Biochimica et biophysica acta. General subjects最新文献

Novel pilot study on plasma metabolites and biomarkers in a rat model of silica-induced lung inflammation and fibrosis 关于二氧化硅诱发肺部炎症和纤维化大鼠模型中血浆代谢物和生物标志物的新型试验研究。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-22 DOI: 10.1016/j.bbagen.2024.130729

Silica-induced lung damage may be associated with changes in distinct metabolites potentially serving as biomarkers. Due to the lack of metabolomic data from animal models, this pilot study aimed to evaluate changes in markers of inflammation and fibrosis, as well as plasma metabolites in rats at 14 and 28 days after silica instillation.

Adult male Wistar rats were administered a single oropharyngeal intratracheal dose of silica suspension or sterile saline in controls. Selected markers of inflammation, oxidative stress, fibrosis, and cell counts in blood and bronchoalveolar lavage fluid have been evaluated. Finally, plasma metabolites were detected using a targeted metabolomics approach with an MxP® Quant 500 kit.

Silica instillation induced noticeable inflammatory, oxidative, and fibrotic changes in lung tissue within the first 14 days. During the next two weeks, the shifts in some markers were further accentuated. After exposure to silica, the metabolomic analysis identified significant changes in metabolites associated with lipid metabolism, biogenic amines, amino acid derivatives, carboxylic acids, bile acids, putrescine, glycosylceramides, and acylcarnitines.

This pilot study provides initial evidence that significant alterations in plasma metabolite profiles accompany silica-induced lung injury in rats. These findings suggest a possible systemic impact, particularly on lipid metabolism, and indicate the urgent need for a deeper understanding of the metabolic reprogramming associated with silica-induced lung injury to pave the way for the discovery of novel biomarkers.

二氧化硅引起的肺损伤可能与可能作为生物标志物的不同代谢物的变化有关。由于缺乏动物模型的代谢组学数据，本试验性研究旨在评估大鼠在灌入二氧化硅后 14 天和 28 天的炎症和纤维化标志物以及血浆代谢物的变化。成年雄性 Wistar 大鼠经口咽部气管内单次灌入二氧化硅悬浮液或无菌生理盐水（对照组）。对血液和支气管肺泡灌洗液中的部分炎症、氧化应激、纤维化和细胞计数指标进行了评估。最后，使用 MxP® Quant 500 试剂盒以靶向代谢组学方法检测了血浆代谢物。在最初的 14 天内，二氧化硅灌入会在肺组织中引起明显的炎症、氧化和纤维化变化。在接下来的两周内，一些标记物的变化进一步加剧。暴露于二氧化硅后，代谢组分析发现与脂质代谢、生物胺、氨基酸衍生物、羧酸、胆汁酸、腐胺、糖基甘油三酯和酰基肉碱相关的代谢物发生了显著变化。这项试验性研究提供了初步证据，证明在二氧化硅诱发大鼠肺损伤的同时，血浆代谢物谱也发生了显著变化。这些研究结果表明，二氧化硅诱发的肺损伤可能会产生系统性影响，尤其是对脂质代谢的影响，并表明迫切需要更深入地了解与二氧化硅诱发的肺损伤相关的代谢重编程，从而为发现新型生物标记物铺平道路。

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引用次数: 0

A comparative study of bioenergetic metabolism on mammary epithelial cells from humans and Göttingen Minipigs 人类和哥廷根小型猪乳腺上皮细胞生物能代谢比较研究

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-20 DOI: 10.1016/j.bbagen.2024.130728

Mammary epithelial cells (MECs) of humans (h) and Göttingen Minipigs (mp) were analyzed to compare their ability to perform ATP production by oxidative phosphorylation and glycolysis. The ATP production under basal and stressor situations highlights the same metabolic potential of both primary cell lines. However, quantitively the ATP production rate of hMECs was higher than mpMECs. Conversely, oxidative cell respiration in mpMECs exploits a maximum respiratory capacity to support pathophysiological circumstances or stress conditions that could require an excessive effort of cell metabolism. Since mpMECs primarily utilize an oxidative metabolism similar to hMECs, the metabolic characterization conducted allows us to confirm that mpMECs represent a potential alternative cellular model in the translational medicine approach.

