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Wind profile light detection and ranging (LiDAR) is an important tool for observing features within the atmospheric boundary layer. Observations of the wind field and boundary layer height from coherent Doppler wind LiDARs (CDWLs) under sandy and dusty weather conditions were evaluated using observations from two CDWLs and one GTS radio sounding located at the northern edge of the Tibetan plateau from 1 May to 30 August 2021. The results showed that CDWL has good applicability in reproducing wind fields in dust, precipitation, and in clear-sky conditions, and that it is superior to the v wind field for real measurements of the u wind fields. In terms of the planetary boundary layer height (PBLH), the validity of the inversion of PBLH in dusty weather was higher than that under clear-sky conditions. It was found that the PBLH retrieved by the CDWL at 20:00 (BJT) was better than that at 08:00 (BJT). The diurnal variation amplitude of the PBLH before the occurrence of a sandstorm was larger than the diurnal variation amplitude of the PBLH occurring during a sandstorm. [ABSTRACT FROM AUTHOR]

Background. EF-hand domain-containing protein D2 (EFHD2) has recently been reported to participate in initiation of cancer. More evidence indicates that EFHD2 plays an important role in tumors, but the pan-cancer analysis of EFHD2 is still very limited. Methods. In this study, we downloaded the original mRNA expression data and SNP data of 33 kinds of tumor data. The gene expression data of different tissues were downloaded from the GTEX database, combined with TCGA data and corrected to calculate the difference of gene expression. The data of total survival time (OS) and progression-free survival (PFS) of TCGA patients were downloaded from the Xena database to further survey the relationship between the EFHD2 expression and prognosis. The CIBERSORT algorithm was used to analyze the RNA-seq data of 33 kinds of cancer patients in different subgroups. In this study, NCI-60 drug sensitivity data and RNA-seq data were downloaded to explore the relationship between genes and common antineoplastic drug sensitivity through correlation analysis. In this study, GSEA analysis was carried out from the Molecular Signature database through the packages of "clusterprofiler" and "enrichplot." By comparing the differences of signal pathways between high and low gene expression groups, the possible molecular mechanism of prognostic differences among 33 kinds of tumors was determined. Results. Our results indicated that EFHD2 was highly expressed in 23 kinds of tumors. In addition, EFHD2 was associated with stage in many kinds of tumors. The expression of EFHD2 was closely related to the OS of 12 kinds of cancer patients. In addition, Kaplan-Meier- (KM-) plot survival analysis indicated that the high expression of EFHD2 was related to the poor OS of 5 kinds of cancer, and the expression of EFHD2 was closely related to the PFI of 5 kinds of cancer patients. The expression of EFHD2 was closely related to immune infiltration, among which 18 cancers were significantly correlated with CD8T cells, 14 cancers were significantly correlated with T regulatory (Tregs) cells, 15 cancers were significantly correlated with CD4 memory activated Tcells, and EFHD2 was significantly correlated with common tumor-related regulatory genes such as TGF beta signaling, TNFA signaling, hypoxia, scorch death, DNA repair, autophagy, and iron death-related genes. The expression level of EFHD2 was significantly correlated with each tumor of TMB, including STAD, SARC, ACC, THYM, KICH, THCA, and TGCT. In MSI, there were significant differences in THYM, STAD, THCA, and TGCT. We used the CellMiner database to explore the sensitivity between EFHD2 gene and common antineoplastic drugs and found that the prediction of high expression of EFHD2 was related to the resistance of many antineoplastic drugs. In renal cell carcinoma, the high expression of EFHD2 is mainly concentrated in ALLOGRAFT_REJECTION, REACTIVE_OXYGEN_SPECIES_PATHWAY, INTERFERON_GAMMA_RESPONSE, IL6_JAK_STAT3_SIGNALING, INTERFERON_ALPHA_RESPONSE, and other signal pathways. GO results showed that the genes were mainly enriched in response to interferon-gamma, antigen processing and presentation, cellular response to interferon-gamma, and other pathways. KEGG results demonstrated that EFHD2 was mainly rich in phagosome, Epstein-Barr virus infection, Staphylococcus aureus infection, and other pathways. The results of Kaplan-Meier survival analysis demonstrated that the high expression of EFHD2 was significantly related to the poor prognosis. Conclusion. Our findings highlight the predictive value of EFHD2 in cancer and provide a potential research direction for elucidating the role of EFHD2 in tumorigenesis and drug resistance. [ABSTRACT FROM AUTHOR]

