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.

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.

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.

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.

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.

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.

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.

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.

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.

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.