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Supplementary Table from Chromatin Remodeling Induced by ARID1A Loss in Lung Cancer Promotes Glycolysis and Confers JQ1 Vulnerability

Supplementary Data from Chromatin Remodeling Induced by ARID1A Loss in Lung Cancer Promotes Glycolysis and Confers JQ1 Vulnerability

Supplemental Table 5 Correlation between the protein level of NME7 and the clinical features of patients with HCC in the tissue array.

Supplemental Materials and Methods and Supplemental Figures and Legends

ARID1A is a key mammalian SWI/SNF complex subunit that is mutated in 5% to 11% of lung cancers. Although recent studies have elucidated the mechanism underlying dysregulation of the switch/sucrose non-fermentable (SWI/SNF) complexes in cancers, the significance of ARID1A loss and its implications in lung cancers remain poorly defined. This study investigates how ARID1A loss affects initiation and progression of lung cancer. In genetically engineered mouse models bearing mutant Kras and a deficient Trp53 allele (KP), ARID1A loss (KPA) promoted lung tumorigenesis. Analysis of the transcriptome profiles of KP and KPA tumors suggested enhanced glycolysis following ARID1A loss, and expression of the glycolytic regulators Pgam1, pyruvate kinase M (Pkm), and Pgk1 was significantly increased in ARID1A-deficient lung tumors. Furthermore, ARID1A loss increased chromatin accessibility and enhanced hypoxia-inducible factor-1α (HIF1α) binding to the promoter regions of Pgam1, Pkm, and Pgk1. Loss of ARID1A in lung adenocarcinoma also resulted in loss of histone deacetylase 1 (HDAC1) recruitment, increasing acetylation of histone-4 lysine at the promoters of Pgam1, Pkm, and Pgk1, and subsequently enhancing BRD4-driven transcription of these genes. Metabolic analyses confirmed that glycolysis is enhanced in ARID1A-deficient tumors, and genetic or pharmacologic inhibition of glycolysis inhibited lung tumorigenesis in KPA mice. Treatment with the small molecule bromodomain and extraterminal protein (BET) inhibitor JQ1 compromised both initiation and progression of ARID1A-deficient lung adenocarcinoma. ARID1A negatively correlated with glycolysis-related genes in human lung adenocarcinoma. Overall, ARID1A loss leads to metabolic reprogramming that supports tumorigenesis but also confers a therapeutic vulnerability that could be harnessed to improve the treatment of ARID1A-deficient lung cancer.Significance:This study links ARID1A loss with enhanced glycolysis in lung cancer and demonstrates the preclinical efficacy of BET inhibitor therapy as a strategy to combat tumor growth.

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/β-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, whereas overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and to promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3β to promote β-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of β-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. In addition, expression levels of NME7, β-catenin, and MTHFD2 correlated with each other and with poor prognosis in patients with HCC. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/β-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC.Significance:The identification of NME7 as an activator of Wnt/β-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.

ARID1A is a key mammalian SWI/SNF complex subunit that is mutated in 5% to 11% of lung cancers. Although recent studies have elucidated the mechanism underlying dysregulation of the switch/sucrose non-fermentable (SWI/SNF) complexes in cancers, the significance of ARID1A loss and its implications in lung cancers remain poorly defined. This study investigates how ARID1A loss affects initiation and progression of lung cancer. In genetically engineered mouse models bearing mutant Kras and a deficient Trp53 allele (KP), ARID1A loss (KPA) promoted lung tumorigenesis. Analysis of the transcriptome profiles of KP and KPA tumors suggested enhanced glycolysis following ARID1A loss, and expression of the glycolytic regulators Pgam1, pyruvate kinase M (Pkm), and Pgk1 was significantly increased in ARID1A-deficient lung tumors. Furthermore, ARID1A loss increased chromatin accessibility and enhanced hypoxia-inducible factor-1α (HIF1α) binding to the promoter regions of Pgam1, Pkm, and Pgk1. Loss of ARID1A in lung adenocarcinoma also resulted in loss of histone deacetylase 1 (HDAC1) recruitment, increasing acetylation of histone-4 lysine at the promoters of Pgam1, Pkm, and Pgk1, and subsequently enhancing BRD4-driven transcription of these genes. Metabolic analyses confirmed that glycolysis is enhanced in ARID1A-deficient tumors, and genetic or pharmacologic inhibition of glycolysis inhibited lung tumorigenesis in KPA mice. Treatment with the small molecule bromodomain and extraterminal protein (BET) inhibitor JQ1 compromised both initiation and progression of ARID1A-deficient lung adenocarcinoma. ARID1A negatively correlated with glycolysis-related genes in human lung adenocarcinoma. Overall, ARID1A loss leads to metabolic reprogramming that supports tumorigenesis but also confers a therapeutic vulnerability that could be harnessed to improve the treatment of ARID1A-deficient lung cancer. Significance: This study links ARID1A loss with enhanced glycolysis in lung cancer and demonstrates the preclinical efficacy of BET inhibitor therapy as a strategy to combat tumor growth.

