Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,r...Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.展开更多
The periderm is a vital protective tissue found in the roots,stems,and woody elements of diverse plant species.It plays an important function in these plants by assuming the role of the epidermis as the outermost laye...The periderm is a vital protective tissue found in the roots,stems,and woody elements of diverse plant species.It plays an important function in these plants by assuming the role of the epidermis as the outermost layer.Despite its critical role for protecting plants from environmental stresses and pathogens,research on root periderm development has been limited due to its late formation during root development,its presence only in mature root regions,and its impermeability.展开更多
We performed large-scale molecular simulation to screen and identify metal-organic framework materials for gaseous iodine capture,as part of our ongoing effort in addressing management and handling issues of various r...We performed large-scale molecular simulation to screen and identify metal-organic framework materials for gaseous iodine capture,as part of our ongoing effort in addressing management and handling issues of various radionuclides in the grand scheme of spent nuclear fuel reprocessing.Starting from the computation-ready experimental(CoRE)metal-organic frameworks(MOFs)database,grand canonical Monte Carlo simulation was employed to predict the iodine uptake values of the MOFs.A ranking list of MOFs based on their iodine uptake capabilities was generated,with the Top 10 candidates identified and their respective adsorption sites visualized.Subsequently,machine learning was used to establish structure-property relationships to correlate MOFs’various structural and chemical features with their corresponding performances in iodine capture,yielding interpretable common features and design rules for viable MOF adsorbents.The research strategy and framework of the present study could aid the development of high-performing MOF adsorbents for capture and recovery of radioactive iodine,and moreover,other volatile environmentally hazardous species.展开更多
Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hemat...Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic traits.Each mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/lymphopoiesis.Our method should be applicable for other types of genetic screening in zebrafish.In addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.展开更多
1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Int...1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Intergovernmental Panel on Climate Change(IPCC)—consistently predict the widespread implementation of CO_(2)geological storage on a global scale.展开更多
Colorectal cancer(CRC)is a prevalent malignancy worldwide,posing a significant public health concern.Mounting evidence has confirmed that timely early screening facilitates the detection of incipient CRC,thereby enhan...Colorectal cancer(CRC)is a prevalent malignancy worldwide,posing a significant public health concern.Mounting evidence has confirmed that timely early screening facilitates the detection of incipient CRC,thereby enhancing patient prognosis.Obviously,non-participation of asymptomatic individuals in screening programs hampers early diagnosis and may adversely affect long-term outcomes for CRC patients.In this letter,we provide a comprehensive overview of the current status of early screening practices,while also thoroughly examine the dilemmas and potential solutions associated with early screening for CRC.In response to these issues,we proffer a set of recommendations directed at governmental authorities and the general public,which focus on augmenting financial investment,establishing standardized screening protocols,advancing technological capabilities,and bolstering public awareness campaigns.The importance of collaborative efforts from various stakeholders cannot be overstated in the quest to enhance early detection rates and alleviate the societal burden of CRC.展开更多
Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of m...Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.展开更多
Rapid screening of inorganic arsenic(iAs)in groundwater used for drinking by hundreds of millions of mostly rural residents worldwide is crucial for health protection.Most commercial field test kits are based on the G...Rapid screening of inorganic arsenic(iAs)in groundwater used for drinking by hundreds of millions of mostly rural residents worldwide is crucial for health protection.Most commercial field test kits are based on the Gutzeit reaction that uses mercury-based reagents for color development,an environmental concern that increasingly limits its utilization.This study further improves the Molybdenum Blue(MB)colorimetric method to allow for faster screening with more stable reagents.More importantly,a portable three-channel colorimeter is developed for screening iAs relative to the WHO drinking water guideline value(10μg/L).Adding the reducing reagents in sequence not only prolongs the storage time to>7 days,but also accelerates the color development time to 6 min in conjunction with lowering the H_(2)SO_(4) concentration in chromogenic reagents.The optimal pH ranges from 1.2 to 1.3 and is achieved by acidifying groundwater to 1%(V/V)HCl.With detection limits of 3.7μg/L for inorganic arsenate(iAs(V))and 3.8μg/L for inorganic arsenite(iAs(Ⅲ)),testing groundwater with-10μg/L of As has a precision<20%.The method works well for a range of phosphate concentrations of 48-950μg/L(0.5-10μmol/L).Concentrations of total_iAs(6-300μg/L),iAs(V)(6-230μg/L)and iAs(Ⅲ)(0-170μg/L)for 14 groundwater samples from Yinchuan Plain,Pearl River Delta,and Jianghan Plain,are in excellent agreements(linear regression slope:0.969-1.029)with the benchmark methods.The improved chemistry here lays the foundation for the MB colorimetric method to become a commercially viable screening tool,with further engineering and design improvement of the colorimeter.展开更多
