111In-Labeled Cystine-Knot Peptides Based on the Agouti-Related Protein for Targeting Tumor Angiogenesis

Agouti-related protein (AgRP) is a 4-kDa cystine-knot peptide of human origin with four disulfide bonds and four solvent-exposed loops. The cell adhesion receptor integrin αvβ3 is an important tumor angiogenesis factor that determines the invasiveness and metastatic ability of many malignant tumors. AgRP mutants have been engineered to bind to integrin αvβ3 with high affinity and specificity using directed evolution. Here, AgRP mutants 7C and 6E were radiolabeled with 111In and evaluated for in vivo targeting of tumor integrin αvβ3 receptors. AgRP peptides were conjugated to the metal chelator 1, 4, 7, 10-tetra-azacyclododecane- N, N′, N″, N‴-tetraacetic acid (DOTA) and radiolabeled with 111In. The stability of the radiopeptides 111In-DOTA-AgRP-7C and 111In-DOTA-AgRP-6E was tested in phosphate-buffered saline (PBS) and mouse serum, respectively. Cell uptake assays of the radiolabeled peptides were performed in U87MG cell lines. Biodistribution studies were performed to evaluate the in vivo performance of the two resulting probes using mice bearing integrin-expressing U87MG xenograft tumors. Both AgRP peptides were easily labeled with 111In in high yield and radiochemical purity (>99%). The two probes exhibited high stability in phosphate-buffered saline and mouse serum. Compared with 111In-DOTA-AgRP-6E, 111In-DOTA-AgRP-7C showed increased U87MG tumor uptake and longer tumor retention (5.74 ± 1.60 and 1.29 ± 0.02%ID/g at 0.5 and 24 h, resp.), which was consistent with measurements of cell uptake. Moreover, the tumor uptake of 111In-DOTA-AgRP-7C was specifically inhibited by coinjection with an excess of the integrin-binding peptidomimetic c(RGDyK). Thus, 111In-DOTA-AgRP-7C is a promising probe for targeting integrin αvβ3 positive tumors in living subjects

Genome-wide Association Study Identifies New Loci Associated With Risk Of HBV Infection And Disease Progression

Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population. Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression

Short-Term Side Effects after Radioiodine Treatment in Patients with Differentiated Thyroid Cancer

Objectives. I-131 therapy for differentiated thyroid cancer (DTC) could induce adverse effects. The purpose of this study was to report and analyze symptoms after I-131 treatment within the hospitalization and present relevant medical intervention. Methods. I-131 doses ranging from 3.7 to 9.25 GBq (100–250 mCi) were administrated for thyroid remnant ablation or treating DTC metastases. 117 patients with DTC for I-131 therapy were monitored through the video and intercommunicating with standardized questionnaire at different time points after I-131 oral administration. Adverse effects were recorded and relevant clinical factors were analyzed. Results. Among all the 117 patients, 55 cases complained of neck’s pain or swelling and 79 cases presented with gastrointestinal symptoms. Pain or swelling of salivary gland occurred in 15 patients, headache and vertigo in 10, insomnia in 9, vocal cord paralysis in 6, fatigue or general malaise in 6, and foreign body sensation in 5. Body numbness and urinary symptoms were observed in only 1 case, respectively. Those side effects were related with sex, pre-I-131 treatment TSH levels, frequency of I-131 therapy, and lymph node metastases. Conclusions. Short-term side effects after I-131 therapy for DTC patients varied individually; severe symptoms were not uncommon but generally did not need emergent medical intervention

A Deep-Neural-Network-Based Aerosol Optical Depth (AOD) Retrieval from Landsat-8 Top of Atmosphere Data

