Low expression of ZSCAN4 predicts unfavorable outcome in urothelial carcinoma of upper urinary tract and urinary bladder.

BACKGROUND: With the advance in genome-wide analyses, genetic alternations have been found to play an important role in carcinogenesis and aggressiveness of UC. Through bioinformatic analysis of gene expression profiles of urinary bladder urothelial carcinoma (UBUC) from publicly available GEO dataset (GSE31684), Zinc finger and SCAN domain containing 4 (ZSCAN4) was identified as a significant downregulated gene in muscle-invasive bladder cancer when compared with non-muscle-invasive bladder cancer. METHODS: The expression of ZSCAN4 was evaluated by immunohistochemistry in 340 upper urinary tract urothelial carcinomas (UTUCs) and 295 UBUCs. The expression profiles of ZSCAN4 and potential signaling pathways were analyzed bioinformatically. RESULTS: In UTUC, low expression of ZSCAN4 was significantly associated with advanced primary pT stage (P = 0.011), increased nodal metastasis (P = 0.002) and increased vascular invasion (P = 0.019). In UBUC, low expression of ZSCAN4 was significantly correlated with advanced primary pT stage (P < 0.001), increased nodal metastasis (P = 0.001), high histological grade (P = 0.003) and increased vascular invasion (P = 0.003). In survival analysis, low expression of ZSCAN4 acted as an independent negative prognostic factor for disease-specific survival and metastasis-free survival both in UTUC and UBUC. Gene ontology analysis showed that ZSCAN4 mRNA and its co-downregulated genes are associated with the mitotic cell cycle. CONCLUSIONS: Low expression of ZSCAN4 predicted worse outcome in urothelial carcinoma and might have potential regulatory role in cell mitosis.

Pixel-scale historical-baseline-based ecological quality: Measuring impacts from climate change and human activities from 2000 to 2018 in China.

Widespread concern about ecological degradation has prompted development of concepts and exploration of methods to quantify ecological quality with the aim of measuring ecosystem changes to contribute to future policy-making. This paper proposes a conceptual framework for ecological quality measurement based on current ecosystem functions and biodiverse habitat, compared with pixel-scale historical baselines. The framework was applied to evaluate the changes and driving factors of ecological quality for Chinese terrestrial ecosystems through remote sensing-based and ecosystem process modeled data at 1 km spatial resolution from 2000 to 2018. The results demonstrated the ecological quality index (EQI) had a very different spatial pattern based upon vegetation distribution. An upward trend in EQI was found over most areas, and variability of 46.95% in EQI can be explained well by change in climate, with an additional 10.64% explained by changing human activities, quantified by population density. This study demonstrated a practical and objective approach for quantifying and assessing ecological quality, which has application potential in ecosystem assessments on scales from local to region and nation, yet would provide a new scientific concept and paradigm for macro ecosystems management and decision-making by governments.

Improvement of ecosystem quality in National Key Ecological Function Zones in China during 2000-2015.

Improving ecosystem quality is the ultimate goal of ecological restoration projects and sustainable ecosystem management. However, previous results of ecosystem quality lack comparability among different regions when assessing the effectiveness of ecological restoration projects on the regional or national scales, due to the influence of geographical and climatic background conditions. Here we proposed a new index, ecosystem quality ratio (EQR), by integrating the status of landscape structure, ecosystem services, ecosystem stability, and human disturbance relative to their reference conditions, and assessed the EQR changes in China's counties and National Key Ecological Function Zones (NKEFZs) from 1990 to 2015. The results showed that the average ecosystem quality of China's counties deviated from the reference condition by 28%. EQR decreased by 1.2% during 1990-2000 but increased by 3.7% during 2000-2015. Those counties with increasing EQR in 2000-2015 occupy 64.7%, with obviously increasing counties mainly located in the water conservation, biodiversity maintenance, and water and soil conservation types of NKEFZs. The EQR increase in counties within NKEFZs was 3.65 times that outside of NKEFZs. Remarkable improvement of ecosystem quality occurred in the forest region in Changbai Mountain, biodiversity and soil conservation region in Wuling Mountains, and hilly and gully region of Loess Plateau, where EQR increases mainly resulted from the conversion of farmland to forest or grassland and consequent increases in ecosystem services and stability. The magnitude of EQR enhancement showed a positive relationship with the increase in forest and grassland coverage in NKEFZs. Our results highlight the important role of ecological restoration projects in improving ecosystem quality in China, and demonstrate the feasibility of the new index (EQR) for the assessment of ecosystem quality in terms of ecosystem management and restoration.

