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A 3D-bioprinted dermal-like scaffold incorporating fibroblasts and DRG neurons to investigate peripheral nerve regeneration† 结合成纤维细胞和DRG神经元的3d生物打印真皮样支架研究周围神经再生。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-19 DOI: 10.1039/D4TB02823F
Francesco Formaggio, Emanuela Saracino, Marianna Barbalinardo, Eva Clemente, Franco Corticelli, Sara Buoso and Simone Bonetti

Peripheral nervous system (PNS) regeneration is a rapidly advancing field with critical implications for addressing sensory impairments and neuropathic conditions. Dorsal root ganglion (DRG) neurons, essential for sensory transmission, exhibit regenerative potential through axonal regeneration. However, the mechanisms driving these processes are not yet understood. This study introduces an innovative 3D-bioprinted fibroblasts/DRG co-culture construct, specifically designed to investigate and characterize PNS regeneration and wiring mechanisms under both physiological and pathophysiological conditions. By characterizing bioink rheology and optimizing bioprinting parameters, we created a stable, biocompatible derma-like construct supporting cell adhesion and growth. Bioprinted 3T3 fibroblasts demonstrate high viability and proliferation, while DRG neurons exhibit enhanced neurite outgrowth and complex branching patterns within the co-culture system. These findings highlight the role of fibroblasts in promoting axonal regeneration and provide a robust in vitro platform for studying sensory system reinnervation. This model lays the foundation for developing personalized therapies for neuropathic pain and sensory dysfunction, advancing both fundamental neuroscience and translational medicine.

外周神经系统(PNS)再生是一个快速发展的领域,对解决感觉障碍和神经性疾病具有重要意义。背根神经节(DRG)神经元对感觉传递至关重要,通过轴突再生表现出再生潜力。然而,驱动这些过程的机制尚不清楚。本研究介绍了一种创新的3d生物打印成纤维细胞/DRG共培养结构,专门用于研究和表征生理和病理生理条件下PNS再生和连接机制。通过表征生物墨水流变学和优化生物打印参数,我们创造了一个稳定的、生物相容性的真皮样结构,支持细胞粘附和生长。生物打印的3T3成纤维细胞表现出高活力和增殖能力,而DRG神经元在共培养系统中表现出增强的神经突生长和复杂的分支模式。这些发现强调了成纤维细胞在促进轴突再生中的作用,并为研究感觉系统神经再生提供了一个强大的体外平台。该模型为神经性疼痛和感觉功能障碍的个性化治疗奠定了基础,促进了基础神经科学和转化医学的发展。
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引用次数: 0
Engineered Ti3C2(O,Cl) MXenes with dual functionalization: a new Frontier in targeted head and neck squamous cell carcinoma and breast adenocarcinoma† 双功能化Ti3C2(O,Cl) MXenes:靶向头颈部鳞状细胞癌和乳腺腺癌的新领域
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-16 DOI: 10.1039/D5TB00302D
Jhansi Chintakindi, Ganesh Panditrao Lahane, Arti Dhar and Afkham Mir

Ti3C2Tx MXenes have attracted significant attention in the realm of anticancer therapeutics owing to their remarkable properties, including cyto-compatibility and targeted drug delivery capabilities. In this study, Ti3C2 was intentionally modified with both chlorine and oxygen surface groups, as each of these functional groups have individually demonstrated promising anticancer properties. Our aim was to combine them in a single compound to explore how this dual-functionalized material might perform in a therapeutic context. This study synthesizes Ti3C2(O,Cl) MXenes using a novel electrochemical etching technique that allows for precise tailoring of the surface terminations with O and Cl groups. The synthesised Ti3C2(O,Cl) has biological activity in two cancerous (FaDu and MCF-7) and two normal (H9C2 and HEK-293) cell lines. The results of cytotoxicity data showed that the observed toxic effects were higher against cancerous cells (∼91%) than normal cells (∼40%). The mechanisms of potential toxicity were also elucidated. The synthesized Ti3C2(O,Cl) MXene has an effect on oxidative stress, resulting in an increase of more than 91.44% in reactive oxygen species (ROS) production in malignant cells. The results of this study provide major insights to date into the biological activity of Ti3C2(O,Cl) MXenes and develop their application in anticancer treatments.

