Large Hollow nanoparticulate aggregates（LHNAs） based on albumin nanoparticles is a promising technology for developing dry powder inhaler（DPI） with good aerodynamic properties in order to provide a new drug delive...Large Hollow nanoparticulate aggregates（LHNAs） based on albumin nanoparticles is a promising technology for developing dry powder inhaler（DPI） with good aerodynamic properties in order to provide a new drug delivery system（DDS） for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide（BUD） interactions with bovine serum albumin（BSA） at the molecular level. The molecular dynamics（MD） simulation revealed that there were three critical stable binding sites of BUD on BSA（P1, P2, P3） mainly by hydrophobic interaction and hydrogen bond. The energy decomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.展开更多
The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Betwee...The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Between February 2021 and February 2023,247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned(1∶1)to receive CDDP(n=126)or placebo(n=121),with a follow-up of 48 weeks.Compared with the placebo group,the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment(least squares mean:3.31;95%confidence interval[CI]:1.72–4.90;P<0.001)and at the 48-week follow-up(least squares mean:4.35;95%CI:2.76–5.94;P<0.001).Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24-and 48-week visits with no significant difference between the two groups(P>0.1 for all).The incidence of major adverse cardiovascular and cerebrovascular events was 6.35%in the CDDP group and 5.79%in the placebo group(P=0.822).Notably,no serious adverse events were attributed to CDDP.These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.展开更多
The first experiments on laser-driven cylindrical gold foam hohlraums have been performed at the 100 kJ SG-Ⅲ laser facility.Measurements of the expanding plasma emission show that there is less expanding plasma fill ...The first experiments on laser-driven cylindrical gold foam hohlraums have been performed at the 100 kJ SG-Ⅲ laser facility.Measurements of the expanding plasma emission show that there is less expanding plasma fill in foam hohlraums with a wall density of 0.8 g/cm^(3) than in solid gold hohlraums.The radiation temperatures at different angles confirm these results.Simulation results show that the expanding plasma density in the foam hohlraums is lower than in the solid hohlraums,resulting in less expanding plasma emission and higher radiation temperature.Thus,foam gold hohlraums have advantages in reducing wall plasma filling and improving X-ray transmission,which has potential applications in achieving a higher fusion yield.展开更多
Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the deve...Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the development and progression of ALI.During ALI,neutrophils generate neutrophil extracellular traps(NETs),and excessive NETs can intensify inflammatory injury.Research indicates that Taohe Chengqi decoction(THCQD)can ameliorate sepsis-induced lung inflammation and modulate immune function.This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients,seeking to provide novel perspectives and interventions for clinical treatment.The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture(CLP)-induced ALI mouse model.Furthermore,THCQD diminished neutrophil and macrophage infiltration,inflammatory responses,and the production of pro-inflammatory cytokines,including interleukin-1β(IL-1β),IL-6,and tumor necrosis factorα(TNF-α).Notably,subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro.Moreover,THCQD significantly decreased the expression of peptidyl arginine deiminase 4(PAD4)protein,and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4.PAD4 overexpression partially reversed THCQD’s inhibitory effects on PAD4.These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.展开更多
Cyclocarya paliurus, an economically valuable tree species, has traditionally been used as a nutraceutical food or medicine in China. However, limited information is available on its genotype selection and cultivation...Cyclocarya paliurus, an economically valuable tree species, has traditionally been used as a nutraceutical food or medicine in China. However, limited information is available on its genotype selection and cultivation under a wide range of environmental conditions for growth and targeted health-promoting substances. We studied the effects of genotype and environment, and their interaction on leaf triterpenoid content and tree growth for 12 genotypes of C. paliurus grown at four sites. We quantified the correlation between leaf triterpenoid accumulation and tree growth. The contents of cyclocaric acid B, cyclocarioside I, and arjunolic acid ranged from 0.06 to 3.89, 0 to 3.71, and 0.65 to 8.86 mg g^-1, respectively. Three individual triterpenoids were primarily influenced by genotype (variation ranged from 53.7 to 68.0%), while environment accounted for most of the variation in total triterpenoid content and tree growth (71.3–89.5%). Most tested environmental parameters were significantly correlated to total triterpenoid content, but not to the contents of the individual triterpenoids measured. Growth in tree height and diameter at breast height were significantly negatively correlated with total triterpenoid content but were non-significantly correlated with individual triterpenoid contents. We conclude that genotypic selection, manipulation of environmental conditions, and implementation of appropriate silvicultural operations would be important strategies for increasing the accumulation of health-promoting phytochemicals.展开更多
AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was r...AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.展开更多
Thermal stable intermetallic particles are important for the heat resistance of magnesium(Mg)alloys.In this work,many lath-like particles formed in α-Mg grains of a Mg-8Gd-3Sm-0.7Al casting alloy when heat-treated at...Thermal stable intermetallic particles are important for the heat resistance of magnesium(Mg)alloys.In this work,many lath-like particles formed in α-Mg grains of a Mg-8Gd-3Sm-0.7Al casting alloy when heat-treated at 873 K.Atomic-resolution high-angle annular dark field scanning transmission electron microscopy(HAADF-STEM) characterizations indicate that most of them are Mg-containing Al_(2)(Gd,Sm),with the atomic ratio of Mg:Al:(Gd,Sm) being ~1:1:1;a small part of them with relatively wider thickness are long-period stacking ordered(LPSO) phases simultaneously containing both 14H and 18R structures.Both followed common orientation relationships with Mg matrix as those reported in previous work.In addition,many Mg laths were observed in the primary blocky Al_(2)(Gd,Sm) phase at grain boundaries,where the atomic ratio of Al:(Gd,Sm) in the Al_(2)(Gd,Sm) matrix was 2:1.Finally,density functional theory(DFT) calculations illustrated the detail structure of the re-constructed Mg/Al_(2)RE interface and simultaneously deduced the underlying reason for the re-dissolution of the newly formed Mg-containing Al_(2)(Gd,Sm) plates in α-Mg matrix.展开更多
Relationship between precipitation strengthening and creep resistance improvement has been an impor-tant topic for the widespread applications of magnesium alloys.Generally,static precipitation strength-ening through ...Relationship between precipitation strengthening and creep resistance improvement has been an impor-tant topic for the widespread applications of magnesium alloys.Generally,static precipitation strength-ening through thermal stable precipitates would generate satisfactory creep resistance.However,an op-posite example is presented in this work and we propose that the size of precipitates plays a crucial role in controlling the operative creep mechanisms.In addition,the precipitate components along with their crystal structures in the crept Mg-4Al-3Sm-0.4Mn samples with/without pre-aging were thor-oughly studied using Cs aberration-corrected high-angle annular dark-field scanning transmission elec-tron microscopy(HAADF-STEM).Previous aging generates a large density of fine precipitates(<~5 nm)homogeneously distributing in Mg matrix and exhibiting satisfactory strengthening effect.However,the number density of precipitate strings consisting of several or even dozens of relatively coarse precipitates(~10 nm)was significantly decreased at the same time.As revealed in this work,the relatively coarse particles in Mg matrix are much more efficient than the fine precipitates in promoting dislocation climb.Therefore,the rate-controlling mechanisms are transferred from dislocation climb to dislocation slip after previous aging,thus leading to degradation of creep resistance.Moreover,there are mainly five types of precipitates/clusters,namelyβ"-(Al,Mg)3Sm,Al5Sm3,ordered Al-Sm cluster,ordered Al-Mn cluster and ordered/unordered AlMnSm clusters.The crystal structures of the former two precipitates were discussed and the formation mechanisms of the precipitates/clusters were revealed.展开更多
The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the p...The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury.All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University,China(approval No.XJTULAC2017-067)on August 26,2017.展开更多
BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), a...BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), and CTCs with both markers(E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer(LC).AIM To clarify the diagnostic value of CTCs categorized by EMT markers in LC.METHODS The study included 106 patients with lung adenocarcinoma, including 42 groundglass opacities(GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol TM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic(ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.RESULTS Of the 106 LC cases, 94(89.6%) had at least one CTC. CTCs were detectable in 35(83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of MCTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients(80.95% for GGO patients) and the specificity was 78.57%.The Kappa value was 0.415,indicating relative consistency between CanPatrol TM and CytoploRare.CONCLUSION CTC detection is valuable for distinguishing LC from controls,and particularly E&M-CTC detection warrants further study.展开更多
