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  • Xiayu Xu, Zhanfeng Xiao, Fan Zhang, Changxiang Wang, Bo Wei, Yaohui Wang, Bo Cheng, Yuanbo Jia, Yuan Li, Bin Li, Hui Guo, Feng Xu
    Research. Vol 6 Article ID 0285

    Visualizing cellular structures especially the cytoskeleton and the nucleus is crucial for understanding mechanobiology, but traditional fluorescence staining has inherent limitations such as phototoxicity and photobleaching. Virtual staining techniques provide an alternative approach to addressing these issues but often require substantial amount of user training data. In this study, we develop a generalizable cell virtual staining toolbox (termed CellVisioner) based on few-shot transfer learning that requires substantially reduced user training data. CellVisioner can virtually stain F-actin and nuclei for various types of cells and extract single-cell parameters relevant to mechanobiology research. Taking the label-free single-cell images as input, CellVisioner can predict cell mechanobiological status (e.g., Yes-associated protein nuclear/cytoplasmic ratio) and perform long-term monitoring for living cells. We envision that CellVisioner would be a powerful tool to facilitate on-site mechanobiological research.

  • Shan Lei, Kejia Jiang, Chenqing Zhang, Wei Sun, Yuantao Pan, Dong Wang, Peng Huang, Jing Lin
    Research. Vol 6 Article ID 0286

    Second near-infrared (NIR-II) window optical molecular imaging kicks off a new revolution in high-quality imaging in vivo, but always suffers from the hurdles of inevitable tissue autofluorescence background and NIR-II probe development. Here, we prepare a Förster resonance energy transfer-based ratiometric NIR-II window hydrogen sulfide (H2S) sensor through the combination of an H2S-responsive NIR-II cyanine dye (acceptor, LET-1055) and an H2S-inert rhodamine hybrid polymethine dye (donor, Rh930). This sensor not only exhibits high sensitivity and selectivity, but also shows rapid reaction kinetics (~20 min) and relatively low limit of detection (~96 nM) toward H2S, allowing in vivo ratiometric NIR-II fluorescence imaging of orthotopic liver and colon tumors and visualization of the drug-induced hepatic H2S fluctuations. Our findings provide the potential for advancing the feasibility of NIR-II activity-based sensing for in vivo clinical diagnosis.

  • Jianan Lu, Huaming Li, Guoqiang Zhang, Fan Yang, Xiaotao Zhang, An Ping, Zhouhan Xu, Yichen Gu, Rui Wang, Dan Ying, Jianjian Liu, Jianmin Zhang, Ligen Shi
    Research. Vol 6 Article ID 0287

    Immunosenescence refers to the multifaceted and profound alterations in the immune system brought about by aging, exerting complex influences on the pathophysiological processes of diseases that manifest upon it. Using a combination of single-cell RNA sequencing, cytometry by time of flight, and various immunological assays, we investigated the characteristics of immunosenescence in the peripheral blood of aged mice and its impact on the cerebral immune environment after ischemic stroke. Our results revealed some features of immunosenescence. We observed an increase in neutrophil counts, concurrent with accelerated neutrophil aging, characterized by altered expression of aging-associated markers like CD62L and consequential changes in neutrophil-mediated immune functions. Monocytes/macrophages in aged mice exhibited enhanced antigen-presentation capabilities. T cell profiles shifted from naive to effector or memory states, with a specific rise in T helper 1 cells and T helper 17 cells subpopulations and increased regulatory T cell activation in CD4 T cells. Furthermore, regulatory CD8 T cells marked by Klra decreased with aging, while a subpopulation of exhausted-like CD8 T cells expanded, retaining potent immunostimulatory and proinflammatory functions. Critically, these inherent disparities not only persisted but were further amplified within the ischemic hemispheres following stroke. In summary, our comprehensive insights into the key attributes of peripheral immunosenescence provide a vital theoretical foundation for understanding not only ischemic strokes but also other age-associated diseases.

