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Abstract Background Mixed forests are better than monoculture forests in biodiversity, stand structure and productivity stability. However, a more comprehensive assessment of the ecosystem functions of monoculture and mixed plantations is lacking. We compared the single functions and ecosystem multifunctionality (EMF) in Fraxinus mandshurica and Larix olgensis mixed plantations with monoculture plantations in Northeast China and discussed the influences of biodiversity and environmental factors on EMF. Results The mixed plantations had higher biodiversity and ecological functions. Biodiversity was significantly higher in mixed plantations (such as CWMMH, Shrub.Shannon, Shrub.Richness, Herb.Shannon, Herb.Richness), but environmental factors differed less among the three forest types, and belowground diversity differed significantly only in the Bacterial.Shannon and Fungal.Shannon. Mixed plantations showed significant differences in single ecological functions relative to monoculture plantations, with more pronounced differences between mixed plantations and Larix olgensis monoculture plantations. Weighted ecosystem multifunctionality was significantly higher in mixed plantations than in monoculture plantations. EMF was mainly driven by tree diversity, environmental factors, shrub and herb species diversity, and soil microbial alpha diversity, which explained 25.35%, 8.94%, 8.83%, and 7.65% of the variation, respectively. Conclusions The establishment of mixed plantations can increase the biodiversity of forest stands and improve the ecosystem functions. These results highlight the advantages of multi-species plantations and the necessity of planting them. They are important for the conservation of biodiversity and the sustainable management of plantations.

Abstract Key message The diameter growth of Dahurian larch (Larix gmelini Rupr.) and white birch (Betula platyphylla Suk.) species in secondary forest of Northeast China was not only influenced by biological factors such as tree size and stand characteristics, but also significantly affected by topographic and climatic factors such as temperature and precipitation. It is necessary to consider the abiotic factors in simulating the diameter growth. Context Climate change, such as global temperature rise, increased frequency of extreme weather events, and rising sea levels, has put forest ecosystems in an unstable state and has an impact on species composition, growth harvest, productivity and other functions of forests. And this impact varies in climate scenarios, regions and forest types. Aims To gain a comprehensive understanding of the adaptation for key species to their environment in secondary forests in Northeast China, the diameter growth responses of Dahurian larch and white birch to biotic and abiotic factors were simulated to assess the effects of climate on diameter growth. Methods China’s National Forest Continuous Inventory (NFCI) data from 2005 to 2015 were used to develop linear mixed-effects diameter growth models with plot-level random effects, and leave-one-out cross-validation was applied to evaluate the developed models. At the beginning of modeling, correlation analysis and best-subset regression were used to analyze the correlation between the diameter increment and the biotic and abiotic factors. Results (i) Sorting the categories of predictors in descending order based on the relative importance of the significant predictors, diameter growth of Dahurian larch was affected by competition, tree size, topographic conditions, stand attributes, diversity index, and climate factors, while the white birch species was affected by competition, tree size, stand attributes, climate factors, diversity index, and topographic conditions; (ii) the plot-level mixed-effects model, which achieved better fit and prediction performance than did basic linear models of individual-tree diameter growth in the cases of prediction calibration, was preferable for modeling individual-tree diameter growth; (iii) the prediction accuracy of the mixed-effects model increased gradually with increasing size of calibration sample, and the best sampling strategy was the use of nine random trees to calibrate and make predictions with the mixed-effects model for the larch and birch species; (iv) Dahurian larch was dominant in terms of interspecific competition, and the growth of this species was enhanced when it was grown with the birch. Conclusion In addition to biotic factors such as tree size and stand characteristics, the impact of climate on the growth of Dahurian larch and white birch should be considered in future management policies.

