Research最新文献

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 (T_reg) and follicular regulatory T (T_FR) 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.