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Ultraviolet (UV) light irradiation on CeO2 nanocrystals catalysts has been observed to largely increase the material’s catalytic activity and reactive surface area. As revealed by x-ray absorption near edge structure (XANES) analysis, the concentration of subvalent Ce3+ ions in the irradiated ceria samples progressively increases with the UV-light exposure time. The increase of Ce3+ concentration as a result of UV irradiation was also confirmed by the UV-vis diffuse reflectance and photoluminescence spectra that indicate substantially increased concentration of oxygen vacancy defects in irradiated samples. First-principle formation-energy calculation for oxygen vacancy defects revealed a valence-hole-dominated mechanism for the irradiation-induced reduction of CeO2 consistent with the experimental results. Based on a Mars-van Krevelen mechanism for ceria catalyzed oxidation processes, as the Ce3+ concentration is increased by UV-light irradiation, an increased number of reactive oxygen atoms will be captured from gas-phase O2 by the surface Ce3+ ions, and therefore leads to the observed catalytic activity enhancement. The unique annealing-free defect engineering method using UV-light irradiation provides an ultraconvenient approach for activity improvement in nanocrystal ceria for a wide variety of catalytic applications.

This study was performed to assess the probability of post-thrombotic syndrome (PTS) after treatment of lower extremity deep venous thrombosis (LEDVT). Patients with LEDVT undergoing their first treatments in Nanjing First Hospital from January 2013 to December 2014 were enrolled in this study (156 patients were enrolled in the training cohort, and 135 patients were enrolled in the validation cohort). 51 and 45 patients developed PTS in the two cohorts, respectively. Independent risk factors for PTS were investigated in the training cohort, and these independent risk factors were employed to develop the APTSD scoring system with which to predict the probability of PTS. Four independent risk factors for PTS were identified: iliac vein compression syndrome, residual iliac-femoral vein thrombosis, residual femoral-popliteal vein thrombosis and insufficient anticoagulation. Patients in the training cohort were divided into 2 groups according to the APTSD score of ≤7.0 and >7.0 points regarding the probability of PTS (median PTS-free time, 21.82 vs. 18.84 months; P 7.0 points may have an increased probability of developing PTS.

Triaxial active and passive mechanical properties of coronary arteries are needed for understanding arterial mechanics in health and disease. The aim of the study was to quantify both active and passive strain energy functions in circumferential, axial and radial directions based on the experimental measurement. Moreover, a two-layer computational model was used to determine the transmural distribution of stresses and strains across the vessel wall. The first Piola-Kirchhoff stresses in the three normal directions had the approximate relationship as:$$\,{T}_{\theta \theta }\cong 2{T}_{zz}\cong 5|{T}_{rr}|$$ T θ θ ≅ 2 T z z ≅ 5 | T r r | . The two-layer model showed that circumferential Cauchy stresses increased significantly from the intima layer to the interface between media and adventitia layers (from ~80 to 160 kPa), dropped abruptly at the interface (from ~160 to

Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have been associated with developmental neurological disorders, including microcephaly and Leigh syndrome. However, little is known about how thiamine metabolism regulates neuronal morphology at the cellular level. Here, using primary rat hippocampal neuronal cultures, we showed that reducing the expression of Tpk1, Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite complexity, as measured by total dendritic branch tip number (TDBTN) and total dendritic branch length (TDBL). The specificity of the RNAi effects were verified by overexpression of RNAi resistant human constructs. Importantly, changes in both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating coordinated regulation of soma and dendrite growth by thiamine. The requirement of thiamine metabolism for coordinated somata and dendrite growth is highly consistent with the microcephaly and neurodegenerative phenotypes observed in thiamine loss-of-function diseases.

Cell culture and protein target-based compound screening strategies, though broadly utilized in selecting candidate compounds, often fail to eliminate candidate compounds with non-target effects and/or safety concerns until late in the drug developmental process. Phenotype screening using intact research animals is attractive because it can help identify small molecule candidate compounds that have a high probability of proceeding to clinical use. Most FDA approved, first-in-class small molecules were identified from phenotypic screening. However, phenotypic screening using rodent models is labor intensive, low-throughput, and very expensive. As a novel alternative for small molecule screening, we have been developing gene expression disease profiles, termed the Transcriptional Disease Signature (TDS), as readout of small molecule screens for therapeutic molecules. In this concept, compounds that can reverse, or otherwise affect known disease-associated gene expression patterns in whole animals may be rapidly identified for more detailed downstream direct testing of their efficacy and mode of action. To establish proof of concept for this screening strategy, we employed a transgenic strain of a small aquarium fish, medaka (Oryzias latipes), that overexpresses the malignant melanoma driver gene xmrk, a mutant egfr gene, that is driven by a pigment cell-specific mitf promoter. In this model, melanoma develops with 100% penetrance. Using the transgenic medaka malignant melanoma model, we established a screening system that employs the NanoString nCounter platform to quantify gene expression within custom sets of TDS gene targets that we had previously shown to exhibit differential transcription among xmrk-transgenic and wild-type medaka. Compound-modulated gene expression was identified using an internet-accessible custom-built data processing pipeline. The effect of a given drug on the entire TDS profile was estimated by comparing compound-modulated genes in the TDS using an activation Z-score and Kolmogorov-Smirnov statistics. TDS gene probes were designed that target common signaling pathways that include proliferation, development, toxicity, immune function, metabolism and detoxification. These pathways may be utilized to evaluate candidate compounds for potential favorable, or unfavorable, effects on melanoma-associated gene expression. Here we present the logistics of using medaka to screen compounds, as well as, the development of a user-friendly NanoString data analysis pipeline to support feasibility of this novel TDS drug-screening strategy.