ABSTRACTThe long non-coding RNA, maternally expressed gene 3 (MEG3), are involved in myocardial fibrosis and compensatory hypertrophy, but its role on cardiomyocyte apoptosis and autophagy in heart failure (HF) remains unclear. The aim of this study was to investigate the effect of MEG3 on cardiomyocyte apoptosis and autophagy and the underlying mechanism. A mouse model of HF was established by subcutaneous injection of isoproterenol (ISO) for 14 days, and an in vitro oxidative stress injury model was replicated with H2O2 for 6 h. SiRNA-MEG3 was administered in mice and in vitro cardiomyocytes to knock down MEG3 expression. Our results showed that cardiac silencing of MEG3 can significantly ameliorate ISO-induced cardiac dysfunction, hypertrophy, oxidative stress, apoptosis, excessive autophagy and fibrosis induced by ISO. In addition, inhibition of MEG3 attenuated H2O2-induced cardiomyocyte oxidative stress, apoptosis and autophagy in vitro. Downregulation of MEG3 significantly inhibited excessive cardiomyocyte apoptosis and autophagy induced by ISO and H2O2 through miRNA-129-5p/ATG14/Akt signaling pathways, and reduced H2O2-induced cardiomyocyte apoptosis by inhibiting autophagy. In conclusion, inhibition of MEG3 ameliorates the maladaptive cardiac remodeling induced by ISO, probably by targeting the miRNA-129-5p/ATG14/Akt signaling pathway and may provide a tool for pharmaceutical intervention.

ObjectiveThe results of follow-up evaluation of GB 2757—2012 National Food Safety Standard- Distilled Wines and Mixed Wines were analyzed to reveal the main problems in the implementation of the standard and provide the basis for revision.MethodsThe comments of “Normal Tracking Evaluation” section on the national food safety standard follow-up evaluation platform were collected. The data was input to the Excel 2019 software for analysis. The key issues were discussed to provide suggestions for the revision of the standard.Results827 valid comments were received. When "no comment" was rejected， 47.95% of the comments were focused on "physicochemical indexes" including methanol and cyanide indicators. It was suggested that some other issues were worthy of attention and research， such as the microbiological risk of mixed wines， new categorization， characteristic index and physicochemical indexes.ConclusionThe comments reflects the key issues in the implementation of GB 2757—2012. The revision of standards should be timely started on the basis of scientific evaluation in the future. At the same time， it is suggested that the publicity， training and consultation should be strenghtened to improve understanding and applying of the standard.

Abstract Background Neuroblastoma is a common extracranial malignant tumor in children. Its main treatment modality is a combination of chemotherapy, radiotherapy, and surgery. Given the advances in chemotherapy regimens and the widespread use of bone marrow transplantation over the decades, there has been improvement in treatment efficacy, which has led to prolonged patient survival. Accordingly, long-term complications have become a growing concern among physicians and patients. This study aimed to analyze the survival rate of patients with neuroblastoma and the risk factors for developing second malignant neoplasms (SMNs). Methods The SEER 18 Regs (1973–2015) and SEER 9 Regs (1973–2015) data of the surveillance, epidemiology, and end results (SEER) database of the US National Cancer Institute were adopted for survival and SMN analysis. Results The 5-, 10-, and 20-year overall survival rates of patients with neuroblastoma were 67%, 65%, and 62%, respectively. Among 38 patients with neuroblastoma who presented with SMNs, those with abdomen as the primary site accounted for the majority (63.2%), followed by those with thorax (26.3%) and other sites (10.5%). SMNs occurred more commonly in non-specific neuroblastoma (incidence: 0.87%) than ganglioneuroblastoma (incidence: 0.3%). Compared with the general population, the risk of SMN is significantly higher (SIR = 4.36). The risk of developing SMNs was significantly higher in the digestive system (SIR = 7.29), bones and joints (SIR = 12.91), urinary system (SIR = 23.48), brain and other nervous systems (SIR = 5.70), and endocrine system (SIR = 5.84). Multivariate analysis revealed that the year of diagnosis (OR = 2.138, 95% CI = 1.634–2.797, p

Heartwood, sapwood, and bark constitute the main components of the tree stem. The stem is the main component of the tree and plays an important role in supporting the tree and transporting nutrients and water. Therefore, quantifying the profiles of heartwood, sapwood, and bark is fundamental to understanding the different components of the tree stem. A seemingly unrelated mixed-effect model system was developed based on 179 destructively sampled trees for 31 permanent sample plots in Korean larch plantation in Northeast China. The heartwood radius and sapwood width were estimated and calibrated only by the observed bark thickness or by all response variables considering the correlations of submodel random effects. The results indicated that the model system achieved good fitting performance and prediction. In addition, after including one to ten bark thickness points and all response variables of sampling below the 2 m height of the tree, the estimated best linear predictor (EBLUP) for local calibration improved the prediction performance, indicating that the heartwood radius and sapwood width could be effectively calibrated by bark thickness while keeping intact the complete inner structure inside the stem. The results provided important information for forest managers and ecologists when selecting appropriate approaches for quantifying the profiles of heartwood, sapwood, and bark.

