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Micro-/nano-structured flexible electronics for biomedical applications 用于生物医学应用的微/纳米结构柔性电子器件
Pub Date : 2023-06-01 DOI: 10.1016/j.bmt.2022.11.013
Yu Wang , Jiahui Guo , Dongyu Xu , Zhuxiao Gu , Yuanjin Zhao

Flexible electronics are attracting considerable attention due to their promising performance including conductivity, stain- or pressure-sensing performance, skin-affinity, flexibility, etc. In particular, the structural design has promoted their properties and brought advanced functions, which make them valuable in biomedical applications including health monitoring, therapeutic applications and implantable devices. Herein, a review on the recent progress of flexible electronics with micro-/nano-structures is provided, involving the manufacturing technologies and applications in biomedical fields. Following these two sections, remaining challenges and the perspectives on future directions are also proposed.

柔性电子产品因其具有良好的导电性、污渍或压力传感性能、皮肤亲和性、灵活性等性能而备受关注。特别是,结构设计提高了其性能并带来了先进的功能,这使其在生物医学应用中具有价值,包括健康监测、,治疗应用和植入式装置。本文综述了具有微/纳米结构的柔性电子器件的最新进展,包括制造技术和在生物医学领域的应用。在这两个部分之后,还提出了剩余的挑战和对未来方向的展望。
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引用次数: 3
Biomedical applications of Janus membrane Janus膜的生物医学应用
Pub Date : 2023-06-01 DOI: 10.1016/j.bmt.2022.11.003
Shutong Qian , Binfan Zhao , Jiayi Mao , Zhimo Liu , Qiuyu Zhao , Bolun Lu , Xiyuan Mao , Liucheng Zhang , Liying Cheng , Yuguang Zhang , Wenguo Cui , Xiaoming Sun

The traditional membrane with single structure cannot satisfy complex clinical applications. Inspired by lotus leaf, a novel structure Janus membrane has achieved more attention recently. Janus membrane is a membrane structure which has two faces with opposite properties. This special structure endows it with asymmetric surface wettability, which can provide an intrinsic driving force to transport along a specified direction, thus achieve unidirectional liquid transport and selective liquid separation. Janus membrane has a promising future, and has been widely used in chemical fields such as self-cleaning, oil/water separation, mist collection, and desalination, while less studied in biomedical field. In this review, the biomedical applications especially in different stages of wound healing process, current challenges in fabrication process and future perspectives of Janus membranes in practical applications under different Janus models, such as hemostasis, bone regeneration, blood cell isolation and gastric mycosal defect will be discussed. It is expected that this unique structure can provide a good therapy prospect in biomedical fields.

传统的单一结构的膜不能满足复杂的临床应用。受荷叶的启发,一种新型结构的Janus膜最近受到了更多的关注。Janus膜是一种具有两个性质相反的表面的膜结构。这种特殊的结构赋予了它不对称的表面润湿性,可以提供沿特定方向传输的内在驱动力,从而实现单向液体传输和选择性液体分离。Janus膜具有广阔的应用前景,已广泛应用于自清洁、油水分离、薄雾收集和脱盐等化学领域,而在生物医学领域的研究较少。在这篇综述中,将讨论Janus膜的生物医学应用,特别是在伤口愈合过程的不同阶段,目前在制造过程中面临的挑战,以及在不同Janus模型下的实际应用前景,如止血、骨再生、血细胞分离和胃分枝杆菌缺损。期望这种独特的结构能够在生物医学领域提供良好的治疗前景。
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引用次数: 5
Characterization of aggrephagy-related genes to predict the progression of liver fibrosis from multi-omics profiles 从多组学分析中预测肝纤维化进展的聚集相关基因特征
Pub Date : 2023-05-09 DOI: 10.1016/j.bmt.2023.04.001
Jing Chen , Zi-Cheng Zhou , Yang Yan , Shu-Zhen Wu , Tao Ma , Han Xuan , Ruo-Chun Wang , Chi-Yu Gu , Yi-Heng Liu , Qing-Qing Liu , Si-Jia Ge , Wei Huang , Cui-Hua Lu

Background

Liver fibrosis is recognized as a consequence of persistent liver damage. Hence, understanding the mechanisms of liver fibrosis could help patients reverse this process. Aggrephagy is a selective type of autophagy which is under study in various diseases. However, the investigation of aggrephagy in liver fibrosis has not been reported yet.