对人类（h）和哥廷根小型猪（mp）的乳腺上皮细胞（MECs）进行了分析，以比较它们通过氧化磷酸化和糖酵解产生 ATP 的能力。在基础和应激情况下产生的 ATP 突出显示了两种原代细胞系相同的代谢潜力。然而，从数量上看，hMECs 的 ATP 生成率高于 mpMECs。相反，mpMECs 的氧化细胞呼吸利用了最大呼吸能力，以支持可能需要细胞代谢过度努力的病理生理情况或应激条件。由于 mpMECs 主要利用与 hMECs 相似的氧化新陈代谢，因此我们通过新陈代谢表征确认 mpMECs 是转化医学方法中一种潜在的替代细胞模型。

引用次数: 0

Effect of modification of siRNA molecules delivered with aminopropylsilanol nanoparticles on suppression of A/H5N1 virus in cell culture 用氨基丙基硅烷醇纳米颗粒递送的 siRNA 分子的修饰对抑制细胞培养中的 A/H5N1 病毒的影响。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-20 DOI: 10.1016/j.bbagen.2024.130727

The application of siRNAs as antiviral agents is limited by several obstacles including their poor penetration into cells and instability in biological media. To overcome these problems, we used non-agglomerated aminopropylsilanol nanoparticles (NP) to deliver siRNA into cells. All studied siRNAs had identical nucleoside sequences comprising phosphodiester or phosphorothioate (PS) internucleotide groups and the 2’-OMe and/or 2’-F groups in nucleoside units at different positions of RNA. The siRNA molecules were attached to NP, thus forming the NP-siRNA nanocomplexes. We studied the effect of siRNA modification in the nanocomplexes on suppressing the highly pathogenic influenza A/H5N1 virus replication. The results demonstrated that all siRNA-containing nanocomplexes inhibited the replication of the A/H5N1 virus by 1–3 orders of magnitude. The nanocomplexes containing partially modified siRNAs exhibited the most pronounced inhibition with an efficacy of 900-fold. This result was achieved by using siRNA consisting of the canonical 19-bp RNA duplex with the 3′-dTdT dangling ends, with the antisense strand in this duplex being protected from endonucleases (one U^MeA site within the strand). The additional modifications of siRNA reduce their antiviral activity. Promising sense strands for loading into the RISC complex are likely to be phosphodiester sequences that contain dTdT at the 3′ end (such as S₄) to be protected against exonucleases. The sense strands of this type can probably be the most suitable for designing siRNAs as therapeutic agents. The proposed NP-siRNA nanocomplexes that consisted of low toxic and non-agglomerated aminopropylsilanol nanoparticles and siRNA molecules could be hopeful agents for gene silencing.

siRNAs 作为抗病毒药物的应用受到几个障碍的限制，包括其对细胞的穿透性差和在生物介质中的不稳定性。为了克服这些问题，我们使用了非凝集的氨基丙基硅烷醇纳米颗粒（NP）将 siRNA 送入细胞。所有研究的 siRNA 都具有相同的核苷序列，包括磷酸二酯或硫代磷酸酯（PS）核苷酸间基团，以及位于 RNA 不同位置的核苷单位中的 2'-OMe 和/或 2'-F 基团。siRNA 分子附着在 NP 上，从而形成 NP-siRNA 纳米复合物。我们研究了纳米复合物中的 siRNA 修饰对抑制高致病性甲型 H5N1 流感病毒复制的影响。结果表明，所有含有 siRNA 的纳米复合物对 A/H5N1 病毒的复制都有 1-3 个数量级的抑制作用。其中，含有部分修饰 siRNA 的纳米复合物的抑制效果最明显，达到了 900 倍。这一结果是通过使用由带有 3'-dTdT 悬挂末端的 19-bp RNA 双链组成的 siRNA 实现的，该双链中的反义链受到内切酶的保护（链中有一个 UMeA 位点）。siRNA 的额外修饰会降低其抗病毒活性。有望装入 RISC 复合物的有义链可能是在 3' 端含有 dTdT 的磷酸二酯序列（如 S4），以防止外切酶。这种类型的有义链可能最适合设计成 siRNA 作为治疗药物。拟议的 NP-siRNA 纳米复合物由低毒、无凝集的氨基丙基硅醇纳米颗粒和 siRNA 分子组成，有望成为基因沉默的药物。

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引用次数: 0

Evaluating cholinesterases inhibition by BAC and DDAC biocides: A combined experimental and theoretical approach 评估 BAC 和 DDAC 生物杀灭剂对胆碱酯酶的抑制作用：实验与理论相结合的方法

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-19 DOI: 10.1016/j.bbagen.2024.130726