A recently proposed octahedral spherical hohlraum with six laser entrance holes(LEHs)is an attractive concept for an upgraded laser facility aiming at a predictable and reproducible fusion gain with a simple target de...A recently proposed octahedral spherical hohlraum with six laser entrance holes(LEHs)is an attractive concept for an upgraded laser facility aiming at a predictable and reproducible fusion gain with a simple target design.However,with the laser energies available at present,LEH size can be a critical issue.Owing to the uncertainties in simulation results,the LEH size should be determined on the basis of experimental evidence.However,determination of LEH size of an ignition target at a small-scale laser facility poses difficulties.In this paper,we propose to use the prepulse of an ignition pulse to determine the LEH size for ignition-scale hohlraums via LEH closure behavior,and we present convincing evidence from multiple diagnostics at the SGIII facility with ignition-scale hohlraum,laser prepulse,and laser beam size.The LEH closure observed in our experiment is in agreement with data from the National Ignition Facility.The total LEH area of the octahedral hohlraum is found to be very close to that of a cylindrical hohlraum,thus successfully demonstrating the feasibility of the octahedral hohlraum in terms of laser energy,which is crucially important for sizing an ignition-scale octahedrally configured laser system.This work provides a novel way to determine the LEH size of an ignition target at a small-scale laser facility,and it can be applied to other hohlraum configurations for the indirect drive approach.展开更多
Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: ...Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies.Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth.Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression.Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance.Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.展开更多
A high-pressure die casting(HPDC)Mg-5Gd-1.5Sm-0.7Al alloy was newly developed and exhibits outstanding strength-ductility synergy,with the yield strength and the tensile elongation to fracture being approximately 200 ...A high-pressure die casting(HPDC)Mg-5Gd-1.5Sm-0.7Al alloy was newly developed and exhibits outstanding strength-ductility synergy,with the yield strength and the tensile elongation to fracture being approximately 200 MPa and 8.5%,respectively.This alloy has two types of a-Mg grains:coarse a_(1)-Mg((46±18)μm)and fine a_(2)-Mg((9.2±2.3)μm)grains,and various Al-GS(GS=Gd and Sm)particles located at grain boundaries while clear solute-atom segregation near grain boundaries with limited or free intermetallic particles.Characterizations using Cs-corrected high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM)indicate the crystal structures of Al-GS phases.After aging,denseβ'precipitates and chain-shapedβ''-like structures precipitated near grain boundaries while a high density of ultrafineβ''-(Mg,Al)3Sm precipitates and Al-GS clusters formed in grain center.Relatively fine grains,Al-GS primary particles,solute-atom segregation near grain boundaries,and/or multiple precipitates contribute to the high strength of the studied alloy,while the multi-scale a-Mg grains,variety of intermetallic particles but discontinuous skeleton,and the multi-typed precipitated lead to its satisfactory ductility.展开更多
A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material...A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed.A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV.The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample.The results agree well owing to the symmetrical radiation in the secondary cavity.A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux,and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis,and also to agree well with the result of a simulation using the HYADES opacity.展开更多
The first laser–plasma interaction experiment using lasers of eight beams grouped into one octad has been conducted on the Shenguang Octopus facility.Although each beam intensity is below its individual threshold for...The first laser–plasma interaction experiment using lasers of eight beams grouped into one octad has been conducted on the Shenguang Octopus facility.Although each beam intensity is below its individual threshold for stimulated Brillouin backscattering(SBS),collective behaviors are excited to enhance the octad SBS.In particular,when two-color/cone lasers with wavelength separation 0.3 nm are used,the backward SBS reflectivities show novel behavior in which beams of longer wavelength achieve higher SBS gain.This property of SBS can be attributed to the rotation of the wave vectors of common ion acoustic waves due to the competition of detunings between geometrical angle and wavelength separation.This mechanism is confirmed using massively parallel supercomputer simulations with the three-dimensional laser–plasma interaction code LAP3D.展开更多
The exact evolutionary history of any set of biological taxa is unknown, and all phylogenetic reconstructions are approximations. The problem becomes harder when one must consider a mix of vertical and lateral phyloge...The exact evolutionary history of any set of biological taxa is unknown, and all phylogenetic reconstructions are approximations. The problem becomes harder when one must consider a mix of vertical and lateral phylogenetic signals. In this paper we propose a game theoretic approach to constructing biological networks. The key hypothesis is that evolution is driven by distinct mechanisms that seek to maximize two competing objectives, taxonomic conservation and diversity. One branch of the mathematical theory of games is brought to bear. It translates this evolutionary game hypothesis into a mathematical model in two-player zero-sum games, with the zero-sum assumption conforming to one of the fundamental constraints in nature in mass and energy conservation. We demonstrate why and how a mechanistic and localized adaptation to seek out greater information for conservation and diversity may always lead to a global Nash equilibrium in phylogenetic affinity. Our game theoretic method, referred to as bioinformatic game theory, is used to construct network clusters. As an example, we applied this method to clustering of a multidomain protein family. The protein clusters identified were consistent with known protein subfamilies, indicating that this game-theoretic approach provides a new framework in biological sequence analysis, especially in studying gene-genome and domain-protein relationships.展开更多