Methods

Five GEO databases were first batched into an integrated dataset by PCA analysis and facilitated for exploration of the aggrephagy-related genes. In addition, the diagnostic model under the aggrephagy-related genes was constructed by random forest. Then Western blot and immunofluorescence were employed in cells treated by autophagy-inhibitor Bafilomycin A1 to analyze whether the aggrephagy induced by liver fibrosis is necessary for aggregates degradation. Furthermore, the single cell data from GEO database and AUCell analysis functioned to detect the aggrephagy score. CellChat analysis compared the interaction strength and underlying receptor ligands between the different aggrephagy score groups. Furthermore, we used the monocle function to display the dynamic process from low aggrephagy score to high aggrephagy score groups. Finally, we used the consensus cluster to compare the clinical characteristics and underlying drug compounds under aggrephagy-score.

Results

First, we observed that aggrephagy score was much higher in the liver fibrosis group than in the normal group. Then our results showed that aggrephagy score was positively correlated with several metabolism pathways. In addition, aggrephagy related diagnostic model showed higher efficiency than other markers of liver fibrosis. Further experiments revealed that the removal of aggregates in liver fibrosis was depended on aggrephagy. We then observed that aggrephagy score and CFTR levels were dominantly located in hepatocytes from single-cell data. Moreover, the high aggrephagy-score group showed increased cell interaction strength, intercellular receptor-ligand signaling, and the transcription factor activity of HNF1B than the low aggrephagy-score groups. Hence, aggrephagy might be a promising target for liver fibrosis.

Conclusions

Our results showed that the aggrephagy score is a promising index for diagnosing liver fibrosis.

背景肝纤维化被认为是持续性肝损伤的结果。因此,了解肝纤维化的机制可以帮助患者逆转这一过程。自噬是一种选择性的自噬,在各种疾病中都有研究。然而,关于聚集蛋白聚集在肝纤维化中的研究还没有报道。方法采用主成分分析法,将5个GEO数据库组成一个完整的数据集,以便于对聚集性饥饿相关基因的探索。此外,利用随机森林法构建了聚集性食物相关基因的诊断模型。然后用Western印迹和免疫荧光法在自噬抑制剂巴氟霉素A1处理的细胞中分析肝纤维化诱导的聚集蛋白聚集是否是聚集体降解所必需的。此外,来自GEO数据库的单细胞数据和AUCell分析有助于检测聚集性抗原评分。CellChat分析比较了不同聚集性评分组之间的相互作用强度和潜在受体配体。此外,我们使用monocle函数来显示从低聚集性得分到高聚集性得分组的动态过程。最后,我们使用一致性聚类来比较聚集蛋白抗原评分下的临床特征和潜在药物化合物。结果首先,我们观察到肝纤维化组的聚集蛋白抗原得分远高于正常组。然后我们的结果表明,聚集蛋白的得分与几种代谢途径呈正相关。此外,聚集蛋白吞噬相关诊断模型显示出比其他肝纤维化标志物更高的效率。进一步的实验表明,肝纤维化中聚集物的去除取决于聚集物的重量。然后,我们从单细胞数据中观察到聚集蛋白聚集评分和CFTR水平主要位于肝细胞中。此外,与低聚集蛋白聚集性评分组相比,高聚集蛋白聚集度评分组显示出细胞相互作用强度、细胞间受体配体信号传导和HNF1B的转录因子活性增加。因此,聚集蛋白聚集可能是肝纤维化的一个有前景的靶点。结论aggrephagy评分是诊断肝纤维化的一个有前景的指标。
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引用次数: 0
Integrin-based prognostic model predicts survival, immunotherapy response, and drug sensitivity in gastric cancer 基于整合素的胃癌预后模型预测生存、免疫治疗反应和药物敏感性
Pub Date : 2023-05-03 DOI: 10.1016/j.bmt.2023.04.002
Yilin Hu , Yu Chen , Menglong Wu , Chenyu Qian , Junjie Chen , Kun Wang , Wanjiang Xue

Background

Extracellular matrix (ECM) acts as a physical barrier to tumors, resulting in the lysis or delay of drug delivery. Integrins (ITGs) are essential for tumor cell-ECM interactions. Thus, we established a novel prognostic model to predict overall survival, immunotherapy benefits, and therapeutic agents in gastric cancer (GC) based on ITGs-related ECM landscape.

