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Layout Optimization of the Six-Axis Industrial Robot Based on an Improved Whale Algorithm for Reducing Energy Consumption in Industry 5.0. 工业5.0中基于改进鲸鱼算法的六轴工业机器人布局优化
IF 22.5 Pub Date : 2025-12-22 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240120
Kaiyue Cui, Yixiong Feng, Zhaoxi Hong, Zhiwu Li, Fathollahi-Fard Amirmohammad, Zengwei Ji, Jianrong Tan

In the advent of Industry 5.0, the harmonious integration of human ingenuity and robotic precision in complex work environments is pivotal for sustainable industrial growth. The six-axis industrial robot, as an essential part of carrying out cyclic pick-and-place tasks in Industry 5.0, usually works in an extremely complex working environment. This intricate working environment makes the six-axis industrial robot difficult to reach the task points effectively, resulting in a lot of energy consumption. This not only impacts productivity but also leads to excessive energy consumption, which stands at odds with the Industry 5.0 principles of resource conservation. To solve this problem, a novel method to optimize the layout scheme of the six-axis industrial robot with the goal of minimizing the energy loss is creatively proposed in this paper. First, the reachable workspace and feasible workspace under constraints are mathematically modeled and then obtained. Second, the operability and the minimum singular value are utilized to evaluate the energy loss of the feasible workspace. Third, the whale algorithm is designed and improved to obtain the optimal layout scheme of the six-axis industrial robot. Finally, a case of the recliner's production line with the six-axis industrial robot (IRB140; ABB) is provided to validate the effectiveness of the proposed method. The results show that after optimization, the optimal layout scheme has been successfully obtained, and the energy loss has reduced from 0.2917 to 0.2309, a decrease of 20.84%, proving that the proposed method can obtain the optimal layout scheme with lower energy consumption.

随着工业5.0的到来,在复杂的工作环境中,人类的聪明才智和机器人的精度的和谐融合是可持续工业增长的关键。六轴工业机器人作为工业5.0中执行循环拾取任务的重要组成部分,通常工作环境极其复杂。这种复杂的工作环境使得六轴工业机器人难以有效到达任务点,造成了大量的能量消耗。这不仅会影响生产力,还会导致过度的能源消耗,这与工业5.0节约资源的原则不一致。针对这一问题,创造性地提出了一种以能量损失最小为目标的六轴工业机器人布局方案优化方法。首先对约束条件下的可达工作空间和可行工作空间进行数学建模,得到可达工作空间;其次,利用可操作性和最小奇异值对可行工作空间的能量损失进行评估;第三,设计并改进鲸鱼算法,得到六轴工业机器人的最优布局方案。最后,以六轴工业机器人(IRB140; ABB)的躺椅生产线为例,验证了所提方法的有效性。结果表明:优化后,成功获得了最优布局方案,能量损失从0.2917降低到0.2309,降低了20.84%,证明所提方法能够以较低的能耗获得最优布局方案。
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引用次数: 0
A Groundbreaking Electric Field-Induced Cascade Gas Therapy Against Large Volume Solid Tumor Through Electro-Stress Storm. 一种开创性的电场诱导级联气体疗法通过电应激风暴治疗大体积实体瘤。
IF 22.5 Pub Date : 2025-12-21 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240410
Gui Chen, Wenjia Zhang, Manchun Wang, Fengling Zhang, Mengliang Zhu, Yan Tang, Yixian Xie, Wen Ma, Peter Timashev, Massimo Bottini, Yingqiu Xie, Xing-Jie Liang, Meng Yu, Zhiqiang Yu