The rational construction of active targeting liposomes will provide an important structural support for its effective brain targeting.However,there is no clear understanding of the structure-activity relationship of ...The rational construction of active targeting liposomes will provide an important structural support for its effective brain targeting.However,there is no clear understanding of the structure-activity relationship of active targeting liposomes.Combining multiscale computational simulation and experimental verification,we established a computational model of RVGP modified PEGylated liposomes(RVGP-PEG-L)and investigated the role of PEG and molecular interaction mechanism of carrier-ligand-receptor.The result indicated that the complex network conformation formed by PEG with 42 monomers(42 PEG)above the density of 8%was the molecular basis for PEG-L to achieve long-circulation function.The lowest monomer number of PEG linker to ensure the targeting ability of RVGP was 42.However,the pose of RVGP binding to nAChR changed after it was linked with PEG-L due to the restraint of PEG chain,leading to a decrease of binding free energy.Increasing the monomer number of PEG linker or improving the non-polarity of polymers was a potential strategy to enhance the combination of RVGP-PEG-L with nAChR on the targeting cell.展开更多
基金The National Natural Science Foundation of China(Grant No.81202469)Founder of new drug research fund(Grant No.20130527)
文摘Large Hollow nanoparticulate aggregates（LHNAs） based on albumin nanoparticles is a promising technology for developing dry powder inhaler（DPI） with good aerodynamic properties in order to provide a new drug delivery system（DDS） for the treatment of lung disease. Improved understanding of molecular interactions could lead to prepare the DDS rationally. Therefore, this investigation utilized computations and experiments to reveal the mechanisms of budesonide（BUD） interactions with bovine serum albumin（BSA） at the molecular level. The molecular dynamics（MD） simulation revealed that there were three critical stable binding sites of BUD on BSA（P1, P2, P3） mainly by hydrophobic interaction and hydrogen bond. The energy decomposition of each residue to the whole BUD-BSA complex system in P1-P3 showed that nonpolar residues in or around the binding site played an important role in the binding of BUD to BSA. The molar ratio was close to 3 in preparations in drug-loading efficiency experiment, which was confirmed to the simulation results. The details of the binding sites from computation provided a guideline for the design of the BSA nanoparticles carrying BUD, which was prepared successfully at last. Combination of the MD simulation and experiment as well as the mechanism of the molecular interaction provided a solid theoretical basis for the preparation of BSA-LHNAs for DPI in the future.
基金supported by Tasly Pharmaceutical Group Co.,Ltd.(Grant No.303100031BA20)。
文摘The current study aimed to evaluate the efficacy and safety of Compound Danshen Dripping Pills(CDDP)in improving cardiac function in patients with acute anterior ST-segment elevation myocardial infarction(AAMI).Between February 2021 and February 2023,247 eligible patients with AAMI after primary percutaneous coronary intervention were enrolled and randomly assigned(1∶1)to receive CDDP(n=126)or placebo(n=121),with a follow-up of 48 weeks.Compared with the placebo group,the CDDP group demonstrated a significant increase in left ventricular ejection fraction values after 24 weeks of treatment(least squares mean:3.31;95%confidence interval[CI]:1.72–4.90;P<0.001)and at the 48-week follow-up(least squares mean:4.35;95%CI:2.76–5.94;P<0.001).Significant reductions in N-terminal pro-B-type natriuretic peptide levels were observed in both groups at the 24-and 48-week visits with no significant difference between the two groups(P>0.1 for all).The incidence of major adverse cardiovascular and cerebrovascular events was 6.35%in the CDDP group and 5.79%in the placebo group(P=0.822).Notably,no serious adverse events were attributed to CDDP.These findings suggest that CDDP may be well tolerated and could improve left ventricular ejection fraction in patients with AAMI at 24 and 48 weeks.
基金support from the National Natural Science Foundation of China(Grant Nos.11775204 and 12105269)the Presidential Foundation of the China Academy of Engineering Physics(Grant No.YZJJLX2018011)。
文摘The first experiments on laser-driven cylindrical gold foam hohlraums have been performed at the 100 kJ SG-Ⅲ laser facility.Measurements of the expanding plasma emission show that there is less expanding plasma fill in foam hohlraums with a wall density of 0.8 g/cm^(3) than in solid gold hohlraums.The radiation temperatures at different angles confirm these results.Simulation results show that the expanding plasma density in the foam hohlraums is lower than in the solid hohlraums,resulting in less expanding plasma emission and higher radiation temperature.Thus,foam gold hohlraums have advantages in reducing wall plasma filling and improving X-ray transmission,which has potential applications in achieving a higher fusion yield.