Abstract Object counting in aquaculture is an important task, and has been widely applied in fish population estimation, estimation of lobster abundance and scallop stocks, and so forth. However, underwater object counting is challenging for biologists and marine scientists because of the diversity of backgrounds of the lake or ocean, the uncertainty of the object motion, and the occlusion between objects. With the rapid development of sensor, computer vision, and acoustic technologies, advanced and efficient counting methods are available in aquaculture. We reviewed underwater object counting methods in aquaculture, provided a survey including more than 50 articles in the recent 10 years, and analyzed the pros and cons of the counting methods and the applicable scenarios of those methods. Finally, the major challenges and future trends of underwater object counting in aquaculture are discussed.

Biomass conversion and expansion factors (BCEFs) are widely utilized in national and regional biomass estimates and greenhouse gas reporting, as they can be used to directly transform the stocking volume into biomass. In this study, the power function was used as the basic model form with biotic variables, and abiotic variables were considered to improve the fitting results. Then, the random effects parameters were also introduced into the models to describe the variation of BCEFs among different forest management units. Random sampling strategies were applied to calibrate the random effects. The results showed that the stocking volume exhibited a negative proportional relationship in the stem BCEF (BCEFst), the root BCEF (BCEFro) and the total tree BCEF (BCEFto) models, and the quadratic mean diameter exhibited a positive proportional relationship in the branch BCEF (BCEFbr) and the foliage BCEF (BCEFfol) models. In addition, the fitting effect of generalized models with abiotic predictors was superior to that of the basic models. Considering the effects of abiotic variables on the BCEFs of each component, the results showed that BCEFst and BCEFto decreased as the mean annual precipitation increased; BCEFbr increased as the annual temperature increased; BCEFfol gradually decreased as the elevation increased; and BCEFro first increased with increasing mean annual temperature and then declined. In conclusion, abiotic factors explained the variation in BCEFs for the biomass components of the natural white birch forest. Although the fitting effect of generalized models with abiotic predictors was superior to that of the basic models, the mixed-effects model was preferable for modeling the BCEFs of each component. In addition, the prediction precision of the mixed-effects models enhanced gradually with increasing sample size, and the selection of eight plots for calibration and prediction based on the mixed-effects model was the best sampling strategy in this study of a natural white birch forest.

To study the environmental impact caused by higher-place shrimp pond aquaculture, Inductively Coupled Plasma Mass Spectrometer (ICP-MS, Agilent 7700x) was used to detect the contents of Cr, Ni, Cu, Zn, As, Cd, and Pb in the sediments of three types of shrimp ponds (the bottom of the shrimp ponds was covered with sand, cement, and mulch, respectively) and their surrounding ditches in Dongying Town, Haikou City. The Vario TOC analyzer was used to detect the Total Nitrogen (TN) and Total Organic Carbon (TOC) contents in the sediments. The detected values were analyzed and evaluated using various parameters, such as the single factor pollution index, geo-accumulation index, and comprehensive potential ecological risk index, to reveal the spatial enrichment, pollution status, and ecological risk of heavy metal contents in the sediments of higher-place shrimp ponds and their surrounding ditches. The major results of this study were as follows: 1) The contents of heavy metals in the sediments of the unwashed shrimp pond increased significantly from the L1 layer to the L4 layer. 2) In the sediments of the surrounding ditches, the contents of all heavy metals (except for those of Ni and Cd, which were the highest in the L1 layer) were the highest in the L4 layer and were 1.29-15.51 times higher than those in the surface layer; 3) In the L1 layer of the sediment of the shrimp pond, Cd showed a significant accumulation (pollution); its content were 5.47-35.18 times higher than the soil background value in the Hainan Province . 4) The evaluation of Igeo indicated that there are two or more heavy metals in all types of sediments that reached a mild-medium pollution degree and above. The most serious pollutant in each sample pond was Cd, ranging from a level of 1.87 to 4.55; the highest level, 5, indicates strong-extremely severe pollution, while the lowest level, 2, indicates a medium pollution level. 5) The single-factor potential risk coefficient (Eri) of all heavy metals, except Cd, in the surface layer sediments of each sample pond was ≤40, which indicates a slight pollution degree. 6) The Comprehensive Potential Ecological Risk Index (RI) of the sediments was 176.97 to 1090.87, and the RIs of all plots showed moderate or higher ecological risks, for which Cd was the main contributing factor. The Cd pollution load sharing rate (the proportion of Cd in RI) in the seven sample plots exceeded 90%, mainly because the biological toxicity response coefficient (Ti =30) of Cd was the highest and the reference value (=0.05) was the lowest; this increased the RI values and the ecological risk index levels. 7) Pearson's correlation analysis showed that the Cr, Ni, Cu, As, Cd, and TOC contents in the bait residues and prawn excreta of shrimp pond bottoms had extremely significant correlations with each other, and the correlation coefficient was as high as 0.9 or more, indicating that the bait used contained the above heavy metals at varying concentrations and that organic carbon is an important factor that affects the enrichment of heavy metals in the substrate.

