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
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
Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynam...Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.展开更多
Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities ofte...Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities often result in the deprioritization of standardized management practices,as they do not yield immediate benefits.The implementation of such systems typically encompasses the integrated phases of "development,construction,utiliz ation,and operation and maintenance".To enhance the overall delivery quality of these systems,it is imperative to dismantle the management barriers among these phases and adopt a holistic approach to standardized management.This paper takes a specific system project as a research object to identify common challenges,and proposes improvement strategies in the implementation of standar dized management.Empirical results indicate a substantial reduction in the system s full-lifecycle costs.展开更多
Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to t...Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.展开更多
This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the ...This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the design process,we transform the studied system into the form of a fully actuated system through a state transformation.Then,to address the unknown nonlinear functions and actuator fault parameters,we employ neural networks and adaptive estimation techniques,respectively.Moreover,to reduce the control cost and improve the control efficiency,we introduce event-triggered inputs into the control strategy.It is proved by the Lyapunov stability analysis that all signals of the closed-loop system are bounded and the output of system eventually converge to a bounded region.The efficacy of the control approach is ultimately demonstrated via the simulation of an actual machine feeding system.展开更多
Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonst...Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.展开更多
This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cel...This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cells,or tissue-specific progenitors,provide a physiologically relevant alternative to traditional animal models.Significant progress has been made in utilizing various cell sources,extracellular matrix materials such as Matrigel and hydrogels,and methods for controlling microenvironments through biochemical and biophysical signals.Applications of IEOs in drug screening,disease modeling,and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing.However,challenges remain,including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments.Future research should focus on optimizing IEO generation,incorporating microfluidic technologies,and advancing high-throughput screening to enhance drug discovery and clinical translation.展开更多
Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR sc...Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.展开更多
Deuterium(D_(2)) is one of the important fuel sources that power nuclear fusion reactors. The existing D_(2)/H_(2) separation technologies that obtain high-purity D_(2) are cost-intensive. Recent research has shown th...Deuterium(D_(2)) is one of the important fuel sources that power nuclear fusion reactors. The existing D_(2)/H_(2) separation technologies that obtain high-purity D_(2) are cost-intensive. Recent research has shown that metal-organic frameworks(MOFs) are of good potential for D_(2)/H_(2) separation application. In this work, a high-throughput computational screening of 12020 computation-ready experimental MOFs is carried out to determine the best MOFs for hydrogen isotope separation application. Meanwhile, the detailed structure-performance correlation is systematically investigated with the aid of machine learning. The results indicate that the ideal D_(2)/H_(2) adsorption selectivity calculated based on Henry coefficient is strongly correlated with the 1/ΔAD feature descriptor;that is, inverse of the adsorbility difference of the two adsorbates. Meanwhile, the machine learning(ML) results show that the prediction accuracy of all the four ML methods is significantly improved after the addition of this feature descriptor. In addition, the ML results based on extreme gradient boosting model also revealed that the 1/ΔAD descriptor has the highest relative importance compared to other commonly-used descriptors. To further explore the effect of hydrogen isotope separation in binary mixture, 1548 MOFs with ideal adsorption selectivity greater than 1.5 are simulated at equimolar conditions. The structure-performance relationship shows that high adsorption selectivity MOFs generally have smaller pore size(0.3-0.5 nm) and lower surface area. Among the top 200 performers, the materials mainly have the sql, pcu, cds, hxl, and ins topologies.Finally, three MOFs with high D_(2)/H_(2) selectivity and good D_(2) uptake are identified as the best candidates,of all which had one-dimensional channel pore. The findings obtained in this work may be helpful for the identification of potentially promising candidates for hydrogen isotope separation.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop r...The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.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
