Research最新文献

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.

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.

Concrete is the most widely used and highest-volume basic material in the word today. Enhancing its toughness, including tensile strength and deformation resistance, can boost the structural load-bearing capacity, minimize cracking, and decrease the amount of concrete and steel required in engineering projects. These advancements are crucial for the safety, durability, energy efficiency, and emission reduction of structural engineering. This paper systematically summarized the brittle characteristics of concrete and the various structural factors influencing its performance at multiple scales, including molecular, nano-micro, and meso-macro levels. It outlines the principles and impacts of concrete toughening and crack prevention from both internal and external perspectives, and discusses recent advancements and engineering applications of toughened concrete. In situ polymerization and fiber reinforcement are currently practical and highly efficient methods for enhancing concrete toughness. These techniques can boost the matrix's flexural strength by 30% and double its fracture energy, achieving an ultimate tensile strength of up to 20 MPa and a tensile strain exceeding 0.6%. In the future, achieving breakthroughs in concrete toughening will probably rely heavily on the seamless integration and effective synergy of multi-scale toughening methods.

Metamaterials hold great potential to enhance the imaging performance of magnetic resonance imaging (MRI) as auxiliary devices, due to their unique ability to confine and enhance electromagnetic fields. Despite their promise, the current implementation of metamaterials faces obstacles for practical clinical adoption due to several notable limitations, including their bulky and rigid structures, deviations from optimal resonance frequency, and inevitable interference with the radiofrequency (RF) transmission field in MRI. Herein, we address these restrictions by introducing a flexible and smart metamaterial that enhances sensitivity by conforming to patient anatomies while ensuring comfort during MRI procedures. The proposed metamaterial selectively amplifies the magnetic field during the RF reception phase by passively sensing the excitation signal strength, remaining "off" during the RF transmission phase. Additionally, the metamaterial can be readily tuned to achieve a precise frequency match with the MRI system through a controlling circuit. The metamaterial presented here paves the way for the widespread utilization of metamaterials in clinical MRI, thereby translating this promising technology to the MRI bedside.

Living microorganisms can perform directed migration for foraging in response to a chemoattractant gradient. We report a biomimetic strategy that rotary F_oF₁-ATPase (adenosine triphosphatase)-propelled flasklike colloidal motors exhibit positive chemotaxis resembling the chemotactic behavior of bacteria. The streamlined flasklike colloidal particles are fabricated through polymerization, expansion, surface rupture, and re-polymerizing nanoemulsions composed of triblock copolymers and ribose. The as-synthesized particles enable the incorporation of thylakoid vesicles into the cavity, ensuring a geometric asymmetric nanoarchitecture. The chemical gradient in the neck channel across flasklike colloidal motors facilitates autonomous movement at a speed of 1.19 μm/s in a ΔpH value of 4. Computer simulations reveal the self-actuated flasklike colloidal motors driven by self-diffusiophoretic force. These flasklike colloidal motors display positive directional motion along an adenosine diphosphate (ADP) concentration gradient during adenosine triphosphate (ATP) synthesis. The positive chemotaxis is ascribed that the phosphorylation reaction occurring inside colloidal motors generates 2 distinct phoretic torques at the bottom and the opening owing to the diffusion of ADP, thereby a continuous reorientation motion. Such a biophysical strategy that nanosized rotary protein molecular motors propel the directional movement of a flasklike colloidal motor holds promise for designing new types of biomedical swimming nanobots.

Photoelectrochemistry provides an important application in the production of high-value-added chemicals. However, photoelectrochemical organic transformation with high product selectivity remains a challenge. Until now, various technologies have been developed to promote the selectivity of photoelectrochemical high-value-added chemical production. Herein, a novel ion-shielding heterogeneous photoelectrocatalysis strategy for the production of trifluoromethyl group (CF₃)-containing compounds with high selectivity is described.

The effective and translational strategy to regenerate knee meniscal fibrocartilage remained challenging. Herein, we first identified vascular smooth muscle cells (VSMCs) transdifferentiated into fibrochondrocytes and participated in spontaneous meniscal regeneration using smooth muscle cell lineage tracing transgenic mice meniscal defect model. Then, we identified low-intensity pulsed ultrasound (LIPUS) acoustic stimulus enhanced fibrochondrogenic transdifferentiation of VSMCs in vitro and in vivo. Mechanistically, LIPUS stimulus could up-regulate mechanosensitive ion channel Piezo1 expression and then activate the transforming growth factor β1 (TGFβ1) signal, following repression of the Notch signal, consequently enhancing fibrochondrogenic transdifferentiation of VSMCs. Finally, we demonstrated that the regular LIPUS stimulus enhanced anisotropic native-like meniscal fibrocartilage tissue regeneration in a beagle canine subtotal meniscectomy model at 6 months postoperatively. The single-cell RNA sequencing analysis confirmed the role of VSMC fibrochondrogenic transdifferentiation in meniscal regeneration.

Radiative cooling has witnessed substantial progress while its performance is constrained by the thermal reciprocal Kirchhoff's law. Violating Kirchhoff's law to pursue nonreciprocal radiative cooling seems promising; however, the energy conservation requirement and radiant flux integrated over the entire hemisphere make the nonreciprocal benefit insignificant. This commentary discusses the practical limits of nonreciprocal radiative cooling and points toward the future direction of directional radiative cooling.

Neutrophils are essential in combating invading pathogens such as Plasmodium parasites, but the participation of their subpopulations and mechanisms in resistance to parasite infection are not fully understood. Our study identified a marked increase in Ly6G⁺ neutrophils in response to P. berghei ANKA infection. Depletion of these cells rendered mice more susceptible to infection. Elevated interleukin-17 (IL-17) levels, which increased the Ly6G⁺ neutrophil population, were also found to contribute to this protective effect. IL-17 depletion led to reduced neutrophil numbers and increased susceptibility. Furthermore, dihydroartemisinin (DHA) treatment enhanced neutrophil-mediated immune responses through up-regulation of CD18 and CXCR4 factors. These findings revealed key mechanisms of neutrophil and IL-17 interactions in malaria protection and highlighted DHA's potential to promote neutrophil function in combating malaria.

MXenes, a class of 2-dimensional transition metal carbides and nitrides, have garnered important attention due to their remarkable electrical and thermal conductivity, high photothermal conversion efficiency, and multifunctionality. This review explores the potential of MXene materials in various thermal applications, including thermal energy storage, heat dissipation in electronic devices, and the mitigation of electromagnetic interference in wearable technologies. Recent advancements in MXene composites, such as MXene/bacterial cellulose aerogel films and MXene/polymer composites, have demonstrated enhanced performance in phase change thermal storage and electromagnetic interference shielding, underscoring their versatility and effectiveness. Although notable progress has been made, challenges remain, including the need for a deeper understanding of photothermal conversion mechanisms, improvements in mechanical properties, exploration of diverse MXene types, and the development of sustainable synthesis methods. This paper discusses these aspects and outlines future research directions, emphasizing the growing importance of MXenes in addressing energy efficiency, health, and safety concerns in modern applications.