Methods

Using the TCGA-STAD dataset, we studied the genetic and transcriptional changes of ITGs. We used a merged cohort for ITGs survival analysis and determined molecular pattern clusters using consensus unsupervised clustering methodology. We confirmed the distinct ECM landscape between constructed clusters by performing gene set variation and Kaplan-Meier analysis. We utilized prognostic differentially expressed genes between clusters to develop a prognostic model utilizing logistic least absolute shrinkage and selection operator cox regression analysis, followed by stepwise multivariate Cox analysis in the training dataset. The model was validated by receiver operating characteristic curves and Kaplan-Meier analysis in the testing dataset and seven validation datasets. We compared our model to 35 previously published models. To analyze immune infiltration, we used multiple algorithms, which were further confirmed by single-cell RNA-sequencing and fluorescent multiplex immunohistochemistry. We explored tumor mutation burden (TMB), microsatellite instability-high (MSI-H) grade, immunotherapy response, chemotherapy sensitivity, and clinical significance between the low-risk and high-risk groups. Finally, we assessed the risk score in five reported molecular subtypes.

Results

The two ITGs-related clusters were identified, and their ECM landscapes were distinct. The prognostic model was constructed and had shown stable performance in internal and external validation. In addition, our model outperformed 35 previously published models. High-risk patients had a bad prognostic ECM landscape, high stromal cell inflammation, a lower TMB, a lower MSI-H grade, a worse tumor stage, a worse response to immunotherapy, and less sensitivity to chemotherapy. In five reported molecular subtypes, the worse subtypes showed a higher risk score.

Conclusions

The prognostic model could be an effective and promising tool for predicting prognosis and therapy response in GC patients.

背景细胞外基质(ECM)作为肿瘤的物理屏障,导致药物释放的裂解或延迟。整合素(ITGs)是肿瘤细胞与ECM相互作用所必需的。因此,我们建立了一个新的预后模型,以基于ITGs相关ECM景观预测癌症(GC)的总体生存率、免疫疗法益处和治疗药物。方法利用TCGA-STAD数据集,研究ITG的遗传和转录变化。我们使用合并队列进行ITG生存分析,并使用一致无监督聚类方法确定分子模式聚类。我们通过进行基因集变异和Kaplan-Meier分析,证实了构建的聚类之间存在明显的ECM景观。我们利用聚类之间的预后差异表达基因,利用逻辑最小绝对收缩和选择算子cox回归分析,然后在训练数据集中进行逐步多元cox分析,开发了预后模型。在测试数据集和七个验证数据集中,通过受试者工作特性曲线和Kaplan-Meier分析对模型进行了验证。我们将我们的模型与之前发布的35个模型进行了比较。为了分析免疫浸润,我们使用了多种算法,通过单细胞RNA测序和荧光多重免疫组织化学进一步证实了这一点。我们探讨了低风险和高危人群的肿瘤突变负荷(TMB)、微卫星不稳定性高(MSI-H)分级、免疫治疗反应、化疗敏感性以及临床意义。最后,我们评估了五种已报道的分子亚型的风险评分。结果确定了两个ITG相关的聚类,并且它们的ECM景观是不同的。构建了预后模型,并在内部和外部验证中显示出稳定的性能。此外,我们的模型优于之前发布的35个模型。高危患者的ECM预后较差,基质细胞炎症程度高,TMB较低,MSI-H分级较低,肿瘤分期较差,对免疫疗法的反应较差,对化疗的敏感性较低。在五种已报道的分子亚型中,较差的亚型显示出较高的风险评分。结论该预后模型可作为预测胃癌患者预后和治疗反应的有效且有前景的工具。
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引用次数: 2
Applications of 3D printing in tumor treatment 3D打印在肿瘤治疗中的应用
Pub Date : 2023-05-02 DOI: 10.1016/j.bmt.2023.03.002
Jiante Li , Danna Liang , Xiang Chen , Weijian Sun , Xian Shen

As an emerging technology relevant to materials science, 3D printing technology simplifies material production process, shortens the preparation cycle, and provides a broader space for disease treatment. This review introduces the latest development in 3D printing, the goal is showing summary of the preparation and the utilization of this technology. We first describe the familiar biological ink for 3d printing. Then, we focus on different applications, including drug delivery, tumor modeling, and organ printing. Later, we described the application of this technology in some disciplines, including neurosurgery, gastrointestinal surgery, and orthopedics. Finally, the recent challenges and prospects of 3D printing are presented.

