Traceless Tandem Lesion Formation in DNA from a Nitrogen-Centered Purine Radical

Nitrogen-centered nucleoside radicals are commonly produced reactive intermediates in DNA exposed to γ-radiolysis and oxidants, but their reactivity is not well understood. Examination of the reactivity of independently generated 2′-deoxyadenosin-<i>N</i>6-yl radical (dA•) reveals that it is an initiator of tandem lesions, an important form of DNA damage that is a hallmark of γ-radiolysis. dA• yields O₂-dependent tandem lesions by abstracting a hydrogen atom from the C5-methyl group of a 5′-adjacent thymidine to form 5-(2′-deoxyuridinyl)­methyl radical (T•). The subsequently formed thymidine peroxyl radical adds to the 5′-adjacent dG, ultimately producing a 5′-OxodGuo-fdU tandem lesion. Importantly, the initial hydrogen abstraction repairs dA• to form dA. Thus, the involvement of dA• in tandem lesion formation is traceless by product analysis. The tandem lesion structure, as well as the proposed mechanism, are supported by LC-MS/MS, isotopic labeling, chemical reactivity experiments, and independent generation of T•. Tandem lesion formation efficiency is dependent on the ease of ionization of the 5′-flanking sequence, and the yields are >27% in the 5′-d­(GGGT) flanking sequence. The traceless involvement of dA• in tandem lesion formation may be general for nitrogen-centered radicals in nucleic acids, and presents a new pathway for forming a deleterious form of DNA damage

Selective and Sensitive Platform for Function-Based Screening of Potentially Harmful Furans

Many furan-containing compounds have been reported to be toxic and/or carcinogenic. Furanoids have been found in a wide range of fruits, herbs, foods, and beverages. The risks for intake of toxic furans have been rising, due to the rapid growth of globe-wide consumption of natural products. The objective of the study was to develop an analytical platform to screen <i>cis</i>-enediones (<i>cis</i>-enedials or γ-ketoenals) resulting from metabolic activation of potentially harmful furans. 2,5-Dimethylfuran (DMF), a model furan compound, was incubated with rat liver microsomes supplemented with glutathione (GSH) and 4-bromobenzylamine (BBA) as trapping agents, to produce a GSH/BBA-derived pyrrole. The incubation mixture was monitored by acquiring neutral loss scan of 129 Da and precursor ion scans of <i>m</i>/<i>z</i> 272, 169, and 171 in polarity switch mode. Four individual chromatograms showed the respective peak with the same retention time. An additional six furan-containing compounds were tested by the same approach, and similar observation was obtained. The system also showed its extremely high sensitivity, and an estimate of the limit of detection for DMF bioactivated in rat liver microsomes was <100 fmol. We also applied inductively coupled plasma mass spectrometry (ICP-MS) to monitor the formation of the bromine-tagged pyrrole derivatives. Crude extracts obtained from traditional Chinese medicine Dioscorea bulbifera L., known to contain furanoditerpenoids, were analyzed by the approach. In conclusion, the platform has been proven selective, sensitive, effective, and reliable, and ICP MS allows us to estimate the resulting bromine-labeled pyrroles without authentic standards

Data_Sheet_1.DOC

<p>Reductive dechlorination is the primary pathway for environmental removal of pentachlorophenol (PCP) in soil under anaerobic condition. This process has been verified to be coupled with other soil redox processes of typical biogenic elements such as carbon, iron and sulfur. Meanwhile, biochar has received increasing interest in its potential for remediation of contaminated soil, with the effect seldom investigated under anaerobic environment. In this study, a 120-day anaerobic incubation experiment was conducted to investigate the effects of biochar on soil redox processes and thereby the reductive dechlorination of PCP under anaerobic condition. Biochar addition (1%, w/w) enhanced the dissimilatory iron reduction and sulfate reduction while simultaneously decreased the PCP reduction significantly. Instead, the production of methane was not affected by biochar. Interestingly, however, PCP reduction was promoted by biochar when microbial sulfate reduction was suppressed by addition of typical inhibitor molybdate. Together with Illumina sequencing data regarding analysis of soil bacteria and archaea responses, our results suggest that under anaerobic condition, the main competition mechanisms of these typical soil redox processes on the reductive dechlorination of PCP may be different in the presence of biochar. In particularly, the effect of biochar on sulfate reduction process is mainly through promoting the growth of sulfate reducer (Desulfobulbaceae and Desulfobacteraceae) but not as an electron shuttle. With the supplementary addition of molybdate, biochar application is suggested as an improved strategy for a better remediation results by coordinating the interaction between dechlorination and its coupled soil redox processes, with minimum production of toxic sulfur reducing substances and relatively small emission of greenhouse gas (CH₄) while maximum removal of PCP.</p

