2026-02-20 2026, Volume 6 Issue 1

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  • RESEARCH ARTICLE
    Zhixia Xu, Shuo Bao, Massimo Moccia, Giuseppe Castaldi, Tie Jun Cui, Vincenzo Galdi

    Electromagnetic metasurfaces with suitably designed spatial modulations of surface impedance can guide surface waves similarly to volumetric dielectric waveguides. As a result, the transverse distribution of the fundamental mode is usually nonuniform (peaked at the center), and its effective index is influenced by the electrical size of the central (core) region. Here, we introduce the concept of scale-invariant surface waveguiding, extending the recent advancements in dielectric waveguides to flatland settings. By leveraging spatial symmetry and fine-tuning the in-plane mode profile at the bound-leaky boundary, we design metasurface waveguides with uniform modal field distribution in the core region, where the effective index remains invariant with respect to the core width. Our findings encompass not only fully capacitive or inductive scenarios but also complex capacitive-inductive junctions supporting coupled line waves. Experimental validation through near-field measurements on a microwave prototype operating in the C band confirms our theoretical predictions. These results hold intriguing potentials for applications in flat optics, sensing, and communications.

  • EDITORIAL
  • REVIEW
    Zi Wei Tan, Neil Felicio Agesta, Ryan Yow Zhong Yeo, Joel Jie Foo, Wee-Jun Ong
    2026, 6(1): 20240008. https://doi.org/10.1002/EXP.20240008

    Electrocatalytic water splitting with carbon nitride (CxNy) materials has gained significant interest, driven by extensive research validating their synthesis, structure, and applications. Among various CxNy stoichiometric ratios, graphitic carbon nitride (g-C3N4) stands out as the most stable configuration and is extensively studied in the literature. However, other CxNy structures like g-CN, C2N, C3N5, and C9N4 have been booming recently as well by exploration of their greatness. Recent progress of CxNy-based electrocatalysts in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting (OWS) has been examined meticulously. More emphasis has been placed on exploring the synthesis-structure-performance and simulate-structure-performance relationships of CxNy electrocatalysts in experimental and computational studies, respectively. This review outlines a clear framework for unifunctional CxNy electrocatalysts in HER and OER, focusing on recent advancements in (1) defect engineering, (2) structural engineering, and (3) hybridization. The research on bifunctional CxNy electrocatalysts is highlighted and explored through two main approaches: intrinsic and extrinsic modifications. Finally, the strategies and perspectives for creating novel highly efficient CxNy electrocatalysts for HER, OER, and OWS are analyzed. This review aims to inspire researchers to incorporate computational methods into experimental studies for developing highly efficient bifunctional CxNy-based electrocatalysts.

  • REVIEW
    Yejoon Kim, Enok Lee, Sanghan Lee
    2026, 6(1): 20240020. https://doi.org/10.1002/EXP.20240020

    This review explores advancements in passivation and encapsulation methods for organic semiconductor (OS) and halide perovskite (HP)-based photoelectrodes, aimed at enhancing stability in photoelectrochemical (PEC) systems. The integration of OS and HP materials in PEC devices offers high photovoltage and impressive current densities, promising efficient solar-to-fuel conversion and pollutant upcycling. However, these materials face significant intrinsic and extrinsic degradation under PEC conditions. We discuss various passivation strategies to mitigate photochemical reactions and defect-related degradation, as well as advanced encapsulation techniques to prevent electrolyte-induced corrosion. The review highlights the latest research on enhancing the operational stability and performance of OS and HP-based photoelectrodes, emphasizing their potential in sustainable energy applications and environmental remediation. Future research directions include optimizing material design, exploring new passivation and encapsulation technologies, and scaling up for practical applications. This comprehensive review underscores the critical role of material innovation in advancing PEC technology for a sustainable future.

