We have carried out a combined experimental and simulation study identifying the key physical and optical parameters affecting the presence and degree of fluorescence intensification measured on zinc oxide nanorod (ZnO NR) ends. Previously, we reported on the highly localized, intensified, and prolonged fluorescence signal measured on the NR ends, termed as fluorescence intensification on NR ends (FINE). As a step towards understanding the mechanism of FINE, the present study aims to provide an insight into the unique optical phenomenon of FINE through experimental and simulation approaches and to elucidate the key factors affecting the occurrence, degree, and temporal stability of FINE. Specifically, we examined the effect of the length, width, and growth orientation of single ZnO NRs on the NR-enhanced biomolecular emission profile after decorating the NR surfaces with different amounts and types of fluorophore-coupled protein molecules. We quantitatively and qualitatively profiled the biomolecular fluorescence signal from individual ZnO NRs as a function of both position along the NR long axis and time. Regardless of the physical dimensions and growth orientations of the NRs, we confirmed the presence of FINE from all ZnO NRs tested by using a range of protein concentrations. We also showed that the manifestation of FINE is not dependent on the spectroscopic signatures of the fluorophores employed. We further observed that the degree of FINE is dependent on the length of the NR with longer NRs showing increased levels of FINE. We also demonstrated that vertically oriented NRs exhibit much stronger fluorescence intensity at the NR ends and a higher level of FINE than the laterally oriented NRs. Additionally, we employed finite-difference time-domain (FDTD) methods to understand the experimental outcomes and to promote our understanding of the mechanism of FINE. Particularly, we utilized the electrodynamic simulations to examine both near-field and far-field emission characteristics when considering various scenarios of fluorophore locations, polarizations, spectroscopic characteristics, and NR dimensions. Our efforts may provide a deeper insight into the unique optical phenomenon of FINE and further be beneficial to highly miniaturized biodetection favoring the use of single ZnO NRs in low-volume and high-throughput protein assays.

SUMMARY The spatiotemporal localization and expression of Dll4 are critical for sprouting angiogenesis. However, the related mechanisms are poorly understood. Here we show that G-protein-coupled receptor-kinase interacting protein-1 (GIT1) is a robust endogenous inhibitor of Dll4-Notch1 signaling that specifically controls stalk cell fate. GIT1 is highly expressed in stalk cells but not in tip cells. GIT1 deficiency remarkably enhances Dll4 expression and Notch1 signaling resulting in impaired retinal sprouting angiogenesis, which can be rescued by treatment with the Notch inhibitor, or Dll4 neutralizing antibody. Notch1 regulates Dll4 expression by binding to recombining binding protein suppressor of hairless (RBP-J, a transcriptional regulator of Notch) via a highly conserved ankyrin (ANK) repeat domain. We show that GIT1, which also contains an ANK domain, inhibits the Notch1-Dll4 signaling pathway by competing with Notch1 ANK domain for binding to RBP-J in stalk cells.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, mainly because of its poor prognosis. A valid mechanism-based prognostic biomarker is urgently needed. c-hydroxy-1,N 2 -propanodeoxyguanosine (c-OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation. We examined the relationship of cOHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in xeroderma pigmentosum group A knockout mice and diethylnitrosamine-injected mice, both prone to HCC development. c-OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on c-OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between c-OHPdG and survival or recurrence-free survival. c-OHPdG levels in liver DNA showed an age-dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased c-OHPdG levels in the liver DNA of xeroderma pigmentosum group A knockout mice and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the diethylnitrosamine-injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of c-OHPdG are strongly associated with low survival (P < 0.0001) and low recurrence-free survival (P 5 0.007). Conclusion: These results support c-OHPdG as a mechanism-based, biologically relevant biomarker for predicting the risk of HCC and its recurrence. (HEPATOLOGY 2018;67:159-170). SEE EDITORIAL ON PAGE 10G enetic and epigenetic alterations in oncogenes and tumor-suppressor genes are crucial for carcinogenesis.(1,2) Somatic mutations may arise from DNA lesions that are not repaired. During a lifetime, the human genome will host a wide spectrum of mutagenic DNA lesions, induced by chemical carcinogens, viruses, and reactive oxygen and nitrogen species. This is believed to be the case for human liver as it is a major detoxifying organ that is exposed to a large number of risk factors. (3)(4)(5) Primary liver cancer is the third most common cause of cancer-related death, which stems from the lack of suitable biomarkers for early detection, inadequate understanding of the molecular features, and resistance

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