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Electrochemical reduction of 2‐allyl‐substituted nitroarenes using a simple, undivided electrochemical cell with non‐precious electrodes to generate nitroarene radical anions was developed. The nitroarene radical anion intermediates participate in 1,5‐hydrogen atom transfer reactions to construct quinoline N‐oxides bearing aryl‐, heteroaryl‐, alkenyl‐, benzyl‐, sulfonyl‐, or carboxyl groups. [ABSTRACT FROM AUTHOR]

Cerebral ischemic stroke remains a leading cause of mortality and morbidity worldwide. Toll‐like receptor 4 (TLR4) has been implicated in neuroinflammatory responses poststroke, particularly in the infiltration of immune cells and polarization of macrophages. This study aimed to elucidate the impact of TLR4 deficiency on neutrophil infiltration and subsequent macrophage polarization after middle cerebral artery occlusion (MCAO), exploring its role in stroke prognosis. The objective was to investigate how TLR4 deficiency influences neutrophil behavior poststroke, its role in macrophage polarization, and its impact on stroke prognosis using murine models. Wild‐type and TLR4‐deficient adult male mice underwent MCAO induction, followed by various analyses, including flow cytometry to assess immune cell populations, bone marrow transplantation experiments to evaluate TLR4‐deficient neutrophil behaviors, and enzyme‐linked immunosorbent assay and Western blot analysis for cytokine and protein expression profiling. Neurobehavioral tests and infarct volume analysis were performed to assess the functional and anatomical prognosis poststroke. TLR4‐deficient mice exhibited reduced infarct volumes, increased neutrophil infiltration, and reduced M1‐type macrophage polarization post‐MCAO compared to wild‐type mice. Moreover, the depletion of neutrophils reversed the neuroprotective effects observed in TLR4‐deficient mice, suggesting the involvement of neutrophils in mediating TLR4's protective role. Additionally, N1‐type neutrophils were found to promote M1 macrophage polarization via neutrophil gelatinase‐associated lipocalin (NGAL) secretion, a process blocked by TLR4 deficiency. The study underscores the protective role of TLR4 deficiency in ischemic stroke, delineating its association with increased N2‐type neutrophil infiltration, diminished M1 macrophage polarization, and reduced neuroinflammatory responses. Understanding the interplay between TLR4, neutrophils, and macrophages sheds light on potential therapeutic targets for stroke management, highlighting TLR4 as a promising avenue for intervention in stroke‐associated neuroinflammation and tissue damage. Significance statement: This study illuminates the beneficial effects of TLR4 deficiency in improving stroke outcomes, demonstrating how it enhances protective N2 neutrophil infiltration and diminishes harmful M1 macrophage polarization. These findings highlight TLR4's pivotal role in stroke‐induced neuroinflammation and brain damage, presenting it as a promising target for therapeutic intervention. By understanding the nuanced interplay between immune responses and stroke pathology, this research opens avenues for developing novel treatments aimed at reducing the devastating impact of stroke, offering hope for improved recovery and quality of life for stroke patients worldwide. [ABSTRACT FROM AUTHOR]

