Multistate, Ultrathin, Back-End-of-Line-Compatible AlScN Ferroelectric Diodes.

The growth in data generation necessitates efficient data processing technologies to address the von Neumann bottleneck in conventional computer architecture. Memory-driven computing, which integrates nonvolatile memory (NVM) devices in a 3D stack, is gaining attention, with CMOS back-end-of-line (BEOL)-compatible ferroelectric (FE) diodes being ideal due to their two-terminal design and inherently selector-free nature, facilitating high-density crossbar arrays. Here, we demonstrate BEOL-compatible, high-performance FE diodes scaled to 5, 10, and 20 nm FE Al0.72Sc0.28N/Al0.64Sc0.36N films. Through interlayer (IL) engineering, we show substantial improvements in the on/off ratios (>166 times) and rectification ratios (>176 times) in these scaled devices. These characteristics also enable 5-bit multistate operation with a stable retention. We also experimentally and theoretically demonstrate the counterintuitive result that the inclusion of an IL can lead to a decrease in the ferroelectric switching voltage of the device. An in-depth analysis into the device transport mechanisms is performed, and our compact model aligns seamlessly with the experimental results. Our results suggest the possibility of using scaled AlxSc1-xN FE diodes for high-performance, low-power, embedded NVM.

Fetal brain response to maternal inflammation requires microglia.

In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. The cell types mediating the fetal brain response to maternal inflammation are largely unknown, hindering the development of novel treatment strategies. Here, we show that microglia, the resident phagocytes of the brain, highly express receptors for relevant pathogens and cytokines throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

Massively parallel in vivo Perturb-seq reveals cell-type-specific transcriptional networks in cortical development.

Leveraging AAVs' versatile tropism and labeling capacity, we expanded the scale of in vivo CRISPR screening with single-cell transcriptomic phenotyping across embryonic to adult brains and peripheral nervous systems. Through extensive tests of 86 vectors across AAV serotypes combined with a transposon system, we substantially amplified labeling efficacy and accelerated in vivo gene delivery from weeks to days. Our proof-of-principle in utero screen identified the pleiotropic effects of Foxg1, highlighting its tight regulation of distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% by lentivirus, to achieve analysis of over 30,000 cells in one experiment and enable massively parallel in vivo Perturb-seq. Compatible with various phenotypic measurements (single-cell or spatial multi-omics), it presents a flexible approach to interrogate gene function across cell types in vivo, translating gene variants to their causal function.

Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer.

The main cause of death in lung cancer patients is metastasis. Thus, efforts to suppress micrometastasis or distant metastasis in lung cancer, identify therapeutic targets and develop related drugs are ongoing. In this study, we identified SET and MYND domain-containing protein 5 (SMYD5) as a novel metastasis regulator in lung cancer and found that SMYD5 was overexpressed in lung cancer based on both RNA-sequencing analysis results derived from the TCGA portal and immunohistochemical analysis results; knockdown of SMYD5 inhibited cell migration and invasion by changing epithelial-mesenchymal transition markers and MMP9 expression in NCI-H1299 and H1703 cell lines. Additionally, SMYD5 knockdown increased Src homology 2-b3 expression by decreasing the level of H4K20 trimethylation. Furthermore, in an in vitro epithelial-mesenchymal transition system using TGF-ß treatment, SMYD5 knockdown resulted in reduced cell migration and invasion in the highly invasive NCI-H1299 and H1703 cell lines. Based on these findings, we propose that SMYD5 could serve as a potential therapeutic target for lung cancer treatment and that cotreatment with an SMYD5 inhibitor and chemotherapy may enhance the therapeutic effect of lung cancer treatment.

Accuracy of a large language model in distinguishing anti- and pro-vaccination messages on social media: The case of human papillomavirus vaccination.

