Intramolecular Charge Transfer in Antiaromatic Donor/Acceptor-Fused s-Indacenes.

Herein we report the synthesis and characterization of four donor/acceptor-fused s-indacenes via the late-stage oxidation of a family of unsymmetrical benzofuran/benzothiophene-s-indacene regioisomers. A thorough study of their properties through experimental and computational analysis has revealed the effect of asymmetry on the molecular properties associated with antiaromaticity, as well as a strong correlation between antiaromaticity and intramolecular charge transfer (ICT). The strength of the charge transfer depends on the fusion orientation of the donor and acceptor motifs relative to the s-indacene core.

Alternatively activated macrophages are associated with faster growth rate in vestibular schwannoma.

The variability in vestibular schwannoma growth rates greatly complicates clinical treatment. Management options are limited to radiological observation, surgery, radiotherapy and, in specific cases, bevacizumab therapy. As such, there is a pressing requirement for growth restricting drugs for vestibular schwannoma.

Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population.

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages.

Raman spectroscopy for monitoring free sulfhydryl formation during monoclonal antibody manufacturing.

During production, harvested cell culture fluid (HCCF) can degrade due to reductases breaking interchain disulfide bonds, forming low molecular weight (LMW) impurities that contain free sulfhydryl and high molecular weight (HMW) impurities through disulfide shuffling. Thus, detecting and quantifying the free sulfhydryl increase in HCCF is critical. Herein, Raman spectroscopy is implemented as a process analytical technology, and multivariate data analysis is applied to characterize and quantify sulfhydryl formation in HCCF with disulfide-containing indicator molecules.

Probing the Influence of Alkyne Substitution on the Electronic and Magnetic Properties of Diindeno[1,2-;1',2'-]anthracenes.

To further the ability to manipulate the properties of open-shell molecules, logical and incremental modifications to molecular structure are key steps that provide fine-tuning of established diradicaloid scaffolds. We report the synthesis of an electronically "pure" diradicaloid based on a 2,6-anthroquinoidal core where the once necessary ethynyl "wings" are removed. Through the simplification of the overall electronic structure, the singlet-triplet energy gap increases by 0.

Does risk stratification with a matched treatment pathway improve clinical outcomes for adults with acute back pain? A systematic review and meta-analysis.

Background: Risk stratification is an approach which has been recommended across a number of international guidelines for the management of back pain.

Objective: To assess whether the use of risk stratification with a matched treatment pathway improves clinical outcomes, when compared with usual care or other interventions, in adults with acute back pain.

Methods: A comprehensive search was conducted of the databases Medline, Embase, PEDro, CINAHL and Cochrane Library in November 2022.

A spatially resolved single-cell lung atlas integrated with clinical and blood signatures distinguishes COVID-19 disease trajectories.

COVID-19 is characterized by a broad range of symptoms and disease trajectories. Understanding the correlation between clinical biomarkers and lung pathology during acute COVID-19 is necessary to understand its diverse pathogenesis and inform more effective treatments. Here, we present an integrated analysis of longitudinal clinical parameters, peripheral blood markers, and lung pathology in 142 Brazilian patients hospitalized with COVID-19.

Electrocatalytic Reduction of Disulfide Bonds across Chemical Modalities.

The chemical properties of disulfides are leveraged in a wide array of applications, ranging from protein-drug conjugates for cancer treatment to self-healing materials. However, disulfide reduction strategies remain severely underdeveloped despite being the key to efficiently accessing the desired targets. Specifically, no homogeneous catalyst has been reported for this reaction, and conditions that allow the use of mild and green reductants (e.

ArcKR expression modifies synaptic plasticity following epileptic activity: Differential effects with in vitro and in vivo seizure-induction protocols.

Objectives: Pathological forms of neural activity, such as epileptic seizures, modify the expression pattern of multiple proteins, leading to persistent changes in brain function. One such protein is activity-regulated cytoskeleton-associated protein (Arc), which is critically involved in protein-synthesis-dependent synaptic plasticity underlying learning and memory. In the present study, we have investigated how the expression of ArcKR, a form of Arc in which the ubiquitination sites have been mutated, resulting in slowed Arc degradation, modifies group I metabotropic glutamate receptor-mediated long-term depression (G1-mGluR-LTD) following seizures.

Disrupting the Hofmeister bias in salt liquid-liquid extraction with an arylethynyl bisurea anion receptor.