Independent Photochemical Generation and Reactivity of Nitrogen-Centered Purine Nucleoside Radicals from Hydrazines

Photochemical precursors that produce dA^• and dG­(N₂–H)^• are needed to investigate their reactivity. The synthesis of two 1,1-diphenylhydrazines (<b>1</b>, <b>2</b>) and their use as photochemical sources of dA^• and dG­(N₂–H)^• is presented. Trapping studies indicate production of these radicals with good fidelity, and <b>1</b> was incorporated into an oligonucleotide via solid-phase synthesis. Cyclic voltammetric studies show that reduction potentials of <b>1</b> and <b>2</b> are lower than those of widely used “hole sinks”, e.g., 8-oxodGuo and 7-deazadGuo, to investigate DNA–hole transfer processes. These molecules could be useful (a) as sources of dA^• and dG­(N₂–H)^• at specific sites in oligonucleotides and (b) as “hole sinks” for the study of DNA–hole transfer processes

Self-Assembly of a Family of Isopolytungstates Induced by the Synergistic Effect of the Nature of Lanthanoids and the pH Variation in the Reaction Process: Syntheses, Structures, and Properties

Three types of new lanthanoid­(Ln)-containing isopolyoxotungstates [H₂N­(CH₃)₂]₆Na₆­[Ln₄(H₂O)₂₂­W₂₈O₉₄H₂]₂<b>·</b>­113H₂O [Ln = Pr³⁺ (<b>1</b>), Nd³⁺ (<b>2</b>), Sm³⁺ (<b>3</b>)], Na₂[Eu­(H₂O)₇]₂­[Eu­(H₂O)₅]₂­[W₂₂O₇₄H₂]<b>­·</b>20H₂O (<b>4</b>), and Na₃H₂[Ln­(H₂O)₄]­[Ln (H₂O)₅]₂­[W₂₂O₇₄H₂]­·36H₂O [Ln = Gd³⁺ (<b>5</b>), Tb³⁺ (<b>6</b>), Er³⁺ (<b>7</b>), Tm³⁺ (<b>8</b>), Yb³⁺ (<b>9</b>), Lu³⁺ (<b>10</b>)] have been obtained by reacting Na₂WO₄­·2H₂O with Ln­(NO₃)₃­·6H₂O in the presence of dimethylamine hydrochloride in the acidic aqueous solution and structurally characterized by elemental analyses, IR spectroscopy, UV spectroscopy, electrospray ionization mass spectrometry (ESI–MS), thermogravimetric (TG) analyses, and single-crystal X-ray diffraction. <b>1</b>, <b>2</b>, and <b>3</b> are isostructural and display a one-dimensional (1-D) chain-like alignment built by hexameric Ln₈-comprising [Ln₄(H₂O)₂₂­W₂₈O₉₄H₂]₂^12– entities via [Ln­(H₂O)₅]³⁺ connectors. The [Ln₄(H₂O)₂₂­W₂₈O₉₄H₂]₂^12– entity consists of two [Ln₄(H₂O)₂₂­W₂₈O₉₄H₂]^6– subunits connected by two W–O–Ln–O–W linkers. Intriguingly, the rare λ-shaped octacosatungstate [W₂₈O₉₄H₂]^18– moiety observed in the [Ln₄(H₂O)₂₂­W₂₈O₉₄H₂]^6– subunit is composed of two undecatungstate [W₁₁O₃₈H]^9– fragments joined through a hexatungstate [W₆O₂₂]^8– fragment by sharing four μ₂-O atoms. In <b>4</b>, 22-isopolytungstate [W₂₂O₇₄H₂]^14– anions are interlinked together by four W–O–Eu1–O–W linkers giving rise to the 1-D chain motif, and then adjacent 1-D chains are further bridged through multiple W–O–Eu2–O–W connectors to engender the two-dimensional extended sheet structure with the 4-connected topology. The isomorphic <b>5</b>–<b>10</b> demonstrate the discrete structure consisting of a [Ln­(H₂O)₄]­[Ln (H₂O)₅]₂­[W₂₂O₇₄H₂]^8– unit. The pH ranges in which <b>3</b>, <b>4</b>, and <b>9</b> are stable in aqueous solution have been examined by virtue of UV and ESI–MS spectra. The solid-state luminescent properties of <b>3</b>, <b>4</b>, and <b>6</b> have been probed at room temperature. <b>3</b> displays the pink emission derived from characteristic emission bands of the Sm³⁺ cations that correspond to transitions from the ⁴G_5/2 excited-state to lower ⁶H_J (<i>J</i> = 5/2, 7/2, 9/2, 11/2) levels, <b>4</b> emits the red light that mainly results from the ⁵D₀ → ⁷F₂ transition of the Eu³⁺ cations, and <b>6</b> manifests the green luminescence mainly originating from the ⁵D₄ → ⁷F₅ transition of the Tb³⁺ cations. Their lifetime decay curves all conform to the single exponential function, affording their lifetimes of 8094.19 ns, 149.00 μs and 384.89 μs, respectively