This research discussed a deep learning method based on an improved generative adversarial network to segment the hippocampus. Different convolutional configurations were proposed to capture information obtained by a segmentation network. In addition, a generative adversarial network based on Pixel2Pixel was proposed. The generator was a codec structure combining a residual network and an attention mechanism to capture detailed information. The discriminator used a convolutional neural network to discriminate the segmentation results of the generated model and that of the expert. Through the continuously transmitted losses of the generator and discriminator, the generator reached the optimal state of hippocampus segmentation. T1-weighted magnetic resonance imaging scans and related hippocampus labels of 130 healthy subjects from the Alzheimer's disease Neuroimaging Initiative dataset were used as training and test data; similarity coefficient, sensitivity, and positive predictive value were used as evaluation indicators. Results showed that the network model could achieve an efficient automatic segmentation of the hippocampus and thus has practical relevance for the correct diagnosis of diseases, such as Alzheimer's disease.

Greenhouse gas intensity (GHGI), the evaluation of GHG emissions per unit yield rather than per unit land area, has recently received much attention. Plastic film mulching (PFM) is one of the major agricultural practices in semi-arid areas, but few studies have synthetically studied the effects of PFM on GHGI, grain yield, soil characteristics, and their potential relationships at different winter wheat (Triticum aestivum L.) growing stages. Here in the semi-arid Chinese Loess Plateau, we simultaneously investigated two cropping systems from 2018 to 2020: PFM with 100 % cover and no film mulching (control). Averaged across two growing seasons, the PFM treatment significantly increased soil temperature, water-filled pore spaces and soil water storage, while sustaining high aboveground biomass (31.9 %) and grain yield (45.5 %). The PFM treatment significantly increased cumulative N2O emissions by 56.2 %, CO2 emissions by 39.7 %, and CH4 uptake by 151.4 % compared to the control treatment. GHGI are on average 14.2 % lower in the PFM treatment than in the control treatment. Moreover, the PFM treatment significantly improved soil enzyme activities (alkaline phosphatase, catalase, invertase, and urease) and microbial biomass carbon and nitrogen from grain filling to maturity stage. Altogether, the reductions in GHGI suggest that PFM-induced increases in grain yield could outweigh the adverse impacts on GHG emissions, underscoring the potential to apply PFM for sustainable intensification of crop production in semi-arid areas.

Zinc oxide nanoparticles (ZnO NPs), have been commonly used in agriculture, and have attracted more attention for researchers. In this study, a 2-year experiment was conducted involving two Zn types (ZnO NPs and ZnSO4), two concentrations of Zn (25 and 100 mg kg−1), and three Zn application stages (basal stage, tillering stage, and panicle stage). This study comprehensively evaluated the effects of ZnO NPs on rice yield, nutrient uptake, Zn biofortification and grain nutritional quality. Our results showed that both ZnO NPs and Zn salt increased grain yield, NPK uptake, and grain Zn concentration. ZnO NPs application enhanced NPK content in rice, with subsequence increasing panicle number (3.8–10.3%), spikelet number per panicle (2.2–4.7%), and total biomass (6.8–7.6%), thereby promoting the rice yield. Compared with conventional fertilization, ZnO NPs enhanced Zn concentration of brown rice by 13.5–39.4%, this had no negative impact on human health. ZnO NPs application at panicle stage have a higher effectiveness in improving Zn concentration of brown rice than at basal and tillering stage. Furthermore, the application of ZnO NPs at panicle stage was more efficient in increasing Zn concentration of brown rice than for Zn salt. ZnO NPs application slightly altered the amino acids content of rice grains, but had no significant impact on total amino acids content. This study highlights that ZnO NPs could be used as a high performance and safe Zn fertilizer in rice production ecosystem.