Solid-state batteries are widely recognized as the next-generation energy storage devices with high specific energy,high safety,and high environmental adaptability.However,the research and development of solid-state b...Solid-state batteries are widely recognized as the next-generation energy storage devices with high specific energy,high safety,and high environmental adaptability.However,the research and development of solid-state batteries are resource-intensive and time-consuming due to their complex chemical environment,rendering performance prediction arduous and delaying large-scale industrialization.Artificial intelligence serves as an accelerator for solid-state battery development by enabling efficient material screening and performance prediction.This review will systematically examine how the latest progress in using machine learning(ML)algorithms can be used to mine extensive material databases and accelerate the discovery of high-performance cathode,anode,and electrolyte materials suitable for solid-state batteries.Furthermore,the use of ML technology to accurately estimate and predict key performance indicators in the solid-state battery management system will be discussed,among which are state of charge,state of health,remaining useful life,and battery capacity.Finally,we will summarize the main challenges encountered in the current research,such as data quality issues and poor code portability,and propose possible solutions and development paths.These will provide clear guidance for future research and technological reiteration.展开更多
This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high con...This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high concentrations of 16 EPA PAHs(∑Parent-PAHs)in smelting subarea of studied petroleum refinery facility,total derivatives of PAHs[named as XPAHs,including nitro PAHs(NPAHs),chlorinated PAHs(Cl-PAHs),and brominated PAHs(Br-PAHs)]in gas(mean=1.57×10^(4)ng/m^(3)),total suspended particulate(TSP)(mean=4.33×10^(3) ng/m^(3))and soil(mean=4.37×10^(3) ng/g)in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility,surrounding residential areas and reference areas,indicating that petroleum refining processes would lead apparent derivation of PAHs.Especially,compared with those in residential and reference areas,gas samples in the petrochemical areas had higher∑NPAH/∑PAHs(mean=2.18),but lower∑Cl-PAH/∑PAHs(mean=1.43×10^(-1))and∑Br-PAH/∑PAHs ratios(mean=7.49×10^(-2)),indicating the richer nitrification of PAHs than chlorination during petrochemical process.The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure,and the ILCR(1.04×10^(-4))for petrochemical workers was considered to be potential high risk.Furthermore,one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area,and another 35 PAHs were found,including alkyl-PAHs,phenyl-PAHs and other species,indicat-ing that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.展开更多
Accurate prediction of drug-target interactions(DTIs)plays a pivotal role in drug discovery,facilitating optimization of lead compounds,drug repurposing and elucidation of drug side effects.However,traditional DTI pre...Accurate prediction of drug-target interactions(DTIs)plays a pivotal role in drug discovery,facilitating optimization of lead compounds,drug repurposing and elucidation of drug side effects.However,traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features.In this study,we proposed KG-CNNDTI,a novel knowledge graph-enhanced framework for DTI prediction,which integrates heterogeneous biological information to improve model generalizability and predictive performance.The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm,which were further enriched with contextualized sequence representations obtained from ProteinBERT.For compound representation,multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated.The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor.Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods,particularly in terms of Precision,Recall,F1-Score and area under the precision-recall curve(AUPR).Ablation analysis highlighted the substantial contribution of knowledge graph-derived features.Moreover,KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease,resulting in 40 candidate compounds.5 were supported by literature evidence,among which 3 were further validated in vitro assays.展开更多
The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF str...The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.展开更多
