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A field experiment employing the rice cultivars Qyou6 and Yixiangyou2115 as materials and different nitrogen application rates was conducted in Huangping County, Guizhou Province in 2019 to determine the effects of nitrogen application rate on photosynthetic pigments, leaf fluorescence characteristics, yield, and their interrelations in indica hybrid rice. The results showed that photosynthetic pigment contents generally increased with increasing nitrogen application rate. As the nitrogen rate increased, the maximal quantum yield of PSII (Fv/Fm), actual quantum yield of PSII (ΦPSII), and relative electron transfer rate at PSII (ETR) first decreased and then increased at the booting stage; Fv/Fm and ΦPSII decreased while ETR first increased and then decreased at the heading stage; nevertheless, Fv/Fm and ΦPSII first decreased and then increased but ETR was just the opposite at the maturity stage. Non-photochemical quenching coefficient (qN) and quantum yield of regulatory energy dissipation at PSII (Y(NPQ)) first increased and then decreased whereas quantum yield of non-regulatory energy dissipation at PSII (Y(NO)) first decreased and then increased at the booting, heading, and maturity stages with increasing nitrogen application rate. Photochemical quenching coefficient (qP) showed an increasing trend as the nitrogen rate increased in the range of 150–300 kg/ha at the heading and maturity stages. Photosynthetic pigments, leaf fluorescence characteristics, and yield and its components were significantly correlated. First, chlorophylls a and b were significantly negatively correlated with Fv/Fm while significantly positively correlated with qP at the heading stage. Secondly, Carotenoids were significantly positively correlated with the effective panicle number (EPN) at the booting stage while significantly negatively correlated with the spikelets per panicle (SPP) at the heading stage. Chlorophyll a and carotenoids were significantly positively correlated with EPN but significantly negatively correlated with spikelet filling (SF) at the maturity stage. In addition, qP was significantly negatively correlated with EPN at the booting stage. At the heading stage, Fv/Fm and Y(NO) were significantly negatively correlated with EPN and SPP, respectively, and Fv/Fm and ΦPSII were significantly positively related to SF. Moreover, qP was extremely significantly positively related to EPN whereas Fv/Fm was extremely significantly negatively correlated with grain yield at the maturity stage. Appropriate nitrogen application rates can enhance photosynthetic pigment contents, improve the photochemical efficiency and proportion of the open part of the reaction center of PSII, and promote the quantum efficiency and self-protection ability of PSII, thereby increasing photosynthetic efficiency and yield. Under the conditions adopted in this experiment, a parabolic relationship was observed between the nitrogen application rate and grain yield. The regression analysis results showed that the best nitrogen application rate of indica hybrid rice is 168.16 kg ha−1 and the highest yield is 11,804.87 kg ha−1.

Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high mortality-to-incidence ratios. Nuclear factor erythroid 2-like 3 (NFE2L3), also known as NRF3, is a member of the cap 'n' collar basic-region leucine zipper family of transcription factors. NFE2L3 is involved in the regulation of various biological processes, whereas its role in HCC has not been elucidated. Aim To explore the expression and biological function of NFE2L3 in HCC. Methods We analyzed the expression of NFE2L3 in HCC tissues and its correlation with clinicopathological parameters based on The Cancer Genome Atlas (TCGA) data portal. Short hairpin RNA (shRNA) interference technology was utilized to knock down NFE2L3 in vitro. Cell apoptosis, clone formation, proliferation, migration, and invasion assays were used to identify the biological effects of NFE2L3 in BEL-7404 and SMMC-7721 cells. The expression of epithelial-mesenchymal transition (EMT) markers was examined by Western blot analysis. Results TCGA analysis showed that NFE2L3 expression was significantly positively correlated with tumor grade, T stage, and pathologic stage. The qPCR and Western blot results showed that both the mRNA and protein levels of NFE2L3 were significantly decreased after shRNA-mediated knockdown in BEL-7404 and SMMC-7721 cells. The shRNA-mediated knockdown of NFE2L3 could induce apoptosis and inhibit the clone formation and cell proliferation of SMMC-7721 and BEL-7404 cells. NFE2L3 knockdown also significantly suppressed the migration, invasion, and EMT of the two cell lines. Conclusion Our study showed that shRNA-mediated knockdown of NFE2L3 exhibited tumor-suppressing effects in HCC cells.