• Supercritical power cycles may experience trans-critical procedures during start-up, shut down, or accident condition. • The thermal–hydraulic code has been upgraded for simulation of trans-critical transients. • A calibration model to IAFB heat transfer correlation at the near critical pressure condition has been developed. • The modified code gets well validated by trans-critical experiments. Though designed to be operated in supercritical conditions, supercritical power systems could experience trans-critical transients in which the pressure transfers between supercritical and subcritical condition during startup, shutdown, or accident condition. In the present work the thermal–hydraulic code ATHLET-SC was upgraded to predict the heat transfer behavior during trans-critical procedures. Prediction model of dispersed droplet flow film boiling (DFFB) heat transfer correlation, critical heat flux (CHF) correlation, and the correlation of minimum film boiling temperature T MFB has been upgraded. It is demonstrated by the validation work that the prediction error is large in the inverted annular film boiling (IAFB) regime. However, steady-state IAFB heat transfer experiment at high-pressure condition is unavailable. Hence, a calibration approach to IAFB heat transfer correlation is developed based on trans-critical transient experiment. As validated, the change of the wall temperature during the trans-critical transient gets well predicted by the corrected Bromley correlation. [ABSTRACT FROM AUTHOR]

• A new PDO heat transfer was established including 31603 data points. • Spearman's rank correlation coefficient method and group-wise statistic method are applied to develop the new PDO correaltion. • Different heat transfer modes among heated wall, vapor and droplet are considered. • The new PDO correlation gets well validated under different working conditions. The present study established a new experimental databank of stable post-dryout (PDO) heat transfer which contains 31,603 data points in total. It is demonstrated by the assessment work with the new databank that previous PDO heat transfer prediction methods could not provide high prediction accuracy to various working conditions. Therefore, this study aims to develop a universal correlation for stable PDO heat transfer. With effect of convective and radiation heat transfer considered, a new prediction model for stable PDO heat transfer is developed, which is a dimensionless one and independent to upstream information. By identifying significant dimensionless parameters with Spearman's rank correlation coefficient method and the group-wise statistic method, three dimensionless parameters (R e T P , Pr W , and x e) are selected to establish the new PDO correlation. Though developed from water experiments for vertical flow in uniformly heated round tubes, the new correlation shows good predictive capability when validated against water experiments with non-uniform heating and R134a experiments with uniform heating, which means the new correlation can be applied to various working conditions. However, if applied to cryogenic pipeline chill-down transient or nuclear power plant accident scenarios, validation with transient experiments needs to be completed in the future. [ABSTRACT FROM AUTHOR]

