Respiratory-resolved 5D Flow MRI: in-vivo validation and respiratory dependent flow changes in healthy volunteers and patients with congenital heart disease.

BACKGROUND: This study aimed to validate respiratory-resolved 5D flow MRI against real-time 2D phase contrast MRI, assess the impact of number of respiratory states, and measure the impact of respiration on hemodynamics in congenital heart disease (CHD) patients. METHODS: Respiratory-resolved 5D flow MRI derived net and peak flow measurements were compared to real-time 2D phase contrast MRI derived measurements in 10 healthy volunteers. Pulmonary to systemic flow ratios (Qp:Qs) were measured in 19 CHD patients and aortopulmonary collateral burden was measured in 5 Fontan patients. Additionally, the impact of number of respiratory states on measured respiratory-driven net flow changes was investigated in 10 healthy volunteers and 19 CHD patients (shunt physiology, n=11, single ventricle disease (SVD), n=8). RESULTS: There was good agreement between 5D flow MRI and real-time 2D phase contrast derived net and peak flow. Respiratory driven changes had good correlation (rho=0.64, p<0.001). In healthy volunteers, fewer than four respiratory states reduced measured respiratory driven flow changes in veins (5.2mL/cycle, p<0.001) and arteries (1.7mL/cycle, p=0.05). Respiration drove substantial venous net flow changes in SVD (64% change) and shunt patients (57% change). Respiration had significantly greater impact in SVD patients compared to shunt patients in the right and left pulmonary arteries (46% vs 15%, p=0.003 & 59% vs 20%, p=0.002). Qp:Qs varied by 37±24% over respiration in SVD patients and 12±20% in shunt patients. Aortopulmonary collateral burden varied by 118±84% over respiration in Fontan patients. The smallest collateral burden was measured during active inspiration in all patients and the greatest burden was during active expiration in 4 of 5 patients. Reduced respiratory resolution blunted measured flow changes in the caval veins of shunt and SVD patients (p<0.005). CONCLUSIONS: Respiratory-resolved 5D flow MRI measurements agree with real-time 2D phase contrast. Venous measurements are sensitive to number of respiratory states, whereas arterial measurements are more robust. Respiration has substantial impact on caval vein flow, Qp:Qs, and collateral burden in CHD patients.

Large-Area Intercalated Two-Dimensional Pb/Graphene Heterostructure as a Platform for Generating Spin-Orbit Torque.

A scalable platform to synthesize ultrathin heavy metals may enable high-efficiency charge-to-spin conversion for next-generation spintronics. Here, we report the synthesis of air-stable, epitaxially registered monolayer Pb underneath graphene on SiC (0001) by confinement heteroepitaxy (CHet). Diffraction, spectroscopy, and microscopy reveal that CHet-based Pb intercalation predominantly exhibits a mottled hexagonal superstructure due to an ordered network of Frenkel-Kontorova-like domain walls. The system's air stability enables ex situ spin torque ferromagnetic resonance (ST-FMR) measurements that demonstrate charge-to-spin conversion in graphene/Pb/ferromagnet heterostructures with a 1.5× increase in the effective field ratio compared to control samples.

Influence of Substrate-Induced Charge Doping on Defect-Related Excitonic Emission in Monolayer MoS2.

Many applications of transition metal dichalcogenides (TMDs) involve transfer to functional substrates that can strongly impact their optical and electronic properties. We investigate the impact that substrate interactions have on free carrier densities and defect-related excitonic (XD) emission from MoS2 monolayers grown by metal-organic chemical vapor deposition. C-plane sapphire substrates mimic common hydroxyl-terminated substrates. We demonstrate that transferring MoS2 monolayers to pristine c-plane sapphire dramatically increases the free electron density within MoS2 layers, quenches XD emission, and accelerates exciton recombination at the optical band edge. In contrast, transferring MoS2 monolayers onto inert hexagonal boron nitride (h-BN) has no measurable influence on these properties. Our findings demonstrate the promise of utilizing substrate engineering to control charge doping interactions and to quench broad XD background emission features that can influence the purity of single photon emitters in TMDs being developed for quantum photonic applications.

Dynamic STEM-EELS for single-atom and defect measurement during electron beam transformations.

