-Functionalization of Pillar[4]arene[1]benzoquinone Monoxime via Selective 1,4-Addition of Grignard Reagents.

-functionalization of pillar[]arenes has been a formidable challenge, partially due to the fragility of their macrocyclic skeletons. In this concise report, we describe a facile synthetic method for monoarylation/alkylation at the position to the oxime functionality in pillar[4]arene[1]benzoquinone monoxime () via addition of Grignard reagents. The described method enables the creation of various mono--alkyl/aryl-substituted pillar[5]arene derivatives that were previously inaccessible.

Using Classifiers To Predict Catalyst Design for Polyketone Microstructure.

We applied a classifier method to predict palladium catalysts for the formation of nonalternating polyketones via the copolymerization of CO and ethylene; current examples are limited to using phosphine sulfonate and diphosphazane monoxide supporting ligands. With the reported workflow, we discovered two new classes of palladium complexes capable of achieving the synthesis of nonalternating polyketones with a lower CO content than those made by known palladium catalysts. Our results show that we doubled the number of classes of palladium compounds that can catalyze the formation of this type of polymer.

Destabilization of Soil Carbon After Saltwater Intrusion in Coastal Agricultural Soils.

Saltwater intrusion (SWI) is a concerning issue impacting agricultural production and soil C cycling, which can have a wider effect on the climate. Complex soil processes driving soil C cycling following saltwater intrusion have not yet been fully quantified. Agricultural fields with varying degrees of saltwater intrusion, unaffected control, and native tidal marsh were studied to understand the impacts of saltwater intrusion on soil properties and soil carbon dynamics.

A Dual-Pathway Responsive Mechanophore for Intelligent Luminescent Polymer Materials.

Mechanoluminescent units, when integrated into polymer matrices, undergo structural transformations in response to mechanical force, resulting in changes in fluorescence. This phenomenon holds considerable promise for the development of stress-sensing materials. Despite the high demand for robust, tunable mechanoluminescent mechanophores for force assessment and smart force-responsive materials, strategies for their design and synthesis remain underdeveloped.

Rats and mice rapidly update timed behaviors.

Keeping track of time intervals is a crucial aspect of behavior and cognition. Many theoretical models of how the brain times behavior make predictions for steady-state performance of well-learned intervals, but the rate of learning intervals in these models varies greatly, ranging from one-shot learning to learning over thousands of trials. Here, we explored how quickly rats and mice adapt to changes in interval durations using a serial fixed-interval task.

Multiplexed single-cell imaging reveals diverging subpopulations with distinct senescence phenotypes during long-term senescence induction.

Cellular senescence is a phenotypic state that contributes to the progression of age-related disease through secretion of pro-inflammatory factors known as the senescence-associated secretory phenotype (SASP). Understanding the process by which healthy cells become senescent and develop SASP factors is critical for improving the identification of senescent cells and, ultimately, understanding tissue dysfunction. Here, we reveal how the duration of cellular stress modulates the SASP in distinct subpopulations of senescent cells.

Pharmacokinetics of Nivolumab and Erythropoietin in a Rat Model of Diet-Induced Obesity.

Purpose: To investigate how obesity affects the pharmacokinetics of biologics in a rat model.

Method: Male Long-Evans rats were fed a high-fat diet from the age of 3 weeks and development of obesity was monitored by measuring body size and composition (fat and lean mass). The animals received nivolumab (1 and 8 mg/kg) or recombinant human erythropoietin (rHuEPO, 1000 IU/kg) by intravenous or subcutaneous injection.

KorB switching from DNA-sliding clamp to repressor mediates long-range gene silencing in a multi-drug resistance plasmid.

Examples of long-range gene regulation in bacteria are rare and generally thought to involve DNA looping. Here, using a combination of biophysical approaches including X-ray crystallography and single-molecule analysis for the KorB-KorA system in Escherichia coli, we show that long-range gene silencing on the plasmid RK2, a source of multi-drug resistance across diverse Gram-negative bacteria, is achieved cooperatively by a DNA-sliding clamp, KorB, and a clamp-locking protein, KorA. We show that KorB is a CTPase clamp that can entrap and slide along DNA to reach distal target promoters up to 1.

Airspace closures due to reentering space objects.

Uncontrolled reentries of space objects create a collision risk with aircraft in flight. While the probability of a strike is low, the consequences could be catastrophic. Moreover, the risk is rising due to increases in both reentries and flights.

YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates.

We recently characterized the potent antiplasmodial activity of the aggregated protein dye YAT2150, whose presumed mode of action is the inhibition of protein aggregation in the malaria parasite. Using single-dose and ramping methods, assays were done to select Plasmodium falciparum parasites resistant to YAT2150 concentrations ranging from 3× to 0.25× the in vitro IC of the compound (in the two-digit nM range) and performed a cross-resistance assessment in P.