Objective: Vaccination has engendered a spectrum of public opinions, with social media acting as a crucial platform for health-related discussions. The emergence of artificial intelligence technologies, such as large language models (LLMs), offers a novel opportunity to efficiently investigate public discourses. This research assesses the accuracy of ChatGPT, a widely used and freely available service built upon an LLM, for sentiment analysis to discern different stances toward Human Papillomavirus (HPV) vaccination. Methods: Messages related to HPV vaccination were collected from social media supporting different message formats: Facebook (long format) and Twitter (short format). A selection of 1,000 human-evaluated messages was input into the LLM, which generated multiple response instances containing its classification results. Accuracy was measured for each message as the level of concurrence between human and machine decisions, ranging between 0 and 1. Results: Average accuracy was notably high when 20 response instances were used to determine the machine decision of each message: .882 (SE = .021) and .750 (SE = .029) for anti- and pro-vaccination long-form; .773 (SE = .027) and .723 (SE = .029) for anti- and pro-vaccination short-form, respectively. Using only three or even one instance did not lead to a severe decrease in accuracy. However, for long-form messages, the language model exhibited significantly lower accuracy in categorizing pro-vaccination messages than anti-vaccination ones. Conclusions: ChatGPT shows potential in analyzing public opinions on HPV vaccination using social media content. However, understanding the characteristics and limitations of a language model within specific public health contexts remains imperative.

Tuning Polarity in WSe2/AlScN FeFETs via Contact Engineering.

Recent advancements in ferroelectric field-effect transistors (FeFETs) using two-dimensional (2D) semiconductor channels and ferroelectric Al0.68Sc0.32N (AlScN) allow high-performance nonvolatile devices with exceptional ON-state currents, large ON/OFF current ratios, and large memory windows (MW). However, previous studies have solely focused on n-type FeFETs, leaving a crucial gap in the development of p-type and ambipolar FeFETs, which are essential for expanding their applicability to a wide range of circuit-level applications. Here, we present a comprehensive demonstration of n-type, p-type, and ambipolar FeFETs on an array scale using AlScN and multilayer/monolayer WSe2. The dominant injected carrier type is modulated through contact engineering at the metal-semiconductor junction, resulting in the realization of all three types of FeFETs. The effect of contact engineering on the carrier injection is further investigated through technology-computer-aided design simulations. Moreover, our 2D WSe2/AlScN FeFETs achieve high electron and hole current densities of ∼20 and ∼10 µA/µm, respectively, with a high ON/OFF ratio surpassing ∼107 and a large MW of >6 V (0.14 V/nm).

Massively parallel in vivo Perturb-seq reveals cell type-specific transcriptional networks in cortical development.

Systematic analysis of gene function across diverse cell types in vivo is hindered by two challenges: obtaining sufficient cells from live tissues and accurately identifying each cell's perturbation in high-throughput single-cell assays. Leveraging AAV's versatile cell type tropism and high labeling capacity, we expanded the resolution and scale of in vivo CRISPR screens: allowing phenotypic analysis at single-cell resolution across a multitude of cell types in the embryonic brain, adult brain, and peripheral nervous system. We undertook extensive tests of 86 AAV serotypes, combined with a transposon system, to substantially amplify labeling and accelerate in vivo gene delivery from weeks to days. Using this platform, we performed an in utero genetic screen as proof-of-principle and identified pleiotropic regulatory networks of Foxg1 in cortical development, including Layer 6 corticothalamic neurons where it tightly controls distinct networks essential for cell fate specification. Notably, our platform can label >6% of cerebral cells, surpassing the current state-of-the-art efficacy at <0.1% (mediated by lentivirus), and achieve analysis of over 30,000 cells in one experiment, thus enabling massively parallel in vivo Perturb-seq. Compatible with various perturbation techniques (CRISPRa/i) and phenotypic measurements (single-cell or spatial multi-omics), our platform presents a flexible, modular approach to interrogate gene function across diverse cell types in vivo, connecting gene variants to their causal functions.

Scanned information exposure and support for tobacco regulations among US youth and young adult tobacco product users and non-users.

The influences of information exposure on youth and young adults' (YYA) support for smoking/vaping regulations have been understudied. This study examines (i) the relationships between routine exposure to (i.e. scanning) anti-smoking/pro-vaping information and YYA support for anti-smoking/vaping regulations and (ii) whether these relationships differ across YYA users and non-users of tobacco products. We analyzed the data from a nationally representative two-wave rolling cross-sectional survey of YYA in the United States, collected from 2014 to 2017 (baseline n = 10 642; follow-up n = 4001). Less than 5% of the participants ever scanned pro-smoking and anti-vaping information. Scanning anti-smoking information had significant positive relationships with support for all anti-smoking policies cross-sectionally, and this pattern was longitudinally significant in two anti-smoking policy contexts. Scanning pro-vaping information had significant negative associations with support for anti-vaping policies cross-sectionally, but not longitudinally. The lagged positive relationships between scanning anti-smoking information and support for anti-smoking regulations were stronger among YYA smokers than among YYA non-smokers, whereas evidence from adult data suggested the opposite pattern. The findings suggest that scanning information can affect YYA support for tobacco regulations. Future efforts are required to investigate mechanisms underlying the influences of scanned information on YYA support for tobacco regulations.

