Advanced Science最新文献

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%-80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c-Myc, further promoting the stability of c-Myc via deacetylation-mediated inhibition of K48-linked ubiquitylation. Stably expressed c-Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p-AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD-L1 and suppressing the antitumor immunity of CD8⁺ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c-Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

Lithium metal batteries (LMBs) have emerged in recent years as highly promising candidates for high-density energy storage systems. Despite their immense potential, mutual constraints arise when optimizing energy density, rate capability, and operational safety, which greatly hinder the commercialization of LMBs. The utilization of oriented structures in LMBs appears as a promising strategy to address three key performance barriers: 1) low efficiency of active material utilization at high surface loading, 2) easy formation of Li dendrites and damage to interfaces under high-rate cycling, and 3) low ionic conductivity of solid-state electrolytes in high safety LMBs. This review aims to holistically introduce the concept of oriented structures, provide criteria for quantifying the degree of orientation, and elucidate their systematic effects on the properties of materials and devices. Furthermore, a detailed categorization of oriented structures is proposed to offer more precise guidance for the design of LMBs. This review also provides a comprehensive summary of preparation techniques for oriented structures and delves into the mechanisms by which these can enhance the energy density, rate capability, and safety of LMBs. Finally, potential applications of oriented structures in LMBs and the crucial challenges that need to be addressed in this field are explored.

The strong ligand effect in B-doped Pd-based (PdB) catalysts renders them a promising anode for constructing formic acid fuel cells (FAFCs) exhibiting high power density and outstanding stability. However, the enhancement of the oxidation barrier is unavoidable in this alloy system owing to the electron transfer (ET) from B to Pd. In this study, a hydrogen doping strategy is employed to open charge freedom in PdB compounds and boost their formic acid oxidation reaction (FAOR) activity by suppressing the ET process. The resulting hydrogen-doped PdB (PdBH) exhibits an ultrahigh mass activity of up to 1.2A mg^-1 _Pd, which is 3.23 times that of the PdB catalyst and 9.55 times that of Pd black. Detailed experimental and theoretical studies show that the interstitial hydrogen leads to enhanced orbital hybridization and reduced electron density around Pd. This optimized ligand effect weakens the carbon monoxide adsorption and increases the direct pathway preference of PdBH, resulting in its outstanding catalytic activity for the FAOR. The development of this high-performance hydrogen-doped PdB catalyst is an important step toward the construction of advanced light element co-doped metal catalysts.

Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical-grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami-structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high-quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post-stroke patients captures the system's significance in measuring multiple physiological signals in real-time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non-invasive alternative for monitoring swallowing and aspiration events.

Near-infrared (NIR) light powdered CO₂ photoreduction reaction is generally restricted to the separation efficiency of photogenerated carriers and the supply of active hydrogen (*H). Herein, the study reports a retrofitting hydrogenated MoO_3-x (H-MoO_3-x) nanosheet photocatalysts with Ru single atom substitution (Ru@H-MoO_3-x) fabricated by one-step solvothermal method. Experiments together with theoretical calculations demonstrate that the synergistic effect of Ru substitution and oxygen vacancy can not only inhibit the recombination of photogenerated carriers, but also facilitate the CO₂ adsorption/activation as well as the supply of *H. Compared with H-MoO_3-x, the Ru@H-MoO_3-x exhibit more favorable formation of *CHO in the process of *CO conversion due to the fast *H generation on electron-rich Ru sites and transfer to *CO intermediates, leading to the preferential photoreduction of CO₂ to CH₄ with high selectivity. The optimized Ru@H-MoO_3-x exhibits a superior CO₂ photoreduction activity with CH₄ evolution rate of 111.6 and 39.0 µmol g_catalyst ^-1 under full spectrum and NIR light irradiation, respectively, which is 8.8 and 15.0 times much higher than that of H-MoO_3-x. This work provides an in-depth understanding at the atomic level on the design of NIR responsive photocatalyst for achieving the goal of carbon neutrality.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder leading to cognitive decline. Excessive cytosolic calcium (Ca²⁺) accumulation plays a critical role in the pathogenesis of AD since it activates the NOD-like receptor family, pyrin domain containing 3 (NLRP3), switches the endoplasmic reticulum (ER) unfolded protein response (UPR) toward proapoptotic signaling and promotes Aβ seeding. Herein, a liposomal nanodrug (felodipine@LND) is developed incorporating a calcium channel antagonist felodipine for Alzheimer's disease treatment through a low-intensity pulse ultrasound (LIPUS) irradiation-assisted blood brain barrier (BBB)-crossing drug delivery. The multifunctional felodipine@LND is effectively delivered to diseased brain through applying a LIPUS irradiation to the skull, which resulted in a series of positive effects against AD. Markedly, the nanodrug treatment switched the ER UPR toward antioxidant signaling, prevented the surface translocation of ER calreticulin (CALR) in microglia, and inhibited the NLRP3 activation and Aβ seeding. In addition, it promoted the degradation of damaged mitochondria via mitophagy, thereby inhibiting the neuronal apoptosis. Therefore, the anxiety-like behavior and cognitive impairment of 5xFAD mice with AD is significantly ameliorated, which manifested the potential of LIPUS - assisted BBB-crossing delivery of felodipine@LND to serve as a paradigm for AD therapy based on the well-recognized clinically available felodipine.