Disinfectant biocides are chemicals that are heavily used for disinfection purposes in households, hospitals, and agrifood industry. The most common type of biocides are quaternary ammonium compounds (QAs), notably benzalkonium chloride (BAC) and didecyldimethylammonium chloride (DDAC), which have been shown to inhibit cholinesterases. This study aims to evaluate the effect of these biocides towards different cholinesterases using both enzyme inhibition and molecular docking experiments. Acetylcholinesterase (AChE) from Drosophila melanogaster (DM-AChE), Electrophorus electricus (EE-AChE), bovine erythrocytes (BE-AChE) and butyrylcholinesterase from horse serum (BChE) were selected for this study. Using a colorimetric assay, all these enzymes were shown to be inhibited in a competitive form by both biocides, BAC and DDAC, with the exception of DM-AChE, which was inhibited in a non-competitive manner by BAC. Molecular docking experiments enabled to identify structural determinants involved in the different modes of inhibition observed. More particularly, our results suggest that non-competitive inhibition of DM-AChE by BAC could be related to the binding of the inhibitor into a more extended active site compared to other cholinesterases.

消毒杀菌剂是家庭、医院和农业食品工业中大量用于消毒的化学品。最常见的杀菌剂是季铵盐化合物（QAs），特别是苯扎氯铵（BAC）和十二烷基二甲基氯化铵（DDAC），它们已被证明能抑制胆碱酯酶。本研究旨在通过酶抑制和分子对接实验来评估这些杀菌剂对不同胆碱酯酶的影响。本研究选择了黑腹果蝇的乙酰胆碱酯酶（AChE）（DM-AChE）、电蝇的乙酰胆碱酯酶（EE-AChE）、牛红细胞的乙酰胆碱酯酶（BE-AChE）和马血清的丁酰胆碱酯酶（BChE）。通过比色法，所有这些酶都被 BAC 和 DDAC 这两种生物杀灭剂以竞争形式抑制，但 DM-AChE 除外，它被 BAC 以非竞争方式抑制。通过分子对接实验，我们确定了与所观察到的不同抑制模式有关的结构决定因素。特别是，我们的研究结果表明，BAC 对 DM-AChE 的非竞争性抑制作用可能与抑制剂结合到比其他胆碱酯酶更扩展的活性位点有关。

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引用次数: 0

Photosensitizing metal–organic framework nanoparticles combined with tumor-sensitization strategies can enhance the phototherapeutic effect upon medullary thyroid carcinoma 光敏金属有机框架纳米粒子与肿瘤增敏策略相结合，可增强对甲状腺髓样癌的光疗效果。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-19 DOI: 10.1016/j.bbagen.2024.130725

Photodynamic therapy (PDT) utilizing metal-organic frameworks (MOFs) has developed as a new and efficacious treatment for malignant tumors located on the surface of the human body. In order to achieve more effective PDT treatment outcomes, the traditional method has been to increase the intensity of the laser irradiation, but this approach can easily lead to tissue burns. In this study, we developed a new type of nanoparticle, F68-PKI@PCN224, aims to achieve effective PDT upon medullary thyroid carcinoma (MTC) which is an uncommon form of thyroid cancer that originates in the parafollicular cells of the thyroid and the therapeutic outlook for patients with MTC remains unsatisfactory. F68-PKI@PCN224 combines the antitumor features of PDT with mammalian target of rapamycin (mTOR) inhibitor PKI-587 (PKI). The tumor sensitization, slow release, and pH response features of F68-PKI@PCN224 was demonstrated by a series of in vitro and in vivo experiments / assays. F68-PKI@PCN224 achieved the long-term activation and slow releasing of PKI and TCPP in MTC tumor tissues. During the process of generating PDT effects, F68-PKI@PCN224 enhanced the tumor's sensitivity to PDT, direct laser irradiation of MTC cells or subcutaneous tumor tissues. As a result, low-dose phototherapy achieves a higher anti-tumor effect upon F68-PKI@PCN224 compared with TCPP. This study reveals the synergistic effect between tumor sensitization by mTOR inhibitor and PDT and initially unveils the mechanism of action of these nanoparticles.

