We report a comprehensive study of transparent and conductive silver nanowire (Ag NW) electrodes, including a scalable fabrication process, morphologies, and optical, mechanical adhesion, and flexibility properties, and various routes to improve the performance. We utilized a synthesis specifically designed for long and thin wires for improved performance in terms of sheet resistance and optical transmittance. Twenty Omega/sq and approximately 80% specular transmittance, and 8 ohms/sq and 80% diffusive transmittance in the visible range are achieved, which fall in the same range as the best indium tin oxide (ITO) samples on plastic substrates for flexible electronics and solar cells. The Ag NW electrodes show optical transparencies superior to ITO for near-infrared wavelengths (2-fold higher transmission). Owing to light scattering effects, the Ag NW network has the largest difference between diffusive transmittance and specular transmittance when compared with ITO and carbon nanotube electrodes, a property which could greatly enhance solar cell performance. A mechanical study shows that Ag NW electrodes on flexible substrates show excellent robustness when subjected to bending. We also study the electrical conductance of Ag nanowires and their junctions and report a facile electrochemical method for a Au coating to reduce the wire-to-wire junction resistance for better overall film conductance. Simple mechanical pressing was also found to increase the NW film conductance due to the reduction of junction resistance. The overall properties of transparent Ag NW electrodes meet the requirements of transparent electrodes for many applications and could be an immediate ITO replacement for flexible electronics and solar cells.

The removal of bacteria and other organisms from water is an extremely important process, not only for drinking and sanitation but also industrially as biofouling is a commonplace and serious problem. We here present a textile based multiscale device for the high speed electrical sterilization of water using silver nanowires, carbon nanotubes, and cotton. This approach, which combines several materials spanning three very different length scales with simple dying based fabrication, makes a gravity fed device operating at 100000 L/(h m(2)) which can inactivate >98% of bacteria with only several seconds of total incubation time. This excellent performance is enabled by the use of an electrical mechanism rather than size exclusion, while the very high surface area of the device coupled with large electric field concentrations near the silver nanowire tips allows for effective bacterial inactivation.

Triple-negative breast cancer (TNBC) is the most intractable cancer in women with a high risk of metastasis. While hyper-methylation of histone H3 catalyzed by disruptor of telomeric silencing 1-like (DOT1L), a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), is reported as a potential target for TNBCs, early developed nucleoside-type DOT1L inhibitors are not sufficient for effective inhibition of growth and metastasis of TNBC cells. We found that TNBC cells had a high expression level of DOT1L and a low expression level of E-cadherin compared to normal breast epithelial cells and non-TNBC cells. Here, a novel psammaplin A analog (PsA-3091) exhibited a potent inhibitory effect of DOT1L-mediated H3K79 methylation. Consistently, PsA-3091 also significantly inhibited the proliferation, migration, and invasion of TNBC cells along with the augmented expression of E-cadherin and the suppression of N-cadherin, ZEB1, and vimentin expression. In an orthotopic mouse model, PsA-3091 effectively inhibited lung metastasis and tumor growth by the regulation of DOT1L activity and EMT biomarkers. Together, we report here a new template of DOT1L inhibitor and suggest that targeting DOT1L-mediated H3K79 methylation by a novel PsA analog may be a promising strategy for the treatment of metastatic breast cancer patients.

Recent studies point out the link between altered mitochondrial metabolism and cancer, and detailed understanding of mitochondrial metabolism requires real-time detection of its metabolites. Employing heteronuclear 2D NMR spectroscopy and C-pyruvate, we propose in-organelle metabolomics that allows for the monitoring of mitochondrial metabolic changes in real time. The approach identified acetyl phosphate from human mitochondria, whose production has been largely neglected in eukaryotic metabolism since its first description about 70 years ago in bacteria. The kinetic profile of acetyl phosphate formation was biphasic, and its transient nature suggested its role as a metabolic intermediate. The method also allowed for the estimation of pyruvate dehydrogenase (PDH) enzyme activity through monitoring of the acetyl-CoA formation, independent of competing cytosolic metabolism. The results confirmed the positive regulation of mitochondrial PDH activity by p53, a well-known tumor suppressor. Our approach can easily be applied to other organelle-specific metabolic studies.

Background Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. Methods Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. Results Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.

Gut microbiome can affect drug metabolism considerably, leading to modified drug response. However, quantitative estimation of host vs. microbial contributions in a living host–gut microbiome system has been challenging. Using the interspecies system of Caenorhabditis elegans and gut bacteria, we developed a real-time approach for monitoring their metabolic interaction in vivo during anticancer drug 5-fluorouracil (5-FU) metabolism. The fluorine NMR-based approach yielded the quantitative contributions to the host 5-FU metabolism made by human gut-microbial species of variable genetic backgrounds. It also experimentally confirmed a bacterial gene–metabolism relationship. Differential 5-FU catabolism among bacterial substrains and the contributions to the host metabolism, unobservable by conventional 16S rRNA metagenomic sequencing, were also found. The metabolic contributions could be correlated with phenotypic developmental toxicity of 5-FU to the host fed with different substrains. Our convenient platform should help to reveal heterogeneity in host–gut microbiome interactions for many drugs in a living symbiotic system.

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Objectives: Using diffusion tensor imaging (DTI), we investigated the state of medial lemniscus (ML), corticospinal tract (CST), and posterior thalamic radiation (PTR), which were expected as probable reasons for clinical hemiplegia in pediatric patients, especially those who showed impaired fine motor control and proprioception, but no definite motor weakness or spasticity. Methods: We recruited 13 hemiplegic patients and 8 age-matched healthy control subjects. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) for the bilateral ML, CST, and PTR were calculated and compared between the affected hemisphere of the patient (AP), the unaffected hemisphere of the patient (UP), and the mean value of the bilateral hemispheres in control subjects (MC). Results: FA and ADC values for the CST and PTR did not differ significantly between the AP, UP, and MC subgroups (p > 0.05). However, the FA value for the ML in AP showed a significant decrease, compared with that in UP (p = 0.012) and MC (p = 0.047). DTT for the CST and PTR showed preserved integrity and ML in the UP also had continuity to the cortex; however, ML in AP showed disruption. Conclusions: Using DTI, we demonstrated that the ML lesion might be related to clinical hemiplegia in pediatric patients.