[Distribution Characteristics and Source Analysis of Atmospheric Mercury Speciation in Suzhou].

To explore the variation of mercury in the atmosphere in Suzhou, continuous monitoring of gaseous element mercury (GEM), gaseous oxidized mercury (GOM), and particulate bound mercury (PBM) was conducted from January 1 to December 31, 2018, in Suzhou. The weights trajectory analysis method (CWT) and concentration rose were used to analyze the atmospheric mercury sources and concentration variation. The results showed that during the monitoring period, the concentration ranges of GEM, GOM, and PBM in Suzhou were 0-53.3 ng·m-3, 0-256 pg·m-3, and 0-5208 pg·m-3, respectively. The corresponding annual average concentrations of the three mercury species were (2.57±2.09) ng·m-3, (5.27±15.7) pg·m-3, and (16.0±157) pg·m-3, respectively. GEM was the main component of atmospheric mercury in Suzhou. During the monitoring period, the average concentration of GEM in Suzhou was highest in winter, higher in spring than in autumn, and lowest in summer. According to the CWT, the mercury-containing air mass in spring and winter predominantly originated from inland; in summer, it mainly originated from the local area, the Yellow Sea, and the East China Sea, and in autumn from inland, the Yellow Sea, and the Bohai Sea. The wind and mercury rose charts showed that atmospheric mercury concentrations were higher from inland and lower from the ocean. During the monitoring period, the average concentrations of GEM and PBM in Suzhou were lower during the day than the night. The diurnal variation of GEM and PBM was significantly and strongly correlated with solar radiation, humidity, and air temperature. The average concentration of GOM showed multiple peaks and valleys in one day. Some peaks were caused by fuel oil combustion emissions, and some by O3 oxidation with GEM.

ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α.

BACKGROUND & AIMS: Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown. METHODS: The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model. Effects of ADRB2 signaling inhibition in HCC cell lines were analyzed in proliferation, apoptosis, colony formation assays. Autophagy regulation by ADRB2 was assessed in immunoblotting, immunofluorescence and immunoprecipitation assays. In vivo tumorigenic properties and anticancer effects of sorafenib were examined in nude mice. Expression levels of ADRB2 and hypoxia-inducible factor-1α (HIF1α) in 150 human HCC samples were evaluated by immunohistochemistry. RESULTS: We uncovered that adrenaline promoted DEN-induced hepatocarcinogenesis, which was reversed by the ADRB2 antagonist ICI118,551. ADRB2 signaling also played an essential role in sustaining HCC cell proliferation and survival. Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization, reprogramming of HCC cells glucose metabolism, and the acquisition of resistance to sorafenib. Conversely, inhibition of ADRB2 signaling by ICI118,551, or knockdown ADRB2 expression, led to enhanced autophagy, HIF1α destabilization, tumor growth suppression, and improved anti-tumor activity of sorafenib. Consistently, ADRB2 expression correlated positively with HIF1α in HCC specimens and was associated with HCC outcomes. CONCLUSIONS: Our results uncover an important role of ADRB2 signaling in regulating HCC progression. Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance. LAY SUMMARY: ADRB2 signaling played an essential role in sustaining hepatocellular carcinoma cell proliferation and survival. ADRB2 signaling negatively regulated autophagy, leading to hypoxia-inducible factor-1α stabilization, reprogramming of hepatocellular carcinoma cells glucose metabolism, and the acquisition of resistance to sorafenib. Adrenoceptor antagonist appears to be a putative novel treatment for hepatocellular carcinoma and chemoresistance.

Epigenetically silenced long noncoding-SRHC promotes proliferation of hepatocellular carcinoma.

PURPOSE: To investigate the expression of SRHC and the role of SRHC in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We analyzed HCC samples and matched non-tumor liver tissues (controls) collected from 81 patients who underwent hepatectomy in Shanghai, China. The expression levels of SRHC were determined by quantitative reverse-transcription polymerase chain reaction. Statistical analyses were used to associate the levels of SRHC with tumor features and patient outcomes. RESULTS: We found that a lower SRHC expression level was significantly more frequent in tissues with a high serum a-fetoprotein level (positive, >20 µg/L, P = 0.004) and a low degree of differentiated tumors (poorly differentiated, P = 0.017). Furthermore, we found that the promoter region of SRHC contains a CpG-rich island and that SRHC is down-regulated in tumors by DNA methylation. CONCLUSION: Here, we identified a new long noncoding RNA designated as SRHC that is capable of inhibiting cancer proliferation and is down-regulated in tumors at least partly by DNA methylation.

Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein.

Increasing evidence suggests that TLR4 expression by tumour cells promotes tumour progression, but it is unclear whether TLR4 is involved in metastasis. Here we show that TLR4 deficiency significantly diminishes experimental lung metastasis without affecting primary tumour growth. Bone marrow transplantation experiment and application of antiplatelet agents in mice demonstrate that TLR4 on platelets plays an important role in metastasis. TLR4 is critical for platelet-tumour cell interaction in vitro. Furthermore, high-mobility group box1 (HMGB1) neutralization attenuates platelet-tumour cell interaction in vitro and metastasis in vivo in a TLR4-dependent manner, indicating that tumour cell-released HMGB1 is the key factor that interacts with TLR4 on platelets and mediates platelet-tumour cell interaction, which promotes metastasis. These findings demonstrate a mechanism by which platelets promote tumour cell metastasis and suggest TLR4, and its endogenous ligand HMGB1 as targets for antimetastatic therapies.

Analysis of midgut gene expression profiles from different silkworm varieties after exposure to high temperature.

The silkworm is a poikilothermic animal, whose growth and development is significantly influenced by environmental temperature. To identify genes and metabolic pathways involved in the heat-stress response, digital gene expression analysis was performed on the midgut of the thermotolerant silkworm variety '932' and thermosensitive variety 'HY' after exposure to high temperature (932T and HYT). Deep sequencing yielded 6,211,484, 5,898,028, 5,870,395 and 6,088,303 reads for the 932, 932T, HY and HYT samples, respectively. The annotated genes associated with these tags numbered 4357, 4378, 4296 and 4658 for the 932, 932T, HY and HYT samples, respectively. In the HY-vs-932, 932-vs-932T, and HY-vs-HYT comparisons, 561, 316 and 281 differentially expressed genes were identified, which could be assigned to 179, 140 and 123 biological pathways, respectively. It was found that some of the biological pathways, which included oxidative phosphorylation, related to glucose and lipid metabolism, are greatly affected by high temperature and may lead to a decrease in the ingestion of fresh mulberry. When subjected to an early period of continuous heat stress, HSP genes, such as HSP19.9, HSP23.7, HSP40-3, HSP70, HSP90 and HSP70 binding protein, are up-regulated but then reduced after 24h and the thermotolerant '932' strain has higher levels of mRNA of some HSPs, except HSP70, than the thermosensitive variety during continuous high temperature treatment. It is suggested that HSPs and the levels of their expression may play important roles in the resistance to high temperature stress among silkworm varieties. This study has generated important reference tools that can be used to further analyze the mechanisms that underlie thermotolerance differences among silkworm varieties.

Tumor size does not independently affect long-term survival after curative resection of solitary hepatocellular carcinoma without macroscopic vascular invasion.

OBJECTIVE: The aim of this study was to investigate the prognostic value of tumor size alone on long-term survival and recurrence after curative resection for solitary hepatocellular carcinoma (HCC) without macroscopic vascular invasion. METHODS: A single-center cohort of 615 patients with solitary HCC (a single tumor, without macroscopic vascular invasion or distant metastasis) undergoing curative hepatic resection from 2002 to 2010 was retrospectively studied. Using 2.0, 3.0, 4.0, 5.0, 8.0, and 10.0 cm as cut-off values of tumor size, the overall survival (OS) and recurrence-free survival (RFS) rates were compared between the groups of patients with tumor size up to a certain cut-off value and the groups of patients with tumor size above that cut-off value. Thus, multiple comparisons were done. The prognostic factors of OS and RFS were evaluated using univariate and multivariate analyses. RESULTS: The median tumor size of all HCCs was 4.0 cm (range 0.9-22.0 cm). The in-hospital mortality rate was 1.0 %, and the overall morbidity rate was 22.3 %. The 1-, 3-, and 5-year OS rates were 96.0, 79.8, and 69.9 %, and the corresponding RFS rates were 83.6, 72.7, and 57.2 %, respectively. On univariate analyses, the 1-, 3-, and 5-year OS and RFS rates were significantly different between the individual two groups of patients as divided by the aforementioned different cut-off values of tumor sizes (all p < 0.05). However, when tumor size was put as a continuous variable into multivariate analysis, it was no longer an independent prognostic factor of OS or RFS after curative resection. CONCLUSIONS: Tumor size did not independently affect long-term survival and recurrence after curative resection of solitary HCC without macroscopic vascular invasion. Therefore, there is no size limit that precludes hepatic resection for solitary HCC, provided the tumor is resectable.