Polybrominated biphenyl ethers (PBDEs) are a group of persistent organic pollutants with endocrine-disrupting, neurotoxic, tumorigenic and DNA-damaging activities. They are hydroxylated by human liver microsomal CYP enzymes, however, their mutagenicity remains unknown. In this study, 2,2′,4,4′-tetrabromobiphenyl ether (BDE-47, relatively abundant in human tissues) was investigated for micronuclei induction and DNA damage in mammalian cells. The results indicated that BDE-47 up to 80 μM under a 6 h/18 h (exposure/recovery, covering 2 cell cycles) regime did not induce micronuclei in V79-Mz and V79-derived cell lines expressing human CYP1A1 or 1A2, while it was moderately positive in human CYP2B6-, 2E1-and 3A4-expressing cell lines (V79-hCYP2B6, V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4-hOR, respectively). Following 24 h exposure, BDE-47 induced micronuclei in V79-hCYP2E1-hSULT1A1 and V79-hCYP3A4 cells at increased potencies. In the human hepatoma (HepG2) cells BDE-47 (48 h exposure) was inactive up to 40 μM, however, pretreatment of the cells with ethanol (0.2%, v:v, inducer of CYP2E1) or rifampicin (10 μM, inducer of CYP3A4) led to significant micronuclei formation by BDE-47; pretreatment with bisphenol AF (100 nM) also potentiated BDE-47-induced micronuclei formation (which was blocked by a CYP2E1 inhibitor trans -1,2-dichloroethylene or a CYP3A inhibitor (ketoconazole). Immunofluorescent staining of centromere protein B with the micronuclei formed by BDE-47 in HepG2 cells pretreated with ethanol or rifampicin demonstrated selective formation of centromere-containing micronuclei. The increased phosphorylation of both histones H2AX and H3 in HepG2 by BDE-47 also indicated an aneugenic potential. Therefore, this study suggests that BDE-47 is an aneugen activated by several human CYP enzymes. [Display omitted] • 2,2′,4,4′-Tetrabromobiphenyl ether (BDE-47) is aneugenic in mammalian cells. • The aneugenicity of BDE-47 depends on metabolic activation by human CYP enzymes. • Human CYP3A4 and 2E1 might be the major enzymes activating BDE-47. [ABSTRACT FROM AUTHOR]

• The safety analysis of supercritical coolant cooled nuclear reactors requires a CHF model for the high-pressure region. • A high-pressure CHF experimental databank with wide range is established. • A new CHF correlation for the high-pressure region is developed. Supercritical coolant cooled reactors may experience the high subcritical pressure region during pressurization or depressurization transients, where the occurrence of the boiling crisis phenomena cannot be avoided. Therefore, a prediction model of CHF for the high-pressure region is required for the design of the supercritical system, but it is still missing. The CHF databank with reduced pressure above 0.7 was compiled from literatures or experiments carried out in IATF, including three different fluids (water, R12, and CO 2). With the knowledge of the two-phase phenomena, we rearranged the sublayer dryout model for DNB and proposed a new mechanism for dryout. By introducing dimensionless theory, a new CHF prediction correlation with a simple structure but relatively high accuracy was proposed for water and shows a good adaptation to water and non-aqueous fluids. As illustrated, the new model can be implemented to safety analysis of supercritical systems. [ABSTRACT FROM AUTHOR]

In this study, a pH-responsive polycaprolactone (PCL)–copper peroxide (CuO2) composite antibacterial coating was developed by suspension flame spraying. The successful synthesis of CuO2 nanoparticles and fabrication of the PCL-CuO2 composite coatings were confirmed by microstructural and chemical analysis. The composite coatings were structurally homogeneous, with the chemical properties of PCL well maintained. The acidic environment was found to effectively accelerate the dissociation of CuO2, allowing the simultaneous release of Cu2+ and H2O2. Antimicrobial tests clearly revealed the enhanced antibacterial properties of the PCL-CuO2 composite coating against both Escherichia coli and Staphylococcus aureus under acidic conditions, with a bactericidal effect of over 99.99%. This study presents a promising approach for constructing pH-responsive antimicrobial coatings for biomedical applications. [ABSTRACT FROM AUTHOR]

To avoid the unexpected aggregation and reduce the cytotoxicity of nanomaterials as optical probes in cell imaging applications, we propose a programmed DNA-cube as a carrier for silver nanoparticles (Ag NPs) to construct a specific hydrogen sulfide (H2S) responsive platform (Ag NP@DNA-cube) for diagnosing colorectal cancer (CRC) in this study. The DNA-cube maintains good dispersion of Ag NPs while providing excellent biocompatibility. Based on the characteristic overexpression of endogenous H2S in CRC cells, the Ag NPs are etched by H2S within target cells into silver sulfide quantum dots, thereby selectively illuminating the target cells. The Ag NP@DNA-cube exhibits a specific fluorescence response to CRC cells and achieves satisfactory imaging. [ABSTRACT FROM AUTHOR]