Ultraviolet (UV) light irradiation on CeO2 nanocrystals catalysts has been observed to largely increase the material’s catalytic activity and reactive surface area. As revealed by x-ray absorption near edge structure (XANES) analysis, the concentration of subvalent Ce3+ ions in the irradiated ceria samples progressively increases with the UV-light exposure time. The increase of Ce3+ concentration as a result of UV irradiation was also confirmed by the UV-vis diffuse reflectance and photoluminescence spectra that indicate substantially increased concentration of oxygen vacancy defects in irradiated samples. First-principle formation-energy calculation for oxygen vacancy defects revealed a valence-hole-dominated mechanism for the irradiation-induced reduction of CeO2 consistent with the experimental results. Based on a Mars-van Krevelen mechanism for ceria catalyzed oxidation processes, as the Ce3+ concentration is increased by UV-light irradiation, an increased number of reactive oxygen atoms will be captured from gas-phase O2 by the surface Ce3+ ions, and therefore leads to the observed catalytic activity enhancement. The unique annealing-free defect engineering method using UV-light irradiation provides an ultraconvenient approach for activity improvement in nanocrystal ceria for a wide variety of catalytic applications.

Recognition and classification of road-related landslides are a critical requirement in pre- and post-disaster hazard analysis. They are primarily done through field mapping or manual image interpretation from commercial satellites images. This paper developed a Normalized Difference Road Landside Index (NDRLI)-based method to delineate road-induced landslides and enhance their presence in remotely sensed digital imagery based on free Landsat Operational Land Imager (OLI) sources. The NDRLI-based method includes NDRLI, Shape Index of Spectral Curve (SISC), and other optimizing steps such as deleting shadow and slope

We use in situ scanning probe microscopy (SPM) to investigate the high temperature oxidation of Ni-based single crystal alloys at the micro-/nanoscale. SiO2 micro-pillar arrays were pre-fabricated on the alloy surface as markers before the oxidation experiment. The SPM measurement of the oxidized surface in the vicinity of SiO2 micro-pillars was conducted real time at temperatures from 300 °C to 800 °C. The full-field evolution of oxide film thickness is quantitatively characterized by using the height of SiO2 micro-pillars as reference. The results reveal the non-uniform oxide growth featuring the nucleation and coalescence of oxide islands on the alloy surface. The outward diffusion of Ni and Co is responsible for the formation and coalescence of first-stage single-grain oxide islands. The second-stage of oxidation involves the formation and coalescence of poly-grain oxide islands.

Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat in response to cold-challenge to maintain core body temperature is essential for organismal survival. While cold activated BAT mitochondrial biogenesis is recognized as critical for thermogenic adaptation, the contribution of mitochondrial quality control to this process remains unclear. Here, we show mitophagy is required for brown adipocyte mitochondrial homeostasis during thermogenic adaptation. Mitophagy is significantly increased in BAT from cold-challenged mice (4 °C) and in β-agonist treated brown adipocytes. Blockade of mitophagy compromises brown adipocytes mitochondrial oxidative phosphorylation (OX-PHOS) capacity, as well as BAT mitochondrial integrity. Mechanistically, cold-challenge induction of BAT mitophagy is UCP1-dependent. Furthermore, our results indicate that mitophagy coordinates with mitochondrial biogenesis, maintaining activated BAT mitochondrial homeostasis. Collectively, our in vivo and in vitro findings identify mitophagy as critical for brown adipocyte mitochondrial homeostasis during cold adaptation.

The formate pathway and NADH pathway as two common hydrogen-producing metabolic pathways have been well characterized to understand and improve biohydrogen production. These two pathways have been thought to be separate and have been independently investigated. However, in this study, perturbation of genes (hycA, fdhF, fhlA, ldhA, nuoB, hybO, fdh1, narP, and ppk) in Enterobacter aerogenes related to the formate pathway or NADH pathway revealed that these two pathways affected each other. Further metabolic analysis suggested that a linear relationship existed between the relative change of hydrogen yield in the formate pathway or NADH pathway and the relative change of NADH yield or ATP yield. Thus, this finding provides new insight into the role of cellular reducing power and energy level in the hydrogen metabolism. It also establishes a rationale for improving hydrogen production from a global perspective.

