Silicon-air(Si-air)batteries have received significant attention owing to their high theoretical energy density and safety profile.However,the actual energy density of the Si-air battery remains significantly lower th...Silicon-air(Si-air)batteries have received significant attention owing to their high theoretical energy density and safety profile.However,the actual energy density of the Si-air battery remains significantly lower than the theoretical value,primarily due to corrosion issues and passivation.This study used various metal-organic framework(MOF)materials,such as MIL-53(Al),MIL-88(Fe),and MIL-101(Cr),to modify Si anodes.The MOFs were fabricated to have different morphologies,particle sizes,and pore sizes by altering their central metal nodes and ligands.This approach aimed to modulate the adsorption behavior of H_(2)O,SiO_(2),and OH^(−),thereby mitigating corrosion and passivation reactions.Under a constant current of 150μA,Si-air batteries with MIL-53(Al)@Si,MIL-88(Fe)@Si,and MIL-101(Cr)@Si as anodes demonstrated lifetimes of 293,412,and 336 h,respectively,surpassing the 276 h observed with pristine silicon anodes.Among these composite anodes,MIL-88(Fe)@Si displayed the best performance due to its superior hydrophobicity and optimal pore size,which enhance OH^(−)migration.This study offers a promising strategy for enhancing Si-air battery performance by developing an anodic protective layer with selective screening properties.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
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
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
BACKGROUND Malnutrition exacerbates the deterioration in patients with advanced gas-trointestinal tumors.AIM To analyze the effect of enteral nutritional support based on Nutrition Risk Screening 2002(NRS2002)risk ass...BACKGROUND Malnutrition exacerbates the deterioration in patients with advanced gas-trointestinal tumors.AIM To analyze the effect of enteral nutritional support based on Nutrition Risk Screening 2002(NRS2002)risk assessment on nutritional function in patients with gastrointestinal tumors.METHODS One hundred twelve patients from April 2022 to April 2024 were included for observation and were divided into a control group and an observation group by random number method,56 each.Both groups received treatment for four consecutive weeks.The control group received routine enteral nutrition support,while the observation group received enteral nutrition support based on the NRS2002 risk assessment.Nutritional function,intestinal mucosal barrier function,quality of life,and complication rate were compared between the two groups.Statistical analysis was completed using SPSS26.0 and Excel.RESULTS After nutritional intervention,transferrin,albumin,hemoglobin,and diamine oxidase levels in the observation group were higher than those in the control group,while C-reactive protein,tumor necrosis factorα,and quality of life scores were lower,with significant differences(P<0.05).There was no significant difference in complications between groups(P>0.05),but the complication rate was lower in the observation group.CONCLUSION Enteral nutritional support based on NRS2002 risk assessment for patients with gastrointestinal tumors positively impacts nutritional status and promotes intestinal mucosal barrier function recovery.Patients’quality of life improved,and the incidence of adverse reactions decreased,indicating clinical promotion and application value.展开更多
The effects of plasma screening on the ^(1)P^(o) resonance states of H-and He below the n=3 and n=4 thresholds of the respective subsystemsare investigated using the stabilization method and correlated exponential wav...The effects of plasma screening on the ^(1)P^(o) resonance states of H-and He below the n=3 and n=4 thresholds of the respective subsystemsare investigated using the stabilization method and correlated exponential wave functions.Two plasma mediums,namely,the Debye plasma and quantum plasma environments are considered.The screened Coulomb potential(SCP)obtained from Debye-Hückel model is used to represent Debye plasma environments and the exponential cosine screened Coulomb potential(ECSCP)obtained from a modified Debye-Hückel model is used to represent quantum plasma environments.The resonance parameters(resonance positions and widths)are presented in terms of the screening parameters.展开更多
The reaction characteristics of calcium-based materials during calcium looping(CaL)process are pivotal in the efficiency of CaL thermochemical energy storage(TCES)and CO_(2)capture systems.Currently,metal oxide doping...The reaction characteristics of calcium-based materials during calcium looping(CaL)process are pivotal in the efficiency of CaL thermochemical energy storage(TCES)and CO_(2)capture systems.Currently,metal oxide doping is the primary method to enhance the reaction characteristics of calcium-based materials over multiple cycles.In particular,co-doping with variable-valence metal oxides(VVMOs)can effectively increase the oxygen vacancy content in calcium-based materials,significantly improving their cyclic reaction characteristics.However,there are so numerous VVMOs co-doping schemes that the experimental screening process is complex,consuming considerable time and economic costs.Density functional theory(DFT)calculations have been widely used to reveal the impact of metal oxide doping on the cyclic reaction characteristics of calcium-based materials,with calculation results showing good agreement with experimental conclusions.Nevertheless,there is still a lack of research on utilizing DFT to screen calcium-based materials,and a systematic research methodology has not yet been established.In this study,a systematic DFT-based screening methodology for calcium-based materials was proposed.A series of key parameters for DFT