利用金属有机框架（MOFs）的光动力疗法（PDT）已发展成为一种治疗人体表面恶性肿瘤的新型有效疗法。为了实现更有效的 PDT 治疗效果，传统方法是增加激光照射强度，但这种方法很容易导致组织灼伤。甲状腺髓样癌是一种不常见的甲状腺癌，起源于甲状腺滤泡旁细胞，其治疗前景仍不令人满意。F68-PKI@PCN224将PDT的抗肿瘤特性与哺乳动物雷帕霉素靶点（mTOR）抑制剂PKI-587（PKI）相结合。一系列体内外实验证明了 F68-PKI@PCN224 的肿瘤敏化、缓释和 pH 响应特性。F68-PKI@PCN224 在 MTC 肿瘤组织中实现了 PKI 和 TCPP 的长期激活和缓释。在产生PDT效应的过程中，F68-PKI@PCN224增强了肿瘤对PDT、直接激光照射MTC细胞或皮下肿瘤组织的敏感性。因此，与 TCPP 相比，F68-PKI@PCN224 的低剂量光疗具有更高的抗肿瘤效果。这项研究揭示了 mTOR 抑制剂对肿瘤的增敏作用与光疗之间的协同效应，并初步揭示了这些纳米粒子的作用机制。

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引用次数: 0

Electroporation-derived melanoma extracellular particles activate fibroblasts 电穿孔衍生的黑色素瘤细胞外颗粒可激活成纤维细胞。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130723

Although the pulse electric field (PEF) has been used in electrochemotherapy (ECT) for many years, the kinetics and profile of extracellular particles (EPs) released as a result of reversible electroporation have yet to be studied. It also needs to be clarified whether and how the profile of released EPs depends on the parameters of the applied PEF. The presented studies investigated the effect of EPs released from human melanoma cells after various parameters of reversible electroporation on markers indicating EP-mediated transformation of normal fibroblasts into tumor-associated fibroblasts. The expression levels of the vascular cell adhesion molecule-1 (VCAM-1) and changes in the expression of phosphor-histone H3 (pHH3), a biomarker specific for cells in mitosis, cell viability, and the migration capacity of the studied fibroblast cells, were analyzed. EPs were isolated from two commercial malignant melanoma cell lines previously subjected to reversible electroporation. Human primary fibroblasts (HPFs) were selected for EPs exposure. It was observed that after incubation with melanoma-derived EPs, HPFs showed differences in cell viability, migration capacity, VCAM-1, pHH3, and N-cadherin expression, depending on PEF parameters and the grade of melanoma cells. This study highlights that small extracellular particles (sEPs) from cancer cells can promote metastasis by carrying specific signals that lead to the upregulation of molecules like FAK, MMP-9, and N-cadherin in recipient cells.

尽管脉冲电场（PEF）已在电化学疗法（ECT）中应用多年，但对可逆电穿孔释放的细胞外微粒（EPs）的动力学和概况仍有待研究。此外，还需要澄清释放的 EPs 的形态是否以及如何取决于所应用的 PEF 参数。本研究调查了人类黑色素瘤细胞在不同参数的可逆电穿孔后释放的 EPs 对显示 EP 介导的正常成纤维细胞向肿瘤相关成纤维细胞转化的标志物的影响。研究人员分析了血管细胞粘附分子-1（VCAM-1）的表达水平、有丝分裂期细胞特异性生物标志物磷组蛋白 H3（pHH3）的表达变化、细胞活力以及所研究成纤维细胞的迁移能力。EPs是从两种商业化恶性黑色素瘤细胞系中分离出来的，这些细胞系曾接受过可逆电穿孔。人类原代成纤维细胞（HPFs）被选中用于暴露于 EPs。结果表明，在与黑色素瘤衍生EPs培养后，HPFs在细胞活力、迁移能力、VCAM-1、pHH3和N-cadherin表达方面表现出差异，这取决于PEF参数和黑色素瘤细胞的等级。这项研究强调，癌细胞的小细胞外颗粒（sEPs）可通过携带特定信号促进转移，这些信号可导致受体细胞中FAK、MMP-9和N-cadherin等分子的上调。

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引用次数: 0

Personalized biocorona as disease biomarker: The challenges and opportunities 作为疾病生物标志物的个性化生物传感器：挑战与机遇。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130724

It is well known that when nanoparticles interact with biological fluids, a layer of proteins and biological components forms on them. This layer may alter the biological fate and efficiency of the nanomaterial. Recent studies have shown that illness states have a major impact on the structure of the biocorona, sometimes referred to as the “personalized protein corona.” Physiological factors like illness, which impact the proteome and metabolome pattern and result in conformational changes in proteins, give rise to this structure of discrimination in biocorona decoration. Improving the efficiency of precise platforms for developing new molecular biomarkers for accurate illness diagnosis is vitally necessary. The biocorona pattern's discrimination may be a diagnostic tool for designing biosensors. As a result, in this review, we summarize the most current studies on the relationship between physiological conditions and the variety of biocorona patterns that influence the biological responses of nanosystems. The biocorona pattern's flexibility may provide new research directions and be utilized to create nanoparticle-based therapeutic and diagnostic products suited to certain physiological situations.