Gas therapy has been limited in its application as a robust standalone antitumor strategy due to the restricted gas production and cytotoxicity. To address this challenge, we employed electrotoxic PtRu composite metal nano-berries (PR) loaded with various therapeutic gas donors to construct a groundbreaking electric field-induced cascade gas therapy (EGT) platform, which generated a great electro-stress storm at tumor sites, exerting electrotoxicity and immunity functions against solid tumors, including those of large volume, through three pathways. Initially, electric field stimulation effectively boosted the release rate and yield of therapeutic gases from the EGT platform. Further, gas molecules reacted with reactive oxygen species (ROS) to either form oxidation coordination (CO and ROS) or generate more potent therapeutic components (RNS produced from ROS and NO), contributing to an electro-stress storm that augmented the cytotoxic potential of the gas components. Subsequently, this electro-stress storm further activated the tumor immune response, identifying and capturing escaped tumor cells, which held significant implications for treating tumors, including non-solid tumors with indistinct boundaries. In summary, the EGT platform leveraged an electro-stress storm to achieve ablation of large volume solid tumors and suppressed metastatic tumors, paving new pathways for gas-based therapeutic strategies.

由于气体产生和细胞毒性的限制,气体疗法作为一种强大的独立抗肿瘤策略的应用受到限制。为了解决这一挑战,我们采用负载各种治疗气体供体的电毒性PtRu复合金属纳米浆果(PR)构建了一个开创性的电场诱导级联气体治疗(EGT)平台,该平台在肿瘤部位产生巨大的电应激风暴,通过三种途径对实体肿瘤(包括大体积肿瘤)发挥电毒性和免疫功能。最初,电场刺激有效地提高了EGT平台治疗气体的释放速度和产量。此外,气体分子与活性氧(ROS)反应形成氧化配合物(CO和ROS)或产生更有效的治疗成分(由ROS和NO产生的RNS),从而导致电应激风暴,增强气体成分的细胞毒性潜能。随后,这种电应激风暴进一步激活肿瘤免疫反应,识别和捕获逃逸的肿瘤细胞,这对治疗肿瘤(包括边界不清的非实体肿瘤)具有重要意义。总之,EGT平台利用电应激风暴实现了大体积实体瘤的消融和转移性肿瘤的抑制,为基于气体的治疗策略铺平了新的途径。
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引用次数: 0
A Bioorthogonal and Programmable Bacterial Delivery System for Spatiotemporally Targeted Therapy of Solid Tumors. 用于实体肿瘤时空靶向治疗的生物正交可编程细菌传递系统。
IF 22.5 Pub Date : 2025-12-18 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240396
Yu-Jia Wang, Wen-Jie Jiang, Hua-Jun Zhao, Jian-Qun Deng, Yi-Min Cai, Yi Li, Xiao-Lin Meng, Jin Hou, Feng-Shan Wang, Ju-Zheng Sheng

Rapid advances in synthetic biology are driving the development of microbes as therapeutic agents. While the immunosuppressive tumor microenvironment creates a favorable niche for the systematic delivery of bacteria and therapeutic payloads, these can be harmful if released into healthy tissues. To address this limitation, we designed a spatiotemporal targeting system for engineered Escherichia coli Nissle 1917, controlled by azide-modified hyaluronic acid hydrogel and near-infrared radiation induction. Using a temperature-driven genetic status switch, the system produced durable therapeutic output and promoted the therapeutic activity in solid tumors. The combination of azide-modified hyaluronic acid hydrogel and temperature-sensitive, engineered Escherichia coli Nissle 1917 provided spatiotemporal targeting of solid tumors, not only showing significant therapeutic effects on primary solid tumors, but also inhibiting the metastasis and recurrence of cancer cells by enhancing tumor-infiltrating lymphocytes. This system has potential for clinical application.

合成生物学的快速发展正在推动微生物作为治疗剂的发展。虽然免疫抑制肿瘤微环境为细菌和治疗有效载荷的系统递送创造了有利的生态位,但如果释放到健康组织中,这些可能是有害的。为了解决这一限制,我们设计了一个时空靶向系统,用于工程大肠杆菌Nissle 1917,由叠氮化物修饰透明质酸水凝胶和近红外辐射诱导控制。利用温度驱动的遗传状态开关,该系统产生持久的治疗输出,并促进了对实体肿瘤的治疗活性。叠氮化物修饰的透明质酸水凝胶与温度敏感的工程大肠杆菌Nissle 1917的结合,提供了实体瘤的时空靶向性,不仅对原发性实体瘤有显著的治疗效果,而且通过增强肿瘤浸润淋巴细胞来抑制癌细胞的转移和复发。该系统具有临床应用潜力。
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引用次数: 0
An Anisotropic and Stable-Conductance Patch for Mechanical-Electrical Coupling With Infarcted Myocardium. 一个各向异性和稳定的电导贴片与梗死心肌的机电耦合。
IF 22.5 Pub Date : 2025-12-16 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20250021
Yimeng Li, Yuchen Miao, Leqian Wei, Wenxin Li, Mengqi Shan, Qianqian Jiang, Fujun Wang, Lu Wang, Ze Zhang, Jizhou Song, Yang Zhu, Jifu Mao

Polymeric conductive patches have conventionally been employed to facilitate the repair of infarcted myocardium by enhancing myocardial electrical conduction and providing mechanical support. However, it remains a challenge to restore the electrical conduction and diastolic-systolic functions with stable and anisotropic mechanical and electrical cues in the dynamic physiological environment. Herein, inspired by the hierarchical myocardial fiber microscopic striated structure, we established a weaving-based processing method to compound a striated polypyrrole conductive coating on the surface of highly oriented elastic fiber bundles. This unique design endows the patch with exceptional stretchability (elongation at break > 400%), stable conductance (ΔR/R = 0.04 within 20% strain), and excellent fatigue resistance (ΔR/R = 0.01 after 1,000,000 cycles). In addition, the precision process grounded on woven molding accomplished the tunable mechanical and electrical properties of the patch, which facilitates the achievement of long-term, stable, and anisotropic mechanical-electrical coupling with the infarcted myocardium. The rat MI model experiments demonstrated that this anisotropic conductive patch can not only improve cardiac function and electrical activity over an extended period, but also effectively inhibit myocardial inflammation and fibrosis and promote angiogenesis. This study proposes a promising MI-treatment patch and highlights the potential of woven technology in processing biomaterials composed of both rigid and elastic materials.

聚合物导电贴片通常通过增强心肌电传导和提供机械支持来促进梗死心肌的修复。然而,在动态的生理环境中,通过稳定和各向异性的机械和电信号来恢复电传导和舒张-收缩功能仍然是一个挑战。本文受分层心肌纤维微观条纹结构的启发,建立了一种基于编织的加工方法,在高取向弹性纤维束表面复合条纹聚吡咯导电涂层。这种独特的设计赋予了贴片卓越的拉伸性(断裂伸长率> 400%),稳定的电导率(ΔR/R 0 = 0.04在20%的应变)和优异的抗疲劳性(ΔR/R 0 = 0.01后,1,000,000次循环)。此外,以编织成型为基础的精密工艺实现了贴片的机电性能可调,有利于与梗死心肌实现长期、稳定、各向异性的机电耦合。大鼠心肌梗死模型实验表明,该各向异性导电贴片不仅能长期改善心功能和心肌电活动,还能有效抑制心肌炎症和纤维化,促进血管生成。本研究提出了一种有前途的mi治疗贴片,并强调了编织技术在加工由刚性和弹性材料组成的生物材料方面的潜力。
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引用次数: 0
Nonporous Adaptive Crystals Based on Pillararene/Calixarene-Inspired Novel Macrocyclic Arenes. 基于柱芳烃/杯芳烃的新型大环芳烃无孔自适应晶体。
IF 22.5 Pub Date : 2025-12-12 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240286
Susu Ren, Haitao Wang, Bowen Zha, Zhongping Li, Guan-Yu Qiao, Jia-Rui Wu

