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AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins1,2. Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process3–7. The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PRR42-Ub and ADPRR42-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases8,9, which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.An effector protein called LnaB from Legionella pneumophila catalyses a unique type of AMPylation, and LnaB and its homologues represent a distinct family of AMPylases with specific structural features. [ABSTRACT FROM AUTHOR]

As global climate change continues, drought episodes have become increasingly frequent. Studying plant stress tolerance is urgently needed to ensure food security. The common ice plant is one of the model halophyte plants for plant stress biology research. This study aimed to investigate the functions of a newly discovered transcription factor, Homeobox 7 (HB7), from the ice plant in response to drought stress. An efficient Agrobacterium-mediated transformation method was established in the ice plant, where ectopic McHB7 expression may be sustained for four weeks. The McHB7 overexpression (OE) plants displayed drought tolerance, and the activities of redox enzymes and chlorophyll content in the OE plants were higher than the wild type. Quantitative proteomics revealed 1910 and 495 proteins significantly changed in the OE leaves compared to the wild type under the control and drought conditions, respectively. Most increased proteins were involved in the tricarboxylic acid cycle, photosynthesis, glycolysis, pyruvate metabolism, and oxidative phosphorylation pathways. Some were found to participate in abscisic acid signaling or response. Furthermore, the abscisic acid levels increased in the OE compared with the wild type. McHB7 was revealed to bind to the promoter motifs of Early Responsive to Dehydration genes and abscisic acid-responsive genes, and protein–protein interaction analysis revealed candidate proteins responsive to stresses and hormones (e.g., abscisic acid). To conclude, McHB7 may contribute to enhance plant drought tolerance through abscisic acid signaling. [ABSTRACT FROM AUTHOR]

Tar-rich coal holds the potential to substitute the supply of oil-gas resources. The in-situ pyrolysis contributes to efficient resource utilization and can potentially achieve net-zero CO2 emissions. However, it is challenging to efficiently separate oil-gas resources, which are predominated by tar, from multiphase products of in-situ pyrolysis of tar-rich coal. Additionally, the difference in fluid properties yields significant influences on separation performance, while the understanding of the separation characteristics of high-viscosity fluid remains insufficient. In this study, the separation process of pyrolysis products from tar-rich coal was investigated using the computational fluid dynamics simulation approach. The flow field, pressure drop, separation efficiency and distribution characteristics were analyzed. The simulation results indicate that the volute cyclone separator exhibits commendable separation efficiency, exceeding 98%. Meanwhile, in handling tars containing a high concentration of light oil, the separator demonstrates remarkable adaptability. The separation efficiency of solid particles decreases from 89% to 83% when the system contains a high content of pitch. The particle diameter exerts great influence on the flow field. The separation efficiencies are 99% and 0.37%, respectively, when the particle sizes are selected as 0.1 mm and 0.001 mm. In the scope of this study, the optimal working conditions of the cyclone separator were determined, which provides data support for improving the separation efficiency and recovery rate of the oil-gas resources. [ABSTRACT FROM AUTHOR]

Zhejiang Province is both the birthplace of the theory that both the mountain of gold and silver and the lushmountain with lucid waters are required (also known as the Two Mountains theory) and the first ecological province in China. The study on the vegetation ecological quality of Zhejiang can be used as an important reference for the construction of ecological civilization. Based on multi - source remote sensing data and meteorological observation data, this study investigated the spatio - temporal variations of vegetation ecological quality in Zhejiang during 2000-2020, as well as their response to climate factors and human activities. The results show that: (1) Both the fractional vegetation cover (FVC) and the net primary production (NPP) in Zhejiang showed an upward trend during 2000-2020, with significantly increased vegetation greenness; (2) The vegetation eco - environmental quality in Zhejiang showed a fluctuating upward trend during 2000-2020, with the vegetation ecological quality indices (VEQIs) of mountainous areas significantly higher than those of basin and plain areas; (3) The dominant factor driving the VEQI variations in Zhejiang during 2000-2020 is human activities, while climate factors occupied a dominant position only in some areas of southwestern Zhejiang. This study deepens the understanding of the spatio - temporal variations of vegetation ecological quality in Zhejiang and their driving factors and, thus, is of great significance for the construction of ecological civilization in Zhejiang and even other regions in China. [ABSTRACT FROM AUTHOR]