  • RESEARCH ARTICLE
    Yanjun Liu, Meishan Lu, Yanpeng Du, Jie Xu, Mingjie Fan, Changhu Xue, Yuanfa Liu
    2026, 6(1): 20240073. https://doi.org/10.1002/EXP.20240073

    Modulation of circadian rhythms impairs homeostasis, resulting in altered susceptibility to disease development. New perspectives on nutrition emphasize the circadian timing of food intake. Here, we found that the ad libitum feeding of oxidized frying oil disrupted the conversion of epoxides to diols in the kidneys, leading to aggravated renal injury. Interestingly, the circadian rhythms of epoxides and their diols in the kidneys and plasma showed differences between the light and dark phases. We demonstrated that time-imposed feeding of fried oil during the active period resulted in limited damage to renal function, conversely, renal function was impaired during the inactive period. Remarkably, feeding with epoxy stearic acid (EpSA) from fried oil during the inactive period disrupted the rhythmicity of epoxide hydrolases and related metabolites, and fueled the progression of renal fibrosis and injury. The effect of EpSA on SMA and E-cadherin, two specific biomarkers for renal inflammation and fibrosis, are lost in knockouts of Ephx1 and Ephx2, which encodes for epoxide hydrolases. In addition, dietary supplementation with linoleic acid, which inhibits epoxide hydrolases, protected mice from damage caused by time-imposed feeding of EpSA. Our findings revealed that the time-of-day dependence of epoxide hydrolases, and circadian disruption induced by time-imposed feeding of EpSA from thermo-induced oxidized oil have adverse effects on kidney function.

  • RESEARCH ARTICLE
    Panpan Xue, Tingjie Bai, Huilan Zhuang, Angelo H. All, Shuangqian Yan, Xuemei Zeng
    2026, 6(1): 20240123. https://doi.org/10.1002/EXP.20240123

    Stimulating the immunogenic cell death (ICD) by chemical and photothermal agents triggers antitumor immune responses to tumor treatments. However, the abnormal cholesterol accumulation in cancer cells promotes tumor survival and metastasis, while the high concentration of cholesterol in the tumor microenvironment will result in T exhaustion. Herein, a cholesterol-regulable nanoliposome (ictLipo) that encapsulated with IR806, tirapazamine, and cholesterol oxidase (ChOx) was fabricated to boost chemo/photothermal-activated ICD and antitumor immune responses. Specifically, the released ChOx oxidizes cholesterol, accompanied by oxygen consumption and ATP reduction. Whereupon, tumoral anabatic hypoxia activates the toxicity of tirapazamine while ATP reduction strengthens photothermal therapy of the IR806 by suppression of HSP70. We found that this interactive strategy evokes robust ICD and reverses T-cell exhaustion. When combined with the immune checkpoint blockade, ictLipo can efficiently restrain breast cancer metastasis in two tumor models. The interactive strategy sheds new light on the immunological facet of cholesterol metabolism and may provide a new therapeutic strategy against breast cancer.

  • RESEARCH ARTICLE
    Ang Ma, Yinhua Zhu, Yi Ying, Shuyuan Wang, Jingsong Zhang, Na Feng, Yazhu Quan, Guangying Shao, Dandan Liu, Shujie Zhang, Xiaoqiang Geng, Hong Zhou, Min Li, Dongmei Lin, Lianfu Wang, Guang Liang, Shaowei Li, Baoxue Yang
    2026, 6(1): 20240147. https://doi.org/10.1002/EXP.20240147

    Neuroinflammation plays a critical role in cerebral ischemic injury, making it an important therapeutic target for stroke treatment. Ganoderic acids (GAs), the primary bioactive compounds isolated from Ganoderma lucidum, exhibit well-demonstrated anti-inflammatory properties. This study aimed to investigate the neuroprotective potential of GAs in the context of ischemic stroke. Mice subjected to transient middle cerebral artery occlusion (tMCAO) served as an in vivo model of focal cerebral ischemia, while LPS-treated microglial cells were utilized as an in vitro model to evaluate microglial activation. GAs treatment significantly alleviated cerebral ischemic injury, inhibited microglial overactivation, and decreased inflammatory cytokine expression in both in vitro and in vivo models. Mechanistically, eight principal monomers in GAs, particularly GA-K, were found to target myeloid differentiation protein 2 (MD2), thereby preventing its interaction with Toll-like receptor 4 (TLR4), and subsequently inhibiting MAPK and NF-κB pathways. MD2 was found to be overexpressed under ischemic conditions. In MD2-deficient mice, microglial activation was inhibited, and neuroprotection against ischemic injury was observed, unaffected by GAs. These findings suggest that GAs, particularly GA-K, provide neuroprotection in ischemic stroke by modulating microglia-mediated neuroinflammation through MD2, which may serve as a promising therapeutic target for stroke patients.