基金supporteded by the National Natural ScienceFoundation of China(Nos.82374183,82405092,82204991,82274246,and 82374341)the Planned Science TechnologyProjectofGuangzhouCity(Nos.2023A03J0419and2023A03J0420)+3 种基金the General Project of Natural Science Foundationof Guangdong Province(No.2023A1515011090)Hong KongScholars Program 2024(No.XJ2024005)the Basic and AppliedBasic Research Foundation of Guangdong Province(No.2021A151510809)the Project of Administration of TraditionalChinese Medicine of Guangdong Province of China(No.20223013).
文摘Acute lung injury(ALI)is a significant complication of sepsis,characterized by high morbidity,mortality,and poor prognosis.Neutrophils,as critical intrinsic immune cells in the lung,play a fundamental role in the development and progression of ALI.During ALI,neutrophils generate neutrophil extracellular traps(NETs),and excessive NETs can intensify inflammatory injury.Research indicates that Taohe Chengqi decoction(THCQD)can ameliorate sepsis-induced lung inflammation and modulate immune function.This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients,seeking to provide novel perspectives and interventions for clinical treatment.The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture(CLP)-induced ALI mouse model.Furthermore,THCQD diminished neutrophil and macrophage infiltration,inflammatory responses,and the production of pro-inflammatory cytokines,including interleukin-1β(IL-1β),IL-6,and tumor necrosis factorα(TNF-α).Notably,subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro.Moreover,THCQD significantly decreased the expression of peptidyl arginine deiminase 4(PAD4)protein,and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4.PAD4 overexpression partially reversed THCQD’s inhibitory effects on PAD4.These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
基金supported by the National Natural Science Foundation of China(Grant No.31470637)the Collaborative Innovation Plan of Jiangsu Higher Educationthe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Cyclocarya paliurus, an economically valuable tree species, has traditionally been used as a nutraceutical food or medicine in China. However, limited information is available on its genotype selection and cultivation under a wide range of environmental conditions for growth and targeted health-promoting substances. We studied the effects of genotype and environment, and their interaction on leaf triterpenoid content and tree growth for 12 genotypes of C. paliurus grown at four sites. We quantified the correlation between leaf triterpenoid accumulation and tree growth. The contents of cyclocaric acid B, cyclocarioside I, and arjunolic acid ranged from 0.06 to 3.89, 0 to 3.71, and 0.65 to 8.86 mg g^-1, respectively. Three individual triterpenoids were primarily influenced by genotype (variation ranged from 53.7 to 68.0%), while environment accounted for most of the variation in total triterpenoid content and tree growth (71.3–89.5%). Most tested environmental parameters were significantly correlated to total triterpenoid content, but not to the contents of the individual triterpenoids measured. Growth in tree height and diameter at breast height were significantly negatively correlated with total triterpenoid content but were non-significantly correlated with individual triterpenoid contents. We conclude that genotypic selection, manipulation of environmental conditions, and implementation of appropriate silvicultural operations would be important strategies for increasing the accumulation of health-promoting phytochemicals.
基金Supported by The National Natural Science Foundation of China,No.30873464the Research Foundation from Ministry of Education of China,No.108019the Natural Science Foundation of Beijing,China,No.7132150
文摘AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.
基金financially supported by the Scientific and Technological Developing Scheme of Jilin Province(Nos.YDZJ202301ZYTS538 and 20220101239JC)the Chinese Academy of Sciences Youth Innovation Promotion Association (No.2023234)+3 种基金the National Natural Science Foundation of China (No.U21A20323)the Scientific and Technological Developing Scheme of Jilin Province (No.SKL202302038)the Major Scientific and Technological Projects of Hebei Province (No.23291001Z)the Scientific and Technology Project of Hanjiang District。
文摘Thermal stable intermetallic particles are important for the heat resistance of magnesium(Mg)alloys.In this work,many lath-like particles formed in α-Mg grains of a Mg-8Gd-3Sm-0.7Al casting alloy when heat-treated at 873 K.Atomic-resolution high-angle annular dark field scanning transmission electron microscopy(HAADF-STEM) characterizations indicate that most of them are Mg-containing Al_(2)(Gd,Sm),with the atomic ratio of Mg:Al:(Gd,Sm) being ~1:1:1;a small part of them with relatively wider thickness are long-period stacking ordered(LPSO) phases simultaneously containing both 14H and 18R structures.Both followed common orientation relationships with Mg matrix as those reported in previous work.In addition,many Mg laths were observed in the primary blocky Al_(2)(Gd,Sm) phase at grain boundaries,where the atomic ratio of Al:(Gd,Sm) in the Al_(2)(Gd,Sm) matrix was 2:1.Finally,density functional theory(DFT) calculations illustrated the detail structure of the re-constructed Mg/Al_(2)RE interface and simultaneously deduced the underlying reason for the re-dissolution of the newly formed Mg-containing Al_(2)(Gd,Sm) plates in α-Mg matrix.