The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the...The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the forging process.Using the previously optimized shape and initial position of preform,the influence of the friction condition(friction factor m=0.1–0.3)on material flow and cavity filling was studied by numerical method with a shear friction model.A novel filling index was defined to reflect material flow into left and right flashes and zoom in on friction-induced results.The results indicate that the workpiece moves rigidly to the right direction,with the displacement decreasing as m increases.When m<0.18,the underfilling defect will occur in the left side of strut forging,while overflow occurs in the right forging die cavity.By combining the filling index and analyses of material flow and filling status,a reasonable friction factor interval of m=0.21–0.24 can be determined.Within this interval,the cavity filling behavior demonstrates robustness,with friction fluctuations exerting minimal influence.展开更多
Diabetic retinopathy(DR)remains a leading cause of vision impairment and blindness among individuals with diabetes,necessitating innovative approaches to screening and management.This editorial explores the transforma...Diabetic retinopathy(DR)remains a leading cause of vision impairment and blindness among individuals with diabetes,necessitating innovative approaches to screening and management.This editorial explores the transformative potential of artificial intelligence(AI)and machine learning(ML)in revolutionizing DR care.AI and ML technologies have demonstrated remarkable advancements in enhancing the accuracy,efficiency,and accessibility of DR screening,helping to overcome barriers to early detection.These technologies leverage vast datasets to identify patterns and predict disease progression with unprecedented precision,enabling clinicians to make more informed decisions.Furthermore,AI-driven solutions hold promise in personalizing management strategies for DR,incorpo-rating predictive analytics to tailor interventions and optimize treatment path-ways.By automating routine tasks,AI can reduce the burden on healthcare providers,allowing for a more focused allocation of resources towards complex patient care.This review aims to evaluate the current advancements and applic-ations of AI and ML in DR screening,and to discuss the potential of these techno-logies in developing personalized management strategies,ultimately aiming to improve patient outcomes and reduce the global burden of DR.The integration of AI and ML in DR care represents a paradigm shift,offering a glimpse into the future of ophthalmic healthcare.展开更多
Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco ...Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.展开更多
Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical...Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical frameworks to systematically examine the evolution,performance,and influencing factors of governance mechanisms within these organizations.Using both quantitative and inductive analytical methods,the paper proposes innovative designs and supporting measures for improving governance mechanisms.The findings reveal that,amid large-scale farmland circulation,the governance mechanisms of agricultural production organizations in Daqing City are evolving from traditional to modern structures.However,challenges remain in areas such as decision-making efficiency,benefit distribution,and supervision mechanisms.In response,this study proposes innovative governance designs focusing on decision-making processes,profit-sharing mechanisms,and risk prevention.Corresponding policy recommendations are also provided to support the sustainable development of agricultural modernization in China.展开更多
BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group ...BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S.CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane re-gulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium.NS is crucial for early diagnosis and management,which ensures a better quality of life.AIM To report a case of the coexistence of sickle cell anemia(SCA)and CF and perform an integrative literature review.METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case.The authors identified only 5 cases of SCA associated with CF.No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.RESULTS Herein,the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin.The diagnosis of CF was confirmed by the Coulometry Sweat Test.The rarity of the co-occurrence of these two severe genetic pathologies(CF and SCA)is a challenge for medical science.CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.展开更多
