Exploiting the DCAF16-SPIN4 interaction to identify DCAF16 ligands for PROTAC development.

Traditional small molecule drugs often target protein activity directly, but challenges arise when proteins lack suitable functional sites. An alternative approach is targeted protein degradation (TPD), which directs proteins to cellular machinery for proteolytic degradation. Recent studies have identified additional E3 ligases suitable for TPD, expanding the potential of this approach.

Carbon Mineralization in Fractured Mafic and Ultramafic Rocks: A Review.

Mineral carbon storage in mafic and ultramafic rock masses has the potential to be an effective and permanent mechanism to reduce anthropogenic CO. Several successful pilot-scale projects have been carried out in basaltic rock (e.g.

Repeated presentation of visual threats drives innate fear habituation and is modulated by environmental and physiological factors.

To survive predation, animals must be able to detect and appropriately respond to predator threats in their environment. Such defensive behaviors are thought to utilize hard-wired neural circuits for threat detection, sensorimotor integration, and execution of ethologically relevant behaviors. Despite being hard-wired, defensive behaviors (i.

Methodological Approaches for Measuring the Association Between Heat Exposure and Health Outcomes: A Comprehensive Global Scoping Review.

Objective: To synthesize the methodologies of studies that evaluate the impacts of heat exposure on morbidity and mortality.

Methods: Embase, MEDLINE, Web of Science, and Scopus were searched from date of inception until 1 March 2023 for English language literature on heat exposure and health outcomes. Records were collated, deduplicated and screened, and full texts were reviewed for inclusion and data abstraction.

Scalable and adaptable two-ligand co-solvent transfer methodology for gold bipyramids to organic solvents.

Large and faceted nanoparticles, such as gold bipyramids, presently require synthesis using alkyl ammonium halide ligands in aqueous conditions to stabilize the structure, which impedes subsequent transfer and suspension of such nanoparticles in low polarity solvents despite success with few nanometer gold nanoparticles of shapes such as spheres. Phase transfer methodologies present a feasible avenue to maintain colloidal stability of suspensions and move high surface energy particles into organic solvent environments. Here, we present a method to yield stable suspensions of gold bipyramids in low-polarity solvents, including methanol, dimethylformamide, chloroform, and toluene, through the requisite combination of two capping agents and the presence of a co-solvent.

Real-time capture of nuclear motions influencing photoinduced electron transfer.

Although vibronic coupling phenomena have been recognized in the excite state dynamics of transition metal complexes, its impact on photoinduced electron transfer (PET) remains largely unexplored. This study investigates coherent wavepacket (CWP) dynamics during PET processes in a covalently linked electron donor-acceptor complex featuring a cyclometalated Pt(ii) dimer as the donor and naphthalene diimide (NDI) as the acceptors. Upon photoexciting the Pt(ii) dimer electron donor, ultrafast broadband transient absorption spectroscopy revealed direct modulation of NDI radical anion formation through certain CWP motions and correlated temporal evolutions of the amplitudes for these CWPs with the NDI radical anion formation.

Conformational modulation and polymerization-induced folding of proteomimetic peptide brush polymers.

Peptide-brush polymers generated by graft-through living polymerization of peptide-modified monomers exhibit high proteolytic stability, therapeutic efficacy, and potential as functional tandem repeat protein mimetics. Prior work has focused on polymers generated from structurally disordered peptides that lack defined conformations. To obtain insight into how the structure of these polymers is influenced by the folding of their peptide sidechains, a set of polymers with varying degrees of polymerization was prepared from peptide monomers that adopt α-helical secondary structure for comparison to those having random coil structures.

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.

Advancements in nanomaterials for nanosensors: a comprehensive review.

Nanomaterials (NMs) exhibit unique properties that render them highly suitable for developing sensitive and selective nanosensors across various domains. This review aims to provide a comprehensive overview of nanomaterial-based nanosensors, highlighting their applications and the classification of frequently employed NMs to enhance sensitivity and selectivity. The review introduces various classifications of NMs commonly used in nanosensors, such as carbon-based NMs, metal-based NMs, and others, elucidating their exceptional properties, including high thermal and electrical conductivity, large surface area-to-volume ratio and good biocompatibility.