calculations including CO_(2)adsorption energy,oxygen vacancy formation energy,and sintering resistance were proposed.Furthermore,a preliminary mathematical model to predict the CaL TCES and CO_(2)capture performance of calcium-based materials was introduced.The aforementioned DFT method was employed to screen for VVMOs co-doped calcium-based materials.The results revealed that Mn and Ce co-doped calcium-based materials exhibited superior DFT-predicted reaction characteristics.These DFT predictions were validated through experimental assessments of cyclic thermochemical energy storage,CO_(2)capture,and relevant characterization.The outcomes demonstrate a high degree of consistency among DFT-based predictions,experimental results,and characterization.Hence,the DFT-based screening methodology for calcium-based materials proposed herein is a viable solution,poised to offer theoretical insights for the efficient design of calcium-based materials.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
Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effective...Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effectiveness of screening depends on factors such as disease prevalence, as well as the sensitivity and specificity of the screening technology employed.展开更多
Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand...Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand binding structure,dynamics and affinity.Currently,the four mainstream drug targets are G protein-coupled receptors(GPCRs),kinases,ion channels,and nuclear receptors,accounting for over 70%of effective drug targets,most of which are membrane proteins and enzymes.In recent years,various new drug targets have been continuously discovered,and the research focus has shifted from simple affinity analysis to high-throughput and high-content screening,as well as exploring drug-target interaction modes.These deepen reliance on the analytical techniques to have higher sensitivity,recognition specificity,and applicability to diversified target structures,which promoting the rapid development of novel screening methods.展开更多
Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for pr...Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for preventing HPVrelated tumors.Although HPV vaccination has significantly reduced the incidence of cervical cancer,achieving universal coverage remains challenging because of cost barriers,particularly in economically disadvantaged regions.This review provides an update of HPV infection characteristics,screening methods,and strategies tailored to low-resource settings.We also discuss the global burden of HPV-related diseases,regional disparities in the implementation of screening,and future research directions.By examining the current challenges and opportunities,this review aims to inform policymakers and healthcare providers in designing effective,affordable,and scalable screening programs.展开更多
In this paper,we present a novel particle filter(PF)-based direct position tracking method utilizing multiple distributed observation stations.Traditional passive tracking methods are anchored on repetitive position e...In this paper,we present a novel particle filter(PF)-based direct position tracking method utilizing multiple distributed observation stations.Traditional passive tracking methods are anchored on repetitive position estimation,where the set of consecutive estimates provides the tracking trajectory,such as Two-step and direct position determination methods.However,duplicate estimates can be computationally expensive.In addition,these techniques suffer from data association problems.The PF algorithm is a tracking method that avoids these drawbacks,but the conventional PF algorithm is unable to construct a likelihood function from the received signals of multiple observatories to determine the weights of particles.Therefore,we developed an improved PF algorithm with the likelihood function modified by the projection approximation subspace tracking with deflation(PASTd)algorithm.The proposed algorithm uses the projection subspace and spectral function to replace the likelihood function of PF.Then,the weights of particles are calculated jointly by multiple likelihood functions.Finally,the tracking problem of multiple targets is solved by multiple sets of particles.Simulations demonstrate the effectiveness of the proposed method in terms of computational complexity and tracking accuracy.展开更多
Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency....Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency.We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population.Methods:This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region,China.We first performed questionnaire assessment involving 23,381 individuals(7,042 outpatients and 16,339 individuals from the community),and those assessed as“high-risk”were then invited to participate in serological assays and endoscopic examinations.The serological biomarker model was derived based on logistic regression,with predictors selected via the Akaike information criterion.Model performance was evaluated by the area under the receiver operating characteristic curve(AUC).Results:A total of 2,011 participants were ultimately included for analysis.The final serological biomarker model had three predictors,comprising pepsinogenⅠ(PGI),pepsinogenⅠ/Ⅱratio(PGR),and anti-Helicobacter pylori immunoglobulin G(anti-H.pylori IgG)antibodies.This model generated an AUC of 0.733(95%confidence interval:0.655-0.812)and demonstrated the best discriminative ability compared with previously developed serological biomarker models.As the risk cut-off value of our model rose,the detection rate increased and the number of endoscopies needed to detect one case decreased.Conclusions:PGI,PGR,and anti-H.pylori Ig G could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment,providing insight for the development of a multi-stage riskbased sequential strategy for GC screening.展开更多
