Mechanistic Study of Reduction of Nitrite to NO by the Copper(II) Complex: Different Concerted Proton–Electron Transfer Reactivity between Nitrite and Nitro Complexes

The literature contains numerous reports of copper complexes for nitrite (NO2–) reduction. However, details of how protons and electrons arrive and how nitric oxide (NO) is released remain unknown. The influence of the coordination mode of nitrite on reactivity is also under debate. Kundu and co-workers have reported nitrite reduction by a copper(II) complex [J. Am. Chem. Soc. 2020, 142, 1726–1730]. In their report, the copper(II) complex reduced nitrite using a phenol derivative as a reductant, resulting in NO, a hydroxyl copper(II) complex, and the corresponding biphenol. Also, the involvement of proton-coupled electron transfer was proposed by mechanistic studies. Herein, density functional theory calculations were performed to determine a mechanism for reduction of nitrite by a copper(II) complex. As a result of geometry optimization of an initial complex, two possible structures were obtained: Cu–ONO and Cu–NO2. Two possible reaction pathways initiated from Cu–ONO or Cu–NO2 were then considered. The calculation results indicated that the Cu–ONO pathway is energetically favorable. When changes in the electronic structure were considered, both pathways were found to involve concerted proton–electron transfer (CPET). In addition, an intrinsic reaction coordinate analysis revealed that the two pathways were achieved by different types of CPET. Furthermore, an intrinsic bond orbital analysis clearly indicated that, in the Cu–ONO pathway, the chemical events involved proceeded concertedly yet asynchronously

Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review

<p><b>Objectives:</b> To identify, describe and summarize evidence on residual symptoms and disease burdens in rheumatoid arthritis (RA) patients qualified as being in remission or low disease activity (LDA).</p> <p><b>Methods:</b> A systematic literature review (SLR) was conducted according to Cochrane collaboration guidelines. The population of interest was adult patients with RA in remission or LDA. The reported outcomes of interest were any symptoms or burdens.</p> <p><b>Results:</b> Fifty-one publications were identified through an eDatabase search. Together with 17 articles found through other sources, 68 were included for full text review. The most commonly reported residual symptoms were pain (number of studies = 25), fatigue (<i>n</i> = 21) and morning stiffness (<i>n</i> = 5). Reported disease burdens included mental health (<i>n</i> = 15), sleep disturbances (<i>n</i> = 7) and work productivity (<i>n</i> = 5), impairment in quality of life (<i>n</i> = 21), and functional disability (<i>n</i> = 34). Substantial residual symptoms and disease burdens were found to be present in patients in remission or LDA.</p> <p><b>Conclusion:</b> This is the first SLR to investigate residual symptoms and disease burdens in RA patients in remission or LDA. The results indicate that despite achieving conventional clinical targets, the disease continues to affect patients, suggesting the existence of unmet need under the current treatment paradigm.</p

Additional file 1 of Single-cell RNA sequencing of submandibular gland reveals collagen type XV-positive fibroblasts as a disease-characterizing cell population of IgG4-related disease

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