Structure-enabled long-lived charge separation in single crystals of an asymmetric donor-acceptor perylenediimide cyclophane.

We report the synthesis and characterization of a covalently linked asymmetric cyclophane comprising a 1,7-di(pyrrolidin-1'-yl)perylene-3,4,9,10-bis(dicarboximide) (pyrPDI) and 1,6,7,12-tetra(4'--butylphenoxy)perylene-3,4,9,10-bis(dicarboximide) (tpPDI), which absorbs light from 400-750 nm. Single crystals of pyrPDI-tpPDI were analyzed by using X-ray diffraction and transient absorption microscopy. The crystal structure contains several types of intermolecular donor-acceptor interactions (pyrPDI-pyrPDI, tpPDI-tpPDI, and pyrPDI-tpPDI) in addition to the covalently installed intramolecular interaction.

Mechanisms of controlled stabilizer-free synthesis of gold nanoparticles in liquid aerosol containing plasma.

The interaction between low-temperature plasma and liquid enables highly reactive solution phase chemistry and fast reaction kinetics. In this work, we demonstrate the rapid synthesis of stabilizer-free, spherical and crystalline gold nanoparticles (AuNP). More than 70% of gold ion complex (AuCl ) conversion is achieved within a droplet residence time in the plasma of ∼10 ms.

Developing, characterizing and modeling CRISPR-based point-of-use pathogen diagnostics.

Recent years have seen intense interest in the development of point-of-care nucleic acid diagnostic technologies to address the scaling limitations of laboratory-based approaches. Chief among these are combinations of isothermal amplification approaches with CRISPR-based detection and readouts of target products. Here, we contribute to the growing body of rapid, programmable point-of-care pathogen tests by developing and optimizing a one-pot NASBA-Cas13a nucleic acid detection assay.

In Vivo Mapping of Myocardial Injury Outside the Infarct Zone: Tissue at an Intermediate Pathological State.

Background: The goal was to determine the feasibility of mapping the injured-but-not-infarcted myocardium using Tc-duramycin in the postischemic heart, with spatial information for its characterization as a pathophysiologically intermediate tissue, which is neither normal nor infarcted.

Methods And Results: Coronary occlusion was conducted in Sprague Dawley rats with preconditioning and 30-minute ligation. In vivo single-photon emission computed tomography was acquired after 3 hours (n=6) using Tc-duramycin, a phosphatidylethanolamine-specific radiopharmaceutical.

A Physical Activity and Diet Just-in-Time Adaptive Intervention to Reduce Blood Pressure: The myBPmyLife Study Rationale and Design.

Background: Smartphone applications and wearable devices are promising mobile health interventions for hypertension self-management. However, most mobile health interventions fail to use contextual data, potentially diminishing their impact. The myBPmyLife Study is a just-in-time adaptive intervention designed to promote personalized self-management for patients with hypertension.

Correction: Ring-opening yields and auto-oxidation rates of the resulting peroxy radicals from OH-oxidation of α-pinene and β-pinene.

[This corrects the article DOI: 10.1039/D2EA00133K.].

Medicinal chemistry approaches to target the MNK-eIF4E axis in cancer.

Aberrant translation of proteins that promote cell proliferation is an essential factor that defines oncogenic processes and cancer. The process for ribosomal translation of proteins from mRNA requires an essential initiation step which is controlled by the protein eIF4E, which binds the RNA 5'-cap and forms the eIF4F complex that subsequently translates protein. Typically, eIF4E is activated by phosphorylation on Ser209 by MNK1 and MNK2 kinases.

Role of graphene quantum dots with discrete band gaps on SnO nanodomes for NO gas sensors with an ultralow detection limit.

NO is a major air pollutant that should be monitored due to its harmful effects on the environment and human health. Semiconducting metal oxide-based gas sensors have been widely explored owing to their superior sensitivity towards NO, but their high operating temperature (>200 °C) and low selectivity still limit their practical use in sensor devices. In this study, we decorated graphene quantum dots (GQDs) with discrete band gaps onto tin oxide nanodomes (GQD@SnO nanodomes), enabling room temperature (RT) sensing towards 5 ppm NO gas with a noticeable response ((/) - 1 = 4.