Prognostic significance of OXR1 in urothelial carcinoma: low OXR1 expression is associated with worse survival.

Background: Bioinformatic analysis has revealed that OXR1 is significantly downregulated in muscle-invasive bladder cancer. Patients & methods: The expression of OXR1 in patients with urothelial carcinoma was evaluated by immunohistochemistry, including 340 cases with urothelial carcinoma in the upper urinary tract and 295 in the urinary bladder. Results: Low expression of OXR1 was significantly correlated with adverse pathological parameters including high primary tumor (pT) stage, high node stage, high histological grade, high mitotic activity and increased vascular or perineural invasion (all p < 0.05). Low expression of OXR1 independently predicted worse metastasis-free survival (p = 0.033) in urothelial carcinoma of the upper urinary tract and worse disease-specific survival (p = 0.022) and metastasis-free survival (p < 0.001) in urothelial carcinoma of the urinary bladder. Conclusion: Low expression of OXR1 is an adverse prognostic factor in urothelial carcinoma.

High FRMD3 expression is prognostic for worse survival in rectal cancer patients treated with CCRT.

BACKGROUND: Rectal cancer patients can conceivably obtain relief from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before resection, but the stratification of risk and clinical outcomes remains challenging. Therefore, identifying effective predictive biomarkers offers clinicians the opportunity to individually tailor early interventions, which would help optimize therapy. METHODS: Using a public rectal cancer transcriptome dataset (GSE35452), we focused on cytoskeletal protein binding (GO: 0008092)-related genes and identified FERM domain containing 3 (FRMD3) as the most significant differentially expressed gene associated with CCRT resistance. We gathered 172 tumor samples from rectal cancer patients treated with neoadjuvant CCRT accompanied by curative resection and estimated the expression level of FRMD3 using immunohistochemistry. RESULTS: The results revealed that high FRMD3 immunoexpression was remarkably associated with advanced pre-CCRT and post-CCRT tumor status (p = 0.004 and p < 0.001), pre-CCRT and post-CCRT lymph node metastasis (both p < 0.001), more perineurial invasion (p = 0.023), and a smaller extent of tumor regression (p = 0.018). High FRMD3 immunoexpression was remarkably correlated with inferior disease-specific survival (DSS) (p = 0.0001), local recurrence-free survival (LRFS) (p = 0.0003), and metastasis-free survival (MeFS) (p = 0.0023) at the univariate level. Furthermore, in multivariate analysis, high FRMD3 immunoexpression remained independently predictive of inferior DSS (p = 0.002), LRFS (p = 0.005), and MeFS (p = 0.015). CONCLUSION: These results suggest that high FRMD3 expression is related to advanced clinicopathological features and inferior therapeutic responses in rectal cancer patients treated with CCRT, validating the promising prognostic value of FRMD3 expression.

Patterns of plant carbon, nitrogen, and phosphorus concentration in relation to productivity in China's terrestrial ecosystems.

Plant nitrogen (N) and phosphorus (P) content regulate productivity and carbon (C) sequestration in terrestrial ecosystems. Estimates of the allocation of N and P content in plant tissues and the relationship between nutrient content and photosynthetic capacity are critical to predicting future ecosystem C sequestration under global change. In this study, by investigating the nutrient concentrations of plant leaves, stems, and roots across China's terrestrial biomes, we document large-scale patterns of community-level concentrations of C, N, and P. We also examine the possible correlation between nutrient content and plant production as indicated by vegetation gross primary productivity (GPP). The nationally averaged community concentrations of C, N, and P were 436.8, 14.14, and 1.11 mg·g-1 for leaves; 448.3, 3.04 and 0.31 mg·g-1 for stems; and 418.2, 4.85, and 0.47 mg·g-1 for roots, respectively. The nationally averaged leaf N and P productivity was 249.5 g C GPP·g-1 N·y-1 and 3,157.9 g C GPP·g-1 P·y-1, respectively. The N and P concentrations in stems and roots were generally more sensitive to the abiotic environment than those in leaves. There were strong power-law relationships between N (or P) content in different tissues for all biomes, which were closely coupled with vegetation GPP. These findings not only provide key parameters to develop empirical models to scale the responses of plants to global change from a single tissue to the whole community but also offer large-scale evidence of biome-dependent regulation of C sequestration by nutrients.

