Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been...Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been established.Methods:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients.The effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor model.Gene knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated neutrophils.Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with PARP-1.Co-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression.Results:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(P<0.001).Neutrophil activation promoted lung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in vivo.Mechanistically,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth.Conclusion:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer progression.展开更多
After the excavation of the roadway,the original stress balance is destroyed,resulting in the redistribution of stress and the formation of an excavation damaged zone(EDZ)around the roadway.The thickness of EDZ is the...After the excavation of the roadway,the original stress balance is destroyed,resulting in the redistribution of stress and the formation of an excavation damaged zone(EDZ)around the roadway.The thickness of EDZ is the key basis for roadway stability discrimination and support structure design,and it is of great engineering significance to accurately predict the thickness of EDZ.Considering the advantages of machine learning(ML)in dealing with high-dimensional,nonlinear problems,a hybrid prediction model based on the random forest(RF)algorithm is developed in this paper.The model used the dragonfly algorithm(DA)to optimize two hyperparameters in RF,namely mtry and ntree,and used mean absolute error(MAE),rootmean square error(RMSE),determination coefficient(R^(2)),and variance accounted for(VAF)to evaluatemodel prediction performance.A database containing 217 sets of data was collected,with embedding depth(ED),drift span(DS),surrounding rock mass strength(RMS),joint index(JI)as input variables,and the excavation damaged zone thickness(EDZT)as output variable.In addition,four classic models,back propagation neural network(BPNN),extreme learning machine(ELM),radial basis function network(RBF),and RF were compared with the DA-RF model.The results showed that the DARF mold had the best prediction performance(training set:MAE=0.1036,RMSE=0.1514,R^(2)=0.9577,VAF=94.2645;test set:MAE=0.1115,RMSE=0.1417,R^(2)=0.9423,VAF=94.0836).The results of the sensitivity analysis showed that the relative importance of each input variable was DS,ED,RMS,and JI from low to high.展开更多
Concentration distribution of the deterrent in single-base propellant during the process of firing plays an important role in the ballistic properties of gun propellant in weapons. However, the diffusion coefficient c...Concentration distribution of the deterrent in single-base propellant during the process of firing plays an important role in the ballistic properties of gun propellant in weapons. However, the diffusion coefficient calculated by molecular dynamics(MD) simulation is 6 orders of magnitude larger than the experimental values. Meanwhile, few simple and comprehensive theoretical models can explain the phenomenon and accurately predict the concentration distribution of the propellant. Herein, an onion model combining with MD simulation and finite element method of diffusion in propellants is introduced to bridge the gap between the experiments and simulations, and correctly predict the concentration distribution of deterrent. Furthermore, a new time scale is found to characterize the diffusion process. Finally, the time-and position-depended concentration distributions of dibutyl phthalate in nitrocellulose are measured by Raman spectroscopy to verify the correctness of the onion model. This work not only provides guidance for the design of the deterrent, but could be also extended to the diffusion of small molecules in polymer with different crystallinity.展开更多
As a promising candidate electrode material in both Li-and Na-ion batteries(L/SIBs),the application of Co_(9)S_(8) is being hindered by its unsatisfactory electrochemical performance caused by the sluggish ion diffusi...As a promising candidate electrode material in both Li-and Na-ion batteries(L/SIBs),the application of Co_(9)S_(8) is being hindered by its unsatisfactory electrochemical performance caused by the sluggish ion diffusion kinetics and drastic volume expansion.Herein,a hybrid material composed of Co_(9)S_(8-x),N-doped carbon foam that seeded with Co nanoparticles(Co_(9)S_(8-x)@Co-NC) is constructed.Particularly,theoretical and experimental results imply that a built-in electric field at the interface of Co and NC is observed due to the variation of Fermi levels,forming rich Mott-Schottky-like heterointerfaces,which can significantly enhance the charge transfer capability between the active materials of Co_(9)S_(8) and conductive NC skeleton.Moreover,the sulfur defects in Co_(9)S_(8-x)can not only effectively lower the energy barrier of the ion diffusion and charge transfer processes,but also endow the target sample with more storage/adsorption/active sites for Li^(+)/Na^(+) ions,thus improving the rate performance of the Co_(9)S_(8-x)@Co-NC composite.As a result,the Co_(9)S_(8-x)@Co-NC exhibits fast surface-controlled redox kinetics and robust cycling stability.For instance,the Co_(9)S_(8-x)@Co-NC displays impressive Li-storage properties in both half and full cells with a high reversible capacity of 1007.4 mA h g^(-1)at 0.1 A g^(-1)after 100 cycles and superior rate capability up to 5 A g^(-1).Moreover,based on these comprehensive merits,the Co_(9)S_(8-x)@Co-NC composite shows decent electrochemical performance(472.2 and 311.1 mA h g^(-1)at 0.1 and 10 A g^(-1),respectively) as an anode for SIBs.This work presents an effective strategy for the construction of Mott-Schottky-like heterointerfaces in Co_(9)S_(8) based materials and provides specific inspiration for future works designing high-performance electrodes via interfacial engineering.展开更多