Interleukin-33 (IL-33) is a cytokine with pleiotropic functions in various diseases; however, its role in the antitumor immune response is still unclear. We found the expression of IL-33/ST2 in nonsmall cell lung tumor microenvironment. Furthermore, we found that IL-33 promoted effector functions of CD8+ T cells that play a critical role in antitumor immune response. In addition, we found that IL-33 enhanced tumor vaccine effector functions in mice. Altogether, these findings suggest that IL-33, through facilitates CD8+ T cells in microenvironment to provide a profound effect in antitumor immunotherapy.

Immunotherapy is effective in improving the survival and prognosis of patients with non-small cell lung cancer (NSCLC), and identifying effective immunomarkers is important for immunotherapy. Interleukin (IL)-36γ is a novel immunomarker that has an important function in the antitumor immune response. The present study investigated the association between IL-36γ and NSCLC to provide novel insight into immunotherapy for patients with NSCLC. Tissue microarrays of lung adenocarcinoma and squamous cell carcinoma were purchased for immunohistochemical analysis of IL-36γ expression levels and clinical parameters. In addition, fresh clinical NSCLC and adjacent normal tissue samples were collected to analyze IL-36γ mRNA expression levels using quantitative PCR. IL-36γ protein was primarily located in the cytoplasm, with a small quantity in the nucleus, and IL-36γ mRNA and protein expression levels in lung cancer tissues were significantly higher compared with those in adjacent normal tissues. Elevated IL-36γ protein expression levels were significantly associated with a higher tumor grade of lung adenocarcinoma; however, IL-36γ mRNA expression levels were inversely associated with the clinical Tumor-Node-Metastasis stage in patients with lung squamous cell carcinoma. In addition, patients with adenocarcinoma with high IL-36γ protein expression levels tended to longer post-operative survival times. These findings indicate that IL-36γ may have potential as an immunomarker for prediction of tumor progression and survival in patients with NSCLC.

Many fertilization models have been created to scientifically determine the amount of fertilization. With the same purpose, we constructed a nitrogen (N) application model, the leaf value model, which can make N fertilizer decisions in a timely, fast and nondestructive manner during rice planting. However, only one area (A1, Jiuzhou Town, Xixiu District, Guizhou Province) and one cultivar (Qyou6) were involved in the construction of the leaf value model. Its stability and applicability could not be well evaluated. Thus, we chose another area (A2, Jiuzhou Town, Huangping County, Guizhou Province) in Guizhou Province and carried out the experiment by using four cultivars (Nie5you5399, Qyou6, Yixiangyou2115 and Zhongzheyou8) for the leaf value model construction. Compared with the average value of apparent total N uptake (Nz) obtained in 2 years in the A1 area, that in the Qyou6 leaf value model in the A2 area increased by 12%, reaching 635.72 kg ha-1, whereas the corresponding target yield changed slightly, reaching 10,999.90 kg ha-1. Simultaneously, the linear relationship between several good SPAD value-derived indexes (Ys) and apparent N supply of the field (Nx) was still significant or extremely significant in the Qyou6 leaf value model. Compared with the A1 area, it slightly differed, and the R2 of SPADL1 was higher than that of SPADL3×L4/mean. In the leaf value model of the other three cultivars, the relationship between yield and Nx and that between Ys and Nx were significant or extremely significant. The Nz of Yixiangyou2115 and Zhongzheyou8 (618.33 and 617.76 kg ha-1) were close to that of Qyou6 and the corresponding target yields were 10313.36 and 10301.99 kg ha-1, respectively. The Nz and target yield of Nie5you5399 were lowest at 546.63 and 10680.24 kg ha-1, respectively. In general, this study showed that relationships used in the construction of leaf value model had certain stability and applicability to difference areas and cultivars. The leaf value model can be considered in N fertilizer decision-making of rice planting management.

