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Pub Date : 2025-06-26
Yang Fu, Lingfeng Zhu, Xiaorui Zheng, Hua Fan, Shiwen Wang, Hui Li and Tianyi Ma*, 
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引用次数: 0
Hydroxychloroquine-Derived Ionizable Lipid Facilitates Spleen-Tropic Transfection and Enhances Cancer Immunotherapy 羟氯喹衍生的可电离脂质促进嗜脾转染和增强癌症免疫治疗。
Pub Date : 2025-06-18 DOI: 10.1021/cbe.5c00031
Jiaqi Fan, Qi Wei, Pengcheng Yuan, Bing Xiao, Shasha Yao, Haoran Xu, Jiwei Liu, Ruoshui Li, Youqing Shen, Nigel K. H. Slater and Jianbin Tang*, 

The success of SARS-CoV-2 mRNA vaccines has boosted their development against various diseases, especially tumors. However, their clinical application is hindered by limited therapeutic efficacy and non-negligible side effects. Many studies attempt to improve therapeutic effect against tumors by using spleen-tropism mRNA delivery systems. Herein, we develop lipid nanoparticles (LNPs) based on hydroxychloroquine (HCQ)-derived ionizable lipid as a spleen-tropism mRNA delivery system that simultaneously modulates the tumor immune-suppressive microenvironment. The screened HCQ LNPs exhibit high mRNA transfection efficiency both in vitro and in vivo. Surprisingly, the HCQ LNP can achieve spleen-tropic transfection after systemic administration, which is conducive to immune cells for antigen presentation. In addition, HCQ LNP passively targeted to tumors significantly repolarizes tumor-associated macrophages to the M1 phenotype, thereby modulating the tumor microenvironment. Therefore, compared to the commercial MC-3 LNP/mOVA, HCQ LNP/mOVA shows significantly improved prophylactic and therapeutic antitumor efficacy and antimetastatic effect. HCQ LNP/mOVA demonstrates a multifaceted strategy that enhances the therapeutic efficacy of mRNA tumor vaccines through functional mRNA delivery system design.

SARS-CoV-2 mRNA疫苗的成功促进了它们针对各种疾病,特别是肿瘤的发展。然而,其治疗效果有限,副作用不可忽视,阻碍了其临床应用。许多研究试图通过使用脾性mRNA传递系统来提高对肿瘤的治疗效果。在此,我们开发了基于羟氯喹(HCQ)衍生的可电离脂质的脂质纳米颗粒(LNPs),作为一个脾性mRNA传递系统,同时调节肿瘤免疫抑制微环境。筛选的HCQ LNPs在体外和体内均表现出较高的mRNA转染效率。令人惊讶的是,HCQ LNP在全身给药后可以实现脾性转染,这有利于免疫细胞的抗原呈递。此外,HCQ LNP被动靶向肿瘤,显著地将肿瘤相关巨噬细胞重极化至M1表型,从而调节肿瘤微环境。因此,与市售的MC-3 LNP/mOVA相比,HCQ LNP/mOVA具有显著提高的预防和治疗性抗肿瘤疗效和抗转移效果。HCQ LNP/mOVA展示了通过功能性mRNA传递系统设计提高mRNA肿瘤疫苗治疗效果的多方面策略。
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引用次数: 0
Pressurized Screw Feeding Reactor Promoted Continuous and Scalable Production of Hydroxycinnamic Acids. 加压螺杆加料反应器促进了羟基肉桂酸的连续化和规模化生产。
Pub Date : 2025-06-10 eCollection Date: 2025-09-25 DOI: 10.1021/cbe.5c00028
Yutao Yang, Binyu Zhang, Junzheng Yu, Tianhan Zhu, Peidong Li, Zhuo He, Tianyu Ren, Yanbin Cui, Chenguang Wang

The valorization of agricultural waste into high-value hydroxycinnamic acids (HCAs) is critical for advancing sustainable biorefineries. However, traditional batch alkaline hydrolysis processes are hindered by cost-prohibitive downtime, labor-intensive operations, and inefficient heat-mass transfer, limiting their industrial applicability. This study presents a continuous high-pressure screw reactor (HPSR) system that integrates intensified mechanical shear, enhanced material mixing, and improved process controllability. These features collectively accelerate reaction kinetics while significantly suppressing product thermal degradation, enabling a high yield of HCAs (25.46 mg/g) and lignin removal (93.6%) within a time scale of minutes. The production efficiency reaches 11.40 mg/g biomass/min, one magnitude higher than that of the batch mode. Further, a high solid/liquid ratio strategy amplifies product stream concentration, coupled with a cascade purification involving adsorption, extraction and crystallization, yielding high-purity (91.04%) p-CA product. In summary, this work demonstrates an efficient conversion strategy to convert herbaceous biomass into HCAs and other industrially relevant components in a continuous fashion.