High glycosyltransferase 8 domain containing two protein levels contribute to poor prognosis in urothelial carcinoma.

OBJECTIVE: To examine the expression levels of the glycosyltransferase 8 domain containing protein 2 and its clinical implications in urothelial carcinoma patients. METHODS: Data mining, immunohistochemistry together with H-score calculation was carried out to evaluate the glycosyltransferase 8 domain containing protein 2 levels on tissue specimens from urothelial carcinoma patients, retrospectively. Correlations between glycosyltransferase 8 domain containing protein 2 H-score and imperative clinicopathological factors were measured. The indication of glycosyltransferase 8 domain containing protein 2 level on disease-specific and metastasis-free survivals were next analyzed. RESULTS: In upper tract urothelial carcinomas (n = 340) and bladder urothelial carcinomas (n = 295), 170 (50%) and 148 (50%) patients, respectively, were identified to have high glycosyltransferase 8 domain containing protein 2 expression. The glycosyltransferase 8 domain containing protein 2 levels were correlated to several clinicopathological characteristics and patient survival. Upregulation of the glycosyltransferase 8 domain containing protein 2 was correlated to primary tumor (P < 0.001), nodal metastasis (P < 0.001), histological grade (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.05) and mitotic rate (P < 0.001). High glycosyltransferase 8 domain containing protein 2 levels independently predicted poor disease-specific survival (P = 0.049) and metastasis-free survival (P = 0.008) in upper tract urothelial carcinoma and urinary bladder urothelial carcinoma, respectively. Gene Ontology enrichment analysis additionally showed that multiple biological processes were enriched including "ECM organization" (Gene Ontology:0030198), "extracellular structure organization" (Gene Ontology:0043062), "biological adhesion" (Gene Ontology:0022610), "cell adhesion" (Gene Ontology:0007155), "collagen fibril organization" (Gene Ontology:0030199) and "vasculature development" (Gene Ontology:0001944). CONCLUSIONS: The present findings suggest that upregulation of the glycosyltransferase 8 domain containing protein 2 is an independent and disadvantageous prognosticator in urothelial carcinoma. High glycosyltransferase 8 domain containing protein 2 level might play a crucial role in progression of urothelial carcinoma.

High G protein subunit beta 4 protein level is correlated to poor prognosis of urothelial carcinoma.

Data mining on a public domain detected eight potential transcripts which were upregulated in advanced UBUCs, suggesting that they may take part in UC development or/and progression. Retrospectively, immunohistochemistry along with H-score recording was carried out to evaluate the GNB4 protein levels on tissues from UC patients. Correlations between GNB4 H-score and imperative clinicopathological factors, as well as the implication of GNB4 protein level on disease-specific and metastasis-free survivals were assessed. In UTUCs (n = 340) and UBUCs (n = 295), 170 (50.0%) and 148 (50.0%) cases, respectively, were identified to be of high GNB4 expression. The GNB4 protein levels were correlated to numerous clinicopathological features and patients' survivals. Upregulation of the GNB4 protein was significantly associated with primary tumor, nodal metastasis, histological grade, vascular invasion and mitotic rate. High GNB4 protein levels independently and significantly predicted poor disease-specific and metastasis-free in UTUC and UBUC, respectively. Ingenuity pathway analysis furthermore showed that multiple signaling pathways were enriched including 'Communication between Innate and Adaptive Immune Cells' and 'NFκB Signaling'. Our findings demonstrated that the upregulation of the GNB4 protein is an independent unfavorable prognosticator in UC. High GNB4 gene expression plays an important role in UC progression.

Underestimated ecosystem carbon turnover time and sequestration under the steady state assumption: A perspective from long-term data assimilation.

