destructive nsSNPs using simulation and docking analysis. Beneficial peptides were shortlisted using docking analysis and simulation with wild type. This research found that the chimeric peptide MP-13 has the best binding affinity and dynamics properties with wild-type and nsSNPs. It also almost restores dynamics properties and improves binding affinity in nsSNPs. It is most effective in influencing CNR1 and CNR2 signaling responses despite nsSNPs. Based on in-silico and in-vitro analysis, the research concludes that MP-13 has the strongest effect on CNR1 and CNR2 nsSNPs. The workflow of the present research is represented in a graphical illustration.
大麻素受体1和2 (CNR1和CNR2)在内源性大麻素系统和细胞内通路中发挥重要作用。一旦发生突变,它们的有益作用就被破坏了。为了消除突变的破坏,确定突变的保护药物是非常必要的。本研究旨在了解嵌合肽在CNR1和CNR2 nssnp中的作用。研究目标是通过计算机预测和蛋白状态分子动力学模拟,寻找具有破坏性的非单核苷酸多态性。通过对接分析和蛋白质-配体状态分子动力学模拟,了解嵌合肽在与nssnp相互作用中的作用。通过体外细胞表达实验验证计算机上的发现。研究方法包括36个在线预测工具、100 ns模拟、29个轨迹分析模块、3个对接程序和western blotting技术。4个CNR1和6个CNR2 nsSNPs被筛选为破坏性nsSNPs。此外,通过模拟和对接分析,CNR1 N134T和CNR2 I298N nssnp被确定为高破坏性nssnp。通过与野生型的对接分析和模拟筛选出有益肽。本研究发现,嵌合肽MP-13与野生型和非单核苷酸多态性具有最佳的结合亲和力和动力学特性。它还几乎恢复了nssnp的动力学特性,并提高了其结合亲和力。它在影响CNR1和CNR2信号应答方面最为有效,尽管存在nssnp。基于芯片和体外分析,本研究认为MP-13对CNR1和CNR2的nssnp影响最大。本研究的工作流程以图形说明。
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引用次数: 0
Automating prostate biopsy guidance: A robust CNN approach for non-rigid 3D/3D MR-TRUS image registration 自动化前列腺活检指导:非刚性3D/3D MR-TRUS图像配准的鲁棒CNN方法
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.compbiomed.2025.111423
Thi Thao Ho , Clément Beitone , Jocelyne Troccaz , Sandrine Voros
Fusing transrectal ultrasound (TRUS) and magnetic resonance (MR) images has significantly improved the accuracy of prostate cancer detection during targeted biopsies. However, automatic MR-TRUS registration remains challenging due to the large anatomical and appearance differences between the two imaging modalities. This study introduces a fully automatic, weakly supervised deep learning (DL) approach for predicting dense displacement fields (DDFs) between 3D MR and 3D TRUS images without requiring segmentation images. The proposed method consists of two main stages: (1) a dl-based preprocessing step that aligns the prostate centroids of the MR and TRUS images to improve initialization, and (2) a UNet-inspired registration network (RegResUNet) combined with a spatial transformer layer (STL) that directly predicts voxel-level DDFs from the aligned 3D input images. The network is trained using weak supervision based on anatomical masks, enabling accurate registration without ground truth DDFs. Experimental results demonstrate that the proposed method achieves substantial improvements over rigid baseline registration, with an average surface registration error (SRE) of 0.97 ± 0.85 mm and an average Dice similarity coefficient (DSC) of 0.93 ± 0.02. Notably, the proposed network outperforms several state-of-the-art non-rigid registration models while maintaining computational efficiency. The whole pipeline eliminates the need for intermediate manual and time-consuming segmentation steps. The automatic and robust capabilities of the proposed approach, combined with its short inference time, highlight its potential for clinical use in prostate cancer interventions, reducing human factors, ensuring consistent results, and contributing to improved patient comfort by minimizing procedure time.