作为一项与材料科学相关的新兴技术,3D打印技术简化了材料生产过程,缩短了制备周期,为疾病治疗提供了更广阔的空间。本文介绍了三维打印技术的最新发展,目的是对该技术的制备和应用进行总结。我们首先描述了人们熟悉的用于3d打印的生物墨水。然后,我们关注不同的应用,包括药物递送、肿瘤建模和器官打印。后来,我们描述了这项技术在一些学科中的应用,包括神经外科、胃肠外科和骨科。最后,介绍了3D打印的最新挑战和前景。
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引用次数: 1
Application of nucleic acid signal amplification in biosensing and bioimaging 核酸信号扩增在生物传感和生物成像中的应用
Pub Date : 2023-05-01 DOI: 10.1016/j.bmt.2023.03.004
Junqi Zhao , Xueqin Li , Dagan Zhang , Sen Wang

Nucleic acid amplification techniques are broadly employed in nucleic acid testing due to their efficient accumulation of nucleic acid sequences. With the development of biotechnology, they are further applied to proteins, living cells, extracellular vesicles (EVs) and even small molecule detection to amplify detection signals for ultra-sensitive bioanalysis. As important amplification techniques, isothermal amplification techniques, CRISPR/Cas system, DNA Walker and DNAzymes are playing an increasingly important role in signal magnification. Cooperating with functional nanomaterials, they present a wide availability in biosensing and bioimaging. This review gives a comprehensive summary of the four main signal amplification techniques mentioned above and their applications in biosensing and bioimaging. Finally, some of the challenges and further opportunities of nucleic acid amplification strategy in the current biomedical technology field are discussed.

核酸扩增技术由于其核酸序列的有效积累而被广泛用于核酸检测。随着生物技术的发展,它们被进一步应用于蛋白质、活细胞、细胞外小泡甚至小分子检测,以放大检测信号,用于超灵敏的生物分析。作为重要的扩增技术,等温扩增技术、CRISPR/Cas系统、DNA Walker和DNA酶在信号放大中发挥着越来越重要的作用。与功能性纳米材料合作,它们在生物传感和生物成像方面具有广泛的可用性。本文综述了上述四种主要的信号放大技术及其在生物传感和生物成像中的应用。最后,讨论了核酸扩增策略在当前生物医学技术领域面临的一些挑战和进一步的机遇。
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引用次数: 0
Overcoming melanoma resistance to immune checkpoint blockade therapy using nano-strategies 利用纳米策略克服黑色素瘤对免疫检查点阻断疗法的抵抗
Pub Date : 2023-04-01 DOI: 10.1016/j.bmt.2023.03.003
Yiqin Ding , Changyi Liu , Yilun Wu , Fanfan Fu

Monoclonal antibodies targeting CTLA-4, PD-1/PD-L1 axis, and LAG-3, have shown unprecedented clinical success in melanoma. However, such immune checkpoint blockade (ICB) therapies failed to initiate primary immune responses or with limited durability. Here, we reviewed the mechanisms eliciting intrinsic resistance and adaptive resistance in melanoma patients. Furthermore, we introduced emerging nano-strategies to overcome the ICB by either enhancing tumour cell phagocytosis through checkpoint-mediated internalization or devising nano-immunomodulators for ICB combination therapy. These strategies may lead to clinical translations in the future.

靶向CTLA-4、PD-1/PD-L1轴和LAG-3的单克隆抗体在黑色素瘤中显示出前所未有的临床成功。然而,这种免疫检查点阻断(ICB)疗法未能启动初级免疫反应或持久性有限。在此,我们综述了引起黑色素瘤患者内在耐药性和适应性耐药性的机制。此外,我们引入了新出现的纳米策略,通过检查点介导的内化增强肿瘤细胞吞噬作用或设计用于ICB联合治疗的纳米免疫调节剂来克服ICB。这些策略可能会导致未来的临床翻译。
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引用次数: 1
Precisely integrated contact lens: An intraocular pressure guard for glaucoma patients 精密集成隐形眼镜:青光眼患者的眼压保护装置
Pub Date : 2023-03-31 DOI: 10.1016/j.bmt.2023.03.001
Meixin Ran , Jiaqi Yan , Hongbo Zhang

Recently, scientists at Pohang University of Science and Technology in South Korea constructed a smart theranostic contact lens. The highly integrated smart contact lens is composed of an intraocular pressure (IOP) biosensor, a drug delivery system (DDS), a wireless communication system, as well as a circuit chip for IOP regulation. This design provides a new opportunity for wearable medical treatment in the individualized treatment of glaucoma and other ocular diseases.

