The Regional Climate Model(RegCM)proves valuable for climate analysis and has been applied to a wide range of climate change aspects and other environmental issues at a regional scale.The model also demonstrated succe...The Regional Climate Model(RegCM)proves valuable for climate analysis and has been applied to a wide range of climate change aspects and other environmental issues at a regional scale.The model also demonstrated success in diverse areas of urban research,including urban heat island studies,extreme climate events analysis,assessing urban resilience,and evaluating urbanization impacts on climate and air quality.Recently,more studies have been conducted in utilizing RegCM to address climate change in cities,due to its enhanced ability over the years to capture meteorological phenomena at city scales.However,there are many challenges associated with its implementation in meso-scale research,which are attributed to various shortcomings and thus create room for further improvement in the model.This paper presents a comprehensive overview of the evolution of the RegCM over the years and its customisation across various parameters,demonstrating its versatility in urban climate studies and underscoring the model’s pivotal role in addressing multifaceted challenges in urban environments.By addressing these aspects,the paper offers valuable insights and recommendations for researchers seeking to enhance the accuracy and efficacy of urban climate simulations using the RegCM system,thereby contributing to the advancement of urban climate science and sustainability.展开更多
Currently,the most cost-effective and efficient method for phosphorus(P)removal from wastewater is enhanced biological P removal(EPBR)via polyphosphate-accumulating organisms(PAOs).This study integrates a literature r...Currently,the most cost-effective and efficient method for phosphorus(P)removal from wastewater is enhanced biological P removal(EPBR)via polyphosphate-accumulating organisms(PAOs).This study integrates a literature review with genomic analysis to uncover the phylogenetic and metabolic diversity of the relevant PAOs for wastewater treatment.The findings highlight significant differences in the metabolic capabilities of PAOs relevant to wastewater treatment.Notably,Candidatus Dechloromonas and Candidatus Accumulibacter can synthesize polyhydroxyalkanoates,possess specific enzymes for ATP production from polyphosphate,and have electrochemical transporters for acetate and C4-dicarboxylates.In contrast,Tetrasphaera,Candidatus Phosphoribacter,Knoellia,and Phycicoccus possess PolyP-glucokinase and electrochemical transporters for sugars/amino acids.Additionally,this review explores various detection methods for polyphosphate and PAOs in activated sludge wastewater treatment plants.Notably,FISH-Raman spectroscopy emerges as one of the most advanced detection techniques.Overall,this review provides critical insights into PAO research,underscoring the need for enhanced strategies in biological phosphorus removal.展开更多
Fruits,vegetables,and dairy products are typically the primary sources of household food waste.Currently,anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of b...Fruits,vegetables,and dairy products are typically the primary sources of household food waste.Currently,anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of biogas.However,to achieve a circular carbon economy,the organics in food waste should be converted to new chemicals with higher value than energy.Here we demonstrate the feasibility of medium-chain carboxylic acid(MCCA)production from expired dairy and beverage waste via a chain elongation platform mediated by lactate.In a two-stage fermentation process,the first stage with optimized operational conditions,including varying temperatures and organic loading rates,transformed expired dairy and beverage waste into lactate at a concentration higher than 900 mM C at 43℃.This lactate was then used to produce>500 mM C caproate and>300 mM C butyrate via microbial chain elongation.Predominantly,lactate-producing microbes such as Lactobacillus and Lacticaseibacillus were regulated by temperature and could be highly enriched under mesophilic conditions in the firststage reactor.In the second-stage chain elongation reactor,the dominating microbes were primarily from the genera Megasphaera and Caproiciproducens,shaped by varying feed and inoculum sources.Cooccurrence network analysis revealed positive correlations among species from the genera Caproiciproducens,Ruminococcus,and CAG-352,as well as Megasphaera,Bacteroides,and Solobacterium,indicating strong microbial interactions that enhance caproate production.These findings suggest that producing MCCAs from expired dairy and beverage waste via lactate-mediated chain elongation is a viable method for sustainable waste management and could serve as a chemical production platform in the context of building a circular bioeconomy.展开更多