1-Methylpyrene (1-MP) is a common environmental pollutant and animal carcinogen. After sequential activation by cytochromes P450 and sulfotransferases, it induced gene mutations and micronuclei in mammalian cells. The type of micronuclei formed, entire chromosomes or fragments, was not analysed. In this study, 1-MP and its primary metabolite, 1-hydroxymethylpyrene (1-HMP), were investigated for the induction of centromere-positive and -negative micronuclei in the human hepatoma cell line HepG2 and its derivative C3A, expressing relevant enzymes at higher levels. Under a short-exposure (9 h)/long-recovery regime (2 cell cycles in total), 1-MP and 1-HMP provided negative test results in HepG2 cells. However, they induced micronuclei in C3A cells, the effect being blocked by 1-aminobenzotriazole (inhibitor of cytochromes P450s) and reduced by pentachlorophenol (inhibitor of sulfotransferases). Immunofluorescence staining of centromere protein B in the micronuclei revealed purely clastogenic effects under this regime. Unexpectedly, 1-MP and 1-HMP at concentrations 1/5–1/4 of that required for micronuclei formation led to mitotic arrest and spindle aberrations, as detected by immunofluorescence staining of β- and γ-tubulin. Following extended exposure (72 h, 2 cell cycles, no recovery), damage to the spindle apparatus and centrosomes was detected at even lower concentrations, with concurrent formation of micronuclei. At low concentrations (1–8 µM 1-MP, 0.25–0.5 µM 1-HMP), the micronuclei induced were unexceptionally centromere-positive. Thus, the chromosome-damaging mechanism of 1-MP was regime and concentration dependent: potently aneugenic under persistent exposure, while clastogenic at higher concentrations following a short-exposure/long-recovery regime. This is a convincing evidence for the existence of metabolic activation-dependent aneugens. [ABSTRACT FROM AUTHOR]

Based on data from the Gurbantunggut Desert, the largest fixed/semi-fixed desert in China, and ERA5-Land reanalysis data, the long-term variations and spatial surface heat source (SHS) differences in the Gurbantunggut Desert are discussed herein. The results show the following: (1) The hourly SHS at the Kelameili station during the 2013–2021 period was a weak heat source at night; contrastingly, it was a strong heat source during the day. The duration of the hourly SHS increased gradually from January to July, but it decreased gradually from July to December. The daily SHS showed obvious seasonal variation, reaching the maximum in summer and the minimum in winter. The ERA5-Land reanalysis can reproduce all the variation characteristics of the SHS well. (2) The climatology (i.e., multi-year mean) of the monthly SHS intensity was lower than 50 W/m2 during the January–March and September–December periods in the Gurbantunggut Desert, indicating a weak heat source. On the other hand, the climatology recorded in April–August was higher than 50 W/m2, with a strong heat source. From the perspective of spatial distribution, the eastern and western regions of the Gurbantunggut Desert show strong heat sources, while the central region shows weak heat sources. The spatial distribution of the first and second modes of the empirical orthogonal function (EOF) decomposition reflected the consistent spatial variability and a north–south (or east–west) polarity variation of the monthly SHS in the Gurbantunggut Desert, respectively. (3) The yearly SHS showed negative anomalies during the 1950–1954, 1964–1982 and 2004–2015 periods, and positive anomalies during the 1955–1963, 1983–2003 and 2016–2021 periods in the Gurbantunggut Desert. Additionally, the time series of the SHS anomalies was positively correlated with the Interdecadal Pacific Oscillation (IPO) index. During the negative IPO phase, the yearly SHS showed a negative anomaly in the Gurbantunggut Desert, while the yearly SHS showed a positive anomaly during the positive IPO phase in most regions of the Gurbantunggut Desert. [ABSTRACT FROM AUTHOR]