Cell-type specific defects in PTEN-mutant cortical organoids converge on abnormal circuit activity.

De novo heterozygous loss-of-function mutations in phosphatase and tensin homolog (PTEN) are strongly associated with autism spectrum disorders; however, it is unclear how heterozygous mutations in this gene affect different cell types during human brain development and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type specific developmental events that are affected by heterozygous mutations in PTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep-layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes of PTEN heterozygosity that later converge on disrupted neuronal activity.

Scalable CMOS back-end-of-line-compatible AlScN/two-dimensional channel ferroelectric field-effect transistors.

Three-dimensional monolithic integration of memory devices with logic transistors is a frontier challenge in computer hardware. This integration is essential for augmenting computational power concurrent with enhanced energy efficiency in big data applications such as artificial intelligence. Despite decades of efforts, there remains an urgent need for reliable, compact, fast, energy-efficient and scalable memory devices. Ferroelectric field-effect transistors (FE-FETs) are a promising candidate, but requisite scalability and performance in a back-end-of-line process have proven challenging. Here we present back-end-of-line-compatible FE-FETs using two-dimensional MoS2 channels and AlScN ferroelectric materials, all grown via wafer-scalable processes. A large array of FE-FETs with memory windows larger than 7.8 V, ON/OFF ratios greater than 107 and ON-current density greater than 250 µA um-1, all at ~80 nm channel length are demonstrated. The FE-FETs show stable retention up to 10 years by extension, and endurance greater than 104 cycles in addition to 4-bit pulse-programmable memory features, thereby opening a path towards the three-dimensional heterointegration of a two-dimensional semiconductor memory with silicon complementary metal-oxide-semiconductor logic.

Wurtzite and fluorite ferroelectric materials for electronic memory.

Ferroelectric materials, the charge equivalent of magnets, have been the subject of continued research interest since their discovery more than 100 years ago. The spontaneous electric polarization in these crystals, which is non-volatile and programmable, is appealing for a range of information technologies. However, while magnets have found their way into various types of modern information technology hardware, applications of ferroelectric materials that use their ferroelectric properties are still limited. Recent advances in ferroelectric materials with wurtzite and fluorite structure have renewed enthusiasm and offered new opportunities for their deployment in commercial-scale devices in microelectronics hardware. This Review focuses on the most recent and emerging wurtzite-structured ferroelectric materials and emphasizes their applications in memory and storage-based microelectronic hardware. Relevant comparisons with existing fluorite-structured ferroelectric materials are made and a detailed outlook on ferroelectric materials and devices applications is provided.

A comprehensive examination of association between belief in vaccine misinformation and vaccination intention in the COVID-19 context.

Misinformation about COVID-19 vaccines is widely available in the public communication environment. Exposure to the misinformation may increase perceived risk of and evoke negative emotions toward COVID-19 vaccines that may eventually reduce COVID-19 vaccination intentions. The negative influences of misinformation may vary by aspects of individuals' social networks. Expanding the reasoned action approach, we proposed a comprehensive model to examine the roles of misinformation beliefs, perceived risk, fear, worry, and social networks in explaining COVID-19 vaccination intentions. We tested the model using survey data of South Korean adults, collected when the Korean government launched its nationwide vaccination program in April 2021 (n = 744). The results from our step-by-step path analyses indicated that COVID-19 vaccination intentions had positive direct associations with vaccination-specific factors such as attitudes toward, injunctive norms on, and perceived behavioral control over COVID-19 vaccination. Perceived risk was also directly linked to intentions. Among these factors, attitudes and injunctive norms were most strongly related to intentions. Misinformation beliefs and worry had negative indirect relationships with intentions via the mediation of these variables directly connected to intentions. The negative influences of misinformation beliefs were greater among respondents reported stronger tie strengths. Theoretical and practical implications were discussed.

Microwave Facilitated Covalent Organic Framework/Transition Metal Dichalcogenide Heterostructures.

Organic/inorganic heterostructures present a versatile platform for creating materials with new functionalities and hybrid properties. In particular, junctions between two dimensional materials have demonstrated utility in next generation electronic, optical, and optoelectronic devices. This work pioneers a microwave facilitated synthesis process to readily incorporate few-layer covalent organic framework (COF) films onto monolayer transition metal dichalcogenides (TMDC). Preferential microwave excitation of the monolayer TMDC flakes result in selective attachment of COFs onto the van der Waals surface with film thicknesses between 1 and 4 nm. The flexible process is extended to multiple TMDCs (MoS2, MoSe2, MoSSe) and several well-known COFs (TAPA-PDA COF, TPT-TFA-COF, and COF-5). Photoluminescence studies reveal a power-dependent defect formation in the TMDC layer, which facilitates electronic coupling between the materials at higher TMDC defect densities. This coupling results in a shift in the A-exciton peak location of MoSe2, with a red or blue shift of 50 or 19 meV, respectively, depending upon the electron donating character of the few-layer COF films. Moreover, optoelectronic devices fabricated from the COF-5/TMDC heterostructure present an opportunity to tune the PL intensity and control the interaction dynamics within inorganic/organic heterostructures.

Proper acquisition of cell class identity in organoids allows definition of fate specification programs of the human cerebral cortex.

Realizing the full utility of brain organoids to study human development requires understanding whether organoids precisely replicate endogenous cellular and molecular events, particularly since acquisition of cell identity in organoids can be impaired by abnormal metabolic states. We present a comprehensive single-cell transcriptomic, epigenetic, and spatial atlas of human cortical organoid development, comprising over 610,000 cells, from generation of neural progenitors through production of differentiated neuronal and glial subtypes. We show that processes of cellular diversification correlate closely to endogenous ones, irrespective of metabolic state, empowering the use of this atlas to study human fate specification. We define longitudinal molecular trajectories of cortical cell types during organoid development, identify genes with predicted human-specific roles in lineage establishment, and uncover early transcriptional diversity of human callosal neurons. The findings validate this comprehensive atlas of human corticogenesis in vitro as a resource to prime investigation into the mechanisms of human cortical development.

Pyramidal neuron subtype diversity governs microglia states in the neocortex.

Microglia are specialized macrophages in the brain parenchyma that exist in multiple transcriptional states and reside within a wide range of neuronal environments1-4. However, how and where these states are generated remains poorly understood. Here, using the mouse somatosensory cortex, we demonstrate that microglia density and molecular state acquisition are determined by the local composition of pyramidal neuron classes. Using single-cell and spatial transcriptomic profiling, we unveil the molecular signatures and spatial distributions of diverse microglia populations and show that certain states are enriched in specific cortical layers, whereas others are broadly distributed throughout the cortex. Notably, conversion of deep-layer pyramidal neurons to an alternate class identity reconfigures the distribution of local, layer-enriched homeostatic microglia to match the new neuronal niche. Leveraging the transcriptional diversity of pyramidal neurons in the neocortex, we construct a ligand-receptor atlas describing interactions between individual pyramidal neuron subtypes and microglia states, revealing rules of neuron-microglia communication. Our findings uncover a fundamental role for neuronal diversity in instructing the acquisition of microglia states as a potential mechanism for fine-tuning neuroimmune interactions within the cortical local circuitry.

Temporally divergent regulatory mechanisms govern neuronal diversification and maturation in the mouse and marmoset neocortex.

Mammalian neocortical neurons span one of the most diverse cell type spectra of any tissue. Cortical neurons are born during embryonic development, and their maturation extends into postnatal life. The regulatory strategies underlying progressive neuronal development and maturation remain unclear. Here we present an integrated single-cell epigenomic and transcriptional analysis of individual mouse and marmoset cortical neuron classes, spanning both early postmitotic stages of identity acquisition and later stages of neuronal plasticity and circuit integration. We found that, in both species, the regulatory strategies controlling early and late stages of pan-neuronal development diverge. Early postmitotic neurons use more widely shared and evolutionarily conserved molecular regulatory programs. In contrast, programs active during later neuronal maturation are more brain- and neuron-specific and more evolutionarily divergent. Our work uncovers a temporal shift in regulatory choices during neuronal diversification and maturation in both mice and marmosets, which likely reflects unique evolutionary constraints on distinct events of neuronal development in the neocortex.

High-Density, Localized Quantum Emitters in Strained 2D Semiconductors.