Host-mediated liquid-liquid extraction is a convenient method for the separation of inorganic salts. However, selective extraction of an anion, regardless of its hydrophilicity or lipophilicity as qualitatively described by its place in the Hofmeister series, remains challenging. Herein we report the complete disruption of the Hofmeister-based ordering of anions in host-mediated extraction by a rigidified tweezer-type receptor possessing remarkably strong anion-binding affinity under the conditions examined.

Fluid Resuscitation and Sepsis Management in Patients with Chronic Kidney Disease or End-Stage Renal Disease: Scoping Review.

Managing sepsis and fluid resuscitation in patients with chronic kidney disease or end-stage renal disease is challenging for health care providers. Nurses are essential for early identification and treatment of these patients. Nurse education on assessing perfusion and implementing 3-hour bundled care can improve mortality rates in patients with sepsis.

From Solution to Surface: Persistence of the Diradical Character of a Diindenoanthracene Derivative on a Metallic Substrate.

Organic diradicals are envisioned as elementary building blocks for designing a new generation of spintronic devices and have been used in constructing prototypical field effect transistors and nonlinear optical devices. Open-shell systems, however, are also reactive, thus requiring design strategies to "protect" their radical character from the environment, especially when they are embedded in solid-state devices. Here, we report the persistence on a metallic surface of the diradical character of a diindeno[,]anthracene (DIAn) core protected by bulky end-groups.

Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.

The human malaria parasite Plasmodium falciparum is responsible for the majority of mortality and morbidity caused by malaria infection and differs from other human malaria species in the degree of accumulation of parasite-infected red blood cells in the microvasculature, known as cytoadherence or sequestration. In P. falciparum, cytoadherence is mediated by a protein called PfEMP1 which, due to its exposure to the host immune system, undergoes antigenic variation resulting in the expression of different PfEMP1 variants on the infected erythrocyte membrane.

Azaphosphinines and their derivatives.

Six-membered heterocycles containing one phosphorus and one nitrogen atom, known as azaphosphinines, have existed in the shadows of their single heteroatom-containing analogues for almost 150 years. Despite this, recent chemistry has seen a rapid increase in publications concerning this uncommon scaffold. Azaphosphinines exist in one of six isomers-there are three possible orientations of the pnictogen atoms and in each of these, the phosphorus is in one of two valences (P P).

The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection.

The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT) or sleeping sickness, accumulates in the meningeal spaces, ultimately inducing severe meningitis and resulting in death if left untreated. Thus, sleeping sickness represents an attractive model to study immunological dynamics in the meninges during infection.

2-λ-Phosphaquinolin-2-ones as Non-cytotoxic, Targetable, and pH-Stable Fluorophores.

Several phosphaquinolinone derivatives have been synthesized and characterized to explore their usefulness in the realm of cell imaging. Solution-state photophysical properties in both aqueous and organic solutions were collected for these derivatives. Additionally, CCK-8 cell viability assays and fluorescent imaging in HeLa cells incubated with the new heterocyclic derivatives show evidence of favorable cell permeability, cell viability, and moderate intracellular localization when appended with the well-known morpholine targeting motif.

Arc expression regulates long-term potentiation magnitude and metaplasticity in area CA1 of the hippocampus in ArcKR mice.

Expression of the immediate early gene Arc/Arg3.1 (Arc), a key mediator of synaptic plasticity, is enhanced by neural activity and then reduced by proteasome-dependent degradation. We have previously shown that the disruption of Arc degradation, in an Arc knock-in mouse (ArcKR), where the predominant Arc ubiquitination sites were mutated, reduced the threshold to induce, and also enhanced, the strength of Group I metabotropic glutamate receptor-mediated long-term depression (DHPG-LTD).

Updates to the Autism Intervention Research Network on Physical Health (AIR-P) Research Agenda.

Introduction: Autistic individuals, now representing one in 36 individuals in the U.S., experience disproportionate physical health challenges relative to non-autistic individuals.

Evaluation of 4-Aminoquinoline Hydrazone Analogues as Potential Leads for Drug-Resistant Malaria.

The emergence of resistance to first-line antimalarial drugs calls for the development of new therapies for drug-resistant malaria. The efficacy of quinoline-based antimalarial drugs has prompted the development of novel quinolines. A panel of 4-aminoquinoline hydrazone analogues were tested on the multidrug-resistant K1 strain of : IC values after a 48 h cycle ranged from 0.