Electrochemistry-enabled Ir-catalyzed C-H/N-N bond activation facilitates [3+2] annulation of phenidones with propiolates.

A mild and efficient [3+2] annulation of phenidones with propiolates has been developed to access -substituted indole alkylamides, enabled by merging electrochemistry with iridium catalysis using an undivided cell at room temperature. The mechanistic studies have confirmed that the electrochemically mediated catalytic cycle of Ir-Ir-Ir exhibits enhanced efficiency, mild reaction conditions, and unconventional selectivity.

Bereaved Family Quality of Life Varies With Comorbid Psychological Distress and ICU-Care Quality.

Context: Health-related quality of life (HRQOL) is highly endorsed, but HRQOL studies scarcely investigate the following: ICU family members; modifiable end-of-life (EOL) ICU-care factors; conjoint associations with prolonged grief disorder (PGD), post-traumatic stress disorder (PTSD), and depression; and long-term bereavement outcomes.

Objectives: Exploratorily investigate associations of PGD-PTSD-depressive-symptom states (resilient, subthreshold-depression dominant, PGD dominant, and PGD-PTSD-depression comorbid) and quality of EOL ICU care with families' HRQOL 6-24 months post loss.

Methods: This cohort study examined symptoms of PGD (11 items of the PG-13), PTSD (Impact of Event Scale-Revised), and depression (Hospital Anxiety and Depression Scale), and HRQOL (Medical Outcomes Study 36-Item Short-Form Health Survey) among 303 ICU family members.

()-Selective Isomerization of 1,1-Disubstituted Alkenes by Scandium-Catalyzed Allylic C-H Activation.

The isomerization of 1,1-disubstituted alkenes through 1,3-hydrogen shift is an atom-efficient route for synthesizing trisubstituted alkenes, which are important moieties in many natural products, pharmaceuticals, and organic materials. However, this reaction often encounters regio- and stereoselectivity challenges, typically yielding /-mixtures of the alkene products or thermodynamically favored ()-alkenes. Herein, we report the ()-selective isomerization of 1,1-disubstituted alkenes to trisubstituted ()-alkenes via the regio- and stereospecific activation of an allylic C-H bond.

A foundation model for clinical-grade computational pathology and rare cancers detection.

The analysis of histopathology images with artificial intelligence aims to enable clinical decision support systems and precision medicine. The success of such applications depends on the ability to model the diverse patterns observed in pathology images. To this end, we present Virchow, the largest foundation model for computational pathology to date.

AgNOx as Nitrogen Source for [1+1+3] Cycloaddition of Isocyanides with Isocyanates: Selective Synthesis of 1,2,4-Triazoles.

A novel [1+1+3] annulation of AgNOx, isocyanides, and isocyanates for the selective synthesis of 1,2,4-triazoles is presented herein. In this transformation, AgNOx and isocyanates are used as nitrogen sources instead of the traditional hydrazine or diazonium reagents. This process also involves N-O/C-H/C═N bond cleavage and the construction of new N-N/C-N bonds with a good substrate scope and functional group tolerance.

Dispersion of Single-Walled Carbon Nanotubes by Aromatic Cyclic Schiff Bases via Non-Covalent Interactions.

One of the challenging issues that hinders the application of single-walled carbon nanotubes (SWCNTs) is the poor solubility and the inevitable formation of bundles. Efforts still need to be made towards solving the problem. Herein, we report a non-covalent strategy to disperse aggregated SWCNTs by aromatic cyclic Schiff bases assisted by ultrasonic techniques.

A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR).

Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5 days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700 mg/day with median area under the plasma concentration-time curve (AUC) of 31.3 μg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR).

A synthetically useful catalytic system for aliphatic C-H oxidation with a nonheme cobalt complex and -CPBA.

We report herein a synthetically useful catalytic system for aliphatic C-H oxidation with a mononuclear nonheme cobalt(II) complex and -chloroperbenzoic acid (-CPBA). Preliminary mechanistic studies suggest that a high-valent cobalt-oxygen species (, cobalt(IV)-oxo or cobalt(III)-oxyl) is the oxidant that effects C-H oxidation a rate-determining hydrogen atom abstraction (HAA) step.

Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity.

Prolonged activation of the type I interferon (IFN-I) pathway leads to autoimmune diseases such as systemic lupus erythematosus (SLE). Metabolic regulation of cytokine signaling is critical for cellular homeostasis. Through metabolomics analyses of IFN-β-activated macrophages and an IFN-stimulated-response-element reporter screening, we identified spermine as a metabolite brake for Janus kinase (JAK) signaling.

-Indole-Substituted Imidazolylidene Pd-PEPPSI Precatalysts: Enhanced Performance with a 3,5-Diisopropyl-4-indolyl Moiety.

Pd-PEPPSI complexes of -(4-indolyl)-'-phenylimidazol-2-ylidene (IIn) ligands with a 5-isopropyl-4-indolyl moiety are synthesized and evaluated in heteroarene C-H arylation, Suzuki-Miyaura cross-coupling, and Buchwald-Hartwig amination reactions. The IIn-Pd complex bearing a 3,5-diisopropyl-4-indolyl substituent () exhibits the best catalytic activity in this series and substantially outperforms commercial precatalyst PEPPSI-Pd-IPr. The results also suggest that the alkyl group at position 3 of the 4-indolyl moiety shows stronger impacts than that at position 5.