It is critical to accurately estimate carbon (C) turnover time as it dominates the uncertainty in ecosystem C sinks and their response to future climate change. In the absence of direct observations of ecosystem C losses, C turnover times are commonly estimated under the steady state assumption (SSA), which has been applied across a large range of temporal and spatial scales including many at which the validity of the assumption is likely to be violated. However, the errors associated with improperly applying SSA to estimate C turnover time and its covariance with climate as well as ecosystem C sequestrations have yet to be fully quantified. Here, we developed a novel model-data fusion framework and systematically analyzed the SSA-induced biases using time-series data collected from 10 permanent forest plots in the eastern China monsoon region. The results showed that (a) the SSA significantly underestimated mean turnover times (MTTs) by 29%, thereby leading to a 4.83-fold underestimation of the net ecosystem productivity (NEP) in these forest ecosystems, a major C sink globally; (b) the SSA-induced bias in MTT and NEP correlates negatively with forest age, which provides a significant caveat for applying the SSA to young-aged ecosystems; and (c) the sensitivity of MTT to temperature and precipitation was 22% and 42% lower, respectively, under the SSA. Thus, under the expected climate change, spatiotemporal changes in MTT are likely to be underestimated, thereby resulting in large errors in the variability of predicted global NEP. With the development of observation technology and the accumulation of spatiotemporal data, we suggest estimating MTTs at the disequilibrium state via long-term data assimilation, thereby effectively reducing the uncertainty in ecosystem C sequestration estimations and providing a better understanding of regional or global C cycle dynamics and C-climate feedback.

Modelling the impacts of climate and land use changes on soil water erosion: Model applications, limitations and future challenges.

The world is experiencing serious soil losses. Soil erosion has become an important environmental problem in certain regions and is strongly affected by climate and land use changes. By selecting and reviewing 13 extensively used soil water erosion models (SWEMs) from the published literature, we summarize the current model-based knowledge on how climate factors (e.g., rainfall, freeze-thaw cycles, rainstorms, temperature and atmospheric CO2 concentrations) and land use change impact soil erosion worldwide. This study also provides a critical review of the application of these 13 SWEMs. By comparing model structures, features, prediction accuracies, and erosion processes, we recommend the most suitable SWEMs for different regions of the globe (Asia, Europe, Africa and the America) based on the evaluations of 13 SWEMs. Future soil erosion could be simulated using the RUSLE, LISEM, WEPP v2010.1, SWAT, EPIC, KINEROS and AGNPS models in Asia; the RUSLE, WEPP v2010.1, SWAT, EPIC, WATEM-SEDEM, MEFIDIS, AGNPS and AnnAGNPS models in Europe; the RUSLE, LISEM, SWAT, and AGNPS models in Africa; and the WEPP v2010.1, SWAT, EPIC, KINEROS, AGNPS and AnnAGNPS models in America. Finally, the limitations and challenges of the 13 SWEMs are highlighted.

Spatiotemporal pattern of gross primary productivity and its covariation with climate in China over the last thirty years.

The uncertainties of China's gross primary productivity (GPP) estimates by global data-oriented products and ecosystem models justify a development of high-resolution data-oriented GPP dataset over China. We applied a machine learning algorithm developing a new GPP dataset for China with 0.1° spatial resolution and monthly temporal frequency based on eddy flux measurements from 40 sites in China and surrounding countries, most of which have not been explored in previous global GPP datasets. According to our estimates, mean annual GPP over China is 6.62 ± 0.23 PgC/year during 1982-2015 with a clear gradient from southeast to northwest. The trend of GPP estimated by this study (0.020 ± 0.002 PgC/year2 from 1982 to 2015) is almost two times of that estimated by the previous global dataset. The GPP increment is widely spread with 60% area showing significant increasing trend (p < .05), except for Inner Mongolia. Most ecosystem models overestimated the GPP magnitudes but underestimated the temporal trend of GPP. The monsoon affected eastern China, in particular the area surrounding Qinling Mountain, seems having larger contribution to interannual variability (IAV) of China's GPP than the semiarid northwestern China and Tibetan Plateau. At country scale, temperature is the dominant climatic driver for IAV of GPP. The area where IAV of GPP dominated by temperature is about 42%, while precipitation and solar radiation dominate 31% and 27% respectively over semiarid area and cold-wet area. Such spatial pattern was generally consistent with global GPP dataset, except over the Tibetan Plateau and northeastern forests, but not captured by most ecosystem models, highlighting future research needs to improve the modeling of ecosystem response to climate variations.

CDKN3 expression is an independent prognostic factor and associated with advanced tumor stage in nasopharyngeal carcinoma.