Ti3C2Tx MXenes由于其卓越的特性,包括细胞相容性和靶向给药能力,在抗癌治疗领域引起了极大的关注。在这项研究中,Ti3C2被有意地用氯和氧表面基团修饰,因为这些官能团中的每一个都单独显示出有希望的抗癌特性。我们的目标是将它们结合在一个单一的化合物中,以探索这种双重功能材料如何在治疗环境中发挥作用。本研究使用一种新的电化学蚀刻技术合成了Ti3C2(O,Cl) MXenes,该技术可以精确地剪裁带有O和Cl基团的表面末端。合成的Ti3C2(O,Cl)在两种癌细胞系(FaDu和MCF-7)和两种正常细胞系(H9C2和HEK-293)中具有生物活性。细胞毒性数据结果显示,观察到的对癌细胞(~ 91%)的毒性作用高于正常细胞(~ 40%)。并对其潜在毒性机制进行了阐述。合成的Ti3C2(O,Cl) MXene对氧化应激有影响,导致恶性细胞的活性氧(ROS)生成增加超过91.44%。这项研究的结果为Ti3C2(O,Cl) MXenes的生物活性提供了重要的见解,并开发了它们在抗癌治疗中的应用。
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引用次数: 0
Pioneering bactericidal efficacy with nitrogen doping and zinc oxide nanoparticle decoration on carbon nanosheets† 在碳纳米片上采用氮掺杂和氧化锌纳米颗粒修饰,具有开创性的杀菌效果。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-16 DOI: 10.1039/D5TB00516G
Omnarayan Agrawal, Bani Preet Kaur, Radhika Chaurasia, Hitesh Kumar Sharma, Geetika Jain, Madhav Krishn Goswami, Sandip Chakrabarti and Monalisa Mukherjee

The escalating prevalence of drug-resistant pathogens poses a significant threat to global health, contributing to elevated mortality rates and inflated healthcare expenses. To combat antibacterial resistance, carbon-based nanocomposites incorporating metal oxides have emerged as a promising solution in the development of advanced antibacterial agents. In this quest, we propose a nascent strategy to synthesize zinc oxide-decorated carbon nanosheets (ZnO@CNSn) via a co-precipitation method. The crystalline ZnO nanoparticles (ZnO-NPs) are homogeneously dispersed throughout a framework of melamine-enriched carbon nanosheets (CNSn). The presence of pyrrolic-N and pyridinic-N functionalities in ZnO@CNSn enhances the charge transfer kinetics and creates nucleation sites for uniform dispersion of ZnO-NPs, mitigating particle aggregation. Remarkably, XPS analysis reveals a distinct shift in peak intensity, characterized by a reduction in pyrrolic-N and a corresponding increase in pyridinic-N. This conversion of pyrrolic-N to pyridinic-N due to incorporation of ZnO-NPs onto CNSn plays a crucial role in improving its bactericidal effect. The antibacterial assays against Gram negative Escherichia coli, Gram positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) confirm the bactericidal activity of ZnO@CNSn. Additionally, the SEM micrographs show altered bacterial morphology on interaction with the nanocomposites, further validating the effective bactericidal properties. Moreover, ZnO@CNSn exhibits enhanced cytocompatibility compared to CNSn. These findings underscore the promising potential of the ZnO-decorated CNSn architecture as a robust platform for advanced antibacterial applications.

耐药病原体的日益流行对全球健康构成重大威胁,导致死亡率上升和医疗费用膨胀。为了对抗抗菌剂耐药性,碳基纳米复合材料结合金属氧化物已经成为开发先进抗菌剂的一个有前途的解决方案。在这项探索中,我们提出了一种通过共沉淀法合成氧化锌修饰碳纳米片的新策略(ZnO@CNSn)。晶体ZnO纳米颗粒(ZnO- nps)均匀分布在富含三聚氰胺的碳纳米片(CNSn)框架中。ZnO@CNSn中吡咯- n和吡啶- n官能团的存在增强了电荷转移动力学,并为ZnO-NPs的均匀分散创造了成核位点,减轻了颗粒聚集。值得注意的是,XPS分析显示了明显的峰强度变化,其特征是吡咯烷- n的减少和吡啶- n的相应增加。通过在CNSn上掺入ZnO-NPs,将吡咯- n转化为吡啶- n,对提高CNSn的杀菌效果起着至关重要的作用。对革兰氏阴性大肠杆菌、革兰氏阳性金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌(MRSA)的抑菌试验证实了ZnO@CNSn的抑菌活性。此外,扫描电镜显示细菌形态的改变与纳米复合材料的相互作用,进一步验证了有效的杀菌性能。此外,与CNSn相比,ZnO@CNSn具有更强的细胞相容性。这些发现强调了zno修饰的CNSn结构作为先进抗菌应用的强大平台的巨大潜力。
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引用次数: 0
Low-cost, robust, and transportable devices based on Cu(i)–I cluster hybrid luminescent compounds as tetracycline sensors for contaminated waters† 基于Cu(I)-I簇杂化发光化合物的低成本,坚固耐用和可运输的器件作为污染水的四环素传感器。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-15 DOI: 10.1039/D5TB00353A
Elena De La Rubia, Ricardo Garsed, Fernando Aguilar-Galindo, Andrea García-Hernán, Gines Lifante-Pedrola and Pilar Amo-Ochoa