To study the transformation and release of fuel K, the combustion of corn stalk and wheat straw were performed in a reactor with a fixed bed between 400–1000°C. Measurements of weight and elemental composition, chemical fractionation analysis, and low‐temperature ashing coupled with X‐ray diffraction (XRD) analysis were conducted on biomass and residual samples. The effects of biomass species, temperature and duration time of combustion, oxygen concentration, and pretreatment of water washing were evaluated. The results show that compared with wheat straw, corn stalk has a lower K release, which is much more sensitive to the combustion temperature than to the oxygen concentration. The inorganic potassium occurs as KClO3 and KClO4 in wheat straw and KCl and KClO4 in corn stalk. K2SO4 appears through sulphation of KCl as combustion happens at 800°C or above. When the combustion temperature reached 900°C for corn stalk and 1000°C for wheat straw, some KCl changed into K2Si2O5, which contains insoluble K. K2Ca(SO4)2 appears as corn stalk and wheat straw are burnt at 1000 and 900°C, respectively. Along with the proceeding of wheat straw combustion, more ion‐exchangeable and water‐soluble K transform to the insoluble K with the increasing temperature. The pretreatment of water washing removes nearly all the water‐soluble K from the corn stalk and significantly decreases the K release from 3.26–0.27 mg g−1 in quantity and from 26.74%–14.84% in ratio at 1000°C, respectively. [ABSTRACT FROM AUTHOR]

The F-box family exists in a wide variety of plants and plays an extremely important role in plant growth, development and stress responses. However, systematic studies of F-box family have not been reported in populus trichocarpa. In the present study, 245 PtrFBX proteins in total were identified, and a phylogenetic tree was constructed on the basis of their C-terminal conserved domains, which was divided into 16 groups (A–P). F-box proteins were located in 19 chromosomes and six scaffolds, and segmental duplication was main force for the evolution of the F-box family in poplar. Collinearity analysis was conducted between poplar and other species including Arabidopsis thaliana, Glycine max, Anemone vitifolia Buch, Oryza sativa and Zea mays, which indicated that poplar has a relatively close relationship with G. max. The promoter regions of PtrFBX genes mainly contain two kinds of cis-elements, including hormone-responsive elements and stress-related elements. Transcriptome analysis indicated that there were 82 differentially expressed PtrFBX genes (DEGs), among which 64 DEGs were in the roots, 17 in the leaves and 26 in the stems. In addition, a co-expression network analysis of four representative PtrFBX genes indicated that their co-expression gene sets were mainly involved in abiotic stress responses and complex physiological processes. Using bioinformatic methods, we explored the structure, evolution and expression pattern of F-box genes in poplar, which provided clues to the molecular function of F-box family members and the screening of salt-tolerant PtrFBX genes. [ABSTRACT FROM AUTHOR]

Extreme environments, especially drought and high salt conditions, seriously affect plant growth and development. Ethylene-responsive factor (ERF) transcription factors play an important role in salt stress response. In this study, a significantly upregulated ERF gene was identified in 84K (Populus alba × P. glandulosa), which was named PagERF072. PagERF072 was confirmed to be a nuclear-localized protein. The results of yeast two-hybrid (Y2H) assay showed that PagERF072 protein exhibited no self-activating activity, and yeast one-hybrid (Y1H) demonstrated that PagERF072 could specifically bind to GCC-box element. Under salt stress, the transgenic poplar lines overexpressing PagERF072 showed improved salt tolerance. The activities of peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) in transgenic poplars were significantly increased relative to those of wild-type (WT) plants, whereas malondialdehyde (MDA) content showed an opposite trend. In addition, reactive oxygen species (ROS) was significantly reduced, and the expression levels of POD- and SOD-related genes were significantly increased in transgenic poplars under salt stress compared with WT. All results indicate that overexpression of the PagERF072 gene can improve the salt tolerance of transgenic poplars. [ABSTRACT FROM AUTHOR]

