Home Archive
Archive
2025 Volume 8 Issue 1  Published: 2025-01-20
    Review Article
  • Xiaozhen Li , Ruohan Zhang , Yanlong Yang , Wei Huang
    doi: 10.34133/research.0534

    Near-infrared (NIR) phototheranostics (PTs) show higher tissue penetration depth, signal-to-noise ratio, and better biosafety than PTs in the ultraviolet and visible regions. However, their further advancement is severely hindered by poor performances and short-wavelength absorptions/emissions of PT agents. Among reported PT agents, conjugated small molecular nanoparticles (CSMNs) prepared from D-A-typed photoactive conjugated small molecules (CSMs) have greatly mediated this deadlock by their high photostability, distinct chemical structure, tunable absorption, intrinsic multifunctionality, and favorable biocompatibility, which endows CSMNs with more possibilities in biological applications. This review aims to introduce the recent progress of CSMNs for NIR imaging, therapy, and synergistic PTs with a comprehensive summary of their molecular structures, structure types, and optical properties. Moreover, the working principles of CSMNs are illustrated from photophysical and photochemical mechanisms and light–tissue interactions. In addition, molecular engineering and nanomodulation approaches of CSMs are discussed, with an emphasis on strategies for improving performances and extending absorption and emission wavelengths to the NIR range. Furthermore, the in vivo investigation of CSMNs is illustrated with solid examples from imaging in different scenarios, therapy in 2 modes, and synergistic PTs in combinational functionalities. This review concludes with a brief conclusion, current challenges, and future outlook of CSMNs.

  • Research Article
  • Kaixiang Zhu , Deepak Rohila , Yuanling Zhao , Dmytro Shytikov , Lize Wu , Fan Zhao , Shurong Hu , Qin Xu , Xuexiao Jin , Linrong Lu
    doi: 10.34133/research.0545

    Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function. We previously showed that PP2A regulates the differentiation of CD4+ T cells and the development of thymocytes. Nevertheless, its role in CD8+ T cells remains elusive. By ablating the catalytic subunit α (Cα) of PP2A in CD8+ T cells, we revealed the essential role of PP2A in promoting the effector functions of CD8+ T cells. Notably, PP2A Cα-deficient CD8+ T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in vitro. In vivo, mice lacking PP2A Cα in T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection, associated with reduced CD8+ T cell expansion and decreased cytokine production. Consistently, the ablation of the PP2A Cα subunit in CD8+ T cells results in attenuated antitumor activity in mice. There is a notable decrease in the infiltration of PP2A Cα-deficient CD8+ T cells within the tumor microenvironment, and the cells that do infiltrate exhibit diminished effector functions. Mechanistically, PP2A Cα deficiency impedes CD28-induced AKT Ser473 phosphorylation, thus impairing CD8+ T cell costimulation signal. Collectively, our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8+ T cell effector function by fine-tuning T cell activation.

  • Research Article
  • Sen Meng , Hao Liu , Jiayu Xu , Chuyin Deng , Xingyou Qian , Sufang Chu , Wei-Guo Zhu , Jiuling Zhu , Hongmei Yong , Zhongwei Li , Jin Bai
    doi: 10.34133/research.0549

    Numerous diseases have been connected to protein arginine methylations mediated by protein arginine methyltransferase 5 (PRMT5). Clinical investigations of the PRMT5-specific inhibitor GSK3326595 are currently being conducted, and the results are promising for preventing cancers. However, the detailed mechanism of PRMT5 promoting colorectal cancer (CRC) malignant progression remains unclear. Here, we found that PRMT5 directly catalyzes AlkB homologue 5 (ALKBH5) symmetric dimethylation at the R316 residue (meR316-ALKBH5), which enhances TRIM28-mediated ALKBH5 ubiquitination degradation. Then, an ALKBH5 decrease attenuates ALKBH5-mediated m6A demethylation on the CD276 transcript 3′ untranslated region, which increases CD276 messenger RNA stability and its expression in CRC cells. Furthermore, a CD276 expression increase facilitates CRC immune evasion by inhibiting cytotoxic T-cell functions. Moreover, we revealed that PRMT5-mediated meR316-ALKBH5 activates CD276 transcription by increasing its messenger RNA m6A modification to increase CRC immune evasion in vitro and in vivo. Furthermore, we consistently showed a strong association between meR316-ALKBH5 and poor outcomes in patients with CRC. Finally, we demonstrated that combining an anti-PD1 antibody with the PRMT5 inhibitor GSK3326595 markedly halts the progression of CRC. Our findings could serve as a basis for the development of a PRMT5–meR316-ALKBH5–CD276 axis-targeting treatment approach for CRC.

  • Research Article
  • Yunlei Zhou , Yanan Wang , Shicheng Qiu , Wei Zhao , Shaolei Wang , Hong Bao , Yunpeng Qu , Zhen Wen
    doi: 10.34133/research.0556

    Metals have traditionally served as the primary functional phase in the development of metamaterials exhibiting epsilon-near-zero (ENZ) and epsilon-negative (EN) responses, albeit with persisting ambiguities regarding their response mechanisms. This paper presents the tunable ENZ (ε′ ~ 0) and EN (ε′ < 0) parameters at the 20-MHz to 1-GHz region based on Cu/CaCu3Ti4O12 (Cu/CCTO) metacomposites. By means of first-principles calculations and multi-physics simulations, the underlying mechanisms governing ENZ and EN responses are unveiled. The intricate pathways through which metacomposites achieve 2 dielectric response mechanisms are delineated: At low Cu content, a weak EN response (|ε′| < 200) was excited by electric dipole resonance, accompanied by ENZ effect; conversely, at high Cu content, due to the increase in effective electron concentration, plasmonic oscillation behavior occurs in the constructed 3-dimensional Cu network, resulting in strong EN response (|ε′| ~ 1,000) in the radio frequency band. These phenomena are explicated through 2 distinct Cu/CCTO models: Cu in an isolated state and a connected network state. This study not only comprehensively elucidates the 2 EN response mechanisms achieved by typical metacomposites with metals as functional phases but also delves into their associated electromagnetic shielding and thermal properties, providing a theoretical basis for their practical applications.