  • RESEARCH ARTICLE
    Hongping Zhang, Shuang Zhao, Qianting Zhang, Chengchen Deng, Chuanrong Zhao, Xiangxiu Wang, Anna Malashicheva, Yi Wang, Juhui Qiu, Guixue Wang
    2026, 6(1): 20240248. https://doi.org/10.1002/EXP.20240248

    Nanoparticles (NPs) are promising for atherosclerosis (AS) drug delivery, which involves exposure to low magnitude shear stress, including low shear stress and oscillatory shear stress. While NPs surface charge affects biodistribution and cellular uptake, its role in AS-targeted accumulation remains unclear. In this study, positively charged NPs (pNPs), near-electrically neutrally charged NPs (eNPs), and negatively charged NPs (nNPs) were employed to investigate their distribution and uptake in mice and endothelial cells (ECs). Here, we found that nNPs exhibited significantly greater accumulation and uptake by ECs at both atherosclerotic sites and regions subjected to low magnitude shear stress compared to pNPs and eNPs. Proteomic analysis revealed that the surface charge of the NPs profoundly influenced the composition of the protein corona. Specifically, nNPs adsorbed several orders of magnitude more apolipoprotein H (APOH) from serum than pNPs. Furthermore, low magnitude shear stress increased the levels of surface phospholipids, which are specific receptors for APOH, on ECs, thereby promoting the uptake of nNPs by ECs. In conclusion, our study uncovers a mechanism by which nNPs preferentially accumulate within atherosclerotic areas and uptake by ECs exposure to low magnitude shear stress, and provides insights for designing charge-optimized NPs for cardiovascular drug delivery.

  • RESEARCH ARTICLE
    Tongyao Zhao, Yao Chen, Haimeng Yuan, Shuqian Yang, Hongyuan Zhang, Yuequan Wang, Shenwu Zhang, Qin Chen, Jin Sun, Zhonggui He, Cong Luo
    2026, 6(1): 20240259. https://doi.org/10.1002/EXP.20240259

    Cancer stem cells (CSCs) are widely recognized as the culprits of chemoresistance, tumor metastasis, and relapse. Moreover, most chemotherapeutic drugs not only fail to eliminate CSCs effectively, but also induce the acquisition of stemness characteristics in non-stem cancer cells. Herein, we propose a cancer cells/CSCs double-killing modality for breast cancer treatment. Specifically, a carrier-free nano-cocktail is developed through the precise co-assembly of a redox-responsive docetaxel (DTX) dimeric prodrug and salinomycin (SAL, an anti-CSCs drug). Precision combination of DTX and SAL not only shows synergistic tumor-killing activity, but also sharply reduces the proportion of CSCs in tumors. More importantly, tumor-specific prodrug activation-initiated drug release from the nano-cocktail confers high drug co-delivery efficiency and low off-target toxicity risk. As expected, such a one-stone-two-birds nanomedicine presents satisfactory performance on tumor stemness eradication, antitumor responses, and safety in both xenograft and orthotopic 4T1 breast cancer mouse models. This study advances cancer cells/CSCs double-killing nanotherapeutics towards clinical breast cancer therapy.

  • RESEARCH ARTICLE
    Chaoqun Ren, Zhaoxu Wu, Min Li, Yaqin Du, Hong Zhou, Yazhu Quan, Mengyao Xiong, Yiming Wang, Zhiwei Qiu, Shuai Zhu, Xiaowei Li, Jinzhao He, Cai Gao, Hui Cai, Tingting Li, Baoxue Yang
    2026, 6(1): 20240285. https://doi.org/10.1002/EXP.20240285

    Autosomal dominant polycystic kidney disease (ADPKD) is marked by aberrant cell proliferation driven by cAMP-PKA and MAPK signaling pathways. EGR1, a transcription factor directly activated by the above two pathways, is critical in the over-proliferation of tumor cells, which share similarities with cystic epithelial cells in ADPKD. This study utilized in vitro cell models, three-dimensional (3D) cyst model, embryonic renal cystic model, and PKD mouse model to clarify the role of EGR1 in cyst development of ADPKD. We found the high expression and nuclear condensates of EGR1 in human ADPKD renal cyst epithelial cells and PKD mouse kidney tissue. Pharmacological inhibition of EGR1 retarded cyst enlargement in in vitro, ex vivo, and in vivo ADPKD models. Furthermore, EGR1 formed nuclear condensates with YAP1 and CBP via phase separation, leading to EGR1-specific transcriptional activation and upregulation of cell-cycle-related genes (e.g., CCND1, CCNE1, and CDK4/6), thus promoting abnormal renal cystic epithelial cell proliferation. Disruption of EGR1 phase separation significantly alleviated cyst growth in the forskolin-induced 3D spheroid model of mIMCD3 cells and MDCK cyst model. These findings demonstrate that phase separation-mediated EGR1 condensates facilitate renal cyst development in ADPKD.