Submicron particles of [Cu4I6(pr-ted)2] (pr-ted = 1-propyl-1,4-diazabicyclo[2.2.2]octan-1-ium) are easy to synthesize in one step under mild conditions. Additionally, they exhibit strong emission at 530 nm, high photoluminescence quantum yield, and excellent thermal (250 °C) and water stability (pH = 4–9). These properties make them a promising candidate for studying luminescence responses to external stimuli, potentially serving as a chemical sensor. Furthermore, their size and morphology make it possible to obtain stable suspensions in ethanol and water, which are extremely useful for subsequent processing. Indeed, submicrometric [Cu4I6(pr-ted)2] particles in deionized water and real river water suspensions can be used to efficiently detect tetracycline (TC) via photoinduced electron transfer, resulting in a detectable fluorescence quenching. It features a low detection limit of 1.18 nM (0.52 ppb) and the reversible quenching of the emission demonstrates recyclability for over 30 cycles. The detection process is unaffected by other antibiotics, including sulfamethazine (SMZ), chloramphenicol (CAP), and ornidazole (ORN). Effective TC detection is supported by the theoretical computations of the energy bands of TC antibiotic and [Cu4I6(pr-ted)2], indicating a good match between their energy bands, which aligns with the fluorescence quenching observed. As a proof of concept, the material has been further processed into various formats – such as pellets, paper strips, fiberglass, polylactic acid (PLA) composite films, and 3D-printed composite meshes using commercial photosensitive resins-for their practical application as robust, high sensitivity, rapid on–off response, and cost-effective tetracycline water sensor devices.

亚微米颗粒[Cu4I6(pr-ted)2] (pr-ted = 1-丙基-1,4-重氮杂环[2.2.2]辛烷-1-ium)在温和的条件下容易一步合成。此外,它们在530 nm处具有强发射,高光致发光量子产率,以及优异的热稳定性(250°C)和水稳定性(pH = 4-9)。这些特性使它们成为研究对外部刺激的发光反应的有希望的候选者,有可能作为化学传感器。此外,它们的大小和形态使其在乙醇和水中获得稳定的悬浮液成为可能,这对后续处理非常有用。事实上,去离子水和真实河水悬浊液中的亚微米[Cu4I6(pr-ted)2]粒子可以通过光诱导电子转移有效地检测四环素(TC),从而导致可检测的荧光猝灭。它具有1.18 nM (0.52 ppb)的低检测限,并且发射的可逆淬火表明可循环30次以上。检测过程不受其他抗生素的影响,包括磺胺乙嗪(SMZ)、氯霉素(CAP)和奥硝唑(ORN)。TC抗生素和[Cu4I6(pr-ted)2]的能带理论计算支持了有效的TC检测,表明它们的能带匹配良好,这与观察到的荧光猝灭一致。作为概念验证,该材料已被进一步加工成各种形式-例如颗粒,纸条,玻璃纤维,聚乳酸(PLA)复合薄膜和使用商业光敏树脂的3d打印复合网格-用于其实际应用,坚固,高灵敏度,快速开关响应,具有成本效益的四环素水传感器设备。
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引用次数: 0
Differentiated strategies for nanovaccines in lymphoma immunotherapy: advances and challenges 纳米疫苗在淋巴瘤免疫治疗中的差异化策略:进展与挑战
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-15 DOI: 10.1039/D5TB00528K
Yongming Xia, Liang Tao, Wenzhong Shang, Guibin Zhang and Ying Lu