BACKGROUND The Asia-Pacific Colorectal Screening(APCS)score was designed with the purpose of distinguishing individuals at high risk(HR)for colorectal advanced neoplasia(AN).Traditional Chinese medicine(TCM)constituti...BACKGROUND The Asia-Pacific Colorectal Screening(APCS)score was designed with the purpose of distinguishing individuals at high risk(HR)for colorectal advanced neoplasia(AN).Traditional Chinese medicine(TCM)constitution was also linked with colorectal cancer(CRC).AIM To integrate the APCS score with TCM constitution identification as a new algorithm to screen for CRC.METHODS A cross-sectional multicenter study was carried out in three hospitals,enrolling 1430 patients who were asymptomatic and undergoing screening colonoscopy from 2022 to 2023.Patients were considered to have average risk,moderate risk,or HR with their APCS score.Odd ratios assessed the relationship between TCM constitution and disease progression.A TCM constitution risk score was created.The sensitivity and specificity of the new algorithm were calculated to evaluate diagnostic performance in detecting advanced adenoma(AA),CRC,and AN.RESULTS Of the 1430 patients,370(25.9%)were categorized as average risk,755(52.8%)as moderate risk,and 305(21.3%)as HR.Using the combined APCS score and the TCM constitution(damp-heat,qi-deficiency,yang-deficiency,phlegm-dampness,and inherited special constitution as positive)algorithm,72.2%of patients with AA and 73.7%of patients with AN were detected.Compared with the APCS score alone,the new algorithm significantly improved the sensitivity for screening AA[72.2%,95%confidence interval(CI):64.4%-80.0%vs 49.2%,95%CI:40.5%-57.9%]and AN(73.7%,95%CI:66.4%-81.1%vs 51.1%,95%CI:42.7%-59.5%).CONCLUSION The combination of APCS and TCM constitution identification questionnaires was valuable in identifying Chinese individuals who were asymptomatic for colorectal screening prioritization.展开更多
Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale opti...Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale optimization problems are solved using computing machines,leading to an enormous computational time being required,which may delay deriving timely solutions.Decomposition methods,which partition a large-scale optimization problem into lower-dimensional subproblems,represent a key approach to addressing time-efficiency issues.There has been significant progress in both applied mathematics and emerging artificial intelligence approaches on this front.This work aims at providing an overview of the decomposition methods from both the mathematics and computer science points of view.We also remark on the state-of-the-art developments and recent applications of the decomposition methods,and discuss the future research and development perspectives.展开更多
This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management m...This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management measures.Through practical observation and logical analysis,this article elaborates on the management connotations of large-scale machinery and equipment in highway construction,affirming its management value from different perspectives.On this basis,it carefully analyzes the problems existing in the management of large-scale machinery and equipment,providing a detailed interpretation of issues such as the weak foundation of the equipment management system and the disconnection between equipment selection and configuration from reality.Combining the manifestations of related problems,this article proposes strategies such as strengthening the institutional foundation of equipment management,selecting and configuring equipment based on actual conditions,aiming to provide references for large-scale machinery and equipment management to relevant enterprises.展开更多
基金supported by the National Key Research and Development Program of China (2018YFA0901500)the National Natural Science Foundation of China (U2032210)。
文摘Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.
基金supported by gifts from the Bezos Earth Fund and the Hess Corporationthrough the TED Audacious Project.
文摘The periderm is a vital protective tissue found in the roots,stems,and woody elements of diverse plant species.It plays an important function in these plants by assuming the role of the epidermis as the outermost layer.Despite its critical role for protecting plants from environmental stresses and pathogens,research on root periderm development has been limited due to its late formation during root development,its presence only in mature root regions,and its impermeability.
基金supported by the National Natural Science Foundation of China(No.22176135,C.L.)Additionally,this research was supported by the Fundamental Research Funds for the Central Universities in China(No.YJ201976,C.L.)start-up funds from the School of Chemical Engineering,Sichuan University(C.L.).
文摘We performed large-scale molecular simulation to screen and identify metal-organic framework materials for gaseous iodine capture,as part of our ongoing effort in addressing management and handling issues of various radionuclides in the grand scheme of spent nuclear fuel reprocessing.Starting from the computation-ready experimental(CoRE)metal-organic frameworks(MOFs)database,grand canonical Monte Carlo simulation was employed to predict the iodine uptake values of the MOFs.A ranking list of MOFs based on their iodine uptake capabilities was generated,with the Top 10 candidates identified and their respective adsorption sites visualized.Subsequently,machine learning was used to establish structure-property relationships to correlate MOFs’various structural and chemical features with their corresponding performances in iodine capture,yielding interpretable common features and design rules for viable MOF adsorbents.The research strategy and framework of the present study could aid the development of high-performing MOF adsorbents for capture and recovery of radioactive iodine,and moreover,other volatile environmentally hazardous species.