High activity and productivity of MoVNbTeO_(x) catalyst are challenging tasks in oxidative dehydrogenation of ethane(ODHE)for industrial application.In this work,phase-pure M1 with 30 wt%CeO_(2) composite catalyst was...High activity and productivity of MoVNbTeO_(x) catalyst are challenging tasks in oxidative dehydrogenation of ethane(ODHE)for industrial application.In this work,phase-pure M1 with 30 wt%CeO_(2) composite catalyst was treated by oxygen plasma to further enhance catalyst performance.The results show that the oxygen vacancies generated by the solid-state redox reaction between M1 and CeO_(2) capture active oxygen species in gas and transform V^(4+)to V^(5+)without damage to M1 structure.The space-time yield of ethylene of the plasma-treated catalyst was significantly increased,in which the catalyst shows an enhancement near~100% than that of phase-pure M1 at 400℃ for ODHE process.Plasma treatment for catalysts demonstrates an effective way to convert electrical energy into chemical energy in catalyst materials.Energy conversion is achieved by using the catalyst as a medium.展开更多
The noncentrosymmetric superconductor CaPtAs with time-reversal symmetry breaking in its superconducting state was previously proposed to host nodal superconductivity.Here,by employing ultralow-temperature thermal con...The noncentrosymmetric superconductor CaPtAs with time-reversal symmetry breaking in its superconducting state was previously proposed to host nodal superconductivity.Here,by employing ultralow-temperature thermal conductivity measurement on CaPtAs single crystal,we study its superconducting gap structure.A negligible residual linear term of thermal conductivity(κ_(0)/T)in zero magnetic field and the field dependence ofκ_(0)/T indicate that CaPtAs has multiple superconducting gaps with a dominant s-wave component.This is consistent with recent nuclear quadrupole resonance measurements on CaPtAs.Our work puts a strong constraint on the theories to describe the superconducting pairing symmetry of CaPtAs.展开更多
Background The modulatory effect of transcutaneous auricular vagus nerve stimulation(taVNS)on attention has varied in previous studies.This inconsistency might be attributed to the combined influence of the modulation...Background The modulatory effect of transcutaneous auricular vagus nerve stimulation(taVNS)on attention has varied in previous studies.This inconsistency might be attributed to the combined influence of the modulation effect on the different attentional functions,including alerting,orienting and executive control.Aims We aimed to preliminarily examine the modulatory effectsoftaVNS on differentattentionalfunctions.Methods Fifty-nine healthy participants were recruited and were randomly assigned to taVNS(receiving taVNS for 20 minutes)or control(receiving taVNS for 30 seconds)groups.All participants underwent a dot-probe task before and after the taVNS/control intervention.Their behavioural performance and electroencephalographic signals during pre-and post-tests were recorded,and different observed variables were extracted and analysed to characterise different attentional systems.Results We observed that active taVNS applied at the left ear significantly improved the overall behavioural performance,that is,shorter reaction time(RT)and lower intra-individual reaction time variability(lIRTV)for right-hand responses when compared with the control condition.In addition,active taVNS resulted in larger P3 and movement-related cortical potential(MRCP)amplitudes associated with right-hand reactions than the control condition.Active taVNS also decreased the difference between the pre-and post-tests in the power spectral density of spontaneous high-αband oscillations at C4 electrode.Importantly,parallel mediation models for right-hand responses showed that the change of P3 amplitude mediated the effects of taVNS on RT and lIRTV.In contrast,the change of MRCP amplitude suppressed the effect of taVNS on the lIRTV.Conclusions Our results provided behavioural and brain evidence supporting the effects of taVNS on different attentional systems,and their interaction further shaped behavioural performance,suggesting a promising role of taVNS in cognitive enhancement.展开更多
It has long been a challenging task to detect an anomaly in a crowded scene.In this paper,a selfsupervised framework called the abnormal event detection network(AED-Net),which is composed of a principal component anal...It has long been a challenging task to detect an anomaly in a crowded scene.In this paper,a selfsupervised framework called the abnormal event detection network(AED-Net),which is composed of a principal component analysis network(PCAnet)and kernel principal component analysis(kPCA),is proposed to address this problem.Using surveillance video sequences of different scenes as raw data,the PCAnet is trained to extract high-level semantics of the crowd’s situation.Next,kPCA,a one-class classifier,is trained to identify anomalies within the scene.In contrast to some prevailing deep learning methods,this framework is completely self-supervised because it utilizes only video sequences of a normal situation.Experiments in global and local abnormal event detection are carried out on Monitoring Human Activity dataset from University of Minnesota(UMN dataset)and Anomaly Detection dataset from University of California,San Diego(UCSD dataset),and competitive results that yield a better equal error rate(EER)and area under curve(AUC)than other state-of-the-art methods are observed.Furthermore,by adding a local response normalization(LRN)layer,we propose an improvement to the original AED-Net.The results demonstrate that this proposed version performs better by promoting the framework’s generalization capacity.展开更多
Lithium-ion battery packs are made by many batteries, and the difficulty in heat transfer can cause many safety issues. It is important to evaluate thermal performance of a battery pack in designing process. Here, a m...Lithium-ion battery packs are made by many batteries, and the difficulty in heat transfer can cause many safety issues. It is important to evaluate thermal performance of a battery pack in designing process. Here, a multiscale method combining a pseudo-two-dimensional model of individual battery and three-dimensional computational fluid dynamics is employed to describe heat generation and transfer in a battery pack. The effect of battery arrangement on the thermal performance of battery packs is investigated. We discuss the air-cooling effect of the pack with four battery arrangements which include one square arrangement, one stagger arrangement and two trapezoid arrangements. In addition, the air-cooling strategy is studied by observing temperature distribution of the battery pack. It is found that the square arrangement is the structure with the best air-cooling effect, and the cooling effect is best when the cold air inlet is at the top of the battery pack. We hope that this work can provide theoretical guidance for thermal management of lithium-ion battery packs.展开更多
Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including contr...Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including control group, model group, silymarin positive control group, and three YGMM treatment groups. Model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg) for 14 days. Silymarin group and YGMM treatment groups were administered intragastrically with silymarin (100 mg/kg) and different doses of YGMM (1, 2.5, 5 mg/kg) 2 hours before INH and RIF administration from day 4 to day 14.?Results: Rats were sacrificed 16 hours after the last day treatment to determine the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as total bilirubin (TB) content. Oxidative stress was evaluated by measuring total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels. Histopathological changes in liver tissues were observed under an optical microscope by using hematoxylin and eosin staining. The mice?in model groups showed significantly (p < 0.05) increased levels in AST, ALT, ALP, TB and MDA compared to their control groups;and showed significantly (p < 0.05) decreased level in T-SOD. These changes were significantly (p < 0.05) reversed by the YGMM treatments in a dose-dependent manner. Hepatic pathological changes were attenuated or even reversed by silymarin or YGMM treatments. Conclusions: YGMM has a good hepatoprotective activity on isoniazid-rifampicin induced liver injuries in rats.展开更多
As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet...As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet.In this study,we investigated the in vivo effect of Pic in streptozotocin(STZ)-induced type 1 diabetic mice.Mice were injected with STZ to establish the type 1 diabetesmellitus(T1DM)model.After stable hyperglycemia was achieved,mice were then orally treated with Pic(40 mg/kg b.w.,i.g.)for 30 days.The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM,including body weight loss,polydipsia,hyperglycemia,and hypoinsulinemia.Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice.In addition,Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-αand IL-6,the expression of endoplasmic reticulum(ER)stress markers GRP78 and CHOP,and the level of oxidative stress in T1DM mice.Moreover,Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by 1H Nuclear Magnetic Resonance(NMR)-based metabolomics.Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress,inflammation,and ER stress.展开更多
The design and development of cheap,abundant,and efficient electrocatalysts for selective CO_(2)electroreduction is highly desirable yet remains an ongoing challenge.Herein,we report on our discovery of the use of two...The design and development of cheap,abundant,and efficient electrocatalysts for selective CO_(2)electroreduction is highly desirable yet remains an ongoing challenge.Herein,we report on our discovery of the use of two-dimensional MgO rich in oxygen vacancies(VO)as an electrocatalyst for the efficient reduction of CO_(2)to yield CO in 1-butyl-3-methylimidazolium hexafluorophosphate dissolved in acetonitrile.The faradaic efficiency toward CO reaches as high as 99.6±0.24%with a current density of up to 40.8 mA cm−2.Density functional theory calculations illustrate that the introduction of VO in MgO substantially lowers the reaction-free energy for the transformation of ^(*)COO^(−) to ^(*)COOH,the potential determining step,which greatly boosts CO_(2)conversion efficiency.This work opens the way to realizing economic and efficient CO_(2)electrolysis of group II metals.展开更多
The projected speckle-based three-dimensional digital image correlation method(3D-DIC)is being increasingly used in the reliability measurement of microelectronic packaging structures because of its noninvasive nature...The projected speckle-based three-dimensional digital image correlation method(3D-DIC)is being increasingly used in the reliability measurement of microelectronic packaging structures because of its noninvasive nature,high precision,and low cost.However,during the measurement of the thermal reliability of packaging structures,the thermal airflow generated by heating introduces distortions in the images captured by the DIC measurement system,impacting the accuracy and reliability of noncontact measurements.To address this challenge,a thermal airflow distortion correction model based on the transformer attention mechanism is proposed specifically for the measurement of thermal warpage in microelectronic packaging structures.This model avoids the oversmoothing issue associated with convolutional neural networks and the lack of physical constraints in generative adversarial networks,ensuring the precision of grayscale gradient changes in speckle patterns and minimizing adverse effects on DIC calculation accuracy.By inputting the distorted images captured by the DIC measurement system into the network,corrected images are obtained for 3D-DIC calculations,thus allowing the thermal warpage measurement results of the sample to be acquired.Through experiments measuring topography with customized step block specimens,the effectiveness of the proposed method in improving warpage measurement accuracy is confirmed;this is particularly true when captured images are affected by thermal airflow at 140°C and 160°C,temperatures commonly encountered in thermal reliability testing of packaging structures.The method successfully reduces the standard deviation from 9.829 to 5.943μm and from 12.318 to 6.418μm,respectively.The results demonstrate the substantial practical value of this method for measuring thermal warpage in microelectronic packaging structures.展开更多