  • Research Article
  • Yiling Han , Qiangwang Geng , Aimeng Dong , Menglu Jiang , Jingyi Ma , Wulian Song , Pan Fan , Yuanyuan Li , Jiawen Gao , Fenghua Zhang , Jinsong Leng , Huiping Yuan
    doi: 10.34133/research.0561

    Excessive fibrosis is the primary factor for the failure of glaucoma drainage device (GDD) implantation. Thus, strategies to suppress scar formation in GDD implantation are crucial. Although it is known that in implanted medical devices, microscale modification of the implant surface can modulate cell behavior and reduce the incidence of fibrosis, in the field of ophthalmic implants, especially the modification and effects of hydrogel micropatterns have rarely been reported. Here, we designed the patterned gelatin/acrylamide double network hydrogel and developed an innovative GDD with micropattern to suppress inflammatory and fibroblast activation after GDD implantation. Pattern topography suppressed F-actin expression and mitigated actin-dependent nuclear migration of myocardin-related transcription factor A (MRTF-A) during the proliferative phase after GDD implantation. Ultimately, the expression of α-smooth muscle actin (α-SMA), a key fibrosis-related gene product, was suppressed. Moreover, the modified GDD effectively controlled intraocular pressure (IOP), mitigated fibrous formation, and remodeled extracellular matrix (ECM) collagen distribution in vivo. Therefore, the novel GDD with surface patterning interventions provides a promising strategy to inhibit scar formation after GDD implantation and raise the efficacy of GDD implantation.

  • Review Article
  • Zhongwei Jin , Jing Lou , Fangzhou Shu , Zhi Hong , Cheng-Wei Qiu
    doi: 10.34133/research.0562

    Recent advancements in nanotechnology have revolutionized terahertz (THz) technology. By enabling the creation of compact, efficient devices through nanoscale structures, such as nano-thick heterostructures, metasurfaces, and hybrid systems, these innovations offer unprecedented control over THz wave generation and modulation. This has led to substantial enhancements in THz spectroscopy, imaging, and especially bio-applications, providing higher resolution and sensitivity. This review comprehensively examines the latest advancements in nanoengineered THz technology, beginning with state-of-the-art THz generation methods based on heterostructures, metasurfaces, and hybrid systems, followed by THz modulation techniques, including both homogeneous and individual modulation. Subsequently, it explores bio-applications such as novel biosensing and biofunction techniques. Finally, it summarizes findings and reflects on future trends and challenges in the field. Each section focuses on the physical mechanisms, structural designs, and performances, aiming to provide a thorough understanding of the advancements and potential of this rapidly evolving technology domain. This review aims to provide insights into the creation of next-generation nanoscale THz devices and applications while establishing a comprehensive foundation for addressing key issues that limit the full implementation of these promising technologies in real-world scenarios.

  • Review Article
  • Shan Liu , Jinkuan Liu , Xue Li , Xiaoxin Du , Cheng Yin , Yong Luo , Chenzhong Li
    doi: 10.34133/research.0564

    In 2001, Tang's team discovered a unique type of luminogens with substantial enhanced fluorescence upon aggregation and introduced the concept of “aggregation-induced emission (AIE)”. Unlike conventional fluorescent materials, AIE luminogens (AIEgens) emit weak or no fluorescence in solution but become highly fluorescent in aggregated or solid states, due to a mechanism known as restriction of intramolecular motions (RIM). Initially considered a purely inorganic chemical phenomenon, AIE was later applied in biomedicine to improve the sensitivity of immunoassays. Subsequently, AIE has been extensively explored in various biomedical applications, especially in cell imaging. Early studies achieved nonspecific cell imaging using nontargeted AIEgens, and later, specific cellular imaging was realized through the design of targeted AIEgens. These advancements have enabled the visualization of various biomacromolecules and intracellular organelles, providing valuable insights into cellular microenvironments and statuses. Neurological disorders affect over 3 billion people worldwide, highlighting the urgent need for advanced diagnostic and therapeutic tools. AIEgens offer promising opportunities for imaging the central nervous system (CNS), including nerve cells, neural tissues, and blood vessels. This review focuses on the application of AIEgens in CNS imaging, exploring their roles in the diagnosis of various neurological diseases. We will discuss the evolution and conclude with an outlook on the future challenges and opportunities for AIEgens in clinical diagnostics and therapeutics of CNS disorders.

  • Research Article
  • Yunhuan Yuan , Xianghua Wu , Bindu Kalleshappa , Martin Pumera
    doi: 10.34133/research.0565

    Microrobots enhance contact with pollutants through their movement and flow-induced mixing, substantially improving wastewater treatment efficiency beyond traditional diffusion-limited methods. g-C3N4 is an affordable and environmentally friendly photocatalyst that has been extensively researched in various fields such as biomedicine and environmental remediation. However, compared to other photocatalytic materials like TiO2 and ZnO, which are widely used in the fabrication of micro- and nanorobots, research on g-C3N4 for these applications is still in its early stages. This work presents microrobots entirely based on g-C3N4 microtubes, which can initiate autonomous movement when exposed to ultraviolet and visible light. We observed distinct motion behaviors of the microrobots under light irradiation of different wavelengths. Specifically, under ultraviolet light, the microrobots exhibit negative photogravitaxis, while under visible light, they demonstrate a combination of 3-dimensional motion and 2-dimensional motion. Therefore, the wavelength of the light can be used for programming the motion style of the microrobots and subsequently their application. We show that the microrobots can effectively degrade the antibiotic tetracycline, displaying their potential for antibiotic removal. This exploration of autonomous motion behaviors under different wavelength conditions helps to expand research on g-C3N4-based microrobots and their potential for environmental remediation.