Background: Through data mining from the public transcriptome of NPC, cyclin-dependent kinase inhibitor 3 (CDKN3) was identified as a significantly upregulated gene in NPC. CDKN3 functions as a key factor in cell cycle regulation. This study was aimed to investigate the expression of CDKN3 in NPC tissues and its prognostic significance. Methods: Immunohistochemistry was performed for 124 NPC patients to assess the protein expression of CDKN3. The stainings of CDKN3 were scored by using H-score method. The relationships between CDKN3 expression status and clinicopathological parameters, disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) were statistically analyzed. Results: High expression of CDKN3 was significantly associated with higher primary nodal status (P=0.030) and higher TNM stage (P=0.019). In univariate analysis, high expression of CDKN3 predicted worse DSS (P<0.0001), DMeFS (P<0.0001), and LRFS (P<0.0001). In multivariate analysis, CDKN3 overexpression still acted as an independent prognostic factor for worse DSS (P<0.001; hazard ratio [HR]=11.999, 95% CI: 5.378-26.771), DMeFS (P<0.001; HR=15.069, 95% CI: 5.884-38.592), and LRFS (P<0.001; HR=5.000, 95% CI: 2.312-10.815). Conclusion: High expression of CDKN3 was an independent negative prognostic factor for NPC and was associated with advanced disease status. It might serve as potential therapeutic target and aid in risk stratification for patients with NPC.

SERPINB5 Expression: Association with CCRT Response and Prognostic Value in Rectal Cancer.

Background: Due to the varying characteristics and conflicting outcomes on the overall survival of rectal cancer patients, many studies have been undertaken to determine various prognostic and predictive factors for the mainstay treatment of CCRT followed by surgery. Cancer cell motility contributes to tumor invasion, migration and eventually metastasis. However, the genes associated with cell motility (i.e., GO:0048870) have not been systemically evaluated in rectal cancers. Methods: A comparative analysis of gene expression profiles was applied to the transcriptomic dataset (GSE35452) with a focus on genes associated with cell motility (GO:0048870), where SERPINB5 was recognized as the most significantly up-regulated gene. Tumor samples from 172 primary rectal cancer patients who underwent neoadjuvant CCRT followed by surgical resection were collected. Immunohistochemistry was used to semi-quantitatively assess the expression level of SERPINB5 protein. Statistical analyses of SERPINB5 expression and various clinicopathological features as well as survival were then performed. Results: High immunoreactivity of SERPINB5 was significantly linked to pre- and post-CCRT advanced disease, lymphovascular invasion, and poor response to CCRT (all P ≤ 0.015). SERPINB5 overexpression was not only negatively associated with disease-specific survival (DSS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) rates in univariate analyses but also was an independent prognostic factor for DSS and MeFS in rectal cancer patients (all P ≤ 0.043). Conclusion: SERPINB5 may play an important role in rectal cancer progression and response to neoadjuvant CCRT and serve as a novel prognostic factor.

High chloride channel accessory 1 expression predicts poor prognoses in patients with rectal cancer receiving chemoradiotherapy.

Background: Concurrent chemoradiotherapy (CCRT) has now become the standard of treatments for advanced rectal cancer before surgery. To search the biological molecules with prognostic and therapeutic potential of CCRT could be beneficial for these patients. Recently, aberrant expression of chloride channels has been linked to radio-resistance in glioblastoma; however, its clinical implication has not been well-studied in rectal cancers. Therefore, we examined the clinical significance of targetable drivers associated with chloride channel activity in patients with rectal cancer receiving CCRT. Methods: After datamining from a published transcriptome of rectal cancers, upregulation of CLCA1 gene was recognized to be significantly correlated with non-responders of CCRT. In validation cohort of rectal cancers, the expression levels of CLCA1 were accessed by using immunohistochemistry assays in 172 tumor specimens that were obtained before any treatment. Expression levels of CLCA1 were statistically analyzed with principal clinicopathological features and survival outcomes in this substantial cohort. Results: In validation cohort, high expression of CLCA1 was significantly associated with higher pre-treatment tumor nodal stages (P=0.032), vascular invasion (P=0.028), and inferior tumor regression grade (P=0.042). In survival evaluations, high expression of CLCA1 was significantly correlated with worse local recurrence-free survival (LRFS; P=0.0012), metastasis-free survival (MeFS; P =0.0114), and disease-specific survival (DSS; P=0.0041). Furthermore, high expression of CLCA1 remained an independent prognosticator of shorter LRFS (P=0.029, hazard ratio=2.555), MeFS (P=0.044, hazard ratio=2.125) and DSS (P=0.044, hazard ratio=2.172). Conclusions: High expression of CLCA1 is significantly associated with poor therapeutic response and survival outcomes in rectal cancer patients with CCRT treatment before surgery. With the development of specific inhibitors, our findings indicate not only prognostic but also therapeutic potential of CLCA1 in rectal cancers.