Titanium(Ti)dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility.However,conventional Ti scaffolds manufactured through machining often do not fit pe...Titanium(Ti)dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility.However,conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site.Laser powder bed fusion(LPBF)technology enables the personalised manufacturing of custom-made Ti scaffolds.A custom-made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing.To enhance the surface roughness,a nitric acid mixed solution with a specific composition of HF:HNO_(3):C_(3)H_(6)O_(3)=2:2:3 was used.The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film.As a result,the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part,with a reduced surface roughness(Ra)of 1.23±0.19μm.The custom-made Ti scaffold also demonstrated favourable mechanical properties,with a bending strength of 335.18±33.62 MPa and stiffness of 2.13±0.21 GPa.Furthermore,in vitro cell tests confirmed the excellent biocompatibility of the custom-made Ti scaffold.The authors present a feasible strategy for the further clinical application of custom-made Ti scaffolds,offering enhanced surface properties and addressing the limitations of conventional machining methods.展开更多
With the deepening understanding for the concept of sustainable development,the utilization of minerals is no longer limited to the traditional way.In this study,an environment friendly method for preparing Fe-Al_(2)O...With the deepening understanding for the concept of sustainable development,the utilization of minerals is no longer limited to the traditional way.In this study,an environment friendly method for preparing Fe-Al_(2)O_(3)composites by using natural minerals was investigated.Additionally,the effects of CeO_(2)on the properties of composites were studied.The mechanical properties of Fe-Al_(2)O_(3)composites prepared by natural minerals are affected by the brittleness of glass phase.The strength and toughness of the glass phase in the composite are improved successfully by using rare earth oxides,indicating that the natural rare earths in Bayan Obo minerals have an enhanced influence on the properties of composite materials.The results show that the properties of glass phase can be significantly improved by addition of CeO_(2).At the optimal addition of 3 wt%CeO_(2),the composite achieves the density of 4.21 g/cm^(3),flexural strength of 401 MPa,Vickers hardness of 13.07 GPa and fracture toughness of 6.58 MPa·m^(1/2).The composite has excellent mechanical properties,which can be used in engineering as a cheap structural material.This study aims at reducing waste emissions,improving energy efficiencies and avoiding waste of rare earth resources during the preparation of composite materials.展开更多
Antimicrobial peptides(AMPs),with their extraordinary properties,such as broad-spectrum activity,rapid action and difficult development of resistance,have become promising molecules as new antibiotics.Despite their va...Antimicrobial peptides(AMPs),with their extraordinary properties,such as broad-spectrum activity,rapid action and difficult development of resistance,have become promising molecules as new antibiotics.Despite their various mechanisms of action,the interaction of AMPs with the bacterial cell membrane is the key step for their mode of action.Moreover,it is generally accepted that the membrane is the primary target of most AMPs,and the interaction between AMPs and eukaryotic cell membranes(causing toxicity to host cells)limits their clinical application.Therefore,researchers are engaged in reforming or de novo designing AMPs as a‘singleedged sword’that contains high antimicrobial activity yet low cytotoxicity against eukaryotic cells.To improve the antimicrobial activity of AMPs,the relationship between the structure and function of AMPs has been rigorously pursued.In this review,we focus on the current knowledge of α-helical cationic antimicrobial peptides,one of the most common types of AMPs in nature.展开更多
Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to...Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.展开更多
A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic a-helical antimicrobial peptide A12L/A20L （Ac-KWKSFLKTF...A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic a-helical antimicrobial peptide A12L/A20L （Ac-KWKSFLKTFKSLK KTVLHTLLKAISS-amide） was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activi- ties of o-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitu- tions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram- positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial pep- tides with enhanced specificity.展开更多
Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large...Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large FOV and DOF microscope imaging technology based on a chip-scale metalens device that is implemented by a SiNxmetalens array with a co-and cross-polarization multiplexed dual-phase design and dispersive spectrum zoom effect.A 4-mm×4-mm FOV is obtained with a resolution of 1.74μm and DOF of200μm within a wavelength range of 450 to 510 nm,which definitely exceeds the performance of traditional microscopes with the same resolution.Moreover,it is realized in a miniaturized compact prototype,showing an overall advantage for portable and convenient microscope technology.展开更多
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFA0900900)the National Natural Science Foundation of China(Grant Nos.82273334,82203172,81871869,and 81400055)+3 种基金the Jiangsu Province Social Development Key Projects(Grant Nos.BE2020641 and BE2020640)the Xuzhou Medical University Excellent Talent Research Start-up Fund(Grant No.RC20552157)the Jiangsu Province Capability Improvement Project through Science,Technology and Education(Grant No.CXZX202234)funded by the China Postdoctoral Science Foundation(Grant No.2023M732970)。
文摘Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been established.Methods:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients.The effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor model.Gene knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated neutrophils.Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with PARP-1.Co-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression.Results:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(P<0.001).Neutrophil activation promoted lung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in vivo.Mechanistically,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth.Conclusion:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer progression.
基金funded by the National Science Foundation of China(42177164)the Distinguished Youth Science Foundation of Hunan Province of China(2022JJ10073)the Innovation-Driven Project of Central South University(2020CX040).