  • Research Article
  • Ben Lei , Gaofeng Zhou , Zhongyou Gong , Chao Liu , Ying Zhou , Vitaliy P. Guro , Yanjuan Sun , Jianping Sheng , Fan Dong
    doi: 10.34133/research.0567

    Solar-driven CO2 photoreduction holds promise for sustainable fuel and chemical productions, but the complex proton-coupled multi-electron transfer processes and sluggish oxidation half-reaction kinetics substantially hinder its efficiency. Here, we devised a rational catalyst design to address these challenges by fabricating ferrocene carboxylic acid-functionalized Cs3Sb2Br9 nanocrystals (CSB-Fc NCs), which facilitate simultaneous benzyl alcohol oxidation and CO2 reduction reactions under visible-light irradiation. The synchronized proton-coupled electron transfer processes between the reduction and oxidation half-reactions on CSB-Fc NCs resulted in a 5-fold increase in the CO2 reduction rate (45.56 μmol g−1 h−1, 97.9% CO selectivity) and a 5.8-fold enhancement in benzyl alcohol conversion (97.7% selectivity for benzaldehyde) compared to the CSB. In situ Raman and ultraviolet-visible diffuse reflectance spectra revealed that the dynamic Fe2+/Fe3+ redox loop within the Fc unit serves as the actual active site, facilitating the activation of substrate molecules. More importantly, in situ attenuated total reflection Fourier transform infrared spectroscopy and gas chromatography–mass spectrometry spectroscopy, with isotope labeling of Deuteron-benzyl alcohol and 13CO2, confirmed that proton transfer from the hydroxyl group generates reactive protons at the Fe2+/Fe3+ site, enabling efficient CO2 photoreduction through subsequent protonation steps. This work offers a cost-effective and efficient approach for synergetic CO2 photoreduction driven by organic synthesis, advancing solar energy utilization.

  • Research Article
  • Yongxin Ge , Jiake Leng , Ziyang Tang , Kanran Wang , Kaicheng U , Sophia Meixuan Zhang , Sen Han , Yiyan Zhang , Jinxi Xiang , Sen Yang , Xiang Liu , Yi Song , Xiyue Wang , Yuchen Li , Junhan Zhao
    doi: 10.34133/research.0568

    Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling. GIST employs histopathology foundation models pretrained on millions of histology images to enhance feature extraction and a hybrid graph transformer model to integrate them with transcriptome features. Validated with datasets from human lung, breast, and colorectal cancers, GIST effectively reveals spatial domains and substantially improves the accuracy of segmenting the microenvironment after denoising transcriptomics data. This enhancement enables more accurate gene expression analysis and aids in identifying prognostic marker genes, outperforming state-of-the-art deep learning methods with a total improvement of up to 49.72%. GIST provides a generalizable framework for integrating histology with spatial transcriptome analysis, revealing novel insights into spatial organization and functional dynamics.

  • Research Article
  • Sumeera Asghar , Zhenyang Yu , Zheng Zhu , Dengyue Zheng , Zimo Zhao , Yuming Xu , Xiao Liu , Chao Yuan , Yan Li , Wei Wang , Jianfeng Xu , Huailong Teng , Jun Li , Wen-Chao Yang , Chunli Chen
    doi: 10.34133/research.0570

    The presence of Hg2+ causes substantial stress to plants, adversely affecting growth and health by disrupting cell cycle divisions, photosynthesis, and ionic homeostasis. Accurate visualization of the spatiotemporal distribution of Hg2+ in plant tissues is crucial for the management of Hg pollution; however, the related research is still at its early stage. Herein, a small-molecule amphiphilic fluorescent probe (termed LJTP2) was developed for the specific detection of Hg2+ with a high sensitivity (~16 nM). Fluorescent imaging applications with LJTP2 not only detected the dynamic distribution of Hg2+ within plant cells at the subcellular level but also enabled the understanding of cell membrane health under Hg2+ stress. This study introduces a valuable imaging tool for elucidating the molecular mechanism of Hg2+ stress in plants, demonstrating the potential of the application of small-molecule fluorescent probes in plant science.

  • Review Article
  • Jianyu Yin , Peixue Jia , Ziqi Ren , Qixiang Zhang , Wenzhong Lu , Qianqian Yao , Mingfang Deng , Xubin Zhou , Yihua Gao , Nishuang Liu
    doi: 10.34133/research.0571

    After years of research and development, flexible sensors are gradually evolving from the traditional “electronic” paradigm to the “ionic” dimension. Smart flexible sensors derived from the concept of ion transport are gradually emerging in the flexible electronics. In particular, ionic hydrogels have increasingly become the focus of research on flexible sensors as a result of their tunable conductivity, flexibility, biocompatibility, and self-healable capabilities. Nevertheless, the majority of existing sensors based on ionic hydrogels still mainly rely on external power sources, which greatly restrict the dexterity and convenience of their applications. Advances in energy harvesting technologies offer substantial potential toward engineering self-powered sensors. This article reviews in detail the self-powered mechanisms of ionic hydrogel self-powered sensors (IHSSs), including piezoelectric, triboelectric, ionic diode, moist-electric, thermoelectric, potentiometric transduction, and hybrid modes. At the same time, structural engineering related to device and material characteristics is discussed. Additionally, the relevant applications of IHSS toward wearable electronics, human–machine interaction, environmental monitoring, and medical diagnostics are further reviewed. Lastly, the challenges and prospective advancement of IHSS are outlined.

