High-resolution magnetic resonance spectroscopy using a solid-state spin sensor.

Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen-vacancy centres in combination with a narrowband synchronized readout protocol to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen-vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.

Time-to-surgery paradigms: wait time and surgical outcomes in critically Ill patients who underwent emergency surgery for gastrointestinal perforation.

BACKGROUND: Waiting time for emergency abdominal surgery have been known to be linked to mortality. However, there is no clear consensus on the appropriated timing of surgery for gastrointestinal perforation. We investigated association between wait time and surgical outcomes in emergency abdominal surgery. METHODS: This single-center retrospective cohort study evaluated adult patients who underwent emergency surgery for gastrointestinal perforations between January 2003 and September 2021. Risk-adjusted restricted cubic splines modeled the probability of each mortality according to wait time. The inflection point when mortality began to increase was used to define early and late surgery. Outcomes among propensity-score matched early and late surgical patients were compared using percent absolute risk differences (RDs, with 95% CIs). RESULTS: Mortality rates began to rise after 16 h of waiting. However, early and late surgery groups showed no significant differences in 30-day mortality (11.4% vs. 5.7%), ICU stay duration (4.3 ± 7.5 vs. 4.3 ± 5.2 days), or total hospital stay (17.4 ± 17.0 vs. 24.7 ± 23.4 days). Notably, patients waiting over 16 h had a significantly higher ICU readmission rate (8.6% vs. 31.4%). The APACHE II score was a significant predictor of 30-day mortality. CONCLUSIONS: Although we were unable to reveal significant differences in mortality in the subgroup analysis, we were able to find an inflection point of 16 h through the RCS curve technique. TRIAL REGISTRATION: Formal consent was waived due to the retrospective nature of the study, and ethical approval was obtained from the institutional research committee of our institution (B-2110-714-107) on 6 October 2021.

Autonomous Interfacial Assembly of Polymer Nanofilms via Surfactant-Regulated Marangoni Instability.

Interfacial polymerization (IP) provides a versatile platform for fabricating defect-free functional nanofilms for various applications, including molecular separation, energy, electronics, and biomedical materials. Unfortunately, coupled with complex natural instability phenomena, the IP mechanism and key parameters underlying the structural evolution of nanofilms, especially in the presence of surfactants as an interface regulator, remain puzzling. Here, we interfacially assembled polymer nanofilm membranes at the free water-oil interface in the presence of differently charged surfactants and comprehensively characterized their structure and properties. Combined with computational simulations, an in situ visualization of interfacial film formation discovered the critical role of Marangoni instability induced by the surfactants via various mechanisms in structurally regulating the nanofilms. Despite their different instability-triggering mechanisms, the delicate control of the surfactants enabled the fabrication of defect-free, ultra-permselective nanofilm membranes. Our study identifies critical IP parameters that allow us to rationally design nanofilms, coatings, and membranes for target applications.

Thin Film Composite Membranes as a New Category of Alkaline Water Electrolysis Membranes.

Alkaline water electrolysis (AWE) is considered a promising technology for green hydrogen (H2 ) production. Conventional diaphragm-type porous membranes have a high risk of explosion owing to their high gas crossover, while nonporous anion exchange membranes lack mechanical and thermochemical stability, limiting their practical application. Herein, a thin film composite (TFC) membrane is proposed as a new category of AWE membranes. The TFC membrane consists of an ultrathin quaternary ammonium (QA) selective layer formed via Menshutkin reaction-based interfacial polymerization on a porous polyethylene (PE) support. The dense, alkaline-stable, and highly anion-conductive QA layer prevents gas crossover while promoting anion transport. The PE support reinforces the mechanical and thermochemical properties, while its highly porous and thin structure reduces mass transport resistance across the TFC membrane. Consequently, the TFC membrane exhibits unprecedentedly high AWE performance (1.16 A cm-2 at 1.8 V) using nonprecious group metal electrodes with a potassium hydroxide (25 wt%) aqueous solution at 80 °C, significantly outperforming commercial and other lab-made AWE membranes. Moreover, the TFC membrane demonstrates remarkably low gas crossover, long-term stability, and stack cell operability, thereby ensuring its commercial viability for green H2 production. This strategy provides an advanced material platform for energy and environmental applications.

Interferon antagonists encoded by SARS-CoV-2 at a glance.