Grassland ecosystems are an important component of global terrestrial ecosystems and play a crucial role in the global carbon cycle. Therefore, it is important to study the carbon dioxide (CO2) process in the Middle Tien Shan grassland ecosystem, which can be regarded as a typical representative of the mountain grasslands in Xinjiang. Eddy covariance (EC) and the global carbon fluxes dataset (GCFD) were utilized to continuously monitor the Middle Tien Shan grassland ecosystem in Xinjiang throughout the 2018 growing season. The findings revealed notable daily and monthly fluctuations in net ecosystem exchange (NEE), gross primary productivity (GPP), and ecosystem respiration (Reco). On a daily basis, there was net absorption of CO2 during the day and net emission during the night. The grassland acted as a carbon sink from 6:00 to 18:00 and as a carbon source for the remaining hours of the day. On a monthly scale, June and July served as carbon sinks, whereas the other months acted as carbon sources. The accumulated NEE, GPP, and Reco during the growing season were −329.49 g C m−2, 779.04 g C m−2, and 449.55 g C m−2, respectively. On the half-hourly and daily scales, soil temperature (Ts) was the main contributor to CO2 fluxes and had the greatest influence on the variations in CO2 fluxes. Additionally, air temperature (Ta) showed a strong correlation with CO2 fluxes. The grassland ecosystems exhibited the strongest CO2 uptake, reaching its peak at soil temperatures of 25 °C. Moreover, as the air temperatures rose above 15 °C, there was a gradual decrease in NEE, while CO2 uptake increased. The applicability of GCFD data is good in the grassland ecosystem of the Middle Tien Shan Mountains, with correlations of 0.59, 0.81, and 0.73 for NEE, GPP, and Reco, respectively, compared to field observations. In terms of remote sensing spatial distribution, the Middle Tien Shan grassland ecosystem exhibits a carbon sink phenomenon. [ABSTRACT FROM AUTHOR]

• Parameters in a common accident are predicted by data- and model-driven approaches. • Data-driven gated recurrent unit network is used for autoregressive prediction. • Model-driven RELAP5 simulation code is used to predict unmeasured parameters. • The methods and predicted results are compared on six aspects. • The comparison results show the characteristics of the two approaches. Nuclear energy plays a crucial role in mitigating climate change as a near carbon-free and clean energy source. Predicting operating parameters is key to the digitalization and intellectualization of nuclear power plants, improving energy efficiency and reducing costs. Parameter prediction methods mainly consist of model-driven and data-driven approaches, and a comparative study is necessary to select the appropriate prediction method or combine them. In this paper, the gated recurrent unit network and the thermal–hydraulic program RELAP5 are chosen as representative data-driven and model-driven approaches to be used for predicting parameters for a specific operating condition to assess the characteristics and capabilities of each. The chosen experiment is a steam generator tube rupture accident which is important to pressurized water reactors. In this paper the modelling process and the prediction results for both approaches are given. The correlation coefficient for dome pressure, dome temperature, and primary outlet temperature of both approaches is greater than 0.993, except that the correlation coefficient of downcomer temperature is 0.83865 using RELAP5 and 0.99392 using gated recurrent unit network. Then the two approaches are compared from six perspectives of practical application, including accuracy (gated recurrent unit network and RELAP5 received scores of 8 and 6, respectively.), data requirements (7 and 5, respectively), model building algorithm (7 and 5, respectively), prediction speed (10 and 6, respectively), expertise requirements (6 and 6, respectively), and interpretability (5 and 9, respectively). It shows that model-driven and data-driven approaches both require specialist knowledge and appropriate data for modelling process. The data-driven gated recurrent unit network exhibits better accuracy and higher speed. The model-driven RELAP5 has better interpretability compared to the black-box gated recurrent unit network. It is suggested that hybrid approaches of model-driven and data-driven approaches could better deal with the prediction problems. [ABSTRACT FROM AUTHOR]