最近,韩国浦项科技大学的科学家制造了一种智能治疗隐形眼镜。高度集成的智能隐形眼镜由眼压(IOP)生物传感器、药物递送系统(DDS)、无线通信系统以及用于IOP调节的电路芯片组成。这种设计为可穿戴医疗在青光眼和其他眼部疾病的个性化治疗中提供了新的机会。
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引用次数: 0
Developing engineering technologies for the treatment of systemic lupus erythematosus 开发治疗系统性红斑狼疮的工程技术
Pub Date : 2023-03-22 DOI: 10.1016/j.bmt.2023.02.002
Xubin Hao , Yuze Wang , Rui Liu , Dagan Zhang , Bin Kong , Jun Liang , Lingyun Sun

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs and tissues. However, only a handful of new drugs have been FDA-approved for SLE since the 1950s. Therefore, novel treatments for SLE are urgently needed to be developed. In recent years, various engineering technologies such as tissue engineering, organs-on-chips, and intelligent delivery systems have been rapidly developed in the field of biomedicine. Notably, engineered nanocarriers and cell-based therapies can address the problems faced by traditional drug delivery and cell transplantation. They have proven effective in the treatment of many areas of disease, including autoimmune diseases. This is an important opportunity to break through the limited treatment options for SLE. In this review, we summarize the application progresses of engineering technologies and also propose their challenges in SLE treatment. This paper aims to help readers to understand the perspective of engineering technologies on the direction of SLE treatments in forthcoming years.

系统性红斑狼疮(SLE)是一种影响多个器官和组织的复杂自身免疫性疾病。然而,自20世纪50年代以来,只有少数新药被美国食品药品监督管理局批准用于SLE。因此,迫切需要开发新的SLE治疗方法。近年来,组织工程、芯片上器官、智能输送系统等各种工程技术在生物医学领域得到了快速发展。值得注意的是,工程化纳米载体和基于细胞的疗法可以解决传统药物递送和细胞移植所面临的问题。它们已被证明在治疗许多疾病领域有效,包括自身免疫性疾病。这是突破系统性红斑狼疮有限治疗选择的重要机会。在这篇综述中,我们总结了工程技术的应用进展,并提出了它们在SLE治疗中的挑战。本文旨在帮助读者理解工程技术对未来几年SLE治疗方向的展望。
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引用次数: 1
Exosomes-based particles as inhalable COVID-19 vaccines 基于外泌体的颗粒作为可吸入性COVID-19疫苗
Pub Date : 2023-03-22 DOI: 10.1016/j.bmt.2023.01.003
Lu Fan , Li Wang , Xiaoju Wang , Hongbo Zhang

Coronavirus disease 2019 (COVID-19), a severely spreading pandemic, has dramatically brought physiological and economical burdens to people. Although the injectable vaccines have some achievements for coronavirus defense, they still generate accompanied pain, untoward reaction and cannot take part in mucosal immunity. Inhalable vaccines, as a safe, facile and efficient strategy, have been presented to protect body from virus by inducing robust mucosal immunity. Here, we give a perspective of an inhalable COVID-19 vaccine composed of lung-derived exosomes (a type of virus-like particle) conjugated with viral receptor-binding domain. The lung-derived exosomes act as carriers, such inhalable particles successfully reach at lung and reveal wider distribution and longer retention on respiratory mucosa. In addition, such vaccines induce the high production of specific antibodies and T cells in lung, significantly protecting host against coronavirus invasion. It is conceived that inhalable virus-like particles with long-term stability wound open a new avenue for vaccines delivery and further achieve vaccine popularization to against with COVID-19 pandemic.

2019冠状病毒病(新冠肺炎)是一种严重传播的流行病,给人们带来了巨大的生理和经济负担。尽管注射疫苗在冠状病毒防御方面取得了一些成就,但它们仍然会产生伴随的疼痛、不良反应,并且不能参与粘膜免疫。可吸入疫苗作为一种安全、简便、有效的策略,已被提出通过诱导强大的粘膜免疫来保护身体免受病毒感染。在此,我们对可吸入的新冠肺炎疫苗进行了展望,该疫苗由肺来源的外泌体(一种病毒样颗粒)与病毒受体结合结构域结合而成。肺来源的外泌体作为载体,这种可吸入颗粒成功到达肺部,并在呼吸道粘膜上显示出更宽的分布和更长的滞留时间。此外,此类疫苗可诱导肺部产生大量特异性抗体和T细胞,显著保护宿主免受冠状病毒入侵。认为具有长期稳定性的可吸入病毒样颗粒物将为疫苗的提供开辟新的途径,并进一步实现针对新冠肺炎大流行的疫苗普及。
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引用次数: 2
期刊
Biomedical Technology
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