The innate immune system is a powerful barrier against invading pathogens. Interferons (IFNs) are a major part of the cytokine-mediated anti-viral innate immune response. After recognition of a pathogen by immune sensors, signaling cascades are activated that culminate in the release of IFNs. These activate cells in an autocrine or paracrine fashion eventually setting cells in an anti-viral state via upregulation of hundreds of interferon-stimulated genes (ISGs). To evade the anti-viral effect of the IFN system, successful viruses like the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved strategies to counteract both IFN induction and signaling. In fact, more than half of the about 30 proteins encoded by SARS-CoV-2 target the IFN system at multiple levels to escape IFN-mediated restriction. Here, we review recent insights into the molecular mechanisms used by SARS-CoV-2 proteins to suppress IFN production and the establishment of an anti-viral state.

Genetic and demographic signatures accompanying the evolution of the selfing syndrome in Daphne kiusiana, an evergreen shrub.

BACKGROUND AND AIMS: The evolution of mating systems from outcrossing to self-fertilization is a common transition in flowering plants. This shift is often associated with the 'selfing syndrome', which is characterized by less visible flowers with functional changes to control outcrossing. In most cases, the evolutionary history and demographic dynamics underlying the evolution of the selfing syndrome remain poorly understood. METHODS: Here, we characterize differences in the demographic genetic consequences and associated floral-specific traits between two distinct geographical groups of a wild shrub, Daphne kiusiana, endemic to East Asia; plants in the eastern region (southeastern Korea and Kyushu, Japan) exhibit smaller and fewer flowers compared to those of plants in the western region (southwestern Korea). Genetic analyses were conducted using nuclear microsatellites and chloroplast DNA (multiplexed phylogenetic marker sequencing) datasets. KEY RESULTS: A high selfing rate with significantly increased homozygosity characterized the eastern lineage, associated with lower levels of visibility and herkogamy in the floral traits. The two lineages harboured independent phylogeographical histories. In contrast to the western lineage, the eastern lineage showed a gradual reduction in the effective population size with no signs of a severe bottleneck despite its extreme range contraction during the last glacial period. CONCLUSIONS: Our results suggest that the selfing-associated morphological changes in D. kiusiana are of relatively old origin (at least 100 000 years ago) and were driven by directional selection for efficient self-pollination. We provide evidence that the evolution of the selfing syndrome in D. kiusiana is not strongly associated with a severe population bottleneck.

Thermococcus argininiproducens sp. nov., an arginine biosynthesis archaeal species isolated from the Central Indian Ocean ridge.

A strictly anaerobic hyperthermophilic archaeon, designated strain IOH2T, was isolated from a deep-sea hydrothermal vent (Onnuri vent field) area on the Central Indian Ocean Ridge. Strain IOH2T showed high 16S rRNA gene sequence similarity to Thermococcus sibiricus MM 739T (99.42 %), Thermococcus alcaliphilus DSM 10322T (99.28 %), Thermococcus aegaeus P5T (99.21 %), Thermococcus litoralis DSM 5473T (99.13 %), 'Thermococcus bergensis' T7324T (99.13 %), Thermococcus aggregans TYT (98.92 %) and Thermococcus prieurii Bio-pl-0405IT2T (98.01 %), with all other strains showing lower than 98 % similarity. The average nucleotide identity and in silico DNA-DNA hybridization values were highest between strain IOH2T and T. sibiricus MM 739T (79.33 and 15.00 %, respectively); these values are much lower than the species delineation cut-offs. Cells of strain IOH2T were coccoid, 1.0-1.2 µm in diameter and had no flagella. Growth ranges were 60-85 °C (optimum at 80 °C), pH 4.5-8.5 (optimum at pH 6.3) and 2.0-6.0 % (optimum at 4.0 %) NaCl. Growth of strain IOH2T was enhanced by starch, glucose, maltodextrin and pyruvate as a carbon source, and elemental sulphur as an electron acceptor. Through genome analysis of strain IOH2T, arginine biosynthesis related genes were predicted, and growth of strain IOH2T without arginine was confirmed. The genome of strain IOH2T was assembled as a circular chromosome of 1 946 249 bp and predicted 2096 genes. The DNA G+C content was 39.44 mol%. Based on the results of physiological and phylogenetic analyses, Thermococcus argininiproducens sp. nov. is proposed with type strain IOH2T (=MCCC 4K00089T=KCTC 25190T).

