Insights into the Reaction Mechanism of Criegee Intermediate CH₂OO with Methane and Implications for the Formation of Methanol

Criegee intermediates (CIs) play a key role in controlling the atmospheric budget of hydroxyl radical, organic acids, and secondary organic aerosols. In this study, the detailed reaction mechanisms of the simplest Criegee intermediate CH₂OO and its derivatives with methane (CH₄) have been systematically investigated theoretically. Two pathways A and B have been identified for the title reaction. In pathway A, CIs can act as an oxygen donor by inserting its terminal oxygen atom into the C–H bond of alkanes, resulting in the formation of alcohol species. The corresponding energy barriers ranging from 6.5 to 24.1 kcal/mol are associated with the O–O bond strength of CIs. Meanwhile, this pathway is more favorable thermodynamically, where the free energy changes (enthalpy changes) range from −81.1 (−78.3) to −110.9 (−109.0) kcal/mol, respectively. In pathway B, an addition reaction to produce the hydroperoxides occurs, accompanying the hydrogen transfer from the alkanes to the terminal oxygen atom of CIs. The corresponding energy barriers ranging from 17.3 to 30.9 kcal/mol are higher than those in pathway A. Further calculations of the rate constants suggest that pathway A is the most favorable reaction channel and the rate constant exhibits a positive temperature dependence. In addition, the conformation-dependent reactivity for the title reaction has been observed. The present findings can enable us to better understand the potential reactivity of CIs in the presence of the alkane species

Highly Crumpled All-Carbon Transistors for Brain Activity Recording

Neural probes based on graphene field-effect transistors have been demonstrated. Yet, the minimum detectable signal of graphene transistor-based probes is inversely proportional to the square root of the active graphene area. This fundamentally limits the scaling of graphene transistor-based neural probes for improved spatial resolution in brain activity recording. Here, we address this challenge using highly crumpled all-carbon transistors formed by compressing down to 16% of its initial area. All-carbon transistors, chemically synthesized by seamless integration of graphene channels and hybrid graphene/carbon nanotube electrodes, maintained structural integrity and stable electronic properties under large mechanical deformation, whereas stress-induced cracking and junction failure occurred in conventional graphene/metal transistors. Flexible, highly crumpled all-carbon transistors were further verified for in vivo recording of brain activity in rats. These results highlight the importance of advanced material and device design concepts to make improvements in neuroelectronics

Table_1_mbtD and celA1 association with ethambutol resistance in Mycobacterium tuberculosis: A multiomics analysis.xlsx

Ethambutol (EMB) is a first-line antituberculosis drug currently being used clinically to treat tuberculosis. Mutations in the embCAB operon are responsible for EMB resistance. However, the discrepancies between genotypic and phenotypic EMB resistance have attracted much attention. We induced EMB resistance in Mycobacterium tuberculosis in vitro and used an integrated genome–methylome–transcriptome–proteome approach to study the microevolutionary mechanism of EMB resistance. We identified 509 aberrantly methylated genes (313 hypermethylated genes and 196 hypomethylated genes). Moreover, some hypermethylated and hypomethylated genes were identified using RNA-seq profiling. Correlation analysis revealed that the differential methylation of genes was negatively correlated with transcription levels in EMB-resistant strains. Additionally, two hypermethylated candidate genes (mbtD and celA1) were screened by iTRAQ-based quantitative proteomics analysis, verified by qPCR, and corresponded with DNA methylation differences. This is the first report that identifies EMB resistance-related genes in laboratory-induced mono-EMB-resistant M. tuberculosis using multi-omics profiling. Understanding the epigenetic features associated with EMB resistance may provide new insights into the underlying molecular mechanisms.</p

Identification of Serum microRNA Biomarkers for Tuberculosis Using RNA-seq

<div><p>Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85–1285.93 fold) and 6 microRNAs that are down-regulated (0.003–0.11 fold) (P<0.05) in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05–2454.58 fold) and 11 were down-regulated (0.001–0.42 fold) (P<0.05) in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9–499.29 fold, 116 down-regulated 0.0002–0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.</p></div

microRNA-gene network for hsa-miR-196b, hsa-miR-516b, hsa-miR-376c and hsa-miR-486-5p.

<p>The microRNA-gene network was built using gene expression data and predicted interactions from the TargetScan and PicTar microRNA databases. Red circles represent microRNAs and blue squares represent genes; their relationship is represented by the edges.</p

Demographic characteristics of the study population.

<p>LTBI, individuals with latent TB infection.</p

Venn diagram illustrating the distribution of microRNAs which showed significantly altered expression in TB patients compared with three control groups (LTBI, BCG-inoculated, and un-inoculated individuals).

<p>A, microRNAs which were up-regulated in serum from TB patients compared with the control groups; B, microRNAs which were down-regulated in serum from TB patients compared with the control groups. BCG, BCG-inoculated; LTBI, individuals with latent TB infection; Healthy, un-inoculated controls.</p

Effects of miRNA overexpression on NFAT5 mRNA levels (2^−ΔΔCT) in HEK293 cells.

<p>HEK293 cells were transfected respectively with four miRNA mimics (<i>hsa-miR-376c</i>, <i>hsa-miR-516b</i>, <i>hsa-miR-486-5p</i> and <i>cel-miR-67-3p</i>) and incubated at 37°C (5% CO₂) for 24 h. NFAT5 mRNA levels were measured in extracts of total RNA using RT-qPCR. NC: negative control (<i>cel-miR-67-3p</i>). Data presented are mean values from three independent experiments, n = 3. Error bars show the s.e.m. The significance of comparisons was tested using the Student’s <i>t</i>-test; *: P<0.05.</p