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Insulin-resistance (IR) is one of the most important precursors of type 2 diabetes (T2D). Recent evidence suggests an association of depression with the onset of T2D. Accumulating evidence shows that depression and T2D share common biological origins, and DNA methylation examination might reveal the link between lifestyle, disease risk, and potential therapeutic targets for T2D. Here we hypothesize that integrative mining of IR and depression cohort data will facilitate predictive biomarkers identification for T2D. We utilized a newly proposed method to extract gene-level information from probe level data on genome-wide DNA methylation array. We identified a set of genes associated with IR and depression in clinical cohorts. By overlapping the IR-related nutraceutical-gene network with depression networks, we identified a common subnetwork centered with Vitamin D Receptor (VDR) gene. Preliminary clinical validation of gene methylation set in a small cohort of T2D patients and controls was established using the Sequenome matrix-assisted laser desorption ionization-time flight mass spectrometry. A set of sites in the promoter regions of VDR showed a significant difference between T2D patients and controls. Using a logistic regression model, the optimal prediction performance of these sites was AUC = 0.902，and an odds ratio = 19.76. Thus, monitoring the methylation status of specific VDR promoter region might help stratify the high-risk individuals who could potentially benefit from vitamin D dietary supplementation. Our results highlight the link between IR and depression, and the DNA methylation analysis might facilitate the search for their shared mechanisms in the etiology of T2D.

On-site screening of diabetes and precise diagnosis of diabetic complications may provide a conduit for early intervention and disease burden reduction. However, stratified metabolic analysis needs designed materials for colorimetric detection of targeted biomarkers and direct metabolic fingerprinting of the native blood. Here, an advanced dual-modal nanoplatform is constructed based on PdPtAu alloys, which serve both as the nanoenzymes in colorimetric sensing for targeted metabolite quantitation and as matrix in laser desorption/ionization mass spectrometry for untargeted metabolic fingerprinting. The platform achieved rapid glucose quantitation toward point-of-care testing of 27 participants and identified diabetic retinopathy from diabetic population with a sensitivity and specificity of 84.6%. We further assessed the generalizability of the nanoplatform for real-case applications, through the captured digital images and computing resources equipped in smartphones. The results advance the design of material-based platforms for stratified metabolic analysis and display promise to fit in the current hierarchical medical system in practice.

ObjectiveThere is a body of evidence that the aging immune system is linked to cancer. Here, we hypothesized that ubiquitination might play a key gatekeeper role in immune system aging and tumorigenesis in CRC. Therefore, we will systematically study the DNA methylation of ubiquitination genes and screen candidate CRC marker that are correlated with both aging and immune cell compositions.DesignThrough aging- and immune-related DNA methylation data, we investigated the DNA methylation regulation changes in promoters with other regions of genes during aging and their association with the immune cell proportion in the circulating whole blood of healthy individuals. Then, by collecting a cohort of 100 colon cancer patients and 50 healthy individuals, we used nucleic acid mass spectrometry to test whether ubiquitination genes can be used as candidate markers for the early screening of CRC.ResultsThe biological analyses for aging- and CD4 T cell proportion-derived differential genes showed that they are associated with ubiquitination. Among them, DZIP3 was significantly associated with both aging (P-value = 3.86E-06) and CD4 T cell proportion (P-value = 1.97E-05) in circulating blood. Then, we validated that the 1st exon DNA methylation of DZIP3 could predict the onset of early stage CRC (AUC = 0.833, OR = 8.82) and all pTNM stages of CRC (AUC = 0.782, OR = 5.70).ConclusionsThe epigenetically regulated ubiquitination plays an important role in immune aging and tumorigenesis. DNA methylation characteristic of DZIP3 can be used as a promising marker of CRC early screening.Summary boxWhat is already known about this subject?The aging immune system is associated with cancer.Ubiquitination plays potent roles in regulating a variety of signals in both innate and adaptive immune cells.The abnormalities of ubiquitination are closely related to the occurrence of various tumors.Blood cell DNA methylome analysis provides a promising tool to probe the key components of immune cell dysregulation in aging and tumorigenesis.What are the new findings?The aging- and immune cell proportion-derived differential genes are associated with ubiquitination.The epigenetically regulated ubiquitination plays an important role in immune aging and tumorigenesis.DNA methylation characteristic of DZIP3, an E3 ubiquitin ligase with no reports on its function in immune cells and tumorigenesis, can be used as a promising markers of CRC early screening.How might it impact on clinical practice in the foreseeable future?The in-depth study for DNA methylome of ubiquitination will open up a new path for the study of CRC pathogenesis, diagnosis and treatment.In addition, DZIP3-focused screening technique only needs to extract the whole blood of individuals for MassARRAY analysis; the samples are easy to obtain, and the results are objective. Therefore, this method may have important applications in clinical CRC screening.