基金Chinese Academy of Sciences Youth Innovation Promotion Association(No.2023234)Scientific and Technological Developing Scheme of Jilin Province(No.20220402012GH)+2 种基金National Natural Science Foundation of China(No.U21A20323)Capital Construction Fund within the Budget of Jilin Province(No.2023C044-2)Major science and technology projects of Jilin Province and Changchun City(No.20220301026GX),the Special high-tech。
文摘Relationship between precipitation strengthening and creep resistance improvement has been an impor-tant topic for the widespread applications of magnesium alloys.Generally,static precipitation strength-ening through thermal stable precipitates would generate satisfactory creep resistance.However,an op-posite example is presented in this work and we propose that the size of precipitates plays a crucial role in controlling the operative creep mechanisms.In addition,the precipitate components along with their crystal structures in the crept Mg-4Al-3Sm-0.4Mn samples with/without pre-aging were thor-oughly studied using Cs aberration-corrected high-angle annular dark-field scanning transmission elec-tron microscopy(HAADF-STEM).Previous aging generates a large density of fine precipitates(<~5 nm)homogeneously distributing in Mg matrix and exhibiting satisfactory strengthening effect.However,the number density of precipitate strings consisting of several or even dozens of relatively coarse precipitates(~10 nm)was significantly decreased at the same time.As revealed in this work,the relatively coarse particles in Mg matrix are much more efficient than the fine precipitates in promoting dislocation climb.Therefore,the rate-controlling mechanisms are transferred from dislocation climb to dislocation slip after previous aging,thus leading to degradation of creep resistance.Moreover,there are mainly five types of precipitates/clusters,namelyβ"-(Al,Mg)3Sm,Al5Sm3,ordered Al-Sm cluster,ordered Al-Mn cluster and ordered/unordered AlMnSm clusters.The crystal structures of the former two precipitates were discussed and the formation mechanisms of the precipitates/clusters were revealed.
基金supported by the Key Research Project of Science and Technology of Henan Province of China,No.14B180007(to LLF)the Development Project of Science and Technology of Luoyang Municipality of China,No.1401087A-5(to LLF)
文摘The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease.However,the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear.To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex,a model of Parkinson’s disease was established by injecting 8μg 6-hydroxydopamine into the substantia nigra compacta of rats.After 1 or 3 weeks,0.3μg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain.At 3 or 5 weeks after the initial injury,neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically.The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining.Results demonstrated that after injury,the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats.Compared with normal medial prefrontal cortical neurons,at 3 and 5 weeks after substantia nigra compacta injury,the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge,with an increased discharge interval.The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge,but the discharge interval was only higher at 3 weeks.At 3 weeks after the combined lesions,the discharge frequency,discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex.These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex.The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury.All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University,China(approval No.XJTULAC2017-067)on August 26,2017.
基金National Natural Science Foundation of China,No.81572285The Natural Science Foundation of Chongqing City,No.cstc2018jcyjAX0592The Army Medical University Clinical Medical Research Talent Training Program,No.2018XLC3062.
文摘BACKGROUND Circulating tumor cells(CTCs) can be clustered into three subtypes according to epithelial-mesenchymal transition(EMT) markers: CTCs with epithelial markers(E-CTCs), CTCs with mesenchymal markers(M-CTCs), and CTCs with both markers(E&M-CTCs). CTC detection has clinical implications in the diagnosis of lung cancer(LC).AIM To clarify the diagnostic value of CTCs categorized by EMT markers in LC.METHODS The study included 106 patients with lung adenocarcinoma, including 42 groundglass opacities(GGO) and 64 solid lesions, who underwent surgery between July 2015 and December 2019. Eleven patients with benign tumors and seventeen healthy controls were included. CTCs in peripheral blood and associated EMT markers were detected preoperatively using the CanPatrol TM technique. The diagnostic power of CTCs for discriminating LC cases from controls was analyzed by the receiver operating characteristic(ROC) curve. The CytoploRare technique was used in 20 cases and 18 controls for validation, and Kappa values were calculated to evaluate consistency between techniques.RESULTS Of the 106 LC cases, 94(89.6%) had at least one CTC. CTCs were detectable in 35(83.3%) of 42 GGO cases. Total CTCs and E&M-CTCs were significantly more frequent in LC cases than in benign or healthy controls. The proportion of MCTCs plus E&M-CTCs increased gradually from healthy controls, to benign controls, to LC cases. The area under the ROC curve of total CTCs and E&M-CTCs was > 0.8 and > 10.75, respectively. The combined sensitivity of total-CTCs and E&M-CTCs was 85.85% for LC patients(80.95% for GGO patients) and the specificity was 78.57%.The Kappa value was 0.415,indicating relative consistency between CanPatrol TM and CytoploRare.CONCLUSION CTC detection is valuable for distinguishing LC from controls,and particularly E&M-CTC detection warrants further study.