Background:The US Preventive Services Task Force updated its colorectal cancer(CRC)screening guidelines in 2021,recommending screening for adults aged 45-49.This study aimed to evaluate CRC screening preva-lence among...Background:The US Preventive Services Task Force updated its colorectal cancer(CRC)screening guidelines in 2021,recommending screening for adults aged 45-49.This study aimed to evaluate CRC screening preva-lence among this newly eligible population and assess its association with healthcare provider supply and CT colonography facility availability in 2022.Methods:Using 2022 Behavioral Risk Factor Surveillance System data(n=25,592),we estimated CRC screening prevalence among adults aged 45-49 and the prevalence of different screening modalities across various sociode-mographic factors.We examined associations between screening rates and state-level healthcare provider supply using 2021-2022 Area Health Resources File data.Spearman rank-order correlations assessed relationships be-tween provider supply,CT colonography facility availability,and screening prevalence.Results:Overall CRC screening prevalence was 34.5%(95%CI:33.4%-35.8%).Endoscopic tests were most common(74.9%),followed by stool-based tests(9.3%)and CT colonography(0.5%).Significant variations in screening modalities were observed across sociodemographic factors.Gastroenterology physician supply posi-tively correlated with overall CRC screening prevalence(ρ=0.42,P=0.002)and endoscopy screening prevalence(ρ=0.38,P=0.005).CT colonography facility availability weakly correlated with CT colonography screening prevalence(ρ=0.15,P=0.316),although this was not significant.Conclusions:CRC screening rates among newly eligible adults aged 45-49 appear to be suboptimal in 2022.Dis-parities in screening methods across sociodemographic factors highlight potential access barriers,particularly for endoscopic tests.The association between gastroenterology physician supply and screening rates emphasizes the importance of addressing projected workforce shortages.Targeted efforts are needed to increase CRC screening uptake in this age group and ensure equitable access to screening services.展开更多
Structure-based virtual screening utilizing the approved drugs is an intriguing and laudable approach to excavate novel alternatives for different indications based on the vast amount of reported experimental data.Vir...Structure-based virtual screening utilizing the approved drugs is an intriguing and laudable approach to excavate novel alternatives for different indications based on the vast amount of reported experimental data.Virus superfamily 1 helicase could resolve hydrogen bonds between base pairs and participate in nucleic acid replication and has emerged as a potential target for managing virus infection.Nonetheless,current drug exploitation targeting viral helicases is still in infancy.This work establishes an intelligent multi-computational screening programme to screen potential inhibitors targeting tobacco mosaic virus(TMV)helicase using Food and Drug Administration(FDA)-approved commercially available molecule library.The ranked top 6 hits were further validated by root mean square deviations/fluctuations(RMSD/F),molecular mechanics Poisson Boltzmann surface area(MM-PBSA),density functional theory(DFT)calculations,and bioactivity evaluation.Encouragingly,lumacaftor(ΔE_(total)=-29.0kcal/mol,K_(d)=0.22μmol/L,half maximal inhibitory concentration(IC_(50))=162.5μmol/L)displayed superior binding strength and enzyme inhibition against TMV helicase compared to ningnanmycin(K_(d)=9.35μmol/L,IC_(50)>200μmol/L).Therefore,lumacaftor may be able to inhibit TMV replication by binding to helicase and interfering with its biofunctionability.Besides,the lumacaftor-helicase binding mode changes from H-bonding/electrostatic interactions to hydrophobic interactions in trajectory analysis.Overall,current findings suggest this state-of-the-art stratagem is fruitful and has the potential to be engaged in rapid mining of other target inhibitors for disease treatment.展开更多
基金financially supported by the National Natural Science Foundation of China (62464010)Spring City Plan-Special Program for Young Talents (K202005007)+3 种基金the Yunnan Talents Support Plan for Yong Talents (XDYC-QNRC-2022-0482)Yunnan Local Colleges Applied Basic Research Projects (202101BA070001-138)Key Laboratory of Artificial Microstructures in Yunnan Higher Educationthe Frontier Research Team of Kunming University 2023
文摘Silicon-air(Si-air)batteries have received significant attention owing to their high theoretical energy density and safety profile.However,the actual energy density of the Si-air battery remains significantly lower than the theoretical value,primarily due to corrosion issues and passivation.This study used various metal-organic framework(MOF)materials,such as MIL-53(Al),MIL-88(Fe),and MIL-101(Cr),to modify Si anodes.The MOFs were fabricated to have different morphologies,particle sizes,and pore sizes by altering their central metal nodes and ligands.This approach aimed to modulate the adsorption behavior of H_(2)O,SiO_(2),and OH^(−),thereby mitigating corrosion and passivation reactions.Under a constant current of 150μA,Si-air batteries with MIL-53(Al)@Si,MIL-88(Fe)@Si,and MIL-101(Cr)@Si as anodes demonstrated lifetimes of 293,412,and 336 h,respectively,surpassing the 276 h observed with pristine silicon anodes.Among these composite anodes,MIL-88(Fe)@Si displayed the best performance due to its superior hydrophobicity and optimal pore size,which enhance OH^(−)migration.This study offers a promising strategy for enhancing Si-air battery performance by developing an anodic protective layer with selective screening properties.
