CsPbI_(3)perovskite quantum dots(QDs)are ideal materials for the next generation of red light-emitting diodes.However,the low phase stability of CsPbI_(3)QDs and long-chain insulating capping ligands hinder the improv...CsPbI_(3)perovskite quantum dots(QDs)are ideal materials for the next generation of red light-emitting diodes.However,the low phase stability of CsPbI_(3)QDs and long-chain insulating capping ligands hinder the improvement of device performance.Traditional in-situ ligand replacement and ligand exchange after synthesis were often difficult to control.Here,we proposed a new ligand exchange strategy using a proton-prompted insitu exchange of short 5-aminopentanoic acid ligands with long-chain oleic acid and oleylamine ligands to obtain stable small-size CsPbI_(3)QDs.This exchange strategy maintained the size and morphology of CsPbI_(3)QDs and improved the optical properties and the conductivity of CsPbI_(3)QDs films.As a result,high-efficiency red QD-based light-emitting diodes with an emission wavelength of 645 nm demonstrated a record maximum external quantum efficiency of 24.45%and an operational half-life of 10.79 h.展开更多
BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primar...BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.展开更多
Perovskite solar cells(PSCs)have attracted aggressive attention in the photovoltaic field in light of the rapid increasing power conversion efficiency.However,their large-scale application and commercialization are li...Perovskite solar cells(PSCs)have attracted aggressive attention in the photovoltaic field in light of the rapid increasing power conversion efficiency.However,their large-scale application and commercialization are limited by the toxicity issue of lead(Pb).Among all the lead-free perovskites,tin(Sn)-based perovskites have shown potential due to their low toxicity,ideal bandgap structure,high carrier mobility,and long hot carrier lifetime.Great progress of Sn-based PSCs has been realized in recent years,and the certified efficiency has now reached over 14%.Nevertheless,this record still falls far behind the theoretical calculations.This is likely due to the uncontrolled nucleation states and pronounced Sn(Ⅳ)vacancies.With insights into the methodologies resolving both issues,ligand engineering-assisted perovskite film fabrication dictates the state-of-the-art Sn-based PSCs.Herein,we summarize the role of ligand engineering during each state of film fabrication,ranging from the starting precursors to the ending fabricated bulks.The incorporation of ligands to suppress Sn~(2+)oxidation,passivate bulk defects,optimize crystal orientation,and improve stability is discussed,respectively.Finally,the remained challenges and perspectives toward advancing the performance of Sn-based PSCs are presented.We expect this review can draw a clear roadmap to facilitate Sn-based PSCs via ligand engineering.展开更多
Oriented ligand immobilization is one of the most effective strategies used in the design and construction of a high-capacity protein A chromatography. In this work, cysteine was introduced as anchoring sites by subst...Oriented ligand immobilization is one of the most effective strategies used in the design and construction of a high-capacity protein A chromatography. In this work, cysteine was introduced as anchoring sites by substituting a specific residue on Helix Ⅰ, Ⅱ, and at C-terminus of antibody binding domain Z from protein A, respectively, to investigate structural evolution and binding behavior of protein A ligands at liquid-solid interfaces. Among the three affinity dextran-coated Fe_(3)O_(4) magnetic nanoparticles(Fe_(3)O_(4)@Dx MNPs), affinity MNPs with the immobilized ligand via N11C on Helix Ⅰ(Fe_(3)O_(4)@Dx-Z_(1) MNPs) had the highest helical content, and MNPs with the immobilized ligand via G29C on Helix Ⅱ(Fe_(3)O_(4)@Dx-Z_(2) MNPs) had the lowest helical content at the same pHs. It was attributed to less electrostatic attraction of ligand to negatively charged surface on Fe_(3)O_(4)@Dx-Z_(1) MNPs because of less positive charged residues on Helix Ⅰ(K6) than Helix Ⅱ(R27/K35). Among the three affinity MNPs, moreover, the highest affinity to immunoglobulin G(IgG) binding was observed on Fe_(3)O_(4)@Dx-Z_(1) MNPs in isothermal titration calorimetry measurement, further validating greater structural integrity of the ligand on Fe_(3)O_(4)@Dx-Z_(1) MNPs. Finally,the study of IgG binding on MNPs and 96-well plates showed that anchoring sites for ligand immobilization had distinct influences on IgG binding and IgG-mediated antigen binding. This work illustrated that anchoring sites of the ligands had a striking significance for the molecular structure of the ligand at liquid-solid interfaces and raised an important implication for the design and optimization of protein A chromatography and protein A-based immunoassay analysis.展开更多
Bimetallic nanoparticles exhibit a synergistic effect that critically depends on their surface composition,but such promotion mechanisms become vague with varying surface compositions.Here,alumina supported Ag@Pd core...Bimetallic nanoparticles exhibit a synergistic effect that critically depends on their surface composition,but such promotion mechanisms become vague with varying surface compositions.Here,alumina supported Ag@Pd core–shell and PdAg alloy structure with controlled size and surface compositions were prepared to demonstrate synergetic mechanisms,particularly,ligand and strain effects on activity and ethylene selectivity for acetylene hydrogenation.The performance evaluation indicates that Ag@Pd catalysts with well-controlled Pd-shell thickness can effectively lower apparent activation energy and improve ethylene selectivity.Hydrogenation activity increases from 0.019 to 0.062 s^(-1) with decreasing Pd-shell thickness under mild conditions,which is 3–6 times higher than their alloyed and monometallic counterparts.Combined characterizations