// Bo Hao 1, * , Zhen Chen 2, * , Baochen Bi 1, * , Miaomei Yu 3 , Shuang Yao 3 , Yuehua Feng 3 , Yang Yu 3 , Lili Pan 3 , Dongmei Di 1 , Guanghua Luo 3 and Xiaoying Zhang 1 1 Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China 2 Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China 3 Comprehensive Laboratory, The Third Affiliated Hospital of Soochow University, Changzhou 213003, P.R. China * These authors contributed equally to this work Correspondence to: Dongmei Di, email: ddm5122@163.com Guanghua Luo, email: shineroar@163.com Keywords: Toll like receptor 4; solid tumor; prognosis; meta-analysis Received: August 15, 2017 Accepted: December 04, 2017 Published: January 12, 2018 ABSTRACT Background: Accumulating evidence showed that high expression of toll like receptor 4 (TLR4) was significantly associated with the outcome of patients with solid cancers. However, other studies failed to draw a similar conclusion. Thus, a systematic meta-analysis was performed to assess the prognostic value of TLR4 in solid tumors. Results: Data from 15 studies and 1294 patients were enrolled. Among the 15 studies, 14 studies demonstrated the association between overall survival(OS) and TLR4 expression, and 7 studies described the relationship between disease-free survival(DFS) and TLR4 expression. High expression of TLR4 was significantly associated with poor OS (pooled hazard ratio (HR) = 2.05; 95% confidence interval (CI) (1.49, 2,49), P < 0.001). The results of meta regression analysis indicated that the subgroups of ethnic (PD = 0.924), tumor type (PD = 0.669), HR obtained method (PD = 0.945), analysis type (PD = 0.898), and cut-off value(PD = 0.835) were not the resource of heterogeneity. Moreover, patients with elevated TLR4 had a significantly worse DFS (pooled HR = 1.79; 95% CI (1.11, 2.88), P < 0.05). Materials and Methods: We searched PubMed, Embase and the Cochrane Library (last update by April 18, 2017) to identify literatures evaluating the value of TLR4 in cancer patients. Combined hazard ratios (HRs) for OS and DFS were assessed using fixed-effects models and random effects models respectively. Conclusions: The meta-analysis suggests that elevated expression of TLR4 is associated with poor OS and shorter DFS of patients with solid tumors. The results indicate that TLR4, as a novel prognostic biomarker in solid tumors, could potentially help to improve treatment decision-making of solid tumors in clinical.

Aims To determine the predictability of diagnosing diabetic nephropathy (DN) versus non-diabetic renal disease (NDRD) from clinical and laboratory data in Chinese patients with type 2 diabetes mellitus (T2DM) manifesting heavy proteinuria. Methods We retrospectively analyzed the clinical and laboratory data of patients with T2DM manifesting heavy proteinuria who underwent renal biopsy from January 2014 to December 2017. Results According to renal biopsy, 220 patients were finally enrolled, including 109 cases diagnosed with DN alone (49.55%), 94 with NDRD alone (42.73%) and 17 with DN plus superimposed NDRD (7.73%). Multivariate analysis showed the significant risk factors for DN alone were age, duration of diabetes, presence of retinopathy, 24-h proteinuria, serum albumin and SBP. Presence of retinopathy achieved the highest overall diagnostic efficiency with the area under the curve of 0.852, sensitivity of 78.9% and specificity of 91.5%. The combined diagnosis with four indicators (duration of diabetes, retinopathy, SBP, and serum albumin) showed the area under the curve of 0.938, sensitivity of 88.1% and specificity of 87.2%. Conclusions The prevalence of DN is high in patients with T2DM manifesting heavy proteinuria. Renal biopsy should be performed in diabetics in the atypical clinical scenario.

Apolipoprotein M (ApoM) is a sphingosine 1-phosphate (S1P) carrier involved in the regulation of S1P. Signaling pathways involving sphingosine kinases (SphKs) and S1P-S1P receptors (S1PRs) play important roles in the oncogenesis of multiple cancers including non-small cell lung cancer (NSCLC). In the present study we have clarified the potential roles of ApoM on the oncogenesis process of NSCLC cells. We detected the ApoM expression in NSCLC tissues and further analyzed its clinical significance. Moreover, we determined effects of ApoM overexpression on tumor cellular behaviours of NSCLC in vitro and in vivo. Our results demonstrated that ApoM protein mass were clearly higher in the NSCLC tissues than in non-NSCLS tissues. Overexpression of ApoM could promote NSCLC cell proliferation and invasion in vitro and tumor growth in vivo, which might be via upregulating S1PR1 and activating the ERK1/2 and PI3K/AKT signaling pathways. It is concluded that up-regulation of ApoM in NSCLC might be associated with the tumor induced inflammation and tumor microenvironment as well as promoting oncogenesis of NSCLC. Further study needs to elucidate the underlying mechanisms.