Lymphomas constitute a molecularly and clinically heterogeneous group of hematological malignancies, classically classified into two distinct types: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). These subtypes demonstrate fundamental divergences in their pathobiology and immune microenvironmental profiles. Nanovaccines—nanoparticle-based platforms encapsulating tumor-associated antigens (TAAs) or neoantigens—offer precision immunotherapy by enabling controlled antigen delivery and enhanced dendritic cell cross-presentation. Subtype-specific designs target EBV-associated HL (using LMP1/2 or EBNA1) or NHL (via CD19/CD20/CD22 or T-cell epitopes). However, challenges persist in the development of nanovaccines, particularly concerning antigen selection, carrier materials, and the optimization of vaccine formulations. These vaccines must overcome the immunosuppressive tumor microenvironment, ensure efficient delivery to tumor sites, and avoid toxicity. Despite these hurdles, evolving research in the immunotherapy field of lymphoma leads to the continued exploration of nanovaccines as promising additions to existing therapeutic regimens. This review serves to highlight the critical nature of further research to achieve a better understanding of the complicated interdependent interactions between nanovaccines, immune responses and tumor biology, culminating in more effective and personalised therapies for victims of lymphomas. This advanced strategy is expected to overcome the shortcomings of classic therapies including chemo and radiotherapy, in terms of improved specificity, fewer systemic side-effects and the potential for prolonged remission in patients with refractory or relapsed lymphomas. In conclusion, the integration of nanotechnology into lymphoma immunotherapy marks a vast advancement in the field of cancer therapy, with nanovaccines poised to play a crucial role in future therapeutic strategies.

淋巴瘤是一种分子和临床异质性的血液系统恶性肿瘤,通常分为两种不同的类型:霍奇金淋巴瘤(HL)和非霍奇金淋巴瘤(NHL)。这些亚型在病理生物学和免疫微环境方面表现出根本的差异。纳米疫苗——包封肿瘤相关抗原(TAAs)或新抗原的基于纳米颗粒的平台——通过控制抗原递送和增强树突状细胞交叉呈递,提供精确的免疫治疗。亚型特异性设计靶向ebv相关HL(使用LMP1/2或EBNA1)或NHL(通过CD19/CD20/CD22或t细胞表位)。然而,纳米疫苗的开发仍然面临挑战,特别是在抗原选择、载体材料和疫苗配方优化方面。这些疫苗必须克服免疫抑制肿瘤微环境,确保有效地递送到肿瘤部位,并避免毒性。尽管存在这些障碍,在淋巴瘤免疫治疗领域不断发展的研究导致纳米疫苗作为现有治疗方案的有希望的补充的继续探索。这篇综述强调了进一步研究的关键性质,以更好地理解纳米疫苗、免疫反应和肿瘤生物学之间复杂的相互依存的相互作用,最终为淋巴瘤患者提供更有效和个性化的治疗。这一先进的策略有望克服包括化疗和放疗在内的经典疗法的缺点,包括提高特异性、减少全身副作用和延长难治性或复发性淋巴瘤患者缓解期的潜力。总之,纳米技术与淋巴瘤免疫治疗的结合标志着癌症治疗领域的巨大进步,纳米疫苗将在未来的治疗策略中发挥关键作用。
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引用次数: 0
Biomass bilayer membranes with an asymmetric structure to promote a tendon–bone interface healing mechanism† 具有不对称结构的生物质双层膜促进肌腱-骨界面愈合机制。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-15 DOI: 10.1039/D5TB00208G
Tiantian Chen, Jian Wang, Xi Li, Jinpeng Liu, Xinding Yu, Peng Pan, Xi Wang and Wentao Liu

Biologically, tendon–bone interface healing needs to overcome two problems: tendon dislocation and scar tissue proliferation at the interface. Because of the above problems, we proposed a bone tunnel membrane to aid tendon–bone interface healing. This study aims to explore the effects of absorbable membranes with different surface morphologies on tendon–bone interface healing. At the tendon–bone interface, the tendon graft was wrapped with a bilayer flexible absorbable membrane and implanted into the bone tunnel. Using the micron topological structure on the surface of the membrane to accelerate tendon healing and osteogenic differentiation provides environmental support for the healing of the two tissue interfaces. The different topological structures on the surface of the material can promote the oriented differentiation of cells. The micron groove structure can arrange fibroblasts according to orientation, promote tendon bundle healing, change cell morphology, and secrete tendon specific proteins to promote tendon repair. The porous structure can promote cell osteogenic differentiation and accelerate bone integration. After in vivo experimental analysis, the material is suitable for the adjuvant treatment of tendon–bone healing. Therefore, this study provides a new treatment idea for accelerating tendon-to-bone healing.