文摘After the excavation of the roadway,the original stress balance is destroyed,resulting in the redistribution of stress and the formation of an excavation damaged zone(EDZ)around the roadway.The thickness of EDZ is the key basis for roadway stability discrimination and support structure design,and it is of great engineering significance to accurately predict the thickness of EDZ.Considering the advantages of machine learning(ML)in dealing with high-dimensional,nonlinear problems,a hybrid prediction model based on the random forest(RF)algorithm is developed in this paper.The model used the dragonfly algorithm(DA)to optimize two hyperparameters in RF,namely mtry and ntree,and used mean absolute error(MAE),rootmean square error(RMSE),determination coefficient(R^(2)),and variance accounted for(VAF)to evaluatemodel prediction performance.A database containing 217 sets of data was collected,with embedding depth(ED),drift span(DS),surrounding rock mass strength(RMS),joint index(JI)as input variables,and the excavation damaged zone thickness(EDZT)as output variable.In addition,four classic models,back propagation neural network(BPNN),extreme learning machine(ELM),radial basis function network(RBF),and RF were compared with the DA-RF model.The results showed that the DARF mold had the best prediction performance(training set:MAE=0.1036,RMSE=0.1514,R^(2)=0.9577,VAF=94.2645;test set:MAE=0.1115,RMSE=0.1417,R^(2)=0.9423,VAF=94.0836).The results of the sensitivity analysis showed that the relative importance of each input variable was DS,ED,RMS,and JI from low to high.
基金sponsored by the National Natural Science Foundation of China (91834301, 22078088, 22005143)the National Natural Science Foundation of China for Innovative Research Groups (51621002)。
文摘Concentration distribution of the deterrent in single-base propellant during the process of firing plays an important role in the ballistic properties of gun propellant in weapons. However, the diffusion coefficient calculated by molecular dynamics(MD) simulation is 6 orders of magnitude larger than the experimental values. Meanwhile, few simple and comprehensive theoretical models can explain the phenomenon and accurately predict the concentration distribution of the propellant. Herein, an onion model combining with MD simulation and finite element method of diffusion in propellants is introduced to bridge the gap between the experiments and simulations, and correctly predict the concentration distribution of deterrent. Furthermore, a new time scale is found to characterize the diffusion process. Finally, the time-and position-depended concentration distributions of dibutyl phthalate in nitrocellulose are measured by Raman spectroscopy to verify the correctness of the onion model. This work not only provides guidance for the design of the deterrent, but could be also extended to the diffusion of small molecules in polymer with different crystallinity.
基金the financial support of the National Natural Science Foundation of China (51902089)the Educational Department of Jilin Province, China (JJKH20230587KJ)the Science and Technology Department of Jilin Province, China (20220101071JC)。
文摘As a promising candidate electrode material in both Li-and Na-ion batteries(L/SIBs),the application of Co_(9)S_(8) is being hindered by its unsatisfactory electrochemical performance caused by the sluggish ion diffusion kinetics and drastic volume expansion.Herein,a hybrid material composed of Co_(9)S_(8-x),N-doped carbon foam that seeded with Co nanoparticles(Co_(9)S_(8-x)@Co-NC) is constructed.Particularly,theoretical and experimental results imply that a built-in electric field at the interface of Co and NC is observed due to the variation of Fermi levels,forming rich Mott-Schottky-like heterointerfaces,which can significantly enhance the charge transfer capability between the active materials of Co_(9)S_(8) and conductive NC skeleton.Moreover,the sulfur defects in Co_(9)S_(8-x)can not only effectively lower the energy barrier of the ion diffusion and charge transfer processes,but also endow the target sample with more storage/adsorption/active sites for Li^(+)/Na^(+) ions,thus improving the rate performance of the Co_(9)S_(8-x)@Co-NC composite.As a result,the Co_(9)S_(8-x)@Co-NC exhibits fast surface-controlled redox kinetics and robust cycling stability.For instance,the Co_(9)S_(8-x)@Co-NC displays impressive Li-storage properties in both half and full cells with a high reversible capacity of 1007.4 mA h g^(-1)at 0.1 A g^(-1)after 100 cycles and superior rate capability up to 5 A g^(-1).Moreover,based on these comprehensive merits,the Co_(9)S_(8-x)@Co-NC composite shows decent electrochemical performance(472.2 and 311.1 mA h g^(-1)at 0.1 and 10 A g^(-1),respectively) as an anode for SIBs.This work presents an effective strategy for the construction of Mott-Schottky-like heterointerfaces in Co_(9)S_(8) based materials and provides specific inspiration for future works designing high-performance electrodes via interfacial engineering.
基金supported by the National Natural Science Foundation of China (No.21776156).
文摘High activity and productivity of MoVNbTeO_(x) catalyst are challenging tasks in oxidative dehydrogenation of ethane(ODHE)for industrial application.In this work,phase-pure M1 with 30 wt%CeO_(2) composite catalyst was treated by oxygen plasma to further enhance catalyst performance.The results show that the oxygen vacancies generated by the solid-state redox reaction between M1 and CeO_(2) capture active oxygen species in gas and transform V^(4+)to V^(5+)without damage to M1 structure.The space-time yield of ethylene of the plasma-treated catalyst was significantly increased,in which the catalyst shows an enhancement near~100% than that of phase-pure M1 at 400℃ for ODHE process.Plasma treatment for catalysts demonstrates an effective way to convert electrical energy into chemical energy in catalyst materials.Energy conversion is achieved by using the catalyst as a medium.
基金Project supported by the National Natural Science Foundation of China (Grant No.12174064)the National Key R&D Program of China (Grant No.2022YFA1402200)the Shanghai Municipal Science and Technology Major Project (Grant No.2019SHZDZX01)。
文摘The noncentrosymmetric superconductor CaPtAs with time-reversal symmetry breaking in its superconducting state was previously proposed to host nodal superconductivity.Here,by employing ultralow-temperature thermal conductivity measurement on CaPtAs single crystal,we study its superconducting gap structure.A negligible residual linear term of thermal conductivity(κ_(0)/T)in zero magnetic field and the field dependence ofκ_(0)/T indicate that CaPtAs has multiple superconducting gaps with a dominant s-wave component.This is consistent with recent nuclear quadrupole resonance measurements on CaPtAs.Our work puts a strong constraint on the theories to describe the superconducting pairing symmetry of CaPtAs.