Additional file 3: Table S4 and Table S5. of Cell cycle control, DNA damage repair, and apoptosis-related pathways control pre-ameloblasts differentiation during tooth development

Selected connections, including gene symbols of nodes and adjacency, in the brown and blue modules. Table S6 and Table S7: Selected connections with membership measure and gene significance in the brown and blue modules. (XLS 933 kb

Additional file 4: of Cell cycle control, DNA damage repair, and apoptosis-related pathways control pre-ameloblasts differentiation during tooth development

Scatterplots between module membership measure (x-axis) and gene significance of GO terms in the brown module (A-E) and blue module (F-J). The grey dashed line in the plot is the threshold for choosing significantly expressed genes, and the threshold value is –log10(0.05). (TIFF 1712 kb

Table_1_Tooth loss, denture use, and all-cause and cause-specific mortality in older adults: a community cohort study.pdf

ObjectivesThe available evidence on the connections between tooth loss, denture use, and mortality from all causes or specific causes among older adults is inconclusive. Therefore, we aimed to investigate the association between tooth loss, denture use, and all-cause and cause-specific mortality in older adults.MethodsA cohort of 5,403 participants aged 65 and older were recruited in the 2014 Chinese Longitudinal Healthy Longevity Survey wave and followed up in the 2018 wave. Cox proportional hazard models were used to examine the association between the number of natural teeth, denture use, and all-cause and cause-specific mortality.ResultsDuring a mean (SD) follow-up of 3.1  years (1.3), 2,126 deaths (39.3%) occurred. Individuals with 0 and 1–9 teeth had higher mortality due to all-cause, cardiovascular disease (CVD), cancer, and other causes (all p-trend ConclusionHaving fewer natural teeth, particularly less than 10 teeth, is linked to an increased risk of mortality from all causes, including CVD, cancer, and other causes, but not respiratory disease. The use of dentures would mitigate the adverse impact of tooth loss on all-cause and some cause-specific mortality.</p

Histological staining of trabecular bone.

<p>(H&E staining) Buccal lingual cross sections of the furcation area between the mesial root and the distal root of the mandibular first molar. The second row consists of magnified images (400X) of trabecular bone. B: Bone marrow space; C: Cancellous bone.</p