基金This work is supported by the National Natural Science Foundation of China(Grant No.12035002).
文摘A recently proposed octahedral spherical hohlraum with six laser entrance holes(LEHs)is an attractive concept for an upgraded laser facility aiming at a predictable and reproducible fusion gain with a simple target design.However,with the laser energies available at present,LEH size can be a critical issue.Owing to the uncertainties in simulation results,the LEH size should be determined on the basis of experimental evidence.However,determination of LEH size of an ignition target at a small-scale laser facility poses difficulties.In this paper,we propose to use the prepulse of an ignition pulse to determine the LEH size for ignition-scale hohlraums via LEH closure behavior,and we present convincing evidence from multiple diagnostics at the SGIII facility with ignition-scale hohlraum,laser prepulse,and laser beam size.The LEH closure observed in our experiment is in agreement with data from the National Ignition Facility.The total LEH area of the octahedral hohlraum is found to be very close to that of a cylindrical hohlraum,thus successfully demonstrating the feasibility of the octahedral hohlraum in terms of laser energy,which is crucially important for sizing an ignition-scale octahedrally configured laser system.This work provides a novel way to determine the LEH size of an ignition target at a small-scale laser facility,and it can be applied to other hohlraum configurations for the indirect drive approach.
基金supported by grants from the National Key Research and Development Program of China (Grant No.2017YFC1601702)China Postdoctoral Science Foundation (Grant No.2011M500825)
文摘Objective: Heat shock factor 1(HSF1), a transcriptional regulator of heat shock proteins(HSPs), is an attractive therapeutic target for cancer. However, only a few HSF1 inhibitors have been identified so far.Methods: The mRNA and protein levels of HSF1, HSPs, cleaved PARP, and phosphorylated HSF1 were examined by real-time PCR and Western blot. Forced expression, RNA interference, and immunofluorescence assay were used for mechanistic studies.Cell viability and apoptosis were measured by WST-8 assay and flow cytometry, respectively. Xenograft studies were performed in nude mice to evaluate the effect of dorsomorphin and an HSP90 inhibitor on tumor growth.Results: Dorsomorphin suppressed multiple stimuli-induced and constitutive HSPs expression in cancer cells. Mechanistic studies revealed that dorsomorphin reduced heat-induced HSP expression independent of adenosine monophosphate activated protein kinase. Dorsomorphin reduced heat-stimulated HSF1 Ser320 phosphorylation and nuclear translocation, as well as resting nuclear HSF1 levels in cancer cells. Dorsomorphin induced cancer cell apoptosis by inhibiting HSF1 expression. A structure-activity study revealed that the 4-pyridyl at the 3-site of the pyrazolo [1, 5-a]pyrimidine ring is critical for the anti-HSF1 activities of dorsomorphin. Dorsomorphin sensitized cancer cells to HSP90 and proteasome inhibitors and inhibited HSP70 expression induced by these inhibitors in vitro. In tumor-bearing nude mice, dorsomorphin enhanced HSP90 inhibitor-induced cancer cell apoptosis, tumor growth inhibition, and HSP70 expression.Conclusions: Dorsomorphin is an HSF1 inhibitor. It induces cancer cell apoptosis, sensitizes cancer cells to both HSP90 and proteasome inhibitors, and suppresses HSP upregulation by these drugs, which may prevent the development of drug resistance.Hence, dorsomorphin and its derivates may serve as potential precursors for developing drugs against cancer.