Background The influence of amyloid protein-binding protein 2 (APPBP2) on lung cancer is unknown. Methods The function and mechanisms of APPBP2 were investigated in the NSCLC cell lines A549 and H1299. The ectopic expression of APPBP2, PPM1D and SPOP in NSCLS were examined in samples collected from ten pairs of human lung adenocarcinoma cancer tissues and adjacent normal lung tissues. shRNA vector was used for APPBP2 knockdown. Quantitative PCR and western blot assays quantified the mRNA and protein level of APPBP2, PPM1D, and SPOP. Cell proliferation was measured with BrdU, MTT, colony formation assays, and xenograft tumour growth experiments. Cell migration and invasion were analysed with transwell and wound healing assays. Co-Immunoprecipitation assay detected protein–protein interactions. Findings APPBP2 was upregulated in NSCLC tissues. Silencing APPBP2 in A549 and H1299 cells resulted in the inhibition of cell proliferation, migration, and invasion, enhancement of apoptosis, and a significant decrease in the expression of PPM1D and SPOP. Overexpression of PPM1D and SPOP attenuated the APPBP2-knockdown inhibition of NSCLC cells. Co-IP assay showed that PPM1D interacted with APPBP2. Interpretation The expression level of APPBP2 positively correlates with NSCLC cell proliferation, migration, and invasiveness. APPBP2 contributes to NSCLC progression through regulating the PPM1D and SPOP signalling pathway. This novel molecular mechanism, underlying NSCLC oncogenesis, suggests APPBP2 is a potential target for diagnosis and therapeutic intervention in NSCLC. Fund Key Program of Natural Science Research of Higher Education of Anhui Province (No. KJ2017A241), the National Natural Science Foundation of China (No. 81772493).

Wildfire is an important ecological disturbance that can have cascading effects on ecosystem carbon (C) fluxes. Ecosystem respiration (ER) and soil respiration (SR) account for two of the largest terrestrial C fluxes to the atmosphere, and they play critical roles in regulating C–climate feedbacks. Here, the responses of ER, SR and their source components to experimental burning in a meadow grassland on the Tibetan Plateau were investigated. Fire treatment increased ER by 9% but decreased SR by 15%. The contrasting post-fire responses of SR and ER can be explained by the behaviour of their source components; that is, fire increased aboveground plant respiration (R agb ) by 37%, but decreased heterotrophic respiration (HR) by 21%. Increases in ER and R agb were mainly related to enhanced plant productivity, whereas smaller SR and HR were associated with reductions in microbial biomass and soil moisture. Accounting for the responses of ER, SR and their intrinsic components has advanced our understanding of how fire affects ecosystem C fluxes. Highlights: Fire treatment increased ecosystem respiration (ER) and aboveground plant respiration. Fire treatment decreased soil respiration (SR) and heterotrophic respiration (HR). Increases in ER and aboveground plant respiration were related to plant productivity. Reductions in SR and HR were caused by the suppressed microbial activity.

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/β-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, whereas overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and to promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3β to promote β-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of β-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. In addition, expression levels of NME7, β-catenin, and MTHFD2 correlated with each other and with poor prognosis in patients with HCC. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/β-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC. Significance: The identification of NME7 as an activator of Wnt/β-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.

BackgroundExcessive nitrogen (N) application rate with low N use efficiency (NUE) caused a considerable amount of N losses, especially ammonia volatilization (AV). Proper N fertilizer reduction (RN) could significantly reduce AV. However, continuous RN led to a nutrient deficiency in the soil and therefore negatively impacted the NUE and rice yield. PaddyAzolla, a good green manure, is considered as a promising measure to decrease AV and improve NUE and grain yield of rice. However, there is limited information on the integrated effects of RN andAzollacover on the AV, NUE, and rice yield, especially in the highly fertilized rice-growing systems.MethodsThe experiment was conducted including eight treatments: the control (without N fertilizer andAzollacover),Azollacover without N fertilizer (A), farmer’s N application rate (FN), FN +Azollacover (FNA), 15% RN from FN (RN15), RN15+Azollacover (RN15A). 30% RN from FN (RN30), RN30+Azollacover (RN30A). The integrated effects of N fertilizer reduction andAzollacover on AV, NUE, and rice grain was evaluated.ResultsRN15A and RN30A substantially reduced total AV by 50.3 and 66.9% compared with FN, respectively, primarily due to the lower surface water ammonia concentrations and pH. RN improved the efficiency ofAzollacover on reducing AV, with 4.1–9.9% higher than for FN. Compared with the FN, RN15A and RN30A enhanced apparent N recovery efficiency (ANRE) by 46.5 and 39.1%, which might be responsible for the lower NH3emission and the increased total N uptake / total chemical N applied. Furthermore, RN15A and RN30A reduced yield-scaled volatilization by 52.3 and 64.3% than for FN, respectively. Thus, combining 15–30% RN withAzollacover may be a way to reduce AV and improve ANRE without decreasing rice grain yield.