High-affinity single and double helical pseudofoldaxanes with cationic guests.

Two aromatic oligoamides, the 8-residue H8 and 16-residue H16, that adopt stable, cavity-containing helical conformations were examined for their complexation of a rodlike dicationic guest, octyl viologen (OV) and -bis(trimethylammonium)benzene (TB). Studies based on 1D and 2D H NMR, isothermal titration calorimetry (ITC), and X-ray crystallography demonstrated that H8 and H16 wraps around two OV ions as a double helix and a single helix, respectively, resulting in 2 : 2 and 1 : 2 complexes. Compared to H8, the longer H16 binds the OV ions with much higher binding affinity and with extraordinary negative cooperativity.

Energy-structure-property relationships in uranium metal-organic frameworks.

Located at the foot of the periodic table, uranium is a relatively underexplored element possessing rich chemistry. In addition to its high relevance to nuclear power, uranium shows promise for small molecule activation and photocatalysis, among many other powerful functions. Researchers have used metal-organic frameworks (MOFs) to harness uranium's properties, and in their quest to do so, have discovered remarkable structures and unique properties unobserved in traditional transition metal MOFs.

Inference of Causal Relationships Between Genetic Risk Factors for Cardiometabolic Phenotypes and Female-Specific Health Conditions.

Background Cardiometabolic diseases are highly comorbid, but their relationship with female-specific or overwhelmingly female-predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross-trait genetic overlap and influence of genetic burden of cardiometabolic traits on health conditions unique to women. Methods and Results Using electronic health record data from 71 008 ancestrally diverse women, we examined relationships between 23 obstetrical/gynecological conditions and 4 cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) by performing 4 analyses: (1) cross-trait genetic correlation analyses to compare genetic architecture, (2) polygenic risk score-based association tests to characterize shared genetic effects on disease risk, (3) Mendelian randomization for significant associations to assess cross-trait causal relationships, and (4) chronology analyses to visualize the timeline of events unique to groups of women with high and low genetic burden for cardiometabolic traits and highlight the disease prevalence in risk groups by age.

Identification of a metastable uranium metal-organic framework isomer through non-equilibrium synthesis.

Since the structure of supramolecular isomers determines their performance, rational synthesis of a specific isomer hinges on understanding the energetic relationships between isomeric possibilities. To this end, we have systematically interrogated a pair of uranium-based metal-organic framework topological isomers both synthetically and through density functional theory (DFT) energetic calculations. Although synthetic and energetic data initially appeared to mismatch, we assigned this phenomenon to the appearance of a metastable isomer, driven by levers defined by Le Châtelier's principle.

Extending BigSMILES to non-covalent bonds in supramolecular polymer assemblies.

As a machine-recognizable representation of polymer connectivity, BigSMILES line notation extends SMILES from deterministic to stochastic structures. The same framework that allows BigSMILES to accommodate stochastic covalent connectivity can be extended to non-covalent bonds, enhancing its value for polymers, supramolecular materials, and colloidal chemistry. Non-covalent bonds are captured through the inclusion of annotations to pseudo atoms serving as complementary binding pairs, minimal key/value pairs to elaborate other relevant attributes, and indexes to specify the pairing among potential donors and acceptors or bond delocalization.

Wearable Sensors Improve Prediction of Post-Stroke Walking Function Following Inpatient Rehabilitation.

Objective: A primary goal of acute stroke rehabilitation is to maximize functional recovery and help patients reintegrate safely in the home and community. However, not all patients have the same potential for recovery, making it difficult to set realistic therapy goals and to anticipate future needs for short- or long-term care. The objective of this study was to test the value of high-resolution data from wireless, wearable motion sensors to predict post-stroke ambulation function following inpatient stroke rehabilitation.

Plant-associate interactions and diversification across trophic levels.

Interactions between species are widely understood to have promoted the diversification of life on Earth, but how interactions spur the formation of new species remains unclear. Interacting species often become locally adapted to each other, but they may also be subject to shared dispersal limitations and environmental conditions. Moreover, theory predicts that different kinds of interactions have different effects on diversification.

Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health-related quality of life. RHAPSODY (rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL-1α and -β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient-reported outcome questionnaire score change during the trial.