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.
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.
文摘BACKGROUND Malnutrition exacerbates the deterioration in patients with advanced gas-trointestinal tumors.AIM To analyze the effect of enteral nutritional support based on Nutrition Risk Screening 2002(NRS2002)risk assessment on nutritional function in patients with gastrointestinal tumors.METHODS One hundred twelve patients from April 2022 to April 2024 were included for observation and were divided into a control group and an observation group by random number method,56 each.Both groups received treatment for four consecutive weeks.The control group received routine enteral nutrition support,while the observation group received enteral nutrition support based on the NRS2002 risk assessment.Nutritional function,intestinal mucosal barrier function,quality of life,and complication rate were compared between the two groups.Statistical analysis was completed using SPSS26.0 and Excel.RESULTS After nutritional intervention,transferrin,albumin,hemoglobin,and diamine oxidase levels in the observation group were higher than those in the control group,while C-reactive protein,tumor necrosis factorα,and quality of life scores were lower,with significant differences(P<0.05).There was no significant difference in complications between groups(P>0.05),but the complication rate was lower in the observation group.CONCLUSION Enteral nutritional support based on NRS2002 risk assessment for patients with gastrointestinal tumors positively impacts nutritional status and promotes intestinal mucosal barrier function recovery.Patients’quality of life improved,and the incidence of adverse reactions decreased,indicating clinical promotion and application value.
基金Supported by the Natural Science Foundation of Heilongjiang Province(LH2024A025)。
文摘The effects of plasma screening on the ^(1)P^(o) resonance states of H-and He below the n=3 and n=4 thresholds of the respective subsystemsare investigated using the stabilization method and correlated exponential wave functions.Two plasma mediums,namely,the Debye plasma and quantum plasma environments are considered.The screened Coulomb potential(SCP)obtained from Debye-Hückel model is used to represent Debye plasma environments and the exponential cosine screened Coulomb potential(ECSCP)obtained from a modified Debye-Hückel model is used to represent quantum plasma environments.The resonance parameters(resonance positions and widths)are presented in terms of the screening parameters.
基金supported by the National Natural Science Foundation of China(52276204 and U22A20435)。
文摘The reaction characteristics of calcium-based materials during calcium looping(CaL)process are pivotal in the efficiency of CaL thermochemical energy storage(TCES)and CO_(2)capture systems.Currently,metal oxide doping is the primary method to enhance the reaction characteristics of calcium-based materials over multiple cycles.In particular,co-doping with variable-valence metal oxides(VVMOs)can effectively increase the oxygen vacancy content in calcium-based materials,significantly improving their cyclic reaction characteristics.However,there are so numerous VVMOs co-doping schemes that the experimental screening process is complex,consuming considerable time and economic costs.Density functional theory(DFT)calculations have been widely used to reveal the impact of metal oxide doping on the cyclic reaction characteristics of calcium-based materials,with calculation results showing good agreement with experimental conclusions.Nevertheless,there is still a lack of research on utilizing DFT to screen calcium-based materials,and a systematic research methodology has not yet been established.In this study,a systematic DFT-based screening methodology for calcium-based materials was proposed.A series of key parameters for DFT calculations including CO_(2)adsorption energy,oxygen vacancy formation energy,and sintering resistance were proposed.Furthermore,a preliminary mathematical model to predict the CaL TCES and CO_(2)capture performance of calcium-based materials was introduced.The aforementioned DFT method was employed to screen for VVMOs co-doped calcium-based materials.The results revealed that Mn and Ce co-doped calcium-based materials exhibited superior DFT-predicted reaction characteristics.These DFT predictions were validated through experimental assessments of cyclic thermochemical energy storage,CO_(2)capture,and relevant characterization.The outcomes demonstrate a high degree of consistency among DFT-based predictions,experimental results,and characterization.Hence,the DFT-based screening methodology for calcium-based materials proposed herein is a viable solution,poised to offer theoretical insights for the efficient design of calcium-based materials.