Understanding the response of tropospheric ozone (O3) to nitrogen dioxide (NO2) change is important for local O3 control. The relationship between O3 and NO2 at county scale in China has been extensively studied using models, but there is a lack of results from direct measurements. In this study, we used measurements of O3, NO2 and meteorological conditions from a dense network in the Yangtze River Delta (YRD), and satellite observed formaldehyde (HCHO) and NO2 column densities for the analysis of O3 variabilities and its relationship to NO2. As a result, severe O3 pollution occurred mainly in Shanghai city, southern Jiangsu and northern Zhejiang provinces in YRD during April–September. In addition, meteorological conditions could explain 54% the diurnal O3 variation over YRD. During April–September 2015–2021, O3 showed a significant positive relationship (r = 0.61 ± 0.10) with NO2 after removing the impact from meteorological conditions. However, the relationship could be reversed with NO2 concentration change. Our result suggested that the controllable O3 related to NO2 change is up to 100 μg·m−3 in megacities over Shanghai and northern Zhejiang province. The O3 is much more sensitive to the NO2 reduction in megacities than surrounding areas. Our results evaluate the different impacts of NO2 changes on O3 formation, which provides explanation for the simultaneously alleviated O3 pollution and reduced NO2 in 2020 in Shanghai and northern Zhejiang, as well as the increased O3 in most counties before 2019 with reduced NO2 during October–March. The driving mechanism as revealed from this study for O3 and NO2 will be valuable for the O3 abatement through NO2 reduction at sub-county scale over YRD in China. [ABSTRACT FROM AUTHOR]

In the context of global warming, how to measure summer climate suitability at a local scale is important for meteorological services. Considering meteorological and ecological conditions, body comfort, and the atmospheric environment, an assessment method for summer climate suitability for Zhejiang Province is proposed. In this paper, a summer suitable index (SSI) for Zhejiang is calculated, including four secondary indices: a summer cool index (SCI), a comfort days index (CDI), a good air days index (GADI) and a vegetation cover index (VCI). Using a local evaluation criterion, summer climate suitable areas are distinguished objectively according to the SSI. The results show that especially suitable regions account for 4.97% of Zhejiang Province, very suitable regions account for 22.2%, suitable regions account for 39.58%, and general regions account for 33.25%. The summer climate suitable areas are located mainly in high mountains and hills and coastal island areas while plain areas cannot be considered a suitable destination for summer tourism. By comparison and discussion, the SSI is demonstrated to capture summer climate suitability well. In contrast to a fixed evaluation index, benchmark values obtained for the SSI depend on the local climate and the index is straightforward to apply. [ABSTRACT FROM AUTHOR]

Background: Salt stress causes inhibition of plant growth and development, and always leads to an increasing threat to plant agriculture. Transcription factors regulate the expression of various genes for stress response and adaptation. It's crucial to reveal the regulatory mechanisms of transcription factors in the response to salt stress. Results: A salt-inducible NAC transcription factor gene PagNAC045 was isolated from Populus alba×P. glandulosa. The PagNAC045 had a high sequence similarity with NAC045 (Potri.007G099400.1) in P. trichocarpa, and they both contained the same conserved motifs 1 and 2, which constitute the highly conserved NAM domain at the N-terminus. Protein-protein interaction (PPI) prediction showed that PagNAC045 potentially interacts with many proteins involved in plant hormone signaling, DNA-binding and transcriptional regulation. The results of subcellular localization and transient expression in tobacco leaves confirmed the nuclear localization of PagNAC045. Yeast two-hybrid revealed that PagNAC045 protein exhibits transcriptional activation property and the activation domain located in its C-terminus. In addition, the 1063 bp promoter of PagNAC045 was able to drive GUS gene expression in the leaves and roots. In poplar leaves and roots, PagNAC045 expression increased significantly by salt and ABA treatments. Tobacco seedlings overexpressing PagNAC045 exhibited enhanced tolerance to NaCl and ABA compared to the wild-type (WT). Yeast one-hybrid assay demonstrated that a bHLH104-like transcription factor can bind to the promoter sequence of PagNAC045. Conclusion: The PagNAC045 functions as positive regulator in plant responses to NaCl and ABA-mediated stresses. [ABSTRACT FROM AUTHOR]