The exchange of energy between the land surface and atmosphere is dependent upon crucial parameters, including surface roughness, emissivity, bulk transfer coefficients for momentum (CD) and heat (CH). These parameters are calculated through site observation data and remote sensing data. The following conclusions are drawn: (1) the aerodynamic roughness of the Gurbantunggut Desert measures 1.1 × 10−2 m, which is influenced by the varying conditions of the underlying surface. The roughness decreases as wind speed increases and is seen to be directly proportional to the growth of vegetation. From April to June, the aerodynamic roughness increases with increasing vegetation cover, but begins to gradually decrease after July. Spatially, the middle regions show higher roughness values than the eastern and western areas. In the central part of the desert, the roughness is between 2.37 × 10−2 m and 2.46 × 10−2 m from April to November. The northwest and northeast regions measure 1.41 × 10−2 m–2.04 × 10−2 m and 1.53 × 10−2 m–2.39 × 10−2 m, respectively. (2) The surface emissivity is 0.93, and it varies depending on the snow and vegetation present in the underlying area. (3) CD and CH exhibit an inverse relationship with wind speed. When wind speed falls below 6 m/s, the CD declines rapidly as wind speed increases. In contrast, once wind speed surpasses 6 m/s, the propensity for the CD to decrease with increasing wind speed slows down and approaches stability. [ABSTRACT FROM AUTHOR]

Based on the daily precipitation data of 96 stations in Xinjiang, China, from 1970 to 2021, the trend of summer extreme precipitation indices and their regional characteristics are analyzed. The generalized extreme value (GEV) model is used to investigate the probability distribution characteristics of summer extreme precipitation indices in northern, southern, and eastern Xinjiang. The results show that (1) The summer maximum 1-day precipitation (RX1day) and maximum 5-day precipitation (RX5day) of most stations in Xinjiang showed an increasing trend, while the summer consecutive dry days (CDD) showed a decreasing trend. (2) The climatology (mean intensity) of RX1day, RX5day, and CDD at most stations in northern Xinjiang were more than 10 mm, more than 15 mm, and less than 25 days, respectively, while those at most stations in southern and eastern Xinjiang were less than 10 mm, less than 15 mm, and more than 25 days. The regional averaged climatology and inter-annual variability of RX1day/RX5day (CDD) in southern and eastern Xinjiang were smaller (larger) than that in northern Xinjiang. (3) The 20-year return level (RL20) of RX1day, RX5day, and CDD at stations in northern Xinjiang were 19.38–56.57 mm, 28.05–70.91 mm, and 22.51–51.05 days, respectively. The RL20 of RX1day, RX5day, and CDD at stations in southern Xinjiang were 21.31–46.07 mm, 23.99–72.89 mm, and 14.94–89.80 days, respectively. The RL20 of RX1day, RX5day, and CDD at stations in eastern Xinjiang were 8.89–36.36 mm, 10.13–50.66 mm, and 26.75–92.00 days, respectively. Compared with northern Xinjiang, there were lesser RX1day and RX5day events, with weaker intensity and smaller variability in southern and eastern Xinjiang. And the CDD events were opposite. [ABSTRACT FROM AUTHOR]

Computational Fluid Dynamics-Discrete Element Method (CFD-DEM) is employed to describe the co-gasification of biomass and coal in bubbling fluidized bed coupled with chemical reaction kinetic model. Six sets of simulations are set up to study the effect of blend ratio on the amount of gasification products compared with experiments. The calorific value of syngas, carbon conversion efficiency, hydrogen conversion efficiency and cold gas efficiency are calculated. Compared with the separate gasification, the hydrogen efficiency and cold gas efficiency in the co-gasification are enhanced. When biomass accounts for 75%, the contents of CO gas and CO 2 gas are the lowest, while the contents of H 2 gas and CH 4 gas are the highest. The high calorific value, carbon conversion efficiency and hydrogen conversion efficiency reach the maximum under this blend ratio. The cold gas efficiency is not obviously affected by the blend ratio, and reaches the maximum when the biomass content is 50%. • CFD-DEM for co-gasification of biomass and coal in bubbling fluidized bed is built. • When biomass accounts for 75%, the contents of H 2 gas and CH 4 gas are the highest. • The carbon conversion efficiency reach the maximum when biomass accounts for 75%. • The hydrogen conversion efficiency reach the maximum when biomass accounts for 75%. • The cold gas efficiency is not obviously affected by the increase of biomass amounts. [ABSTRACT FROM AUTHOR]