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Cancer screening is a strategy focused on highrisk populations rather than universal populationwide screening, based on a comprehensive evaluation of epidemiological principles and practical feasibility. The effectiveness of screening depends on factors such as disease prevalence, as well as the sensitivity and specificity of the screening technology employed.
文摘Target-based and phenotype-based methods are the two main approaches for drug screening.Target-based drug screening focuses on specific targets CPA highly correlated with disease mechanisms,by detecting protein-ligand binding structure,dynamics and affinity.Currently,the four mainstream drug targets are G protein-coupled receptors(GPCRs),kinases,ion channels,and nuclear receptors,accounting for over 70%of effective drug targets,most of which are membrane proteins and enzymes.In recent years,various new drug targets have been continuously discovered,and the research focus has shifted from simple affinity analysis to high-throughput and high-content screening,as well as exploring drug-target interaction modes.These deepen reliance on the analytical techniques to have higher sensitivity,recognition specificity,and applicability to diversified target structures,which promoting the rapid development of novel screening methods.
文摘Human papillomavirus(HPV)infection is a common sexually transmitted disease and a leading cause of cervical,other anogenital,and oropharyngeal cancers.Screening for precancerous lesions is an effective strategy for preventing HPVrelated tumors.Although HPV vaccination has significantly reduced the incidence of cervical cancer,achieving universal coverage remains challenging because of cost barriers,particularly in economically disadvantaged regions.This review provides an update of HPV infection characteristics,screening methods,and strategies tailored to low-resource settings.We also discuss the global burden of HPV-related diseases,regional disparities in the implementation of screening,and future research directions.By examining the current challenges and opportunities,this review aims to inform policymakers and healthcare providers in designing effective,affordable,and scalable screening programs.
基金supported by China NSF Grants(62371225,62371227)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX250590).
文摘In this paper,we present a novel particle filter(PF)-based direct position tracking method utilizing multiple distributed observation stations.Traditional passive tracking methods are anchored on repetitive position estimation,where the set of consecutive estimates provides the tracking trajectory,such as Two-step and direct position determination methods.However,duplicate estimates can be computationally expensive.In addition,these techniques suffer from data association problems.The PF algorithm is a tracking method that avoids these drawbacks,but the conventional PF algorithm is unable to construct a likelihood function from the received signals of multiple observatories to determine the weights of particles.Therefore,we developed an improved PF algorithm with the likelihood function modified by the projection approximation subspace tracking with deflation(PASTd)algorithm.The proposed algorithm uses the projection subspace and spectral function to replace the likelihood function of PF.Then,the weights of particles are calculated jointly by multiple likelihood functions.Finally,the tracking problem of multiple targets is solved by multiple sets of particles.Simulations demonstrate the effectiveness of the proposed method in terms of computational complexity and tracking accuracy.
基金supported by the Tencent Charity Foundationthe Ningxia Hui Autonomous Region Key Research and Development Program(No.2021BEG 02025)+1 种基金the Flexible Introduction of Technological Innovation Teams of Ningxia Hui Autonomous Region(No.2021RXTDLX15)the Natural Science Foundation of China(No.82160644)。
文摘Objective:A risk-based sequential screening strategy,from questionnaire-based assessment to biomarker measurement and then to endoscopic examination,has the potential to enhance gastric cancer(GC)screening efficiency.We aimed to evaluate the ability of five common stomach-specific serum biomarkers to further enrich high-risk individuals for GC in the questionnaire-identified high-risk population.Methods:This study was conducted based on a risk-based screening program in Ningxia Hui Autonomous Region,China.We first performed questionnaire assessment involving 23,381 individuals(7,042 outpatients and 16,339 individuals from the community),and those assessed as“high-risk”were then invited to participate in serological assays and endoscopic examinations.The serological biomarker model was derived based on logistic regression,with predictors selected via the Akaike information criterion.Model performance was evaluated by the area under the receiver operating characteristic curve(AUC).Results:A total of 2,011 participants were ultimately included for analysis.The final serological biomarker model had three predictors,comprising pepsinogenⅠ(PGI),pepsinogenⅠ/Ⅱratio(PGR),and anti-Helicobacter pylori immunoglobulin G(anti-H.pylori IgG)antibodies.This model generated an AUC of 0.733(95%confidence interval:0.655-0.812)and demonstrated the best discriminative ability compared with previously developed serological biomarker models.As the risk cut-off value of our model rose,the detection rate increased and the number of endoscopies needed to detect one case decreased.Conclusions:PGI,PGR,and anti-H.pylori Ig G could be jointly used to further enrich high-risk individuals for GC among those selected by questionnaire assessment,providing insight for the development of a multi-stage riskbased sequential strategy for GC screening.