Background: Salt stress causes inhibition of plant growth and development, and always leads to an increasing threat to plant agriculture. Transcription factors regulate the expression of various genes for stress response and adaptation. It's crucial to reveal the regulatory mechanisms of transcription factors in the response to salt stress. Results: A salt-inducible NAC transcription factor gene PagNAC045 was isolated from Populus alba×P. glandulosa. The PagNAC045 had a high sequence similarity with NAC045 (Potri.007G099400.1) in P. trichocarpa, and they both contained the same conserved motifs 1 and 2, which constitute the highly conserved NAM domain at the N-terminus. Protein-protein interaction (PPI) prediction showed that PagNAC045 potentially interacts with many proteins involved in plant hormone signaling, DNA-binding and transcriptional regulation. The results of subcellular localization and transient expression in tobacco leaves confirmed the nuclear localization of PagNAC045. Yeast two-hybrid revealed that PagNAC045 protein exhibits transcriptional activation property and the activation domain located in its C-terminus. In addition, the 1063 bp promoter of PagNAC045 was able to drive GUS gene expression in the leaves and roots. In poplar leaves and roots, PagNAC045 expression increased significantly by salt and ABA treatments. Tobacco seedlings overexpressing PagNAC045 exhibited enhanced tolerance to NaCl and ABA compared to the wild-type (WT). Yeast one-hybrid assay demonstrated that a bHLH104-like transcription factor can bind to the promoter sequence of PagNAC045. Conclusion: The PagNAC045 functions as positive regulator in plant responses to NaCl and ABA-mediated stresses. [ABSTRACT FROM AUTHOR]

The low‐low temperature electrostatic precipitator (LLT‐ESP) has been applied in many power plants to improve the emission performance. In this study, a number of fix‐bed experiments were conducted, which simulated the operation condition of LLT‐ESP. The effect of chemical composition on the adsorption characteristics of ash samples and the agglomeration after adsorption were studied. The results show that the agglomeration of ash particles occurs in three forms, including agglomeration among small particles, adhesion of loose pellets to large particles, and agglomeration among large particles. The capacity of ash particles to adsorb sulphuric acid is less affected by the increase of added amounts of NaCl or KCl. At the same time, the added amount of NaCl or KCl also has little effect on the agglomeration degree of ash particles. The addition of MgO, CaO, Fe2O3, Na2CO3, or K2CO3 from 0% to 13.3%, 22.4%, 23.9%, 18.4%, or 14.2%, promotes the adsorption of sulphuric acid by ash particles from 1.95 mg g−1 to 7.33, 7.71, 6.72, 5.1, or 5.44 mg g−1 (based on sulphur content), respectively, thereby promoting the agglomeration between ash particles. As the addition amount increases, the agglomeration phenomenon among particles becomes more conspicuous. The form of agglomeration changes from agglomeration among small particles to agglomeration among large particles. In addition, the addition of MgO or CaO has great influence on the adsorption and agglomeration. [ABSTRACT FROM AUTHOR]

Gaofen-3 (GF-3) is the first Chinese space-borne multi-polarization synthetic aperture radar (SAR) instrument at C-band (5.43 GHz). In this paper, we use data collected from GF-3 to observe Super Typhoon Lekima (2019) in the East China Sea. Using a VH-polarized wide ScanSAR (WSC) image, ocean surface wind speeds at 100m horizontal resolution are obtained at 21:56:59 UTC on 8 August 2019, with the maximum wind speed, 38.9 m·s−1. Validating the SAR-retrieved winds with buoy-measured wind speeds, we find that the root mean square error (RMSE) is 1.86 m·s−1, and correlation coefficient, 0.92. This suggests that wind speeds retrieved from GF-3 SAR are reliable. Both the European Centre for Medium-Range Weather Forecasts (ECMWF) fine grid operational forecast products with spatial resolution, and China Global/Regional Assimilation and Prediction Enhance System (GRAPES) have good performances on surface wind prediction under weak wind speed condition (< 24 m·s−1), but underestimate the maximum wind speed when the storm is intensified as a severe tropical storm (> 24 m·s−1). With respect to SAR-retrieved wind speeds, the RMSEs are 5.24 m·s−1 for ECMWF and 5.17 m·s−1 for GRAPES, with biases of 4.16 m·s−1 for ECMWF and 3.84 m·s−1 for GRAPES during Super Typhoon Lekima (2019). [ABSTRACT FROM AUTHOR]