将农业废弃物转化为高价值的羟基肉桂酸(HCAs)对于推进可持续生物炼制至关重要。然而,传统的间歇式碱性水解工艺受到成本过高的停机时间、劳动密集型操作和低效的热质传递的阻碍,限制了它们的工业适用性。本研究提出了一种连续高压螺杆反应器(HPSR)系统,该系统集成了强化的机械剪切、增强的材料混合和改进的过程可控性。这些特性共同加速了反应动力学,同时显著抑制了产物的热降解,在几分钟的时间尺度内实现了HCAs的高产率(25.46 mg/g)和木质素的去除率(93.6%)。生产效率达到11.40 mg/g生物质/min,比间歇式生产效率提高一个数量级。此外,高固液比策略提高了产品流浓度,再加上包括吸附、提取和结晶在内的级联纯化,得到高纯度(91.04%)的p-CA产品。总之,这项工作证明了一种有效的转化策略,可以将草本生物质持续转化为HCAs和其他工业相关成分。
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引用次数: 0
Development Strategies for Influenza Vaccines Utilizing Phage RNA Polymerase and Capping Enzyme NP868R 利用噬菌体RNA聚合酶和盖帽酶NP868R开发流感疫苗的策略
Pub Date : 2025-06-09 DOI: 10.1021/cbe.5c00030
Weijun Wang, Zihan Ma, Qiuli Lou, Tingting Li, Zhaoying Huang, Wen Yin, Chunbo Lou* and Yanhui Xiang*, 

Influenza remains a highly contagious respiratory disease with profound global health and economic implications. Although traditional vaccines, including inactivated influenza vaccines (IIVs), live attenuated influenza vaccines (LAIVs), and recombinant subunit influenza vaccines (RIVs), are widely available, their efficacy against emerging viral strains is often limited. This limitation underscores the urgent need for novel vaccine strategies. In this study, we explored both DNA and RNA vaccine platforms for influenza, utilizing phage RNA polymerase (RNAP) and the capping enzyme NP868R. For the influenza DNA vaccine strategy, we employed a phage RNAP-dependent positive feedback transcription system to achieve high-efficiency expression of the influenza hemagglutinin (HA) antigen. Utilizing the transcription mechanism dependent on phage RNAP polymerase, our DNA vaccine strategy confines antigen transcription and translation within the cytoplasm, thereby reducing the risk of genomic integration inherent to conventional DNA vaccines. In parallel, for the influenza RNA vaccine, we developed a replication-deficient vesicular stomatitis virus (rdVSV) expressing HA as a self-amplifying RNA vaccine. By replacing the traditional T7 vaccinia virus with T7 RNAP fused to a capping enzyme in the rdVSV rescue process, we achieved a high titer of 1.2 × 107 PFU/mL in a single round of rescue. This modification not only shortened the time required for recombinant VSV (rdVSV) rescue but also mitigated the safety concerns associated with T7 vaccinia virus usage. Moreover, this innovation facilitates faster RNA vaccine production, reduces manufacturing costs, and relaxes environmental requirements for RNA vaccine production. In animal studies, BALB/c mice immunized with the DNA vaccine exhibited significantly enhanced HA protein expression and higher antibody titers when dendritic cells (DCs) were employed as delivery carriers. Similarly, RNA vaccine immunized mice exhibited robust humoral and cellular immune responses, marked by increased HA-specific IgG levels and elevated cytokine production. These findings highlight the potential of both platforms as versatile tools for rapidly responding to emerging pathogens and advancing vaccine design for infectious diseases and therapeutic applications. With further technological optimization and clinical validation, this strategy is expected to provide a promising new solution for influenza prevention and control.

流感仍然是一种高度传染性的呼吸道疾病,对全球卫生和经济产生深远影响。虽然传统疫苗,包括灭活疫苗(IIVs)、减毒活疫苗(LAIVs)和重组亚单位流感疫苗(RIVs)广泛可用,但它们对新出现的病毒株的效力往往有限。这一限制强调了迫切需要新的疫苗策略。在这项研究中,我们利用噬菌体RNA聚合酶(RNAP)和capping酶NP868R,探索了流感的DNA和RNA疫苗平台。对于流感DNA疫苗策略,我们采用噬菌体rnap依赖的正反馈转录系统来实现流感血凝素(HA)抗原的高效表达。利用依赖于噬菌体RNAP聚合酶的转录机制,我们的DNA疫苗策略将抗原转录和翻译限制在细胞质内,从而降低了传统DNA疫苗固有的基因组整合风险。同样,对于流感RNA疫苗,我们开发了一种表达HA的复制缺陷水疱性口炎病毒(rdVSV)作为一种自我扩增的RNA疫苗。在rdVSV的拯救过程中,我们用融合了capping酶的T7 RNAP取代了传统的T7牛痘病毒,在单轮拯救中获得了1.2 × 107 PFU/mL的高滴度。这种修饰不仅缩短了重组VSV (rdVSV)救援所需的时间,而且减轻了与T7痘苗病毒使用相关的安全性问题。此外,这一创新促进了RNA疫苗的更快生产,降低了制造成本,并放宽了RNA疫苗生产的环境要求。在动物实验中,当树突状细胞(dc)作为递送载体时,用DNA疫苗免疫的BALB/c小鼠表现出显著增强的HA蛋白表达和更高的抗体滴度。同样,RNA疫苗免疫小鼠表现出强大的体液和细胞免疫反应,其特征是ha特异性IgG水平升高和细胞因子产量升高。这些发现突出了这两个平台作为快速响应新出现病原体和推进传染病疫苗设计和治疗应用的多功能工具的潜力。随着进一步的技术优化和临床验证,该策略有望为流感预防和控制提供一个有希望的新解决方案。
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引用次数: 0
Advancing Wearable VOC Sensors: A Roadmap for Sustainable Agriculture and Real-Time Plant Health Monitoring 推进可穿戴VOC传感器:可持续农业和实时植物健康监测的路线图
Pub Date : 2025-06-02 DOI: 10.1021/cbe.5c00027
Sina Jamalzadegan, Jin Xu, Yiyang Shen, Belinda Mativenga, Mingzhuo Li, Mohammadreza Zare, Akhil Penumudy, Zach Hetzler, Yong Zhu and Qingshan Wei*, 