Emotions are closely linked to the life of human beings. Studying the difference of brain mechanism and brain function of human emotional expression helps to improve the human-computer interaction ability and realize the automatic diagnosis of related mental diseases. However, the emotion recognition rate is generally low. In this study, phase lock is used to construct EEG functional brain network based on static connection and dynamic connection under the condition of audiovisual stimuli of different core emotions. The network features are extracted for emotion recognition. The results demonstrate that the use of non-singular local attributes can effectively improve the rate of emotional recognition compared to the traditional use of global attributes of the network. At the same time, the dynamic brain network is introduced for the deficiency of the brain network analysis method based on a static connection. Constructing a dynamic connection-based EEG brain network whose network characteristics can further improve the emotional recognition rate. This conclusion provides some experimental basis and methods for relating emotion recognition based on brain network.

Background Excessive nitrogen (N) application rate with low N use efficiency (NUE) caused a considerable amount of N losses, especially ammonia volatilization (AV). Proper N fertilizer reduction (RN) could significantly reduce AV. However, continuous RN led to a nutrient deficiency in the soil and therefore negatively impacted the NUE and rice yield. Paddy Azolla, a good green manure, is considered as a promising measure to decrease AV and improve NUE and grain yield of rice. However, there is limited information on the integrated effects of RN and Azolla cover on the AV, NUE, and rice yield, especially in the highly fertilized rice-growing systems. Methods The experiment was conducted including eight treatments: the control (without N fertilizer and Azolla cover), Azolla cover without N fertilizer (A), farmer’s N application rate (FN), FN + Azolla cover (FNA), 15% RN from FN (RN15), RN15 + Azolla cover (RN15A). 30% RN from FN (RN30), RN30 + Azolla cover (RN30A). The integrated effects of N fertilizer reduction and Azolla cover on AV, NUE, and rice grain was evaluated. Results RN15A and RN30A substantially reduced total AV by 50.3 and 66.9% compared with FN, respectively, primarily due to the lower surface water ammonia concentrations and pH. RN improved the efficiency of Azolla cover on reducing AV, with 4.1–9.9% higher than for FN. Compared with the FN, RN15A and RN30A enhanced apparent N recovery efficiency (ANRE) by 46.5 and 39.1%, which might be responsible for the lower NH3 emission and the increased total N uptake / total chemical N applied. Furthermore, RN15A and RN30A reduced yield-scaled volatilization by 52.3 and 64.3% than for FN, respectively. Thus, combining 15–30% RN with Azolla cover may be a way to reduce AV and improve ANRE without decreasing rice grain yield.

Background Integrating a chemical nitrogen (N) fertilizer with an organic fertilizer and using slow-release mechanism are important N management strategies to increase the N utilization efficiency (NUE) and grain yield of rice. However, the performances of both N management strategies on the productivity, the nutrient absorption and utilization efficiency, and the economic benefits of rice have not yet been comprehensively evaluated. Methods A 2-year field experiment was conducted with seven N management strategies without fertilizer (control), 100% conventional N fertilizer (conventional compound fertilizer and urea) (N100), 75% conventional N fertilizer with 25% organic–inorganic compound fertilizer (N75+OICF25), 50% conventional N fertilizer with 50% organic–inorganic compound fertilizer (N50+OICF50), 100% organic–inorganic compound fertilizer (OICF100), slow-release compound fertilizer with urea (SRCF+U), compound fertilizer with sulfur-coated urea (CF+SCU). The responses of the productivity, the nutrient absorption and utilization efficiency, and the economic benefits of rice to the different N management strategies were evaluated. Results CF+SCU performed comparably or better than N100, judging by the grain yield (GY), the N, phosphate (P) and potassium (K) agronomic efficiency (NAE, PAE and KAE), and the apparent N, P and K recovery efficiency (ANRE, APRE and AKRE). SRCF+U significantly increased the GY by an average of 7.7%, the NAE and the ANRE by 23.8 and 26.7%, the PAE and the APRE by 90.6 and 109.3%, and the KAE and the AKRE by 74.2 and 57.7%. The higher GY and nutrient utilization efficiency when using SRCF+U were attributed to the higher total biomass and total nutrient absorption. N75+OICF25 and N50+OICF50 produced a comparable grain yield than N100, whereas a significant yield reduction was observed when using OICF100. Compared with N100, N75+OICF25 resulted in a comparable or higher fertilizer use efficiency (0.3 and 4.7% for NAE and ANRE, 0.3 and 3.2% for PAE and APRE, 0.3 and −2.8% for KAE and AKRE). However, the fertilizer use efficiency when using N50+OICF50 and OICF100 were lower than with N100. The highest net return (NR) (5,845.03 yuan ha−1) and benefit to cost (B:C) ratio (0.34) were obtained when using SRCF+U. The NR and the B:C ratio when using N75+OICF25 were slightly higher than when using N100. However, N50+OICF50 and OICF100 significantly decreased the NR and the B:C ratio compared with N100 by 14.5 and 12.1% and by 35.1 and 29.0%, respectively. Conclusions SRCF+U and CF+SCU enhanced the crop productivity, the nutrient uptake and utilization efficiency, and the economic benefits compared with N100. The comprehensive performance of SRCF+U was better than that of CF+SCU. N75+OICF25 produced almost similar productivity, nutrient uptake and use efficiency compared with N100. It demonstrated that N75+OICF25 stabilized the grain yield production of rice and reduced the input of chemical N fertilizer.