Antibiotic filter residue (AFR) is a typical deep-utilized biomass waste residue with high yield, which is difficult to burn be individually utilized as fuel due to its poor combustion characteristics. The co-combustion of AFR with vegetal biomass is likely to be an effective approach to enhance the combustion performance of AFR, while the co-firing mechanism and kinetics have yet to be fully understood. The present study aimed to investigate the co-combustion characteristics and kinetics of antibiotic filter residue and vegetal biomass (forestall biomass and agricultural biomass) by thermogravimetric experiments and kinetics analysis. The experimental results showed that the co-firing of AFR with peanut shell and poplar improved the combustion characteristics of AFR. Kinetic analysis indicated that the optimal solid-phase reaction models of the blend combustion were diffusion models. The specific form of the reaction function varied with the type and mass fraction of the blends. The present study can provide an improved understanding of the clean and efficient utilization of antibiotic filter residue by co-combustion. [ABSTRACT FROM AUTHOR]

The ANSYS Fluent 2020 R2 software is used to study the flow and combustion characteristics of a new type biomass circulating fluidized bed boiler. The velocity distribution characteristics, particle separation efficiency and temperature field distribution in the built-in cyclone separator are studied. The results show that the velocity distribution of the flue gas in the cyclone separator decreases gradually from periphery to center, which can form the vortex area. When excess air coefficient is between 1.15-1.2, the separation effect of the separator is the best, which can reach more than 96.5%. The excess air coefficient obviously affects the combustion condition in the boiler, with the increase of excess air coefficient, the temperature increases first and then decreases, and the optimal excess air coefficient is 1.15. [ABSTRACT FROM AUTHOR]

Background: The Late Embryogenesis-Abundant (LEA) gene families, which play significant roles in regulation of tolerance to abiotic stresses, widely exist in higher plants. Poplar is a tree species that has important ecological and economic values. But systematic studies on the gene family have not been reported yet in poplar. Results: On the basis of genome-wide search, we identified 88 LEA genes from Populus trichocarpa and renamed them as PtrLEA. The PtrLEA genes have fewer introns, and their promoters contain more cis-regulatory elements related to abiotic stress tolerance. Our results from comparative genomics indicated that the PtrLEA genes are conserved and homologous to related genes in other species, such as Eucalyptus robusta, Solanum lycopersicum and Arabidopsis. Using RNA-Seq data collected from poplar under two conditions (with and without salt treatment), we detected 24, 22 and 19 differentially expressed genes (DEGs) in roots, stems and leaves, respectively. Then we performed spatiotemporal expression analysis of the four up-regulated DEGs shared by the tissues, constructed gene co-expression-based networks, and investigated gene function annotations. Conclusion: Lines of evidence indicated that the PtrLEA genes play significant roles in poplar growth and development, as well as in responses to salt stress. [ABSTRACT FROM AUTHOR]

This work investigates the effect of the resampling spatial resolution (RSR) on the retrieval of ocean surface wind speed from satellite-borne Synthetic Aperture Radar (SAR) images. For this purpose, 358 RADARSAT-2(RS-2) fine-beam quad-polarized SAR images and in-situ National Data Buoy Centre (NDBC) and China State Oceanic Administration (SOA) buoy measurements from selected geographic locations are used in this paper. In order to obtain better accuracy SAR-retrieved wind speeds, CMOD5.N function, Z2011 polarization ratio (PR) model and C2PO model constitute the best models for VV-, HH- and cross-polarized SAR images, respectively. The resulting statistical analysis suggests that better accuracy wind speeds can be retrieved at somewhat coarser resolutions. The optimal RSR for the VV-, HH-, VH- and HV-polarized channels are 850, 1050,1350 and 1450 m, respectively, with RMSEs of 1.74, 2.03, 1.61 and 1.83 m/s. [ABSTRACT FROM AUTHOR]