Objective: Disuse osteoporosis is known to be primarily caused by a lack of exercise. However, the causal relationships between zinc and immunity and disuse osteoporosis remain unknown. This study investigated these relationships and their potential mechanisms. Methods: This study was an integrative study combining genome‐wide association studies and transcriptomics. Two‐sample Mendelian randomization analysis (MR) was used to analyze the causal relationships between exposures (zinc, immunity, physical activity) and the outcome (osteoporosis) with the aid of single‐nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Four models, MR‐Egger, inverse variance weighted, weighted median and MR‐Pleiotrophy RESidual Sum and Outlier (MRPRESSO), were used to calculate odds ratio values. Sensitivity and heterogeneity analyses were also performed using MRPRESSO and MR‐Egger methods. The mRNA transcriptomic analysis was subsequently conducted. Zinc metabolism scores were acquired through single‐sample Gene Set Enrichment Analysis algorithms. Stromal scores were obtained using the R Package "estimate" algorithms. Important Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathways were also derived through gene set variation analysis. Cytoscape software helped construct the transcription factor (TF)–mRNA–microRNA (miRNA) network. Virtual screening and molecular docking were performed. Polymerase chain reaction validation was also carried out in vivo. Results: Causal relationships were demonstrated between zinc and exercise (95% confidence interval [CI] = 1.30–2.95, p = 0.001), exercise and immunity (95% CI = 0.36–0.80, p = 0.002), exercise and osteoporosis (95% CI = 0.97–0.99, p = 0.0007), and immunity disorder and osteoporosis (95% CI = 1.30–2.03, p = 0.00002). One hundred and seventy‐nine mRNAs in important modules were screened. Combining the differential expressional genes (DEGs) and the Boruta selection, six DEGs were screened (AHNAK, CSF2, ADAMTS12, SRA1, RUNX2, and SLC39A14). TF HOXC10 and miRNA hsa‐miR‐204 were predicted. Then, the TF–mRNA–miRNA network was successfully constructed. RUNX2 and SLC39A14 were identified as hub mRNAs in the TF–mRNA–miRNA network. Eventually, the novel small drug C6O4NH5 was designed according to the pharmacophore structure of SLC39A14. The docking energy for the novel drug was −5.83 kcal/mol. SLC39A14 and RUNX2 were downregulated (of statistical significance p‐value < 0.05) in our animal experiment. Conclusion: This study revealed that zinc had a protective causal relationship with disuse osteoporosis by promoting exercise and immunity. SLC39A14 and RUNX2 mRNA participated in this zinc‐related mechanism. [ABSTRACT FROM AUTHOR]

In this study, the rust conversion coating that acts directly on the surface of rust layer, was studied from the preparation of rust conversion agents gallic acid (GA), 2‐hydroxyphosphonyl acetic acid (HPAA), and their compound (GA/HPAA), rust conversion effect and anticorrosive mechanism. Results show that 1) when GA and HPAA were combined to form GA/HPAA with a mass ratio of 2:1, the strengthening effect of rust conversion was observed, and a more complete, dense, and smooth covering film was generated on the rust surface. In this case, the corrosion current of GA/HPAA was reduced to 4.10 × 10−7 A cm−2, while the GA was 2.35 × 10−6 A cm−2 and HPAA was 2.16 × 10−6 A cm−2. 2) The mechanism of rust conversion and corrosion resistance can be expressed as that the chelation reaction can occur between the rust and rust conversion agent, which can generate new coordination covalent bonds O–Fe–O, P–O–Fe, and C–Fe–O. In this case, they can firmly lock the rust and prevent it from spreading further. Meanwhile, a highly cross‐linked dense anticorrosion protective film can be formed. Due to the presence of these chelating products, they can act as obstacles, prolonging the diffusion path of corrosive medium and slowing down the interaction with the metal matrix. [ABSTRACT FROM AUTHOR]

To investigate the impact of magnesium on the inclusions, carbides, and microstructure of the 21‐4N valve steel, the magnesium modification industrial experiment is carried out. Optical microscope, a scanning electron microscope with an energy‐dispersive spectrometer, thermodynamic calculation, and a 3D etching method are used. In the results, it is shown that the oxide inclusions in steel modifies from Al2O3–MnO to MgO–MnO–SiO2 after magnesium modification, which presents a more dispersed size distribution. The primary precipitates in the steel remain as massive carbide M23C6 and lamellar precipitate γ + M23C6, and the maximum size of large carbides and lamellar precipitates in the magnesium‐modified steel decreases from 15.1 to 13.4 μm and from 98.8 to 68.8 μm, respectively. Furthermore, Mg‐containing inclusions act as more heterogeneous nucleation cores for austenite precipitation, resulting in the refinement of austenite grain and a reduction in the last‐to‐solidify region. The reduction in the last‐to‐solidify region limits the growth space of carbides and contributes to their size refinement. [ABSTRACT FROM AUTHOR]