This study introduces the integration of dynamic computer vision-enabled imaging with electron energy loss spectroscopy (EELS) in scanning transmission electron microscopy (STEM). This approach involves real-time discovery and analysis of atomic structures as they form, allowing us to observe the evolution of material properties at the atomic level, capturing transient states traditional techniques often miss. Rapid object detection and action system enhances the efficiency and accuracy of STEM-EELS by autonomously identifying and targeting only areas of interest. This machine learning (ML)-based approach differs from classical ML in that it must be executed on the fly, not using static data. We apply this technology to V-doped MoS2, uncovering insights into defect formation and evolution under electron beam exposure. This approach opens uncharted avenues for exploring and characterizing materials in dynamic states, offering a pathway to increase our understanding of dynamic phenomena in materials under thermal, chemical, and beam stimuli.

Maternal asthma during pregnancy and risks of allergy and asthma in progeny: A systematic review and meta-analysis.

BACKGROUND: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear. OBJECTIVES: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538). SEARCH STRATEGY: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023. SELECTION CRITERIA: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma. CONCLUSIONS: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation.

Gravidity influences distinct transcriptional profiles of maternal and fetal placental macrophages at term.

Introduction: Maternal intervillous monocytes (MIMs) and fetal Hofbauer cells (HBCs) are myeloid-derived immune cells at the maternal-fetal interface. Maternal reproductive history is associated with differential risk of pregnancy complications. The molecular phenotypes and roles of these distinct monocyte/macrophage populations and the influence of gravidity on these phenotypes has not been systematically investigated. Methods: Here, we used RNA sequencing to study the transcriptional profiles of MIMs and HBCs in normal term pregnancies. Results: Our analyses revealed distinct transcriptomes of MIMs and HBCs. Genes involved in differentiation and cell organization pathways were more highly expressed in MIMs vs. HBCs. In contrast, HBCs had higher expression of genes involved in inflammatory responses and cell surface receptor signaling. Maternal gravidity influenced monocyte programming, as expression of pro-inflammatory molecules was significantly higher in MIMs from multigravidae compared to primigravidae. In HBCs, multigravidae displayed enrichment of gene pathways involved in cell-cell signaling and differentiation. Discussion: Our results demonstrated that MIMs and HBCs have highly divergent transcriptional signatures, reflecting their distinct origins, locations, functions, and roles in inflammatory responses. Furthermore, maternal gravidity influences the gene signatures of MIMs and HBCs, potentially modulating the interplay between tolerance and trained immunity. The phenomenon of reproductive immune memory may play a novel role in the differential susceptibility of primigravidae to pregnancy complications.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome ß5 active-site (Pfß5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto ß7. Inhibition of Pfß5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the ß5/ß6/ß3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Analyzing high-throughput assay data to advance the rapid screening of environmental chemicals for human reproductive toxicity.

While high-throughput (HTP) assays have been proposed as platforms to rapidly assess reproductive toxicity, there is currently a lack of established assays that specifically address germline development/function and fertility. We assessed the applicability domains of yeast (S. cerevisiae) and nematode (C. elegans) HTP assays in toxicity screening of 124 environmental chemicals, determining their agreement in identifying toxicants and their concordance with reproductive toxicity in vivo. We integrated data generated in the two models and compared results using a streamlined, semi-automated benchmark dose (BMD) modeling approach. We then extracted and modeled relevant mammalian in vivo data available for the matching chemicals included in the Toxicological Reference Database (ToxRefDB). We ranked potencies of common compounds using the BMD and evaluated correlation between the datasets using Pearson and Spearman correlation coefficients. We found moderate to good correlation across the three data sets, with r = 0.48 (95% CI: 0.28-1.00, p<0.001) and rs = 0.40 (p=0.002) for the parametric and rank order correlations between the HTP BMDs; r = 0.95 (95% CI: 0.76-1.00, p=0.0005) and rs = 0.89 (p=0.006) between the yeast assay and ToxRefDB BMDs; and r = 0.81 (95% CI: 0.28-1.00, p=0.014) and rs = 0.75 (p=0.033) between the worm assay and ToxRefDB BMDs. Our findings underscore the potential of these HTP assays to identify environmental chemicals that exhibit reproductive toxicity. Integrating these HTP datasets into mammalian in vivo prediction models using machine learning methods could further enhance the predictive value of these assays in future rapid screening efforts.