Paddy Azolla is considered as a promising technical approach to reduce ammonia (NH3) volatilization and increase nitrogen use efficiency (NUE). However, it is not effective in highly fertilized paddy fields as the high ammonium N (NH4+-N) concentrations adversely inhibit the growth and N uptake of Azolla. Urease inhibitors could effectively decrease NH4+-N concentrations in surface water and NH3 volatilization. However, a lack of information still exists regarding the combined effects of Azolla and urease inhibitors on NH3 volatilization, NUE, and grain yield (GY) of rice. A two-year field experiment was conducted including five treatments (no urea application (control), urea (N), urea + Azolla (NA), urea + urease inhibitor (NUI), and urea + Azolla + urease inhibitor (NAUI)). Results showed that NA treatment (−25.2%) was not effective in reducing NH3 volatilization compared with NUI treatment (−43.3%). The NAUI treatment substantially reduced NH3 volatilization (−54.6%) more than that by NA and NUI treatments, primarily because of the lower NH4+-N concentrations, pH, and temperature in surface water. Furthermore, NAUI treatments significantly increased the grain yield (GY) and the apparent N recovery efficiency (ANRE) of rice by 9.0–9.7% and 66.0–71.3%, respectively. The significant increase in GY was mainly from the increased panicle number (4.0%), spikelet number per panicle (15.9%), and total biomass (22.9%), which caused by the enhanced total N uptake (35.8%). NAUI treatment also decreased the yield-scaled NH3 volatilization by 61.1–63.6%. Overall, the co-application of Azolla and urease inhibitor in the rice field substantially decreased NH3 volatilization, and increased NUE and rice yield.

Climate warming affects soil carbon (C) dynamics, with possible serious consequences for soil C stocks and atmospheric CO2 concentrations. However, the mechanisms underlying changes in soil C storage are not well understood, hampering long-term predictions of climate C-feedbacks. The activity of the extracellular enzymes ligninase and cellulase can be used to track changes in the predominant C sources of soil microbes and can thus provide mechanistic insights into soil C loss pathways. Here we show, using meta-analysis, that reductions in soil C stocks with warming are associated with increased ratios of ligninase to cellulase activity. Furthermore, whereas long-term (≥5 years) warming reduced the soil recalcitrant C pool by 14%, short-term warming had no significant effect. Together, these results suggest that warming stimulates microbial utilization of recalcitrant C pools, possibly exacerbating long-term climate-C feedbacks.