Nonporous adaptive crystals (NACs) represent a unique class of supramolecular macrocycle-based crystalline organic materials that have garnered significant attention in supramolecular chemistry and beyond over the past decade. Unlike traditional porous materials, NACs are initially nonporous but can induce porosity through host-guest interactions in the solid-state, enabling exceptional performance in hydrocarbon separation. This review surveys the development of NACs based on novel macrocyclic arenes inspired by pillararene and calixarene structures, encompassing biphen[n]arene, tiara[n]arene, leaning pillararene, hybrid[n]arene, leggero pillararene, geminiarene, bowtiearene, rhombicarene, and other derivatives. Emphasizing their preparation, structural characteristics, and mechanisms of adsorptive selectivity, this comprehensive overview highlights their contributions to advancing supramolecular chemistry, functional materials, and beyond. Finally, the remaining challenges and perspectives are outlined. It is anticipated that this review will serve as a timely and valuable reference for researchers interested in NACs and related materials, stimulating further impactful studies in related fields.

无孔自适应晶体(NACs)是一类独特的基于大环的超分子有机晶体材料,在过去十年中在超分子化学及其他领域引起了极大的关注。与传统的多孔材料不同,NACs最初是无孔的,但可以通过固态的主客体相互作用诱导孔隙,从而实现优异的碳氢化合物分离性能。本文综述了基于柱芳烃和杯芳烃结构的新型大环芳烃的研究进展,包括联苯[n]芳烃、冠状[n]芳烃、斜柱芳烃、杂化[n]芳烃、柱状[n]芳烃、双烯芳烃、弓形[n]芳烃、菱双芳烃等衍生物。强调它们的制备、结构特征和吸附选择性机制,这篇综合综述突出了它们在推进超分子化学、功能材料等方面的贡献。最后,概述了剩余的挑战和前景。希望本文能够为研究NACs及相关材料的研究人员提供及时、有价值的参考,促进相关领域的深入研究。
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引用次数: 0
Caffeic Acid Acts as a Potent Senomorphic and Alleviates Inflammation and Lung Fibrosis by Covalently Targeting Annexin A5 Protein in Mice. 咖啡酸共价靶向膜联蛋白A5减轻小鼠炎症和肺纤维化。
IF 22.5 Pub Date : 2025-12-12 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240069
Yinhua Zhu, Ying Zhang, Qianyu Zhang, Ping Song, Junzhe Zhang, Ang Ma, Chen Wang, Peng Gao, Tong Yang, Lirun Zhou, Qiaoli Shi, Yin Kwan Wong, Yongting Luo, Huan Tang, Jigang Wang

The accumulation of senescent cells and their secretion of senescence-associated secretory phenotype (SASP) play important roles in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Small molecules, known as senolytics or senomorphics, have been effective in targeting senescent cells. Although senolytic drugs have been well-studied in pulmonary fibrosis, senomorphics with defined protein targets and potential applications are rarely investigated. In this study, we identified a widely sourced natural product, caffeic acid (CA), to act as a potent senomorphic that effectively inhibits the secretion of SASP in senescent lung cells. We demonstrated that the covalent binding of CA to Annexin A5 protein triggered its degradation, PKCθ deactivation, and the inhibition of the NF-κB inflammatory pathway in senescent cells. Notably, CA exhibited a promising effect in limiting inflammation in the lung and circulatory system, alleviating pulmonary pathology, and improving physical function in a bleomycin-induced pulmonary fibrosis mouse model. Our investigation suggests that Annexin A5 could be used as the target for the precise intervention of aging-related diseases such as IPF.