and density functional theory are conducted to reveal such shell-thickness-dependent performance.The ligand effect arising from Ag alloying in the interface of Ag@Pd2ML observes the strongest binding of acetylene,but it diminished sharply and the strain effect gets more prevailing with increasing shell thickness.The competition of ethylene desorption and deephydrogenation were also investigated to understand the selectivity governing factors,and the selectivity descriptor(0.5BE(C_(2)H_(4))–BE(H))was built to match the contribution of ligand and strain effect on the different surfaces of Pd-Ag bimetallic NPs.The exploration of synergetic mechanisms among bimetallic NPs with varied structure and surface compositions in this work can help us to deepen the understanding catalyst structure–activity relationship and provide a feasible way to optimize the overall catalytic performance.展开更多
The design of efficient and robust non-precious metal electrocatalysts towards oxygen evolution reaction(OER)is of great value for developing green energy technologies.The in-situ formed high-valence(oxy)hydroxides sp...The design of efficient and robust non-precious metal electrocatalysts towards oxygen evolution reaction(OER)is of great value for developing green energy technologies.The in-situ formed high-valence(oxy)hydroxides species during the reconstruction process of pre-catalysts are recognized as the real contributing sites for OER.However,pre-catalysts generally undergo a slow and inadequate self-reconstruction.Herein,we reported a PO^(3-)_(4)optimized CoFe-based OER catalysts with amorphous structure,which enables a fast and deep reconstruction during the OER process.The amorphous structure induced by ligands PO^(3-)_(4)is prone to evolution and further form active species for OER.The electron interaction between metal sites can be modulated by electron-rich PO^(3-)_(4),which promotes generation of high active CoOOH.Simultaneously,the etching of PO^(3-)_(4)from the pre-catalysts during the catalytic process is in favor of accelerating the self-reconstruction.As a result,as-prepared precatalyst can generate high active CoOOH at a low potential of 1.4 V and achieve an in-depth reconstructed nanosheet structure with abundant OER active sites.Our work provides a promising design of pre-catalysts for realizing efficient catalysis of water oxidation.展开更多
Deep-level defects and random oriented configuration in perovskite crystallization process would cause the nonradiative recombination and further affect the performance of perovskite solar cells(PSCs).Herein,two metal...Deep-level defects and random oriented configuration in perovskite crystallization process would cause the nonradiative recombination and further affect the performance of perovskite solar cells(PSCs).Herein,two metal-organic frameworks(MOFs)with tunable Lewis-base passivation sites have been constructed(Cd-Httb and Cd-Httb-BDC,Httb=5-(4-(1H-1,2,4-triazole-1-yl)benzyl)-1h-tetrazole,BDC=1,4-dicarboxybenzene)to eliminate deep-level defects and simultaneously as nanostructured heterogeneous nucleation seed to assist the growth of large-grained perovskite films.Compared with the control and Cd-Httb,Cd-Httb-BDC designed with mix-ligands strategy exhibited the enhanced inducted effect on the crystallization and nucleation of high-quality perovskite films during annealing process.Consequently,the resultant Cd-Httb-BDC-modified device achieved higher power conversion efficiency(PCE)(22.18%)than the control(20.89%)and Cd-Httb(21.56%).Meanwhile,the unencapsulated Cd-Httb-BDC-modified device still maintained 90%of initial PCE after 1500 h in ambient conditions and exhibited enhanced thermal stability(85℃ in N_(2) atmosphere).This work presented a successful example of mixligands strategy on construction of high-quality MOF-assisted perovskite films for high-efficient and stable PSCs.展开更多
The performance of inverted quantum-dot light-emitting diodes(QLEDs)based on solution-processed hole transport layers(HTLs)has been limited by the solvent-induced damage to the quantum dot(QD)layer during the spin-coa...The performance of inverted quantum-dot light-emitting diodes(QLEDs)based on solution-processed hole transport layers(HTLs)has been limited by the solvent-induced damage to the quantum dot(QD)layer during the spin-coating of the HTL.The lack of compatibility between the HTL’s solvent and the QD layer results in an uneven surface,which negatively impacts the overall device performance.In this work,we develop a novel method to solve this problem by modifying the QD film with 1,8-diaminooctane to improve the resistance of the QD layer for the HTL’s solvent.The uniform QD layer leads the inverted red QLED device to achieve a low turn-on voltage of 1.8 V,a high maximum luminance of 105500 cd/m2,and a remarkable maximum external quantum efficiency of 13.34%.This approach releases the considerable potential of HTL materials selection and offers a promising avenue for the development of high-performance inverted QLEDs.展开更多
Colloidal synthesis of metal nanoclusters will inevitably lead to the blockage of catalytically active sites by organic ligands.Here,taking[Au_(25)(PET)_(18)]-(PET=2-phenylethanethiol)nanocluster as a model catalyst,t...Colloidal synthesis of metal nanoclusters will inevitably lead to the blockage of catalytically active sites by organic ligands.Here,taking[Au_(25)(PET)_(18)]-(PET=2-phenylethanethiol)nanocluster as a model catalyst,this work reports a feasible procedure to achieve the controllably partial removal of thiolate ligands from unsupported[Au_(25)(PET)_(18)]-nanoclusters with the preservation of the core structure.This procedure shortens the processing duration by rapid heating and cooling on the basis of traditional annealing treatment,avoiding the reconfiguration or agglomeration of Au_(25)nanoclusters,where the degree of dethiolation can be regulated by the control of duration.This work finds that a moderate degree of dethiolation can expose the Au active sites while maintaining the suppression of the competing hydrogen evolution reaction.Consequently,the activity and selectivity towards CO formation in electrochemical CO_(2)reduction reaction of Au_(25)nanoclusters can be promoted.This work provides a new approach for the removal of thiolate ligands from atomically precise gold nanoclusters.展开更多