Current marine research primarily depends on weighty and invasive sensory equipment and telemetric network to understand the marine environment,including the diverse fauna it contains,as a function of animal behavior ...Current marine research primarily depends on weighty and invasive sensory equipment and telemetric network to understand the marine environment,including the diverse fauna it contains,as a function of animal behavior and size,as well as equipment longevity.To match animal morphology and activity within the surrounding marine environment,here we show a physically flexible and stretchable skin-like and waterproof autonomous multifunctional system,integrating Bluetooth,memory chip,and high performance physical sensors.The sensory tag is mounted on a swimming crab(Portunus pelagicus)and is capable of continuous logging of depth,temperature,and salinity within the harsh ocean environment.The fully packaged,ultra-lightweight(<2.4 g in water),and compliant“Marine Skin”system does not have any wired connection enabling safe and weightless cuttingedge approach to monitor and assess marine life and the ecosystem’s health to support conservation and management of marine ecosystems.展开更多
The number of available protein sequences in public databases is increasing exponentially.However,a sig-nificant percentage of these sequences lack functional annotation,which is essential for the understanding of how...The number of available protein sequences in public databases is increasing exponentially.However,a sig-nificant percentage of these sequences lack functional annotation,which is essential for the understanding of how bio-logical systems operate.Here,we propose a novel method,Quantitative Annotation of Unknown STructure(QAUST),to infer protein functions,specifically Gene Ontology(GO)terms and Enzyme Commission(EC)numbers.QAUST uses three sources of information:structure information encoded by global and local structure similarity search,biological network information inferred by protein–protein interaction data,and sequence information extracted from functionally discriminative sequence motifs.These three pieces of information are combined by consensus averaging to make the final prediction.Our approach has been tested on 500 protein targets from the Critical Assessment of Functional Annotation(CAFA)benchmark set.The results show that our method provides accurate functional annotation and outperforms other prediction methods based on sequence similarity search or threading.We further demonstrate that a previously unknown function of human tripartite motif-containing 22(TRIM22)protein predicted by QAUST can be experimentally validated.展开更多
Lipid Droplets(LDs)are emerging as crucial players in colon cancer development and maintenance.Their expression has been associated with high tumorigenicity in Cancer Stem Cells(CSCs),so that they have been proposed a...Lipid Droplets(LDs)are emerging as crucial players in colon cancer development and maintenance.Their expression has been associated with high tumorigenicity in Cancer Stem Cells(CSCs),so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells(CR-CSCs).They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules.There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists,although the effects of nutrients,primarily glucose,on the CSC behavior are still mostly unexplored.Glucose is an essential fuel for cancer cells,and the connections with LDs in the healthy and CSC populations merit to be more deeply investigated.Here,we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC markers.Additionally,glucose was responsible for the increased amount of Reactive Oxygen Species(ROS)and LDs in both healthy and CR-CSC samples.We also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most affected.Lastly,Atorvastatin,a lipidlowering drug,induced the highest mortality on CR-CSCs without affecting the healthy counterpart.展开更多
Anchorene,identified as an endogenous bioactive carotenoid-derived dialdehyde and diapocarotenoid,affects root development by modulating auxin homeostasis.However,the precise interaction between anchorene and auxin,as...Anchorene,identified as an endogenous bioactive carotenoid-derived dialdehyde and diapocarotenoid,affects root development by modulating auxin homeostasis.However,the precise interaction between anchorene and auxin,as well as the mechanisms by which anchorene modulates auxin levels,remain largely elusive.In this study,we conducted a comparative analysis of anchorene's bioactivities alongside auxin and observed that anchorene induces multifaceted auxin-like effects.Through genetic and pharmacological examinations,we revealed that anchorene's auxin-like activities depend on the indole-3-pyruvate-dependent auxin biosynthesis pathway,as well as the auxin inactivation pathway mediated by Group II Gretchen Hagen 3(GH3)proteins that mainly facilitate the conjugation of indole-3-acetic acid(IAA)to amino acids,leading to the formation of inactivated storage forms.Our measurements indicated that anchorene treatment elevates IAA levels while reducing the quantities of inactivated IAA–amino acid conjugates and ox IAA.RNA sequencing further revealed that anchorene triggers the expression of numerous auxin-responsive genes in a manner reliant on Group II GH3s.Additionally,our in vitro enzymatic assays and biolayer interferometry(BLI)assay demonstrated anchorene's robust suppression of GH3.17-mediated IAA conjugation with glutamate.Collectively,our findings highlight the significant role of carotenoid-derived metabolite anchorene in modulating auxin homeostasis,primarily through the repression of GH3-mediated IAA conjugation and inactivation pathways,offering novel insights into the regulatory mechanisms of plant bioactive apocarotenoids.展开更多
