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Abstract This study investigated the impact of novel copper ionophores on the prognosis of clear cell renal cell carcinoma (ccRCC) and the tumor microenvironment (TME). The differential expression of 10 cuproptosis and 40 TME-pathway-related genes were measured in 531 tumor samples and 71 adjacent kidney samples in The Cancer Genome Atlas database. A risk score model was constructed with LASSO cox to predict the prognosis of ccRCC patients. Forest plot and function enrichment were used to study the biological function of the key genes in depth. The study found that the risk score model accurately predicted the prognosis of ccRCC patients. Patients with high scores had higher immune responses with a higher proportion of anti-tumor lymphocytes and a lower proportion of immunosuppressive M2-like macrophages. However, the high-score group also exhibited a higher proportion of T follicular helper cells and regulatory T cells. These results suggest that cuproptosis-based therapy may be worth further investigation for the treatment of ccRCC and TME. Subsequently, by using RNAi, we established the stable depletion models of FDX1 and PDHB in ccRCC cell lines 786-O and ACHN. Through CCK8, colony formation, and Transwell assays, we observed that the knockdown of FDX1 and PDHB could significantly reduce the capabilities of proliferation and migration in ccRCC cells. In conclusion, this study illuminates the potential effectiveness of copper ionophores in the treatment of ccRCC, with higher risk scores correlating with better TME immune responses. It sets the stage for future cuproptosis-based therapy research in ccRCC and other cancers, focusing on copper’s role in TME.

Abstracts: Aims: The prevalence of depression is higher in heart failure (HF) patients. Early screening of depressive symptoms in HF patients and timely intervention can help to improve patients' quality of life and prognosis. This study aims to explore diagnostic biomarkers by examining the expression profile of serum exosomal miRNAs in HF patients with depressive symptoms. Methods: Serum exosomal RNA was isolated and extracted from 6 HF patients with depressive symptoms (HF-DS) and 6 HF patients without depressive symptoms (HF-NDS). High-throughput sequencing was performed to obtain miRNA expression profiles and target genes were predicted for the screened differentially expressed miRNAs. Biological functions of the target genes were analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, we collected serum exosomal RNAs from HF-DS (n = 20) and HF-NDS (n = 20). The differentially expressed miRNAs selected from the sequencing results were validated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Finally, the diagnostic efficacy of the differentially expressed exosomal miRNAs for HF-DS was evaluated by using receiver operating characteristic (ROC) curves. Results: A total of 19 significantly differentially expressed exosomal miRNAs were screened by high-throughput sequencing, consisting of 12 up-regulated and 7 down-regulated exosomal miRNAs. RT-qPCR validation demonstrated that the expression level of exo-miR-144-3p was significantly down-regulated in the HF-DS group, and the expression levels of exo-miR-625-3p and exo-miR-7856-5p were significantly up-regulated. In addition, the expression level of exo-miR-144-3p was negatively correlated with the severity of depressive symptoms in HF patients, and that the area under the curve (AUC) of exo-miR-144-3p for diagnosing HF-DS was 0.763. Conclusions: In this study, we examined the serum exosomal miRNA expression profiles of HF patients with depressive symptoms and found that lower level of exo-miR-144-3p was associated with more severe depressive symptoms. Exo-miR-144-3p is a potential biomarker for the diagnosis of HF-DS.

Abstract Background Prostate cancer (PCa) is one of the common malignant tumors worldwide. MiR-183-5p has been reported involved in the initiation of human PCa, this study aimed to investigate whether miR-183-5p affects the development of prostate cancer. Methods In this study, we analyzed the expression of miR-183-5p in PCa patients and its correlation with clinicopathological parameters based on TCGA data portal. CCK-8, migration assay and invasion and wound-healing assay were performed to detect proliferation, migration and invasion in PCa cells. Results We found the expression of miR-183-5p was significantly increased in PCa tissues, and high expression of miR-183 was positively associated with poor prognosis of PCa patients. Over-expression of miR-183-5p promoted the migration, invasion capacities of PCa cells, whereas knockdown of miR-183-5p showed reversed function. Furthermore, luciferase reporter assay showed TET1 was identified as a direct target of miR-183-5p, which was negatively correlation with miR-183-5p expression level. Importantly, rescue experiments demonstrated TET1 over-expression could reverse miR-183-5p mimic induced-acceleration of PCa malignant progression. Conclusion Our results indicated that miR-183-5p could act as a tumor promoter in PCa and it accelerated the malignant progression of PCa by directly targeting and down-regulating TET1.