Effect-Directed Analysis Combined with Nontarget Screening to Identify Unmonitored Toxic Substances in the Environment.

Effect-directed analysis (EDA) combined with nontarget screening (NTS) has established a valuable tool for the identification of unmonitored toxic substances in environmental samples. It consists of three main steps: (1) highly potent fraction identification, (2) toxicant candidate selection, and (3) major toxicant identification. Here, we discuss the methodology, current status, limitations, and future challenges of EDA combined with NTS. This method has been applied successfully to various environmental samples, such as sediments, wastewater treatment plant effluents, and biota. We present several case studies and highlight key results. EDA has undergone significant technological advancements in the past 20 years, with the establishment of its key components: target chemical analysis, bioassays, fractionation, NTS, and data processing. However, it has not been incorporated widely into environmental monitoring programs. We provide suggestions for the application of EDA combined with NTS in environmental monitoring programs and management, with the identification of further research needs.

Identification of Mid-Polar and Polar AhR Agonists in Cetaceans from Korean Coastal Waters: Application of Effect-Directed Analysis with Full-Scan Screening.

Major aryl hydrocarbon receptor (AhR) agonists were identified in extracts of blubber, liver, and muscle from six long-beaked common dolphins (Delphinus capensis) and one fin whale (Balaenoptera physalus) collected from Korean coastal waters using effect-directed analysis. Results of the H4IIE-luc bioassay indicated that the polar fractions of blubber and liver extracts from the fin whale exhibited relatively high AhR-mediated potencies. Based on full-scan screening with high-resolution mass spectrometry, 37 AhR agonist candidates, spanning four use categories: pharmaceuticals, pesticides, cosmetics, and natural products, were selected. Among these, five polar AhR agonists were newly identified through toxicological confirmation. Concentrations of polar AhR agonists in cetaceans were tissue-specific, with extracts of blubber and liver containing greater concentrations than muscle extracts. Polar AhR agonists with great log KOA values (>5) were found to biomagnify in the marine food chain potentially. Polar AhR agonists contributed 8.9% of the observed AhR-mediated potencies in blubber and 49% in liver. Rutaecarpine and alantolactone contributed significantly to the total AhR-mediated potencies of blubber, whereas hydrocortisone was a major AhR contributor in the liver of the fin whale. This study is the first to identify the tissue-specific accumulation of polar AhR agonists in blubber and liver extracts of cetaceans.

Sub-10 nm Precision Engineering of Solid-State Defects via Nanoscale Aperture Array Mask.

Engineering a strongly interacting uniform qubit cluster would be a major step toward realizing a scalable quantum system for quantum sensing and a node-based qubit register. For a solid-state system that uses a defect as a qubit, various methods to precisely position defects have been developed, yet the large-scale fabrication of qubits within the strong coupling regime at room temperature continues to be a challenge. In this work, we generate nitrogen vacancy (NV) color centers in diamond with sub-10 nm scale precision using a combination of nanoscale aperture arrays (NAAs) with a high aspect ratio of 10 and a secondary E-beam hole pattern used as an ion-blocking mask. We perform optical and spin measurements on a cluster of NV spins and statistically investigate the effect of the NAAs during an ion-implantation process. We discuss how this technique is effective for constructing a scalable system.

Molecular Characterization of Estrogen Receptor Agonists during Sewage Treatment Processes Using Effect-Directed Analysis Combined with High-Resolution Full-Scan Screening.

Endocrine-disrupting potential was evaluated during the sewage treatment process using in vitro bioassays. Aryl hydrocarbon receptor (AhR)-, androgen receptor (AR)-, glucocorticoid receptor (GR)-, and estrogen receptor (ER)-mediated activities were assessed over five steps of the treatment process. Bioassays of organic extracts showed that AhR, AR, and GR potencies tended to decrease through the sewage treatment process, whereas ER potencies did not significantly decrease. Bioassays on reverse-phase high-performance liquid chromatography fractions showed that F5 (log KOW 2.5-3.0) had great ER potencies. Full-scan screening of these fractions detected two novel ER agonists, arenobufagin and loratadine, which are used pharmaceuticals. These compounds accounted for 3.3-25% of the total ER potencies and 4% of the ER potencies in the final effluent. The well-known ER agonists, estrone and 17ß-estradiol, accounted for 60 and 17% of the ER potencies in F5 of the influent and primary treatment, respectively. Fourier transform ion cyclotron resonance mass spectrometry analysis showed that various molecules were generated during the treatment process, especially CHO and CHOS (C: carbon, H: hydrogen, O: oxygen, and S: sulfur). This study documented that widely used pharmaceuticals are introduced into the aquatic environments without being removed during the sewage treatment process.