Current FDA-approved kinase inhibitors cause diverse adverse effects,some of which are due to the me-chanism-independent effects of these drugs.Identifying these mechanism-independent interactions could improve drug s...Current FDA-approved kinase inhibitors cause diverse adverse effects,some of which are due to the me-chanism-independent effects of these drugs.Identifying these mechanism-independent interactions could improve drug safety and support drug repurposing.Here,we develop iDTPnd(integrated Drug Target Predictor with negative dataset),a computational approach for large-scale discovery of novel targets for known drugs.For a given drug,we construct a positive structural signature as well as a negative structural signature that captures the weakly conserved structural features of drug-binding sites.To facilitate assessment of unintended targets,iDTPnd also provides a docking-based interaction score and its statistical significance.We confirm the interactions of sorafenib,imatinib,dasatinib,sunitinib,and pazopanib with their known targets at a sensitivity of 52%and a specificity of 55%.We also validate 10 predicted novel targets by using in vitro experiments.Our results suggest that proteins other than kinases,such as nuclear receptors,cytochrome P450,and MHC class I molecules,can also be physiologically relevant targets of kinase inhibitors.Our method is general and broadly applicable for the identification of protein–small molecule interactions,when sufficient drug–target 3D data are available.The code for constructing the structural signatures is available at https://sfb.kaust.edu.sa/Documents/iDTP.zip.展开更多
文摘The Regional Climate Model(RegCM)proves valuable for climate analysis and has been applied to a wide range of climate change aspects and other environmental issues at a regional scale.The model also demonstrated success in diverse areas of urban research,including urban heat island studies,extreme climate events analysis,assessing urban resilience,and evaluating urbanization impacts on climate and air quality.Recently,more studies have been conducted in utilizing RegCM to address climate change in cities,due to its enhanced ability over the years to capture meteorological phenomena at city scales.However,there are many challenges associated with its implementation in meso-scale research,which are attributed to various shortcomings and thus create room for further improvement in the model.This paper presents a comprehensive overview of the evolution of the RegCM over the years and its customisation across various parameters,demonstrating its versatility in urban climate studies and underscoring the model’s pivotal role in addressing multifaceted challenges in urban environments.By addressing these aspects,the paper offers valuable insights and recommendations for researchers seeking to enhance the accuracy and efficacy of urban climate simulations using the RegCM system,thereby contributing to the advancement of urban climate science and sustainability.
基金supported by King Abdullah University of Science and Technology(KAUST).
文摘Currently,the most cost-effective and efficient method for phosphorus(P)removal from wastewater is enhanced biological P removal(EPBR)via polyphosphate-accumulating organisms(PAOs).This study integrates a literature review with genomic analysis to uncover the phylogenetic and metabolic diversity of the relevant PAOs for wastewater treatment.The findings highlight significant differences in the metabolic capabilities of PAOs relevant to wastewater treatment.Notably,Candidatus Dechloromonas and Candidatus Accumulibacter can synthesize polyhydroxyalkanoates,possess specific enzymes for ATP production from polyphosphate,and have electrochemical transporters for acetate and C4-dicarboxylates.In contrast,Tetrasphaera,Candidatus Phosphoribacter,Knoellia,and Phycicoccus possess PolyP-glucokinase and electrochemical transporters for sugars/amino acids.Additionally,this review explores various detection methods for polyphosphate and PAOs in activated sludge wastewater treatment plants.Notably,FISH-Raman spectroscopy emerges as one of the most advanced detection techniques.Overall,this review provides critical insights into PAO research,underscoring the need for enhanced strategies in biological phosphorus removal.
基金supported by a Competitive Research Grant(URF/1/4069-01-01)Research Translation Fund(REI/1/4576-01-01)from King Abdullah University of Science and Technology(KAUST),Saudi Arabia.
文摘Fruits,vegetables,and dairy products are typically the primary sources of household food waste.Currently,anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of biogas.However,to achieve a circular carbon economy,the organics in food waste should be converted to new chemicals with higher value than energy.Here we demonstrate the feasibility of medium-chain carboxylic acid(MCCA)production from expired dairy and beverage waste via a chain elongation platform mediated by lactate.In a two-stage fermentation process,the first stage with optimized operational conditions,including varying temperatures and organic loading rates,transformed expired dairy and beverage waste into lactate at a concentration higher than 900 mM C at 43℃.This lactate was then used to produce>500 mM C caproate and>300 mM C butyrate via microbial chain elongation.Predominantly,lactate-producing microbes such as Lactobacillus and Lacticaseibacillus were regulated by temperature and could be highly enriched under mesophilic conditions in the firststage reactor.In the second-stage chain elongation reactor,the dominating microbes were primarily from the genera Megasphaera and Caproiciproducens,shaped by varying feed and inoculum sources.Cooccurrence network analysis revealed positive correlations among species from the genera Caproiciproducens,Ruminococcus,and CAG-352,as well as Megasphaera,Bacteroides,and Solobacterium,indicating strong microbial interactions that enhance caproate production.These findings suggest that producing MCCAs from expired dairy and beverage waste via lactate-mediated chain elongation is a viable method for sustainable waste management and could serve as a chemical production platform in the context of building a circular bioeconomy.
基金This publication is based upon work supported by the King Abdullah University of Science and Technology(KAUST)Office of Sponsored Research(OSR)under Award No.Sensor Innovation Initiative OSR-2015-Sensors-2707.
文摘Current marine research primarily depends on weighty and invasive sensory equipment and telemetric network to understand the marine environment,including the diverse fauna it contains,as a function of animal behavior and size,as well as equipment longevity.To match animal morphology and activity within the surrounding marine environment,here we show a physically flexible and stretchable skin-like and waterproof autonomous multifunctional system,integrating Bluetooth,memory chip,and high performance physical sensors.The sensory tag is mounted on a swimming crab(Portunus pelagicus)and is capable of continuous logging of depth,temperature,and salinity within the harsh ocean environment.The fully packaged,ultra-lightweight(<2.4 g in water),and compliant“Marine Skin”system does not have any wired connection enabling safe and weightless cuttingedge approach to monitor and assess marine life and the ecosystem’s health to support conservation and management of marine ecosystems.
基金supported by the King Abdullah University of Science and Technology(KAUST)Office of Sponsored Research(OSR)(Grant Nos.URF/1/1976-04,URF/1/1976-06)。
文摘The number of available protein sequences in public databases is increasing exponentially.However,a sig-nificant percentage of these sequences lack functional annotation,which is essential for the understanding of how bio-logical systems operate.Here,we propose a novel method,Quantitative Annotation of Unknown STructure(QAUST),to infer protein functions,specifically Gene Ontology(GO)terms and Enzyme Commission(EC)numbers.QAUST uses three sources of information:structure information encoded by global and local structure similarity search,biological network information inferred by protein–protein interaction data,and sequence information extracted from functionally discriminative sequence motifs.These three pieces of information are combined by consensus averaging to make the final prediction.Our approach has been tested on 500 protein targets from the Critical Assessment of Functional Annotation(CAFA)benchmark set.The results show that our method provides accurate functional annotation and outperforms other prediction methods based on sequence similarity search or threading.We further demonstrate that a previously unknown function of human tripartite motif-containing 22(TRIM22)protein predicted by QAUST can be experimentally validated.