Two-dimensional chalcogenide semiconductors have recently emerged as a host material for quantum emitters of single photons. While several reports on defect- and strain-induced single-photon emission from 2D chalcogenides exist, a bottom-up, lithography-free approach to producing a high density of emitters remains elusive. Further, the physical properties of quantum emission in the case of strained 2D semiconductors are far from being understood. Here, we demonstrate a bottom-up, scalable, and lithography-free approach for creating large areas of localized emitters with high density (∼150 emitters/um2) in a WSe2 monolayer. We induce strain inside the WSe2 monolayer with high spatial density by conformally placing the WSe2 monolayer over a uniform array of Pt nanoparticles with a size of 10 nm. Cryogenic, time-resolved, and gate-tunable luminescence measurements combined with near-field luminescence spectroscopy suggest the formation of localized states in strained regions that emit single photons with a high spatial density. Our approach of using a metal nanoparticle array to generate a high density of strained quantum emitters will be applied to scalable, tunable, and versatile quantum light sources.

High-Efficiency WSe2 Photovoltaic Devices with Electron-Selective Contacts.

A rapid surge in global energy consumption has led to a greater demand for renewable energy to overcome energy resource limitations and environmental problems. Recently, a number of van der Waals materials have been highlighted as efficient absorbers for very thin and highly efficient photovoltaic (PV) devices. Despite the predicted potential, achieving power conversion efficiencies (PCEs) above 5% in PV devices based on van der Waals materials has been challenging. Here, we demonstrate a vertical WSe2 PV device with a high PCE of 5.44% under one-sun AM1.5G illumination. We reveal the multifunctional nature of a tungsten oxide layer, which promotes a stronger internal electric field by overcoming limitations imposed by the Fermi-level pinning at WSe2 interfaces and acts as an electron-selective contact in combination with monolayer graphene. Together with the developed bottom contact scheme, this simple yet effective contact engineering method improves the PCE by more than five times.

The Effects of Tobacco Coverage in the Public Communication Environment on Young People's Decisions to Smoke Combustible Cigarettes.

In today's complex media environment, does media coverage influence youth and young adults' (YYA) tobacco use and intentions? We conceptualize the "public communication environment" and effect mediators, then ask whether over time variation in exogenously measured tobacco media coverage from mass and social media sources predicts daily YYA cigarette smoking intentions measured in a rolling nationally representative phone survey (N = 11,847 on 1,147 days between May 2014 and June 2017). Past week anti-tobacco and pro-tobacco content from Twitter, newspapers, broadcast news, Associated Press, and web blogs made coherent scales (thetas = 0.77 and 0.79). Opportunities for exposure to anti-tobacco content in the past week predicted lower intentions to smoke (Odds ratio [OR] = 0.95, p < .05, 95% confidence interval [CI] = 0.91-1.00). The effect was stronger among current smokers than among nonsmokers (interaction OR = 0.88, p < .05, 95% CI = 0.77-1.00). These findings support specific effects of anti-tobacco media coverage and illustrate a productive general approach to conceptualizing and assessing effects in the complex media environment.

Autism genes converge on asynchronous development of shared neuron classes.

Genetic risk for autism spectrum disorder (ASD) is associated with hundreds of genes spanning a wide range of biological functions1-6. The alterations in the human brain resulting from mutations in these genes remain unclear. Furthermore, their phenotypic manifestation varies across individuals7,8. Here we used organoid models of the human cerebral cortex to identify cell-type-specific developmental abnormalities that result from haploinsufficiency in three ASD risk genes-SUV420H1 (also known as KMT5B), ARID1B and CHD8-in multiple cell lines from different donors, using single-cell RNA-sequencing (scRNA-seq) analysis of more than 745,000 cells and proteomic analysis of individual organoids, to identify phenotypic convergence. Each of the three mutations confers asynchronous development of two main cortical neuronal lineages-γ-aminobutyric-acid-releasing (GABAergic) neurons and deep-layer excitatory projection neurons-but acts through largely distinct molecular pathways. Although these phenotypes are consistent across cell lines, their expressivity is influenced by the individual genomic context, in a manner that is dependent on both the risk gene and the developmental defect. Calcium imaging in intact organoids shows that these early-stage developmental changes are followed by abnormal circuit activity. This research uncovers cell-type-specific neurodevelopmental abnormalities that are shared across ASD risk genes and are finely modulated by human genomic context, finding convergence in the neurobiological basis of how different risk genes contribute to ASD pathology.