基金supported by the National Natural Science Foundation of China(Nos.30828020 and 31171403)the Human Talent Recruiting Funding from the Southern Medical University and Department of Education of Guangdong Province,China
文摘Zebrafish is a powerful model for the investigation of hematopoiesis.In order to isolate novel mutants with hematopoietic defects, large-scale mutagenesis screening of zebrafish was performed.By scoring specific hematopoietic markers,52 mutants were identified and then classified into four types based on specific phenotypic traits.Each mutant represented a putative mutation of a gene regulating the relevant aspect of hematopoiesis,including early macrophage development,early granulopoiesis,embryonic myelopoiesis,and definitive erythropoiesis/lymphopoiesis.Our method should be applicable for other types of genetic screening in zebrafish.In addition,further study of the mutants we identified may help to unveil the molecular basis of hematopoiesis.
基金supported by the National Key Research and Development Program of China(2022YFE0206700)。
文摘1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Intergovernmental Panel on Climate Change(IPCC)—consistently predict the widespread implementation of CO_(2)geological storage on a global scale.
文摘Colorectal cancer(CRC)is a prevalent malignancy worldwide,posing a significant public health concern.Mounting evidence has confirmed that timely early screening facilitates the detection of incipient CRC,thereby enhancing patient prognosis.Obviously,non-participation of asymptomatic individuals in screening programs hampers early diagnosis and may adversely affect long-term outcomes for CRC patients.In this letter,we provide a comprehensive overview of the current status of early screening practices,while also thoroughly examine the dilemmas and potential solutions associated with early screening for CRC.In response to these issues,we proffer a set of recommendations directed at governmental authorities and the general public,which focus on augmenting financial investment,establishing standardized screening protocols,advancing technological capabilities,and bolstering public awareness campaigns.The importance of collaborative efforts from various stakeholders cannot be overstated in the quest to enhance early detection rates and alleviate the societal burden of CRC.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82373835,82304437,and 82173781)Regional Joint Fund Project of Guangdong Basic and Applied Basic Research Fund,China(Grant Nos.:2023A1515110417 and 2023A1515140131)+2 种基金Regional Joint Fund-Key Project of Guangdong Basic and Applied Basic Research Fund,China(Grant No.:2020B1515120033)the Key Field Projects of General Universities in Guangdong Province,China(Grant Nos.:2020ZDZX2057 and 2022ZDZX2056)Medical Scientific Research Foundation of Guangdong Province of China(Grant No.:A2022061).
文摘Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membranemediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP databases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.
基金the National Key R&D Program of China(No.2021YFA0715900)the National Natural Science Foundation of China(No.41831279)+2 种基金the Shenzhen Key Laboratory of Precision Measurement and Early Warning Technology for Urban Environmental Health Risks(No.ZDSYS20220606100604008)the Guangdong Province Bureau of Education(No.2020KCXTD006)the Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control(No.2023B1212060002).
文摘Rapid screening of inorganic arsenic(iAs)in groundwater used for drinking by hundreds of millions of mostly rural residents worldwide is crucial for health protection.Most commercial field test kits are based on the Gutzeit reaction that uses mercury-based reagents for color development,an environmental concern that increasingly limits its utilization.This study further improves the Molybdenum Blue(MB)colorimetric method to allow for faster screening with more stable reagents.More importantly,a portable three-channel colorimeter is developed for screening iAs relative to the WHO drinking water guideline value(10μg/L).Adding the reducing reagents in sequence not only prolongs the storage time to>7 days,but also accelerates the color development time to 6 min in conjunction with lowering the H_(2)SO_(4) concentration in chromogenic reagents.The optimal pH ranges from 1.2 to 1.3 and is achieved by acidifying groundwater to 1%(V/V)HCl.With detection limits of 3.7μg/L for inorganic arsenate(iAs(V))and 3.8μg/L for inorganic arsenite(iAs(Ⅲ)),testing groundwater with-10μg/L of As has a precision<20%.The method works well for a range of phosphate concentrations of 48-950μg/L(0.5-10μmol/L).Concentrations of total_iAs(6-300μg/L),iAs(V)(6-230μg/L)and iAs(Ⅲ)(0-170μg/L)for 14 groundwater samples from Yinchuan Plain,Pearl River Delta,and Jianghan Plain,are in excellent agreements(linear regression slope:0.969-1.029)with the benchmark methods.The improved chemistry here lays the foundation for the MB colorimetric method to become a commercially viable screening tool,with further engineering and design improvement of the colorimeter.