  • REVIEW
    Wenxuan Mao, Xiaoye Li, Ao He, Meng Ding, Yu Zhang, Zhuo Dai, Qiang Li, Weijun Xiu, Yanling Hu, Yongbin Mou, Dongliang Yang, Heng Dong
    2026, 6(1): 20240315. https://doi.org/10.1002/EXP.20240315

    The increasing incidence of infections and impaired tissue healing underscores the urgent need for effective therapeutic strategies for antibacterial treatment and regenerative medicine. Piezoelectric catalytic therapy represents an innovative approach that converts mechanical energy into electrochemical energy, providing a versatile platform for biomedical applications. However, conventional piezoelectric materials face significant limitations, including poor biocompatibility and insufficient catalytic efficiency, restricting their clinical translation. Piezoelectric biomaterials, characterized by excellent biocompatibility and enhanced piezoelectric performance, have recently emerged as promising candidates to overcome these challenges. This review systematically summarizes the latest advancements in piezoelectric biomaterials designed for pathogenic eradication and tissue regeneration. We provide a comprehensive overview of piezoelectric biomaterial classifications, fundamental mechanisms of piezoelectric catalysis, and methods to enhance material properties. Furthermore, we explore current applications of piezoelectric biomaterials in antibacterial therapies and regenerative medicine. Finally, critical challenges and potential future directions in material optimization and clinical application are identified, aiming to stimulate further innovation and research in this transformative field.

  • RESEARCH ARTICLE
    Hao Chen, Man Qiao, Zhixiang Yuan, Dazhi Yao, Dongdong Zhu, Ping Chen
    2026, 6(1): 20240327. https://doi.org/10.1002/EXP.20240327

    Electrochemical oxidation of amines to nitriles, with water as the O source, is a green and sustainable route to synthesize nitriles under mild conditions. However, developing highly efficient electrocatalysts for amine oxidation with large current densities is quite challenging. Herein, it is demonstrated that NiMoO4 with high oxidation states can efficiently catalyze benzylamine oxidation reaction (BAOR) to benzonitrile (BN) with a large anodic current density of 300.0 mA cm−2 at 1.47 V versus RHE. Impressively, NiMoO4 simultaneously achieves high BA conversion, BN selectivity, and faradaic efficiency of BN above 95%, together with a large BN yield of 0.366 mmol h−1 at 1.45 V versus RHE. Such excellent performance is also verified in a practical continuous-flow membrane electrode assembly reactor. Electrochemical measurements and in situ techniques uncover that NiOOH is the catalytically active species for BAOR, while the generation of NiOOH is more facile and effective on NiMoO4 than on Ni(OH)2. Theoretical calculations reveal that Mo doping in NiOOH facilitates the adsorption of BA, and reduces the energy barriers for the subsequent dehydrogenation steps, leading to excellent BAOR performance.

  • RESEARCH ARTICLE
    Huihuang Fang, Zefeng Wang, Jiangping Chen, Jiacheng You, Yiting Jiang, Puxin Yang, Qian Lin, Haoyu Zhang, Fulan Zhong, Yu Luo, Lilong Jiang
    2026, 6(1): 20240431. https://doi.org/10.1002/EXP.20240431

    Direct ammonia proton ceramic fuel cell is one of the most attractive strategies for ammonia to power at intermediate temperatures (400°C–600°C). Yet, it still remains greatly challenging, involving complex and sluggish processes, such as ammonia oxidation, ammonia decomposition (ADR), and hydrogen oxidation reaction (HOR), which always proceeds with high overpotential and low current density. Herein, we adopt the relay thermo-electrocatalysis strategy via catalyst functionalization for enhancing the performance of NH3-PCFCs, where ammonia undergoes ADR at the catalytic layer and then enters the anode to undergo HOR. The strategy not only promotes the performance of NH3-PCFCs (in the case of H2 and NH3) but also enhances the absolute performance in the same fuel gas compared with bare cells. The Ru/CZ4 was synthesized for catalyst functionalization for enhanced NH3-PCFCs and a general principle for designing well-matched catalysts was proposed. Indeed, the peak power density (PPD) of Ru/CZ4 cell achieves 615 and 576 mW cm2 for using H2 and NH3, respectively, which are 1.8- and 2.0-fold higher than bare cells (327 and 283 mW cm2 for using H2 and NH3). Additionally, the ammonia-to-hydrogen PPD ratio reaches to 93.7%, revealing the superior performance in both H2 and NH3 fuels. Furthermore, the detailed experiments and discussion were conducted to gain insight into the incorporated anode for the superior performance of NH3-PCFC. This research offers valuable insights into the structural design and performance optimization of solid oxide fuel cells using hydrogen-rich fuels.