Abstract Background Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy. Surgical resection is the standard treatment for localized ACC, but the local recurrence remains high. Adjuvant radiation (ART) has been proposed as a means to reduce recurrence rates in ACC after surgery with conflicting results from nonrandomized studies. We performed a retrospective study and a meta-analysis to determine the impact of ART on survival outcomes. Methods A retrospective study of the adrenocortical cancer database in Peking Union Medical College was conducted. We selected postoperative ACC patients with or without ART. A meta-analysis is also performed to compare the outcomes between ART and only surgical resection in ACC patients. The obtained data were analyzed using SPSS 23.0 and Stata 15.0 statistical software. Differences between two groups were compared using the log-rank test for retrospective analysis and estimated by calculating the odds ratio (OR) and 95% confidence interval (CI) for meta-analysis. Results Of a total of 75 patients available in the database, 12 patients underwent postoperative ART and were matched one to one to patients with only surgical resection. There was no significant difference on overall survival between ART group and control group (log-rank P = 0.149). Locoregional recurrence was diagnosed in 2 of the ART group, and in 4 of the control group (P = 0.64). A total of 238 participants were selected for the meta-analysis, of which 111 and 127 patients underwent ART after surgical resection and only surgical resection, respectively. Overall survival is significantly higher in ART group, with an odds ratio (OR) of 2.41 (95% CI of 1.33, 4.38; P = 0.004). Besides, meta-analysis significantly favored ART for locoregional recurrence-free survival and disease-free survival, with an OR of 4.08 and 2.27, respectively. Conclusions Our results show that compared to only surgical resection, ART is an effective postoperative treatment for ACC.

Abstract Background The new staging system of cervical cancer issued in 2018 by the International Federation of Gynecology and Obstetrics (FIGO), calls for a new evaluation of the efficacy of prophylactic extended field irradiation (EFI) in the concomitant chemoradiotherapy/brachytherapy treatment of locally advanced cervical cancer patients (stage IIIB). Methods We performed a retrospective study consisting of 133 FIGO IIIB cervical cancer patients treated in the Peking Union Medical College Hospital from 2002 to 2010. The patients were distributed in two groups depending whether they were treated with EFI or pelvic only irradiation. The therapeutic efficacy, toxicity and prognostic factors of EFI were evaluated in the frame of the new FIGO staging system. Results When compared to patients who received pelvic only irradiation, patients who received prophylactic EFI showed significantly less distant metastasis and a significant improvement in their 5 years overall survival (OS), disease free survival (DFS), out of field recurrence free survival (OFRFS) and para-aortic lymph node metastasis free survival (PALNMFS). Multivariate analysis revealed that EFI is an independent prognosis factor for DFS, OFRFS and PALNMFS. Finally, although more acute complications were observed in the EFI group, there is no significantly worst acute toxicity in the EFI group. Conclusion Our retrospective analysis supports the prophylactic effect of EFI in the concomitant chemoradiotherapy treatment of IIIB patients and suggests that this prophylactic effect is associated with a clear improvement in 5-years OS, DFS, OFRFS and PALNMFS. Consequently, EFI appears to be a very valid treatment option for FIGO IIIB cervical cancer patients.