Zhundong high-alkali coal has been studied a lot owing to its abundant reserve but serious ash-related issues. Oxy-fuel combustion profits the reduction of pollutant emissions and coal blending alleviates the ash-related problems practically. Nevertheless, little work if any has been carried out on oxy-fuel co-combustion of Zhundong coal, while the influences of blending on the migration of iron and alkali alkaline-earth metals have yet to be adequately understood. This study aims to illuminate the release and migration behaviors of alkali alkaline-earth metals, iron and aluminum in oxy-fuel co-combustion via a lab-scale experimental system. Experimental results showed that the yield, color, bulk, and composition of ash were greatly temperature-dependent and significantly affected by the blending ratio in oxy-fuel co-combustion. As the blending ratio was 50%, the transformation and release features of iron, sodium and calcium in the blend with combustion temperature were close to those of non-Zhundong coal. The blending of Lingxin coal into Zhundong coal could benefit the transformation from NH 4 Ac-soluble calcium to H 2 O-soluble form, and facilitate the transformation of HCl-soluble aluminum and iron to insoluble form. The occurrence modes of elements and the ash yield of individual coal both exerted profound impacts on the element release ratio and chemical forms within ash of the blends. The present research has potential to offer an improved knowledge on the functional mechanisms of alkali alkaline-earth metals, aluminum, and iron on ash-related issues during high-alkali coal oxy-fuel co-combustion. • The transformations of AAEMs and iron in oxy-fuel co-combustion were investigated. • The effects of temperature and blending ratio on element chemical form were explored. • The physicochemical features of ash were highly dependent on blending ratio. • The sodium release rule in oxy-fuel co-combustion differed from the ash yield rule. • Coal blending affected the element occurrence mode in ash substantially. [ABSTRACT FROM AUTHOR]

Optical connectivity, which has been widely deployed in today's datacenters and high-performance computing (HPC) systems, is a disruptive technological revolution to the IT industry in the new Millennium. In our journey to debut an Exascale supercomputer, a completely new computing concept, called memory-driven computing, was innovated recently. This new computing architecture brings challenges and opportunities for novel optical interconnect solutions. Here, we first discuss our strategy to develop appropriate optical link solutions for different data traffic scenarios in memory-driven HPCs. Then, we present detailed review on recent work to demonstrate fully photonics-electronics-integrated single- and multi-wavelength directly modulated laser (DML) transmitters on silicon for the first time. Compact heterogeneous microring lasers and laser arrays were fabricated as photonic engines to work with a customized complementary metal-oxide semiconductor (CMOS) driver circuit. Microring lasers based on conventional quantum well and new quantum dot lasing medium were compared in the experiment. Thermal shunt and MOS capacitor structures were integrated into the lasers for effective thermal management and ultra low-energy tuning. It enables a controllable dense wavelength division multiplexing (DWDM) link architecture in an HPC environment. An equivalent microring laser circuit model was constructed to allow photonics-electronics co-simulation. Equalization functionality in the CMOS driver circuit proved to be critical to achieve up to 14 Gb/s direct modulation with 6 dB extinction ratio. Finally, the on-going and future work is discussed towards more robust, higher speed, and more energy efficient DML transmitters. [ABSTRACT FROM AUTHOR]

Uncontrolled metastasis significantly contributes to high lethality of patients suffering from ovarian cancer. To date, the detailed molecular mechanisms which account for ovarian tumor cell spreading and metastasis remain largely unknown. In a recent study, we have demonstrated that aberrantly high expression of the non-receptor tyrosine kinase FER is responsible for ovarian tumor cell metastasis both in vitro and in vivo. Mechanistically, we indentified Hepatocyte Growth Factor Receptor HGFR/MET as a novel substrate of FER, and through which the kinase FER modulates ovarian cancer cell motility and invasiveness in a ligand-independent manner. We also observed aberrantly high expression of PAK1 kinase in cancer cells, and RNAi-mediated knockdown of FER kinase inactivated the RAC1-PAK1 signaling pathway and decreased metastatic potential of CAOV4 ovarian cancer cells. Overall, our study revealed a previously uncharacterized, pro-metastatic role of the kinase FER in ovarian cancer through the MET-RAC1-PAK1 pathway. Further efforts are essential to investigating beneficial outcomes towards targeting the RAC1-PAK1 signaling pathway in reducing metastatic burden of this deadly disease. [ABSTRACT FROM AUTHOR]