从生物学上讲,肌腱-骨界面愈合需要克服两个问题:肌腱脱位和界面处疤痕组织增生。由于上述问题,我们提出了一种骨隧道膜来帮助肌腱-骨界面愈合。本研究旨在探讨不同表面形态的可吸收膜对肌腱-骨界面愈合的影响。在肌腱-骨界面处,用双层柔性可吸收膜包裹肌腱移植物,植入骨隧道。利用膜表面的微米拓扑结构加速肌腱愈合和成骨分化,为两种组织界面的愈合提供环境支持。材料表面不同的拓扑结构可以促进细胞的定向分化。微米槽结构可使成纤维细胞按取向排列,促进肌腱束愈合,改变细胞形态,分泌肌腱特异性蛋白,促进肌腱修复。多孔结构可促进细胞成骨分化,加速骨整合。经体内实验分析,该材料适用于肌腱-骨愈合的辅助治疗。因此,本研究为加速肌腱-骨愈合提供了新的治疗思路。
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引用次数: 0
A platinum(iv)–crocetin nanoplatform with intracellular morphological transformation for enhanced colorectal cancer therapy† 一种具有细胞内形态转化的铂(IV)-芥菜素纳米平台用于增强结直肠癌治疗。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-14 DOI: 10.1039/D5TB00127G
Xue Rui, Zhetong Jin, Lu Li, Jia Liu, Jiarong Mao, Xuejiao Leng, Hongzhi Qiao, Wei Li, Lingchong Wang, Yugen Chen and Jingjing Wang

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy worldwide. Platinum(II)-based drugs, a cornerstone in CRC treatment, are often limited by significant side effects and suboptimal efficacy. Herein, we present a platinum(IV) prodrug nanoplatform (Pt(IV)–Cro NPs) designed to overcome these challenges through intracellular morphological transformation, enhancing therapeutic outcomes against CRC. Pt(IV)–Cro NPs are formed via the self-assembly of Pt(IV)–crocetin (Pt(IV)–Cro) and mPEG–crocetin (mPEG–Cro), driven by hydrophilic–hydrophobic interactions. These nanoparticles exhibit concentration-dependent morphology, transitioning from rod-shaped structures at lower concentrations to spherical forms at higher concentrations. Notably, Pt(IV)–Cro NPs undergo time-dependent morphological changes within cells. Upon uptake by CT26 cells, the nanoparticles retain a nanorod shape during the first hour but transform into spherical structures within 3 h. These morphological transitions contribute to a remarkable 141-fold reduction in the half-inhibitory concentration (IC50) against CT26 cells compared to cisplatin alone. Pt(IV)–Cro NPs induced 3.14-fold greater apoptosis, 51.2% mitochondrial depolarization, and 55.9% ROS elevation compared to cisplatin. In vivo studies in CT26 tumor-bearing mice reveal that Pt(IV)–Cro NPs significantly outperform cisplatin alone, reducing tumor growth by up to 8.08 times relative to controls. This innovative nanoplatform combines enhanced efficacy with minimized side effects, offering a transformative approach to CRC therapy. The concentration-responsive self-assembly of Pt(IV)–Cro NPs and the occurrence of morphologic transformations within the cell characterize a major advancement in clinical CRC therapeutic strategies.