Rapid identification of reproductive toxicants among environmental chemicals using an in vivo evaluation of gametogenesis in budding yeast Saccharomyces cerevisiae.

Infertility affects ∼12 % of couples, with environmental chemical exposure as a potential contributor. Of the chemicals that are actively manufactured, very few are assessed for reproductive health effects. Rodents are commonly used to evaluate reproductive effects, which is both costly and time consuming. Thus, there is a pressing need for rapid methods to test a broader range of chemicals. Here, we developed a strategy to evaluate large numbers of chemicals for reproductive toxicity via a yeast, S. cerevisiae high-throughput assay to assess gametogenesis as a potential new approach method (NAM). By simultaneously assessing chemicals for growth effects, we can distinguish if a chemical affects gametogenesis only, proliferative growth only or both. We identified a well-known mammalian reproductive toxicant, bisphenol A (BPA) and ranked 19 BPA analogs for reproductive harm. By testing mixtures of BPA and its analogs, we found that BPE and 17 ß-estradiol each together with BPA showed synergistic effects that worsened reproductive outcome. We examined an additional 179 environmental chemicals including phthalates, pesticides, quaternary ammonium compounds and per- and polyfluoroalkyl substances and found 57 with reproductive effects. Many of the chemicals were found to be strong reproductive toxicants that have yet to be tested in mammals. Chemicals having affect before meiosis I division vs. meiosis II division were identified for 16 gametogenesis-specific chemicals. Finally, we demonstrate that in general yeast reproductive toxicity correlates well with published reproductive toxicity in mammals illustrating the promise of this NAM to quickly assess chemicals to prioritize the evaluation for human reproductive harm.

Placental Malaria Induces a Unique Placental Methylation Profile Associated with Fetal Growth Restriction.

Background: Fetal growth restriction (FGR) is associated with perinatal death and other adverse birth outcomes, as well as long term complications including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. FGR has been associated with placental epigenetic reprogramming, which may mediate these long term outcomes. Placental malaria (PM) is the leading cause of FGR globally, but the impact on placental epigenetics is unknown. We hypothesized that methylomic profiling of placentas from non-malarial and malarial FGR would reveal common and distinct mechanistic pathways associated with FGR. Results: We used a methylation array to compare the CpG profiles between FGR from a cohort with no malaria exposure and a cohort of pregnancies complicated by both PM and FGR. Non-malarial FGR was associated with 65 differentially methylated CpGs, whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls. One DMC (cg16389901) was commonly hypomethylated in both groups, corresponding to the promoter region of BMP4 . Comparison of FGR vs. PM-FGR identified 522 DMCs between these two groups, which was not attributable to geographic location or different cellular compositions of these two groups. Conclusion: Placentas from pregnancies with PM-associated FGR showed distinct methylation profiles as compared to non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. There may be distinct long-term health outcomes in FGR pregnancies also complicated by PM.

RosetteArray® Platform for Quantitative High-Throughput Screening of Human Neurodevelopmental Risk.

Neural organoids have revolutionized how human neurodevelopmental disorders (NDDs) are studied. Yet, their utility for screening complex NDD etiologies and in drug discovery is limited by a lack of scalable and quantifiable derivation formats. Here, we describe the RosetteArray® platform's ability to be used as an off-the-shelf, 96-well plate assay that standardizes incipient forebrain and spinal cord organoid morphogenesis as micropatterned, 3-D, singularly polarized neural rosette tissues (>9000 per plate). RosetteArrays are seeded from cryopreserved human pluripotent stem cells, cultured over 6-8 days, and immunostained images can be quantified using artificial intelligence-based software. We demonstrate the platform's suitability for screening developmental neurotoxicity and genetic and environmental factors known to cause neural tube defect risk. Given the presence of rosette morphogenesis perturbation in neural organoid models of NDDs and neurodegenerative disorders, the RosetteArray platform could enable quantitative high-throughput screening (qHTS) of human neurodevelopmental risk across regulatory and precision medicine applications.

High rates of placental inflammation among samples collected by the Multi-Omics for Mothers and Infants consortium.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (≥37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population-based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Tailoring amorphous boron nitride for high-performance two-dimensional electronics.