  • REVIEW
    Yamei Zhang, Jianfei Yu, Haixia Wu, Zhijun Zhao, Hongjin Xia, Qingyang Li, Yiran Wang, Dongyang Li, Qian Wang
    2026, 6(1): 20240438. https://doi.org/10.1002/EXP.20240438

    Synthetic ammonia is of great significance to the development of industry and agriculture. At present, its manufacturing production is still dominated by century-old Haber–Bosch process, involving in huge amounts of energy consumptions and carbon dioxide emissions. Hence, it is of great significance to develop green and sustainable alternative technologies, such as photo-, thermo-, and electro-catalytic syntheses of ammonia. Nevertheless, the intrinsic inertness of nitrogen results in low ammonia yield of above candidates, which still cannot meet commercialization expectations. Recent researches have successfully demonstrated that plasma can effectively activate the decomposition of nitrogen and hydrogen under ambient conditions, thereby significantly improving the ammonia yield of these alternative strategies. This review systematically summarizes the classification and reaction mechanism of plasma for this reason, and discusses the synergy between different plasma and catalytic methods along with energy consumptions in detail. In the meantime, the future development trend is also forecasted.

  • REVIEW
    Yong Kang, Yiwen Yang, Bin Yao, Zhuhong Zhang, Xiaoyuan Ji
    2026, 6(1): 20240517. https://doi.org/10.1002/EXP.20240517

    Scar inhibition plays a crucial role in wound healing, particularly in the prevention of excessive scar formation during skin repair. While scar formation is a natural part of the healing process, improper scarring can lead to functional impairment, cosmetic defects, and psychological impacts. Therefore, understanding the mechanisms behind scar inhibition and exploring therapeutic strategies is essential for improving clinical outcomes. This review summarizes the primary mechanisms of scar formation and inhibition, including the regulation of collagen deposition, modulation of the inflammatory response, and control of cell proliferation and migration. In recent years, novel therapeutic approaches have emerged for scar inhibition, including gene therapy, stem cell treatments, and localized drug delivery systems, and the use of biomaterials. These methods not only enhance the effectiveness of scar treatment but also improve the biocompatibility and durability of the healing process. Although some of these approaches have shown promising results in early-stage studies, challenges remain for clinical applications, such as the individualization of treatment plans and the sustainability of outcomes. Finally, this review discusses future research directions and proposes strategies to enhance the potential of scar inhibition therapies and their clinical translation.

  • RESEARCH ARTICLE
    Ruijia Wang, Hongda Guo, Tao Zhang, Xiaoxia Chen, Min Ge, Shujun Li, Jian Li, Bing Tian, Bernd Strehmel, Shouxin Liu, Andrey L. Rogach, Tony D. James, Zhijun Chen
    2026, 6(1): 20250043. https://doi.org/10.1002/EXP.20250043

    Fixation of CO2 through photocatalytic cycloaddition with epoxides to synthesize cyclic carbonates is an important but challenging process. In this work, carbon dots (CDs) synthesized from gallic acid and polyethylenimine are used for the efficient catalytic cycloaddition of CO2 with epoxides in the absence of any solvent, additives, and halides, and importantly upon irradiation by natural sunlight. Specifically, carbon dots generated thermal energy and electrons upon solar irradiation, which together with their surface N-sites activated the inert CO2. Meanwhile, epoxides were activated by the surface hydroxyl and carboxylic groups of the carbon dots, which reacted with activated CO2 at solar thermal-induced high temperatures. The CDs shows excellent stability and recyclability during the catalysis. A 1000 mmol scale reaction for cyclic carbonate synthesis performed well upon irradiation with natural sunlight in the presence of CDs, showing great potential for the industrial application due to the simple, mild, and energy-saving process.