结直肠癌(CRC)是全球第三大最常诊断的恶性肿瘤。以铂(II)为基础的药物是CRC治疗的基石,但往往受到严重副作用和疗效欠佳的限制。在此,我们提出了一种铂(IV)前药纳米平台(Pt(IV)-Cro NPs),旨在通过细胞内形态转化克服这些挑战,提高对结直肠癌的治疗效果。Pt(IV)-Cro NPs是由Pt(IV)- croo (Pt(IV)-Cro)和mpeg - croo (mPEG-Cro)在亲疏水相互作用的驱动下自组装形成的。这些纳米颗粒表现出浓度依赖的形态,从低浓度的棒状结构转变为高浓度的球形结构。值得注意的是,Pt(IV)-Cro NPs在细胞内会发生随时间变化的形态变化。在被CT26细胞摄取后,纳米颗粒在第一个小时内保持纳米棒形状,但在3小时内转变为球形结构。这些形态转变有助于与单用顺铂相比,对CT26细胞的半抑制浓度(IC50)显著降低141倍。与顺铂相比,Pt(IV)-Cro NPs诱导的细胞凋亡增加3.14倍,线粒体去极化增加51.2%,ROS升高55.9%。在CT26肿瘤小鼠体内的研究表明,Pt(IV)-Cro NPs显著优于单用顺铂,与对照组相比,肿瘤生长减少高达8.08倍。这种创新的纳米平台结合了增强的疗效和最小化的副作用,为结直肠癌治疗提供了一种变革性的方法。Pt(IV)-Cro NPs的浓度响应性自组装和细胞内形态转化的发生是临床CRC治疗策略的重大进展。
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引用次数: 0
Ultrasensitive detection of arsenic in water using laser-scribed graphene-based electrodes† 利用激光刻写石墨烯基电极对水中砷的超灵敏检测。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-14 DOI: 10.1039/D5TB00041F
Abhinandan Mohanty, Shubham Upadhye, Gopal K. Pradhan and Pranati Nayak

Arsenic contamination in water poses a serious health risk due to its high toxicity, even at ppb levels. In this work, we report a cost-effective graphene-based sensor with ultralow detection capabilities for arsenic. This is achieved by enhancing the catalytic efficiency of graphene electrodes through sunlight-assisted photothermal oxidation of a metal salt into metal oxide nanoparticles. The sensor demonstrated high sensitivity (34.81 ± 1.74 μA cm−2 ppb−1) and an ultralow detection limit (LOD 0.0636 ppb). Field tests on water samples from arsenic-contaminated zones in West Bengal, India, showed results consistent with the state-of-the-art ICP-OES analysis, highlighting the sensor's potential for practical, on-site arsenic monitoring.

水中的砷污染由于其高毒性,即使达到ppb水平,也会造成严重的健康风险。在这项工作中,我们报告了一种具有超低砷检测能力的低成本石墨烯传感器。这是通过提高石墨烯电极的催化效率来实现的,通过阳光辅助光热氧化金属盐成金属氧化物纳米颗粒。该传感器具有高灵敏度(34.81±1.74 μA cm-2 ppb-1)和超低检出限(LOD 0.0636 ppb)。对印度西孟加拉邦砷污染地区的水样进行的现场测试显示,结果与最先进的ICP-OES分析结果一致,突出了该传感器在实际的现场砷监测方面的潜力。
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引用次数: 0
GPT-driven generation and biological activity evaluation of novel mRNA trinucleotide Cap1 analogs for mRNA vaccine or immunotherapy† gpt驱动的新型mRNA三核苷酸Cap1类似物用于mRNA疫苗或免疫治疗的生成和生物活性评价。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-14 DOI: 10.1039/D5TB00750J
Honglei Zhang, Jingxuan Ma, Teng Ma, Yuqing Ma, Lijie Jin, Lijie Liu, Yangjian Liu, Kai Dong, Man Zhang, Dawei Huang, Fei Yu and Gengshen Song

Analogs of the mRNA 5′-cap are indispensable for mRNA translation, stability, translation efficiency, and immunogenicity, with emerging potential applications in novel preventive and therapeutic interventions. Here, this study presents a novel approach for designing mRNA Cap1 analogs with optimized biological activity. We leveraged the power of generative pre-trained transformer (GPT) architecture to generate novel cap analog sequences. A discriminative model is then employed to select promising candidates based on their predicted expression levels. Our results demonstrate that the GPT-based generative model significantly outperforms a traditional recurrent neural network (RNN) in terms of perplexity, indicating its superior ability to generate diverse and accurate cap analog sequences. Furthermore, the expression screening model achieves high accuracy in identifying potential high-expression candidates. Then, we synthesized a set of designed novel trinucleotide mRNA Cap1 analogs with modified ribose and incorporated it into mRNA using T7 polymerase. A series of experiments revealed that mRNA capped with YK-CAP-01–06 analogs exhibited increased translation efficiency and decapping enzyme stability compared to the commercially available cap-analog-capped mRNA. Finally, the potential application value was explored by constructing OVA, RSV preF- and VZV gE-mRNA vaccines, which resulted in significant (vs. controls) inhibition of tumor growth and an increase in IgG antibody levels in mice.

