JACS Au最新文献

Wearable sweat sensors have emerged as promising tools for noninvasive health monitoring, yet the low analyte concentrations in sweat compared to blood pose significant challenges for the limit of detection. In this study, we developed a high-sensitivity electrochemical biosensor using carbon nanotube (CNT)-induced enzyme polymerization to detect uric acid and glucose with ultralow detection limits. The CNTs were functionalized via EDC/NHS to achieve covalent enzyme immobilization, enhancing catalytic efficiency, electron transfer, and sensor stability. To enable multifunctional sensing, we integrated glucose and uric acid detection with a pH sensor into a single wearable platform. A radially symmetric microfluidic module was designed through finite element analysis to optimize sweat flow and minimize refresh time, ensuring real-time biomarker tracking. The system also incorporated pH-based signal correction to improve detection accuracy in complex sweat environments. Finally, the sensing performance was validated through on-body sweat collection and analysis from six human volunteers, demonstrating its robustness, reliability, and potential for advancing next-generation personalized healthcare applications. This work provides a framework for designing multifunctional wearable sweat sensors and highlights the role of material and device innovations in overcoming key challenges in this field.

Recent investigations have demonstrated the appeal of using Ni-(II) complexes with redox-active ligands in fields like catalysis, electrochemistry, or materials sciences. Ni-(salen) complexes have particularly been shown to exhibit temperature-dependent equilibrium based on the localization of the unpaired spin. However, the usage of salen as a ligand has always restricted the characterization of a Ni-(IV) species with Ni bearing both the oxidizing equivalents. Hence, the current work aims to develop the biologically relevant pseudopeptide-based Ni complex that enables the formation and trapping of a high-valent Ni-(IV) species from its Ni-(II) precursor. The synthesized [LNi^II] (2) (L = N,N'-(4,5-dimethyl-1,2-phenylene)-bis-(pyrrolidine-2-carboxamide)) was shown to form a high-valent [LNi^IVCl₂] (4Cl) species, depending on the axial coordination, upon the addition of excess ceric ammonium nitrate, in the presence of chloride ions as an exogenous ligand, as supported by X-ray absorption spectroscopic analysis. Favorably, the formed Ni-(IV) species has also demonstrated electron transfer and oxygen atom transfer (OAT) reactions toward thioanisoles. Computational analysis of the mechanism revealed that the oxidation of thioanisoles proceeds via a stepwise pathway involving a single electron transfer from thioanisole, followed by OAT to the subsequent radical cation. The rate of these reactions demonstrated a strong dependence on the electronics of the substituents.

Aptamer-based lysosome-targeting chimeras (Apt-LYTACs) have emerged as a promising strategy for the selective degradation of cell surface proteins by linking a target-specific aptamer to a lysosome-trafficking receptor ligand. However, their degradation efficiency is often limited by weak noncovalent interactions, heterogeneous receptor distribution, and the constraints of a 1:1 complex stoichiometry. To address these challenges, we developed aptamer-mediated covalent dual lysosome-targeting chimeras (Apt-cdLYTACs), which enable specific covalent anchoring to the protein of interest with spatiotemporal control by combining the specificity of aptamer recognition with proximity-induced photoreactive cross-linking. These chimeras incorporate two lysosomal receptor ligands to enhance the local avidity and promote multivalent complex formation. Compared to conventional noncovalent or single-ligand covalent Apt-LYTAC, Apt-cdLYTAC forms more stable degradation complexes, exhibits prolonged intracellular retention, and reduces efflux, thereby significantly improving degradation efficiency. Apt-cdLYTAC provides a modular, efficient, and user-friendly platform for the selective degradation of membrane proteins, with broad potential for applications in biochemical research and therapeutic development.