Combined stabilizing piles are an effective measure to reinforce large-scale landslides with complex strata. However, the reinforcement mechanism of h-type stabilizing piles in composite strata, such as strata with upper hard and lower weak bedrock, still needs to be studied in depth. Based on a set of self-developed physical devices for landslide-h-type stabilizing piles in bedrock with upper hard and lower weak strata, monitoring of stress and strain, laser range finder, high speed camera, and particle image velocimetry (PIV) techniques were adopted to study the internal forces and displacement of h-type stabilizing piles in landslides bedrock with upper hard and lower weak strata and the deformation characteristics of landslides, through which the interaction mechanism between h-type anti-sliding piles and landslides were revealed. The results showed that under the loading at the tope of the landslide, the h-type stabilizing pile reinforced landslide exhibited progressive failure characterized by four stages of creep, constant-speed deformation, accelerated deformation, and failure. Influenced by the beam, the displacement of the pile head and front and rear piles is small, but the piles have the maximum strain near the sliding mass. The bending moment of the rear piles showed an "S" type distribution curve, while that of the front piles showed a triangular distribution curve, and the maximum negative bending moment occurred at a depth of 20 cm below the beam. With the increase in the volume content of the hard stratum (φβ), the displacement of the pile head gradually decreased, and the maximum bending moment of the front and rear piles gradually decreased and tended to be stable as φβ exceeded 60%. When φβ was 20% and 40%, the soil pressure behind the rear piles showed a parabolic distribution curve; when φβ was 60% and 80%, it changed to the reverse "S" distribution curve, and the second maximum value occurred near the sliding surface. The soil pressure behind the front piles showed a parabolic distribution type versus the change of φβ. The results of this study can provide a theoretical reference for understanding the reinforcement mechanisms and design theories of combined stabilizing piles.

Accurately estimating aboveground dry biomass (ADB) is crucial. The ADB of rice has primarily been estimated using vegetation indices with several discrete bands; nevertheless, these indices cannot take advantage of continuous bands available with hyperspectral remote sensing. This study analyzed the quantitative relationship between canopy hyperspectral characteristic parameters (HCPs) and the ADB of rice. Twenty HCPs were used, including red edge area (SDr), blue edge area (SDb), and others. The variable-screening methods involved stepwise regression (SR), a regression coefficient (RC), variable importance in projection (vip), and random forest (RF). Stepwise and partial least squares regression methods were employed with traditional linear regression as well as machine learning methods including random forest (RF), a support vector machine (SVM), a BP artificial neural network (BPNN), and an extreme learning machine. Whole- and screening-variable models were constructed to estimate rice ADB at jointing, booting, heading, and maturing stages and across growth stages. Screening-variable models include SVM models based on SR (SVM-sr), RF models based on vip (RF-vip), and others. The results show that the HCPs had a significant correlation with ADB containing elements in the red edge region, namely SDr, SDr/SDb, and (SDr − SDb)/(SDr + SDb) at each growth stage. In addition, the screening performance of vip and SR was better than that of RC and RF, and fewer variables were screened. Moreover, the HCPs of the red edge region were screened using different screening methods at each growth stage. Among them, SDr/SDb and (SDr − SDb)/(SDr + SDb) appeared frequently, indicating they are important. Furthermore, at each growth stage, ADB could be well-estimated using diverse models with the RF modeling method based on vip screening variables found to be the best modeling method for ADB estimation; the independent variables of the RF-vip model involved the (SDr − SDb)/(SDr + SDb) at each growth stage.

In the rice–rapeseed rotation system, straw incorporation plays an important role in achieving the rational utilization of resources and maintaining crop production. However, in the study of rice–rapeseed rotation, there was no study on the effect of straw and nitrogen (N) fertilizer in the rice season on the dry matter accumulation (DMA) and nutrient accumulation of subsequent rapeseed. So, this study relied on the localization experiment of rice–rapeseed rotation and annual straw incorporation (full straw returning to the field, SR; the control is full straw removal from the field, CK) with different N fertilizer application rates (N1: 0 kg ha−1, N2: 75 kg ha−1, N3: 150 kg ha−1, and N4: 225 kg ha−1) in the rice season. Based on the fourth year of experiment implementation, the effects of annual straw incorporation combined with the N fertilizer application rate in the rice season on the leaf area index (LAI), photosynthetic potential (PP), DMA and its distribution proportion and rate, and nutrient uptake and its allocation proportion in rapeseed were discussed. At the bolting stage (BS), initial flowering stage (IFS), terminal flowering stage (TFS), and mature stage (MS), the DMA of rapeseed in SR was significantly higher than that in CK by 69.90, 64.27, 62.90, and 41.27%, respectively. The accumulation of N, phosphorus (P), and potassium (K) in SR was significantly higher than that in CK at the BS, IFS, TFS, and MS. Straw treatment had a significant impact on the apparent surplus of N, P, and K in the rice, rapeseed, and annual seasons, while the application of N fertilizer in the rice season had a significant or extremely significant impact on the apparent surplus (AS) of N in the rice, rapeseed, and annual seasons, indicating that fertilization of previous crops had a certain aftereffect. Therefore, straw incorporation is a sustainable farmland management measure.