ObjectiveRhabdomyosarcoma (RMS) is a rare malignant tumor. The main treatment modality is comprehensive with chemotherapy, radiotherapy, and surgery. With the advancement in recent decades, patient survival has been prolonged, and long-term complications are attracting increasing attention among both physicians and patients. This study aimed to present the survival of patients with RMS and analyze the risk factors for the development of a second malignant neoplasm (SMN).MethodsThe Surveillance, Epidemiology, and End Results (SEER) Program 18 registry database from 1973 to 2015 of the National Cancer Institute of the United States was used for the survival analyses, and the SEER 9 for the SMN analysis.ResultsThe 5-, 10-, and 20-year overall survival rates of the patients with RMS were 45%, 43%, and 33%, respectively. The risk of SMN was significantly higher in patients with RMS compared to the general population (SIR=1.95, 95% CI: 1.44 – 2.57, p < 0.001). The risk of developing SMN was increased in multiple locations, including the bones and joints (SIR = 35.25) soft tissues including the heart (SIR = 22.5), breasts (SIR = 2.10), male genital organs (SIR = 118.14), urinary system (SIR = 2.36), brain (SIR = 9.21), and all nervous system organs (SIR = 8.59). The multivariate analysis indicated that RMS in the limbs and earlier diagnosis time were independent risk factors for the development of SMN. Patients with head and neck (OR = 0.546, 95% CI: 0.313 – 0.952, p = 0.033) and trunk RMS (OR = 0.322, 95% CI: 0.184 – 0.564. p < 0.001) and a later diagnosis time were less likely to develop SMN (OR = 0.496, 95% CI: 0.421 – 0.585, p < 0.001).ConclusionThis study describes the risk factors associated with the development of SMN in patients with RMS, which is helpful for the personalized screening of high-risk patients with RMS.

ObjectiveThe role of salvage radiotherapy (RT) in the treatment for vaginal recurrence of cervical cancer in patients after prior surgery remains controversial. The aim of this study was to evaluate the efficacy and toxicity of salvage RT and explore prognostic factors associated with the survival after recurrence.MethodsPatients with cervical cancer, treated for vaginal recurrences at Peking Union Medical College Hospital between July 2011 and November 2019, were identified. All the patients underwent prior surgery for primary tumor and received salvage RT including external beam radiotherapy (EBRT), brachytherapy (BT), or both. The irradiation field and dose depended on the conditions of patients. Recurrence patterns were classified into four categories according to the site of recurrence. Prognostic factors on the overall survival (OS), progression-free survival (PFS), and local control (LC) were analyzed, and late toxicity was evaluated.ResultsA total of 141 patients were included in the analysis, with a median follow-up time of 40.8 months. The estimated 5-year OS, PFS, and LC rates were 81%, 75%, and 87%, respectively. In multivariate analysis, endovaginal recurrence and no irradiation history were favorable prognostic factors associated with OS (all p < 0.05), PFS (all p < 0.05), and LC (all p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) of the recurrence pattern is larger than the stage of primary tumor (0.734 vs. 0.670).ConclusionsRT was an effective treatment with tolerable toxicity for vaginal recurrences of cervical cancer in patients with prior surgery. Recurrence pattern and irradiation history were important prognostic factors.

In the process of modeling height–diameter models for Mongolian pine (Pinus sylvestris var. mongolica), the fitting abilities of six models were compared: (1) a basic model with only diameter at breast height (D) as a predictor (BM); (2) a plot-level basic mixed-effects model (BMM); (3) quantile regression with nine quantiles based on BM (BQR); (4) a generalized model with stand or competition covariates (GM); (5) a plot-level generalized mixed-effects model (GMM); and (6) quantile regression with nine quantiles based on GM (GQR). The prediction bias of the developed models was assessed in cases of total tree height (H) predictions with calibration or without calibration. The results showed that extending the Chapman–Richards function with the dominant height and relative size of individual trees improved the prediction accuracy. Prediction accuracy was improved significantly when H predictions were calibrated for all models, among which GMM performed best because random effect calibration provided the lowest prediction bias. When at least 8% of the trees were selected from a new plot, relatively accurate and low-cost prediction results were obtained by all models. When predicting the H values of Mongolian pine for a new stand, GMM and BMM were preferable if there were available height measurements for calibration; otherwise, GQR was the best choice.