基金supported by the National Natural Science Foundation of China(32071061,32171077)the Beijing Natural Science Foundation(JQ22018)and the Scientific Foundation of the Institute of Psychology,Chinese Academy of Sciences(E2CX4015).
文摘Background The modulatory effect of transcutaneous auricular vagus nerve stimulation(taVNS)on attention has varied in previous studies.This inconsistency might be attributed to the combined influence of the modulation effect on the different attentional functions,including alerting,orienting and executive control.Aims We aimed to preliminarily examine the modulatory effectsoftaVNS on differentattentionalfunctions.Methods Fifty-nine healthy participants were recruited and were randomly assigned to taVNS(receiving taVNS for 20 minutes)or control(receiving taVNS for 30 seconds)groups.All participants underwent a dot-probe task before and after the taVNS/control intervention.Their behavioural performance and electroencephalographic signals during pre-and post-tests were recorded,and different observed variables were extracted and analysed to characterise different attentional systems.Results We observed that active taVNS applied at the left ear significantly improved the overall behavioural performance,that is,shorter reaction time(RT)and lower intra-individual reaction time variability(lIRTV)for right-hand responses when compared with the control condition.In addition,active taVNS resulted in larger P3 and movement-related cortical potential(MRCP)amplitudes associated with right-hand reactions than the control condition.Active taVNS also decreased the difference between the pre-and post-tests in the power spectral density of spontaneous high-αband oscillations at C4 electrode.Importantly,parallel mediation models for right-hand responses showed that the change of P3 amplitude mediated the effects of taVNS on RT and lIRTV.In contrast,the change of MRCP amplitude suppressed the effect of taVNS on the lIRTV.Conclusions Our results provided behavioural and brain evidence supporting the effects of taVNS on different attentional systems,and their interaction further shaped behavioural performance,suggesting a promising role of taVNS in cognitive enhancement.
基金This work is partially supported by the National Key Research and Development Program of China(2016YFE0204200)the National Natural Science Foundation of China(61503017)+3 种基金the Fundamental Research Funds for the Central Universities(YWF-18-BJ-J-221)the Aeronautical Science Foundation of China(2016ZC51022)the Platform CAPSEC(capteurs pour la sécurité)funded by Région Champagne-ArdenneFEDER(fonds européen de développement régional).
文摘It has long been a challenging task to detect an anomaly in a crowded scene.In this paper,a selfsupervised framework called the abnormal event detection network(AED-Net),which is composed of a principal component analysis network(PCAnet)and kernel principal component analysis(kPCA),is proposed to address this problem.Using surveillance video sequences of different scenes as raw data,the PCAnet is trained to extract high-level semantics of the crowd’s situation.Next,kPCA,a one-class classifier,is trained to identify anomalies within the scene.In contrast to some prevailing deep learning methods,this framework is completely self-supervised because it utilizes only video sequences of a normal situation.Experiments in global and local abnormal event detection are carried out on Monitoring Human Activity dataset from University of Minnesota(UMN dataset)and Anomaly Detection dataset from University of California,San Diego(UCSD dataset),and competitive results that yield a better equal error rate(EER)and area under curve(AUC)than other state-of-the-art methods are observed.Furthermore,by adding a local response normalization(LRN)layer,we propose an improvement to the original AED-Net.The results demonstrate that this proposed version performs better by promoting the framework’s generalization capacity.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 91834301 and 22078088)the National Natural Science Foundation of China for Innovative Research Groups (Grant No. 51621002)the Shanghai Rising-Star Program (Grant No. 21QA1401900)。
文摘Lithium-ion battery packs are made by many batteries, and the difficulty in heat transfer can cause many safety issues. It is important to evaluate thermal performance of a battery pack in designing process. Here, a multiscale method combining a pseudo-two-dimensional model of individual battery and three-dimensional computational fluid dynamics is employed to describe heat generation and transfer in a battery pack. The effect of battery arrangement on the thermal performance of battery packs is investigated. We discuss the air-cooling effect of the pack with four battery arrangements which include one square arrangement, one stagger arrangement and two trapezoid arrangements. In addition, the air-cooling strategy is studied by observing temperature distribution of the battery pack. It is found that the square arrangement is the structure with the best air-cooling effect, and the cooling effect is best when the cold air inlet is at the top of the battery pack. We hope that this work can provide theoretical guidance for thermal management of lithium-ion battery packs.