基金the National Key Research Program of China under granted No.92164201National Natural Science Foundation of China for Distinguished Young Scholars No.62325403+2 种基金Natural Science Foundation of Jiangsu Province(BK20230498)Jiangsu Funding Program for Excellent Postdoctoral Talent(2024ZB427)the National Natural Science Foundation of China(62304147).
文摘Solid-state batteries are widely recognized as the next-generation energy storage devices with high specific energy,high safety,and high environmental adaptability.However,the research and development of solid-state batteries are resource-intensive and time-consuming due to their complex chemical environment,rendering performance prediction arduous and delaying large-scale industrialization.Artificial intelligence serves as an accelerator for solid-state battery development by enabling efficient material screening and performance prediction.This review will systematically examine how the latest progress in using machine learning(ML)algorithms can be used to mine extensive material databases and accelerate the discovery of high-performance cathode,anode,and electrolyte materials suitable for solid-state batteries.Furthermore,the use of ML technology to accurately estimate and predict key performance indicators in the solid-state battery management system will be discussed,among which are state of charge,state of health,remaining useful life,and battery capacity.Finally,we will summarize the main challenges encountered in the current research,such as data quality issues and poor code portability,and propose possible solutions and development paths.These will provide clear guidance for future research and technological reiteration.
基金supported by the National Key Research and Development Program of China(No.2019YFC1804501)the National Natural Science Foundation of China(Nos.22036007 and 22122611)+1 种基金the Natural Science Foundation of Shandong Province(No.ZR2020ME228)the Introduction and Cultivation Plan for Young Innovative Talents of Colleges and Universities.
文摘This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons(PAHs)and their derivatives in one Chinese petroleum refinery facility.It was found that,following with high concentrations of 16 EPA PAHs(∑Parent-PAHs)in smelting subarea of studied petroleum refinery facility,total derivatives of PAHs[named as XPAHs,including nitro PAHs(NPAHs),chlorinated PAHs(Cl-PAHs),and brominated PAHs(Br-PAHs)]in gas(mean=1.57×10^(4)ng/m^(3)),total suspended particulate(TSP)(mean=4.33×10^(3) ng/m^(3))and soil(mean=4.37×10^(3) ng/g)in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility,surrounding residential areas and reference areas,indicating that petroleum refining processes would lead apparent derivation of PAHs.Especially,compared with those in residential and reference areas,gas samples in the petrochemical areas had higher∑NPAH/∑PAHs(mean=2.18),but lower∑Cl-PAH/∑PAHs(mean=1.43×10^(-1))and∑Br-PAH/∑PAHs ratios(mean=7.49×10^(-2)),indicating the richer nitrification of PAHs than chlorination during petrochemical process.The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure,and the ILCR(1.04×10^(-4))for petrochemical workers was considered to be potential high risk.Furthermore,one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area,and another 35 PAHs were found,including alkyl-PAHs,phenyl-PAHs and other species,indicat-ing that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.