The control strategy is crucial for the effective and safe operation of the ORC system. A transient model of the ORC system was developed in the present work and validated by the experimental data of a 4 kW ORC prototype. Then, the effect of heat source temperature on the dynamic response and operation characteristics of the ORC system were analyzed. Five control strategies were compared: the constant working fluid mass flow rate mode, constant vapor superheat mode, constant vapor temperature mode, constant evaporation pressure mode and constant output power load mode. Under the constraint that the working fluid at the expander inlet should be superheated, we found that the constant vapor superheat mode enabled the safe operation with the largest range of heat source temperature, while the other four modes were only available for a certain temperature range. Apart from the constant output power mode, the constant evaporation pressure mode can also provide a relatively stable performance for the ORC unit. The variation of the thermal efficiency was limited when the heat source temperature was higher than 125 °C, except for the constant vapor temperature mode. Considering the high performance and stable operation of the ORC system, it is necessary to have different operation modes combined in the control strategy according to the specific working scenarios.

A multi-objective optimization based on the non-dominated sorting genetic algorithm (NSGA-II) is carried out in the present work for the basic organic Rankine cycle (BORC) and regenerative ORC (RORC) systems. The selection of working fluids is integrated into multi-objective optimization by parameterizing the pure working fluids into a two-dimensional array. Two sets of decision indicators, exergy efficiency vs. thermal efficiency and exergy efficiency vs. levelized energy cost (LEC), are adopted and examined. Five decision variables including the turbine inlet temperature, vapor superheat degree, the evaporator and condenser pinch temperature differences, and the mass fraction of the mixture are optimized. It is found that the turbine inlet temperature is the most effective factor for both the BORC and RORC systems. Compared to the reverse variation of exergy efficiency and thermal efficiency, only a weak conflict exists between the exergy efficiency and LEC which tends to make the binary objective optimization be a single objective optimization. The RORC provides higher thermal efficiency than BORC at the same exergy efficiency while the LEC of RORC also becomes higher because the bare module cost of buying one more heat exchange is higher than the cost reduction due to the reduced heat transfer area. Under the heat source temperature of 423.15 K, the final obtained exergy and thermal efficiencies are 45.6% and 16.6% for BORC, and 38.6% and 20.7% for RORC, respectively.

Abstract Background Currently, the standard treatment for locally advanced cervical cancer patients is concurrent chemoradiotherapy. Here we aim to evaluate therapeutic efficacy, treatment failure, toxicity and prognostic factors for FIGO IIIB cervical cancer patients. Methods A comprehensive retrospective analysis was performed to understand various factors which contribute to IIIB cervical cancer prognosis. In total 223 well defined patients were assigned according to their pathological subtype, age, pre-treatment HGB level, tumor size, pelvic lymph node (LN) metastasis, para-aortic LN metastasis as well as external irradiation technologies, treatment duration, point A EQD2 dose and concurrent chemotherapy cycles. We then performed correlation studies of these factors and OS, DFS, LCR, DMFS using univariate and multivariate analysis respectively. Results We managed to achieve 207 (92.8%) complete response (CR) and 16 (7.2%) partial response (PR) with acceptable adverse effects. Notably, the 5 years OS, DFS, LCR, DMFS for these patients were 61.1, 55.2, 83.6 and 66.4% respectively. Importantly, our studies suggest that escalated point A EQD2 can significantly improve OS, DFS and LCR for FIGO IIIB cervical cancer patients, furthermore, patients without para-aortic LN metastasis who received prophylactic extended field irradiation have significant survival advantage for DFS and a tendency to improve OS and DMFS. Conclusions Our results suggest that FIGO IIIB cervical cancer patients should receive higher EQD2 (≥98Gy10) radiotherapy, moreover, patients without para-aortic LN metastasis should receive prophylactic extended field nodal irradiation to improve prognosis.

ObjectiveLow-grade endometrial stromal sarcoma (LG-ESS) is a rare gynecological tumor. Whether adjuvant radiotherapy benefits survival in patients with resected early-stage ESS remains controversial. This study was designed to explore the role of adjuvant radiotherapy in stage I to II LG-ESS.MethodsWe retrospectively reviewed patients with stage I to II LG-ESS in our center from Jan. 1998 to Feb. 2018. All patients underwent a total hysterectomy and postoperative radiotherapy was administrated based on clinical and pathological characteristics.ResultsA total of 152 patients with stage I to II resected LG-ESS were included. Forty patients received adjuvant radiotherapy (RT group) while 112 patients did not receive adjuvant radiotherapy (no RT group). The baseline characteristics of the two groups were comparable, except that the proportion of stage II patients in the RT group was higher than that in the no RT group (32.5% vs. 11.6%, in RT vs. no RT groups, respectively; p = 0.003). For both patient groups, median overall survival was not reached. The median disease-free survival (DFS) was 144 months. Radiotherapy was associated with significantly improved DFS (92 months vs. not reached in RT vs. no RT groups, respectively; p = 0.008) and pelvic failure-free survival (PFFS) (92 months vs. not reached in RT vs. no RT groups, respectively; p=0.004). Subgroup analysis revealed that RT benefited survival most among patients with stage IB to IIB disease. Adjuvant radiotherapy significantly reduced the pelvic recurrence rate (10.0%, 4/40 vs. 28.6%, 32/112, p = 0.018). No radiotherapy-induced grade 4 to 5 toxicity was observed.ConclusionFor patients with stage I to II LG-ESS, adjuvant radiotherapy showed significant improvement in DFS and PFFS with tolerable adverse effects, especially in patients with stage IB to IIB disease.