  • Research Article
  • Tian Gu , Wei Zhang , Lu Tan , Rong Xiang , Peiqiang Liu , Jingyu Huang , Qin Deng , Yuqin Deng , Zezhang Tao , Shiming Chen , Yu Xu
    doi: 10.34133/research.0573

    Allergen-specific immunotherapy (AIT) is the only treatment that addresses the root cause of immunoglobulin E (IgE)-mediated allergies, but conventional methods face challenges with treatment duration, patient compliance, and adverse effects. In this study, we propose intratonsillar immunotherapy (ITIT) as a new effective and safer route for AIT. Prior to clinical trials, we analyzed tonsil samples from human subjects to assess immune responses, measuring interleukin-4 (IL-4), IL-21, total IgE (tIgE), and allergen-specific IgE concentrations using ELISA and BioIC. Our results indicated that tonsils contained higher levels of allergen-specific IgE compared to peripheral blood. In the clinical phase, 120 allergic rhinitis (AR) patients were treated with either 3 intratonsillar allergen injections over 2 months or conventional subcutaneous immunotherapy (SCIT) over 1 year. ITIT demonstrated superior and faster symptom relief, especially in younger patients, while requiring markedly fewer doses and injections than SCIT. Immunological analysis revealed reduced eosinophil counts, increased regulatory T (Treg) and follicular regulatory T (TFR) cell levels, and a favorable shift in cytokine profiles. Adverse events were minimal, and the treatment showed high patient compliance. These findings suggest that ITIT could provide an effective, safer, and more convenient alternative to AIT.

  • Research Article
  • Chao Wang , Bing Yu , Han Zhou , Huanting Li , Shifang Li , Xiaolu Li , Wentao Wang , Yugong Feng , Tao Yu
    doi: 10.34133/research.0574

    Transfer RNA-derived small RNAs, a recently identified class of small noncoding RNAs, play a crucial role in regulating gene expression and are implicated in cerebrovascular diseases. However, the specific biological roles and mechanisms of transfer RNA-derived small RNAs in intracranial aneurysms (IAs) remain unclear. In this study, we identified that the transfer RNA-Asp-GTC derived fragment (tRF-AspGTC) is highly expressed in the IA tissues of both humans and mice. tRF-AspGTC promotes IA formation by facilitating the phenotypic switching of vascular smooth muscle cells, increasing of matrix metalloproteinase 9 expression, and inducing of oxidative stress and inflammatory responses. Mechanistically, tRF-AspGTC binds to galectin-3, inhibiting tripartite motif 29-mediated ubiquitination and stabilizing galectin-3. This stabilization activates the toll-like receptor 4/MyD88/nuclear factor kappa B pathway, further driving phenotypic switching and inflammation. Clinically, circulating exosomal tRF-AspGTC demonstrates strong diagnostic efficacy for IAs and is identified as an independent risk factor for IA occurrence. These findings highlight the potential of tRF-AspGTC as a promising diagnostic biomarker and therapeutic target for IAs.

  • Research Article
  • Shuo Yang , Caojun Wang , Yuanjian Zhang , Yuming Yin , Yanjun Huang , Shengbo Eben Li , Hong Chen
    doi: 10.34133/research.0575

    Autonomous vehicles with self-evolution capabilities are expected to improve their performance through learning algorithms, to automatically adapt to the external environment. However, due to the infinity, complexity, and variability of the actual traffic environment, it is necessary to develop quantitative representation indicators of scenario difficulty and generate targeted scenarios to ensure the evolution gradually, so as to quickly approach the performance limit of the algorithm. Therefore, this paper proposes a data-driven quantitative representation method of scenario difficulty. Specifically, the concept of environment agent is proposed, and a reinforcement learning method combined with mechanism knowledge is constructed for policy search to obtain an agent with an adversarial behavior. The model parameters of the environment agent at different stages in the training process are extracted to construct a policy group, and then agents with different adversarial intensities are obtained, which are used to realize data generation in different difficulty scenarios through the simulation environment. Finally, a data-driven scenario difficulty quantitative representation model is constructed, which is used to output the environment agent policy under different difficulties. Experimental results show the effectiveness of the proposed method. The result analysis shows that the proposed algorithm can generate reasonable and interpretable scenarios with high discrimination and can provide quantifiable difficulty representation without any expert logic rule design. Compared with the rule-based discrete scenario difficulty representation method, the proposed algorithm can achieve continuous difficulty representation. The video link is https://www.youtube.com/watch?v=GceGdqAm9Ys.

  • Research Article
  • Xiaolan Zhou , Xiaofeng Zhu , Weixu Wang , Jing Wang , Haimei Wen , Yuqi Zhao , Jiayu Zhang , Qiushi Xu , Zhaozhao Zhao , Ting Ni
    doi: 10.34133/research.0576

    Drug resistance to a single agent is common in cancer-targeted therapies, and rational drug combinations are a promising approach to overcome this challenge. Many Food and Drug Administration-approved drugs can induce cellular senescence, which possesses unique vulnerabilities and molecular signatures. However, there is limited analysis on the effect of the combination of cellular-senescence-inducing drugs and targeted therapy drugs. Here, we conducted a comprehensive evaluation of cellular senescence using 7 senescence-associated gene sets. We quantified the cellular senescence states of ~10,000 tumor samples from The Cancer Genome Atlas and examined their associations with targeted drug responses. Our analysis revealed that tumors with higher cellular senescence scores exhibited increased sensitivity to targeted drugs. As a proof of concept, we experimentally confirmed that etoposide-induced senescence sensitized lung cancer cells to 2 widely used targeted drugs, erlotinib and dasatinib. Furthermore, we identified multiple genes whose dependencies were associated with senescence status across ~1,000 cancer cell lines, suggesting that cellular senescence generates unique vulnerabilities for therapeutic exploitation. Our study provides a comprehensive overview of drug response related to cellular senescence and highlights the potential of combining senescence-inducing agents with targeted therapies to improve treatment outcomes in lung cancer, revealing novel applications of cellular senescence in targeted cancer therapies.