文摘Background:The US Preventive Services Task Force updated its colorectal cancer(CRC)screening guidelines in 2021,recommending screening for adults aged 45-49.This study aimed to evaluate CRC screening preva-lence among this newly eligible population and assess its association with healthcare provider supply and CT colonography facility availability in 2022.Methods:Using 2022 Behavioral Risk Factor Surveillance System data(n=25,592),we estimated CRC screening prevalence among adults aged 45-49 and the prevalence of different screening modalities across various sociode-mographic factors.We examined associations between screening rates and state-level healthcare provider supply using 2021-2022 Area Health Resources File data.Spearman rank-order correlations assessed relationships be-tween provider supply,CT colonography facility availability,and screening prevalence.Results:Overall CRC screening prevalence was 34.5%(95%CI:33.4%-35.8%).Endoscopic tests were most common(74.9%),followed by stool-based tests(9.3%)and CT colonography(0.5%).Significant variations in screening modalities were observed across sociodemographic factors.Gastroenterology physician supply posi-tively correlated with overall CRC screening prevalence(ρ=0.42,P=0.002)and endoscopy screening prevalence(ρ=0.38,P=0.005).CT colonography facility availability weakly correlated with CT colonography screening prevalence(ρ=0.15,P=0.316),although this was not significant.Conclusions:CRC screening rates among newly eligible adults aged 45-49 appear to be suboptimal in 2022.Dis-parities in screening methods across sociodemographic factors highlight potential access barriers,particularly for endoscopic tests.The association between gastroenterology physician supply and screening rates emphasizes the importance of addressing projected workforce shortages.Targeted efforts are needed to increase CRC screening uptake in this age group and ensure equitable access to screening services.
基金financially supported by National Natural Science Foundation of China(Nos.32372610,U23A20201,32160661,32202359)National Key Research and Development Program of China(No.2022YFD1700300)the Central Government Guides Local Science and Technology Development Fund Projects(Nos.[Qiankehezhongyindi(2023)001]and[Qiankehezhongyindi[2024]007])。
文摘Structure-based virtual screening utilizing the approved drugs is an intriguing and laudable approach to excavate novel alternatives for different indications based on the vast amount of reported experimental data.Virus superfamily 1 helicase could resolve hydrogen bonds between base pairs and participate in nucleic acid replication and has emerged as a potential target for managing virus infection.Nonetheless,current drug exploitation targeting viral helicases is still in infancy.This work establishes an intelligent multi-computational screening programme to screen potential inhibitors targeting tobacco mosaic virus(TMV)helicase using Food and Drug Administration(FDA)-approved commercially available molecule library.The ranked top 6 hits were further validated by root mean square deviations/fluctuations(RMSD/F),molecular mechanics Poisson Boltzmann surface area(MM-PBSA),density functional theory(DFT)calculations,and bioactivity evaluation.Encouragingly,lumacaftor(ΔE_(total)=-29.0kcal/mol,K_(d)=0.22μmol/L,half maximal inhibitory concentration(IC_(50))=162.5μmol/L)displayed superior binding strength and enzyme inhibition against TMV helicase compared to ningnanmycin(K_(d)=9.35μmol/L,IC_(50)>200μmol/L).Therefore,lumacaftor may be able to inhibit TMV replication by binding to helicase and interfering with its biofunctionability.Besides,the lumacaftor-helicase binding mode changes from H-bonding/electrostatic interactions to hydrophobic interactions in trajectory analysis.Overall,current findings suggest this state-of-the-art stratagem is fruitful and has the potential to be engaged in rapid mining of other target inhibitors for disease treatment.