The relative growth rate (RGRnv) is the standardized measurement of forest growth, whereby excluding the size differences between individuals allows their performance to be compared equally. The RGRnv model was developed using the National Forest Inventory (NFI) data on the Daxing’an Mountains, in Northeast China, which contain Dahurian larch (Larix gmelinii Rupr.), white birch (Betula platyphylla Suk.), and mixed coniferous–broadleaf forests. Four predictor variables—i.e., quadratic mean diameter (Dq), stand basal area (G), average tree height (Ha), and altitude (A)—and four different methods—i.e., the nonlinear mixed-effects models (NLME), three nonlinear quantile regression (NQR3), five nonlinear quantile regression (NQR5), and nine nonlinear quantile regression (NQR9) models—were used in this study. All the models were validated using the leave-one-out method. The results showed that (1) the mixed coniferous–broadleaf forest presented the highest RGRnv; (2) the RGRnv was negatively correlated with the four predictors, and the heteroscedasticity reduced significantly after the weighting function was integrated into the models; and (3) the quantile regression models performed better than NLME, and NQR9 outperformed both NQR3 and NQR5. To make more accurate predictions, parameters of the adjusted mixed-effects and quantile regression models should be recalculated and localized using sampled RGRnv in each region and then applied to predict all the other RGRnv of plots. MAPE% indicates the mean absolute percentage error. The values were stable when the sample numbers were greater than or equal to six across the three forest types, which showed relatively accurate and lowest-cost prediction results.

Organic Rankine cycle (ORC) power generation is an effective way to convert medium and low temperature heat into high-grade electricity. In this paper, the subcritical saturated organic Rankine cycle system with a heat source temperature of 100~150 °C is studied with four different organic working fluids. The variations of the exergy efficiencies for the single-stage/two-stage systems, heaters, and condensers with the heat source temperature are analyzed. Based on the condition when the exergy efficiency is maximized for the two-stage system, the effects of the mass split ratio of the geothermal fluid flowing into the preheaters and the exergy efficiency of the heater are studied. The main conclusions include: The exergy efficiency of the two-stage system is affected by the evaporation temperatures of the organic working fluid in both the high temperature and low temperature cycles and has a maximum value. Under the same heat sink and heat source parameters, the exergy efficiency of the two-stage system is larger than that of the single-stage system. For example, when the heat source temperature is 130 °C, the exergy efficiency of the two-stage system is increased by 9.4% compared with the single-stage system. For the two-stage system, analysis of the four organic working fluids shows that R600a has the highest exergy efficiency, although R600a is only suitable for heat source temperature below 140 °C, while other working fluids can be used in systems with higher heat source temperatures. The mass split ratio of the fluid in the preheaters of the two-stage system depends on the working fluid and the heat source temperature. As the heat source temperature increases, the range of the split ratio becomes narrower, and the curves are in the shape of an isosceles triangle. Therefore, different working fluids are suitable for different heat source temperatures, and appropriate working fluid and split ratio should be determined based on the heat source parameters.

We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.

The transport phenomena in a passive direct methanol fuel cell (DMFC) were numerically simulated by the proposed two-dimensional two-phase nonisothermal mass transport model. The anisotropic transport characteristic and deformation of the gas diffusion layer (GDL) were considered in this model. The natural convection boundary conditions were adopted for the transport of methanol, oxygen, and heat at the GDL outer surface. The effect of methanol concentration in the reservoir on cell performance was examined. The distribution of multiphysical fields in the membrane electrode assembly (MEA), especially in the catalyst layers (CLs), was obtained and analyzed. The results indicated that transport resistance for the methanol mainly existed in the MEA while that for oxygen and heat was primarily due to natural convection at the GDL outer surface. Because of the relatively high methanol concentration, the local reaction rate in CLs was mainly determined by the overpotential. Methanol concentration between 3 M and 4 M was recommended for passive liquid feed DMFC in order to achieve a balance between the cell performance and the methanol crossover.