A selective colon cancer cell therapy was effectively achieved with catalase-mediated intra-cellular heterogeneous Fenton reactions triggered by cellular uptake of SnFe2O4 nanocrystals. The treatment was proven effective for eradicating colon cancer cells, whereas was benign to normal colon cells, thus effectively realizing the selective colon cancer cell therapeutics. Cancer cells possess much higher innate hydrogen peroxide (H2O2) but much lower catalase levels than normal cells. Catalase, an effective H2O2 scavenger, prevented attacks on cells by reactive oxygen species induced from H2O2. The above intrinsic difference between cancer and normal cells was utilized to achieve selective colon cancer cell eradication through endocytosing efficient heterogeneous Fenton catalysts to trigger the formation of highly reactive oxygen species from H2O2. In this paper, SnFe2O4 nanocrystals, a newly noted outstanding paramagnetic heterogeneous Fenton catalyst, have been verified an effective selective colon cancerous cell treatment reagent of satisfactory blood compatibility.

Aged garlic extract (AGE) is widely used as a dietary supplement on account of its protective effects against oxidative stress and inflammation. But less is known about specific molecular targets of AGE and its bioactive components, including N-α-(1-deoxy-D-fructos-1-yl)-L-arginine (FruArg). Our recent study showed that both AGE and FruArg significantly attenuate lipopolysaccharide (LPS)-induced neuroinflammatory responses in BV-2 microglial cells. This study aims to unveil effects of AGE and FruArg on gene expression regulation in LPS stimulated BV-2 cells. Results showed that LPS treatment significantly altered mRNA levels from 2563 genes. AGE reversed 67% of the transcriptome alteration induced by LPS, whereas FruArg accounted for the protective effect by reversing expression levels of 55% of genes altered by LPS. Key pro-inflammatory canonical pathways induced by the LPS stimulation included toll-like receptor signaling, IL-6 signaling, and Nrf2-mediated oxidative stress pathway, along with elevated expression levels of genes, such as Il6, Cd14, Casp3, Nfkb1, Hmox1, and Tnf. These effects could be modulated by treatment with both AGE and FruArg. These findings suggests that AGE and FruArg are capable of alleviating oxidative stress and neuroinflammatory responses stimulated by LPS in BV-2 cells.

Fructose-based 3-acetyl-2,3-dihydro-1,3,4-oxadiazole (GLB) is a novel antitumor agent and belongs to glycosylated spiro-heterocyclic oxadiazole scaffold derivative. This research first reported a simple, specific, sensitive and stable high performance liquid chromatography -ultraviolet detector (HPLC-UV) method for the quantitative determination of GLB in plasma. In this method, the chromatographic separation was achieved with a reversed phase C18 column. The calibration curve for GLB was linear at 300 nm. The lower limit of quantification was 10 ng/mL. The precision, accuracy and stability of the method were validated adequately. This method was successfully applied to the pharmacokinetic study in rats for detection of GLB after oral administration. Moreover, the structures of parent compound GLB and its two major metabolites M1 and M2 were identified in plasma using an ultra performance liquid chromatography- electrospray ionization-quadrupole-time of flight- mass spectrometry (UPLC-ESI-QTOF-MS) method. Our results indicated that the di-hydroxylation (M1) and hydroxylation (M2) of GLB are the major metabolites. In conclusion, the present study provided valuable information on an analytical method for the determination of GLB and its metabolites in rats, can be used to support further developing of this antitumor agent.

We report the development of a well-defined flagellin-based nanoparticle stimulator and also provide a new mechanism of action model explaining how flagellin-triggered innate immunity has evolved to favor localized rather than potentially debilitating systemic immune stimulation. Cell-free protein synthesis (CFPS) was used to facilitate mutational analysis and precisely orientated display of flagellin on Hepatitis B core (HBc) protein virus-like particles (VLPs). The need for product stability and an understanding of mechanism of action motivated investigations indicating that the D0 domain of flagellin is sensitive to amino acid sequence independent hydrolysis – apparently due to the need for structural flexibility during natural flagellin polymerization. When D0-stabilized flagellin was attached to HBc VLPs with the D0 domain facing outward, flagellin’s tendency to polymerize caused the VLPs to precipitate. However, attaching the D0 domain to the VLP surface produced a stable nanoparticle adjuvant. Surprisingly, attaching only 2 flagellins per VLP provided the same 1 pM potency as did VLPs with about 33 attached flagellins suggesting that the TLR5 receptor is highly effective in delivering its intracellular signal. These observations suggest that flagellin’s protease sensitivity, tendency to aggregate and very high affinity for TLR5 receptors limit its systemic distribution to favor localized immune stimulation.

Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy.

Germline/embryonic-specific genes have been found to be activated in somatic tumors. In this study, we further showed that cells functioning as germline could be present in mouse fibrosarcoma cells (L929 cell line). Early germline-like cells spontaneously appeared in L929 cells and further differentiated into oocyte-like cells. These germline-like cells can, in turn, develop into blastocyst-like structures in vitro and cause teratocarcinomas in vivo, which is consistent with natural germ cells in function. Generation of germline-like cells from somatic tumors might provide a novel way to understand why somatic cancer cells have strong features of embryonic/germline development. It is thought that the germline traits of tumors are associated with the central characteristics of malignancy, such as immortalization, invasion, migration and immune evasion. Therefore, germline-like cells in tumors might provide potential targets to tumor biology, diagnosis and therapy.