The Li4Ti5O12 is applied in lithium ion batteries as anode material, which can be synthesized by various synthesis techniques. In this study, the molten salt synthesis technique at low temperatures, i.e. 350 °C, was applied to synthesize Li4Ti5O12. Surprisingly, the Li4Ti5O12 was not formed according to XRD analysis, which raised question about the stability range of Li4Ti5O12. To investigate the stability of Li4Ti5O12 at low temperatures, the high-temperature calcined Li4Ti5O12 powder was equilibrated in the LiCl-KCl eutectic salt at 350 °C. The result of experiment revealed that the Li4Ti5O12 is not decomposed. Results of ab initio calculations also indicated that the Li4Ti5O12 phase is a stable phase at 0 K. The products of molten salt synthesis technique were then annealed at 900 °C, which resulted in the Li4Ti5O12 formation. It was concluded that the Li4Ti5O12 is a stable phase at low temperatures and the reasons for not forming the Li4Ti5O12 by molten salt technique at low temperature are possibly related to activation energy and kinetic barriers. The Li4Ti5O12 formation energy is also very small, due to the results of ab initio calculations.

Tetramethylpyrazine (TMP), extracted from the Chinese herbal medicine Ligusticum wallichii franchat (chuan xiong in Chinese), is a potent anti-free radical and calcium antagonist. Correspondingly, two important hypotheses in the causation of cataracts are free radical toxicity and calcium ion overload. In this study we investigated the effect of TMP on lens opacification induced by sodium selenite in rats, addressing the potential of TMP eye drops to prevent and treat cataracts. Results showed that the extent of lens opacification in the untreated Normal Control group (NC group) was significantly less than that of selenite-injected untreated rats (MC group) on days 3, 5, 7 and 10 (p 0.001), while TMP treated selenite-injected rats (TMP group) had less lens opacification than the MC group on days 3, 5, 7 and 10 (p 0.05). Compared with the NC group, the MC group had significantly decreased activity of super-oxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) and significantly elevated malondialdehyde (MDA) and calcium ion content (p 0.001). Compared with the MC group, the activity of (SOD), (GSH-PX) and (CAT) were significantly higher while (MDA) and calcium ion levels were significantly lower in the TMP group at all time points (p 0.01). The findings demonstrate that the selenite-induced cataract rat models were successfully built and the TMP eye drops can delay lens opacification induced by sodium selenite in rats. The mechanism by which TMP preserves lens transparency from selenite treated animals is associated with the lenses' ability to maintain normal levels of activity of SOD, GSH-PX and CAT and normal concentrations of MDA and calcium ion.