Identification of candidate genes involved in Zika virus-induced reversible paralysis of mice.

Zika virus (ZIKV) causes a variety of peripheral and central nervous system complications leading to neurological symptoms such as limb weakness. We used a mouse model to identify candidate genes potentially involved in causation or recovery from ZIKV-induced acute flaccid paralysis. Using Zikv and Chat chromogenic and fluorescence in situ RNA hybridization, electron microscopy, immunohistochemistry, and ZIKV RT-qPCR, we determined that some paralyzed mice had infected motor neurons, but motor neurons are not reduced in number and the infection was not present in all paralyzed mice; hence infection of motor neurons were not strongly correlated with paralysis.

Altered olfactory responses in Fmr1 KO mice.

Fragile X syndrome (FXS) is a neurodevelopmental disorder oftentimes associated with abnormal social behaviors and altered sensory responsiveness. It is hypothesized that the inappropriate filtering of sensory stimuli, including olfaction, can lead to aberrant social behavior in FXS. However, previous studies investigating olfaction in animal models of FXS have shown inconsistent results.

Characterizing safety, toxicity, and breast cancer risk reduction using a long-term fulvestrant eluting implant.

For individuals at high risk of developing breast cancer, interventions to mitigate this risk include surgical removal of their breasts and ovaries or five years treatment with the anti-estrogen tamoxifen or aromatase inhibitors. We hypothesized that a silicone based anti-estrogen-eluting implant placed within the breast would provide the risk reduction benefit of hormonal therapy, but without the adverse effects that limit compliance. To this end, we demonstrate that when placed adjacent to mammary tissue in the 7,12-dimethylbenz[a]anthracene-induced rat breast cancer model a fulvestrant-eluting implant delays breast cancer with minimal systemic exposure.

[Translated article] Protocol for the adaptation and consensus of the Community Pharmacy Survey on Patient Safety Culture to hospital pharmacy in Spain.

Introduction: The Community Pharmacy Survey on Patient Safety Culture (CPSOPSC) is a tool created by the Agency for Healthcare Research and Quality and used in the United States to assess the patient safety culture among community pharmacy workers. This survey has been adapted for use in hospital pharmacies in other countries. However, it has not yet been implemented in Spanish hospital pharmacies due to the lack of an applicable version in Spain.

Pain Management Among Older Farsi and Azeri Speaking Immigrant Adults With Limited English Proficiency (LEP): Interpretive Approach.

Objectives: Pain is a major public health issue in the United States. The ability to communicate the severity of pain with healthcare providers is crucial to receiving appropriate pain management. Many factors can limit this ability, including limited proficiency in the language spoken by providers.

Modulating the Coordination Environment of Atomically Dispersed Nickel for Efficient Electrocatalytic CO Reduction at Low Overpotentials and Industrial Current Densities.

Electrocatalytic CO-to-CO conversion with a high CO Faradaic efficiency (FE) at low overpotentials and industrial-level current densities is highly desirable but a huge challenge over non-noble metal catalysts. Herein, graphitic N-rich porous carbons supporting atomically dispersed nickel (NiN-O sites with an axial oxygen) were synthesized (denoted as O-Ni-N-GC) and applied as the cathode catalyst in a CORR flow cell. O-Ni-N-GC showed excellent selectivity with a FE over 92% at low overpotentials ranging from 17 to 60 mV, and over 99% at 80 mV.

Discovery of Orally Available Prodrugs of Itaconate and Derivatives.

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.

Cross-Point Ferroelectric HfZrO Capacitors for Remanent Polarization-Driven In-Memory Computing.

Ferroelectric HfZrO (HZO) capacitors have been extensively explored for in-memory computing (IMC) applications due to their nonvolatility and back-end-of-line (BEOL) compatible process. Several IMC approaches using resistance and capacitance states in ferroelectric HZO have been proposed for vector-matrix multiplication (VMM), but previous approaches suffer from limited accuracy and reliability. In this work, we propose a promising approach centered on the remanent polarization (P) switching of binary ferroelectric HZO capacitor synapses.

Improving Mental Health and Well-Being Through the Paradym App: Quantitative Study of Real-World Data.

Background: With growing evidence suggesting that levels of emotional well-being have been decreasing globally over the past few years, demand for easily accessible, convenient, and affordable well-being and mental health support has increased. Although mental health apps designed to tackle this demand by targeting diagnosed conditions have been shown to be beneficial, less research has focused on apps aiming to improve emotional well-being. There is also a dearth of research on well-being apps structured around users' lived experiences and emotional patterns and a lack of integration of real-world evidence of app usage.