  • Research Article
  • Ruomei Cheng , Xiaopeng Tang , Qiyu Zhao , Yuming Wang , Wenlin Chen , Gan Wang , Chenxi Wang , James Mwangi , Qiumin Lu , Dawit Adisu Tadese , Xudong Zhao , Caiwen Ou , Ren Lai
    doi: 10.34133/research.0578

    Immune recognition and activation by the peptide-laden major histocompatibility complex–T cell receptor (TCR)–CD3 complex is essential for anti-tumor immunity. Tumors may escape immune surveillance by dissembling the complex. Here, we report that transferrin, which is overexpressed in patients with liver metastasis, disassociates TCR from the CD3 signaling apparatus by targeting the constant domain (CD) of T cell receptor α (TCRα), consequently suppresses T cell activation, and inhibits anti-metastatic and anti-tumor immunity. In mouse models of melanoma and lymphoma, transferrin overexpression exacerbates liver metastasis, while its knockdown, antibody, designed peptides, and CD mutation interfering with transferrin–TCRα interaction inhibit metastasis. This work reveals a novel strategy of tumor evasion of immune surveillance by blocking the coupling between TCRs and the CD3 signaling apparatus to suppress TCR activation. Given the conservation of CD and transferrin up-regulation in metastatic tumors, the strategy might be a common metastatic mechanism. Targeting transferrin–TCRα holds promise for anti-metastatic treatment.

  • Research Article
  • Huang Lin , Cong Luo , Fangyuan Cheng , Kui Xie
    doi: 10.34133/research.0579

    The engineering design and construction of active interfaces represents a promising approach amidst numerous initiatives aimed at augmenting catalytic activity. Herein, we present a novel approach to incorporate interconnected pores within bulk single crystals for the synthesis of macroscopic porous single-crystalline rutile titanium oxide (R-TiO2). The porous single crystal (PSC) R-TiO2 couples a nanocrystalline framework as the solid phase with pores as the fluid phase within its structure, providing unique advantages in localized structure construction and in the field of catalysis. We successfully construct well-defined Ni cluster/TiO2 active interfaces by directly confining Ni clusters on the continuous lattice surface of PSC R-TiO2. We confirm that the lattice oxygen connected to the Ni clusters exhibits exceptional activation capability at temperatures close to room temperature compared to the pure phase PSC R-TiO2 monoliths. The PSC Ni/TiO2 catalyst demonstrates complete CO oxidation and stable catalytic performance during continuous operation in air at ~80 °C for 200 h.

  • Research Article
  • Jun Xie , Xuanyu Shan , Ningbo Zou , Ya Lin , Zhongqiang Wang , Ye Tao , Xiaoning Zhao , Haiyang Xu , Yichun Liu
    doi: 10.34133/research.0580

    The optoelectronic memristor integrates the multifunctionalities of image sensing, storage, and processing, which has been considered as the leading candidate to construct novel neuromorphic visual system. In particular, memristive materials with all-optical modulation and complementary metal oxide semiconductor (CMOS) compatibility are highly desired for energy-efficient image perception. As a p-type oxide material, Cu2O exhibits outstanding theoretical photoelectric conversion efficiency and broadband photoresponse. In this work, an all-optically controlled memristor based on the Cu2O/TiO2/sodium alginate nanocomposite film is developed. Optical potentiation and depression behaviors have been implemented by utilizing visible (680 nm) and ultraviolet (350 nm) light. Furthermore, a 7 × 9 optoelectronic memristive array with satisfactory device variation and environment stability is constructed to emulate the image preprocessing function in biological retina. The random noise can be reduced effectively by utilizing bidirectional optical input. Beneficial from the image preprocessing function, the accuracy of handwritten digit classification increases more than 60%. Our work presents a pathway toward high-efficient neuromorphic visual system and promotes the development of artificial intelligence technology.

  • Research Article
  • Jiayi Mao , Wenzheng Xia , Yanglin Wu , Minxiong Li , Yun Zhao , Peisong Zhai , Yuguang Zhang , Tao Zan , Wenguo Cui , Xiaoming Sun
    doi: 10.34133/research.0581

    Hyperglycemia and bacterial colonization in diabetic wounds aberrantly activate Nod-like receptor protein 3 (NLRP3) in macrophages, resulting in extensive inflammatory infiltration and impaired wound healing. Targeted suppression of the NLRP3 inflammasome shows promise in reducing macrophage inflammatory disruptions. However, challenges such as drug off-target effects and degradation via lysosomal capture remain during treatment. In this study, engineered apoptotic bodies (BHB-dABs) derived from adipose stem cells loaded with β-hydroxybutyric acid (BHB) were synthesized via biosynthesis. These vesicles target M1-type macrophages, which highly express the folic acid receptor in the inflammatory microenvironment, and facilitate lysosomal escape through 1,2-distearoyl-sn-propyltriyl-3-phosphatidylethanolamine–polyethylene glycol functionalization, which may enhance the efficacy of NLRP3 inhibition for managing diabetic wounds. In vitro studies demonstrated the biocompatibility of BHB-dABs, their selective targeting of M1-type macrophages, and their ability to release BHB within the inflammatory microenvironment via folic acid and folic acid receptor signaling. These nanovesicles exhibited lysosomal escape, anti-inflammatory, mitochondrial protection, and endothelial cell vascularization properties. In vivo experiments demonstrated that BHB-dABs enhance the recovery of diabetic wound inflammation and angiogenesis, accelerating wound healing. These functionalized apoptotic bodies efficiently deliver NLRP3 inflammasome inhibitors using a dual strategy of targeting macrophages and promoting lysosomal escape. This approach represents a novel therapeutic strategy for effectively treating chronic diabetic wounds.

