ACS Publications最新文献

Hepatic fibrosis, a pathological consequence of chronic liver injury, is characterized by excessive extracellular matrix (ECM) deposition, increasing the risk of hepatocellular carcinoma. The carbon tetrachloride (CCl₄)-induced mouse model is well-established for studying the pathogenesis and treatment of hepatic fibrosis, yet the effect of administration routes on fibrotic development and characteristics remains unclear. This study employed comparative proteomics to evaluate fibrosis induced via three CCl₄ delivery methods: intraperitoneal (IP), subcutaneous (SC), and intragastric (IG) administration. The results demonstrated that the administration route critically determined fibrotic severity, with IG causing the most severe fibro-inflammatory injury, followed by SC and IP. Proteomic profiling identified distinct molecular pathways: IG and SC were closely associated with tissue remodeling, while IP was correlated with immune activation. Cross-species analysis further highlighted conserved profibrotic mechanisms and the hub gene patterns of hepatic ECM remodeling and metabolism differing from mice and humans. These findings underscore the importance of the CCl₄ administration method as a crucial variable influencing the extent and nature of fibrosis in mouse models, and identify IG as the most effective modeling for advanced fibrosis. These insights offer a valuable foundation for refining experimental approaches to better mimic human hepatic fibrosis and enhance the translational relevance of research outcomes.

Polyethylene glycol (PEG) is used to graft liposomes with different densities to enhance their colloidal stability or blood circulation time, such as 0.3 mol % for commercial Onivyde and 5 mol % for DOXIL. However, the influence of PEG density on the mechanism of the accelerated blood clearance (ABC) of PEGylated liposomes remains unclear. In this study, we comparatively investigate the ABC phenomenon of liposomes modified with 0.3% and 5% molar ratios of PEG, and found that they displayed completely different mechanisms induced by anti-PEG antibodies. The ABC of liposomes grafted with 0.3 mol % PEG was induced by high-affinity anti-PEG antibodies, whereas the ABC of liposomes grafted with 5 mol % PEG was caused by both high and low-affinity anti-PEG antibodies. Free PEG can bind to high-affinity anti-PEG antibodies but not to low-affinity antibodies. Therefore, preinjecting a low dose of PEG completely inhibits the ABC of 0.3 mol % PEGylated liposomes while only partially decreasing the ABC of 5 mol % PEGylated liposomes in the PEG-immunized rats. These results suggest that the interfacial PEG density determines the mechanism of the ABC phenomenon of PEGylated liposomes, and the ABC of Onivyde can be readily inhibited by removing high-affinity anti-PEG antibodies in blood through preinjection of a low dose of PEG.

Understanding complex chemical reaction cascades remains a major challenge in chemistry. Scalable investigation of their thermodynamic and kinetic properties requires the use of automated reaction prediction tools, which is a rapidly growing area in the study of chemical reactivity. However, the systematic exploration of intricate reaction networks involving highly reactive intermediates continues to pose significant difficulties. Here, we introduce RxnNet, a novel artificial intelligence-assisted platform for the automated prediction of chemical reaction mechanisms. RxnNet integrates heuristic rules with domain-specific chemical knowledge including stereochemistry, regiochemistry, conformational preferences, and isotope labeling, to construct mechanistically informed reaction networks. These networks are represented as graphs and are coupled with on-the-fly quantum chemical evaluations to identify all feasible intermediates and transition states. In this work, we apply RxnNet to carbocation chemistry, a notoriously complex and computationally demanding type of reaction. We demonstrate the method's capabilities by analyzing three multistep reactions with known mechanisms, each of which poses significant challenges even for expert computational and synthetic chemists. RxnNet provides a robust approach for uncovering reaction mechanisms, which can accelerate the understanding and design of transformations in complex chemical systems.

Tuning crystallographic orientation is a crucial strategy for optimizing metal-semiconductor contacts and reducing the Schottky barrier height (SBH) to achieve low contact resistance. Based on density functional theory calculations, this study systematically investigates van der Waals heterostructures composed of MoS₂ and low-index crystallographic planes (0001, 011̅2, and 101̅0) of VA-group (Sb, As, and P) and VIA-group (α/β-Te) elements. Among the 15 constructed configurations, 11 exhibit structural stability. The results demonstrate that the crystallographic orientation and elemental species jointly regulate the electronic properties of heterostructures: MoS₂/Sb (0001) forms an n-type Ohmic contact (Φ_n = -0.12 eV) due to strong p-d orbital hybridization; Sb (101̅0)/MoS₂ and MoS₂/Sb (011̅2) exhibit n-type Schottky contact owing to weakened hybridization. In MoS₂/As and MoS₂/P systems, the SBH varies with crystallographic planes, primarily attributed to indirect mechanisms such as work function differences and interfacial charge transfer. Meanwhile, MoS₂/Te heterostructures undergo a transition from metallic to semiconducting behavior depending on the crystal phase and facet orientation. This work elucidates the mechanism by which crystallographic orientation modulates interfacial charge transfer and orbital hybridization through dangling bond density and work function, enabling precise design from tunable Schottky barriers to ohmic contacts, thereby providing theoretical guidance for the development of two-dimensional semiconductor devices.

