ACS Publications最新文献

Cancers remain among the most lethal diseases worldwide, accounting for a substantial proportion of human mortality. Despite significant advances, conventional therapeutic strategies are often limited by tumor microenvironment-mediated resistance, non-specific biodistribution, and severe systemic toxicity, underscoring the urgent need for more effective and targeted treatment modalities. Magnetic hyperthermia (MHT), coupled with magnetically guided drug delivery using biocompatible magnetic nanoparticles (MNPs), has emerged as a promising clinical approach for selective cancer therapy. This strategy enables precise localization at tumor sites, enhanced colloidal stability, and the effective preservation of surrounding healthy tissues. This review consolidates recent progress in the design, synthesis, and physicochemical characterization of MNPs developed for dual-modality cancer treatment. Various material platforms are critically examined, including iron oxide-based nanoparticles, ferromagnetic alloys, lanthanum strontium manganites, zirconium-based materials, carbon-based nanostructures, bioactive glasses, and glass-ceramic composites, with a particular emphasis on the structure-property correlations influencing magnetic performance and therapeutic outcomes. Key mechanisms governing alternating magnetic field-induced heat generation and thermally triggered drug release are discussed. The strategic tuning of the Curie temperature within biologically safe limits, combined with thermoresponsive surface functionalization, enables controlled hyperthermia and spatiotemporally regulated drug release. This integrated nanoplatform significantly enhances tumor selectivity while minimizing systemic toxicity.

The development of novel one-pot cascade protocols for synthesizing biologically significant nitrogen heterocycles plays a vital role in drug discovery and development. We report here a new and unexpected T3P-mediated one-pot transformation of amines and β-ketoesters into 4-pyridones via an enaminoester cascade cyclization process. This method affords structurally diverse and readily multi-tailorable 4-pyridones with up to 99% yields in 1 h at 70 °C, providing rapid access to a pharmaceutically significant heterocyclic motif. Furthermore, this method shows a low E-factor (5.18), a low process mass intensity (PMI, 6.18), and an excellent GreenScore (86). To the best of our knowledge, this study presents the first highly efficient and straightforward multicomponent synthesis of 4-pyridones using readily available substrates.

An efficient visible-light photoredox-catalyzed Sp3 C-H sulfonylation protocol for the synthesis of β-keto sulfones has been developed. The utilization of Ir{dF(CF3)(ppy)2dtbpy}PF6 as the photocatalyst and blue LEDs as the light sources enabled the formation of alkyl carbon radical and sulfonyl radical species from oxime ester and sodium sulfinate, allowing the radical-radical cross-coupling process to form C-S bonds, following a subsequent hydrolysis to deliver the corresponding β-keto sulfones in moderate to excellent isolated yields.

Designed anthraquinone photosensitizers enable selective switching between chalcone [2 + 2] cycloaddition and E/Z isomerization. The α-trifluoromethyl group drives isomerization (5:95), whereas the β-tert-butyl group with polychloro substituents promotes cycloaddition (98% yield), a result supported by DFT-derived triplet energies and binding energies. In addition, a relatively high chalcone concentration favors cycloaddition (98%), whereas a low chalcone concentration favors isomerization (98%).

We report a visible-light-induced photoredox method for the regioselective C3 α-carbonyl alkylation of 4-aminocoumarin derivatives. The protocol avoids transition metals and uses 10-phenylphenothiazine (PTH) as an efficient, inexpensive organic photocatalyst in place of the costly Ir(ppy)3. With α-carbonyl alkyl bromides as radical precursors, the reaction shows a broad substrate scope and delivers a range of C3 α-carbonyl alkylated 4-aminocoumarins in moderate to excellent yields.

Substrate stiffness is a critical mechanical cue that regulates cellular behaviors, yet its role in governing lipid homeostasis of human corneal endothelial cells (HCECs) remains poorly understood. Here, we developed a polyacrylamide hydrogel platform with tunable stiffnesses (25, 50, and 100 kPa) covering the pathophysiological range of Descemet's membrane to investigate stiffness-dependent lipid metabolic reprogramming in HCECs. All hydrogels exhibited excellent transparency (>95%) and good biocompatibility. We found that soft substrates (25 kPa) promoted substantial accumulation of neutral lipids and free cholesterol in HCECs. Mechanistically, soft substrates upregulated SREBP1 and its target genes to enhance fatty acid synthesis while suppressing CPT1-mediated fatty acid oxidation, and simultaneously upregulated LDLR and SREBP2 to promote cholesterol uptake and synthesis while downregulating the LXRα-ABCA1/ABCG1 axis to impair cholesterol efflux. Notably, PPARγ emerged as a key regulator of stiffness-dependent lipid homeostasis; its expression was positively correlated with substrate stiffness, and pharmacological activation of PPARγ reversed soft substrate-induced lipid accumulation. Furthermore, the Piezo1-PI3K/AKT-mTOR signaling axis was identified as an upstream mechanotransduction pathway mediating stiffness-regulated PPARγ expression. Analysis of transcriptomic datasets from Fuchs endothelial corneal dystrophy (FECD) patients revealed dysregulation of lipid metabolism genes consistent with our findings. Together, these results demonstrate that substrate stiffness governs HCEC lipid homeostasis through a Piezo1-PI3K/AKT-mTOR-PPARγ mechanotransduction cascade, and that matrix softening promotes abnormal lipid accumulation by reprogramming fatty acid and cholesterol metabolic networks. Our findings establish a mechanistic link between the mechanical microenvironment and lipid metabolism in corneal endothelial cells, providing insights into FECD pathogenesis and a theoretical framework for designing stiffness-tuned biomaterials for corneal endothelial regeneration.