融合经直肠超声(TRUS)和磁共振(MR)图像在靶向活检中显著提高了前列腺癌检测的准确性。然而,由于两种成像方式之间存在巨大的解剖和外观差异,自动MR-TRUS配准仍然具有挑战性。本研究引入了一种全自动、弱监督深度学习(DL)方法,用于预测3D MR和3D TRUS图像之间的密集位移场(ddf),而不需要分割图像。提出的方法包括两个主要阶段:(1)基于dl的预处理步骤,对MR和TRUS图像的前列腺质心进行对齐,以改善初始化;(2)基于unet的配准网络(RegResUNet)结合空间转换层(STL),直接从对齐的3D输入图像中预测体素级ddf。该网络使用基于解剖掩模的弱监督进行训练,实现了准确的配准,而不需要ground truth ddf。实验结果表明,与刚性基线配准相比,该方法取得了显著的改进,平均表面配准误差(SRE)为0.97±0.85 mm,平均Dice相似系数(DSC)为0.93±0.02。值得注意的是,所提出的网络在保持计算效率的同时优于几种最先进的非刚性配准模型。整个管道消除了中间手工和耗时的分割步骤的需要。所提出的方法的自动和强大的能力,加上其短的推断时间,突出了其在前列腺癌干预的临床应用潜力,减少了人为因素,确保了结果的一致性,并通过减少手术时间来提高患者的舒适度。
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引用次数: 0
Molecular characterization of palmitoylation in prostate cancer reveals KIFC2 as a prognostic biomarker and potential therapeutic target 前列腺癌中棕榈酰化的分子特征揭示了KIFC2作为预后生物标志物和潜在的治疗靶点。
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.compbiomed.2026.111450
Liang Huang , Shusuan Jiang , Fuhua Zeng , Gongqian Zeng , Hong Shan
Protein palmitoylation, a reversible post-translational lipid modification, has been implicated in regulating cancer cell signaling and progression; however, its role in prostate cancer (PCa) remains unclear. In this study, we comprehensively analyzed palmitoylation-related genes (PRGs) in PCa by integrating bulk transcriptomic, single-cell RNA sequencing, and spatial transcriptomic datasets. Unsupervised consensus clustering based on PRG expression identified two molecular subtypes with distinct prognoses, immune infiltration profiles, and pathway activities. Differential expression and weighted gene co-expression network analyses revealed five key feature genes, among which KIFC2 was highly expressed in tumor cells and correlated with poor clinical outcomes. The KIFC2 was predominantly enriched in high-grade adenocarcinoma regions. Functional experiments demonstrated that silencing KIFC2 significantly inhibited proliferation and promoted apoptosis in PC3 and DU145 prostate cancer cell lines. Additionally, high KIFC2 expression was associated with increased cell cycle progression and oncogenic signaling pathways, including KRAS and PI3K-AKT. Collectively, these results suggest that palmitoylation and KIFC2 play critical roles in PCa progression and may serve as promising biomarkers and therapeutic targets.
蛋白棕榈酰化是一种可逆的翻译后脂质修饰,与调节癌细胞信号传导和进展有关;然而,其在前列腺癌(PCa)中的作用尚不清楚。在这项研究中,我们通过整合大量转录组学、单细胞RNA测序和空间转录组学数据集,全面分析了PCa中棕榈酰化相关基因(PRGs)。基于PRG表达的无监督共识聚类鉴定出两种具有不同预后、免疫浸润谱和途径活性的分子亚型。差异表达和加权基因共表达网络分析揭示了5个关键特征基因,其中KIFC2在肿瘤细胞中高表达,与临床预后差相关。KIFC2主要富集于高级别腺癌区域。功能实验表明,沉默KIFC2可显著抑制PC3和DU145前列腺癌细胞的增殖,促进细胞凋亡。此外,KIFC2的高表达与细胞周期进程和致癌信号通路的增加有关,包括KRAS和PI3K-AKT。总的来说,这些结果表明棕榈酰化和KIFC2在PCa的进展中起着关键作用,可能作为有希望的生物标志物和治疗靶点。
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引用次数: 0
Photoplethysmography imaging reveals frequency-specific microvascular responses to histamine in human skin 光体积脉搏成像揭示了人类皮肤对组胺的频率特异性微血管反应。
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-10 DOI: 10.1016/j.compbiomed.2026.111464
Stefan Borik , Miriam Zemanikova , Patrik Procka , Jan Seleng , Michal Labuda , Aymen A. Alian