文摘Background: To explore the hepatoprotective effect of Yigan mingmu oral liquid (YGMM) on isoniazid-rifampicin induced liver injury in rats. Methods: Total 38 SD rats were randomly divided into 6 groups including control group, model group, silymarin positive control group, and three YGMM treatment groups. Model group was administered intragastrically with INH (100 mg/kg) and RIF (100 mg/kg) for 14 days. Silymarin group and YGMM treatment groups were administered intragastrically with silymarin (100 mg/kg) and different doses of YGMM (1, 2.5, 5 mg/kg) 2 hours before INH and RIF administration from day 4 to day 14.?Results: Rats were sacrificed 16 hours after the last day treatment to determine the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as total bilirubin (TB) content. Oxidative stress was evaluated by measuring total superoxide dismutase (T-SOD) and malondialdehyde (MDA) levels. Histopathological changes in liver tissues were observed under an optical microscope by using hematoxylin and eosin staining. The mice?in model groups showed significantly (p < 0.05) increased levels in AST, ALT, ALP, TB and MDA compared to their control groups;and showed significantly (p < 0.05) decreased level in T-SOD. These changes were significantly (p < 0.05) reversed by the YGMM treatments in a dose-dependent manner. Hepatic pathological changes were attenuated or even reversed by silymarin or YGMM treatments. Conclusions: YGMM has a good hepatoprotective activity on isoniazid-rifampicin induced liver injuries in rats.
基金the National Natural Science Foundation of China under Grant 21677076 and 31970897 to DWOutstanding Youth Foundation of Jiangsu Province(BK20190093)to DWQing Lan Project of Jiangsu Province to DW,the Fundamental Research Funds for the Central Universities No.30919011102 to DW,the Innovative and Entrepreneurial Talent Cultivation(Shuangchuang)Program of Jiangsu Province to DW.
文摘As a natural analog of resveratrol,piceatannol(Pic)exhibits good antioxidant and anti-inflammatory activities in different disease models.However,the role of Pic in type 1 diabetes mousemodel has not been reported yet.In this study,we investigated the in vivo effect of Pic in streptozotocin(STZ)-induced type 1 diabetic mice.Mice were injected with STZ to establish the type 1 diabetesmellitus(T1DM)model.After stable hyperglycemia was achieved,mice were then orally treated with Pic(40 mg/kg b.w.,i.g.)for 30 days.The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM,including body weight loss,polydipsia,hyperglycemia,and hypoinsulinemia.Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice.In addition,Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-αand IL-6,the expression of endoplasmic reticulum(ER)stress markers GRP78 and CHOP,and the level of oxidative stress in T1DM mice.Moreover,Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by 1H Nuclear Magnetic Resonance(NMR)-based metabolomics.Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress,inflammation,and ER stress.
基金supported by the National Natural Science Foundation of China(grant no.21972010)the National Key Research and Development Program of China(grant no.2022YFC2105900)+2 种基金the Beijing Natural Science Foundation(grant no.2192039)Fundamental Research Funds for the Central Universities(grant nos.JD2310,ZY2317,and buctrc202226)the NRF Korea(grant no.NRF-2019M3D3A1A01069099).
文摘The design and development of cheap,abundant,and efficient electrocatalysts for selective CO_(2)electroreduction is highly desirable yet remains an ongoing challenge.Herein,we report on our discovery of the use of two-dimensional MgO rich in oxygen vacancies(VO)as an electrocatalyst for the efficient reduction of CO_(2)to yield CO in 1-butyl-3-methylimidazolium hexafluorophosphate dissolved in acetonitrile.The faradaic efficiency toward CO reaches as high as 99.6±0.24%with a current density of up to 40.8 mA cm−2.Density functional theory calculations illustrate that the introduction of VO in MgO substantially lowers the reaction-free energy for the transformation of ^(*)COO^(−) to ^(*)COOH,the potential determining step,which greatly boosts CO_(2)conversion efficiency.This work opens the way to realizing economic and efficient CO_(2)electrolysis of group II metals.
基金supported by the National Natural Science Foundation of China[grant number:U20A6004 and grant number:52075208].
文摘The projected speckle-based three-dimensional digital image correlation method(3D-DIC)is being increasingly used in the reliability measurement of microelectronic packaging structures because of its noninvasive nature,high precision,and low cost.However,during the measurement of the thermal reliability of packaging structures,the thermal airflow generated by heating introduces distortions in the images captured by the DIC measurement system,impacting the accuracy and reliability of noncontact measurements.To address this challenge,a thermal airflow distortion correction model based on the transformer attention mechanism is proposed specifically for the measurement of thermal warpage in microelectronic packaging structures.This model avoids the oversmoothing issue associated with convolutional neural networks and the lack of physical constraints in generative adversarial networks,ensuring the precision of grayscale gradient changes in speckle patterns and minimizing adverse effects on DIC calculation accuracy.By inputting the distorted images captured by the DIC measurement system into the network,corrected images are obtained for 3D-DIC calculations,thus allowing the thermal warpage measurement results of the sample to be acquired.Through experiments measuring topography with customized step block specimens,the effectiveness of the proposed method in improving warpage measurement accuracy is confirmed;this is particularly true when captured images are affected by thermal airflow at 140°C and 160°C,temperatures commonly encountered in thermal reliability testing of packaging structures.The method successfully reduces the standard deviation from 9.829 to 5.943μm and from 12.318 to 6.418μm,respectively.The results demonstrate the substantial practical value of this method for measuring thermal warpage in microelectronic packaging structures.