基金Project supported by the Scientific and Technological Developing Scheme of Jilin Province(20220101239JC,YDZJ202301ZYTS538)the Chinese Academy of Sciences Youth Innovation Promotion Association(2023234)。
文摘A high-pressure die casting(HPDC)Mg-5Gd-1.5Sm-0.7Al alloy was newly developed and exhibits outstanding strength-ductility synergy,with the yield strength and the tensile elongation to fracture being approximately 200 MPa and 8.5%,respectively.This alloy has two types of a-Mg grains:coarse a_(1)-Mg((46±18)μm)and fine a_(2)-Mg((9.2±2.3)μm)grains,and various Al-GS(GS=Gd and Sm)particles located at grain boundaries while clear solute-atom segregation near grain boundaries with limited or free intermetallic particles.Characterizations using Cs-corrected high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM)indicate the crystal structures of Al-GS phases.After aging,denseβ'precipitates and chain-shapedβ''-like structures precipitated near grain boundaries while a high density of ultrafineβ''-(Mg,Al)3Sm precipitates and Al-GS clusters formed in grain center.Relatively fine grains,Al-GS primary particles,solute-atom segregation near grain boundaries,and/or multiple precipitates contribute to the high strength of the studied alloy,while the multi-scale a-Mg grains,variety of intermetallic particles but discontinuous skeleton,and the multi-typed precipitated lead to its satisfactory ductility.
基金This work was supported by the National Natural Science Foundation of China(Grant No.12004351).
文摘A self-consistent and precise method to determine the time-dependent radiative albedo,i.e.,the ratio of the reemission flux to the incident flux,for an indirect-drive inertial confinement fusion Hohlraum wall material is proposed.A specially designed symmetrical triple-cavity gold Hohlraum is used to create approximately constant and near-equilibrium uniform radiation with a peak temperature of 160 eV.The incident flux at the secondary cavity waist is obtained from flux balance analysis and from the shock velocity of a standard sample.The results agree well owing to the symmetrical radiation in the secondary cavity.A self-consistent and precise time-dependent radiative albedo is deduced from the reliable reemission flux and the incident flux,and the result from the shock velocity is found to have a smaller uncertainty than that from the multi-angle flux balance analysis,and also to agree well with the result of a simulation using the HYADES opacity.
基金supported by the Natural Science Foundation of China(Grant Nos.11975059,12005021,and 11875241).
文摘The first laser–plasma interaction experiment using lasers of eight beams grouped into one octad has been conducted on the Shenguang Octopus facility.Although each beam intensity is below its individual threshold for stimulated Brillouin backscattering(SBS),collective behaviors are excited to enhance the octad SBS.In particular,when two-color/cone lasers with wavelength separation 0.3 nm are used,the backward SBS reflectivities show novel behavior in which beams of longer wavelength achieve higher SBS gain.This property of SBS can be attributed to the rotation of the wave vectors of common ion acoustic waves due to the competition of detunings between geometrical angle and wavelength separation.This mechanism is confirmed using massively parallel supercomputer simulations with the three-dimensional laser–plasma interaction code LAP3D.
文摘The exact evolutionary history of any set of biological taxa is unknown, and all phylogenetic reconstructions are approximations. The problem becomes harder when one must consider a mix of vertical and lateral phylogenetic signals. In this paper we propose a game theoretic approach to constructing biological networks. The key hypothesis is that evolution is driven by distinct mechanisms that seek to maximize two competing objectives, taxonomic conservation and diversity. One branch of the mathematical theory of games is brought to bear. It translates this evolutionary game hypothesis into a mathematical model in two-player zero-sum games, with the zero-sum assumption conforming to one of the fundamental constraints in nature in mass and energy conservation. We demonstrate why and how a mechanistic and localized adaptation to seek out greater information for conservation and diversity may always lead to a global Nash equilibrium in phylogenetic affinity. Our game theoretic method, referred to as bioinformatic game theory, is used to construct network clusters. As an example, we applied this method to clustering of a multidomain protein family. The protein clusters identified were consistent with known protein subfamilies, indicating that this game-theoretic approach provides a new framework in biological sequence analysis, especially in studying gene-genome and domain-protein relationships.
基金National Natural Science Foundation of China(Grant No.81202469)
文摘The rational construction of active targeting liposomes will provide an important structural support for its effective brain targeting.However,there is no clear understanding of the structure-activity relationship of active targeting liposomes.Combining multiscale computational simulation and experimental verification,we established a computational model of RVGP modified PEGylated liposomes(RVGP-PEG-L)and investigated the role of PEG and molecular interaction mechanism of carrier-ligand-receptor.The result indicated that the complex network conformation formed by PEG with 42 monomers(42 PEG)above the density of 8%was the molecular basis for PEG-L to achieve long-circulation function.The lowest monomer number of PEG linker to ensure the targeting ability of RVGP was 42.However,the pose of RVGP binding to nAChR changed after it was linked with PEG-L due to the restraint of PEG chain,leading to a decrease of binding free energy.Increasing the monomer number of PEG linker or improving the non-polarity of polymers was a potential strategy to enhance the combination of RVGP-PEG-L with nAChR on the targeting cell.