Oligonucleotide-based aptamers are increasingly being used as recognition elements in biosensors to detect analytes relevant to diverse applications including medical diagnostics and therapeutic drug monitoring. Nevertheless, the utility of aptamers is often hindered by their insufficient target-binding affinity. We recently developed an affinity maturation approach termed Motif-SELEX that can improve aptamer binding affinity by up to an order of magnitude. This approach entails performing in vitro selection with a library containing conserved sequence motifs of an existing aptamer flanked by variable-length random domains that serve to enhance interactions with the target. Here, we demonstrate the application of Motif-SELEX to a DNA aptamer that binds to fentanyl with highalbeit inadequateaffinity to enable the detection of fentanyl at clinically relevant concentrations in biofluids. The matured aptamers discovered through Motif-SELEX are somewhat more complex than previous-generation aptamers, with additional nucleobases in their binding domain, and display 3-fold improved affinity toward fentanyl. We then use these aptamers to develop molecular beacon sensors that can detect fentanyl at concentrations as low as 6 nM in diluted filtered serum. Our findings indicate that Motif-SELEX offers an effective means to improve the affinity of underperforming aptamers toward levels suitable for practical use.

Iron-rich minerals, such as hematite (α-Fe₂O₃), are prominent constituents of the Martian surface; they are considered to be potential indicators of past aqueous activity and habitability. This study investigated the interaction between the extremophilic black fungus Rhinocladiella similis LaBioMMi 1217 and hematite under simulated laboratory conditions on Mars, focusing on redox-mediated dissolution processes, metabolic adaptations, and biosignature formation. The fungus was cultivated with powdered and polished hematite substrates, and mineral alteration was monitored through physicochemical measurements and scanning electron microscopy (SEM). Genome mining was performed to identify and map genes involved in iron metabolism. The metabolic profile of the fungus under hematite treatment was assessed via untargeted metabolomics. Over 15 days, the cultures exhibited marked acidification (pH decreased from 7.0 to 4.7) and a 10-fold increase in the dissolved Fe²⁺ ion concentration (26-270 mg/L), indicating metabolically driven iron reduction. SEM revealed surface etching and localized roughening consistent with microbially induced weathering, whereas these changes were absent in the abiotic controls. Genes linked to siderophore biosynthesis (sidA, sidC, sidD, sidF, sidH, sidI, and sidL) and reductive iron assimilation (FET3, FTR1, and FRE1) were identified. Untargeted metabolomics confirmed the secretion of organic acids, iron-chelating siderophores (e.g., ferrichrome C), and redox-active aromatic compounds in the presence of hematite, supporting a multifaceted strategy that combines acidification, chelation, and redox mediation. Collectively, these results show that the fungus actively promotes hematite dissolution through organic molecule-mediated mechanisms. Such interactions hold astrobiological relevance, as fungal modification of hematite might lead to the production of diagnostic chemical and mineralogical biosignatures, informing future life-detection strategies on Mars.

Melanoma is a life-threatening cancer, requiring more effective treatments. Photodynamic therapy (PDT) is a promising approach with favorable biosafety, although its clinical efficacy remains limited. In this work, we developed a nanoplatform combining poly-(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) and 1-[3-(methoxycarbonyl)-propyl]-1-phenyl-[6.6]-C₆₁ (PCBM), forming PFBT/PCBM (PP) nanoparticles, which contain a type II heterojunction that enables efficient charge transfer (≥97.7%) under irradiation. The resulting PFBT^+• and PCBM^-• radicals enable the generation of diverse reactive oxygen species (ROS) at high levels, including superoxide, hydroxyl radicals, and singlet oxygen (both type I and II ROS), through efficient electron and hole transfer processes. These multiple ROS species culminate in potent antitumor activity in vitro and in melanoma-bearing mice. Importantly, endogenous melanin accelerated the photocatalytic cycle, further amplifying the generation of ROS, thus enhancing the therapeutic outcome. Furthermore, PP-based PDT also demonstrated promising results in combating postsurgical infection and supporting wound healing, highlighting its potential as a multifunctional tool for comprehensive melanoma management. This work presents a PFBT/PCBM (PP) nanoplatform formed by coassembling poly-(9,9-dioctylfluorene-alt-benzothiadiazole) (PFBT) and PCBM to achieve highly efficient photoinduced charge transfer efficiency (≥97.7%). The resulting PFBT^+• and PCBM^-• radicals enable the generation of diverse reactive oxygen species (ROS) at high levels, while endogenous melanin accelerates the photocatalytic cycle, further amplifying the generation of ROS and enhancing the therapeutic outcome.