Abstract 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.

The stochastic modification and irreducible modification in PageRank produce large web link changes correspondingly. To get a minimal irreducible web link adjustment, a PageRank model of minimal irreducible adjustment and its lumping method are discussed by Li, Chen, and Song. In this paper, we provide alternative proofs for the minimal irreducible PageRank by a new type of similarity transformation matrices. To further provide theorems and fast algorithms on a reduced matrix, an 4×4 block matrix partition case of the minimal irreducible PageRank model is utilized and analyzed. For some real applications of our results, a lumping algorithm used for speeding up PageRank vector computations is also presented. Numerical results are also reported to show the efficiency of the proposed algorithm.

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.

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.

Abstract Background The aberrant expression of long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been demonstrated to be involved in the tumourigenesis and the development of various cancers. Therefore, we conducted a meta-analysis to assess the prognostic role of lncRNA XIST expression in solid tumors. Methods The databases of PubMed, EMBase, Web of Science, Cochrane library (up to Dec 31, 2017) were searched for the related studies and identified 15 eligible studies containing 1209 patients to include in the meta-analysis. Hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) were pooled to estimate the association between lncRNA XIST expression and survival of cancer patients from Asian. Results The result showed that higher lncRNA XIST expression in cancer tissue was related to a worse overall survival (OS) (HR = 1.54, 95% CI 1.07–2.23). In subgroup analysis, it revealed that lncRNA XIST overexpression was significantly associated with worse OS in digestive system tumors (HR = 1.67, 95% CI 1.11–2.51, p = 0.031). In addition, the association between high lncRNA XIST expression and poor OS was also statistically significant in other subgroups, including multivariate analysis (HR = 2.39, 95% CI 1.28–4.46, p = 0.006, random-effect), patients’ number was greater than 65 (HR = 1.75, 95% CI 1.24–2.47, p = 0.001, random-effect), and reported in text (HR = 2.50, 95% CI 1.49–4.18, p = 0.000, random-effect). Conclusions The expression of lncRNA XIST could be regarded as a poor prognostic biomarker for solid tumors, which might shed new light on epigenetic diagnostics and therapeutics in tumors.

Completeness are comprehensive evaluation of the development status of irrigated areas. The study of their main influencing factors can provide strong data support for the high-quality development of irrigated areas. The paper choose the data during 2005 to 2014 of Sanyizhai Irrigation Area as analysis samples, clear different key factors affecting the evaluation target, in which six factors equal, according to different evaluation subjects and goals, the same impact factor of direct effect and indirect effect, decision coefficient and significant contribution to total R2. For the comprehensive completeness of Yellow River Sanyizhai Irrigation Area, the channel length is the most important influencing factor. The actual irrigation area, mechanism setting and channel lining rate have a significant influence on the comprehensive completeness evaluation of Yellow River Sanyizhai Irrigation Area, while the direct effect of the actual water amount is the least. Compared with the simple correlation coefficient and regression analysis method, the path analysis method can accurately calculate the direct and indirect effects of the independent variables on the dependent variables, which has the advantages of intuitive, scientific and reasonable. According to the analysis results, it can make clear the direction of efforts for the upgrading and transformation of the irrigation area and the development of high quality.

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).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.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.

Super hybrid rice Liangyoupeijiu was grown by transplanting (TP) at a spacing of 20 cm×20 cm with one seedling per hill and by direct-seeding (DS) at a seeding rate of 22.5 kg ha-1 (about 120 seeds m-2) in Changsha, Hunan Province, China in 2004 – 2010. Grain yield and yield components were measured each year, and some physiological factors were determined in 2009. There was no significant difference in mean grain yield across years between DS and TP. DS produced more panicles per m2 but less spikelets per panicle than TP. The differences in number of spikelets per m2, spikelet filling percentage and grain weight between DS and TP were not significant. A large number of panicles per m2 in DS was derived from the increased number of tillers per m2 rather than increased rate of panicle-bearing tillers, and the number of tillers per m2 was mainly determined by the number of hills per m2 because the number of tillers per hill was small in DS plants. Tillering rate, tillering duration as well as carbohydrate and nitrogen metabolism were critical to the reduced number of tillers per hill in DS. In DS plants with fewer spikelets per panicle, the numbers of primary branches and secondary branches per panicle, spikelets per primary and secondary branches, and also panicle length and spikelets per unit panicle length were smaller. These differences were attributed to the smaller source leaf size as well as lower root activity and the nutritional status at panicle initiation.

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.