Zinc-indium-sulfide favors efficient C - H bond activation by concerted proton-coupled electron transfer.

C - H bond activation is a ubiquitous reaction that remains a major challenge in chemistry. Although semiconductor-based photocatalysis is promising, the C - H bond activation mechanism remains elusive. Herein, we report value-added coupling products from a wide variety of biomass and fossil-derived reagents, formed via C - H bond activation over zinc-indium-sulfides (Zn-In-S).

Visible-light-mediated C-H amidation of imidazoheterocycles with -amidopyridiniums.

C-3 amidated imidazoheterocycles were synthesized a visible light-promoted reaction of imidazoheterocycles with -amidopyridinium salts catalyzed by 4CzIPN under mild conditions. For imidazoheterocycles and -amidopyridinium salts with various substituents, the reaction proceeded smoothly to give the corresponding products in moderate to good yields. The reaction provides a new strategy for the synthesis of secondary amides with the imidazo[1,2-]pyridine core.

Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization.

Ethnopharmacological Relevance: The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored.

Aim Of The Study: This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

Background: It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM).

Methods: From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed.

Determining the mechanical and decomposition properties of high energetic materials (α-RDX, β-HMX, and ε-CL-20) using a neural network potential.

Molecular simulations of high energetic materials (HEMs) are limited by efficiency and accuracy. Recently, neural network potential (NNP) models have achieved molecular simulations of millions of atoms while maintaining the accuracy of density functional theory (DFT) levels. Herein, an NNP model covering typical HEMs containing C, H, N, and O elements is developed.

A manganese-based catalyst system for general oxidation of unactivated olefins, alkanes, and alcohols.

Non-noble metal-based catalyst systems consisting of inexpensive manganese salts, picolinic acid and various heterocycles enable epoxidation of the challenging (terminal) unactivated olefins, selective C-H oxidation of unactivated alkanes, and O-H oxidation of secondary alcohols with aqueous hydrogen peroxide. In the presence of the generated optimal manganese catalyst, epoxides are generated with up to 81% yield from alkenes and ketone products with up to 51% yield from unactivated alkanes. This convenient protocol allows the formation of the desired products under ambient conditions (room temperature, 1 bar) by employing only a slight excess of hydrogen peroxide with 2,3-butadione as a sub-stoichiometric additive.

Tumor-secreted FGF21 acts as an immune suppressor by rewiring cholesterol metabolism of CD8T cells.

Tumors employ diverse strategies for immune evasion. Unraveling the mechanisms by which tumors suppress anti-tumor immunity facilitates the development of immunotherapies. Here, we have identified tumor-secreted fibroblast growth factor 21 (FGF21) as a pivotal immune suppressor.

Oxygenation of Phenols with Water as the Oxygen Source and Oxoammonium Salt as the Oxidant.

Aromatic C-H oxygenation is important in both industrial production and organic synthesis. Here we report a metal-free approach for phenol oxygenation with water as the oxygen source using oxoammonium salts as the renewable oxidant. Employing this protocol, various alkyl-substituted phenols were converted into benzoquinones in yields of 59-98%.

Enhancing Sodium-Ion Transport by Hollow Nanotube Structure Design of a VS@C Anode for Sodium-Ion Batteries.

VS has received extensive attention in the field of sodium-ion batteries (SIBs) due to its two-dimensional (2D) layered structure, and weak van der Waals forces between V-S accelerate the transport of sodium ions. However, the long-term cycling of VS still suffers from volume expansion and low conductivity. Herein, a hollow nanotube VS@C (H-VS@C) with improved conductivity was synthesized by a solvothermal method to alleviate cracking caused by volume expansion.

KARR-seq reveals cellular higher-order RNA structures and RNA-RNA interactions.

RNA fate and function are affected by their structures and interactomes. However, how RNA and RNA-binding proteins (RBPs) assemble into higher-order structures and how RNA molecules may interact with each other to facilitate functions remain largely unknown. Here we present KARR-seq, which uses N-kethoxal labeling and multifunctional chemical crosslinkers to covalently trap and determine RNA-RNA interactions and higher-order RNA structures inside cells, independent of local protein binding to RNA.

Synthesis of spiropyrans Ru(II)-catalyzed coupling of 3-aryl-2-benzo[][1,4]oxazines with benzoquinones.

An efficient Ru(II)-catalyzed C-H activation-based spiroannulation of benzoxazines with the easily available benzoquinone and -sulfonyl quinone monoimine has been realized, providing a straightforward strategy to access NH-containing spiropyrans in moderate to good yields with good functional group compatibility. The procedure features atom- and step-economy, mild conditions, and excellent chemoselectivity. Moreover, a catalytically competent five-membered cycloruthenated complex has been isolated.

Factors Associated With Family Surrogate Decisional-Regret Trajectories.

Context/objectives: The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care.

Methods: This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference.