Polypyrimidine tract-binding protein 3/insulin-like growth factor 2 mRNA-binding proteins 3/high-mobility group A1 axis promotes renal cancer growth and metastasis.

Polypyrimidine tract-binding protein 3 (PTBP3) plays an important role in the post-transcriptional regulation of gene expression, including mRNA splicing, translation, and stability. Increasing evidence has shown that PTBP3 promotes cancer progression in several tumor types. However, the molecular mechanisms of PTBP3 in renal cell carcinoma (RCC) remain unknown. Here, tissue microarrays (TMAs) suggested that PTBP3 expression was increased in human RCC and that high PTBP3 expression was correlated with poor five-year overall survival and disease-free survival. We also showed that PTBP3 binds with HMGA1 mRNA in the 3'UTR region and let-7 miRNAs. PTBP3 interacted with IGF2BP3, and the PTBP3/IGF2BP3 axis prevented let-7 mediated HMGA1 mRNA silencing. PTBP3 promotes renal cancer cell growth and metastasis in vitro and in vivo. Taken together, our findings indicate PTBP3 serves as a regulator of HMGA1 and suggest its potential as a therapeutic agent for RCC.

Controlling Nutritional Status (CONUT) score is a prognostic marker in III-IV NSCLC patients receiving first-line chemotherapy.

BACKGROUND: To investigate the prognostic impact of the controlling nutritional status (CONUT) score in non-small-cell lung cancer (NSCLC) patients receiving first-line chemotherapy. METHODS: We retrospectively reviewed 278 consecutive patients undergoing chemotherapy for stage III-IV NSCLC between May 2012 and July 2020. CONUT score was calculated by incorporating serum albumin, total cholesterol, and total lymphocyte count. The patients were divided into two groups: CONUT ≥ 3 and CONUT < 3, according to receiver operating characteristic (ROC) analysis. The associations of CONUT with clinicopathological factors and survival were evaluated. RESULTS: A high CONUT score was significantly associated with older age(P = 0.003), worse ECOG-PS(P = 0.018), advanced clinical stage(P = 0.006), higher systematic inflammation index (SII) (P < 0.001)and lower prognostic nutritional index (PNI) (P < 0.001).The high CONUT group had a significantly shorter progression-free survival(PFS) and overall survival(OS) than the low CONUT group. In the univariate analysis, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse PFS (Pall < 0.05). Worse ECOG-PS, higher SII, higher CONUT, advanced clinical stage and lower PNI were associated with worse OS (Pall < 0.05). In multivariate analysis, CONUT(HR, 2.487; 95%CI 1.818 ~ 3.403; P < 0.001) was independently associated with PFS, while PNI(HR, 0.676; 95%CI 0.494 ~ 0.927; P = 0.015) and CONUT(HR, 2.186; 95%CI 1.591 ~ 3.002; P < 0.001)were independently associated with OS. In ROC analysis, CONUT had a higher area under the ROC curve (AUC) for the prediction of 24-month PFS and OS than the SII or PNI. When the time-dependent AUC curve was used to predict PFS and OS, CONUT tended to maintain its predictive accuracy for long-term prognosis at a significantly higher level for an extended period after chemotherapy when compared with the other markers tested. The CONUT score showed better accuracy of predicting OS (C-index: 0.711) and PFS(C-index: 0.753). CONCLUSION: CONUT score is an independent prognostic indicator of poor outcomes for patients with stage III-IV NSCLC and is superior to the SII and PNI in terms of prognostic ability.

The near-global ocean mesoscale eddy atmospheric-oceanic-biological interaction observational dataset.

Amongst the variety of oceanic processes running the gamut of spatiotemporal scales, mesoscale eddies are the most common and often have region-specific characteristics. The large kinetic energy inherent to eddies themselves is a strong modulator of the global climate, ocean circulation, productivity, and freshwater transport. This study uses multi-source satellite remote sensing observation data to construct a multi-parameter eddy dataset for the 1993-2019 period, which differs significantly from a few of previous published eddy datasets that include only basic sea surface eddy physical features. Eddies within the dataset have life cycles of greater than four weeks, and their corresponding sea surface chlorophyll, sea surface temperature, and wind fields are provided. Atmospheric and oceanic variables are used to present a comprehensive picture of a given mesoscale eddy's impact on the local physical, but also biological environment. The dataset would find immense value in research on mesoscale eddies, their impact on the atmosphere, and related biological processes.

CUL4B facilitates HBV replication by promoting HBx stabilization.

OBJECTIVE: Hepatitis B virus (HBV) infection is a major public health problem worldwide. However, the regulatory mechanisms underlying HBV replication remain unclear. Cullin 4B-RING ubiquitin E3 ligase (CRL4B) is involved in regulating diverse physiological and pathophysiological processes. In our study, we aimed to explain the role of CUL4B in HBV infection. METHODS: Cul4b transgenic mice or conditional knockout mice, as well as liver cell lines with CUL4B overexpression or knockdown, were used to assess the role of CUL4B in HBV replication. Immunoprecipitation assays and immunofluorescence staining were performed to study the interaction between CUL4B and HBx. Cycloheximide chase assays and in vivo ubiquitination assays were performed to evaluate the half-life and the ubiquitination status of HBx. RESULTS: The hydrodynamics-based hepatitis B model in Cul4b transgenic or conditional knockout mice indicated that CUL4B promoted HBV replication (P < 0.05). Moreover, the overexpression or knockdown system in human liver cell lines validated that CUL4B increased HBV replication in an HBx-dependent manner. Importantly, immunoprecipitation assays and immunofluorescence staining showed an interaction between CUL4B and HBx. Furthermore, CUL4B upregulated HBx protein levels by inhibiting HBx ubiquitination and proteasomal degradation (P < 0.05). Finally, a positive correlation between CUL4B expression and HBV pgRNA level was observed in liver tissues from HBV-positive patients and HBV transgenic mice. CONCLUSIONS: CUL4B enhances HBV replication by interacting with HBx and disrupting its ubiquitin-dependent proteasomal degradation. CUL4B may therefore be a potential target for anti-HBV therapy.

Antibacterial Performance of a Gold-Loaded g-C3 N4 Nanocomposite System in Visible Light-Dark Dual Mode.

Semiconductor photocatalysis technology, which can kill pathogenic microorganisms in a green and broad-spectrum way, is a new research field with great application potential. Due to the dependence on light, semiconductor materials have the problems of low utilization rate of sunlight and inactivation under dark conditions. A simple Au-loaded g-C3 N4 (Au/g-C3 N4 ) nanocomposites was studied. Under dark conditions, the antibacterial efficiency of 1.2 % Au/g-C3 N4 reached 99.1 % relative to 105  CFU (Colony-FormingUnits)/mL E. coli. Under light conditions, the antibacterial efficiency of 0.9 % Au/g-C3 N4 reached 94.1 % relative to 107  CFU/mL E. coli. The influence of contact time, Au loading and bacterial concentration on its antibacterial performance under dark conditions was discussed in detail. Through photoelectrochemistry, SEM, TEM and reactive oxygen species (ROS) detection the microscopic charge behaviour was revealed in the system, and a light-dark dual-mode antibacterial mechanism was proposed.

Efficacy of everolimus combined with endocrine therapy in HR-positive/HER-2-negativeadvanced breast cancer.

PURPOSE: To explore the efficacy and safety of everolimus combined with endocrine therapy in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER-2)-negative advanced breast cancer. METHODS: The clinical information of 108 patients with HR-positive/HER-2-negative advanced breast cancer, who were admitted to and treated in our hospital from June 2014 to June 2016, was retrospectively analyzed. Of them, 54 patients were treated with everolimus combined with endocrine drugs (Everolimus group), while the other 54 patients underwent endocrine monotherapy (Control group). The clinical response rate and incidence of adverse reactions were compared between the two groups of patients, and the patients were followed up to record survival. Besides, the possible influencing factors for progression-free survival (PFS) were analyzed. RESULTS: The objective response rate (ORR) was 22.2% and 14.8%, respectively, in everolimus group and the Control group, while the clinical benefit rate (CBR) was 66.7% and 37.0%, respectively, in the two groups. There were statistically significant differences in the CBRs of the first-line and second-line therapies. The majority of adverse reactions were in grade I and II, with lower incidence rates of grade III and IV adverse reactions. The median PFS of the two groups of patients was 7.3±5.6 months and 6.7±5.1 months, respectively. The log-rank test revealed that there was a statistically significant difference in the PFS between the two groups of patients. According to the multivariate regression analysis results, progesterone receptor (PR)+, absence of visceral metastases, and sensitivity to endocrine therapy were the protective prognostic factors for PFS. CONCLUSION: Everolimus combined with endocrine therapy has significant clinical efficacy in patients with HR-positive/HER-2-negative advanced breast cancer, and can effectively improve the survival of patients with tolerable adverse reactions. PR+, absence of visceral metastases and sensitivity to endocrine therapy are the protective prognostic factors for PFS.