Crop straw management plays important roles in sustainable agriculture and environmental protection. Straw incorporation has multiple influences on soil organic carbon (SOC) sequestration, greenhouse gas (GHG) emissions, and crop yields, but these influences have rarely been studied simultaneously in a single cropping system. This study was conducted to examine the influence of long-term straw incorporation on the SOC sequestration rate, methane (CH4) and nitrous oxide (N2O) emissions and crop yields in a Chinese rice (Oryza sativa L.) –wheat (Triticum aestivum L.) cropping system in Hydragric Anthrosols under a subtropical monsoon climate. Four straw incorporation treatments were applied: wheat straw incorporation only (WS), rice straw incorporation only (RS), both wheat and rice straw incorporation (WSRS), and no straw incorporation (as a control). The SOC sequestration rate was estimated from the changes in SOC stock in the topsoil (0–20 cm) from 2007 to 2016. The emissions of CH4 and N2O were measured every 7 d when possible using a static chamber method from the 2013 rice season to the 2016 wheat season. Our results showed that the straw incorporation treatments significantly influenced the seasonal CH4 and N2O emissions and rice yield but had no influence on wheat yield. Straw incorporation significantly increased the annual topsoil SOC sequestration rate by 0.24–0.43 t C ha−1 yr−1 and the annual CH4 and N2O emissions by 44–138 kg CH4-C ha−1 yr−1 and 0.68–1.49 kg N2O-N ha−1 yr−1, respectively. Relative to the RS treatment, the WS and WSRS treatments significantly increased annual CH4 emissions by 38% and 61%, respectively. Relative to the RS treatment, the WSRS treatment significantly increased the annual N2O emissions, by 35%. The average annual yields were significantly higher in the WSRS (16.8 t ha−1 yr−1) and RS (16.7 t ha−1 yr−1) treatments than in the WS (15.7 t ha−1 yr−1) and control (15.2 t ha−1 yr−1) treatments. Across the three rotation cycles, the annual net global warming potential and greenhouse gas intensity were similar between the control and RS treatments but were significantly lower in these treatments than in the WSRS and WS treatments. These findings suggest that the RS treatment can simultaneously increase crop yields and environmental sustainability in rice–wheat cropping systems.

Double-layer absorbing cement-based composites with the thickness of 10 mm were prepared, including different replacement levels of fly ash (FA) in the absorbing layer as well as the matching layer for impedance matching. Waste polyethylene terephthalate bottle fragment was introduced as electromagnetic transparent reinforcement aggregate. Carbon black was used to be original absorbent in the absorbing layer. The microstructure and electromagnetic parameters of FA were closely looked at through scanning electron microscope, X-ray diffraction, and analyzer of vector network. The absorption and mechanical properties of cement-based composites were tested. It turned out that when the optimal replacement ratio of FA in the absorbing layer and matching layer gets to 50%:30%, the minimum value of reflection loss achieves −22.3 dB at 13.2 GHz; also, the value of absorption bandwidth that is effective (

recent years, alternative rice cultivation methods have been widely developed in Asia, and the environmental consequences of these practices on nitrogen (N) runoff losses from intensively cultivated rice fields deserve attention. A two-year field experiment (2013–2014) was conducted in a rice field in southeastern China to evaluate the N losses in runoff resulting from four rice cultivation methods: (1) conventional, manually transplanted seedling rice (CTSR); (2) mechanically transplanted seedling rice (MTSR); (3) dry direct-seeded rice (DDSR); and (4) wet direct-seeded rice (WDSR). Runoff volumes; runoff concentrations of NH4+-N, NO3−-N, and total N (TN); N uptake; and grain yield were measured. The seasonal runoff volumes varied from 775 to 2397 m3 ha−1 in 2013 and 2014. Compared with CTSR, WDSR and DDSR significantly increased the total runoff volumes by 76% and 30%in 2013, and by 46% and 26% in 2014, respectively. The seasonal TN losses in runoff from the rice fields ranged from 1.99 to 10.18 kg N ha−1, accounting for 0.74–3.77% of the seasonal N input during the two years. In contrast with CTSR, WDSR increased TN losses by 169% in 2013 and by 143% in 2014, while DDSR increased TN losses by 31% in 2013 and by 84% in 2014. Direct-seeded rice significantly increased runoff N losses during the early growth period largely by increasing runoff volumes and/or the N concentrations in runoff water. The main forms of N lost in runoff were NH4+-N for CTSR, MTSR and WDSR and NO3−-N for DDSR. The grain yield, N uptake at mid-tillering and panicle initiation stages were similar in WDSR and DDSR and significantly lower than those under CTSR and MTSR. The results show that direct-seeded rice increased N runoff losses from intensively cultivated rice fields in southeastern China.

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, in which core symptoms are defects of social interaction and evidently repetitive behaviors. Although around 50-70 % of ASD patients have comorbidity of intellectual disabilities (ID) or developmental delay (DD), there are some ASD patients who exhibit only core symptoms but without ID/DD, raising the question whether there are genetic components and neural circuits specific for core symptoms of ASD. Here, by focusing on ASD patients who do not show compound ID or DD, we identified ade novoheterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene, coding the small ubiquitin-like modifiers (SUMO) deconjugating enzyme, as a potentially new candidate gene for ASD. We found thatSenp1haploinsufficient mice exhibited core symptoms of autism such as deficits in social interaction and repetitive behaviors, but normal learning and memory ability. Moreover, we found that the inhibitory and excitatory synaptic functions were severely affected in the retrosplenial agranular (RSA) cortex ofSenp1haploinsufficient mice. Lack ofSenp1led to over SUMOylation and degradation of fragile X mental retardation protein (FMRP) proteins, which is coded by theFMR1gene, also implicated in syndromic ASD. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescued the defects of synaptic functions and core autistic-like symptoms ofSenp1haploinsufficient mice. Together, these results demonstrated that disruption of the SENP1-FMRP regulatory axis in the RSA may cause core autistic symptoms, which provide a candidate brain region of ASD for potential therapeutic intervene by neural modulation approaches.