Metastasis is the leading cause of high ovarian-cancer-related mortality worldwide. Three major processes constitute the whole metastatic cascade: invasion, intravasation, and extravasation. Tumor cells often reprogram their metabolism to gain advantages in proliferation and survival. However, whether and how those metabolic alterations contribute to the invasiveness of tumor cells has yet to be fully understood. Here we performed a genome-wide CRISPR-Cas9 screening to identify genes participating in tumor cell dissemination and revealed that PTGES3 acts as an invasion suppressor in ovarian cancer. Mechanistically, PTGES3 binds to phosphofructokinase, liver type (PFKL) and generates a local source of prostaglandin E2 (PGE2) to allosterically inhibit the enzymatic activity of PFKL. Repressed PFKL leads to downgraded glycolysis and the subsequent TCA cycle for glucose metabolism. However, ovarian cancer suppresses the expression of PTGES3 and disrupts the PTGES3-PGE2-PFKL inhibitory axis, leading to hyperactivation of glucose oxidation, eventually facilitating ovarian cancer cell motility and invasiveness. [Display omitted] • CRISPR-Cas9 screening identifies PTGES3 as an invasion suppressor in ovarian cancer • PTGES3 is associated with the glycolytic rate-limiting enzyme PFKL • PTGES3-mediated prostaglandin E2 production elicits allosteric inhibition of PFKL • Loss of PTGES3 facilitates the epithelial-mesenchymal transition Chen et al. identify a tumor-suppressive gene, PTGES3 , and a tumor-suppressive metabolite, PGE2, in ovarian cancer cells, which behave as a "glycolytic rheostat." They elucidate the mechanism of how PGE2 allosterically inhibits the activity of the glycolytic rate-limiting enzyme PFKL, providing a potential molecular vulnerability for treating ovarian cancer metastasis. [ABSTRACT FROM AUTHOR]

A typhoon is one of the most dangerous natural disasters in the Yangtze River Delta of China. Based on an integrated assessment of the disaster risk elements, including hazard factor, exposure, and vulnerability, the risk level of a typhoon disaster for the Yangtze River Delta as a county-level unit was ultimately determined. The result shows that the risk levels of typhoon hazard factor are gradually weakened from the southeastern coastal areas to the northwest, and the highest-risk areas are located in the southeastern coastal regions. Due to many towns, dense population, a developed economy, and a huge disaster-bearing body in the north of the Yangtze River Delta, which is also located on the plain for a high susceptibility to a disaster-breeding environment, the exposure risk level in the northern areas is higher than in the south. The most vulnerable counties are Chun'an, Xianju, Tiantai, and Sanmen in Zhejiang Province, and Baoying and Xinghua in Jiangsu Province. The highest-risk areas for a typhoon disaster are primarily located in the southeastern coastal areas of Zhejiang Province, Hangzhou Bay, and Shanghai near the Yangtze River Estuary, while the lowest-risk areas are distributed in the western portion of Hangzhou and the northern area of the Yangtze River Delta. [ABSTRACT FROM AUTHOR]

The risk of drought in the Yangtze River Delta Region (YRDR) was assessed using the method of natural disaster risk assessment. Based on the index of disaster risk, the assessment results of risk elements such as drought hazard and vulnerability were calculated in the YRDR. The division of relative drought risk levels in the YRDR was produced at the scale of county (city, district) and township. The results indicated that the areas of highest hazard of drought are located in the northern area of the YRDR. Areas with the greatest vulnerability of drought included Shanghai, Jiaxing, Wuxi, and Hangzhou. The highest risks of drought were mainly distributed in the north of the YRDR; the proportion of slightly high and extremely high risk areas in Shanghai, Nantong, Zhenjiang, Yangzhou, and Taizhou (Jiangsu province) is over 95%. The lowest-risk areas included the southeast coastal area of the YRDR, especially in Hangzhou, and Taizhou (Zhejiang province), where the proportion of slightly high and extremely high risk areas is below 5%. Based on this drought risk assessment, it is critical to establish a drought assessment system including both guarding against and addressing drought. [ABSTRACT FROM AUTHOR]

