Stimulated emission depletion microscopy provides a powerful sub-diffraction imaging modality for life science studies. Conventionally, stimulated emission depletion requires a relatively high light intensity to obtain an adequate depletion efficiency through only light–matter interaction. Here we show efficient emission depletion for a class of lanthanide-doped upconversion nanoparticles with the assistance of interionic cross relaxation, which significantly lowers the laser intensity requirements of optical depletion. We demonstrate two-color super-resolution imaging using upconversion nanoparticles (resolution ~ 66 nm) with a single pair of excitation/depletion beams. In addition, we show super-resolution imaging of immunostained cytoskeleton structures of fixed cells (resolution ~ 82 nm) using upconversion nanoparticles. These achievements provide a new perspective for the development of photoswitchable luminescent probes and will broaden the applications of lanthanide-doped nanoparticles for sub-diffraction microscopic imaging.
Hepatitis B virus (HBV) mutations and signal transducer and activator of transcription 3 (STAT3) activation are closely associated with hepatocellular carcinoma (HCC). However, single nucleotide polymorphisms (SNPs) of STAT3 have not been implicated in HCC susceptibility. This study was designed to evaluate the effect of STAT3 SNPs and their interactions with HBV mutations on HCC risk. A total of 2,011 HBV-infected subjects (including 1,021 HCC patients) and 1,012 healthy controls were involved in this study. SNPs rs4796793 (21697, C>G), rs2293152 (intron 11, C>G), and rs1053004 (3 0 untranslated region, T>C) were genotyped using quantitative polymerase chain reaction. HBV mutations were determined via direct sequencing. It was found that rs2293152 (GG versus CC) was significantly associated with HCC risk compared with the subjects without HCC, adjusting for age and sex (adjusted odds ratio [AOR], 1.30; 95% confidence interval [CI], 1.04-1.62). The impact of rs2293152 was greater in women compared with men. Compared with HCC-free HBV-infected subjects, rs2293152 GG was solely associated with HCC in women (AOR, 2.04; 95% CI, 1.15-3.61). rs2293152 GG was significantly associated with high viral load (!1 3 10 4 copies/mL) (AOR, 1.37; 95%, CI 1.01-1.88) and increased frequencies of T1674C/G (AOR, 1.61; 95% CI, 1.06-2.46) and A1762T/ G1764A (AOR, 1.64; 95% CI, 1.14-2.35). In multivariate regression analyses, multiplicative interaction of rs1053004 with T1674C/G significantly increased HCC risk, whereas rs2293152 and A1726C interaction reduced it, adjusting for covariates including HBV mutations in the enhancer II/basal core promoter/precore region; the interaction of rs4796793 with preS2 start codon mutation significantly increased HCC risk, adjusting for covariates including HBV mutations in the preS region. Conclusion: STAT3 SNPs appear to predispose the host with HBV mutations to hepatocarcinogenesis, and this effect may differ in men versus women. STAT3 SNPs may have applicability in future HCC surveillance algorithms. (HEPATOLOGY 2013; 57:2369-2377 L iver cancer in males is the fifth most frequently diagnosed cancer and the second most frequent cause of cancer-related death; in females, it is the seventh most commonly diagnosed cancer and the sixth leading cause of cancer death worldwide.1 Hepatocellular carcinoma (HCC) accounts for 70% to 85% of the total liver cancer burden.1 The highest HCC incidence rates are found in East and Southeast Asia and in sub-Saharan Africa. The rate is three-fold higher in males than in females. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), aflatoxin B1 exposure, alcohol drinking,
Background: SARS-CoV-2-caused coronavirus disease (COVID-19) is posing a large casualty. The features of COVID-19 patients with and without pneumonia, SARS-CoV-2 transmissibility in asymptomatic carriers, and factors predicting disease progression remain unknown. Methods: We collected information on clinical characteristics, exposure history, and laboratory examinations of all laboratory-confirmed COVID-19 patients admitted to PLA General Hospital. Cox regression analysis was applied to identify prognostic factors. The last follow-up was February 18, 2020. Results: We characterized 55 consecutive COVID-19 patients. The mean incubation was 8.42 (95% confidence interval [CI], 6.55-10.29) days. The mean SARS-CoV-2-positive duration from first positive test to conversion was 9.71 (95%CI, 8.21-11.22) days. COVID-19 course was approximately 2 weeks. Asymptomatic carriers might transmit SARS-CoV-2. Compared to patients without pneumonia, those with pneumonia were 15 years older and had a higher rate of hypertension, higher frequencies of having a fever and cough, and higher levels of interleukin-6 (14.61 vs. 8.06pg/mL, P=0.040), B lymphocyte proportion (13.0% vs.10.0%, P=0.024), low account (<190/µL) of CD8 + T cells (33.3% vs. 0, P=0.019). Multivariate Cox regression analysis indicated that circulating interleukin-6 and lactate independently predicted COVID-19 progression, with a hazard ratio (95%CI) of 1.052 (1.000-1.107) and 1.082 (1.013-1.155), respectively. During disease course, T lymphocytes were .CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not peer-reviewed) The copyright holder for this preprint .
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