Background The COVID-19 pandemic disrupted the United States (US) medical education system with the necessary, yet unprecedented Association of American Medical Colleges (AAMC) national recommendation to pause all student clinical rotations with in-person patient care. This study is a quantitative analysis investigating the educational and psychological effects of the pandemic on US medical students and their reactions to the AAMC recommendation in order to inform medical education policy. Methods The authors sent a cross-sectional survey via email to medical students in their clinical training years at six medical schools during the initial peak phase of the COVID-19 pandemic. Survey questions aimed to evaluate students’ perceptions of COVID-19’s impact on medical education; ethical obligations during a pandemic; infection risk; anxiety and burnout; willingness and needed preparations to return to clinical rotations. Results Seven hundred forty-one (29.5%) students responded. Nearly all students (93.7%) were not involved in clinical rotations with in-person patient contact at the time the study was conducted. Reactions to being removed were mixed, with 75.8% feeling this was appropriate, 34.7% guilty, 33.5% disappointed, and 27.0% relieved. Most students (74.7%) agreed the pandemic had significantly disrupted their medical education, and believed they should continue with normal clinical rotations during this pandemic (61.3%). When asked if they would accept the risk of infection with COVID-19 if they returned to the clinical setting, 83.4% agreed. Students reported the pandemic had moderate effects on their stress and anxiety levels with 84.1% of respondents feeling at least somewhat anxious. Adequate personal protective equipment (PPE) (53.5%) was the most important factor to feel safe returning to clinical rotations, followed by adequate testing for infection (19.3%) and antibody testing (16.2%). Conclusions The COVID-19 pandemic disrupted the education of US medical students in their clinical training years. The majority of students wanted to return to clinical rotations and were willing to accept the risk of COVID-19 infection. Students were most concerned with having enough PPE if allowed to return to clinical activities.

Synthesizing urea from nitrate and carbon dioxide through an electrocatalysis approach under ambient conditions is extraordinarily sustainable. However, this approach still lacks electrocatalysts developed with high catalytic efficiencies, which is a key challenge. Here, we report the high-efficiency electrocatalytic synthesis of urea using indium oxyhydroxide with oxygen vacancy defects, which enables selective C–N coupling toward standout electrocatalytic urea synthesis activity. Analysis by operando synchrotron radiation–Fourier transform infrared spectroscopy showcases that *CO2NH2 protonation is the potential-determining step for the overall urea formation process. As such, defect engineering is employed to lower the energy barrier for the protonation of the *CO2NH2 intermediate to accelerate urea synthesis. Consequently, the defect-engineered catalyst delivers a high Faradaic efficiency of 51.0%. In conjunction with an in-depth study on the catalytic mechanism, this design strategy may facilitate the exploration of advanced catalysts for electrochemical urea synthesis and other sustainable applications.

The platelet-derived growth factor receptor β (PDGFR-β) signaling pathway is a validated and important target for the treatment of certain malignant and nonmalignant pathologies. We previously identified a G-quadruplex-forming nuclease hypersensitive element (NHE) in the human PDGFR-β promoter that putatively forms four overlapping G-quadruplexes. Therefore, we further investigated the structures and biological roles of the G-quadruplexes and i-motifs in the PDGFR-β NHE with the ultimate goal of demonstrating an alternate and effective strategy for molecularly targeting the PDGFR-β pathway. Significantly, we show that the primary G-quadruplex receptor for repression of PDGFR-β is the 3′-end G-quadruplex, which has a GGA sequence at the 3′-end. Mutation studies using luciferase reporter plasmids highlight a novel set of G-quadruplex point mutations, some of which seem to provide conflicting results on effects on gene expression, prompting further investigation into the effect of these mutations on the i-motif-forming strand. Herein we characterize the formation of an equilibrium between at least two different i-motifs from the cytosine-rich (C-rich) sequence of the PDGFR-β NHE. The apparently conflicting mutation results can be rationalized if we take into account the single base point mutation made in a critical cytosine run in the PDGFR-β NHE that dramatically affects the equilibrium of i-motifs formed from this sequence. We identified a group of ellipticines that targets the G-quadruplexes in the PDGFR-β promoter, and from this series of compounds, we selected the ellipticine analog GSA1129, which selectively targets the 3′-end G-quadruplex, to shift the dynamic equilibrium in the full-length sequence to favor this structure. We also identified a benzothiophene-2-carboxamide (NSC309874) as a PDGFR-β i-motif-interactive compound. In vitro, GSA1129 and NSC309874 downregulate PDGFR-β promoter activity and transcript in the neuroblastoma cell line SK-N-SH at subcytotoxic cell concentrations. GSA1129 also inhibits PDGFR-β-driven cell proliferation and migration. With an established preclinical murine model of acute lung injury, we demonstrate that GSA1129 attenuates endotoxin-mediated acute lung inflammation. Our studies underscore the importance of considering the effects of point mutations on structure formation from the G- and C-rich sequences and provide further evidence for the involvement of both strands and associated structures in the control of gene expression.