α-Aminoalkyl radicals have emerged as practical halogen-atom transfer (XAT) agents, enabling the formation of carbon radicals from unactivated alkyl and aryl halides under mild conditions. A recent study correctly revised some of the XAT rate constants for these radicals downward, prompting broad mechanistic conclusions that contradict the key importance of polar effects and challenge the XAT reactivity for α-aminobenzyl radicals. Herein we report a comprehensive kinetic and computational analysis of XAT reactions of α-aminoalkyl and α-aminobenzyl radicals with alkyl iodides under both thermal and photochemical conditions. Laser flash photolysis experiments reveal a clear structure-reactivity relationship shaped by polar and steric effects, which is well supported by the computational results. These findings reaffirm the key importance of the nucleophilic character of α-aminoalkyl radicals in providing significant transition state stabilization to XAT processes. This confirms the prominent role played by polar effects in these reactions and the possibility for reactivity tuning using α-aminobenzyl radicals.

Herein, we report a cobalt-catalyzed method for γ-selective C-H functionalization of aliphatic alcohols via a hydrogen atom transfer (HAT)-based radical relay. This strategy employs a readily available cobalt-salen catalyst under mild conditions, enabling diverse γ-C-H functionalization with excellent site-selectivity. Mechanistic insights were gained through spectroscopic experiments and DFT calculations, confirming the formation of carbon-centered radicals as key intermediates in the reaction pathway. This study offers a powerful tool for site-selective derivatization of alcohols and contributes to the development of sustainable and modular C-H functionalization strategies.

Supramolecular ionic polymers (SIPs) exhibit distinctive dynamic properties, which arise from the synergistic combination of substantial strength and pronounced reversibility of ionic interactions. However, conventional SIPs formed by coassembly using anionic and cationic separated double monomers suffer from complicated synthesis and heterogeneous structures, which obscure in-depth investigation of their dynamic behaviors. In response, we developed a zwitterionic monomer, namely TPE-2N2S, that incorporates both charged motifs into one fluorescent tetraphenylethylene (TPE) skeleton. This zwitterionic and single-component monomer design strategy enables the efficient formation of supramolecular zwitterionic polymers (SZIPs) with a uniform and orderly structure, and it can further enhance the understanding of structure-property relationships. In this perspective, we examine the dynamic features of ionic interactions in SZIPs, emphasizing their structural advantages, controllable assembly, and ionic interaction characteristics. We further investigate the dynamic behavior driven by ionic interactions at the intramolecular, intermolecular, and supramolecular architecture levels. Finally, we discuss key challenges and future opportunities in this emerging field, aiming to advance the design and application of SZIPs.

The human proteome represents a vast, largely untapped source of encrypted bioactive peptides with therapeutic potential. Here, we report the discovery and functional characterization of three antimicrobial encrypted peptides (EPs) derived from human matrix metallopeptidase-19 (residues 1-19, 1-33, and 247-279). These peptides exhibit potent, broad-spectrum activity against Gram-positive and Gram-negative bacteria, including clinical isolates and multidrug-resistant strains. Mechanistic studies reveal membrane depolarization and permeabilization as the primary mechanism of action. The peptides also inhibit biofilm formation, eradicate preformed biofilms, and exhibit selective antiviral activity against enveloped viruses. Importantly, they display negligible hemolysis and cytotoxicity toward mammalian cells while modulating inflammation through LPS neutralization. Synergy assays reveal synergistic or additive interactions with last-line antibiotics, and no resistance emerged after serial bacterial passaging. A fully d-amino acid analog of the lead peptide retained activity and exhibited cytocompatibility and in vivo efficacy in a murine skin infection model. These findings underscore the therapeutic promise of human protein-derived encrypted peptides and highlight proteome mining as a viable strategy for identifying host-compatible anti-infectives.