The insufficient charge carrier mobility in the hole transport layer (HTL) and the energy level mismatch with the emissive layer have long been critical factors limiting the electroluminescence performance and carrier balance of quantum dot light-emitting diodes (QLEDs). To address this issue, we employed 4-tert-butylpyridine (4-TBP) as a dopant in poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-sec-butylphenyl)diphenylamine))] (TFB) as the HTL. By modulating the highest occupied molecular orbital energy level of TFB and enhancing the hole mobility, 4-TBP doping effectively reduces the hole injection barrier and suppresses interfacial charge accumulation. The optimized TFB:4-TBP HTL significantly improves hole injection efficiency in red QLEDs, leading to a decrease in turn-on voltage from 1.74 V to 1.65 V and an increase in external quantum efficiency (EQE) from 22.21 to 26.47%. Moreover, at an initial luminance of 1000 cd m-2, the QLED with the TFB:4-TBP HTL reaches a T95 operational lifetime of 11,708.67 h, which is 2.4 times longer than that of the undoped one. 1.22- and 1.37-fold improvements in EQEmax are obtained for green and blue QLEDs, respectively. This strategy demonstrates that 4-TBP doping, combined with interface engineering, provides an effective method to achieve efficient and stable hole transport, offering new insights for carrier balance control in solution-processed QLEDs.

Urine is a convenient, noninvasive specimen for molecular diagnostics, offering advantages in scalability, patient compliance, and suitability for decentralized testing. However, its clinical adoption for molecular pathogen detection remains limited by intrinsic physicochemical variability, low target abundance, and the presence of inhibitors of enzymatic nucleic acid amplification that may seriously compromise assay sensitivity and reproducibility. In this review, we introduce a urine-first design paradigm in which device architecture and assay chemistry are codesigned around the unique biochemical constraints of urine rather than adapted from conventional blood-based workflows. This paradigm is built on three interdependent principles: matrix-aware sample processing with efficient inhibitor removal and multifraction nucleic acid capture; amplification chemistry with built-in tolerance to pH fluctuations, ionic variability, and residual urinary inhibitors; and closed, integrated microfluidic architectures that minimize contamination risk. We compare on-chip amplification strategies, including PCR, isothermal amplification methods such as LAMP and RPA, digital PCR, and CRISPR-assisted detection, and evaluate trade-offs in sensitivity, inhibitor tolerance, and deployability. Detection modalities, including fluorescence, colorimetric, electrochemical, and lateral-flow readouts, are assessed for analytical performance and compatibility with resource-limited settings. By integrating biological insight with engineering design, this review provides a practical roadmap for developing accessible, field-ready urine-based diagnostic platforms.

The development of novel methodologies for olefin synthesis remains a central objective in synthetic chemistry, as olefins represent ubiquitous building blocks and versatile precursors for downstream transformations. The conventional Wittig reaction relies on phosphonium salts as carbon synthons, yet their synthesis requires alkyl halides that are often inaccessible for structurally complex substrates. Herein, we employ Cu(I)-photosensitizer catalysis to transform commercially available vinyl phosphonium salt into various elongated Wittig precursors under visible light irradiation, which subsequently react with aldehydes in a one-pot fashion to afford structurally diverse alkenes. This protocol synergistically combines the advantages of photoredox catalysis and the Wittig reaction, operates under mild conditions with excellent functional group tolerance, and accommodates readily available 1,4-dihydropyridines or silicates as modular radical sources, underscoring the practicality and flexibility of this approach.

Stereoselective cascade annulation reaction of vinyl/propargyl sulfonium salts with C-nucleophiles enables rapid construction of functionalized bicyclo[3.1.0]hexanes, bearing contiguous stereocenters, in good yields. This transformation proceeds via a Michael addition reaction of a C-nucleophile to a vinyl/allenyl sulfonium system, followed by an intramolecular Corey-Chaykovsky-type reaction, and consequently affords structurally complex bicyclic frameworks. This operationally simple strategy provides an efficient entry to synthetically challenging and densely functionalized carbocyclic scaffolds under mild conditions.