Artificial nitrogen conversion reactions, such as the production of ammonia via dinitrogen or nitrate reduction and the synthesis of organonitrogen compounds via C−N coupling, play a pivotal role in the modern life. As alternatives to the traditional industrial processes that are energy-and carbon-emission-intensive, electrocatalytic nitrogen conversion reactions under mild conditions have attracted significant research interests. However, the electrosynthesis process still suffers from low product yield and Faradaic efficiency, which highlight the importance of developing efficient catalysts. In contrast to the transition-metal-based catalysts that have been widely studied, the p-block-element-based catalysts have recently shown promising performance because of their intriguing physiochemical properties and intrinsically poor hydrogen adsorption ability. In this Perspective, we summarize the latest breakthroughs in the development of p-block-elementbased electrocatalysts toward nitrogen conversion applications, including ammonia electrosynthesis from N 2 reduction and nitrate reduction and urea electrosynthesis using nitrogen-containing feedstocks and carbon dioxide. The catalyst design strategies and the underlying reaction mechanisms are discussed. Finally, major challenges and opportunities in future research directions are also proposed.

High‐entropy materials, composed of five or more elements in near‐equiatomic percentage, have been attracting tremendous interests due to their advantageous properties in a variety of applications. Recently, electrocatalysis on high‐entropy alloys (HEAs) and high‐entropy compounds (HECs) has emerged as a new and promising material owing to the tailored composition and the disordered configuration of HEAs and HECs. Though extensive efforts have been devoted to investigating the catalytic nature of HEAs and HECs, the details related to the active sites and intrinsic activity of such catalysts still remain uncertain due to the complexity of the multicomponent systems. In this review, the recent progress of HEAs and HECs is systematically reviewed in terms of their synthetic strategies and electrocatalytic applications. Importantly, the computationally assisted methods (e.g., density functional theory [DFT]) are also presented to discover and design the optimum HEA‐ and HEC‐based catalysts. Subsequently, the applications of HEAs and HECs in electrocatalytic energy conversion reactions will be discussed, including hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, carbon dioxide reduction reaction, nitrogen reduction reaction, methanol oxidation reaction, and ethanol oxidation reaction (EOR). Moreover, the prospects and future opportunities for this research field are cautiously discussed. A series of upcoming challenges and questions are thoroughly proposed from the experimental and theoretical aspects as well as other future applications in electrocatalysis.

No abstract

Magnetic resonance contrast agents that can be activated in response to specific triggers hold potential as molecular biosensors that may be of great utility in non-invasive disease diagnosis. We developed an activatable agent based on superparamagnetic iron oxide nanoparticles (SPIOs) that is sensitive to oxidative stress, a factor in the pathophysiology of numerous diseases. SPIOs were coated with poly(ethylene glycol) (PEG) and complexed with poly(gallol), a synthetic tannin. Hydrogen bonding between PEG and poly(gallol) creates a complexed layer around the SPIO that decreases the interaction of solute water with the SPIO, attenuating its magnetic resonance relaxivity. The complexed interpolymer nanoparticle is in an OFF state (decreased T2 contrast), where the contrast agent has a low T2 relaxivity of 7 ± 2 mM−1 s−1. In the presence of superoxides, the poly(gallol) is oxidized and the polymers decomplex, allowing solute water to again interact with the SPIO, representing an ON state (increased T2 contrast) with a T2 relaxivity of 70 ± 10 mM−1 s−1. These contrast agents show promise as effective sensors for diseases characterized in part by oxidative stress such as atherosclerosis, diabetes, and cancer.

Background: The COVID-19 pandemic disrupted the United States (US) medical education system with the necessary, yet unprecedented Association of American Medical Colleges (AAMC) national recommendation to pause all student clinical rotations with in-person patient care. This study is a quantitative analysis investigating the educational and psychological effects of the pandemic on US medical students and their reactions to the AAMC recommendation in order to inform medical education policy.Methods: The authors sent a cross-sectional survey via email to medical students in their clinical training years at six medical schools during the initial peak phase of the COVID-19 pandemic. Survey questions aimed to evaluate students' perceptions of COVID-19's impact on medical education; ethical obligations during a pandemic; infection risk; anxiety and burnout; willingness and needed preparations to return to clinical rotations. Results: 741 (29.5%) students responded. Nearly all students (93.7%) were not involved in clinical rotations with in-person patient contact at the time the study was conducted. Reactions to being removed were mixed, with 75.8% feeling this was appropriate, 34.7% guilty, 33.5% disappointed, and 27.0% relieved.Most students (74.7%) agreed the pandemic had significantly disrupted their medical education, and believed they should continue with normal clinical rotations during this pandemic (61.3%). When asked if they would accept the risk of infection with COVID-19 if they returned to the clinical setting, 83.4% agreed. Students reported the pandemic had moderate effects on their stress and anxiety levels with 84.1% of respondents feeling at least somewhat anxious. Adequate personal protective equipment (PPE) (53.5%) was the most important factor to feel safe returning to clinical rotations, followed by adequate testing for infection (19.3%) and antibody testing (16.2%). Conclusions: The COVID-19 pandemic disrupted the education of US medical students in their clinical training years. The majority of students wanted to return to clinical rotations and were willing to accept the risk of COVID-19 infection. Students were most concerned with having enough PPE if allowed to return to clinical activities.