  • Jianing Xu, Juan Meng, Yi Hu, Yongzhuang Liu, Yuhan Lou, Wenjing Bai, Shuo Dou, Haipeng Yu, Shuangyin Wang
    Research. Vol 6 Article ID 0288

    Lignin is the most promising candidate for producing aromatic compounds from biomass. However, the challenge lies in the cleavage of C−C bonds between lignin monomers under mild conditions, as these bonds have high dissociation energy. Electrochemical oxidation, which allows for mild cleavage of C−C bonds, is considered an attractive solution. To achieve low-energy consumption in the valorization of lignin, the use of highly efficient electrocatalysts is essential. In this study, a meticulously designed catalyst consisting of cobalt-doped nickel (oxy)hydroxide on molybdenum disulfide heterojunction was developed. The presence of molybdenum in a high valence state promoted the adsorption of tert-butyl hydroperoxide, leading to the formation of critical radical intermediates. In addition, the incorporation of cobalt doping regulated the electronic structure of nickel, resulting in a lower energy barrier. As a result, the heterojunction catalyst demonstrated a selectivity of 85.36% for cleaving the Cα−Cβ bond in lignin model compound, achieving a substrate conversion of 93.69% under ambient conditions. In addition, the electrocatalyst depolymerized 49.82 wt% of soluble fractions from organosolv lignin (OL), resulting in a yield of up to 13 wt% of aromatic monomers. Significantly, the effectiveness of the prepared electrocatalyst was also demonstrated using industrial Kraft lignin (KL). Therefore, this research offers a practical approach for implementing electrocatalytic oxidation in lignin refining.

  • Yuhui Tang, Wenwen Tian, Shaoquan Zheng, Yutian Zou, Jindong Xie, Junsheng Zhang, Xing Li, Yuying Sun, Jing Lan, Ning Li, Xiaoming Xie, Hailin Tang
    Research. Vol 6 Article ID 0289

    Triple-negative breast cancer (TNBC) is considered as the most hazardous subtype of breast cancer owing to its accelerated progression, enormous metastatic potential, and refractoriness to standard treatments. Long noncoding RNAs (lncRNAs) are extremely intricate in tumorigenesis and cancerous metastasis. Nonetheless, their roles in the initiation and augmentation of TNBC remain elusive. Here, in silico analysis and validation experiments were utilized to analyze the expression pattern of clinically effective lncRNAs in TNBC, among which a protective lncRNA LYPLAL1-DT was essentially curbed in TNBC samples and indicated a favorable prognosis. Gain- and loss-of-function assays elucidated that LYPLAL1-DT considerably attenuated the proliferative and metastatic properties along with epithelial-mesenchymal transition of TNBC cells. Moreover, forkhead box O1 (FOXO1) was validated to modulate the transcription of LYPLAL1-DT. Mechanistically, LYPLAL1-DT impinged on the malignancy of TNBC mainly by restraining the aberrant reactivation of the Wnt/β-catenin signaling pathway, explicitly destabilizing and diminishing β-catenin protein by interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK) and constricting the formation of the hnRNPK/β-catenin complex. Conclusively, our present research revealed the anti-oncogenic effects of LYPLAL1-DT in TNBC, unraveling the molecular mechanisms of the FOXO1/LYPLAL1-DT/hnRNPK/β-catenin signaling axis, which shed innovative light on the potential curative medicine of TNBC.

  • Meng Wang, Yen Wei, Ruoxin Li, Xin Wang, Chengyu Wang, Nanqi Ren, Shih-Hsin Ho
    Research. Vol 6 Article ID 0290

    Solar-driven desalination systems have been recognized as an effective technology to address the water crisis. Recently, evaporators prepared based on advanced manufacturing technologies have emerged as a promising tool in enhancing ocean energy utilization. In this review, we discussed the thermal conversion, energy flow, salt deposition mechanisms, and design strategies for solar-driven desalination systems, and explored how to improve the desalination performance and energy use efficiency of the systems through advanced manufacturing technologies. In future perspectives, we determined the feasibility of coupling solar-driven solar desalination systems with multi-stage energy utilization systems and emerging artificial intelligence technologies, for which conclusions are given and new directions for future desalination system development are envisioned. Finally, exciting opportunities and challenges in the face of basic research and practical implementation are discussed, providing promising solutions and blueprints for green and novel desalination technologies while achieving sustainable development.