Two-dimensional (2D) materials have garnered significant attention in recent years due to their atomically thin structure and unique electronic and optoelectronic properties. To harness their full potential for applications in next-generation electronics and photonics, precise control over the dielectric environment surrounding the 2D material is critical. The lack of nucleation sites on 2D surfaces to form thin, uniform dielectric layers often leads to interfacial defects that degrade the device performance, posing a major roadblock in the realization of 2D-based devices. Here, we demonstrate a wafer-scale, low-temperature process (<250 °C) using atomic layer deposition (ALD) for the synthesis of uniform, conformal amorphous boron nitride (aBN) thin films. ALD deposition temperatures between 125 and 250 °C result in stoichiometric films with high oxidative stability, yielding a dielectric strength of 8.2 MV/cm. Utilizing a seed-free ALD approach, we form uniform aBN dielectric layers on 2D surfaces and fabricate multiple quantum well structures of aBN/MoS2 and aBN-encapsulated double-gated monolayer (ML) MoS2 field-effect transistors to evaluate the impact of aBN dielectric environment on MoS2 optoelectronic and electronic properties. Our work in scalable aBN dielectric integration paves a way towards realizing the theoretical performance of 2D materials for next-generation electronics.

Screening and characterization of 133 physiologically-relevant environmental chemicals for reproductive toxicity.

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals would benefit significantly from scalable and innovative approaches to testing using functionally comparable reproductive models such as the nematode C. elegans. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in the average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

A substitutional quantum defect in WS2 discovered by high-throughput computational screening and fabricated by site-selective STM manipulation.

Point defects in two-dimensional materials are of key interest for quantum information science. However, the parameter space of possible defects is immense, making the identification of high-performance quantum defects very challenging. Here, we perform high-throughput (HT) first-principles computational screening to search for promising quantum defects within WS2, which present localized levels in the band gap that can lead to bright optical transitions in the visible or telecom regime. Our computed database spans more than 700 charged defects formed through substitution on the tungsten or sulfur site. We found that sulfur substitutions enable the most promising quantum defects. We computationally identify the neutral cobalt substitution to sulfur (Co S 0 ) and fabricate it with scanning tunneling microscopy (STM). The Co S 0 electronic structure measured by STM agrees with first principles and showcases an attractive quantum defect. Our work shows how HT computational screening and nanoscale synthesis routes can be combined to design promising quantum defects.

Ambient carbon dioxide concentration correlates with SARS-CoV-2 aerostability and infection risk.

An improved understanding of the underlying physicochemical properties of respiratory aerosol that influence viral infectivity may open new avenues to mitigate the transmission of respiratory diseases such as COVID-19. Previous studies have shown that an increase in the pH of respiratory aerosols following generation due to changes in the gas-particle partitioning of pH buffering bicarbonate ions and carbon dioxide is a significant factor in reducing SARS-CoV-2 infectivity. We show here that a significant increase in SARS-CoV-2 aerostability results from a moderate increase in the atmospheric carbon dioxide concentration (e.g. 800 ppm), an effect that is more marked than that observed for changes in relative humidity. We model the likelihood of COVID-19 transmission on the ambient concentration of CO2, concluding that even this moderate increase in CO2 concentration results in a significant increase in overall risk. These observations confirm the critical importance of ventilation and maintaining low CO2 concentrations in indoor environments for mitigating disease transmission. Moreover, the correlation of increased CO2 concentration with viral aerostability need to be better understood when considering the consequences of increases in ambient CO2 levels in our atmosphere.

Screening and characterization of 133 physiologically-relevant environmental chemicals for reproductive toxicity.