众所周知，当纳米粒子与生物液体相互作用时，会在其上形成一层蛋白质和生物成分层。这一层可能会改变纳米材料的生物学命运和效率。最近的研究表明，疾病状态对生物冠层（有时称为 "个性化蛋白质冠层"）的结构有重大影响。疾病等生理因素会影响蛋白质组和代谢组模式，导致蛋白质构象发生变化，从而在生物电晕装饰中产生这种辨别结构。提高精确平台的效率，为准确诊断疾病开发新的分子生物标志物是非常必要的。生物电晕图案的辨别力可以作为设计生物传感器的诊断工具。因此，在这篇综述中，我们总结了有关生理条件与影响纳米系统生物反应的各种生物电晕模式之间关系的最新研究。生物电晕模式的灵活性可能会为我们提供新的研究方向，并可利用它创造出适合特定生理情况的基于纳米粒子的治疗和诊断产品。

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引用次数: 0

FAHFA promotes intracellular calcium signaling via activating the fat taste receptor, CD36 and Src protein kinases in mice taste bud cells FAHFA 通过激活小鼠味蕾细胞中的脂肪味觉受体、CD36 和 Src 蛋白激酶促进细胞内钙信号转导。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130722

Two lipid sensors, CD36 and GPR120, are crucial for the orosensory detection of fat taste and for mediating fat preference. However, the mechanism by which endogenous lipid (FAHFA) binds to CD36 to initiate intracellular signaling remains unexplained. Hence, the primary objective of this study is to investigate the binding mechanism of FAHFA to CD36 and its role in isolated mouse taste bud cells (mTBCs). The Schrodinger platform was used to assess the molecular dynamics of protein and ligand interactions, and an in vitro experiment was used to validate the findings. Based on the docking score of the ligand, the molecular mechanistic activities of the targeted complexes, CD36–5-POHSA (−8.2 kcal/mol), were investigated using the dynamic simulation. In comparison to linoleic acid (LA), POHSA rapidly increased [Ca²⁺]i via acting on CD36, and 5-POHSA treatment in mTBCs activated src-kinase at 20 μM. CD36 siRNA transfection in TBCs downregulate the CD36 protein expression as well as [Ca²⁺]i flux. This study suggests that 5-POHSA may help combat taste abnormalities and the adverse effects of obesity by binding to the lingual CD36 receptor and activating the tongue-brain axis.

CD36和GPR120这两个脂质传感器对于脂肪味道的口感检测和脂肪偏好的介导至关重要。然而，内源性脂质（FAHFA）与 CD36 结合以启动细胞内信号传导的机制仍未解释。因此，本研究的主要目的是探讨 FAHFA 与 CD36 的结合机制及其在离体小鼠味蕾细胞（mTBCs）中的作用。本研究利用薛定谔平台评估了蛋白质和配体相互作用的分子动力学，并利用体外实验验证了研究结果。根据配体的对接得分，利用动态模拟研究了目标复合物 CD36-5-POHSA（-8.2 kcal/mol）的分子机理活性。与亚油酸（LA）相比，POHSA 可通过作用于 CD36 快速增加[Ca2+]i，5-POHSA 在 20 μM 时可激活 mTBC 中的 src 激酶。转染 CD36 siRNA 的 TBCs 可下调 CD36 蛋白表达和[Ca2+]i 通量。这项研究表明，5-POHSA 可通过与舌 CD36 受体结合并激活舌脑轴，帮助对抗味觉异常和肥胖的不良影响。

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引用次数: 0

VotePLMs-AFP: Identification of antifreeze proteins using transformer-embedding features and ensemble learning VotePLMs-AFP：利用变压器嵌入特征和集合学习识别抗冻蛋白

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-18 DOI: 10.1016/j.bbagen.2024.130721