The 30 m resolution Landsat data have been used for high resolution aerosol optical depth (AOD) retrieval based on radiative transfer models. In this paper, a Landsat-8 AOD retrieval algorithm is proposed based on the deep neural network (DNN). A total of 6390 samples were obtained for model training and validation by collocating 8 years of Landsat-8 top of atmosphere (TOA) data and aerosol robotic network (AERONET) AOD data acquired from 329 AERONET stations over 30°W–160°E and 60°N–60°S. The Google Earth Engine (GEE) cloud-computing platform is used for the collocation to avoid a large download volume of Landsat data. Seventeen predictor variables were used to estimate AOD at 500 nm, including the seven bands TOA reflectance, two bands TOA brightness (BT), solar and viewing zenith and azimuth angles, scattering angle, digital elevation model (DEM), and the meteorological reanalysis total columnar water vapor and ozone concentration. The leave-one-station-out cross-validation showed that the estimated AOD agreed well with AERONET AOD with a correlation coefficient of 0.83, root-mean-square error of 0.15, and approximately 61% AOD retrievals within 0.05 + 20% of the AERONET AOD. Theoretical comparisons with the physical-based methods and the adaptation of the developed DNN method to Sentinel-2 TOA data with a different spectral band configuration are discussed

Evaluation of the Multi-Angle Implementation of Atmospheric Correction (MAIAC) Aerosol Algorithm for Himawari-8 Data

Himawari-8, operated by the Japan Meteorological Agency (JMA), is a new generation geostationary satellite that provides remote sensing data to retrieve atmospheric aerosol optical depth (AOD) at high spatial (1 km) and high temporal (10 min) resolutions. The Geostationary- National Aeronautics and Space Administration (NASA) Earth exchange (GeoNEX) project recently adapted the multiangle implementation of atmospheric correction (MAIAC) algorithm, originally developed for joint retrieval of AOD and surface anisotropic reflectance with the moderate resolution imaging spectroradiometer (MODIS) data, to generate Earth monitoring products from the latest geostationary satellites including Himawari-8. This study evaluated the GeoNEX Himawari-8 ~1 km MAIAC AOD retrieved over all the aerosol robotic network (AERONET) sites between 6°N–30°N and 91°E–127°E. The corresponding JMA Himawari-8 AOD products were also evaluated for comparison. We only used cloud-free and the best quality satellite AOD retrievals and compiled a total of 16,532 MAIAC-AERONET and 21,737 JMA-AERONET contemporaneous pairs of AOD values for 2017. Statistical analyses showed that both MAIAC and JMA data are highly correlated with AERONET AOD, with the correlation coefficient (R) of ~0.77, and the root mean squared error (RMSE) of ~0.16. The absolute bias of MAIAC AOD (0.02 overestimation) appears smaller than that of the JMA AOD (0.05 underestimation). In comparison with the JMA data, the time series of MAIAC AOD were more consistent with AERONET AOD values and better capture the diurnal variations of the latter. The dependence of MAIAC AOD bias on scattering angles is also discussed

Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism

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New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus (HBV) infection failed to clear HBV, even persistently continue to produce antibodies to HBV. Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV. The first stage involved genome wide exome sequencing of 101 cases (HBsAg plus anti-HBs positive) compared with 102 control patients (anti-HBs positive, HBsAg negative). Over 80% of individual sequences displayed 20 × sequence coverage. Adapters, uncertain bases \u3e 10% or low-quality base calls (\u3e 50%) were filtered and compared to the human reference genome hg19. In the second stage, 579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage. Although there were no significant associated gene variants in the first stage, two significant gene associations were discovered when the two stages were assessed in a combined analysis. One association showed rs506121-“T” allele [within the dedicator of cytokinesis 8 (DOCK8) gene] was higher in chronic HBV infection group than that in clearance group (P = 0.002, OR = 0.77, 95% CI [0.65, 0.91]). The second association involved rs2071676—A allele within the Carbonic anhydrase (CA9) gene that was significantly elevated in chronic HBV infection group compared to the clearance group (P = 0.0003, OR = 1.35, 95% CI [1.15, 1.58]). Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection