The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.

Background: Previous studies have shown that MCM3 plays a key role in initiating DNA replication. However, the mechanism of MCM3 function in most cancers is still unknown. The aim of our study was to explore the expression, prognostic role, and immunological characteristics of MCM3 across cancers. Methods: We explored the expression pattern of MCM3 across cancers. We subsequently explored the prognostic value of MCM3 expression by using univariate Cox regression analysis. Spearman correlation analysis was performed to determine the correlations between MCM3 and immune-related characteristics, mismatching repair (MMR) signatures, RNA modulator genes, cancer stemness, programmed cell death (PCD) gene expression, tumour mutation burden (TMB), microsatellite instability (MSI), and neoantigen levels. The role of MCM3 in predicting the response to immune checkpoint blockade (ICB) therapy was further evaluated in four immunotherapy cohorts. Single-cell data from CancerSEA were analysed to assess the biological functions associated with MCM3 in 14 cancers. The clinical correlation and independent prognostic significance of MCM3 were further analysed in the TCGA and CGGA lower-grade glioma (LGG) cohorts, and a prognostic nomogram was constructed. Immunohistochemistry in a clinical cohort was utilized to validate the prognostic utility of MCM3 expression in LGG. Results: MCM3 expression was upregulated in most tumours and strongly associated with patient outcomes in many cancers. Correlation analyses demonstrated that MCM3 expression was closely linked to immune cell infiltration, immune checkpoints, MMR genes, RNA modulator genes, cancer stemness, PCD genes and the TMB in most tumours. There was an obvious difference in outcomes between patients with high MCM3 expression and those with low MCM3 expression in the 4 ICB treatment cohorts. Single-cell analysis indicated that MCM3 was mainly linked to the cell cycle, DNA damage and DNA repair. The expression of MCM3 was associated with the clinical features of LGG patients and was an independent prognostic indicator. Finally, the prognostic significance of MCM3 in LGG was validated in a clinical cohort. Conclusion: Our study suggested that MCM3 can be used as a potential prognostic marker for cancers and may be associated with tumour immunity. In addition, MCM3 is a promising predictor of immunotherapy responses.

Identifying the Preoperative Radiological Risk Features in Patients with Leptomeningeal Carcinomatosis Undergoing Cerebrospinal Fluid Drainage.

BACKGROUND: Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. METHODS: A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. RESULTS: A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0-40.0). The median survival time after surgery was 5 months (IQR, 0.00-10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00-0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. CONCLUSIONS: Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

Quantifying global colonization pressures of alien vertebrates from wildlife trade.

The global trade in live wildlife elevates the risk of biological invasions by increasing colonization pressure (the number of alien species introduced to an area). Yet, our understanding of species traded as aliens remains limited. We created a comprehensive global database on live terrestrial vertebrate trade and use it to investigate the number of traded alien species, and correlates of establishment richness for aliens. We identify 7,780 species involved in this trade globally. Approximately 85.7% of these species are traded as aliens, and 12.2% of aliens establish populations. Countries with greater trading power, higher incomes, and larger human populations import more alien species. These countries, along with island nations, emerge as hotspots for establishment richness of aliens. Colonization pressure and insularity consistently promote establishment richness across countries, while socio-economic factors impact specific taxa. Governments must prioritize policies to mitigate the release or escape of traded animals and protect global biosecurity.

g-C3N4/MoO3 composite with optimized crystal face: A synergistic adsorption-catalysis for boosting cathode performance of lithium-sulfur batteries.

The commercial application of lithium-sulfur batteries (LSBs) has been seriously hindered by the shuttle effect of lithium polysulfides (LiPSs) and their slow redox kinetics. In this work, g-C3N4/MoO3 composed of graphite carbon nitride (g-C3N4) nanoflake and MoO3 nanosheet is designed and applied to modify the separator. The polar MoO3 can form chemical bond with LiPSs, effectively slowing down the dissolution of LiPSs. And based on the principle of "Goldilocks", LiPSs will be oxidized by MoO3 to thiosulfate, which will promote the rapid conversion from long-chain LiPSs to Li2S. Moreover, g-C3N4 can promote the electron transportation, and its high specific surface area can facilitate the deposition and decomposition of Li2S. What's more, the g-C3N4 promotes the preferential orientation on the MoO3(021) and MoO3(040) crystal planes, which optimizes the adsorption capacity of g-C3N4/MoO3 for LiPSs. As a result, the LSBs with g-C3N4/MoO3 modified separator with a synergistic adsorption-catalysis, can achieve an initial capacity of 542 mAh g-1 at 4C with capacity decay rate of 0.0053% per cycle for 700 cycles. This work achieves the synergy of adsorption and catalysis of LiPSs through the combination of two materials, providing a material design strategy for advanced LSBs.

A Nomogram Model for Stratifying the Risk of Recurrence in Patients with Meningioma After Surgery.

BACKGROUND: Here, we aimed to investigate the clinical parameters affecting the recurrence of meningiomas, and to construct a predictive nomogram model, so as to predict the recurrence-free survival (RFS) of meningiomas more accurately. METHODS: The Clinical, imaging, and pathological data of 155 primary meningioma patients treated surgically from January 2014 to March 2021 were retrospectively analyzed. Independent prognostic factors affecting postoperative recurrence of meningioma were identified by univariate and multivariate Cox regression analyses. A predictive nomogram was established based on independent influence parameters. Subsequently, time-dependent receiver operating characteristic curve, calibration curve, and Kaplan-Meier method were utilized to evaluate the predictive ability of the model. RESULTS: The multivariate Cox regression analysis showed that tumor size, Ki-67 index, and resection extent had independent prognostic significance, and these parameters were subsequently used to construct a predictive nomogram. Receiver operating characteristic curves indicated that the model was more accurate in predicting RFS than independent factors. Calibration curves suggested that the predicted RFS were similar to the actual observed RFS. In the Kaplan-Meier analysis, the RFS of high-risk cases was obviously shorter than that of low-risk cases. CONCLUSIONS: The tumor size, Ki-67 index, and extent of resection were independent factors affecting the RFS of meningioma. The predictive nomogram based on these factors can be used as an effective method to stratify the recurrence risk of meningioma and provide a reference for patients to choose personalized treatment.

Construction of a pyroptosis-related lncRNAs signature for predicting prognosis and immunotherapy response in glioma.

Recent studies have proved that pyroptosis-related long non-coding RNAs (PRlncRNAs) are closely linked to tumor progression, prognosis, and immunity. Here, we systematically evaluated the correlation of PRlncRNAs with glioma prognosis. This study included 3 glioma cohorts (The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Gravendeel). Through Pearson correlation analysis, PRlncRNAs were screened from these 3 cohorts. Univariate Cox regression analysis was then carried out to determine the prognostic PRlncRNAs. A pyroptosis-related lncRNAs signature (PRLS) was then built by least absolute shrinkage and selection operator and multivariate Cox analyses. We systematically evaluated the correlation of the PRLS with the prognosis, immune features, and tumor mutation burden in glioma. A total of 14 prognostic PRlncRNAs overlapped in all cohorts and were selected as candidate lncRNAs. Based on The Cancer Genome Atlas cohort, a PRLS containing 7 PRlncRNAs was built. In all cohorts, the PRLS was proved to be a good predictor of glioma prognosis, with a higher risk score related to a poorer prognosis. We observed obvious differences in the immune microenvironment, immune cell infiltration level, and immune checkpoint expression in low- and high-risk subgroups. Compared with low-risk cases, high-risk cases had lower Tumor Immune Dysfunction and Exclusion scores and greater tumor mutation burden, indicating that high-risk cases can be more sensitive to immunotherapy. A nomogram combining PRLS and clinical parameters was constructed, which showed more robust and accurate predictive power. In conclusion, the PRLS is a potentially useful indicator for predicting prognosis and response to immunotherapy in glioma. Our findings may provide a useful insight into clinically individualized treatment strategies for patients.

Global economic costs of mammal invasions.

Invasive alien mammals cause huge adverse ecological impact on human society and natural ecosystems. Although studies have estimated economic costs of mammal invasions at regional scales, there is lacking the large-scale comprehensive assessment of currency costs for this taxon. Here, we estimated the economic cost of invasive alien mammals on a global scale using the most comprehensive global database compiling economic costs of invasive species (InvaCost). From 1960 to 2021, mammal invasions caused costs (summing damage costs and management costs) of US$ 462.49 billion to the global economy, while the total amount of robust costs reached US$ 52.49 billion. The majority of the total economic costs corresponded to damage costs (90.27 %), while only 7.43 % were related to management cost. Economic costs showed an increasing trend over time. The distribution of costs was uneven among taxonomic groups and regions, with the global total cost highly biasing toward to 5 species (European rabbit, Domestic cat, Black rat, Wild boar and Coypu), and North America reporting much higher costs (60.78 % of total economic costs) than other regions. The total costs were borne by agriculture, environment, authorities stakeholders and other sectors. Geographic and taxonomic biases suggested that total economic costs caused by invasive alien mammals were underestimated. Integrated research efforts are needed to fill in knowledge gaps in the economic costs generated by mammal invasions and to identify the drivers of the economic costs.

Expression and Prognostic Value of Melanoma-Associated Antigen D2 in Gliomas.

INTRODUCTION: The melanoma-associated antigen D2 (MAGED2) is one of the melanoma-associated antigen family members. It is commonly overexpressed in a variety of malignancies. However, the mechanism and function of MAGED2 in glioma remain unknown. METHODS: The MAGED2 expression level and the correlations between clinical characteristics were analyzed with the data from the CGGA and TCGA datasets. MAGED2 expression in 98 glioma tissues was measured using RT-qPCR, Western blot, and immunohistochemistry. CCK-8, colony formation, and EdU assays were used to assess the effect of MAGED2 on U251-MG cell proliferation. Flow cytometry was used to track changes in the cell cycle and cell apoptosis following plasmid transfection with CRISPRi. RESULTS: MAGED2 was shown to be highly expressed in glioma tissues, and high MAGED2 expression predicted poor prognosis. Furthermore, MAGED2 knockdown significantly inhibited the proliferation of U251-MG cells by preventing cell cycle arrest at the G0/G1 phase and triggering apoptosis. In line with in vitro findings, the results of the xenograft experiment and immunohistochemistry also showed that MAGED2 suppression inhibited tumor development and decreased Ki-67 expression levels. CONCLUSIONS: MAGED2 may be a possible biomarker for glioma and an important prognostic factor for glioma patients.

Effects of face shield on an emitter during a cough process: A large-eddy simulation study.

Face shield is a common personal protection equipment for pandemic. In the present work, three-dimensional computational fluid dynamic (CFD) method is used to simulate a cough jet from an emitter who wears a face shield. A realistic manikin model with a simplified mouth cavity is employed. A large eddy simulation with a dynamic structure subgrid scale model is applied to model the turbulence. An Eulerian-Lagrangian approach is adopted to model the two-phase flows, with which the droplets are represented by a cloud of particles. The droplet breakup, evaporation, dispersion, drag force, and wall impingement are considered in this model. An inlet velocity profile that is based on a variable mouth opening area is considered. Special attentions have been put the vortex structure and droplet re-distribution induced by the face shield. It is found that the multiple vortices are formed when the cough jet impinges on the face shield. Some droplets move backward and others move downward after the impinging. It is also found that a small modification of the face shield significantly modifies the flow field and droplet distribution. We conclude that face shield significantly reduces the risk factor in the front of the emitter, meanwhile the risk factor in the back of the emitter increases. When the receiver standing in front of the emitter is shorter than the emitter, the risk is still very high. More attentions should be paid on the design of the face field, clothes cleaning and floor cleaning of the emitters with face shields. Based on the predicted droplet trajectory, a conceptual model for droplet flux is proposed for the scenario with the face shield.

Identification of an m6A RNA Methylation Regulator Risk Score Model for Prediction of Clinical Prognosis in Astrocytoma.

Astrocytoma (AS) is the most ubiquitous primary malignancy of the central nervous system (CNS). The vital involvement of the N6-methyladenosine (m6A) RNA modification in the growth of multiple human tumors is known. This study entailed probing m6A regulators with AS prognosis to construct a risk prediction model (RS) for potential clinical use. A total of 579 AS patients' (of the Chinese Glioma Genome Atlas,CGGA) data and the expression of 12 published m6A-related genes were included in this study. Cox and selection operator (LASSO) regression analyses for independent prognostic factors and multifactor Cox analysis established an R.S. model to predict the AS patient prognosis. This was subject to verification employing 331 samples from the TCGA data set followed by gene ontology and pathway enrichment study with gene set enrichment analysis (GSEA). The R.S. constructed with three m6A genes inclusive of WTAP, RBM15, and YTHDF2 emerged as independent prognostic factors in AS patients with vital involvement in the advancement and development of the malignancy. In a nutshell, this work reported an m6A-related gene risk model to predict the prognosis of AS patients to pave the way for discerning diagnostic and prognostic biomarkers. Further corroboration employing relevant wet-lab assays of this model is warranted.

Enrichment and speciation of chromium during basalt weathering: Insights from variably weathered profiles in the Leizhou Peninsula, South China.

Basalt-derived soils are widespread worldwide. Such soils contain high levels of heavy metals like chromium (Cr), which is a serious environmental concern. However, little is known regarding the enrichment and speciation of Cr during the basalt weathering process. Therefore, two basalt-derived soil profiles (Nitisol and Ferralsol) in the Leizhou Peninsula, south tropical China, were investigated to explore the redistribution and transformation of Cr during basalt weathering. All profiles could be divided into three layers: rocks, saprolites, and soils. The Nitisol and Ferralsol profiles exhibited strong (kaolinization) and extreme (laterization) degrees of weathering, respectively. Results showed that Cr concentrations in the saprolites (234 to 315 mg·kg-1) were higher than those in basalt rocks (139 to 159 mg·kg-1), indicating that Cr was enriched with the continuous loss of Si and other mobile macro-elements. While high levels of Cr were also enriched in the soils (178 to 430 mg·kg-1) accompanied with Fe. However, in the upper soils of the Ferralsol profile, the acidity and organic matter could promote the leaching of Cr. Geochemical fractions and EPMA mapping showed that chromite and olivine were the main Cr-bearing minerals in basalt, but Fe-oxides (e.g., goethite and hematite) contained the highest portion of Cr in weathered saprolites and soils. The availability of Cr in the soil was extremely low due to the high stability of Cr bound to Fe-oxides. However, the decreasing contents of Cr bound to Fe-oxides in the upper soils of the Ferralsol profile indicated that Cr could also be released during Fe leaching. In conclusion, the weathering of basalt can lead to the enrichment of Cr in Fe-(hydro)oxides, which are the main controlling minerals for Cr mobility in basalt-derived soils. Further research is needed to evaluate the effect of Fe-(hydro)oxide formation and dissolution on the release of soil Cr.

Autophagy regulates inflammation in intracerebral hemorrhage: Enemy or friend?

Intracerebral hemorrhage (ICH) is the second-largest stroke subtype and has a high mortality and disability rate. Secondary brain injury (SBI) is delayed after ICH. The main contributors to SBI are inflammation, oxidative stress, and excitotoxicity. Harmful substances from blood and hemolysis, such as hemoglobin, thrombin, and iron, induce SBI. When cells suffer stress, a critical protective mechanism called "autophagy" help to maintain the homeostasis of damaged cells, remove harmful substances or damaged organelles, and recycle them. Autophagy plays a critical role in the pathology of ICH, and its function remains controversial. Several lines of evidence demonstrate a pro-survival role for autophagy in ICH by facilitating the removal of damaged proteins and organelles. However, many studies have found that heme and iron can aggravate SBI by enhancing autophagy. Autophagy and inflammation are essential culprits in the progression of brain injury. It is a fascinating hypothesis that autophagy regulates inflammation in ICH-induced SBI. Autophagy could degrade and clear pro-IL-1ß and apoptosis-associated speck-like protein containing a CARD (ASC) to antagonize NLRP3-mediated inflammation. In addition, mitophagy can remove endogenous activators of inflammasomes, such as reactive oxygen species (ROS), inflammatory components, and cytokines, in damaged mitochondria. However, many studies support the idea that autophagy activates microglia and aggravates microglial inflammation via the toll-like receptor 4 (TLR4) pathway. In addition, autophagy can promote ICH-induced SBI through inflammasome-dependent NLRP6-mediated inflammation. Moreover, some resident cells in the brain are involved in autophagy in regulating inflammation after ICH. Some compounds or therapeutic targets that regulate inflammation by autophagy may represent promising candidates for the treatment of ICH-induced SBI. In conclusion, the mutual regulation of autophagy and inflammation in ICH is worth exploring. The control of inflammation by autophagy will hopefully prove to be an essential treatment target for ICH.

Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma.

OBJECTIVE: The present study used the RNA sequencing (RNA-seq) dataset to identify prognostic snoRNAs and construct a prognostic signature of The Cancer Genome Atla (TCGA) lower grade glioma (LGG) cohort, and comprehensive analysis of this signature. METHODS: RNA-seq dataset of 488 patients from TCGA LGG cohort were included in this study. Comprehensive analysis including function enrichment, gene set enrichment analysis (GSEA), immune infiltration, cancer immune microenvironment, and connectivity map (CMap) were used to evaluate the snoRNAs prognostic signature. RESULTS: We identified 21 LGG prognostic snoRNAs and constructed a novel eleven-snoRNA prognostic signature for LGG patients. Survival analysis suggests that this signature is an independent prognostic risk factor for LGG, and the prognosis of LGG patients with a high-risk phenotype is poor (adjusted P = 0.003, adjusted hazard ratio = 2.076, 95% confidence interval = 1.290-3.340). GSEA and functional enrichment analysis suggest that this signature may be involved in the following biological processes and signaling pathways: such as cell cycle, Wnt, mitogen-activated protein kinase, janus kinase/signal transducer and activator of tran-ions, T cell receptor, nuclear factor-kappa B signaling pathway. CMap analysis screened out ten targeted therapy drugs for this signature: 15-delta prostaglandin J2, MG-262, vorinostat, 5155877, puromycin, anisomycin, withaferin A, ciclopirox, chloropyrazine and megestrol. We also found that high- and low-risk score phenotypes of LGG patients have significant differences in immune infiltration and cancer immune microenvironment. CONCLUSIONS: The present study identified a novel eleven-snoRNA prognostic signature of LGG and performed a integrative analysis of its molecular mechanisms and relationship with tumor immunity.

Quantification of nickel and cobalt mobility and accumulation via the phloem in the hyperaccumulator Noccaea caerulescens (Brassicaceae).

Hyperaccumulators have exceptional phloem translocation capability for heavy metals. This study aims at quantifying the mobility and accumulation of Ni and Co via the phloem in the model hyperaccumulator Noccaea caerulescens. "Phloem loading capability (PLC)," which is calculated by the "Metal content in phloem sap/Metal content in leaves," was introduced to evaluate the metal phloem mobility, while "Phloem mobility value (PMV)" was used for the normalization of PLC, which sets the PLC of Sr as PMV 0 and that of Rb as 100. The results showed that the PMVs of Ni and Co were 63 and 47, respectively. And the phloem mobility of Rb, Ni, Co, and Sr could be graded as highly mobile, mobile, intermediate, and immobile accordingly. The phloem stream can supply up to 19.1% and 16.0% of the total Ni and Co accumulated in the young leaves, respectively, while for Rb and Sr, the phloem contributes to 29% and 1.4% of the total Rb or Sr, indicating phloem contribution of certain metal is directly linked with its mobility. The results of this study raise the importance of phloem translocation on metal accumulation in shoots and provide insights on the metal cycling process in hyperaccumulators.