Predicting post-fire ecosystem CO2 exchange requires an explicit understanding of the sensitivity of gross primary production (GPP), ecosystem respiration (ER) and net ecosystem exchange (NEE) to post-fire conditions. However, the simultaneous effects of fire on GPP, ER and NEE are rarely evaluated. We established a three-year manipulative fire experiment in a meadow grassland on the Tibetan Plateau to investigate the responses of GPP, ER and NEE to prescribed fire. We found that fire on average increased GPP by 13% and ER by 9%, leading to an increase in NEE by 20% across the three years. There was no clear relationship between post-fire changes in soil temperature and ecosystem CO2 exchange, yet reductions in soil volumetric moisture were positively related to changes in GPP, ER and NEE. These results suggest that post-fire stimulation of GPP, ER and NEE cannot be fully explained by changes in soil temperature and soil moisture. Besides, changes in GPP, ER and NEE were positively related to fire-induced increases in graminoid biomass, legume biomass and soil inorganic nitrogen. Taken together, our results suggest the interwoven control of biotic and abiotic factors on post-fire GPP, ER and NEE, yet also that shifts in plant functional type biomass may outweigh the negative effects of reduced soil moisture on ecosystem CO2 exchange. These results underscore how simultaneous documentation of GPP, ER and NEE dynamics can advance a mechanistic understanding of CO2 exchange under fire disturbance.

A facile in situ polymerization process was introduced for the preparation of RGO–PANI hybrids with investigation of their microwave absorbing properties. The structural and morphological characterization were performed using Fourier transform infrared (FTIR), X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results indicated that the hierarchical nanocomposites of aligned polyaniline nanorods grown vertically on the surface of RGO were successfully synthesized. The hybrids with special structure possessed more distinct dielectric response characteristics and better electromagnetic absorption properties than pure PANI. The maximum reflection loss value of the composites is up to −43 dB at 12.4 GHz and the absorption bandwidth exceeding −10 dB is 3.5 GHz with a thickness of 2 mm. The results indicate that hierarchical nanocomposites of aligned polyaniline nanorods on reduced graphene oxide nanosheets are efficient materials for microwave absorption.

Background Amyotrophic lateral sclerosis (ALS) is a late onset neurodegenerative disease with fast progression. ALS has heavy genetic components in which a series of genetic mutations have been identified. In 2013, Mutations of the CREST gene (also known as SS18L1), which functions as a calcium-regulated transcriptional activator, were found in sporadic ALS patients. However, the pathogenic causality and mechanisms of ALS-associated mutations of CREST remain to be determined. Methods In this study, we constructed CREST knockout and Q394X knock-in mice with CRISPR/Cas9 system. Using biochemical and imaging tools, we illustrated core pathological phenotypes in CREST mutant mice and claimed the possible pathogenic mechanisms. Furthermore, we also observed locomotion defects in CREST mutant mice with behavioural tests. Results We demonstrate that ALS-related CREST-Q388X mutation exhibits loss-of-function effects. Importantly, the microglial activation was prevalent in CREST haploinsufficiency mice and Q394X mice mimicking the human CREST Q388X mutation. Furthermore, we showed that both CREST haploinsufficiency and Q394X mice displayed deficits in motor coordination. Finally, we identified the critical role of CREST-BRG1 complex in repressing the expression of immune-related cytokines including Ccl2 and Cxcl10 in neurons, via histone deacetylation, providing the molecular mechanisms underlying inflammatory responses within mice lack of CREST. Conclusion Our findings indicate that elevated inflammatory responses in a subset of ALS may be caused by neuron-derived factors, suggesting potential therapeutic methods through inflammation pathways. Electronic supplementary material The online version of this article (10.1186/s40035-019-0152-1) contains supplementary material, which is available to authorized users.