Magnetic resonance imaging of parotid gland tumors: a pictorial essay.

Imaging of parotid gland tumors is challenging due to the wide variety of differential diagnoses. Malignant parotid tumors can have very similar features to benign ones, such as slow growth and displacement instead of infiltration of neighboring structures. Malignant and benign tumors may therefore not be clinically distinguishable. Correct characterization of parotid tumors (i.e., benign or malignant) determines preoperative treatment planning and is important in optimizing the individualized surgical plan. Magnetic resonance imaging (MRI) is the imaging modality of choice for evaluation of suspected parotid gland lesions and differentiation between benign and malignant lesions. Certain conventional MRI features can suggest whether a mass is more likely to be a benign or low-grade malignancy or a high-grade malignancy and adding diffusion-weighted imaging or advanced MRI techniques like perfusion can aid in this distinction. Morphological features seen on MRI, such as low signal on T2-w, infiltrative changes or ill-defined margins, change over time and diffusion restriction can point to the malignant nature of the lesion. MRI is useful for detection and localization of the lesion(s), and associated findings like perineural spread of tumor, lymph node involvement and infiltrative changes of the surrounding tissues. In this pictorial essay, we present selected images of a variety of benign and malignant parotid tumors and emphasize the MRI features that may be useful in their characterization.

Development and validation of an ensemble artificial intelligence model for comprehensive imaging quality check to classify body parts and contrast enhancement.

BACKGROUND: Despite the dramatic increase in the use of medical imaging in various therapeutic fields of clinical trials, the first step of image quality check (image QC), which aims to check whether images are uploaded appropriately according to the predefined rules, is still performed manually by image analysts, which requires a lot of manpower and time. METHODS: In this retrospective study, 1669 computed tomography (CT) images with five specific anatomical locations were collected from Asan Medical Center and Kangdong Sacred Heart Hospital. To generate the ground truth, two radiologists reviewed the anatomical locations and presence of contrast enhancement using the collected data. The individual deep learning model is developed through InceptionResNetv2 and transfer learning, and we propose Image Quality Check-Net (Image QC-Net), an ensemble AI model that utilizes it. To evaluate their clinical effectiveness, the overall accuracy and time spent on image quality check of a conventional model and ImageQC-net were compared. RESULTS: ImageQC-net body part classification showed excellent performance in both internal (precision, 100%; recall, 100% accuracy, 100%) and external verification sets (precision, 99.8%; recovery rate, 99.8%, accuracy, 99.8%). In addition, contrast enhancement classification performance achieved 100% precision, recall, and accuracy in the internal verification set and achieved (precision, 100%; recall, 100%; accuracy 100%) in the external dataset. In the case of clinical effects, the reduction of time by checking the quality of artificial intelligence (AI) support by analysts 1 and 2 (49.7% and 48.3%, respectively) was statistically significant (p < 0.001). CONCLUSIONS: Comprehensive AI techniques to identify body parts and contrast enhancement on CT images are highly accurate and can significantly reduce the time spent on image quality checks.

The Analyses of Cetacean Virus-Responsive Genes Reveal Evolutionary Marks in Mucosal Immunity-Associated Genes.

Viruses are the most common and abundant organisms in the marine environment. To better understand how cetaceans have adapted to this virus-rich environment, we compared cetacean virus-responsive genes to those from terrestrial mammals. We identified virus-responsive gene sequences in seven species of cetaceans, which we compared with orthologous sequences in seven terrestrial mammals. As a result of evolution analysis using the branch model and the branch-site model, 21 genes were selected using at least one model. IFN-ε, an antiviral cytokine expressed at mucous membranes, and its receptor IFNAR1 contain cetacean-specific amino acid substitutions that might change the interaction between the two proteins and lead to regulation of the immune system against viruses. Cetacean-specific amino acid substitutions in IL-6, IL-27, and the signal transducer and activator of transcription (STAT)1 are also predicted to alter the mucosal immune response of cetaceans. Since mucosal membranes are the first line of defense against the external environment and are involved in immune tolerance, our analysis of cetacean virus-responsive genes suggests that genes with cetacean-specific mutations in mucosal immunity-related genes play an important role in the protection and/or regulation of immune responses against viruses.