Manipulation of mouse genome has merged as one of the most important approaches for studying genefunction and establishing the disease model because of the high homology between human genome and mouse genome. In this ...Manipulation of mouse genome has merged as one of the most important approaches for studying genefunction and establishing the disease model because of the high homology between human genome and mouse genome. In this study, the chemical mutagen ethylnitrosourea (ENU) was employed for inducing germ cell mutations in maleC57BL/6J mice. The first generation (G1) of the backcrossof these mutated mice, totally 3172, was screened for abnor-mal phenotypes on gross morphology, behavior, learning and memory, auditory brainstem response (ABR), electrocardio-gram (ECG), electroretinogram (ERG), flash-visual evoked potential (F-VEP), bone mineral density, and blood sugarlevel. 595 mice have been identified with specific dominantabnormalities. Fur color changes, eye defects and hearing loss occurred at the highest frequency. Abnormalities related to metabolism alteration are least frequent. Interestingly, eye defects displayed significant left-right asymmetry and sexpreference. Sex preference is also observed in mice with ab-normal bone mineral density. Among 104 G1 generation mutant mice examined for inheritability, 14 of them have been confirmed for passing abnormal phenotypes to their progenies. However, we did not observe behavior abnormali-ties of G1 mice to be inheritable, suggesting multi-gene con-trol for these complicated functions in mice. In conclusion, the generation of these mutants paves the way for under-standing molecular and cellular mechanisms of these ab-normal phenotypes, and accelerates the cloning of disease-related genes.展开更多
Background: This study aimed to explore the best screening measure of myopia and its associated optimal referral criteria for children aged between 6 and 16.Methods: After informed consent of cycloplegia was obtained,...Background: This study aimed to explore the best screening measure of myopia and its associated optimal referral criteria for children aged between 6 and 16.Methods: After informed consent of cycloplegia was obtained, a total of 6,321 children aged between 6 and 16 from 53 primary or junior middle schools in Jiading District of Shanghai were included in our populationbased study. Receiver operating characteristic(ROC) curve was performed to determine the best cutoff points, sensitivities and specii cities of different screening tests, including uncorrected visual acuity(UCVA), noncycloplegic autorefraction(NCAR) and the combination of these two tests.Results: There was significant difference in prevalence of myopia between boys and girls(χ~2=6.358, P=0.012). Compared with children of low age, the prevalence of older children was significantly higher(χ~2=1,386.404, P<0.001). For the combination of UCVA and NCAR, the best cutoff point was UCVA less than or equal to 0.2 logarithm of minimum angle of resolution(MAR)(20/30) and NCAR spherical equivalent refraction(SER) less than or equal to -0.75 diopters(D), with associated sensitivity and specificity of 75.0% and 85.0%, respectively, which were higher than those of UCVA and NCAR alone. After stratified by age, the best cutof points were varied among children. The accuracy for children aged between 9 and 12 was higher than that for other ages.Conclusions: The best screening measure of myopia was the combination of UCVA and NCAR. The optimal referral criteria of myopia for children should be age-determined.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
The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,...The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,in combination with numerical simulation,was conducted to investigate the influence of ground fissures on a metro shield tunnel.The results indicate that the lining contact pressure at the vault increases in the hanging wall while decreases in the footwall,resulting in a two-dimensional stress state of vertical shear and axial tension-compression,and simultaneous vertical dislocation and axial tilt for the segments around the ground fissure.In addition,the damage to curved bolts includes tensile yield,flexural yield,and shear twist,leading to obvious concrete lining damage,particularly at the vault,arch bottom,and hance,indicating that the joints in these positions are weak areas.The shield tunnel orthogonal to the ground fissure ultimately experiences shear failure,suggesting that the maximum actual dislocation of ground fissure that the structure can withstand is approximately 20 cm,and five segment rings in the hanging wall and six segment rings in the footwall also need to be reinforced.This study could provide a reference for metro design in ground fissure sites.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
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 (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 the National Natural Science Foundation of China(Nos.52293472,22473096 and 22471164)。
文摘Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.
文摘Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities often result in the deprioritization of standardized management practices,as they do not yield immediate benefits.The implementation of such systems typically encompasses the integrated phases of "development,construction,utiliz ation,and operation and maintenance".To enhance the overall delivery quality of these systems,it is imperative to dismantle the management barriers among these phases and adopt a holistic approach to standardized management.This paper takes a specific system project as a research object to identify common challenges,and proposes improvement strategies in the implementation of standar dized management.Empirical results indicate a substantial reduction in the system s full-lifecycle costs.
基金supported by the National Natural Science Foundation of China(Grant No.42275041)the Hainan Province Science and Technology Special Fund(Grant No.SOLZSKY2025006).
文摘Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.
基金supported by the Science Center Program of National Natural Science Foundation of China under Grant 62188101the National Natural Science Foundation of China under Grant 62573265.
文摘This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the design process,we transform the studied system into the form of a fully actuated system through a state transformation.Then,to address the unknown nonlinear functions and actuator fault parameters,we employ neural networks and adaptive estimation techniques,respectively.Moreover,to reduce the control cost and improve the control efficiency,we introduce event-triggered inputs into the control strategy.It is proved by the Lyapunov stability analysis that all signals of the closed-loop system are bounded and the output of system eventually converge to a bounded region.The efficacy of the control approach is ultimately demonstrated via the simulation of an actual machine feeding system.
基金supported by the National Natural Science Foundation of China(No.82104353)China Postdoctoral Science Foundation funded project(No.2022M711680).