Role of ß-Catenin in regulating the balance between TNF-α- and Fas-induced acute liver injury.

ß-Catenin plays many critical roles during various liver physiological and pathological processes. However, the role of ß-Catenin in acute liver failure remains unclear. Using hepatocyte specific ß-Catenin knockout mice, we found that loss of ß-Catenin in hepatocyte significantly reduced GalN/LPS-induced liver damage and hepatocyte apoptosis, but exacerbated Jo2-mediated liver injury. Mechanistically, the dual effects of ß-Catenin attributes on its function of inhibiting NF-κB signaling, which aggravates oxidative stress but decreases Fas expression under injury conditions. In conclusion, ß-Catenin plays an important role in regulating the balance between TNF-α and Fas-induced liver injury via its effect on NF-κB.

Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats.

BACKGROUND & AIMS: Due to its anatomic connection, the liver is constantly exposed to gut-derived bacterial products or metabolites. Disruption of gut homeostasis is associated with many human diseases. The aim of this study was to determine the role of gut homeostasis in initiation and progression of hepatocellular carcinoma (HCC). METHODS: Disruption of intestinal homeostasis by penicillin or dextran sulfate sodium (DSS) and its restoration by probiotics were applied in a diethylnitrosamine (DEN) model of rat hepatocarcinogenesis. RESULTS: Patients with liver cirrhosis and HCC had significantly increased serum endotoxin levels. Chronic DEN treatment of rats was associated with an imbalance of subpopulations of the gut microflora including a significant suppression of Lactobacillus species, Bifidobacterium species and Enterococcus species as well as intestinal inflammation. Induction of enteric dysbacteriosis or intestinal inflammation by penicillin or DSS, respectively, significantly promoted tumor formation. Administration of probiotics dramatically mitigated enteric dysbacteriosis, ameliorated intestinal inflammation, and most importantly, decreased liver tumor growth and multiplicity. Interestingly, probiotics not only inhibited the translocation of endotoxin, which bears pathogen-associated molecular patterns (PAMPs) but also the activation of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1). As a result, the production of pro- and anti-inflammatory cytokines was skewed in favor of a reduced tumorigenic inflammation in the liver. CONCLUSIONS: The data highlights the importance of gut homeostasis in the pathogenesis of HCC. Modulation of the gut microbiota by probiotics may represent a new avenue for therapeutic intervention to treat or prevent HCC development.

[Precision measurement of the birefringence of quartz crystal at 1 310 nm based on the spectroscopic ellipsometer].

In order to get the precision measurement of birefringence of quartz crystal at the communication wavelength 1310nm, based on the principle of precision measurement of phase difference between P and S polarized lights of spectroscopic ellipsometer, a method for precision measurement of birefringence of crystal was designed through the analysis of the Jones matrix under the transmission mode, and the precision measurement of birefringence of quartz crystal at 1 310 nm at room temperature (22 degrees C) was made, the measuring results and error analysis show that the precision reached 10(-6) level, this is the most precise birefringence parameter available, and it is of important significance for the improvement of designing precision of phase retardation devices of quartz.

OV6⁺ tumor-initiating cells contribute to tumor progression and invasion in human hepatocellular carcinoma.

