Research最新文献

Platelets are small, versatile blood cells that are critical for hemostasis/thrombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. However, the anti-inflammatory/immunosuppressive potential of platelets has been poorly explored. Here, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both platelet-associated and -independent antigen challenges. Utilizing multispectral photoacoustic tomography, we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in the liver, a process that we identified to be synergistically dependent on platelet glycoprotein Ibα and hepatic Ashwell-Morell receptor. Mechanistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with increased anti-inflammatory cytokines and circulating CD4⁺ regulatory T cells, abolishable by Kupffer cell depletion. Last, in a clinically relevant model of hemophilia A, presensitization with dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, these findings open new avenues toward understanding immune homeostasis and potentiate the therapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

Organic mechanophores have been widely adopted for polymer mechanotransduction. However, most examples of polymer mechanotransduction inevitably experience macromolecular chain rupture, and few of them mimic mussel's mechanochemical regeneration, a mechanically mediated process from functional units to functional materials in a controlled manner. In this paper, inorganic mechanoluminescent (ML) materials composed of CaZnOS-ZnS-SrZnOS: Mn²⁺ were used as a mechanotransducer since it features both piezoelectricity and mechanolunimescence. The utilization of ML materials in polymerization enables both mechanochemically controlled radical polymerization and the synthesis of ML polymer composites. This procedure features a mechanochemically controlled manner for the design and synthesis of diverse mechanoresponsive polymer composites.

Despite substantial progress in the treatment of castration-resistant prostate cancer (CRPC), including radiation therapy and immunotherapy alone or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we exploited the bioreactivity of novel polymer-lipid manganese dioxide nanoparticles (PLMDs) to remodel the tumor immune microenvironment (TIME) by increasing the local oxygen levels and extracellular pH and enhancing radiation-induced immunogenic cell death. This study demonstrated that PLMD treatment sensitized hypoxic human and murine CRPC cells to radiation, significantly increasing radiation-induced DNA double-strand breaks and ultimately cell death, which enhanced the secretion of damage-associated molecular patterns, attributable to the induction of autophagy and endoplasmic reticulum stress. Reoxygenation via PLMDs also polarized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor alpha release, and thus reducing the viability of murine CRPC TRAMP-C2 cells. In a syngeneic TRAMP-C2 tumor model, intravenous injection of PLMDs suppressed, while radiation alone enhanced recruitment of regulatory T cells and myeloid-derived suppressor cells. Pretreatment with PLMDs followed by radiation down-regulated programmed death-ligand 1 and promoted the infiltration of antitumor CD8⁺ T cells and M1 macrophages to tumor sites. Taken together, TIME modulation by PLMDs plus radiation profoundly delayed tumor growth and prolonged median survival compared with radiation alone. These results suggest that PLMDs plus radiation is a promising treatment modality for improving therapeutic efficacy in radioresistant and immunosuppressive solid tumors.

The recently discovered ATi₃Bi₅ (A=Cs, Rb) exhibit intriguing quantum phenomena including superconductivity, electronic nematicity, and abundant topological states. ATi₃Bi₅ present promising platforms for studying kagome superconductivity, band topology, and charge orders in parallel with AV₃Sb₅. In this work, we comprehensively analyze various properties of ATi₃Bi₅ covering superconductivity under pressure and doping, band topology under pressure, thermal conductivity, heat capacity, electrical resistance, and spin Hall conductivity (SHC) using first-principles calculations. Calculated superconducting transition temperature (T_c) of CsTi₃Bi₅ and RbTi₃Bi₅ at ambient pressure are about 1.85 and 1.92 K. When subject to pressure, T_c of CsTi₃Bi₅ exhibits a special valley and dome shape, which arises from quasi-two-dimensional compression to three-dimensional isotropic compression within the context of an overall decreasing trend. Furthermore, T_c of RbTi₃Bi₅ can be effectively enhanced up to 3.09 K by tuning the kagome van Hove singularities (VHSs) and flat band through doping. Pressures can also induce abundant topological surface states at the Fermi energy (E_F) and tune VHSs across E_F. Additionally, our transport calculations are in excellent agreement with recent experiments, confirming the absence of charge density wave. Notably, SHC of CsTi₃Bi₅ can reach up to 226ℏ ·(e· Ω ·cm)^-1 at E_F. Our work provides a timely and detailed analysis of the rich physical properties for ATi₃Bi₅, offering valuable insights for further experimental verifications and investigations in this field.

Circulating tumor DNA (ctDNA) detection has found widespread applications in tumor diagnostics and treatment, where the key is to obtain accurate quantification of ctDNA. However, this remains challenging due to the issue of background noise associated with existing assays. In this work, we developed a synthetic gene circuit-based assay with multilevel switch (termed CATCH) for background-free and absolute quantification of ctDNA. The multilevel switch combining a small transcription activating RNA and a toehold switch was designed to simultaneously regulate transcription and translation processes in gene circuit to eliminate background noise. Moreover, such a multilevel switch-based gene circuit was integrated with a Cas9 nickase H840A (Cas9n) recognizer and a molecular beacon reporter to form CATCH for ctDNA detection. The CATCH can be implemented in one-pot reaction at 35 °C with virtually no background noise, and achieve robust absolute quantification of ctDNA when integrated with a digital chip (i.e., digital CATCH). Finally, we validated the clinical capability of CATCH by detecting drug-resistant ctDNA mutations from the plasma of 76 non-small cell lung cancer (NSCLC) patients, showing satisfying clinical sensitivity and specificity. We envision that the simple and robust CATCH would be a powerful tool for next-generation ctDNA detection.