Strong Zero-Phonon Transition from Point Defect-Stacking Fault Complexes in Silicon Carbide Nanowires.

Crystallographic defects such as vacancies and stacking faults engineer electronic band structure at the atomic level and create zero- and two-dimensional quantum structures in crystals. The combination of these point and planar defects can generate a new type of defect complex system. Here, we investigate silicon carbide nanowires that host point defects near stacking faults. These point-planar defect complexes in the nanowire exhibit outstanding optical properties of high-brightness single photons (>360 kcounts/s), a fast recombination time (<1 ns), and a high Debye-Waller factor (>50%). These distinct optical properties of coupled point-planar defects lead to an unusually strong zero-phonon transition, essential for achieving highly efficient quantum interactions between multiple qubits. Our findings can be extended to other defects in various materials and therefore offer a new perspective for engineering defect qubits.

Development and Validation of a Difficulty Scoring System for Laparoscopic Liver Resection to Treat Hepatolithiasis.

Background and Objectives: A difficulty scoring system was previously developed to assess the difficulty of laparoscopic liver resection (LLR) for liver tumors; however, we need another system for hepatolithiasis. Therefore, we developed a novel difficulty scoring system (nDSS) and validated its use for predicting postoperative outcomes. Materials and Methods: This was a retrospective study. We used clinical data of 123 patients who underwent LLR for hepatolithiasis between 2003 and 2021. We analyzed the data to determine which indices were associated with operation time or estimated blood loss (EBL) to measure the surgical difficulty. We validated the nDSS in terms of its ability to predict postoperative outcomes, namely red blood cell (RBC) transfusion, postoperative hospital stay (POHS), and major complications defined as grade ≥IIIa according to the Clavien−Dindo classification (CDC). Results: The nDSS included five significant indices (range: 5−17; median: 8). The RBC transfusion rate (p < 0.001), POHS (p = 0.002), and major complication rate (p = 0.002) increased with increasing nDSS score. We compared the two groups of patients divided by the median nDSS (low: 5−7; high: 8−17). The operation time (210.7 vs. 240.7 min; p < 0.001), EBL (281.9 vs. 702.6 mL; p < 0.001), RBC transfusion rate (5.3% vs. 37.9%; p < 0.001), POHS (8.0 vs. 13.3 days; p = 0.001), and major complication rate (8.8% vs. 25.8%; p = 0.014) were greater in the high group. Conclusions: The nDSS can predict the surgical difficulty and outcomes of LLR for hepatolithiasis and may help select candidates for the procedure and surgical approach.

α-Poly-L-lysine functions as an adipogenic inducer in 3T3-L1 preadipocytes.

α-Poly-L-lysine (PLL) has been used for various purposes such as cell attachment, immunization, and molecular delivery, and is known to be cytotoxic to several cell lines. Here, we studied the effect of PLL on the adipogenesis of 3T3-L1 cells and investigated the underlying mechanism. Differentiation media containing PLL with a molecular weight (MW) greater than 4 kDa enhanced lipid droplet formation and increased adipogenic marker levels, indicating an increase in adipocyte differentiation. PLL with a molecular weight between 30 and 70 kDa was more effective than PLL of other sizes in 3T3-L1 cell differentiation. Moreover, PLL induced 3T3-L1 adipogenesis in insulin-free adipocyte differentiation medium. Incubation with insulin and PLL exhibited greater adipogenesis than insulin treatment only even at a high concentration. PLL stimulated insulin signaling and augmented the signaling pathway when it was added with insulin. While PLL did not activate the glucocorticoid receptor, which is phosphorylated by dexamethasone (DEX), it showed a positive effect on the cAMP signal pathway when preadipocytes were treated with PLL and 3-isobutyl-1-methylxanthine (IBMX). Consistent with these results, incubation with PLL and DEX without IBMX induced adipocyte differentiation. We also observed that the mitotic clonal expansion phase was the critical stage in adipogenesis for inducing the effects of PLL. These results suggest that PLL functions as an adipogenic inducer in 3T3-L1 preadipocytes and PLL has a direct effect on insulin signaling, one of the main regulatory pathways.