Antifreeze proteins (AFPs) are a unique class of biomolecules capable of protecting other proteins, cell membranes, and cellular structures within organisms from damage caused by freezing conditions. Given the significance of AFPs in various domains such as biotechnology, agriculture, and medicine, several machine learning methods have been developed to identify AFPs. However, due to the complexity and diversity of AFPs, the predictive performance of existing methods is limited. Therefore, there is an urgent need to develop an efficient and rapid computational method for accurately predicting AFPs. In this study, we proposed a novel predictor based on transformer-embedding features and ensemble learning for the identification of AFPs, termed VotePLMs-AFP. Firstly, three types of feature descriptors were extracted from pre-trained protein language models (PLMs) during the feature extraction process. Subsequently, we analyzed six combinations generated by these three embeddings to explore the optimal feature set, which was input into the soft voting-based ensemble learning classifier for the identification of AFPs. Finally, we evaluated the model on the two benchmark datasets. The experimental results show that our model achieves high prediction accuracy in 10-fold cross-validation (CV) and independent set testing, outperforming existing state-of-the-art methods. Therefore, our model could serve as an effective tool for predicting AFPs.

抗冻蛋白（AFPs）是一类独特的生物大分子，能够保护生物体内的其他蛋白质、细胞膜和细胞结构免受冷冻条件的破坏。鉴于抗冻蛋白在生物技术、农业和医学等各个领域的重要性，人们开发了多种机器学习方法来识别抗冻蛋白。然而，由于 AFP 的复杂性和多样性，现有方法的预测性能有限。因此，迫切需要开发一种高效、快速的计算方法来准确预测 AFPs。在这项研究中，我们提出了一种基于变压器嵌入特征和集合学习的新型预测方法，用于识别 AFP，称为 VotePLMs-AFP。首先，在特征提取过程中，我们从预先训练好的蛋白质语言模型（PLMs）中提取了三种类型的特征描述符。随后，我们分析了由这三种嵌入产生的六种组合，以探索最佳特征集，并将其输入基于软投票的集合学习分类器，用于识别 AFP。最后，我们在两个基准数据集上对模型进行了评估。实验结果表明，我们的模型在 10 倍交叉验证（CV）和独立集测试中都达到了很高的预测准确率，优于现有的先进方法。因此，我们的模型可以作为预测 AFP 的有效工具。

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引用次数: 0

Supplementation with ions enhances the efficiency of nucleic acid delivery with cell-penetrating peptides 补充离子可提高细胞穿透肽递送核酸的效率。

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects

Pub Date : 2024-10-05 DOI: 10.1016/j.bbagen.2024.130719

The successful delivery of therapeutic nucleic acids (NAs) into eukaryotic cells is essential for numerous biomedical applications, including gene therapy, gene silencing, and genome editing. Cell-penetrating peptides (CPPs) have claimed significant attention as delivery vehicles due to their inherent ability to penetrate cellular membranes and efficiently transport cargo, including NAs, into the cells. However, further optimization and a deeper understanding of underlying mechanisms are necessary for such transfection methods. Previous studies have demonstrated that Ca²⁺ ions can significantly enhance NA delivery efficiency when included in transfection media or CPP/NA nanoparticles during preparation. Similar effects have been observed for Mg²⁺, but the impact of other ions in this context has not been thoroughly investigated. In this study, we supplemented the CPP/NA formulations with various inorganic biocompatible ions by introducing solutions of the respective salts to colloidal nanoparticles at the preparation stage. Our results indicated that supplementing the CPP/NA formulations with certain salt solutions enhanced the biological effect achieved with NAs while also influencing nanoparticle size, surface charge, complexation stability, and, to some extent, the internalization route. Our findings offer valuable insights for optimizing the formation of CPP nanoparticles to improve NA delivery efficiency.

成功地将治疗性核酸（NAs）输送到真核细胞中对于基因治疗、基因沉默和基因组编辑等众多生物医学应用至关重要。细胞穿透肽（CPPs）具有穿透细胞膜并将货物（包括核酸）高效转运到细胞内的固有能力，因此作为转运载体备受关注。然而，这种转染方法还需要进一步优化和深入了解其潜在机制。先前的研究表明，在转染介质或 CPP/NA 纳米颗粒制备过程中加入 Ca2+ 离子可显著提高 NA 的输送效率。在 Mg2+ 中也观察到了类似的效果，但其他离子在这方面的影响尚未得到深入研究。在本研究中，我们通过在制备阶段向胶体纳米粒子中引入相应的盐溶液，在 CPP/NA 配方中补充了各种无机生物相容性离子。结果表明，在 CPP/NA 制剂中添加某些盐溶液可增强 NAs 的生物效应，同时还可影响纳米粒子的大小、表面电荷、复合物稳定性，并在一定程度上影响内化途径。我们的研究结果为优化 CPP 纳米粒子的形成以提高 NA 的递送效率提供了宝贵的见解。

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引用次数: 0