Background/Aims: microRNAs (miRNAs) are known to act as oncogenes or tumor suppressors in diverse cancers. Although miR-10b is an oncogene implicated in many tumors, its role in cervical cancer (CC) remains largely unclear. Here, we investigated the function and underlying mechanisms of miR-10b in human CC. Methods: Quantitative RT-PCR was used to measure miR-10b expression in CC and normal tissues, and its association with clinicopathologic features was analyzed. Methylation of CpG sites in the miR-10b promoter was analyzed by methylation sequencing. Cell proliferation, apoptosis, migration, and invasion assays were used to elucidate the biological effects of miR-10b and expression of the target gene was assayed with Western blot. Results: miR-10b was downregulated in CC tissues compared with normal tissues, and less miR-10b expression was associated with larger tumors, vascular invasion and HPV-type 16 positivity. miR-10b expression decreased in HeLa (HPV18-positive) and SiHa (HPV16-positive) cells compared with C-33A (HPV-negative), but increased after treatment with 5-Aza-CdR. Methylation ratio of site -797 in the miR-10b promoter in C-33A was lower than that in HeLa and SiHa. Further analysis indicates that site -797 is located within a transcription factor AP-2A (TFAP2A) binding element. Functionally, overexpression of miR-10b in HeLa and SiHa suppressed cell proliferation, migration and invasion, and induced apoptosis and miR-10b downregulation had opposite effects. Mechanistically, T-cell lymphoma invasion and metastasis 1 (Tiam1) was identified as a direct and functional target of miR-10b. Conclusion: miR-10b acts as a tumor suppressor in CC by suppressing oncogenic Tiam1, and its expression may be downregulated through methylation of TFAP2A binding element by HPV.

Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAl and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAl in HepG2 cell cultures in a dose- and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor. (C) 2011 Elsevier B.V. All rights reserved.

Objective Lung cancer is one of the deadliest malignancies. The immune checkpoint-blockade (ICB) tumor therapy has led to striking improvement of long-term survival for some lung cancer patients. However, the response rate of immunotherapy is still low for lung cancer. Studying the tumor microenvironment (TME) should shed light on improvement of immunotherapy of lung cancer. Interleukin-33 (IL-33), an “alarmin” cytokine, has been implicated in tumor associated immune responses and inflammatory diseases of the lung. The role of IL-33 in lung cancer progression, however, remains elusive. This study is designed to characterize IL-33 expression in lung tumor tissues and establish the clinical significance of IL-33 in non-small cell lung cancer lung cancer (NSCLC). Materials and methods Tumor tissue specimens from patients suffering from NSCLC were analyzed for expression of IL-33 protein by immunohistochemistry and expression of IL-33 and ST2 mRNA by RT-quantitative PCR (RT-QPCR). The expression data were analyzed for their association with clinical and pathological parameters of NSCLC. In addition, the association between expression levels of IL-33 mRNA and patient survival was determined using 5 independent expression profiling datasets of human lung cancer. Results and conclusion The expression levels of IL-33 and ST2 were significantly down-regulated in both adenocarcinoma and squamous cell carcinoma of the lung when compared to adjacent normal lung tissues. In addition, the level of IL-33 protein was inversely correlated with tumor grade and size. Moreover, analysis of TCGA and GEO lung cancer expression datasets revealed that higher expression levels of IL-33 mRNA were correlated with longer overall survival of patients suffering from adenocarcinoma of the lung. These data indicate that the expression levels of IL-33 are inversely associated with lung cancer progression, consistent with the hypothesis that IL-33 is involved in immune surveillance of NSCLC.