基金supported by the National Natural Science Foundation of China(Nos.82173746 and U23A20530)Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission)。
文摘Accurate prediction of drug-target interactions(DTIs)plays a pivotal role in drug discovery,facilitating optimization of lead compounds,drug repurposing and elucidation of drug side effects.However,traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features.In this study,we proposed KG-CNNDTI,a novel knowledge graph-enhanced framework for DTI prediction,which integrates heterogeneous biological information to improve model generalizability and predictive performance.The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm,which were further enriched with contextualized sequence representations obtained from ProteinBERT.For compound representation,multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated.The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor.Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods,particularly in terms of Precision,Recall,F1-Score and area under the precision-recall curve(AUPR).Ablation analysis highlighted the substantial contribution of knowledge graph-derived features.Moreover,KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease,resulting in 40 candidate compounds.5 were supported by literature evidence,among which 3 were further validated in vitro assays.
基金financial support from the National Key Research and Development Program of China(2021YFB 3501501)the National Natural Science Foundation of China(No.22225803,22038001,22108007 and 22278011)+1 种基金Beijing Natural Science Foundation(No.Z230023)Beijing Science and Technology Commission(No.Z211100004321001).
文摘The high porosity and tunable chemical functionality of metal-organic frameworks(MOFs)make it a promising catalyst design platform.High-throughput screening of catalytic performance is feasible since the large MOF structure database is available.In this study,we report a machine learning model for high-throughput screening of MOF catalysts for the CO_(2) cycloaddition reaction.The descriptors for model training were judiciously chosen according to the reaction mechanism,which leads to high accuracy up to 97%for the 75%quantile of the training set as the classification criterion.The feature contribution was further evaluated with SHAP and PDP analysis to provide a certain physical understanding.12,415 hypothetical MOF structures and 100 reported MOFs were evaluated under 100℃ and 1 bar within one day using the model,and 239 potentially efficient catalysts were discovered.Among them,MOF-76(Y)achieved the top performance experimentally among reported MOFs,in good agreement with the prediction.
基金National Natural Science Foundation of China(52375378)National Key Laboratory of Metal Forming Technology and Heavy Equipment(S2308100.W12)Huxiang High-Level Talent Gathering Project of Hunan Province(2021RC5001)。
文摘The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the forging process.Using the previously optimized shape and initial position of preform,the influence of the friction condition(friction factor m=0.1–0.3)on material flow and cavity filling was studied by numerical method with a shear friction model.A novel filling index was defined to reflect material flow into left and right flashes and zoom in on friction-induced results.The results indicate that the workpiece moves rigidly to the right direction,with the displacement decreasing as m increases.When m<0.18,the underfilling defect will occur in the left side of strut forging,while overflow occurs in the right forging die cavity.By combining the filling index and analyses of material flow and filling status,a reasonable friction factor interval of m=0.21–0.24 can be determined.Within this interval,the cavity filling behavior demonstrates robustness,with friction fluctuations exerting minimal influence.
文摘Diabetic retinopathy(DR)remains a leading cause of vision impairment and blindness among individuals with diabetes,necessitating innovative approaches to screening and management.This editorial explores the transformative potential of artificial intelligence(AI)and machine learning(ML)in revolutionizing DR care.AI and ML technologies have demonstrated remarkable advancements in enhancing the accuracy,efficiency,and accessibility of DR screening,helping to overcome barriers to early detection.These technologies leverage vast datasets to identify patterns and predict disease progression with unprecedented precision,enabling clinicians to make more informed decisions.Furthermore,AI-driven solutions hold promise in personalizing management strategies for DR,incorpo-rating predictive analytics to tailor interventions and optimize treatment path-ways.By automating routine tasks,AI can reduce the burden on healthcare providers,allowing for a more focused allocation of resources towards complex patient care.This review aims to evaluate the current advancements and applic-ations of AI and ML in DR screening,and to discuss the potential of these techno-logies in developing personalized management strategies,ultimately aiming to improve patient outcomes and reduce the global burden of DR.The integration of AI and ML in DR care represents a paradigm shift,offering a glimpse into the future of ophthalmic healthcare.
文摘Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.
基金Supported by Daqing City Philosophy and Social Sciences Planning Research Project(DSGB 2025011)the Heilongjiang Province Education Science Planning Key Project(GJB1320229).