AMACR overexpression acts as a negative prognostic factor in oral squamous cell carcinoma.

Background: Alpha-methylacyl-CoA racemase (AMACR) is a key enzyme responsible for the metabolism of branched-chain fatty acids. It has been found to be an important prognostic factor in numerous types of cancers. This study was aimed to investigate the expression of AMACR and its prognostic significance in patients with oral squamous cell carcinoma (SCC). Methods: Analysis of publicly available microarray data of oral SCC revealed that AMACR was significantly upregulated in tumor tissue compared with normal mucosa. We further assessed the protein expression of AMACR in 164 patients with oral SCC by immunohistochemistry. The prognostic impact of AMACR expression and its association with various clinicopathological parameters were statistically analyzed. Results: AMACR overexpression was significantly associated with advanced tumor status (P=0.001), advanced nodal status (P=0.036), increased vascular invasion (P=0.026) and increased perineural invasion (P=0.004). Patients with high expression level of AMACR had significantly worse disease-specific survival (DSS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) (all P<0.0001). In multivariate analysis, AMACR overexpression was also an independent negative prognostic factor for DSS (hazard ratio [HR]: 4.410, 95% confidence interval [CI]: 2.285-8.511, P<0.001), DMFS (HR: 5.157, 95% CI: 2.756-9.651, P<0.001) and LRFS (HR: 4.462, 95% CI: 2.429-8.198, P<0.001). Conclusions: High expression of AMACR was not only a key adverse prognostic factor but also a potential therapeutic target in oral SCC.

Proteomic Identification of the Galectin-1-Involved Molecular Pathways in Urinary Bladder Urothelial Carcinoma.

Among various heterogeneous types of bladder tumors, urothelial carcinoma is the most prevalent lesion. Some of the urinary bladder urothelial carcinomas (UBUCs) develop local recurrence and may cause distal invasion. Galectin-1 de-regulation significantly affects cell transformation, cell proliferation, angiogenesis, and cell invasiveness. In continuation of our previous investigation on the role of galectin-1 in UBUC tumorigenesis, in this study, proteomics strategies were implemented in order to find more galectin-1-associated signaling pathways. The results of this study showed that galectin-1 knockdown could induce 15 down-regulated proteins and two up-regulated proteins in T24 cells. These de-regulated proteins might participate in lipid/amino acid/energy metabolism, cytoskeleton, cell proliferation, cell-cell interaction, cell apoptosis, metastasis, and protein degradation. The aforementioned dys-regulated proteins were confirmed by western immunoblotting. Proteomics results were further translated to prognostic markers by analyses of biopsy samples. Results of cohort studies demonstrated that over-expressions of glutamine synthetase, alcohol dehydrogenase (NADP⁺), fatty acid binding protein 4, and toll interacting protein in clinical specimens were all significantly associated with galectin-1 up-regulation. Univariate analyses showed that de-regulations of glutamine synthetase and fatty acid binding protein 4 in clinical samples were respectively linked to disease-specific survival and metastasis-free survival.

Production of bioactive recombinant rat soluble receptor for advanced glycation end products (rrsRAGE) in Pichia pastoris.

Soluble receptor for advanced glycation end products (sRAGE), a natural inhibitor of RAGE, is considered to be a putative therapeutic molecule for a variety of diseases and a biomarker for certain conditions. To further study the function of sRAGE, recombinant rat sRAGE (rrsRAGE) was expressed and produced in a eukaryotic system. The open reading frame of rat sRAGE was cloned downstream of the methanol-inducible alcohol oxidase promoter of pPICZαA vector, and Pichia pastoris strain X-33 was used as the host strain. The expression of rrsRAGE was achieved by fermentation in a 15-L bioreactor and the resulting fermentation broth was subjected to purification on a cation exchange chromatography column. The purification of rrsRAGE reached 95% after size exclusion chromatography(SEC). The bioactivity of the purified protein was confirmed in a SH-SY5Y cell proliferation assay. The biological function of the purified rrsRAGE protein rat CCl4-induced model was then examined. Treatment with rrsRAGE resulted in significantly lower liver fibrosis and lower serum level of ALT, suggesting that sRAGE prevent liver from injury and fibrosis. In conclusion, we achieved high-efficiency production of bioactive rrsRAGE in P. pastoris.

BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.

AIMS: Amino acid biosynthesis is one of the cardinal events of carcinogenesis that has not been investigated in urothelial carcinoma (UC). By data-mining a published transcriptomic database of UCs of urinary bladder (UBUCs) (GSE31684), we identified branched-chain amino acid transaminase 1 (BCAT1) as the most significantly stepwise up-regulated gene during tumour progression among those associated with the amino acid biosynthetic process (GO:0008652). Accordingly, we analysed BCAT1 transcript and protein expression with their clinicopathological significance. METHODS AND RESULTS: We used real-time reverse transcription-polymerase chain reaction (RT-PCR) to detect BCAT1 transcript levels in 20 UCs of upper tract (UTUCs) and 20 UBUCs, respectively. Immunohistochemical study was performed to determine BCAT1 protein expression in 340 UTUCs and 295 UBUCs. Higher BCAT1 transcript levels were associated with higher pT status in both groups (P < 0.05). BCAT1 protein overexpression was also associated significantly with adverse clinicopathological features, e.g. advanced pT stage, nodal metastasis, high pathological grade, etc. (P < 0.05). BCAT1 overexpression predicted worse disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (P ≤ 0.001). CONCLUSION: BCAT1 overexpression is associated with advanced tumour status, and implies adverse clinical outcomes of UCs, suggesting that its role in tumour progression could serve as a prognostic biomarker and a novel therapeutic target in UC.

The permafrost carbon inventory on the Tibetan Plateau: a new evaluation using deep sediment cores.

The permafrost organic carbon (OC) stock is of global significance because of its large pool size and the potential positive feedback to climate warming. However, due to the lack of systematic field observations and appropriate upscaling methodologies, substantial uncertainties exist in the permafrost OC budget, which limits our understanding of the fate of frozen carbon in a warming world. In particular, the lack of comprehensive estimates of OC stocks across alpine permafrost means that current knowledge on this issue remains incomplete. Here, we evaluated the pool size and spatial variations of permafrost OC stock to 3 m depth on the Tibetan Plateau by combining systematic measurements from a substantial number of pedons (i.e. 342 three-metre-deep cores and 177 50-cm-deep pits) with a machine learning technique (i.e. support vector machine, SVM). We also quantified uncertainties in permafrost carbon budget by conducting Monte Carlo simulations. Our results revealed that the combination of systematic measurements with the SVM model allowed spatially explicit estimates to be made. The OC density (OC amount per unit area, OCD) exhibited a decreasing trend from the south-eastern to the north-western plateau, with the exception that OCD in the swamp meadow was substantially higher than that in surrounding regions. Our results also demonstrated that Tibetan permafrost stored a large amount of OC in the top 3 m, with the median OC pool size being 15.31 Pg C (interquartile range: 13.03-17.77 Pg C). 44% of OC occurred in deep layers (i.e. 100-300 cm), close to the proportion observed across the northern circumpolar permafrost region. The large carbon pool size together with significant permafrost thawing suggests a risk of carbon emissions and positive climate feedback across the Tibetan alpine permafrost region.

Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy.

AIM: This study aimed to investigate the prognostic significance of DSG3 and its association with response to neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer. MATERIALS & METHODS: Data mining of a publicly available dataset was performed to find genes associated with CCRT response. Immunohistochemistry was applied to evaluate DSG3 expression. The relationships between DSG3 expression and various clinicopathological parameters and survival were analyzed. RESULTS: The DSG3 gene was significantly associated with CCRT response. The expression of DSG3 negatively correlated with poorer tumor regression (p < 0.001) and had an independent negative impact on disease-specific survival (p = 0.011), local recurrence-free survival (p = 0.031) and metastasis-free survival (p = 0.029). CONCLUSION: DSG3 was a key prognostic factor and predictor for CCRT response in rectal cancer patients.