PM2.5 (particulate matter <2.5 μm in diameter) is proven to contribute to the development of atherosclerosis. Endothelial cell dysfunction is the initial step of atherosclerosis. The underlying mechanisms of endothelial cell damage exposed to PM2.5 are still obscure. In our study, PM2.5 was administrated to C57BL/6 male mice by intranasal instillation for 2 weeks. Human umbilical vein endothelial cells (HUVECs) were also treated with PM2.5 to evaluate the adverse effect in vitro. The immunohistochemical staining of aortas showed that the expressions of proinflammatory cytokines and endothelial adhesion markers were significantly increased in PM2.5‐exposed mice than that in saline‐exposed mice. In vitro, PM2.5 could inhibit HUVECs viability and impair cell migration in a concentration‐dependent manner. Besides, PM2.5 exposure downregulated eNOS expression while upregulated reactive oxygen species (ROS) levels. Mechanistically, PM2.5 activated the NLRP3 inflammasome in HUVECs while knockdown of NLRP3 could effectively reverse the downregulation of eNOS expression and production of ROS after PM2.5 exposure. In summary, our data showed that PM2.5 could cause endothelial dysfunction, and probably via NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

tert‐Butoxide unlocks new reactivity patterns embedded in nitroarenes. Exposure of nitrostilbenes to sodium tert‐butoxide was found to produce N‐hydroxyindoles at room temperature without an additive. Changing the counterion to potassium changed the reaction outcome to yield solely oxindoles through an unprecedented dioxygen‐transfer reaction followed by a 1,2‐phenyl migration. Mechanistic experiments established that these reactions proceed via radical intermediates and suggest that counterion coordination controls whether an oxindole or N‐hydroxyindole product is formed. [ABSTRACT FROM AUTHOR]

A reductive amination process that constructs indoles, carbazoles or benzimidazoles from nitroarenes – irrespective of their electronic or steric nature – was developed that uses CO2 as the source of CO. The process is robust, tolerating common gaseous components of flue gas (H2S, SO2, NO and H2O) without adversely affecting the reductive cyclization. [ABSTRACT FROM AUTHOR]

Cystathionine β-synthase (CBS) regulates homocysteine metabolism and contributes to hydrogen sulfide (H2S) biosynthesis through which it plays multifunctional roles in the regulation of cellular energetics, redox status, DNA methylation, and protein modification. Inactivating mutations in CBS contribute to the pathogenesis of the autosomal recessive disease CBS-deficient homocystinuria. Recent studies demonstrating that CBS promotes colon and ovarian cancer growth in preclinical models highlight a newly identified oncogenic role for CBS. On the contrary, tumor-suppressive effects of CBS have been reported in other cancer types, suggesting context-dependent roles of CBS in tumor growth and progression. Here, we review the physiological functions of CBS, summarize the complexities regarding CBS research in oncology, and discuss the potential of CBS and its key metabolites, including homocysteine and H2S, as potential biomarkers for cancer diagnosis or therapeutic targets for cancer treatment. [ABSTRACT FROM AUTHOR]

Ice clouds are an important part of precipitation systems and their thermal (radiative and latent heat) and microphysical effects may impact rainfall. In this study, the thermal and microphysical effects of ice clouds on rainfall are investigated through the diagnostic analysis of rainfall and heat budgets of a torrential rainfall simulation in north China during July 2013. During evening, the maximum reduction in rainfall caused by the inclusion of the thermal effects of ice clouds is mainly associated with the inclusion of latent‐heat effects of ice clouds, which suppresses instability and upward motions. During early morning, the maximum increase in rainfall caused by the inclusion of the thermal effects of ice clouds is mainly related to the inclusion of radiative effects of ice clouds, which enhances radiative cooling in the upper troposphere and suppresses radiative cooling in the lower troposphere and thus increases instability and upward motions. The inclusion of microphysical effects of ice clouds increases rainfall directly by the inclusion of deposition and indirectly by the increase in condensation. Key Points: The inclusion of the thermal effects of ice clouds weakens daytime rainfall mainly by the inclusion of latent‐heat effects of ice cloudsThe inclusion of the thermal effects of ice clouds increases nighttime rainfall mainly by the inclusion of radiative effects of ice cloudsThe inclusion of microphysical effects of ice clouds increases rainfall directly by the inclusion of deposition [ABSTRACT FROM AUTHOR]