  • Review Article
  • Md. Rayid Hasan Mojumder , Seongchan Kim , Cunjiang Yu
    doi: 10.34133/research.0582

    Soft electronics, known for their bendable, stretchable, and flexible properties, are revolutionizing fields such as biomedical sensing, consumer electronics, and robotics. A primary challenge in this domain is achieving low power consumption, often hampered by the limitations of the conventional von Neumann architecture. In response, the development of soft artificial synapses (SASs) has gained substantial attention. These synapses seek to replicate the signal transmission properties of biological synapses, offering an innovative solution to this challenge. This review explores the materials and device architectures integral to SAS fabrication, emphasizing flexibility and stability under mechanical deformation. Various architectures, including floating-gate dielectric, ferroelectric-gate dielectric, and electrolyte-gate dielectric, are analyzed for effective weight control in SASs. The utilization of organic and low-dimensional materials is highlighted, showcasing their plasticity and energy-efficient operation. Furthermore, the paper investigates the integration of functionality into SASs, particularly focusing on devices that autonomously sense external stimuli. Functionalized SASs, capable of recognizing optical, mechanical, chemical, olfactory, and auditory cues, demonstrate promising applications in computing and sensing. A detailed examination of photo-functionalized, tactile-functionalized, and chemoreception-functionalized SASs reveals their potential in image recognition, tactile sensing, and chemosensory applications, respectively. This study highlights that SASs and functionalized SAS devices hold transformative potential for bioelectronics and sensing for soft-robotics applications; however, further research is necessary to address scalability, long-time stability, and utilizing functionalized SASs for prosthetics and in vivo applications through clinical adoption. By providing a comprehensive overview, this paper contributes to the understanding of SASs, bridging research gaps and paving the way toward transformative developments in soft electronics, biomimicking and biointegrated synapse devices, and integrated systems.

  • Review Article
  • Dehong Hu , Menglei Zha , Hairong Zheng , Duyang Gao , Zonghai Sheng
    doi: 10.34133/research.0583

    Fluorescence imaging, a highly sensitive molecular imaging modality, is being increasingly integrated into clinical practice. Imaging within the second near-infrared biological window (NIR-II; 1,000 to 1,700 nm), also referred to as shortwave infrared, has received substantial attention because of its markedly reduced autofluorescence, deeper tissue penetration, and enhanced spatiotemporal resolution as compared to traditional near-infrared (NIR) imaging. Indocyanine green (ICG), a US Food and Drug Administration-approved NIR fluorophore, has long been used in clinical applications, including blood vessel angiography, vascular perfusion monitoring, and tumor detection. Recent advancements in NIR-II imaging technology have revitalized interest in ICG, revealing its extended tail fluorescence beyond 1,000 nm and reaffirming its potential as a clinically translatable NIR-II fluorophore for in vivo imaging and theranostic applications for diagnosing various diseases. This review emphasizes the notable advances in the use of ICG and its derivatives for NIR-II imaging and image-guided therapy from both fundamental and clinical perspectives. We also provide a concise conclusion and discuss the challenges and future opportunities with NIR-II imaging using clinically approved fluorophores.

  • Erratum
  • Jian Ji , Yongli Ye , Lina Sheng , Jiadi Sun , Qianqian Hong , Chang Liu , Jun Ding , Shuxiang Geng , Deping Xu , Yinzhi Zhang , Xiulan Sun
    doi: 10.34133/research.0585
  • Review Article
  • Jing Li , Xianjin Deng , Yangmei Li , Jie Hu , Wei Miao , Changxing Lin , Jun Jiang , Shengcai Shi
    doi: 10.34133/research.0586

    This paper reviews recent developments and key advances in terahertz (THz) science, technology, and applications, focusing on 3 core areas: astronomy, telecommunications, and biophysics. In THz astronomy, it highlights major discoveries and ongoing projects, emphasizing the role of advanced superconducting technologies, including superconductor–insulator–superconductor (SIS) mixers, hot electron boundedness spectroscopy (HEB), transition-edge sensors (TESs), and kinetic inductance detectors (KIDs), while exploring prospects in the field. For THz telecommunication, it discusses progress in solid-state sources, new communication technologies operating within the THz band, and diverse modulation methods that enhance transmission capabilities. In THz biophysics, the focus shifts to the physical modulation of THz waves and their impact across biological systems, from whole organisms to cellular and molecular levels, emphasizing nonthermal effects and fundamental mechanisms. This review concludes with an analysis of the challenges and perspectives shaping the future of THz technology.

  • Perspective
  • Hao Chi Zhang , Sen Gong , Le Peng Zhang , Yaxin Zhang , Tie Jun Cui
    doi: 10.34133/research.0587

    Electromagnetic (EM) metamaterials represent a cutting-edge field that achieves anomalously macroscopic properties through artificial design and arrangement of microstructure arrays to freely manipulate EM fields and waves in desired ways. The unit cell of a microstructure array is also called a meta-atom, which can construct effective medium parameters that do not exist in traditional materials or are difficult to realize with traditional technologies. By deep integration with digital information, the meta-atom is evolved to a digital meta-atom, leading to the emergence of information metamaterials. Information metamaterials break the inherent barriers between the EM and digital domains, providing a physical platform for controlling EM waves and modulating digital information simultaneously. The concepts of meta-atoms and metamaterials are also introduced to high-frequency integrated circuit designs to address issues that cannot be solved by traditional methods, since lumped-parameter models become unsustainable at microscopic scales. By incorporating several meta-atoms to form a metachip, precise manipulation of the EM field distribution can be achieved at microscopic scales. In this perspective, we summarize the physical connotations and main classifications of meta-atoms and briefly discuss their future development trends. Through this article, we hope to draw more research attention to explore the potential values of meta-atoms, thereby opening up a broader stage for the in-depth development of metamaterials.

  • Perspective
  • Wenbo Wei , Haifei Liu , Qi-Long Zhu
    doi: 10.34133/research.0589

    The electrocatalytic carbon dioxide reduction reaction (CO2RR) at industrial-level current densities provides a sustainable approach to converting CO2 into value-added fuels and feedstocks using renewable electricity. However, the CO2RR conducted typically in alkaline and neutral electrolytes encounters some challenges due to the inevitable reaction between CO2 and OH ions, which undermines CO2 utilization and leads to poor operational stability. Acidic media present a viable alternative by reducing (bi)carbonate production, thereby enhancing the carbon efficiency and stability in CO2RR. The objective of this paper is to provide a concise account of the recent advancements and challenges in the field of acidic CO2RR, with an emphasis on future developments and opportunities.

  • Research Article
  • Jie Mei , Zhiwen Luo , Yun Cai , Renwen Wan , Zhiwen Qian , Jiahui Chu , Yaying Sun , Yuxin Shi , Ying Jiang , Yan Zhang , Yongmei Yin , Shiyi Chen
    doi: 10.34133/research.0590

    Increasing evidence has shown that physical exercise remarkably inhibits oncogenesis and progression of numerous cancers and exercise-responsive microRNAs (miRNAs) exert a marked role in exercise-mediated tumor suppression. In this research, expression and prognostic values of exercise-responsive miRNAs were examined in breast cancer (BRCA) and further pan-cancer types. In addition, multiple independent public and in-house cohorts, in vitro assays involving multiple, macrophages, fibroblasts, and tumor cells, and in vivo models were utilized to uncover the tumor-suppressive roles of miR-29a-3p in cancers. Here, we reported that miR-29a-3p was the exercise-responsive miRNA, which was lowly expressed in tumor tissues and associated with unfavorable prognosis in BRCA. Mechanistically, miR-29a-3p targeted macrophages, fibroblasts, and tumor cells to down-regulate B7 homolog 3 (B7-H3) expression. Single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) demonstrated that miR-29a-3p attacked the armored and cold tumors, thereby shaping an immuno-hot tumor microenvironment (TME). Translationally, liposomes were developed and loaded with miR-29a-3p (lipo@miR-29a-3p), and lipo@miR-29a-3p exhibited promising antitumor effects in a mouse model with great biocompatibility. In conclusion, we uncovered that miR-29a-3p is a critical exercise-responsive miRNA, which attacked armored and cold tumors by inhibiting B7-H3 expression. Thus, miR-29a-3p restoration could be an alternative strategy for antitumor therapy.

  • Review Article
  • Fang Wang , Wenqing He , Bing Dai , Xueji Zhang , Yongqiang Wen
    doi: 10.34133/research.0591

    The management of wound exudate is of vital importance for wound healing. Exudate accumulation around wound prolongs inflammation and hinders healing. Although traditional dressings can absorb wound exudate, they are unable to drain exudate in time, often resulting in a poor feature with wound healing. In recent years, the appearance of asymmetric wettability dressings has shown great potential in exudate management. Here, we summarize the latest progress of 3 kinds of asymmetric wettability wound dressings in exudate management, including Janus structure, sandwich structure, and gradient structure. The most common Janus structural dressing among asymmetric wettability dressings is highlighted from 2 aspects: single-layer modified Janus structure and double-layer Janus structure. The challenges faced by asymmetric wettability wound dressings are discussed, and the developing trends of smart wound dressings in this field are prospected.

  • Review Article
  • Wenting Ji , Ruzhen Luo , Yumei Sun , Maiping Yang , Yueheng Liu , Hua Chen , Dongmei Lin , Ziyi Su , Guangming Tao , Diansheng Chen , Hongyu Sun
    doi: 10.34133/research.0592

    As global populations become increasingly aged, existing elderly care models are proving insufficient. The development and application of nursing robots have shown potential in addressing the challenges of elder care in aging societies. This perspective outlines current state and potential applications of nursing robots in promoting healthy aging. Given this background, a networked intelligent elderly care model for nursing robots, which integrates technologies such as big data, artificial intelligence, the Internet of Things, and nursing robotics, is proposed. This model would synergistically combine elderly health monitoring, capability assessment, and intelligent allocation functions to revolutionize global elderly care practices and promote healthy aging.

  • Research Article
  • Jiankun Xiao , Xiong Xiong , Xinhang Shi , Shiyuan Liu , Shenwu Zhu , Yue Zhang , Ru Huang , Yanqing Wu
    doi: 10.34133/research.0593

    Edge contact is essential for achieving the ultimate device pitch scaling of stacked nanosheet transistors with monolayer 2-dimensional (2D) channels. However, due to large edge-contact resistance between 2D channels and contact metal, there is currently a lack of high-performance edge-contact device technology for 2D material channels. Here, we report high-performance edge-contact monolayer molybdenum disulfide (MoS2) field-effect transistors (FETs) utilizing well-controlled plasma etching techniques. Plasma etching with pure argon improves the edge dangling bonds and thus improves the edge-contact quality. Edge-contact monolayer MoS2 FET shows good ohmic contact even at cryogenic temperatures (20 K), achieving a record-low contact resistance (R c) of 1.25 kΩ·μm among all edge-contact MoS2 devices. The record-high on-state current of 436 μA/μm and transconductance of 123 μS/μm at V ds = 1 V are achieved on an edge-contact monolayer MoS2 FET with L ch = 120 nm. This work highlights the great potential of edge contacts for high-performance monolayer transition metal dichalcogenide (TMD) material electronics.

  • Research Article
  • Yao Wang , Xunlei Pang , Ruirui Li , Jiuzhou Chen , Chen Wen , Huihuang Zhu , Tingyu Long , Jianjie Li , Lijun Zheng , Youcai Deng , Junnian Zheng , Bo Xu
    doi: 10.34133/research.0594

    Background: Chimeric antigen receptor (CAR)-based immune cell therapies attack neighboring cancer cells after receptor recognition but are unable to directly affect distant tumor cells. This limitation may contribute to their inefficiency in treating solid tumors, given the restricted intratumoral infiltration and immunosuppressive tumor microenvironment. Therefore, cell–cell fusion as a cell-killing mechanism might develop a novel cytotherapy aimed at improving the efficacy against solid tumors. Methods: We constructed a fusogenic protein, fusion-associated small transmembrane (FAST) p14 of reptilian reovirus, into cancer cells and mesenchymal stem cells (MSCs), which cocultured with various colon cancer cells and melenoma cells to validate its ability to induce cell fusion and syncytia formation. RNA sequencing, quantitative reverse transcription polymerase chain reaction, and Western blot were performed to elucidate the mechanism of syncytia death. Cell viability assay was employed to assess the killing effects of MSCs carrying the p14 protein (MSCs-p14), which was also identified in the subcutaneous tumor models. Subsequently, the Tet-On system was introduced to enhance the controllability and safety of therapy. Results: Cancer cells incorporated with fusogenic protein p14 FAST from reovirus fused together to form syncytia and subsequently died through apoptosis and pyroptosis. MSCs-p14 cocultured with different cancer cells and effienctly induced cancer cell fusion and caused widespread cancer cell death in vitro. In mouse tumor models, mMSCs-p14 treatment markedly suppressed tumor growth and also enhanced the activity of natural killer cells and macrophages. Controllability and safety of MSCs-p14 therapy were further improved by introducing the tetracycline-controlled transcriptional system. Conclusion: MSC-based cytotherapy carrying viral fusogenic protein in this study kills cancer cells by inducing cell–cell fusion. It has demonstrated definite efficacy in treating solid tumors and is worth considering for clinical development.

  • Research Article
  • Dandan Zhu , Peng Wang , Xiyue Chen , Kaituo Wang , Yunsong Wu , Min Zhang , Jianhua Qin
    doi: 10.34133/research.0598

    Sepsis-associated encephalopathy (SAE) is a severe and frequent septic complication, characterized by neuronal damage as key pathological features. The astrocyte–microglia crosstalk in the central nervous system (CNS) plays important roles in various neurological diseases. However, how astrocytes interact with microglia to regulate neuronal injury in SAE is poorly defined. In this study, we aim to investigate the molecular basis of the astrocyte–microglia crosstalk underlying SAE pathogenesis and also to explore the new therapeutic strategies targeting this crosstalk in this devastating disease. We established a human astrocyte/microglia coculture system on a microfluidic device, which allows real-time and high-resolution recording of glial responses to inflammatory stimuli. Based on this microfluidic system, we can test the responses of astrocytes and microglia to lipopolysaccharide (LPS) treatment, and identify the molecular cues that mediate the astrocyte–microglia crosstalk underlying the pathological condition. In addition, the SAE mouse model was utilized to determine the state of glial cells and evaluate the therapeutic effect of drugs targeting the astrocyte–microglia crosstalk in vivo. Here, we found that activated astrocytes and microglia exhibited close spatial interaction in the SAE mouse model. Upon LPS exposure for astrocytes, we detected that more microglia migrated to the central astrocyte culture compartment on the microfluidic device, accompanied by M1 polarization and increased cell motility in microglia. Cytokine array analysis revealed that less interleukin 11 (IL11) was secreted by astrocytes following LPS treatment, which further promoted reprogramming of microglia to pro-inflammatory M1 phenotype via the nuclear factor-κB (NF-κB) signaling pathway. Intriguingly, we found that IL11 addition markedly rescued LPS-induced neuronal injuries on the microfluidic system and brain injury in the SAE mouse model. This study defines an unknown crosstalk of astrocyte–microglia mediated by IL11, which contributed to the neuropathogenesis of SAE, and suggested a potential therapeutic value of IL11 in the devastating disease.

  • Research Article
  • Gaoang Wang , Hang Wu , Yingying Wang , Xiangying Liu , Shuijiao Peng , Wenxing Wang , Meijing Wu , Yifei Liu , Ercheng Wang , Zhe Wang , Lei Xu , Xiaojian Wang , Wei Yang , Haiyi Chen , Xi Zhou , Tingjun Hou
    doi: 10.34133/research.0599

    Nav1.7 is considered a promising target for developing next-generation analgesic drugs, given its critical role in human pain pathologies. Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold, they failed to demonstrate marked clinical efficacy. Therefore, exploring new Nav1.7-selective antagonists is quite urgent to the development of next-generation analgesic drugs. Here, we report a highly effective 1H-indole-3-propionamide inhibitor, WN2, identified through an integrated drug discovery strategy. Notably, the structure of WN2 is quite different from previously reported aryl sulfonamide inhibitors. Molecular dynamics simulations and experimental findings reveal that the R configuration of WN2 (WN2-R) is the preferred form (IC50 = 24.7 ± 9.4 nM) within the VSDIV pocket of Nav1.7. WN2-R exhibits impressive analgesic effects in acute and chronic inflammatory pain, as well as neuropathic pain models in mice. Additionally, it displays favorable subtype selectivity and positive drug safety in acute toxicity studies. Pharmacokinetic studies indicate that WN2-R has high bioavailability (F = 20.29%), highlighting its considerable potential for drug development. Our study establishes WN2-R as a novel Nav1.7-selective inhibitor with a unique structural scaffold, offering a promising candidate for the next generation of analgesic drugs.

  • Perspective
  • Yuhui Tang , Qiaoting Cai , Zhi Tian , Wenkuan Chen , Hailin Tang
    doi: 10.34133/research.0600

    Gut microbiota is crucial for protecting the homeostasis of immune locally and systemically, and its dysbiosis is essentially correlated to tumorigenesis, cancer progression, and refractoriness to cancer treatments, including the novel immunotherapy. Increasing evidence unravel the intricate role of gut microbiota in reshaping tumor microenvironment and affecting the efficacy and toxicities of immunotherapy, which shed more light on the future applications of gut microbiota in efficacious biomarker and combination treatment of immunotherapy. To better grasp the underlying crosstalk between gut microbiota and immunotherapy, more experimental and clinical trials are indispensable for the customized gut microbiota-based treatments in cancer patients undergoing immunotherapy.