Background

Skin prick testing (SPT) remains the gold standard for allergy diagnostics, yet it relies on subjective assessment of wheal size and provides limited insight into the underlying vascular mechanisms. In this study, the histamine positive control within the SPT framework was used as a standardized model to characterize frequency-specific microvascular responses using photoplethysmography imaging (PPGI).

Methods

PPGI data were analyzed from 16 healthy volunteers who underwent SPT with histamine and saline control sites. Vascular oscillations were analyzed in the cardiac (0.6–2.5 Hz), respiratory (0.15–0.6 Hz), and myogenic (0.05–0.15 Hz) frequency bands using 1-min segments to characterize time-resolved changes across the post-application stages.

Results

A significant suppression of myogenic oscillations was detected at the histamine site, with an 80 % reduction observed 10–15 min post-application and a 60 % reduction at 15–20 min relative to baseline. Respiratory-band energy showed no significant changes during the experiment. No significant changes were observed at the negative control sites. Skin blood-volume-oscillation maps supported these observations, showing localized reduction of myogenic vasomotion in the affected areas.

Conclusion

Histamine-induced allergic responses produce localized, frequency-specific alterations in cutaneous blood flow, characterized by a sustained suppression of myogenic oscillations accompanied with flare-related hyperemia. These results support the hypothesis of “vascular locking,” wherein vasodilation attenuates smooth muscle contractility, and highlight the potential of PPGI to enhance the diagnostic resolution of allergy testing by capturing vascular dynamics across multiple frequency bands.
背景:皮肤点刺试验(SPT)仍然是过敏诊断的金标准,但它依赖于对车轮大小的主观评估,对潜在血管机制的了解有限。在这项研究中,SPT框架内的组胺阳性对照被用作标准化模型,使用光容积脉搏波成像(PPGI)来表征频率特异性微血管反应。方法:对16名接受组胺和生理盐水对照部位SPT的健康志愿者的PPGI数据进行分析。血管振荡在心脏(0.6-2.5 Hz)、呼吸(0.15-0.6 Hz)和肌源性(0.05-0.15 Hz)频段进行分析,使用1分钟片段来表征应用后各阶段的时间分辨变化。结果:在组胺部位检测到明显的肌原性振荡抑制,应用后10-15分钟观察到80%的减少,15-20分钟相对于基线减少60%。呼吸带能量在实验过程中无明显变化。阴性对照部位未见明显变化。皮肤血容量振荡图支持这些观察,显示局部肌源性血管舒缩在受影响的区域减少。结论:组胺诱导的过敏反应会产生局部的、频率特异性的皮肤血流改变,其特征是肌源性振荡的持续抑制伴随着与耀斑相关的充血。这些结果支持“血管锁定”假说,其中血管舒张减弱平滑肌收缩力,并强调PPGI通过捕获多个频带的血管动力学来提高过敏测试的诊断分辨率的潜力。
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引用次数: 0
Designing of a multi-epitope vaccine targeting enterovirus D68: An integrated immunoinformatic and reverse vaccinology approach 针对肠病毒D68的多表位疫苗的设计:免疫信息学和反向疫苗学的综合方法
IF 6.3 2区 医学 Q1 BIOLOGY Pub Date : 2026-02-01 Epub Date: 2026-01-02 DOI: 10.1016/j.compbiomed.2025.111433
Hailah M. Almohaimeed , Amany I. Almars , Nada Alkhorayef , Ahmed M. Basri , Fayez Alsulaimani , Muhammad Shahbaz , Fahad M. Alshabrmi , Sarfaraz Alam , Tahir Muhammad , Muhammad Shahab
Enterovirus D68 (EV-D68) is an enterovirus known for causing respiratory infections, as well as flaccid myelitis, meningitis and encephalitis. Despite the efforts, no licensed vaccine against EV-D68 is currently available. Vaccine development efforts are ongoing; however, the process is complex and requires extensive clinical validation. In contrast, immunoinformatic is a rapidly expanding area with the potential to significantly influence the therapeutic interventions and vaccine development for infectious diseases. Herein, immunoinformatic and reverse vaccinology strategies were utilized to design a multi-epitope vaccine construct targeting EV-D68 virus. In this connection, three virulent proteins were selected for analysis based on their immunogenic characteristics. Further, B-cells and T-cells epitopes were predicted and connected through suitable linkers and adjuvant. The predicted T-cell epitopes within the vaccine construct exhibited a significant worldwide population coverage. Moreover, Robetta was utilized to predict the 3D structure of the vaccine construct. Subsequently the molecular docking simulation of construct was employed to study the molecular interactions by using Toll-like receptors as target proteins and further subjected to MD simulation. The results reveal the stability of the vaccine-receptor complex throughout the simulation. Finally, in silico cloning showed potential for the predicted vaccine within the Escherichia coli expression system. These findings provide valuable insights that may guide subsequent experimental studies and contribute meaningfully to the early phases of EV-D68 vaccine research and development. By streamlining candidate selection and optimizing design parameters, our findings holds promise for accelerating the transition from computational predictions to effective vaccine formulations.
肠病毒D68 (EV-D68)是一种已知可引起呼吸道感染以及弛缓性脊髓炎、脑膜炎和脑炎的肠道病毒。尽管做出了努力,但目前尚无针对EV-D68的许可疫苗。正在进行疫苗开发工作;然而,这个过程是复杂的,需要广泛的临床验证。相比之下,免疫信息学是一个迅速发展的领域,有可能对传染病的治疗干预和疫苗开发产生重大影响。本研究利用免疫信息学和反向疫苗学策略设计了一种针对EV-D68病毒的多表位疫苗结构。在此基础上,选择了三种毒力蛋白进行免疫原性分析。进一步预测b细胞和t细胞表位,并通过合适的连接体和佐剂连接。在疫苗构建中预测的t细胞表位显示出显著的全球人口覆盖率。此外,利用Robetta预测疫苗结构的三维结构。随后采用构建体分子对接模拟,以toll样受体为靶蛋白,研究分子间相互作用,并进一步进行MD模拟。结果揭示了整个模拟过程中疫苗受体复合物的稳定性。最后,在硅克隆中显示了在大肠杆菌表达系统中预测疫苗的潜力。这些发现提供了有价值的见解,可以指导后续的实验研究,并对EV-D68疫苗研发的早期阶段做出有意义的贡献。通过简化候选物选择和优化设计参数,我们的发现有望加速从计算预测到有效疫苗配方的转变。
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Computers in biology and medicine
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