Estimating soil erosion and nutrient losses from surface runoff in paddy fields is essential for the assessment of sustainable rice (Oryza sativa L.) production and water quality protection. Different rice establishment methods have been used in the last three decades in Asia; however, it is still unclear how these methods influence sustainable agriculture and environmental protection in humid areas. The aim of this study was to evaluate the impacts of rice establishment method on soil erosion and phosphorus (P) losses from surface runoff in Hydragric Anthrosols under a subtropical monsoon climate. Total suspended solids (TSS), total P (TP), dissolved P (DP), and particulate P (PP) runoff losses were measured under four rice establishment treatments in 2013 and 2014, including traditional manual transplanting (TT), mechanical transplanting (MT), dry direct seeding (DD), and wet direct seeding (WD). The results showed that the seasonal TSS in the runoff varied from 59.9 to 829.8 kg ha−1 in the two years. Compared with TT, the DD significantly increased the TSS by 481% in 2013 and by 349% in 2014, while the WD significantly increased TSS by 783% in 2013 and by 571% in 2014. In the 2013 and 2014 rice seasons, the field-observed TP runoff losses were from 0.18 to 1.51 kg ha−1. Compared with TT, the DD significantly increased the TP lost by 222% in 2013 and by 197% in 2014, whereas the WD significantly increased the TP lost by 483% in 2013 and by 387% in 2014. However, the TSS and P losses from the MT and TT were similar in both years. The PP runoff losses accounted for 58–77% of the seasonal TP lost. These findings demonstrate that the conversion of traditional manual transplanting to direct seeding increased soil erosion and P runoff losses in subtropical China.

Table S1. Key Resources Table. (DOCX 74 kb)

Background Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Methods We developed single-strand library preparation and hybrid-capture-based cfDNA sequencing (SLHC-seq) to analysis degraded cfDNA fragments. Next we used SLHC-seq to perform cfDNA profiling in 112 pancreatic cancer patients, and the results were compared with 13 previous reports. Extensive analysis was performed in terms of cfDNA fragments to explore the reasons for higher detection rate of KRAS mutations in the circulation of pancreatic cancers. Findings By applying the new approach, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. 791 cancer-specific mutations were detected in plasma of 88% patients with KRAS hotspots detected in 70% of all patients. Only 8 mutations were detected in 28 healthy controls without any known oncogenic or truncating alleles. cfDNA profiling by SLHC-seq was largely consistent with results of tissue-based sequencing. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumour DNA detection. Interpretation We found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based detection of pancreatic cancer. The new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

Ammonia (NH 3 ) and greenhouse gas (GHG) emission during pig rearing on deep litter has been rarely reported. To evaluate the emission of NH 3 and GHGs according to the compositions of the deep-litter systems during pig rearing, we selected three different types of deep-litter systems: (a) RM, composed of 60% mushroom growth media and 40% rice husk; (b) RS, composed of 60% sawdust and 40% rice husk; and (c) RV, composed of 60% vinasse and 40% rice husk. Samples of the gases emitted were collected continuously using the static box method during one production cycle (150 d). The results showed that the patterns of NH 3 volatilization and CH 4 emission differed across the three deep-litter systems, but no significant differences were found in the pattern of N 2 O and CO 2 emission. Further, the total quantity of NH 3 and GHG emission showed significant differences. Material flow analysis indicated that gaseous loss was the main pathway for escape of N or C. Thus, the use of RS could mitigate the emission of NH 3 , N 2 O and CH 4 (3.82 kg, 1.50 kg and 5.46 kg, respectively) and limit the effect of GHGs in terms of the emission equivalent carbon value (28% and 86% lower than that of RM and RV, respectively). Thus, the RS system was the most suitable with regard to reduction of environmental pollution.

Predicting how shifts in plant phenology affect species dominance remains challenging, because plant phenology and species dominance have been largely investigated independently. Moreover, most phenological research has primarily focused on phenological firsts (leaf-out and first flower dates), leading to a lack of representation of phenological lasts (leaf senescence and last flower) and full phenological periods (growing season length and flower duration). Here, we simultaneously investigated the effects of experimental warming on different phenological events of various species and species dominance in an alpine meadow on the Tibetan Plateau. Warming significantly advanced phenological firsts for most species but had variable effects on phenological lasts. As a result, warming tended to extend species' full phenological periods, although this trend was not significant for all species. Experimental warming reduced community evenness and differentially impacted species dominance. Shifts in full phenological periods, rather than a single shift in phenological firsts or phenological lasts, were associated with changes in species dominance. Species with lengthened full phenological periods under warming increased their dominance. Our results advance the understanding of how altered species-specific phenophases relate to changes in community structure in response to climate change.