mRNA 5'-cap的类似物对于mRNA翻译、稳定性、翻译效率和免疫原性是不可或缺的,在新的预防和治疗干预中具有潜在的应用前景。本研究提出了一种设计具有优化生物活性的mRNA Cap1类似物的新方法。我们利用生成预训练变压器(GPT)架构的力量来生成新的帽模拟序列。然后采用判别模型根据预测的表达水平选择有希望的候选者。我们的研究结果表明,基于gpt的生成模型在困惑度方面显著优于传统的递归神经网络(RNN),表明其具有生成多样化和准确的帽模拟序列的优越能力。此外,表达筛选模型在识别潜在的高表达候选物方面具有很高的准确性。然后,我们用修饰的核糖合成了一组新的三核苷酸mRNA Cap1类似物,并利用T7聚合酶将其整合到mRNA中。一系列实验表明,与市售的盖帽类似物相比,用YK-CAP-01-06盖帽的mRNA具有更高的翻译效率和脱帽酶稳定性。最后,通过构建OVA、RSV preF-和VZV gE-mRNA疫苗来探索其潜在的应用价值,这些疫苗对小鼠肿瘤生长有显著的抑制作用(与对照组相比),并提高了IgG抗体水平。
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引用次数: 0
Multifunctional carbon dot-based dual-channel and dual-signal sensors for ribonucleotide discrimination and Fe3+ detection† 核糖核酸识别和Fe3+检测的多功能碳点双通道双信号传感器。
IF 6.1 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-05-14 DOI: 10.1039/D5TB00324E
Runjie Miao, Yu Zhang, Haifeng Sha, Wenyan Ma, Yuefeng Huang and Hangrong Chen

Ribonucleotides and Fe3+ are crucial for numerous biological processes, hence their effective discrimination and detection are imperative for the investigation of metabolic processes and the early diagnosis of diseases, yet current sensing strategies based on a single signal output are hard to fulfill the demands for practical detection accuracy. Herein, a dual-channel sensor based on copper-doped fluorescent carbon dots (Cu-CDs) as a single sensing unit has been developed for the precise discrimination of ribonucleotides. Combined with statistical analyses of the data arrays, accurate discrimination and quantification of the four most vital ribonucleotide triphosphates (ATP, CTP, UTP, and GTP) are achieved, providing a valuable reference to improve the design of complex sensor arrays. Furthermore, given the merits of dual-signal detection, a silica-based aggregation-induced emission material is further introduced as the second fluorophore. The constructed novel dual-fluorescence signal sensing system enables rapid quantitative detection (2 min) and visual semi-quantitative sensing of Fe3+ with enhanced accuracy and a detection limit of 1.53 μM. Briefly, such dual-signal sensors based on Cu-CDs feature easy operation, simplicity, and accuracy, offering valuable references for the design and construction of dual-channel detection tools and hold potential for practical applications.

核糖核苷酸和Fe3+在许多生物过程中都是至关重要的,因此它们的有效识别和检测对于研究代谢过程和疾病的早期诊断是必不可少的,但目前基于单一信号输出的传感策略难以满足实际检测精度的要求。本文研制了一种基于铜掺杂荧光碳点(Cu-CDs)作为单个传感单元的双通道传感器,用于精确识别核糖核苷酸。结合数据阵列的统计分析,实现了四种最重要的三磷酸核糖核苷酸(ATP、CTP、UTP和GTP)的准确区分和定量,为改进复杂传感器阵列的设计提供了有价值的参考。此外,考虑到双信号检测的优点,进一步引入了硅基聚集诱导发射材料作为第二荧光团。所构建的新型双荧光信号传感系统可实现Fe3+的快速定量检测(2 min)和视觉半定量检测,精度提高,检测限为1.53 μM。总之,这种基于Cu-CDs的双信号传感器操作方便、简单、准确,为双通道检测工具的设计和构建提供了有价值的参考,具有实际应用潜力。
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Journal of Materials Chemistry B
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