基金Jiangxi Provincial Cultivation Program for Academic and Technical Leaders of Major Subjects,Grant/Award Number:20225BCJ23008Jiangxi Provincial Natural Science Foundation,Grant/Award Number:20224ACB214008+2 种基金Xiamen Major Science and Technology Plan Program,Grant/Award Number:3502Z20221014National Natural Science Foundation of China,Grant/Award Number:52165043Anhui Natural Science Foundation,Grant/Award Number:2308085ME171。
文摘Titanium(Ti)dental scaffolds are widely used in dental prosthetics due to their excellent mechanical properties and biocompatibility.However,conventional Ti scaffolds manufactured through machining often do not fit perfectly with the bone defect site.Laser powder bed fusion(LPBF)technology enables the personalised manufacturing of custom-made Ti scaffolds.A custom-made Ti scaffold was prepared using LPBF and its surface roughness was improved through chemical polishing.To enhance the surface roughness,a nitric acid mixed solution with a specific composition of HF:HNO_(3):C_(3)H_(6)O_(3)=2:2:3 was used.The polishing mechanism was investigated by adjusting the F/Ti ratio to control the formation and dissolution of the oxide film.As a result,the surface of the Ti scaffold after polishing exhibited a smooth and flat appearance compared to the LPBF part,with a reduced surface roughness(Ra)of 1.23±0.19μm.The custom-made Ti scaffold also demonstrated favourable mechanical properties,with a bending strength of 335.18±33.62 MPa and stiffness of 2.13±0.21 GPa.Furthermore,in vitro cell tests confirmed the excellent biocompatibility of the custom-made Ti scaffold.The authors present a feasible strategy for the further clinical application of custom-made Ti scaffolds,offering enhanced surface properties and addressing the limitations of conventional machining methods.
基金supported by the National Key R&D Program of China(2020YFC1909105)。
文摘With the deepening understanding for the concept of sustainable development,the utilization of minerals is no longer limited to the traditional way.In this study,an environment friendly method for preparing Fe-Al_(2)O_(3)composites by using natural minerals was investigated.Additionally,the effects of CeO_(2)on the properties of composites were studied.The mechanical properties of Fe-Al_(2)O_(3)composites prepared by natural minerals are affected by the brittleness of glass phase.The strength and toughness of the glass phase in the composite are improved successfully by using rare earth oxides,indicating that the natural rare earths in Bayan Obo minerals have an enhanced influence on the properties of composite materials.The results show that the properties of glass phase can be significantly improved by addition of CeO_(2).At the optimal addition of 3 wt%CeO_(2),the composite achieves the density of 4.21 g/cm^(3),flexural strength of 401 MPa,Vickers hardness of 13.07 GPa and fracture toughness of 6.58 MPa·m^(1/2).The composite has excellent mechanical properties,which can be used in engineering as a cheap structural material.This study aims at reducing waste emissions,improving energy efficiencies and avoiding waste of rare earth resources during the preparation of composite materials.
基金This work was supported by Natural Science Foundation of China Grant No.30840029Grants for Doctorate Program of New Teacher,Ministry of Education of China,No.20070183062,No.200801831064the Excellent Youth Program of the Jilin Provincial Science&Technology Department,China,Grant No.20070111.
文摘Antimicrobial peptides(AMPs),with their extraordinary properties,such as broad-spectrum activity,rapid action and difficult development of resistance,have become promising molecules as new antibiotics.Despite their various mechanisms of action,the interaction of AMPs with the bacterial cell membrane is the key step for their mode of action.Moreover,it is generally accepted that the membrane is the primary target of most AMPs,and the interaction between AMPs and eukaryotic cell membranes(causing toxicity to host cells)limits their clinical application.Therefore,researchers are engaged in reforming or de novo designing AMPs as a‘singleedged sword’that contains high antimicrobial activity yet low cytotoxicity against eukaryotic cells.To improve the antimicrobial activity of AMPs,the relationship between the structure and function of AMPs has been rigorously pursued.In this review,we focus on the current knowledge of α-helical cationic antimicrobial peptides,one of the most common types of AMPs in nature.
基金partially supported by the grant of the Project from the State Key Laboratory of Cancer Biology(No.CBSKL2019ZZ07).
文摘Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.
基金This work was supported by the National Natural Science Founda- tion of China （Grant Nos. 81373445 to Y. X. C. and 81272471 to H. Y. J.）, the Innovative Team of Peptide Drugs of Jilin Province （No. 20121807, Y. X. C.）, the Natural Science Foundation of Jilin Prov- ince （No. 20140101042JC, Y. B. H.）, and a Basic Scientific Research Grants from Jilin University （Y. X. C. and Y. B. H）.
文摘A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic a-helical antimicrobial peptide A12L/A20L （Ac-KWKSFLKTFKSLK KTVLHTLLKAISS-amide） was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activi- ties of o-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitu- tions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram- positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial pep- tides with enhanced specificity.
基金financial support from the National Key R&D Program of China(2017YFA0303701)the National Natural Science Foundation of China(91850204 and 12174186)support from the Dengfeng Project B of Nanjing University。
文摘Microscopy is very important in research and industry,yet traditional optical microscopy suffers from the limited field-of-view(FOV)and depth-of-field(DOF)in high-resolution imaging.We demonstrate a simultaneous large FOV and DOF microscope imaging technology based on a chip-scale metalens device that is implemented by a SiNxmetalens array with a co-and cross-polarization multiplexed dual-phase design and dispersive spectrum zoom effect.A 4-mm×4-mm FOV is obtained with a resolution of 1.74μm and DOF of200μm within a wavelength range of 450 to 510 nm,which definitely exceeds the performance of traditional microscopes with the same resolution.Moreover,it is realized in a miniaturized compact prototype,showing an overall advantage for portable and convenient microscope technology.