  • RESEARCH ARTICLE
    Yifan Ding, Yixin Cai, Weizhen Pan, Na Hu, Yunyun Wang, Huan Wang, Huang Fang, Songwei Tan, Zhiping Zhang
    2026, 6(1): 20250061. https://doi.org/10.1002/EXP.20250061

    Intervertebral disc degeneration (IDD) is a multifactorial condition characterized by excessive inflammation, immune dysfunction, and metabolic disorders. Current therapeutic strategies primarily rely on local injection, a traumatic approach associated with risks of tissue damage and infection. Therefore, developing safer, non-invasive, and precisely targeted drug delivery systems capable of multi-targeted interventions for the degenerating nucleus pulposus remains a significant challenge in IDD treatment. In this study, we designed a novel biomimetic oral delivery system featuring targeted drug delivery to degenerated intervertebral discs (IVDs) and on-demand drug release. This system utilizes yeast microcapsules (YC) and reactive oxygen species (ROS)-responsive nanoparticles to deliver Celastrol (Cel), a bioactive compound derived from traditional Chinese medicine. After oral administration, the system achieves targeted transport to IVDs through macrophage “hitchhiking,” where the inflammatory microenvironment rich in ROS triggers accelerated Cel release. Importantly, this strategy embodies a “One-Stone-Three-Birds” therapeutic approach, simultaneously exerting multi-targeted biological effects: inhibiting inflammasome activation, reprogramming macrophage polarization, and modulating lipid metabolism. These synergistic actions reverse the adverse degenerative microenvironment of the nucleus pulposus, promote tissue regeneration, and effectively suppress the progression of IDD. This research presents a novel, non-invasive oral targeted delivery strategy for IDD treatment, integrating biomimetic engineering with on-demand drug release. This innovative approach offers a comprehensive framework for microenvironmental remodeling and provides new insights into intervertebral disc regeneration.

  • REVIEW
    Zuhao Shen, Yiqun Liu, Yingjie Hao, Yifan Bo, Xiaochuan Dai, Shihui Wang, Tian Xia, Xin Su, Huiyu Liu
    2026, 6(1): 20250065. https://doi.org/10.1002/EXP.20250065

    Double-stranded DNA (dsDNA) serves as a fundamental repository of genetic information and plays a pivotal role in the diagnosis and therapeutic management of diseases. However, the inherent stability of the DNA double helix under physiological conditions presents a challenge in accessing internal bases. To address this, various molecular targeting technologies have been developed, offering high specificity while destabilizing the DNA structure. This review provides a comprehensive overview of current dsDNA targeting tools, such as hybridization probes, modified nucleic acid probes, zinc finger proteins (ZFPs), transcription activator-like effector nucleases (TALENs), the CRISPR/Cas system, Argonaute proteins (Agos), and the lambda exonuclease-pDNA system (λ Exo-pDNA), and some cutting-edge molecular tools. It delves into the mechanisms behind these technologies. It highlights their applications in diverse areas, including in vitro detection, in situ imaging, gene editing, and their integration with artificial intelligence (AI)-driven tools. Additionally, the review compares these techniques, discusses future technological opportunities, and identifies challenges in integrating these tools into diagnostic and therapeutic practices. By providing a holistic view of these rapidly evolving technologies, this review aims to fill a gap in the current literature and explore the future potential of dsDNA targeting innovations.

  • RESEARCH ARTICLE
    Rui Niu, Meichen Liu, Qingshan Yang, Jinlong Yin
    2026, 6(1): 20250153. https://doi.org/10.1002/EXP.20250153

