Latest ArticlesLithium−oxygen (Li−O2) batteries exhibit a superior energy density compared with any other battery currently available on the market. However, the practical application has been impeded by the insulated, insoluble discharge product (Li2O2). The limitations caused by Li2O2 are hardly to be addressed through the conventional catalyst design, which relies on the electronic structure and interfacial charge transfer characteristics. Herein, a magnetic/thermal coupling assisted Li−O2 batteries based on the thermoelectric material of MoS2 and magnetism single atom cobalt (SA−Co/MoS2) was constructed for the first time, by combing the magnetic heating and the thermoelectric catalytic effect. The spin polarization of the single atom Co may be promoted and a magnetic heating effect is generated by an external magnetic field, speeding up the oxygen evolution process (OER) and oxygen reduction reaction (ORR), as well as promoting the parallel spin arrangement of oxygen atoms. Because of its special SA−Co/MoS2 cathode, the Li−O2 battery with magnetic/thermal coupling assistance offers an ultra-low charging platform of 3.33 V and an ultra-high discharge platform of 2.90 V. The proposed novel method of sustaining the magnetic and thermal fields provides a crucial guidance for adjusting the excessive overpotential in metal−air battery systems.
A composite solid-state electrolyte with a triplex ionic transport architecture (TITA) was developed by integrating nanoscale fillers, short-chain crosslinkers and polymer matrix via solution casting and in situ photopolymerization. This structure creates efficient ion-conduction pathways, reduces ion aggregation, and enhances mechanical stability. As a result, the electrolyte achieves a high ionic conductivity of 7.36 × 10−4 S/cm and demonstrates excellent cycling performance when paired with an NCM622 cathode, showing great promise for solid-state lithium battery applications.
The key to electrolytic water includes two half-reaction processes: hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Transition metal phosphides (TMPs) are a class of prospective bifunctional electrocatalysts, but their performances are still far from the commercial catalysts. In this work, we design several kinds of Ni2P@CoP hetero-structured catalysts by the modification of Ru atom. The 0.1Ru-Ni2P@CoP catalyst presents the overpotentials of 82.7 (HER) and 245.3 mV (OER) at 10 mA/cm2 in 1 mol/L KOH solution. Moreover, it effectively promotes water splitting under alkaline conditions (ƞ10 = 1.21 V) and seawater conditions (ƞ10 = 1.13 V). The surface self-reconfiguration also makes it remain stable under prolonged cycling in both electrolytes. Density functional theory (DFT) calculations further indicate that doping engineering and heterostructures cause electronic modulation and electron transfer thereby increasing the intrinsic activity of the catalyst.
To mitigate the slow conversion kinetics and "shuttle effect" of polysulfides, a flexible, self-supporting Ni-nitrilotriacetic acid coordination polymer nanowires/few layer Ti3C2Tx MXene (Ni-NTA/f-Ti3C2Tx) interlayers with three-dimensional network is elaborately devised and fabricated. In this framework, the M–O–M (M = metal ion) linkages on polymer nanowires present superior catalytic activity towards the conversion of lithium polysulfides (LiPSs). Meanwhile, physical blocking and chemical trapping of LiPSs are also achieved, owing to the hierarchical porous structure and polar surface of hybrid interlayer. As a result, the lithium sulfur batteries assembled with Ni-NTA/f-Ti3C2Tx exhibit a high specific capacity of 899.5 mAh/g at 1 C and 529.6 mAh/g can be kept after 500 cycles with a decay rate of 0.08% per cycle, confirming the efficient alleviation of shuttle effect.
Coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus exacerbates pulmonary inflammation and tissue damage, significantly increasing the risks of respiratory failure, acute respiratory distress syndrome (ARDS), and secondary bacterial infections. Currently, there are no approved therapeutic agents specifically targeting these two viruses' coinfection. Human dihydroorotate dehydrogenase (DHODH), a key enzyme catalyzing the fourth step in the de novo pyrimidine biosynthesis pathway through the oxidation of dihydroorotate to orotate, serves as the rate-limiting enzyme in pyrimidine biosynthesis. This critical metabolic checkpoint has emerged as a promising broad-spectrum antiviral target. In this study, we designed and synthesized a series of DHODH-targeting proteolysis-targeting chimeras (PROTACs), among which PROTACs 17 and 19 connected via flexible alkyl linkers were identified as the most potent molecules. Mechanistic investigations revealed that 17 and 19 induced DHODH degradation through the proteasome- and cereblon (CRBN)-dependent pathways. Remarkably, 17 and 19 exhibited significant antiviral activities against both influenza virus and SARS-CoV-2 in vitro. These findings collectively present a novel and effective strategy for the treatment of coinfection caused by SARS-CoV-2 and influenza virus.
Genetically encoded fluorescence (FL) sensors play vital roles in monitoring cell metabolism dynamics, gene transcription, DNA repair, apoptosis, and nutrient sensing. In genetically encoded FL sensors study, microscope acquires multimodal images that contain bright-field (BF) and FL images. BF and FL images can provide different information on cell phenotypes and gray level. Here, we developed an artificial intelligence (AI)-driven system “AI-cell metabolism dynamic analyzer (AI-CMDA)” for high-throughput automatically cell division metabolism dynamics processing by fusing multimodal information. The system consists of a deep learning model based on multimodal images dedicated to division nodes extraction and an adaptive correlation filter tracker for associating cell sequences. The division extraction method enables fast filtering of dividing cells without manual selection, and the adaptive correlation filter can achieve robust, accurate tracking during cell transforms with time. We apply the system with 3 genetically encoded FL sensors for nicotinamide adenine dinucleotides (NAD+/NADH) ratio, reduced nicotinamide adenine dinucleotide phosphate (NADPH) and H2O2, respectively, to monitor the redox metabolism within cell division sequences. The results show that this system can reduce the processing time to seconds compared with several hours’ manual labeling and can achieve accuracy and fastness.