Photodeformable polymer materials have a far influence in the fields of flexibility and intelligence. The stimulation energy is converted into mechanical energy through molecular synergy. Among kinds of photodeformable polymer materials, liquid crystalline polymer (LCP) photodeformable materials have been a hot topic in recent years. Chromophores such as azobenzene, α-cyanostilbene, and 9,10-dithiopheneanthracene have been widely used in LCP, which are helpful for designing functional molecules to increase the penetration depth of light to change physical properties. Due to the various applications of photodeformable polymer materials, there are many excellent reports in intelligent field. In this review, we have systematized LCP containing azobenzene into 3 categories depending on the degree of crosslinking liquid crystalline elastomers, liquid crystalline networks, and linear LCPs. Other structural, typical polymer materials and their applications are discussed. Current issues faced and future directions to be developed for photodeformable polymer materials are also summarized.

Achieving color-tunable emission in single-component organic emitters with multistage stimuli-responsiveness is of vital significance for intelligent optoelectronic applications, but remains enormously challenging. Herein, we present an unprecedented example of a color-tunable single-component smart organic emitter (DDOP) that simultaneously exhibits multistage stimuli-responsiveness and multimode emissions. DDOP based on a highly twisted amide-bridged donor-acceptor-donor structure has been found to facilitate intersystem crossing, form multimode emissions, and generate multiple emissive species with multistage stimuli-responsiveness. DDOP pristine crystalline powders exhibit abnormal excitation-dependent emissions from a monomer-dominated blue emission centered at 470 nm to a dimer-dominated yellow emission centered at 550 nm through decreasing the ultraviolet (UV) excitation wavelengths, whereas DDOP single crystals show a wide emission band with a main emission peak at 585 nm when excited at different wavelengths. The emission behaviors of pristine crystalline powders and single crystals are different, demonstrating emission features that are closely related to the aggregation states. The work has developed color-tunable single-component organic emitters with simultaneous multistage stimuli-responsiveness and multimode emissions, which is vital for expanding intelligent optoelectronic applications, including multilevel information encryption, multicolor emissive patterns, and visual monitoring of UV wavelengths.

The identification of protein-protein interaction (PPI) sites is essential in the research of protein function and the discovery of new drugs. So far, a variety of computational tools based on machine learning have been developed to accelerate the identification of PPI sites. However, existing methods suffer from the low predictive accuracy or the limited scope of application. Specifically, some methods learned only global or local sequential features, leading to low predictive accuracy, while others achieved improved performance by extracting residue interactions from structures but were limited in their application scope for the serious dependence on precise structure information. There is an urgent need to develop a method that integrates comprehensive information to realize proteome-wide accurate profiling of PPI sites. Herein, a novel ensemble framework for PPI sites prediction, EnsemPPIS, was therefore proposed based on transformer and gated convolutional networks. EnsemPPIS can effectively capture not only global and local patterns but also residue interactions. Specifically, EnsemPPIS was unique in (a) extracting residue interactions from protein sequences with transformer and (b) further integrating global and local sequential features with the ensemble learning strategy. Compared with various existing methods, EnsemPPIS exhibited either superior performance or broader applicability on multiple PPI sites prediction tasks. Moreover, pattern analysis based on the interpretability of EnsemPPIS demonstrated that EnsemPPIS was fully capable of learning residue interactions within the local structure of PPI sites using only sequence information. The web server of EnsemPPIS is freely available at http://idrblab.org/ensemppis.

The influence of a mechanical structure's volume increment on the volume power density (VPD) of triboelectric nanogenerators (TENGs) is often neglected when considering surface charge density and surface power density. This paper aims to address this gap by introducing a standardized VPD metric for a more comprehensive evaluation of TENG performance. The study specifically focuses on 2 frequency-up mechanisms, namely, the integration of planetary gears (PG-TENG) and the implementation of a double-cantilever structure (DC-TENG), to investigate their impact on VPD. The study reveals that the PG-TENG achieves the highest volume average power density, measuring at 0.92 W/m³. This value surpasses the DC-TENG by 1.26 times and the counterpart TENG by a magnitude of 69.9 times. Additionally, the PG-TENG demonstrates superior average power output. These findings introduce a new approach for enhancing TENGs by incorporating frequency-up mechanisms, and highlight the importance of VPD as a key performance metric for evaluating TENGs.

Simulated reality encompasses virtual, augmented, and mixed realities-each characterized by different degrees of truthfulness in the visual perception: "all false," "coexistence of true and false," and "difficult distinction between true and false," respectively. In all these technologies, however, the temperature rendering of virtual objects is still an unsolved problem. Undoubtedly, the lack of thermal tactile functions substantially reduces the quality of the user's real-experience perception. To address this challenge, we propose theoretically and realize experimentally a technological platform for the in situ simulation of thermal reality. To this purpose, we design a thermal metadevice consisting of a reconfigurable array of radiating units, capable of generating the thermal image of any virtual object, and thus rendering it in situ together with its thermal signature. This is a substantial technological advance, which opens up new possibilities for simulated reality and its applications to human activities.