BACKGROUND & AIMS: Accumulating evidence suggests the involvement of tumor-initiating cells (T-ICs) in cancer genesis, but whether liver T-ICs contribute to HCC invasion and metastasis remains unclear. METHODS: OV6(+) T-ICs were isolated from SMMC7721 and HuH7 cell lines by magnetic sorting. Characteristics of T-ICs were assessed by in vitro and mouse xenograft assays. Expression of OV6 was determined by immunostaining in specimens from 218 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of OV6 expression with prognosis. RESULTS: OV6(+) T-ICs isolated from HCC cell lines not only possess a higher capacity to form tumor spheroids in vitro, but also had a greater potential to form tumors when implanted in non-obese diabetic/severe combined immunodeficient mice, suggesting their elevated self-renewal capacity and tumorigenicity. Moreover, OV6(+) T-ICs exhibited more invasive and metastatic potentials both in vitro and in vivo. Patients with more OV6(+) tumor cells were associated with aggressive clinicopathologic features and poor prognosis. CXCR4 is expressed at higher levels in OV6(+) cells. Recombinant stromal cell-derived factor-1 (SDF-1) treatment expanded the OV6(+) HCC T-ICs population, by sustaining the stem cell property of OV6(+) cells. The SDF-1 effect was blocked by a specific CXCR4 inhibitor, AMD3100, or transfection of siRNA targeting CXCR4. CONCLUSIONS: OV6(+) HCC cells may represent a subpopulation of T-ICs with augmented invasion and metastasis potential, which contribute to progression and metastasis of HCC. The SDF-1/CXCR4 axis also provides therapeutic targets for elimination of liver T-ICs.

Hepatitis B virus X (HBx) induces tumorigenicity of hepatic progenitor cells in 3,5-diethoxycarbonyl-1,4-dihydrocollidine-treated HBx transgenic mice.

UNLABELLED: Hepatitis B virus X (HBx) protein is implicated in hepatitis B virus (HBV)-associated liver carcinogenesis. However, it remains unclear whether HBx-expressing hepatic progenitor cells (HPCs) are attributed to liver tumor formation. In this study, by using HBx transgenic mice and a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver injury model, the relationship between HBx expression and tumorigenicity of HPCs was analyzed. Compared with control mice, an elevated number of EpCAM(+) cells with characteristics of HPCs was observed in HBx mice after 1 month and 4 months of DDC diet feeding. All HBx transgenic mice developed liver tumors characterized by histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma after 7 months of DDC feeding. Notably, EpCAM(+) HPCs isolated from premalignant HBx mice exposed to a DDC diet for 4 months formed subcutaneous mixed-lineage tumors (four out of six) in nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice, and none of the cells from wildtype (WT) induced tumor, indicating that HBx may induce malignant transformation of HPCs that contributes to tumorigenesis. We also found higher titers of circulating interleukin (IL)-6, activities of IL-6/STAT3, and Wnt/ß-catenin signaling pathways in HBx transgenic mice, suggesting HBx may induce intrinsic changes in HPCs by way of the above signaling that enables HPCs with tumorigenicity potential. Finally, clinical evidence showed that high HBx expression in human HBV-related HCC was statistically associated with expansion of EpCAM(+) or OV6(+) tumor cells and aggressive clinicopathologic features. CONCLUSION: HBx induces intrinsic cellular transformation promoting the expansion and tumorigenicity of HPCs in DDC-treated mice, which may be a possible origin for liver cancer induced by chronic hepatitis infection.

[Spectral analysis method for precisely measuring specific rotation of quartz].

A spectral analysis method for precisely measuring specific rotation of quartz is proposed. The measuring principle is analyzed by using the method of optical matrix. The result indicates that the specific rotation of quartz can be exactly calculated by measuring the transmittance curve of a sample quartz plate sandwiched between two paralleled polarizing prisms, and the correctness of the method is validated by a designed experiment using a spectrophotometer. The data is analyzed, and the rotary dispersion formula of quartz is fitted. Compared with Lowry' formula, our formula is more accurate in visible spectral scope. Errors in the experiment is analyzed and the result shows that the measuring accuracy will be improved by choosing thicker quartz plate, longer wave band, lower scan speed, and smaller slit width.

[Testing research of achromatic phase retarder's spectral character].

Using established testing system by principle of normalized polarizing modulation, we measured the spectral characters of normal Fresnel rhomb, improved Fresnel rhomb, oblique-incidence rhomb and rectangle prism compound rhomb phase retarders. Through the measured spectral we yield the characteristic achromatism curves of all kinds of achromatic phase retarders, and analyse the results. The results indicate that the achromatism of the improved Fresnel rhomb and rectangle prism compound rhomb phase retarders is superior to others. Currently the improved Fresnel rhomb and retangle prism compound rhomb phase retarders are the ideal and utility-type achromatic phase retarders.