文摘Insects represent emerging sources of bioactive peptides and functional materials.Mantidis Oötheca(Sang-Piao-Xiao in Chinese,SPX)serves as an insect-derived medicine for treating kidney disease.This study demonstrated that supernatant(SPX)improved kidney function in adriamycin(ADR)-induced nephropathy mice model.Transcriptomic analysis revealed that SPX inhibited complement activation by targeting the MASP1-C3/C3a receptor(C3aR)pathway.Peptidomic analysis identified 304 peptides from SPX,with 49 peptides selected for evaluation using prediction tools and molecular docking with complement core protein C3.Three peptides(PMGFPFDR,FNDPK,AAQFFNR)exhibiting docking scores below-8.0 were synthesized to verify complement inhibition and anti-fibrotic activities.The synthetic peptide AAQFFNR demonstrated complement inhibitory activity,with an inhibitory complement hemolytic 50%(ICH_(50))value of 24.54μmol·L^(-1),and exhibited superior protective effects in ADR-induced HK-2 cells.Surface plasmon resonance(SPR)assay revealed direct interaction between AAQFFNR and complement C3 with K_(d)value of 16.8μmol·L^(-1).The reno-protective effect of AAQFFNR was subsequently verified in ADR-induced mice.This research provides initial evidence that complement C3-inhibiting peptides from insects demonstrate potential in preventing nephropathy through in silico and in vivo validation approaches.
基金supported by the National Natural Science Foundation of China(82222017 and 82271183)Hubei Province’s Key Research and Development Program(2022BCA046)the Start-up Research Fund of Southeast University(RF1028623028).
文摘This review highlights advances in inner ear organoids(IEOs)as a novel platform for drug screening and disease modeling,particularly for hearing loss.IEOs,derived from embryonic stem cells,induced pluripotent stem cells,or tissue-specific progenitors,provide a physiologically relevant alternative to traditional animal models.Significant progress has been made in utilizing various cell sources,extracellular matrix materials such as Matrigel and hydrogels,and methods for controlling microenvironments through biochemical and biophysical signals.Applications of IEOs in drug screening,disease modeling,and personalized medicine enable exploration of hearing loss mechanisms and therapeutic testing.However,challenges remain,including the incomplete maturation of cochlear cells and difficulty replicating in vivo environments.Future research should focus on optimizing IEO generation,incorporating microfluidic technologies,and advancing high-throughput screening to enhance drug discovery and clinical translation.
基金funded by the Chronic Disease Management Research Project of National Health Commission Capacity Building and Continuing Education Center 2025(GWJJMB202510024146)the Post-Subsidy Project for Standard Development of Guizhou Provincial Market Supervision and Administration Bureau 2025(DB52/T1726-2023)the Guizhou Provincial Health Commission Science and Technology Fund Project(gzwkj2024-076,gzwkj2026-146).
文摘Diabetic retinopathy(DR)is a leading cause of vision loss among working-age populations,with early screening significantly reducing the risk of blindness.However,resource-limited regions often face challenges in DR screening due to a shortage of ophthalmologists.This study reports the implementation and outcomes of the Chinese local standard DB52/T 1726-2023,Regulations for the application of diabetic retinopathy screening artificial intelligence,in Cambodian healthcare institutions.A pilot DR screening program with independent operational capability is established by providing a non-mydriatic fundus camera and deploying a localized diabetic retinopathy artificial intelligence(DR-AI)screening platform at the Cambodia-Kingdom Friendship Hospital in Phnom Penh,along with comprehensive training.From January to August 2025,a total of 565 patients with type 2 diabetes were screened,yielding a DR detection rate of 26.0%(147 cases).Research findings demonstrate that applying mature Chinese DR-AI screening standards and technological solutions through international collaboration in regions with a scarcity of ophthalmic professionals is both feasible and effective.This project serves as a reference for promoting DR-AI in resource-constrained countries and regions,highlighting its significant potential to leverage AI in addressing the global burden of chronic diseases and advancing the modernization of health systems.
基金supported by the National Natural Science Foundation of China (22078004)the Research Development Fund from Xi’an Jiaotong-Liverpool University (RDF-16-02-03 and RDF15-01-23)key program special fund (KSF-E-03)。
文摘Deuterium(D_(2)) is one of the important fuel sources that power nuclear fusion reactors. The existing D_(2)/H_(2) separation technologies that obtain high-purity D_(2) are cost-intensive. Recent research has shown that metal-organic frameworks(MOFs) are of good potential for D_(2)/H_(2) separation application. In this work, a high-throughput computational screening of 12020 computation-ready experimental MOFs is carried out to determine the best MOFs for hydrogen isotope separation application. Meanwhile, the detailed structure-performance correlation is systematically investigated with the aid of machine learning. The results indicate that the ideal D_(2)/H_(2) adsorption selectivity calculated based on Henry coefficient is strongly correlated with the 1/ΔAD feature descriptor;that is, inverse of the adsorbility difference of the two adsorbates. Meanwhile, the machine learning(ML) results show that the prediction accuracy of all the four ML methods is significantly improved after the addition of this feature descriptor. In addition, the ML results based on extreme gradient boosting model also revealed that the 1/ΔAD descriptor has the highest relative importance compared to other commonly-used descriptors. To further explore the effect of hydrogen isotope separation in binary mixture, 1548 MOFs with ideal adsorption selectivity greater than 1.5 are simulated at equimolar conditions. The structure-performance relationship shows that high adsorption selectivity MOFs generally have smaller pore size(0.3-0.5 nm) and lower surface area. Among the top 200 performers, the materials mainly have the sql, pcu, cds, hxl, and ins topologies.Finally, three MOFs with high D_(2)/H_(2) selectivity and good D_(2) uptake are identified as the best candidates,of all which had one-dimensional channel pore. The findings obtained in this work may be helpful for the identification of potentially promising candidates for hydrogen isotope separation.