    Glioblastoma (GBM) is the most aggressive type of primary brain tumor, and its invasive properties contribute significantly to incomplete surgical resection and tumor recurrence. Despite extensive clinical efforts to mitigate GBM invasion, targeted therapies against GBM stem cells (GSCs), which drive invasion, remain incompletely understood. Here, we report that MGAT4A, a key glycosyltransferase involved in N-glycosylation, orchestrates EGFR-ERK1/2 signaling to promote GSC invasion. Elevated MGAT4A expression correlates with poor survival outcomes in GBM patients, highlighting its potential as a therapeutic target. Silencing MGAT4A inhibits GSC invasion and tumorigenic capacities, including self-renewal and proliferation, both in vitro and in an orthotopic brain tumor xenograft model. Proteomic N-glycosylation mapping and co-immunoprecipitation assays reveal that MGAT4A interacts with EGFR and catalyzes N-glycosylation at the EGFR N604 site. This modification triggers ERK1/2 phosphorylation, thereby driving the invasion and tumorigenic potential of GSCs. Notably, tunicamycin, an N-glycosylation inhibitor, significantly impedes GSC invasion and disrupts downstream EGFR-ERK1/2 signaling, extending survival in mice bearing orthotopic tumors. To specifically target MGAT4A, we developed a CRISPR-Cas9 sgRNA-based nanotechnology, which notably reduced GSC invasion and improved survival in mice. Collectively, our study elucidates a novel mechanistic pathway driving GSC invasion and positions MGAT4A as a promising therapeutic target for GBM.

  • RESEARCH ARTICLE
    Yuanfang Chen, Xueyin Hu, Ze Hu, Yuwei Yang, Changfen Bi, Guangyou Shi, Lumeng Zhang, Wenqing Xu, Shuqin Li, Luntao Liu
    2026, 6(1): 20250179. https://doi.org/10.1002/EXP.20250179

    Cancer stem-like cells (CSCs) within deep tumors are a fundamental contributor to radiotherapy (RT) resistance due to their pronounced stemness resulting in unique unlimited self-renewal and differentiation capabilities. Alleviating hypoxic microenvironment of deep tumors to attenuate the stemness of CSCs remains a significant challenge, as the dense extracellular matrix (ECM) severely restricts oxygen diffusion into deep tumors. Herein, a nano-delivery particle (AMPM) is constructed to improve ECM permeability for deep tumor oxygen and radiosensitizer delivery. Natural fatty acid low-melting eutectic mixtures are employed as phase change materials (PCM) to encapsulate thermoresponsive self-assembled micelles, O2 pre-saturated perfluoropentane, and nitroimidazole sensitizers (metronidazole, MTZ), with the goal of enhancing RT. Under 808 nm light irradiation, PCM acts as a temperature-sensitive gatekeeper that undergoes solid-to-liquid phase transition under mild hyperthermic conditions (40°C), precisely controlling the release of MTZ and oxygen. Additionally, this design enhances the ECM permeability of the tumor, facilitating the delivery of oxygen and MTZ to deep-seated tumors. In TNBC (triple-negative breast cancer) mouse models, the combination of oxygen and MTZ effectively reverses radioresistance caused by hypoxic tumor microenvironment and CSCs, while significantly enhancing the efficacy of RT. Combination treatment with AMPM and RT (4 Gy) achieves a tumor inhibition rate of 91.2%, substantially surpassing high-dose RT alone (12 Gy, 52.1% inhibition). This study presents an innovative sensitization strategy with considerable clinical application potential for radiosensitization.

  • RESEARCH ARTICLE
    Haotian Hao, Xiong Jiao, Guangdong Zhou, Lin Chen, Mixue Wang, Jintao He, Xiaochen Lang, Jiyun Zhang, Linlin Shi, Meiwen An, Lingpeng Yan, Yizhi Zhu, Yongzhen Yang
    2026, 6(1): 20250234. https://doi.org/10.1002/EXP.20250234

    Artificial synapses have emerged as a pivotal technological advancement in mimicking brain functions. Organic memristors are desirable for hardware implementation of artificial synapses, owing to their remarkable mechanical flexibility, high biocompatibility at cell-device interfaces, and adjustable material structure. Developing appropriate organic polymers with carbon dots modification will enable the memristor to possess analog-type resistive switching behavior, crucial for realizing brain-like associative learning and adapting dynamic variations of neuron connection strength. In this work, an artificial synapse based on the analogue organic memristor integrating neuromorphic computing and neural interface functions is proposed, utilizing synthetic conjugated porous polymers to construct composites with boron-doped carbon dots. The structure-property relationship of alkynyl and alkyl chains in polymers is elucidated, alongside the synergistic effect of local photoinduced redox and hole templating in composites that endows the device with analog-type resistive switching behavior. Moreover, the memristor presents impressive synaptic plasticity and associative memory learning potential for neuromorphic computing, and further serves as a core unit in flexible artificial neural interface chips, demonstrating dynamic information transmission with neural systems. This study will promote the further development of organic artificial synapses for neuromorphic computing and brain-machine interfaces.