  • Xiaoyu He, Yidian Fu, Liang Ma, Yizheng Yao, Shengfang Ge, Zhi Yang, Xianqun Fan
    Research. Vol 6 Article ID 0291

    Owing to the promising therapeutic effect and one-time treatment advantage, gene therapy may completely change the management of eye diseases, especially retinal diseases. Adeno-associated virus (AAV) is considered one of the most promising viral gene delivery tools because it can infect various types of tissues and is considered as a relatively safe gene delivery vector. The eye is one of the most popular organs for gene therapy, since its limited volume is suitable for small doses of AAV stably transduction. Recently, an increasing number of clinical trials of AAV-mediated gene therapy are underway. This review summarizes the biological functions of AAV and its application in the treatment of various ocular diseases, as well as the characteristics of different AAV delivery routes in clinical applications. Here, the latest research progresses in AAV-mediated gene editing and silencing strategies to modify that the genetic ocular diseases are systematically outlined, especially by base editing and prime editing. We discuss the progress of AAV in ocular optogenetic therapy. We also summarize the application of AAV-mediated gene therapy in animal models and the difficulties in its clinical transformation.

  • Wanying Ruan, Haibin Duan, Yongbin Sun, Wanmai Yuan, Jie Xia
    Research. Vol 6 Article ID 0297
  • Shiyu Yan, Fenghua Zhang, Lan Luo, Linlin Wang, Yanju Liu, Jinsong Leng
    Research. Vol 6 Article ID 0234

    Shape memory polymers (SMPs) and their composites (SMPCs) are smart materials that can be stably deformed and then return to their original shape under external stimulation, thus having a memory of their shape. Three-dimensional (3D) printing is an advanced technology for fabricating products using a digital software tool. Four-dimensional (4D) printing is a new generation of additive manufacturing technology that combines shape memory materials and 3D printing technology. Currently, 4D-printed SMPs and SMPCs are gaining considerable research attention and are finding use in various fields, including biomedical science. This review introduces SMPs, SMPCs, and 4D printing technologies, highlighting several special 4D-printed structures. It summarizes the recent research progress of 4D-printed SMPs and SMPCs in various fields, with particular emphasis on biomedical applications. Additionally, it presents an overview of the challenges and development prospects of 4D-printed SMPs and SMPCs and provides a preliminary discussion and useful reference for the research and application of 4D-printed SMPs and SMPCs.

  • Wanying Ruan, Haibin Duan, Yongbin Sun, Wanmai Yuan, Jie Xia
    Research. Vol 6 Article ID 0246

    This paper investigates a multiplayer reach–avoid differential game in 3-dimensional (3D) space, which involves multiple pursuers, multiple evaders, and a designated target region. The evaders aim to reach the target region, while the pursuers attempt to guard the target region by capturing the evaders. This class of research holds significant practical value. However, the complexity of the problem escalates substantially with the growing number of players, rendering its solution extremely challenging. In this paper, the multiplayer game is divided into many subgames considering the cooperation among pursuers, reducing the computational burden, and obtaining numerically tractable strategies for players. First, the Apollonius sphere, a fundamental geometric tool for analyzing the 3D differential game, is formulated, and its properties are proved. Based on this, the optimal interception point for the pursuer to capture the evader is derived and the winning conditions for the pursuer and evader are established. Then, based on the Apollonius sphere, the optimal state feedback strategies of players are designed, and simultaneously, the optimal one-to-one pairings are obtained. Meanwhile, the Value function of the multiplayer reach–avoid differential game is explicitly given and is proved to satisfy Hamilton–Jacobi–Isaacs (HJI) equation. Moreover, the matching algorithm for the case with pursuers outnumbered evaders is provided through constructing a weighted bipartite graph, and the cooperative tactics for multiple pursuers are proposed, inspired by the Harris’ Hawks intelligent cooperative hunting tactics. Finally, numerical simulations are conducted to illustrate the effectiveness of the theoretical results for both cases where the number of adversary players is equal and unequal between the 2 groups.