基金supported by the National Natural Science Foundation of China(31570170)the National Key Research and Development Program of China(2016YFC1200401)。
文摘The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.
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 State“863”High-Tech Project and the National Gongguan Project
文摘Manipulation of mouse genome has merged as one of the most important approaches for studying genefunction and establishing the disease model because of the high homology between human genome and mouse genome. In this study, the chemical mutagen ethylnitrosourea (ENU) was employed for inducing germ cell mutations in maleC57BL/6J mice. The first generation (G1) of the backcrossof these mutated mice, totally 3172, was screened for abnor-mal phenotypes on gross morphology, behavior, learning and memory, auditory brainstem response (ABR), electrocardio-gram (ECG), electroretinogram (ERG), flash-visual evoked potential (F-VEP), bone mineral density, and blood sugarlevel. 595 mice have been identified with specific dominantabnormalities. Fur color changes, eye defects and hearing loss occurred at the highest frequency. Abnormalities related to metabolism alteration are least frequent. Interestingly, eye defects displayed significant left-right asymmetry and sexpreference. Sex preference is also observed in mice with ab-normal bone mineral density. Among 104 G1 generation mutant mice examined for inheritability, 14 of them have been confirmed for passing abnormal phenotypes to their progenies. However, we did not observe behavior abnormali-ties of G1 mice to be inheritable, suggesting multi-gene con-trol for these complicated functions in mice. In conclusion, the generation of these mutants paves the way for under-standing molecular and cellular mechanisms of these ab-normal phenotypes, and accelerates the cloning of disease-related genes.
文摘Background: This study aimed to explore the best screening measure of myopia and its associated optimal referral criteria for children aged between 6 and 16.Methods: After informed consent of cycloplegia was obtained, a total of 6,321 children aged between 6 and 16 from 53 primary or junior middle schools in Jiading District of Shanghai were included in our populationbased study. Receiver operating characteristic(ROC) curve was performed to determine the best cutoff points, sensitivities and specii cities of different screening tests, including uncorrected visual acuity(UCVA), noncycloplegic autorefraction(NCAR) and the combination of these two tests.Results: There was significant difference in prevalence of myopia between boys and girls(χ~2=6.358, P=0.012). Compared with children of low age, the prevalence of older children was significantly higher(χ~2=1,386.404, P<0.001). For the combination of UCVA and NCAR, the best cutoff point was UCVA less than or equal to 0.2 logarithm of minimum angle of resolution(MAR)(20/30) and NCAR spherical equivalent refraction(SER) less than or equal to -0.75 diopters(D), with associated sensitivity and specificity of 75.0% and 85.0%, respectively, which were higher than those of UCVA and NCAR alone. After stratified by age, the best cutof points were varied among children. The accuracy for children aged between 9 and 12 was higher than that for other ages.Conclusions: The best screening measure of myopia was the combination of UCVA and NCAR. The optimal referral criteria of myopia for children should be age-determined.
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 Key Research&Development Program of China(Grant No.2023YFC3008404)the Key Laboratory of Earth Fissures Geological Disaster,Ministry of Natural Resources,China(Grant Nos.EFGD20240609 and EFGD20240610).
文摘The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,in combination with numerical simulation,was conducted to investigate the influence of ground fissures on a metro shield tunnel.The results indicate that the lining contact pressure at the vault increases in the hanging wall while decreases in the footwall,resulting in a two-dimensional stress state of vertical shear and axial tension-compression,and simultaneous vertical dislocation and axial tilt for the segments around the ground fissure.In addition,the damage to curved bolts includes tensile yield,flexural yield,and shear twist,leading to obvious concrete lining damage,particularly at the vault,arch bottom,and hance,indicating that the joints in these positions are weak areas.The shield tunnel orthogonal to the ground fissure ultimately experiences shear failure,suggesting that the maximum actual dislocation of ground fissure that the structure can withstand is approximately 20 cm,and five segment rings in the hanging wall and six segment rings in the footwall also need to be reinforced.This study could provide a reference for metro design in ground fissure sites.
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.