Recent studies have demonstrated that neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is highly expressed in various tumor tissues and cell lines. However, research on the role of NEDD9 in gastric cancer (GC) is rare, and the potential mechanism in tumor progression has not yet been explored. In this study, we investigated the role and mechanism of NEDD9 in GC. The expression of NEDD9 in GC tissues and cell lines was measured by immunohistochemistry, qRT-PCR, and Western blot, respectively. Inhibiting NEDD9 expression was carried out by siRNA transfection, and upregulating of NEDD9 was via NEDD9 overexpression plasmid. The ability of proliferation, migration, and invasion was detected by MTT assay, scratch wound assay, and transwell assay, respectively. The expression of vimentin, E-cadherin, Zeb1, and Zeb2 was measured by Western blot and qRT-PCR. We found that NEDD9 expression was dramatically increased both in GC tissues and cell lines, and the expression was significantly related to GC development. Knockdown of NEDD9 in SGC-7901 strongly inhibited its malignant capacity in vitro. Meanwhile, upregulation of NEDD9 in GES-1 increased the malignant capacity. In addition, the expression of vimentin, Zeb1, and Zeb2 was positively correlated with NEDD9, while E-cadherin was opposite. Collectively, our findings suggest that NEDD9 acts as an oncogene and promotes GC metastasis via EMT.

BACKGROUND: Apolipoprotein M (ApoM) is a constituent of high-density lipoproteins (HDL). It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs) levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD) rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR) were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK) rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8) was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

Apolipoprotein M (APOM) has been suggested as a vasculoprotective constituent of high density lipoprotein (HDL), which plays a crucial role behind the mechanism of HDL-mediated anti-atherosclerosis. Previous studies demonstrated that insulin resistance could associate with decreased APOM expressions. In agreement with our previous reports, here, we further confirmed that the insulin sensitivity was also reduced in rats treated with high concentrations of glucose; such effect could be reversed by administration of rosiglitazone, a peroxisome proliferator-activated receptor-γ (PPARγ). The present study shows that Apom expression is significantly affected by either rosiglitazone or hyperglycemia alone without cross interaction with each other, which indicates that the pathway of Apom expression regulating by hyperglycemia might be differed from that by rosiglitazone. Further study indicated that hyperglycemia could significantly inhibit mRNA levels of Lxrb (P=0.0002), small heterodimer partner 1 (Shp1) (P

It has been demonstrated that apolipoprotein M (APOM) is a vasculoprotective constituent of high density lipoprotein (HDL), which could be related to the anti-atherosclerotic property of HDL. Investigation of regulation of APOM expression is of important for further exploring its pathophysiological function in vivo. Our previous studies indicated that expression of APOM could be regulated by platelet activating factor (PAF), transforming growth factors (TGF), insulin-like growth factor (IGF), leptin, hyperglycemia and etc., in vivo and/or in vitro. In the present study, we demonstrated that palmitic acid could significantly inhibit APOM gene expression in HepG2 cells. Further study indicated neither PI-3 kinase (PI3K) inhibitor LY294002 nor protein kinase C (PKC) inhibitor GFX could abolish palmitic acid induced down-regulation of APOM expression. In contrast, the peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) antagonist GSK3787 could totally reverse the palmitic acid-induced down-regulation of APOM expression, which clearly demonstrates that down-regulation of APOM expression induced by palmitic acid is mediated via the PPARβ/δ pathway.

Renal ischemia/reperfusion (I/R) injury occurs in both native and transplanted kidneys. Hyperbaric oxygen (HBO) has been shown to prevent I/R injury in different tissues. The aim of this study was to evaluate the effect of HBO on renal I/R injury in rats.Male Sprague-Dawley rats were randomly assigned to three groups. The sham group (n = 8) received right nephrectomy. The I/R (n = 8) and HBO + I/R groups (n = 8) received 45 min left renal ischemia followed by 24 h of reperfusion after right nephrectomy. The HBO + I/R group (n = 8) received 100% oxygen at 2.5 atmosphere absolute (ATA), for 1 h at every 12 h interval for 2 d. Reperfusion was performed 24 h later after the last HBO exposure.In HBO + I/R group, blood urea nitrogen (BUN) and creatinine levels decreased significantly compared with the sham and I/R groups (P0.01). Activities of superoxide dismutase (SOD) were increased in renal tissue in the HBO + I/R groups. The content of malondialdehyde (MDA) were decreased in the HBO + I/R groups. Kidney samples from HBO + I/R group rats revealed markedly reduced histological damage under histopathological examination. The animals treated with HBO showed significantly elevated heme oxygenase-1 (HO-1) protein and mRNA levels expression compared with I/R group (P0.05).Hyperbaric oxygen preconditioning (HBO-PC) can protect renal I/R injury against oxidative stress, and the up-regulation of HO-1 expression plays an essential role in HBO induced preconditioning effect.