Adenomyosis remains a poorly understood condition characterized by the limited efficacy of current pharmacotherapy. Traditional treatments using dydrogesterone (DG) for adenomyosis often yield suboptimal outcomes due to poor targeting and susceptibility to immune rejection. Therefore, there is an urgent need to identify an effective approach to enhancing the therapeutic efficacy of DG. Given the enrichment of macrophages in the uterus associated with adenomyosis, this study sought to develop a supramolecular cell-based macrophage membrane-encapsulated DG nanoparticle (MM-DG-NP) delivery system for targeted drug delivery and effective treatment of adenomyosis. The MM-DG-NP system leverages a multifaceted therapeutic mechanism by evading phagocytic clearance and enhancing targeted drug delivery efficacy. The supramolecular cell framework, constructed through dynamic non-covalent interactions, provides structural stability and biofunctional adaptability to the MM-DG-NP system, enabling precise homing to uterine macrophage-rich pathological sites. The MM-DG-NP system demonstrated therapeutic efficacy superior to that of traditional DG therapy in murine models, characterized by a pronounced reduction in endometrial invasion depth within the myometrium; effective inhibition of epithelial–mesenchymal transition (EMT) progression in the glandular epithelium; significant attenuation of local inflammatory cytokine release in the uterus, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ); and notable alleviation of pain responses. These results highlight the critical role of supramolecular cell engineering in enhancing the biocompatibility and targeting precision of nanomedicines. MM-DG-NPs thus represent a promising strategy for overcoming current pharmacotherapeutic limitations in adenomyosis, warranting further investigation to explore their potential clinical translation.
As the most common primary intracranial brain tumor, glioma is confronted with critical therapeutic dilemmas characterized by dismal prognosis and restricted treatment modalities. The current standard treatment for glioma includes maximally safe resection combined with radiotherapy and temozolomide (TMZ) chemotherapy. However, the presence of the blood-brain barrier (BBB) significantly impedes drug penetration into the brain, further exacerbating the therapeutic challenges in glioma treatment. Consequently, developing effective strategies to deliver drugs across the BBB remains pivotal for glioma therapy. Hence, this comprehensive review examines innovative drug delivery strategies designed to overcome BBB through two principal approaches: in-situ drug depots and advanced systemic delivery systems. The first section analyzes the fundamental biological and anatomical barriers impeding effective glioma management. Then, we critically evaluate emerging in-situ delivery modalities, including biodegradable wafer implants, intratumoral injectable depots, and convection-enhanced delivery (CED) systems. The last section explores advanced systemic drug delivery systems (DDS) and summarizes cutting-edge strategies using functionalized nanoparticles (NPs), biomimetic delivery vectors, and stimulus-responsive DDS for efficient and safe systemic drug delivery. Challenges and future developments related to the application of drug-delivery strategies for glioma treatment are also discussed. In summary, this review not only maps the current landscape of drug delivery strategies but also illuminates transformative research trajectories that can pave the way for precision medicine in glioma treatment.
Deubiquitinases (DUBs) that remove conjugated ubiquitin from substrates are critical regulators of protein homeostasis and cellular signaling. Understanding the spatial distribution of DUBs in subcellular compartments is essential for uncovering their roles in stress responses and disease pathogenesis. Herein, we developed an Escherichia coli (E. coli)-based biosynthetic strategy for the expedient generation of biotin-labeled ubiquitin probe (Biotin-Ub-PA) through co-expression of Avi-Ub and BirA in E. coli, thus bypassing tedious chemical synthesis. Combined with affinity purification and proteomics, we utilized the biosynthetic probe to covalently capture active DUBs in subcellular compartments and revealed the distribution of DUBs in the cytoplasm and nucleus. As a proof of concept, hydrogen peroxide-induced activity changes of DUBs in the cytoplasm and nucleus were analyzed by the same probe. The results suggest that some DUBs, such as ubiquitin-specific protease 36 (USP36) and USP16, may undergo subcellular translocation and activity alterations under oxidative stress. Our study presents a reliable workflow for the spatial distribution analysis of DUBs under different stimuli or disease conditions.
Triggering mitochondria-targeted ferroptosis is the effective way to bypass apoptotic resistance of sonodynamic therapy (SDT), but it suffers from discounted therapeutic efficacy due to the anti-ferroptosis mechanism via mitochondrial dihydroorotate dehydrogenase (DHODH). Herein, iron porphyrin-based nanometal organic frameworks (PCN-600) were synthesized by hydrothermal method for loading the ferroptosis inducer sulfasalazine (SAS) and DHODH inhibitor brequinar (BQR), and finally surface-modified with short chains of mitochondria-targeting triphenylphosphine (TPP) and long chains contained tumor-targeting groups of biotin that can be cleaved by intratumoral glutathione (GSH) to re-expose TPP. The nanosystem could be successfully delivered into the mitochondria of cancer cells which was an important location of cell apoptosis and ferroptosis, released SAS/BQR, and produced amounts of ROS under ultrasound activation to induce ferroptosis and overcome ferroptosis resistance for dual-synergism with apoptosis to enhance the anti-tumor efficacy of SDT both in vitro and in vivo. The GSH-activated mitochondria-targeting nanosystem for devasting mitochondrial anti-ferroptosis provides a novel method for ferroptosis-based enhancement of anti-tumor efficacy of SDT.