Chloride-Mediated Enhancement in Heat-Induced Activation of Peroxymonosulfate: New Reaction Pathways for Oxidizing Radical Production.

This study is the first to demonstrate the capability of Cl- to markedly accelerate organic oxidation using thermally activated peroxymonosulfate (PMS) under acidic conditions. The treatment efficiency gain allowed heat-activated PMS to surpass heat-activated peroxydisulfate (PDS). During thermal PMS activation at excess Cl-, accelerated oxidation of 4-chlorophenol (susceptible to oxidation by hypochlorous acid (HOCl)) was observed along with significant degradation of benzoic acid and ClO3- occurrence, which involved oxidants with low substrate specificity. This indicated that heat facilitated HOCl formation via nucleophilic Cl- addition to PMS and enabled free chlorine conversion into less selective oxidizing radicals. HOCl acted as a key intermediate in the major oxidant transition based on temperature-dependent variation in HOCl concentration profiles, kinetically retarded organic oxidation upon NH4+ addition, and enabled rapid organic oxidation in heated PMS/HOCl mixtures. Chlorine atom that formed via the one-electron oxidation of Cl- by the sulfate radical served as the primary oxidant and was involved in hydroxyl radical production. This was corroborated by the quenching effects of alcohols and bicarbonates, reactivity toward multiple organics, and electron paramagnetic resonance spectral features. PMS outperformed PDS in degrading benzoic acid during thermal activation operated in reverse osmosis concentrate, which was in conflict with the well-established superiority of heat-activated PDS.

HIV Nef, paxillin, and Pak1/2 regulate activation and secretion of TACE/ADAM10 proteases.

The HIV Nef protein recruits the polycomb protein Eed and mimics an integrin receptor signal for reasons that are not entirely clear. Here we demonstrate that Nef and Eed complex with the integrin effector paxillin to recruit and activate TNFα converting enzyme (TACE alias ADAM 17) and its close relative ADAM10. The activated proteases cleaved proTNFα and were shuttled into extracellular vesicles (EVs). Peripheral blood mononuclear cells that ingested these EVs released TNFα. Analyzing the mechanism, we found that Pak2, an established host cell effector of Nef, phosphorylated paxillin on Ser272/274 to induce TACE-paxillin association and shuttling into EVs via lipid rafts. Conversely, Pak1 phosphorylated paxillin on Ser258, which inhibited TACE association and lipid raft transfer. Interestingly, melanoma cells used an identical mechanism to shuttle predominantly ADAM10 into EVs. We conclude that HIV-1 and cancer cells exploit a paxillin/integrin-controlled mechanism to release TACE/ADAM10-containing vesicles, ensuring better proliferation/growth conditions in their microenvironment.

Ultrasensitive Plasmon-Free Surface-Enhanced Raman Spectroscopy with Femtomolar Detection Limit from 2D van der Waals Heterostructure.

Two-dimensional (2D) materials have been promoted as an ideal platform for surface-enhanced Raman spectroscopy (SERS), as they mitigate the drawbacks of noble metal-based SERS substrates. However, the inferior limit of detection has limited the practical applicability of 2D material-based SERS substrates. Here, we synthesize uniform large-area ReOxSy thin films via solution-phase deposition without post-treatments and demonstrate a graphene/ReOxSy vertical heterostructure as an ultrasensitive SERS platform. The electronic structure of ReOxSy can be modulated by changing the oxygen concentration in the lattice structure, obtaining efficient complementary resonance effects between ReOxSy and the probe molecule. In addition, the oxygen atoms in the ReOxSy lattice generate a dipole moment on the thin-film surface, which increases the electron transition probability. These synergistic effects outstandingly enhance the Raman effect in the ReOxSy thin film. When ReOxSy forms a vertical heterostructure on a graphene as the SERS substrate, the enhanced charge-transfer and exciton resonances improve the limit of detection to the femtomolar level, while achieving remarkable flexibility, reproducibility, and operational stability. Our results provide important insights into 2D material-based ultrasensitive SERS based on chemical mechanisms.