• Vortex-related data using continuous observations at Kelameili Station in the Gurbantunggut Desert. • The correlation analysis of NEE, GPP, Reco and various environmental factors was carried out. • Assess the carbon sequestration capacity of China's second largest desert and largest fixed semi-fixed desert (Gurbantunggut Desert). • The comparison of carbon source/sink functions in different terrestrial ecosystems provides a reference. • a new direction for finding "carbon failures". Although previous studies have illustrated the variation of CO 2 fluxes in different terrestrial ecosystems, more needs to be reported on desert ecosystems. This study, based on the eddy covariance (EC) measurements data over the Gurbantunggut Desert, analyzed the controlling factors and variations of net ecosystem exchange (NEE), gross primary production (GPP), and ecosystem respiration (Reco) during the growing season (April-September2021) in Gurbantunggut Desert. The results were as follows: 1) Carbon fluxes in the Gurbantunggut Desert had prominent daily and seasonal variations during the growing season. On the daily scale, it showed a net uptake during the day and a net release at night, and the monthly average daily change curve of NEE was "U" shaped; on the seasonal scale, carbon uptake was observed in all months, with a peak of −37.76 gC m−2 month−1 in May. 2)The cumulative amounts of NEE, GPP, and Reco in the Gurbantunggut Desert were −193.74, 235.43, and 41.69 g C m−2, respectively, throughout the growing season, showing carbon sinks. 3) Correlation analysis with environmental factors revealed that NEE, GPP, and Reco of desert ecosystems were highly significantly correlated with photosynthetically active radiation (PAR) at different time scales (p < 0.01). Second, at the half-hourly scale, all environmental factors showed vital significance, with a high correlation with air temperature (Tair) and soil temperature (Tsoil); at the monthly scale, they were significantly correlated with Precipitation (p < 0.05). 4) Photosynthetically active radiation is the dominant factor affecting the daily net ecosystem carbon exchange rate. The two are consistent with the rectangle hyperbola model where the daily net ecosystem carbon exchange rate decreases with increasing photosynthetically active radiation. The results indicate that carbon fluxes in the growing season of the Gurbantunggut Desert ecosystem are more sensitive to the response of photosynthetically active radiation. The results have significant reference value for further understanding and research in predicting the source-sink function and influence mechanism of desert ecosystems. [ABSTRACT FROM AUTHOR]

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC 50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC 50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g ; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed. Image 1 • A series of tetrahydroquinolines and benzomorpholines was discovered as novel RORγt agonists. • The structure-activity relationships of the left-hand-side moiety, linker and right-hand-side moiety were explored. • The representative lead compounds 8g and 9g showed greatly increased RORγt agonistic activity in dual FRET assay. • 8g and 9g also performed good RORγt agonistic effect in Gal4 reporter gene assay and Th17 cell differentiation assay. • The binding modes of 8g and 9g in RORγt ligand binding domain were discussed by docking studies. [ABSTRACT FROM AUTHOR]

1-Methylpyrene (1-MP) is a ubiquitous environmental pollutant and rodent carcinogen. Its mutagenic activity depends on sequential activation by various CYP and sulfotransferase (SULT) enzymes. Previously we have observed induction of micronuclei and mitotic arrest by 1-MP in a Chinese hamster (V79)-derived cell line expressing both human CYP1A2 and SULT1A1 (V79-hCYP1A2-hSULT1A1), however, the mode of chromosome damage and the involvement of mitotic tubulin structures have not been clarified. In this study, we used immunofluorescent staining of centromere protein B (CENP-B) with the formed micronuclei, and that of β- and γ-tubulin reflecting the structures of mitotic spindle and centrioles, respectively, in V79-hCYP1A2-hSULT1A1 cells. The results indicated that 1-MP induced micronuclei in V79-hCYP1A2-hSULT1A1 cells from 0.125 to 2 μM under a 24 h/0 h (exposure/recovery) regime, while in the parental V79-Mz cells micronuclei were induced by 1-MP only at concentrations ≥ 8 μM; in both cases, the micronuclei induced by 1-MP were predominantly CENP-B positive. Following 54 h of exposure, 1-MP induced mitotic spindle non-congression and centrosome amplification (multipolar mitosis) in V79-hCYP1A2-hSULT1A1 cells, and anaphase/telophase retardation, at concentrations ≥ 0.125 μM with concentration-dependence; while in V79-Mz cells it was inactive up to 8 μM. This study suggests that in mammalian cells proficient in activating enzymes 1-MP may induce chromosome loss and mitotic disturbance, probably by interfering with the mitotic spindle and centrioles. 1-Methylpyrene is potently aneugenic in metabolism-proficient mammalian cells. 1-Methylpyrene may disrupt mitotic apparatus by interfering with tubulin. 1-Methylpyrene may retard mitotic progression. [ABSTRACT FROM AUTHOR]