Magnetic topological insulators (TIs) herald a wealth of applications in spin-based technologies, relying on the novel quantum phenomena provided by their topological properties. Particularly promising is the (MnBi₂Te₄)(Bi₂Te₃)_n layered family of established intrinsic magnetic TIs that can flexibly realize various magnetic orders and topological states. High tunability of this material platform is enabled by manganese-pnictogen intermixing, whose amounts and distribution patterns are controlled by synthetic conditions. Here, nuclear magnetic resonance and muon spin spectroscopy, sensitive local probe techniques, are employed to scrutinize the impact of the intermixing on the magnetic properties of (MnBi₂Te₄)(Bi₂Te₃)_n and MnSb₂Te₄. The measurements not only confirm the opposite alignment between the Mn magnetic moments on native sites and antisites in the ground state of MnSb₂Te₄, but for the first time directly show the same alignment in (MnBi₂Te₄)(Bi₂Te₃)_n with n = 0, 1 and 2. Moreover, for all compounds, the static magnetic moment of the Mn antisite sublattice is found to disappear well below the intrinsic magnetic transition temperature, leaving a homogeneous magnetic structure undisturbed by the intermixing. The findings provide a microscopic understanding of the crucial role played by Mn-Bi intermixing in (MnBi₂Te₄)(Bi₂Te₃)_n and offer pathways to optimizing the magnetic gap in its surface states.

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

Targeted therapy remains the future of anti-cancer drug development, owing to the lack of specificity of current treatments which lead to damage in healthy normal tissues. ATR inhibitors have in recent times demonstrated promising clinical potential, and are currently being evaluated in the clinic. However, despite the considerable optimism for clinical success of these inhibitors, reports of associated normal tissues toxicities remain a concern and can compromise their utility. Here, ICT10336 is reported, a newly developed hypoxia-responsive prodrug of ATR inhibitor, AZD6738, which is hypoxia-activated and specifically releases AZD6738 only in hypoxic conditions, in vitro. This hypoxia-selective release of AZD6738 inhibited ATR activation (T1989 and S428 phosphorylation) and subsequently abrogated HIF1a-mediated adaptation of hypoxic cancers cells, thus selectively inducing cell death in 2D and 3D cancer models. Importantly, in normal tissues, ICT10336 is demonstrated to be metabolically stable and less toxic to normal cells than its active parent agent, AZD6738. In addition, ICT10336 exhibited a superior and efficient multicellular penetration ability in 3D tumor models, and selectively eradicated cells at the hypoxic core compared to AZD6738. In summary, the preclinical data demonstrate a new strategy of tumor-targeted delivery of ATR inhibitors with significant potential of enhancing the therapeutic index.

Nanographene oxide (nGO) flakes-graphene oxide with a lateral size of ≈100 nm or less-hold great promise for superior flux and energy-efficient nanofiltration membranes for desalination and precise ionic sieving owing to their unique high-density water channels with less tortuousness. However, their potential usage is currently limited by several challenges, including the tricky self-assembly of nano-sized flakes on substrates with micron-sized pores, severe swelling in aqueous solutions, and mechanical instability. Herein, the successful fabrication of a robust membrane stacked with nGO flakes on a substrate with a pore size of 0.22 µm by vacuum filtration is reported. This membrane achieved an unprecedented water permeance above 819.1 LMH bar^-1, with a high rejection rate of 99.7% for multivalent metal ions. The nGO flakes prepared using an electron beam irradiation method, have uniquely pure hydroxyl groups and abundant aromatic regions. The calculations revealed the strong hydrogen bonds between two nGO flakes, which arise from hydroxyl groups, coupled with hydrophobic aromatic regions, greatly enhance the stability of stacked flakes in aqueous solutions and increase their effective lateral size. The research presents a simple yet effective approach toward the fabrication of advanced 2D nanographene membranes with superior performance for ion sieving applications.