Although DNA encodes the molecular instructions that underlie the control of cell function, it is the proteins that are primarily responsible for implementing those instructions. Therefore quantitative analyses of the proteome would be expected to yield insights into important candidates for the detection and treatment of disease. We present an iTRAQ (isobaric tag for relative and absolute quantification)-based proteomic analysis of ten ovarian cancer cell lines and two normal ovarian surface epithelial cell lines. We profiled the abundance of 2659 cellular proteins of which 1273 were common to all 12 cell lines. Of the 1273, 75 proteins exhibited elevated expression and 164 proteins had diminished expression in the cancerous cells compared with the normal cell lines. The iTRAQ expression profiles allowed us to segregate cell lines based upon sensitivity and resistance to carboplatin. Importantly, we observed no substantial correlation between protein abundance and RNA expression or epigenetic DNA methylation data. Furthermore, we could not discriminate between sensitivity and resistance to carboplatin on the basis of RNA expression and DNA methylation data alone. The present study illustrates the importance of proteomics-based discovery for defining the basis for the carboplatin response in ovarian cancer and highlights candidate proteins, particularly involved in cellular redox regulation, homologous recombination and DNA damage repair, which otherwise could not have been predicted from whole genome and expression data sources alone. [ABSTRACT FROM AUTHOR]

Although tumor-infiltrating lymphocytes (TILs) maintain their ability to proliferate, persist, and eradicate tumors, they are frequently dysfunctional in situ. By performing both whole-genome CRISPR and metabolic inhibitor screens, we identify that nicotinamide phosphoribosyltransferase (NAMPT) is required for T cell activation. NAMPT is low in TILs, and its expression is controlled by the transcriptional factor Tubby (TUB), whose activity depends on the T cell receptor-phospholipase C gamma (TCR-PLCγ) signaling axis. The intracellular level of NAD+, whose synthesis is dependent on the NAMPT-mediated salvage pathway, is also decreased in TILs. Liquid chromatography-mass spectrometry (LC-MS) and isotopic labeling studies confirm that NAD+ depletion led to suppressed glycolysis, disrupted mitochondrial function, and dampened ATP synthesis. Excitingly, both adoptive CAR-T and anti-PD1 immune checkpoint blockade mouse models demonstrate that NAD+ supplementation enhanced the tumor-killing efficacy of T cells. Collectively, this study reveals that an impaired TCR-TUB-NAMPT-NAD+ axis leads to T cell dysfunction in the tumor microenvironment, and an over-the-counter nutrient supplement of NAD+ could boost T-cell-based immunotherapy. [Display omitted] • Levels of NAD+ and NAMPT are decreased in TILs compared to those of other T cells • Tubby is a transcriptional factor for NAMPT in T cells • NAMPT-mediated NAD+ production is essential for T cell activation by generating ATP • NAD+ supplementation enhances the tumor-killing function of T cells Wang et al. report that NAD+ biosynthesis through the TCR-PLCγ-TUB-NAMPT-mediated salvage pathway is important for T cell activation. Metabolically, NAD+ deficiency causes defects in aerobic glycolysis and oxidative phosphorylation. NAD+ supplementation rescues these defects and enhances the tumor-killing efficacy of T cells in both CAR-T and anti-PD1 mouse models. [ABSTRACT FROM AUTHOR]

In order to achieve the industrial application of ultrasonic energy in the continuous casting and rolling production of aluminum alloy, a new type of L-shaped ultrasonic rod was used to introduce an ultrasonic bending vibration into the aluminum melt in the launder during the horizontal twin-roll continuous casting and rolling process of a 1060 aluminum alloy. The effects of the ultrasonic bending vibration on the microstructure and properties of the 1060 aluminum alloy cast rolling strip and its subsequent cold rolling strip were studied experimentally, and the effect of the ultrasonic-assisted refining with different amounts of Al-Ti-B refiner was explored. The results show that under the same addition amount of Al-Ti-B refiner, the ultrasonic bending vibration can refine the grains of the cast rolling strip, make the distribution of precipitates more uniform, reduce the slag inclusion defects, and improve the mechanical properties to a certain extent. The microstructure and properties of the ultrasonic cast rolling strip with 0.18 wt% Al-Ti-B refiner or 0.12 wt% Al-Ti-B refiner are better than those of the conventional cast rolling strip, but the microstructure and properties of the ultrasonic cast rolling strip with 0.09 wt% Al-Ti-B refiner are slightly worse than those of the conventional cast rolling strip. Moreover, after cold rolling, the effect of the ultrasonic bending vibration on the improvement of the microstructure and properties of the aluminum alloy strip is inherited. A comprehensive analysis shows that the use of ultrasonic energy in this paper cannot completely replace the effect of the Al-Ti-B refiner, but it can reduce the addition amount of the Al-Ti-B refiner by 1/3. [ABSTRACT FROM AUTHOR]