GSK805 (1) is a potent RORγt inverse agonist, but a drawback of 1 is its low solubility, leading to a limited absorption in high doses. We have explored detailed structure-activity relationship on the amide linker, biaryl and arylsulfonyl moieties of 1 trying to improve solubility while maintaining RORγt activity. As a result, a novel series of carboxyl-containing biaryl urea derivatives was discovered as potent RORγt inverse agonists with improved drug-like properties. Compound 3i showed potent RORγt inhibitory activity and subtype selectivity with an IC 50 of 63.8 nM in RORγ FRET assay and 85 nM in cell-based RORγ-GAL4 promotor reporter assay. Reasonable inhibitory activity of 3i was also achieved in mouse Th17 cell differentiation assay (76% inhibition at 0.3 μM). Moreover, 3i had greatly improved aqueous solubility at pH 7.4 compared to 1 , exhibited decent mouse PK profile and demonstrated some in vivo efficacy in an imiquimod-induced psoriasis mice model. Image 1 • A series of carboxyl-containing biaryl ureas was discovered as novel RORγt inverse agonists. • 3i exhibited greatly improved aqueous solubility compared to the lead compound 1 (GSK805). • 3i showed potent RORγt inhibitory activity in FRET assay and in Th17-cell based assay. • 3i demonstrated good in vivo PK profile in mice and in vivo efficacy in IMQ-induced psoriasis mice model. [ABSTRACT FROM AUTHOR]

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with human carcinogenicity. Many lower chlorinated and non-dioxin-like PCBs have been observed to be mutagenic following activation by human CYP2E1, while activation of dioxin-like (DL-) PCBs by this enzyme has never been evidenced. In this study, each DL-PCB was analyzed by molecular docking to human CYP2E1 protein for predicting a substrate interaction. All compounds demonstrated high affinities with the active site of human CYP2E1, binding energy being −8.7 ∼ −9.7 kcal/mol. However, most compounds demonstrated ligand-heme distances as ≥ 6.8 Å, while the values for 2,3,3′,4,4′- (PCB 105) and 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118) were 5.3 and 5.4 Å, respectively (valid for electron transfer). Experimentally, both PCB 105 and 118 induced micronuclei in a V79-derived cell line engineered for expression of human CYP2E1 at low micromolar concentrations, while inactive or weakly positive in V79-Mz control cells; these effects were blocked or reduced by 1-aminobenzotriazole, a suicide CYP inhibitor. However, DL-PCBs 77, 81 and 126 were all negative in both cell lines. In a human hepatoma (C3A) cell line, PCB 105 and 118 induced micronuclei marginally, while with ethanol pretreatment (to stabilize CYP2E1) both compounds induced micronuclei efficiently, and co-exposure to trans -1,2-dichloroethylene (a selective CYP2E1 inhibitor) led to clearly negative results with both compounds. Finally, both PCB 105 and 118 induced PIG-A gene mutations in C3A cells, which was blocked by trans -1,2-dichloroethylene. In summary, in silico and experimental results consistently suggest that DL- PCBs 105 and 118 may be activated by human CYP2E1 for mutagenic activities. [ABSTRACT FROM AUTHOR]