DKC1 serves as a potential prognostic biomarker for human clear cell renal cell carcinoma and promotes its proliferation, migration and invasion via the NF­κB pathway.

DKC1, an X­linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post­-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry. The percentage of DKC1 expression in ccRCC (61.3%) was markedly higher than that in paracancerous tissues (34.7%) (P=0.001). Positive DKC1 expression tends to significantly be associated with unfavorable clinicopathological characteristics such as tumor diameter >7 cm (P=0.002) and tumor­node­metastasis (TNM) stage III or IV (P<0.001). Multivariate COX analysis revealed that positive DKC1 expression was an independent unfavorable factor for prognosis of ccRCC patients [hazard ratio (HR)=1.932, 95% CI, 1.290­2.893, P=0.001 for 5­year overall survival; HR=1.778, 95% CI,1.150­2.748, P=0.010 for disease­free survival]. In the PROGgeneV2 platform, we also found that ccRCC patients with high DKC1 mRNA expression had a poorer prognosis than patients with low DKC1 expression in The Cancer Genome Atlas (TCGA). Furthermore, we found that knockdown of DKC1 inhibited proliferation, migration and invasion of ccRCC through regulation of the NF­κB/MMP­2 signaling pathway in vitro. We also demonstrated that DKC1 regulated ccRCC proliferation and the expression of NF­κB­p65 and MMP­2 in vivo. In summary, the expression of DKC1 was upregulated in ccRCC, which was associated with unfavorable clinicopathological characteristics and DKC1 may act as an independent prognostic indicator of ccRCC patients.

PTBP1 knockdown in renal cell carcinoma inhibits cell migration, invasion and angiogenesis in vitro and metastasis in vivo via the hypoxia inducible factor-1α pathway.

Polypyrimidine tract-binding protein 1 (PTBP1), a heterogeneous nuclear ribonucleoprotein, is a multi-functional RNA-binding protein. PTBP1 participates in a number of biological processes, including maintaining cell structure and motility, immunity, protein metabolism and the cell cycle. The present study aimed to investigate the association between PTBP1 expression and the prognosis and clinicopathological characteristics of patients with renal cell cancer (RCC). The potential mechanism of action of PTBP1 in the metastasis of RCC was also investigated. The results demonstrated that PTBP1 was overexpressed in RCC tissues compared with normal renal tissues. Furthermore, PTBP1 expression was negatively associated with patient prognosis and positively associated with tumor size, pathological tumor (pT) and pathological metastasis (pM) status and tumor lymph node metastasis (TNM) stage. PTBP1 knockdown in vitro inhibited RCC cell migration, invasion, proliferation and angiogenesis, and it was demonstrated that PTBP1 affected RCC cells primarily via the hypoxia inducible factor-1α pathway. Furthermore, PTBP1 knockdown decreased RCC lung metastasis in vivo. The present study demonstrated that PTBP1 knockdown suppresses tumor progression and metastasis, indicating that PTBP1 is an important prognostic factor in RCC and that it may be developed as a novel method of treating patients with RCC.

ZHX2 enhances the cytotoxicity of chemotherapeutic drugs in liver tumor cells by repressing MDR1 via interfering with NF-YA.

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated suppression of liver tumor growth in vivo. Furthermore, immunohistochemical staining demonstrated the inverse correlation of ZHX2 and MDR1 expression in HCC tissues. Luciferase report assay showed that ZHX2 repressed the MDR1 promoter activity, while knockdown of NF-YA or mutating the NF-Y binding site eliminated this ZHX2-mediated repression of MDR1 transcription. Co-IP and ChIP assay further suggested that ZHX2 interacted with NF-YA and reduced NF-Y binding to the MDR1 promoter. Taken together, we clarify that ZHX2 represses NF-Y-mediated activation of MDR1 transcription and, in doing so, enhances the effects of chemotherapeutics in HCC cells both in vitro and in vivo.

Hepatitis B virus core protein enhances human telomerase reverse transcriptase expression and hepatocellular carcinoma cell proliferation in a c-Ets2-dependent manner.