衰老细胞的积累及其分泌衰老相关分泌表型(senescence-associated secretory phenotype, SASP)在特发性肺纤维化(idiopathic pulmonary fibrosis, IPF)的发病机制中起重要作用。被称为senolytics或senomorphics的小分子在靶向衰老细胞方面很有效。虽然抗衰老药物在肺纤维化中的应用已经得到了很好的研究,但具有明确蛋白靶点和潜在应用的senomorphics却很少被研究。在这项研究中,我们发现了一种广泛来源的天然产物,咖啡酸(CA),作为一种有效的senomorphic,有效抑制衰老肺细胞中SASP的分泌。我们证明了CA与膜联蛋白A5蛋白的共价结合引发了其降解,PKCθ失活,并抑制了衰老细胞中NF-κB炎症通路。值得注意的是,在博莱霉素诱导的肺纤维化小鼠模型中,CA在限制肺部和循环系统炎症、减轻肺部病理和改善身体功能方面表现出了有希望的效果。本研究提示,Annexin A5可作为精准干预IPF等衰老相关疾病的靶点。
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引用次数: 0
Synergistic Effects of MHD Dynamics and Oxygen Vacancies on Electrode Polarization in Photoelectrocatalysis CO2 Reduction Systems. MHD动力学和氧空位对光电催化CO2还原体系电极极化的协同效应
IF 22.5 Pub Date : 2025-12-08 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240243
Lei Zhao, Feng Xiao, Xianghui Zeng, Zhaohui Huang, Wei Fang, Xing Du, Xuan He, Weixin Li, Daheng Wang, Hui Chen

Photoelectrocatalysis reduction of CO2 into products such as CO and CH4 is an effective strategy for improving carbon utilization and advancing the development of renewable energy. Improving the catalytic efficiency by regulating the polarization behavior of the electrode has been proven to be an effective method. In this study, a method for preparing a Ti:Fe2O3/CuFeO2-v photoanode with oxygen vacancies and heterojunctions for PEC CO2 reduction is reported. Oxygen vacancies not only enhance the carrier transport ability of the electrode and improve the resistance polarization, but also regulate the material's magnetic properties. Based on this, we utilize the magnetic fluid dynamics (MHD) effect to reduce the thickness of the diffusion layer on the electrode surface, thereby improving mass transfer and solving the concentration polarization problem. This adjustment increased the current density to 1.49 mA cm-2 and increased the CO yield to 154.27 mL h-1. This method innovatively applies the MHD insights of the electrochemical oxygen evolution reaction (OER) to photoelectrochemical CO2 reduction, aiming to optimize the electrode reaction kinetics for efficient CO2 conversion, marking a significant progress in the field of photocatalytic CO2 reduction.

光电催化将CO2还原为CO和CH4等产物是提高碳利用率和推进可再生能源发展的有效策略。通过调节电极的极化行为来提高催化效率是一种有效的方法。本文报道了一种制备具有氧空位和异质结的Ti:Fe2O3/CuFeO2-v光阳极用于PEC CO2还原的方法。氧空位不仅可以增强电极的载流子输运能力,改善电阻极化,还可以调节材料的磁性能。在此基础上,利用磁流体动力学(MHD)效应减小电极表面扩散层的厚度,从而改善传质,解决浓度极化问题。这一调整将电流密度提高到1.49 mA cm-2,并将CO产率提高到154.27 mL h-1。该方法创新地将电化学析氧反应(OER)的MHD见解应用于光电化学CO2还原,旨在优化电极反应动力学以实现高效的CO2转化,标志着光催化CO2还原领域的重大进展。
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引用次数: 0
Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process. 骨膜类器官:受骨愈合过程启发的仿生设计。
IF 22.5 Pub Date : 2025-12-07 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240298
Shuyue Hao, Fuxiao Wang, Jingtao Huang, Zhidao Xia, James T Triffitt, Chenjie Xu, Long Bai, Jiacan Su

Large bone defects present major problems in plastic, maxillofacial, and orthopedic reconstructive surgery. With respect to osseous tissues, currently, autologous and allogeneic bone grafts are commonly used clinical treatments, but there are limitations in terms of donor availability, morbidity, and risk of immunogenic reactions. Tissue-engineered bone constructs offer promising alternatives but struggle to replicate the complex biological functions of native bone, leading to suboptimal outcomes. The periosteum has been shown to be a key factor in bone regeneration and has a bilayered structure that is essential for bone integrity and repair. However, large bone defects cause damage to the periosteum and weaken its regenerative capacity. Therefore, periosteum organoids have been developed with the help of new organoid technology to achieve accelerated bone regeneration. This technology incorporates a variety of natural/synthetic materials and biologically derived factors that can be endowed with key biological functions for bone regeneration, such as, antimicrobial, immunomodulatory, neuromodulatory, angiogenic, and osteogenic capabilities. This review explores the structure and function of periosteum, the design and application of periosteum organoids and their potential integration with bone organoids. In addition, the recent advances and future directions for the use of such organoids in novel regenerative medicine and bone repair strategies are highlighted.

大骨缺损是整形外科、颌面外科和骨科重建外科的主要问题。就骨组织而言,目前,自体和异体骨移植是常用的临床治疗方法,但在供体可用性、发病率和免疫原性反应风险方面存在局限性。组织工程骨结构提供了有希望的替代方案,但难以复制天然骨的复杂生物功能,导致不理想的结果。骨膜已被证明是骨再生的关键因素,具有双层结构,对骨完整性和修复至关重要。然而,较大的骨缺损会对骨膜造成损伤,削弱其再生能力。因此,在新的类器官技术的帮助下,骨膜类器官得到了发展,以实现骨的加速再生。该技术结合了多种天然/合成材料和生物衍生因子,这些因子可以被赋予骨再生的关键生物学功能,如抗菌、免疫调节、神经调节、血管生成和成骨能力。本文就骨膜的结构和功能、骨膜类器官的设计和应用以及骨膜类器官与骨类器官结合的潜力作一综述。此外,还重点介绍了类器官在新型再生医学和骨修复策略中的应用的最新进展和未来发展方向。
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引用次数: 0
Ferrimagnetic Vortex Nanorings Facilitate Efficient and Safe Deep-Brain Magnetothermal Stimulation in Freely Moving Mice. 铁磁涡旋纳米环促进自由运动小鼠高效安全的脑深部磁热刺激。
IF 22.5 Pub Date : 2025-12-04 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240118
Galong Li, Xin Qiao, Yu Zhao, Dongyan Li, Guigen Zhang, Xiaoli Liu, Fulin Chen, Huaning Wang, Hongbing Lu, Jin Zhou, Changyong Wang, Haiming Fan

Magnetothermal neuromodulation is a minimally invasive, deep-brain accessible, and tether-free technique. The precisely timed activation of thermosensitive ion channels, such as TRPV1, with local heat generated using magnetic nanoparticles is crucial for efficient neuromodulation. Nevertheless, this technique is greatly hindered by its long stimulus-response time and high safety risks due to the poor heat-generating performance of the nanomediators. Herein, we report the establishment of a ferrimagnetic vortex iron oxide nanoring (FVIO)-mediated magnetothermal neurostimulation technique that is efficient and safe. Compared with widely used superparamagnetic iron oxide nanomediators (SPIOs), the FVIOs triggered Ca2+ influx into HEK293T cells and cortical neurons at an Fe concentration of 51 µg mL-1, which is 20.27-fold lower than that needed for SPIOs. In vivo magnetothermal stimulation in the central nucleus of the amygdala of mice further demonstrated that FVIOs with the optimal dose of 0.05 µg evoked fear behaviors with an average latency of 2.51 s, which was 2.3-fold faster than that in the SPIO (0.80 µg)-treated group. More importantly, FVIOs-mediated stimulation not only exhibited negligible histopathological alterations and proinflammatory cytokine expression but also successfully elicited fear behaviors in transgene-free mice. The FVIO-mediated efficient and safe neuromodulation has the potential for future neuroscience exploitation and neurological disease treatment.

磁热神经调节是一种微创的、可深入大脑的、无系绳的技术。利用磁性纳米颗粒产生的局部热量,精确定时激活热敏离子通道,如TRPV1,对于有效的神经调节至关重要。然而,由于纳米介质的发热性能差,该技术的刺激响应时间长,安全风险高,极大地阻碍了该技术的发展。本文报道了一种高效、安全的铁磁涡旋氧化铁纳米环(FVIO)介导的磁热神经刺激技术的建立。与广泛使用的超顺磁性氧化铁纳米介质(SPIOs)相比,FVIOs在铁浓度为51 μ g mL-1时触发Ca2+内流进入HEK293T细胞和皮质神经元,比SPIOs所需的低20.27倍。体内磁热刺激小鼠杏仁核中央核进一步证实,最佳剂量0.05µg的FVIOs诱发的恐惧行为平均潜伏期为2.51 s,比SPIO(0.80µg)处理组快2.3倍。更重要的是,fvios介导的刺激不仅表现出可忽略不计的组织病理学改变和促炎细胞因子的表达,而且还成功地引发了无转基因小鼠的恐惧行为。fvio介导的高效、安全的神经调节在未来的神经科学开发和神经系统疾病治疗中具有潜力。
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引用次数: 0
Global Stress Responses Identify the Functionally Divergent Regulators Required for Candida auris Commensalism and Pathogenicity. 全球应激反应识别耳念珠菌共通性和致病性所需的功能差异调节因子。
IF 22.5 Pub Date : 2025-11-11 eCollection Date: 2025-12-01 DOI: 10.1002/EXP.20240482
Chaoyue Xu, Wanxing Xu, Yushun Yuan, Xiaoqing Chen, Ouyang Mo, Zhe Yin, Xinhua Huang, Yuanyuan Wang, Lingfei Hu, Wenwen Xue, Yun Zou, Luyao Zhang, Kunlin Li, Yueru Tian, Jihong Liu, Sichu Xiong, Lei Wu, Yanmei Dong, Guangsheng Chen, Yuping Zhang, Zili Zhou, Ming Guan, Xiaotian Huang, Zhiyi He, Lin Zhong, Lingbing Zeng, Pei Hao, Xiaoqi Zheng, Changbin Chen, Ning-Ning Liu, Dongsheng Zhou

Given its global distribution and high transmissibility in the environment, Candida auris poses a serious threat to global public health. However, the underlying mechanisms of its adaptive strategies remain poorly understood. Here we delineate the pan-genome structures of 1,306 representative C. auris isolates collected from 28 countries. In addition to the clade-related genetic diversity and highly variable pan-genomes, we identify the key regulatory modules and genes specific to C. auris in response to 32 different host microenvironment-mimicking stresses. Through comparative analysis with evolutionarily close fungal relatives, we uncover both shared and species-specific transcriptional responses in C. auris. Intriguingly, our results reveal a distinct pathogenic role for the conserved iron regulon in this species. Unexpectedly, we also identify an evolutionarily divergent functional role for RIM101 in regulating both pathogenicity and commensalism of C. auris. Mechanistically, the high-affinity glucose transporters were found to enhance the tolerance to alkaline stress through alleviation of RIM101-dependent glucose repression in the host microenvironment. These findings provide mechanistic insights into the evolutionarily divergent adaptive strategies in both commensalism and virulence of the emerging critical priority fungal pathogen, C. auris.

鉴于其全球分布和在环境中的高传播性,耳念珠菌对全球公共卫生构成严重威胁。然而,其适应策略的潜在机制仍然知之甚少。在这里,我们描绘了从28个国家收集的1,306个具有代表性的金黄色葡萄球菌分离株的泛基因组结构。除了进化支相关的遗传多样性和高度可变的泛基因组外,我们还确定了金黄色葡萄球菌对32种不同宿主微环境模拟胁迫的关键调控模块和特异性基因。通过与进化上接近的真菌亲戚的比较分析,我们发现了C. auris的共享和物种特异性转录反应。有趣的是,我们的结果揭示了该物种中保守的铁调控子的独特致病作用。出乎意料的是,我们还发现RIM101在调节金黄色葡萄球菌的致病性和共体性方面具有进化上不同的功能作用。在机制上,高亲和力的葡萄糖转运蛋白通过减轻宿主微环境中rim101依赖性的葡萄糖抑制来增强对碱性胁迫的耐受性。这些发现为新出现的关键优先真菌病原体C. auris的共栖性和毒力的进化差异适应策略提供了机制见解。
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引用次数: 0
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Exploration (Beijing, China)
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