Quantum materials that combine magnetism with topological order are emerging as key platforms for next-generation spintronics and low-energy electronics. They enable the realization of emergent quantum phenomena, such as the quantum anomalous Hall effect and axion insulator states. The ferromagnetic insulator (FMI)/topological insulator (TI)/FMI sandwich structure of a single-septuple layer (1SL) MnBi₂Te₄/four-quintuple layer (4QL) Bi₂Te₃/1SL MnBi₂Te₄ holds great potential to achieve such desirable quantum phenomena at an elevated temperature, owing to its large Dirac point band gap and high Curie temperature. Here, spin- and angle-resolved photoemission spectroscopy (spin-ARPES) is employed to directly verify that the band gap arises from broken time-reversal symmetry via proximity-driven magnetization. This study demonstrates direct control of the spin state via external magnetic fields and unambiguously confirms the exchange interaction as the gap-opening mechanism. The robust magnetic gap and controllable spin texture make this heterostructure a suitable candidate for spintronic applications and magnetic topological quantum phases.

Local chemical order (LCO) is a key descriptor linking composition, atomic arrangement, and function in high-entropy alloys (HEAs) yet remains difficult to quantify. This perspective highlights how X-ray absorption spectroscopy (XAS) provides element-specific, quantitative insight into LCO in complex alloys. We outline practical considerations for XAS data collection and fitting, including the width of spectra range, multitemperature analysis, and X-ray absorption edge choice for 5d elements. We then highlight a coordination-number-based framework for LCO analysis and use model HEAs to show how single-atom and near-single-atom motifs naturally emerge as component number increases, bridging HEAs and single-atom alloys. Finally, we identify priorities, including standardized protocols, uncertainty quantification, expanded operando and time-resolved XAS, and integration with complementary characterization and modeling.

In this study, we evaluate multiconfigurational trial wave function protocols for phaseless auxiliary field quantum Monte Carlo (ph-AFQMC) on transition metal containing systems. First, we benchmark vertical ionization potentials for 22 3d transition metal complexes against published high-accuracy ph-AFQMC values in a double-ζ basis set. We then compute the vertical ionization potential for a set of six metallocenes using our best-performing protocol, alongside ph-AFQMC using a configuration interaction singles and doubles (CISD) trial state. We also analyze the performance of canonical coupled-cluster theory with singles, doubles and perturbative triples (CCSD(T)), as well as its local approximation using domain-based local pair natural orbitals (DLPNO-CCSD(T1)) using different reference orbitals. To reach the complete-basis-set (CBS) limit, we examine several extrapolation schemes and report CBS-limit ph-AFQMC and CCSD(T) values alongside experimental results. We find that ph-AFQMC with the best-performing trial in a triple-ζ basis, followed by CBS correction from DLPNO-CCSD(T1) with unrestricted B3LYP reference orbitals, yields small deviations from experiment at modest cost. Using a CISD trial state in ph-AFQMC gives the closest agreement with experiment (errors <2 kcal/mol), albeit with lower scalability.

Development of synthetic ion transporters and in situ chemical reaction-mediated communication systems that mimic cellular signaling processes is crucial for preparing protocells to understand complex cellular signaling and related functions. Although there have been advances in synthetic ion transporters, the role of this synthetic ion transporter-mediated inter-vesicular signal transduction remains largely unexplored. Herein, we describe a photoregulated inter-vesicular molecular communication system that employs synthetic ion transporters and a photoresponsive precatalyst. This artificial communication system regulates the transformation of one chemical signal (Zn²⁺) from the sender vesicle into another chemical signal (Cl^-) to the receiver vesicle through a photoregulated chemical reaction in the extravesicular environment. Fluorescence-based ion transport and electrophysiological studies showed that the potent salicylaldehyde-based imine derivatives of 9-alkyl-9H-carbazole-3,6-diamine self-assemble within the lipid bilayer to form supramolecular nanochannels that selectively efflux Zn²⁺ from the sender vesicles. The use of a photoresponsive precatalyst anchored to the outer membrane of the receiver vesicle and the protransporter plays a crucial role in transforming the Zn²⁺-based chemical signal from the sender vesicles to a Cl^--based chemical signal into the receiver vesicle in a controlled manner. The Zn²⁺-bound catalyst-driven hydrolysis facilitates the release of an active transporter, a salicylanilide derivative, from its protransporter to transport Cl^- to a larger population of receiver vesicles, resulting in inter-vesicle signal transduction.

Selective control of the emission pattern of valley-polarized excitons in monolayer transition metal dichalcogenides is essential for advancing valleytronic, quantum information, and optoelectronic devices. Although substantial progress has been made in directionally routing photoluminescence from these materials, key challenges persist: specifically, establishing how observed routing effects relate to the degree of valley polarization and distinguishing genuine valley-dependent routing from spin-momentum coupling, an optical scattering effect unrelated to the emitter. In this work, we address these challenges by experimentally and numerically demonstrating a direct link between excitonic valley polarization and the resulting farfield emission pattern, enabling quantitative evaluation of valley-selective emission routing. We report valley-dependent manipulation of the angular emission pattern of monolayer tungsten diselenide using gold nanobar dimer antennas at cryogenic temperatures. By probing the emission under opposite circularly polarized excitation, we observe a valley-selective asymmetry in the photoluminescence circular dichroism of 2%. These measurements are supported by a reciprocity-based numerical framework that enables modeling of valley-selective emission in periodic systems. Our calculations further reveal that the observed valley-dependent directionality is a symmetry-protected property of the nanoantenna array arising from its extrinsic chirality at oblique emission angles, and that it can be substantially enhanced by tailoring the emitter distribution. Together, these results establish our nanoantenna platform as a robust route toward valleytronic signal processing.