Climate extremes, variability, and trade shape biogeographical patterns of alien species.

Understanding how alien species assemble is crucial for predicting changes to community structure caused by biological invasions and for directing management strategies for alien species, but patterns and drivers of alien species assemblages remain poorly understood relative to native species. Climate has been suggested as a crucial filter of invasion-driven homogenization of biodiversity. However, it remains unclear which climatic factors drive the assemblage of alien species. Here, we compiled global data at both grid scale (2,653 native and 2,806 current grids with a resolution of 2° × 2°) and administrative scale (271 native and 297 current nations and sub-nations) on the distributions of 361 alien amphibians and reptiles (herpetofauna), the most threatened vertebrate group on the planet. We found that geographical distance, a proxy for natural dispersal barriers, was the dominant variable contributing to alien herpetofaunal assemblage in native ranges. In contrast, climatic factors explained more unique variation in alien herpetofaunal assemblage after than before invasions. This pattern was driven by extremely high temperatures and precipitation seasonality, 2 hallmarks of global climate change, and bilateral trade which can account for the alien assemblage after invasions. Our results indicated that human-assisted species introductions combined with climate change may accelerate the reorganization of global species distributions.

Oncogene PLCE1 may be a diagnostic biomarker and prognostic biomarker by influencing cell cycle, proliferation, migration, and invasion ability in hepatocellular carcinoma cell lines.

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide. HCC has traits of late diagnosis and high recurrence. This study explored potential diagnosis and prognosis significance of phospholipase C epsilon 1 (PLCE1) in HCC. The messenger RNA (mRNA) levels and diagnostic value of PLCE1 were determined by real-time polymerase chain reaction and online databases GEPIA, oncomine, and GSE14520 data set. Survival analysis used the Kaplan-Meier Plotter website. Cell cycle, proliferation, migration, and invasion assays were performed with downregulated PLCE1 expression in HCC-M and HepG2 cell lines. PLCE1 was differentially expressed and highly expressed in tumors and had low expression in nontumor tissues (all p < .05). The diagnostic value of PLCE1 was validated with the datasets (all p < .01, all areas under curves > 0.7). PLCE1 mRNA expression was associated with the overall and relapse-free survival (both p < .05). Functional experiments indicated that downregulation of PLCE1 expression led to increased G1 stage in cell cycle and decreased cell proliferation, migration, and invasion compared with a negative control group (all p ≤ .05). The oncogene PLCE1 was differentially expressed in HCC and non-HCC tissues. It is a candidate for diagnosis and serves as prognosis biomarker. PLCE1 influenced survival by affecting the cell cycle, proliferation, migration, and invasion ability.

Ammonium nutrition mitigates cadmium toxicity in rice (Oryza sativa L.) through improving antioxidase system and the glutathione-ascorbate cycle efficiency.

Nitrogen (N) forms not only affect cadmium (Cd) accumulation in plants, but also affect plant resistance to Cd toxicity. However, few researches have been reported underlying the mechanism of the relationship between nitrogen forms and plant resistance under Cd exposure. Here, we explored the mechanism on how different NO3-/NH4+ ratios affect antioxidase system and the glutathione-ascorbate cycle under five different ratios of NO3-/NH4+ (1:0, 2:1, 1:1, 1:2, 0:1) and three dosages of Cd exposure (0, 1, 5 µmol L-1 Cd) in rice (Oryza sativa L.). The results showed that high NO3- and high Cd exposure both significantly inhibited tissue growth of rice plants, and this inhibiting trend was mitigated with increasing NH4+ ratios as proved by the increased biomass and the decreased concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2), as well as the levels of Cd contents in rice tissues. Additionally, high NH4+ ratios elevated the SOD activities in rice tissues, especially at high Cd treatment. However, other two antioxidases (CAT and APX) were insensitive to changes of NO3-/NH4+ ratios (except the full NO3-). Furthermore, high NH4+ ratios induced increasing of the efficiency of glutathione-ascorbate cycle (GSH-AsA) under two levels of Cd exposure, as evidenced by increasing concentrations of GSH and AsA and the activities of GR and DHAR in rice tissues. Overall, these results revealed that ammonium nutrition caused an enhancement resistance to Cd stress in rice plants was responsible for increasing of partial antioxidase system and the efficiencies of GSH-AsA cycle.