This protocol describes the synthesis of peptides for affinity testing and bioconjugate with solid phase peptide synthesizer at a small scale.

BackgroundThe Ecballium elaterium trypsin inhibitor (EETI-II), a 28-amino acid member of the knottin family of peptides, contains three interwoven disulfide bonds that form multiple solvent-exposed loops. Previously, the trypsin binding loop of EETI-II has been engineered to confer binding to several alternative molecular targets. Here, EETI-II was further explored as a molecular scaffold for polypeptide engineering by evaluating the ability to mutate two of its structurally adjacent loops.Methodology/principal findingsYeast surface display was used to engineer an EETI-II mutant containing two separate integrin binding epitopes. The resulting knottin peptide was comprised of 38 amino acids, and contained 11- and 10-residue loops compared to wild-type EETI-II, which naturally contains 6- and 5-residue loops, respectively. This knottin peptide bound to α(v)β(3) and α(v)β(5) integrins with affinities in the low nanomolar range, but bound weakly to the related integrins α(5)β(1) and α(iib)β(3). In addition, the engineered knottin peptide inhibited tumor cell adhesion to vitronectin, an extracellular matrix protein that binds to α(v)β(3) and α(v)β(5) integrins. A (64)Cu radiolabeled version of this knottin peptide demonstrated moderate serum stability and excellent tumor-to-muscle and tumor-to-blood ratios by positron emission tomography imaging in human tumor xenograft models. Tumor uptake was ∼3-5% injected dose per gram (%ID/g) at one hour post injection, with rapid clearance of probe through the kidneys.Conclusions/significanceWe demonstrated that multiple loops of EETI-II can be mutated to bind with high affinity to tumor-associated integrin receptors. The resulting knottin peptide contained 21 (>50%) non-native amino acids within two mutated loops, indicating that extended loop lengths and sequence diversity were well tolerated within the EETI-II scaffold. A radiolabeled version of this knottin peptide showed promise for non-invasive imaging of integrin expression in living subjects. However, reduced serum and metabolic stability were observed compared to an engineered integrin-binding EETI-II knottin peptide containing only one mutated loop.

The papain family of cysteine cathepsins are actively involved in multiple stages of tumorigenesis. Because elevated cathepsin activity can be found in many types of human cancers, they are promising biomarkers that can be used to target radiological contrast agents for tumor detection. However, currently there are no radiological imaging agents available for these important molecular targets. We report here the development of positron emission tomography (PET) radionuclide-labeled probes that target the cysteine cathepsins by formation of an enzyme activity-dependent bond with the active site cysteine. These probes contain an acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active site cysteine of papain family proteases attached to a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with (64)Cu for PET imaging studies. We performed biodistribution and microPET imaging studies in nude mice bearing subcutaneous tumors expressing various levels of cysteine cathepsin activity and found that the extent of probe uptake by tumors correlated with overall protease activity as measured by biochemical methods. Furthermore, probe signals could be reduced by pre-treatment with a general cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe increased tumor uptake relative to probes lacking this fluorogenic dye. Overall, these results demonstrate that small molecule activity-based probes carrying radio-tracers can be used to image protease activity in living subjects.

Optical imaging (OI) techniques such as bioluminescence and fluorescence imaging have been widely used to track diseases in a non-invasive manner within living subjects. These techniques generally require bioluminescent and fluorescent probes. Here we demonstrate the feasibility of using radioactive probes for in vivo molecular OI.By taking the advantages of low energy window of light (1.2-3.1 eV, 400-1000 nm) resulting from radiation, radionuclides that emit charged particles such as beta(+) and beta(-) can be successfully imaged with an OI instrument. In vivo optical images can be obtained for several radioactive probes including 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), Na(18)F, Na(131)I, (90)YCl(3) and a (90)Y labeled peptide that specifically target tumors.These studies demonstrate generalizability of radioactive OI technique. It provides a new molecular imaging strategy and will likely have significant impact on both small animal and clinical imaging.