基金This study was supported by Italian Association for Cancer Research(AIRC)and from the European Union’s Horizon 2020 Research And Innovation Programme under the Marie Skłodowska-Curie grant agreement No 800924This work was also supported by AIRC(5x1000 Clinical Oncology Extension Program 9979 and IG 16746).The authors acknowledge financial support from King Abdullah University of Science and Technology for OCRF-2014-CRG and OCRF-2016-CRG grants and from Piedmont Region through European Funds for Regional Development(“Food Digital Monitoring”project)This work is dedicated to the memory of our beloved Prof.Giovanni Morrone。
文摘Lipid Droplets(LDs)are emerging as crucial players in colon cancer development and maintenance.Their expression has been associated with high tumorigenicity in Cancer Stem Cells(CSCs),so that they have been proposed as a new functional marker in Colorectal Cancer Stem Cells(CR-CSCs).They are also indirectly involved in the modulation of the tumor microenvironment through the production of pro-inflammatory molecules.There is growing evidence that a possible connection between metabolic alterations and malignant transformation exists,although the effects of nutrients,primarily glucose,on the CSC behavior are still mostly unexplored.Glucose is an essential fuel for cancer cells,and the connections with LDs in the healthy and CSC populations merit to be more deeply investigated.Here,we showed that a high glucose concentration activated the PI3K/AKT pathway and increased the expression of CD133 and CD44v6 CSC markers.Additionally,glucose was responsible for the increased amount of Reactive Oxygen Species(ROS)and LDs in both healthy and CR-CSC samples.We also investigated the gene modulations following the HG treatment and found out that the healthy cell gene profile was the most affected.Lastly,Atorvastatin,a lipidlowering drug,induced the highest mortality on CR-CSCs without affecting the healthy counterpart.
基金supported by the National Natural Science Foundation of China(32170271)by the Natural Science Foundation of Henan Province(222300420024)the Project of Sanya Yazhou Bay Science and Technology City(SCKJ-JYRC-2022-19)。
文摘Anchorene,identified as an endogenous bioactive carotenoid-derived dialdehyde and diapocarotenoid,affects root development by modulating auxin homeostasis.However,the precise interaction between anchorene and auxin,as well as the mechanisms by which anchorene modulates auxin levels,remain largely elusive.In this study,we conducted a comparative analysis of anchorene's bioactivities alongside auxin and observed that anchorene induces multifaceted auxin-like effects.Through genetic and pharmacological examinations,we revealed that anchorene's auxin-like activities depend on the indole-3-pyruvate-dependent auxin biosynthesis pathway,as well as the auxin inactivation pathway mediated by Group II Gretchen Hagen 3(GH3)proteins that mainly facilitate the conjugation of indole-3-acetic acid(IAA)to amino acids,leading to the formation of inactivated storage forms.Our measurements indicated that anchorene treatment elevates IAA levels while reducing the quantities of inactivated IAA–amino acid conjugates and ox IAA.RNA sequencing further revealed that anchorene triggers the expression of numerous auxin-responsive genes in a manner reliant on Group II GH3s.Additionally,our in vitro enzymatic assays and biolayer interferometry(BLI)assay demonstrated anchorene's robust suppression of GH3.17-mediated IAA conjugation with glutamate.Collectively,our findings highlight the significant role of carotenoid-derived metabolite anchorene in modulating auxin homeostasis,primarily through the repression of GH3-mediated IAA conjugation and inactivation pathways,offering novel insights into the regulatory mechanisms of plant bioactive apocarotenoids.
基金supported by funding from King Abdullah University of Science and Technology,Office of Sponsored Research(Grant No.FCC/1/1976-25).
文摘Current FDA-approved kinase inhibitors cause diverse adverse effects,some of which are due to the me-chanism-independent effects of these drugs.Identifying these mechanism-independent interactions could improve drug safety and support drug repurposing.Here,we develop iDTPnd(integrated Drug Target Predictor with negative dataset),a computational approach for large-scale discovery of novel targets for known drugs.For a given drug,we construct a positive structural signature as well as a negative structural signature that captures the weakly conserved structural features of drug-binding sites.To facilitate assessment of unintended targets,iDTPnd also provides a docking-based interaction score and its statistical significance.We confirm the interactions of sorafenib,imatinib,dasatinib,sunitinib,and pazopanib with their known targets at a sensitivity of 52%and a specificity of 55%.We also validate 10 predicted novel targets by using in vitro experiments.Our results suggest that proteins other than kinases,such as nuclear receptors,cytochrome P450,and MHC class I molecules,can also be physiologically relevant targets of kinase inhibitors.Our method is general and broadly applicable for the identification of protein–small molecule interactions,when sufficient drug–target 3D data are available.The code for constructing the structural signatures is available at https://sfb.kaust.edu.sa/Documents/iDTP.zip.