Diagnostic and prognostic significance of mRNA expressions of apolipoprotein A and C family genes in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common and lethal malignancies worldwide. Apolipoproteins (APOs) have been reported increasingly for their relationships with tumors. We aim at exploring the potential relationships of apolipoprotein A (APOA) and apolipoprotein C (APOC) family members with HCC. METHODS: A data set, containing 212 hepatitis B virus-related HCC patients, was used for analysis. The diagnostic and prognostic ability of APOA and APOC family genes was figured out. Risk score models and nomograms were developed for the HCC prognosis prediction. Moreover, molecular mechanism exploration were identified biological processes and metabolic pathways of these genes involved in. Validation analysis was carried out using online website. RESULTS: APOA1, APOC1, APOC3, and APOC4 showed robust diagnosis significance (all P < 0.05). APOA4, APOC3, and APOC4 were associated with the overall survival (OS) while APOA4 and APOC4 were linked to recurrence-free survival (RFS, all P ≤ 0.05). Risk score models and nomograms had the advantage of predicting OS and RFS for HCC. Molecular mechanism exploration indicated that these genes were involved in the steroid metabolic process, the PPAR signaling pathway, and fatty acid metabolism. Besides that, validation analysis revealed that APOC1 and APOC4 had an association with OS; and APOC3 was associated with OS and RFS (all P ≤ 0.05). CONCLUSIONS: APOA1, APOC1, APOC3, and APOC4 are likely to be potential diagnostic biomarkers and APOC3 and APOC4 are likely to be potential prognostic biomarkers for hepatitis B virus-related HCC. They may be involved in the steroid metabolic process, PPAR signaling pathway, and fatty acid metabolism.

Use of Genome-Scale Integrated Analysis to Identify Key Genes and Potential Molecular Mechanisms in Recurrence of Lower-Grade Brain Glioma.

BACKGROUND The aim of this study was to identify gene signals for lower-grade glioma (LGG) and to assess their potential as recurrence biomarkers. MATERIAL AND METHODS An LGG-related mRNA sequencing dataset was downloaded from The Cancer Genome Atlas (TCGA) Informix. Multiple bioinformatics analysis methods were used to identify key genes and potential molecular mechanisms in recurrence of LGG. RESULTS A total of 326 differentially-expressed genes (DEGs), were identified from 511 primary LGG tumor and 18 recurrent samples. Gene ontology (GO) analysis revealed that the DEGs were implicated in cell differentiation, neuron differentiation, negative regulation of neuron differentiation, and cell proliferation in the forebrain. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database suggests that DEGs are associated with proteoglycans in cancer, the Wnt signaling pathway, ECM-receptor interaction, the PI3K-Akt signaling pathway, transcriptional deregulation in cancer, and the Hippo signaling pathway. The hub DEGs in the protein-protein interaction network are apolipoprotein A2 (APOA2), collagen type III alpha 1 chain (COL3A1), collagen type I alpha 1 chain (COL1A1), tyrosinase (TYR), collagen type I alpha 2 chain (COL1A2), neurotensin (NTS), collagen type V alpha 1 chain (COL5A1), poly(A) polymerase beta (PAPOLB), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and anomalous homeobox (ANHX). GSEA revealed that the following biological processes may associated with LGG recurrence: cell cycle, DNA replication and repair, regulation of apoptosis, neuronal differentiation, and Wnt signaling pathway. CONCLUSIONS Our study demonstrated that hub DEGs may assist in the molecular understanding of LGG recurrence. These findings still need further molecular studies to identify the assignment of DEGs in LGG.