In the last three decades, solid oxide fuel cells (SOFCs) have garnered significant interest for viable distributed power generation systems. In this work, we focus on the cathode in SOFCs, where oxygen reduction occurs in two steps—adsorption and electronation, and surface/bulk diffusion to incorporation sites. Transition metal oxides such as strontium-doped lanthanum manganite (LSM) and strontium-doped cobalt iron oxide (LSCF) have been used as cathode materials, however both individually lack the key characteristics to successfully complete oxygen reduction. Furthermore, the accumulation of chromium (chromium poisoning) on SOFC cathodes is known to significantly hinder the performance of the cells. Incorporating core-shell hetero-structures as the cathode material could alleviate this problem: effectively combining the functionalities of both materials, and providing a nanoscale protection from Cr poisoning with a shell such as Cr-doped LSM (LSCM). However, synthesizing core-shell cathode structures previously has proved difficult requiring multiple steps, resulting in non-uniform core-shell structures. In this work we propose utilizing a molten salt synthesis process to create core-shell structures with precise composition with relative ease. The core is synthesized using high-temperature calcination and ball milled with the precursors of the target shell material. The milled powder mixtures are added to a LiCl-KCl eutectic melt to form core-shell hetero-structures via heterogeneous nucleation. Prior results have shown the successful formation of LSM and LSCF using the molten salt synthesis, along with the formation of core-shell LSCF-LSM hetero-structures. Synthesis temperatures dropped from the conventional 1000 ºC to 500 ºC, with dwell times as low as 10 minutes. Furthermore, SOFC cathodes consisting of LSCM were found to have stable polarization resistances, whereas the polarization resistance in LSM cathodes steadily increased. This result provides a strong motivation to further explore LSCM as a shell for core-shell cathodes to ensure protection from chromium poisoning. In essence, this work demonstrates an inexpensive method to synthesize core-shell cathodes that can simultaneously provide high power densities and low rates of degradation arising from Cr-poisoning. Figure 1

Solid oxide fuel cells (SOFCs) address critical needs in the energy infrastructure due to their high efficiency, low emisssions and noiseless operation. The intermediate temperature SOFCs(IT-SOFCs) enable the use of metallic interconnect instead of traditional ceramic interconnect. However, chromium poisoning due to transport from metallic interconnect and BOP components is deleterious to cell performance. To prevent the chromium poisoning, either a new cathode material with a high tolerance of chromium poisoning needs to be deployed, or a protective coating with a high electrical conductivity needs to applied to the interconnect. In this study, electrolyte-supported baseline half-cell with 8mol% YSZ as the electrolyte and (La0.8Sr0.2)0.95MnO3-δ as the working and counter electrode was fabricated. Its electrochemical characteristics were tested in dry air and 50 mA/cm2 cathodic current in the present of bare chromia-forming interconnect, and an interconnect with a protective coating. Further, to investigate the effect of alternate electrode compositions, new electrodes, e.g. Cr- doped LSM, were employed as the working electrode instead of LSM in the baseline cell, and tested under same conditions.

Solid oxide fuel cells (SOFCs) offer a clean, efficient and environmental-friendly technique to convert chemical energy to electricity . In order to achieve high performance at lower operating temperature, anode-supported planar solid oxide fuel cells are usually preferred. The lower operating temperature enables the deployment of metallic interconnects based on ferritic stainless steel. The leading candidate alloy is Crofer 22 APU which is a state-of-the-art material with good high-temperature stability, high electrical conductivity and low coefficient of thermal expansion. However, the chromia oxide scale that forms on the surface of the Crofer 22 APU alloy reacts with the oxygen and water vapor to form volatile chromium species, chromium trioxide, CrO3, and chromium oxyhydroxide, CrO2(OH)2which deposit on the electrochemically active regions of the cathode. In order to understand the mechanism of chromium poisoning in SOFCs, electrolyte-supported half-cells have been fabricated. 8mol%-yttria-stabilized-zirconia pellets are used as electrolyte by uniaxial pressing. Lanthanum strontium manganite is screen printed on both side of the YSZ pellet, and a silver wire is used as the reference electrode. These half-cells have been tested at different temperatures with different humidity levels in the air, with and without contacting the Crofer 22 APU alloy. Galvanostatic current interruption (GCI) has been employed during the electrochemical test, and after the test, scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX) have been used to detect the composition near the TBPs. Figure 1