Reproduction is a functional outcome that relies on complex cellular, tissue, and organ interactions that span the developmental period to adulthood. Thus, the assessment of its disruption by environmental chemicals is remarkably painstaking in conventional toxicological animal models and does not scale up to the number of chemicals present in our environment and requiring testing. We adapted a previously described low-throughput in vivo chromosome segregation assay using C. elegans predictive of reproductive toxicity and leveraged available public data sources (ToxCast, ICE) to screen and characterize 133 physiologically-relevant chemicals in a high-throughput manner. The screening outcome was further validated in a second, independent in vivo assay assessing embryonic viability. In total, 13 chemicals were classified as reproductive toxicants with the two most active chemicals belonging to the large family of Quaternary Ammonium Compounds (QACs) commonly used as disinfectants but with limited available reproductive toxicity data. We compared the results from the C. elegans assay with ToxCast in vitro data compiled from 700+ cell response assays and 300+ signaling pathways-based assays. We did not observe a difference in the bioactivity or in average potency (AC50) between the top and bottom chemicals. However, the intended target categories were significantly different between the classified chemicals with, in particular, an over-representation of steroid hormone targets for the high Z-score chemicals. Taken together, these results point to the value of in vivo models that scale to high-throughput level for reproductive toxicity assessment and to the need to prioritize the assessment of QACs impacts on reproduction.

Air-Stable, Large-Area 2D Metals and Semiconductors.

Two-dimensional (2D) materials are popular for fundamental physics study and technological applications in next-generation electronics, spintronics, and optoelectronic devices due to a wide range of intriguing physical and chemical properties. Recently, the family of 2D metals and 2D semiconductors has been expanding rapidly because they offer properties once unknown to us. One of the challenges to fully access their properties is poor stability in ambient conditions. In the first half of this Review, we briefly summarize common methods of preparing 2D metals and highlight some recent approaches for making air-stable 2D metals. Additionally, we introduce the physicochemical properties of some air-stable 2D metals recently explored. The second half discusses the air stability and oxidation mechanisms of 2D transition metal dichalcogenides and some elemental 2D semiconductors. Their air stability can be enhanced by optimizing growth temperature, substrates, and precursors during 2D material growth to improve material quality, which will be discussed. Other methods, including doping, postgrowth annealing, and encapsulation of insulators that can suppress defects and isolate the encapsulated samples from the ambient environment, will be reviewed.

Charge state-dependent symmetry breaking of atomic defects in transition metal dichalcogenides.

The functionality of atomic quantum emitters is intrinsically linked to their host lattice coordination. Structural distortions that spontaneously break the lattice symmetry strongly impact their optical emission properties and spin-photon interface. Here we report on the direct imaging of charge state-dependent symmetry breaking of two prototypical atomic quantum emitters in mono- and bilayer MoS2 by scanning tunneling microscopy (STM) and non-contact atomic force microscopy (nc-AFM). By changing the built-in substrate chemical potential, different charge states of sulfur vacancies (VacS) and substitutional rhenium dopants (ReMo) can be stabilized. Vac S - 1 as well as Re Mo 0 and Re Mo - 1 exhibit local lattice distortions and symmetry-broken defect orbitals attributed to a Jahn-Teller effect (JTE) and pseudo-JTE, respectively. By mapping the electronic and geometric structure of single point defects, we disentangle the effects of spatial averaging, charge multistability, configurational dynamics, and external perturbations that often mask the presence of local symmetry breaking.

Tuning the Fermi Level of Graphene by Two-Dimensional Metals for Raman Detection of Molecules.

Graphene-enhanced Raman scattering (GERS) offers great opportunities to achieve optical sensing with a high uniformity and superior molecular selectivity. The GERS mechanism relies on charge transfer between molecules and graphene, which is difficult to manipulate by varying the band alignment between graphene and the molecules. In this work, we synthesized a few atomic layers of metal termed two-dimensional (2D) metal to precisely and deterministically modify the graphene Fermi level. Using copper phthalocyanine (CuPc) as a representative molecule, we demonstrated that tuning the Fermi level can significantly improve the signal enhancement and molecular selectivity of GERS. Specifically, aligning the Fermi level of graphene closer to the highest occupied molecular orbital (HOMO) of CuPc results in a more pronounced Raman enhancement. Density functional theory (DFT) calculations of the charge density distribution reproduce the enhanced charge transfer between CuPc molecules and graphene with a modulated Fermi level. Extending our investigation to other molecules such as rhodamine 6G, rhodamine B, crystal violet, and F16CuPc, we showed that 2D metals enabled Fermi level tuning, thus improving GERS detection for molecules and contributing to an enhanced molecular selectivity. This underscores the potential of utilizing 2D metals for the precise control and optimization of GERS applications, which will benefit the development of highly sensitive, specific, and reliable sensors.