文摘Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical frameworks to systematically examine the evolution,performance,and influencing factors of governance mechanisms within these organizations.Using both quantitative and inductive analytical methods,the paper proposes innovative designs and supporting measures for improving governance mechanisms.The findings reveal that,amid large-scale farmland circulation,the governance mechanisms of agricultural production organizations in Daqing City are evolving from traditional to modern structures.However,challenges remain in areas such as decision-making efficiency,benefit distribution,and supervision mechanisms.In response,this study proposes innovative governance designs focusing on decision-making processes,profit-sharing mechanisms,and risk prevention.Corresponding policy recommendations are also provided to support the sustainable development of agricultural modernization in China.
文摘BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S.CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane re-gulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium.NS is crucial for early diagnosis and management,which ensures a better quality of life.AIM To report a case of the coexistence of sickle cell anemia(SCA)and CF and perform an integrative literature review.METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case.The authors identified only 5 cases of SCA associated with CF.No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.RESULTS Herein,the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin.The diagnosis of CF was confirmed by the Coulometry Sweat Test.The rarity of the co-occurrence of these two severe genetic pathologies(CF and SCA)is a challenge for medical science.CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.
文摘BACKGROUND The Asia-Pacific Colorectal Screening(APCS)score was designed with the purpose of distinguishing individuals at high risk(HR)for colorectal advanced neoplasia(AN).Traditional Chinese medicine(TCM)constitution was also linked with colorectal cancer(CRC).AIM To integrate the APCS score with TCM constitution identification as a new algorithm to screen for CRC.METHODS A cross-sectional multicenter study was carried out in three hospitals,enrolling 1430 patients who were asymptomatic and undergoing screening colonoscopy from 2022 to 2023.Patients were considered to have average risk,moderate risk,or HR with their APCS score.Odd ratios assessed the relationship between TCM constitution and disease progression.A TCM constitution risk score was created.The sensitivity and specificity of the new algorithm were calculated to evaluate diagnostic performance in detecting advanced adenoma(AA),CRC,and AN.RESULTS Of the 1430 patients,370(25.9%)were categorized as average risk,755(52.8%)as moderate risk,and 305(21.3%)as HR.Using the combined APCS score and the TCM constitution(damp-heat,qi-deficiency,yang-deficiency,phlegm-dampness,and inherited special constitution as positive)algorithm,72.2%of patients with AA and 73.7%of patients with AN were detected.Compared with the APCS score alone,the new algorithm significantly improved the sensitivity for screening AA[72.2%,95%confidence interval(CI):64.4%-80.0%vs 49.2%,95%CI:40.5%-57.9%]and AN(73.7%,95%CI:66.4%-81.1%vs 51.1%,95%CI:42.7%-59.5%).CONCLUSION The combination of APCS and TCM constitution identification questionnaires was valuable in identifying Chinese individuals who were asymptomatic for colorectal screening prioritization.
基金The Australian Research Council(DP200101197,DP230101107).
文摘Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale optimization problems are solved using computing machines,leading to an enormous computational time being required,which may delay deriving timely solutions.Decomposition methods,which partition a large-scale optimization problem into lower-dimensional subproblems,represent a key approach to addressing time-efficiency issues.There has been significant progress in both applied mathematics and emerging artificial intelligence approaches on this front.This work aims at providing an overview of the decomposition methods from both the mathematics and computer science points of view.We also remark on the state-of-the-art developments and recent applications of the decomposition methods,and discuss the future research and development perspectives.
文摘This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management measures.Through practical observation and logical analysis,this article elaborates on the management connotations of large-scale machinery and equipment in highway construction,affirming its management value from different perspectives.On this basis,it carefully analyzes the problems existing in the management of large-scale machinery and equipment,providing a detailed interpretation of issues such as the weak foundation of the equipment management system and the disconnection between equipment selection and configuration from reality.Combining the manifestations of related problems,this article proposes strategies such as strengthening the institutional foundation of equipment management,selecting and configuring equipment based on actual conditions,aiming to provide references for large-scale machinery and equipment management to relevant enterprises.