Hepatitis B virus core protein can regulate viral replication and host gene expression. However, it is unclear whether and how hepatitis B virus core protein regulates hepatocellular carcinoma cell proliferation. Induction of hepatitis B virus core protein over-expression significantly enhanced the proliferation of hepatocellular carcinoma cells, while knockdown of hepatitis B virus core protein expression inhibited the proliferation of hepatocellular carcinoma cells. Altered hepatitis B virus core protein expression significantly changed the growth of implanted hepatocellular carcinoma in vivo. Microarray analysis indicated that hepatitis B virus core protein up-regulated human telomerase reverse transcriptase expression, which was further validated by over-expression and knockdown assays in vitro. Furthermore, knockdown of human telomerase reverse transcriptase expression mitigated the hepatitis B virus core protein-enhanced hepatocellular carcinoma cell proliferation and clone formation in vitro. Luciferase assays indicated that hepatitis B virus core protein enhanced the promoter activity of human telomerase reverse transcriptase, which was dependent on the binding of c-Ets2 to the promoter region between -192 and -187. In addition, hepatitis B virus core protein enhanced human telomerase reverse transcriptase transcription in HepG2 cells, but not in the c-Ets2-silencing HepG2 cells. Moreover, hepatitis B virus core protein promoted c-Ets2 nuclear translocation. Finally, significantly higher levels of human telomerase reverse transcriptase expression and nuclear c-Ets2 accumulation were detected in hepatitis B virus core protein-positive hepatocellular carcinoma samples. Our findings demonstrate that hepatitis B virus core protein promotes hepatocellular carcinoma cell proliferation by up-regulating the c-Ets2-dependent expression of human telomerase reverse transcriptase.

Direct N-alkylation of amino-azoles with alcohols catalyzed by an iridium complex/base system.

The direct and regioselective N-alkylation of amino-azoles to the corresponding 2-N-(alkylamino)azoles using various alcohols as alkylating agents with good to excellent yields has been accomplished by an iridium complex/base system.

Regioselective N-alkylation of 2-aminobenzothiazoles with benzylic alcohols.

The preparation of 2-(N-alkylamino)benzothiazoles via regioselecive N-alkylation of 2-aminobenzothiazoles has been accomplished by using benzylic alcohols as alkylating agents.

[Novel ionic liquid as solvent for preconcentration of trace lead in dialysis fluids and its determination by graphite furnace atomic absorption spectrometry].

A novel room temperature ionic liquid 1-butyl-3-trimethylsilylimidazolium hexafluorophosphate was designed and synthesized, and was applied to the preconcentration of ultra trace lead in a relatively large volume of dialysis fluids (such as 1 000 mL or bigger). In the present work, dithizone was employed as chelator to form a neutral lead- dithizone complex, and the ionic liquid 1-butyl-3-trimethylsilylimidazolium hexafluorophosphate was used to displace CCl4 as solvent for liquid/liquid extraction of lead complex. The ionic liquid was collected and the lead (II) was back-extracted into aqueous solution by adding nitric acid solution, and the above solution was directly applied to determine lead in the dialysis fluids by graphite furnace atomic absorption spectrometry. Experiments indicated that the proposed extraction system is superior over other systems in which organic solvent such as CCl4 or classical room temperature ionic liquid1-butyl-3-methylimidazolium hexafluorophosphate was selected as extraction medium, and its extraction efficiency of once extraction and enrichment factor of lead was more than 99% and 200 times, respectively. The preconcentration combined with graphite furnace atomic absorption spectrometry has been applied to the determination of trace lead in dialysis fluid samples with satisfactory results.

A new room temperature ionic liquid 1-butyl-3-trimethylsilylimidazolium hexafluorophosphate as a solvent for extraction and preconcentration of mercury with determination by cold vapor atomic absorption spectrometry.

A new room temperature ionic liquid 1-butyl-3-trimethylsilylimidazolium hexafluorophosphate abbreviated as [C(4)tmsim][PF(6)] was synthesized and developed as a novel medium for liquid/liquid extraction of inorganic mercury in this work. Under optimal condition, o-carboxyphenyldiazoamino-p-azobenzene abbreviated as CDAA reacted with inorganic mercury to form a neutral Hg-CDAA complex, the complex was rapidly extracted into ionic liquid phase. After back-extracting into aqueous phase with sulfide sodium solution, the mercury concentration was detected by cold vapor atomic absorption spectrometry. The extraction and back-extraction efficiencies were 99.9 and 100.1% for 5.0microg L(-1) standard mercury in 1000mL of water solution, respectively. The detection limit, calculated using three times the standard error of estimate of the calibration graph, is 0.01ng of mercury per milliliter water sample. The proposed method has been used to the determination of trace inorganic mercury in natural water with satisfactory results. Moreover, Zeta potential and surface tension of [C(4)tmsim][PF(6)] solution were measured and applied to explain the extraction mechanism of [C(4)tmsim][PF(6)] system.