Plant diseases account for nearly one-third of annual global crop losses, making early and real-time detection essential for safeguarding agricultural productivity. Wearable technology has emerged as a promising real-time plant health monitoring approach that detects specific physiological and chemical changes associated with plant diseases or stresses. In this review, we highlight the role of volatile organic compounds (VOCs) as noninvasive biomarkers for tracking plant health and diagnosing diseases. We explore the materials, fabrication techniques, and recent applications of wearable VOC sensors for the real-time monitoring of plant diseases and stresses. Finally, we discuss the current challenges in wearable VOC sensor development and future directions to improve their design, fabrication, and practical implementation. This mini-review aims to guide the advancement of wearable sensing technologies for sustainable agriculture and enhanced crop protection.

植物病害占全球年度作物损失的近三分之一,因此及早和实时检测对保障农业生产力至关重要。可穿戴技术已经成为一种有前途的实时植物健康监测方法,可以检测与植物疾病或胁迫相关的特定生理和化学变化。在这篇综述中,我们重点介绍了挥发性有机化合物(VOCs)作为无创生物标志物在植物健康跟踪和疾病诊断中的作用。我们探讨了可穿戴VOC传感器的材料、制造技术和最新应用,用于植物病害和胁迫的实时监测。最后,我们讨论了当前可穿戴VOC传感器发展面临的挑战,以及改进其设计、制造和实际实施的未来方向。这篇综述旨在指导可穿戴传感技术在可持续农业和加强作物保护方面的发展。
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引用次数: 0
Mechanisms and Strategies for Engineering Oxidative Stress Resistance in Saccharomyces cerevisiae 酿酒酵母抗氧化应激工程的机制与策略。
Pub Date : 2025-05-28 DOI: 10.1021/cbe.5c00021
Taotao Feng, Hongwei Yu and Lidan Ye*, 

Oxidative stress, driven by the accumulation of reactive oxygen species (ROS), poses a significant challenge to the productivity and robustness of Saccharomyces cerevisiae in industrial applications. This review provides an overview of oxidative stress mechanisms, focusing on transcription factors (Yap1p, Skn7p, Msn2/4p) and their regulation through different stress signaling pathways such as HOG, CWI, TOR, and cAMP/PKA. Advanced strategies for enhancing oxidative stress resistance are discussed, including antioxidant enzyme overexpression, redox cofactor optimization, transcription factor modulation, and promoter engineering. Emerging tools like omics-guided gene discovery, biosensor-based feedback regulation, and machine learning-driven optimization are highlighted as promising approaches for constructing robust yeast cell factories. These insights pave the way for intelligent strain design to improve industrial performance under oxidative stress conditions.

由活性氧(ROS)积累驱动的氧化应激对酿酒酵母在工业应用中的生产力和稳健性提出了重大挑战。本文综述了氧化应激机制,重点介绍了转录因子(Yap1p, Skn7p, Msn2/4p)及其通过不同应激信号通路(如HOG, CWI, TOR和cAMP/PKA)的调控。讨论了提高氧化应激抗性的先进策略,包括抗氧化酶过表达、氧化还原辅助因子优化、转录因子调节和启动子工程。新兴工具,如组学引导的基因发现、基于生物传感器的反馈调节和机器学习驱动的优化,被强调为构建健壮的酵母细胞工厂的有前途的方法。这些见解为智能应变设计铺平了道路,以提高氧化应激条件下的工业性能。
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引用次数: 0
Pub Date : 2025-05-22
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引用次数: 0
Pub Date : 2025-05-22
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引用次数: 0
Pub Date : 2025-05-22
Wei Shao, Xiao-Feng Zhong, Yi-Le Chen, Zhen Chen, Miao-Miao Jia, Wen-Yong Yang, Jing-Ran Yu, Pan-Pan Zhang, Yi Li* and Ming Xue*, 
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引用次数: 0
Pub Date : 2025-05-22
Jiahong Liao, Wenyi Wang, Weicheng Tong, Lixia Qiu, Hao Cheng, Xinben Zhao, Yi He, Chunlin Yu* and Xingwang Zhang*, 
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引用次数: 0
期刊
Chem & Bio Engineering
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