We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More impor...We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.展开更多
Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activit...Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.展开更多
Cancer is one of the most prevalent diseases worldwide,which causes significant morbidity and mortality.Designing and developing a potential anti-cancer drug is an active field of research worldwide.Microorganisms hav...Cancer is one of the most prevalent diseases worldwide,which causes significant morbidity and mortality.Designing and developing a potential anti-cancer drug is an active field of research worldwide.Microorganisms have been considered a potential source of anti-cancer drugs.One such microbe-derived compound is surfactin,which shows potential anti-cancer activities.In this study,we evaluated the binding potential of surfactin with several cancer cell ligands via an in-silico approach.Hence,molecular docking studies were performed to test the binding potential of surfactin against four targets.The analyses revealed that surfactin from Bacillus sp.can bind with the targeted ligands(coenzyme A,D-leucine,glycerol,and(R)-3-hydroxytetradecanal)with significant affinity.Surfactin showed the highest binding affinity(-7.7 kcal mol-1)to coenzyme A among the targeted ligands.These results may be useful for developing anti-cancer drugs.Nevertheless,further experimental studies are needed to investigate the ligand binding capacity and anti-cancer potential of such surfactin-like molecules.展开更多
N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning m...N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.展开更多
Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface li...Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells(LECs)were treated with or without PM2.5.Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity.Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs.Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding.Many other ligands showed no change in binding activity.For example,apolipoprotein E(ApoE),Notch2,and growth arrest-specific 6(Gas6)represent ligands with increased,decreased,or unchanged binding activity,respectively.Both ApoE and Gas6 are phagocytosis ligands,suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5.Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors,as quantified by ligand binding activity.This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.展开更多
BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene ...BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma(HCC).AIM To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.METHODS Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.RESULTS Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PDL1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes,fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence(P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival.CONCLUSION Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PDL1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.展开更多
In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is...In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.展开更多
AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing hum...AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.展开更多
基金This work was financially supported by the National Key Research and Development Program of China(2022YFB3602902)the Key Projects of National Natural Science Foundation of China(62234004)+5 种基金Innovation and Entrepreneurship Team of Zhejiang Province(2021R01003)Science and Technology Innovation 2025 Major Project of Ningbo(2022Z085)Ningbo 3315 Programme(2020A-01-B)YONGJIANG Talent Introduction Programme(2021A-038-B)Flexible Electronics Zhejiang Province Key Laboratory Fund Project(2022FEO02)Zhejiang Provincial Natural Science Foundation of China(LR21F050001).
文摘CsPbI_(3)perovskite quantum dots(QDs)are ideal materials for the next generation of red light-emitting diodes.However,the low phase stability of CsPbI_(3)QDs and long-chain insulating capping ligands hinder the improvement of device performance.Traditional in-situ ligand replacement and ligand exchange after synthesis were often difficult to control.Here,we proposed a new ligand exchange strategy using a proton-prompted insitu exchange of short 5-aminopentanoic acid ligands with long-chain oleic acid and oleylamine ligands to obtain stable small-size CsPbI_(3)QDs.This exchange strategy maintained the size and morphology of CsPbI_(3)QDs and improved the optical properties and the conductivity of CsPbI_(3)QDs films.As a result,high-efficiency red QD-based light-emitting diodes with an emission wavelength of 645 nm demonstrated a record maximum external quantum efficiency of 24.45%and an operational half-life of 10.79 h.
基金The study was approved by the hospital ethics committee and registered online(https://plataformabrasil.saude.gov.br,CAAE:26380019.6.0000.0065).
文摘BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.
基金supported by the National Natural Science Foundation of China(61935016,62275213 and 62205264),the National Natural Science Foundation of China(21961160720)the Fundamental Research Funds for Xi'an Jiaotong University(xzy012022092,xzd012022003 and xzy022022057)+1 种基金the National Key Research and Development Program of China(2022YFB3803300)the open research fund of Songshan Lake Materials Laboratory(2021SLABFK02)。
文摘Perovskite solar cells(PSCs)have attracted aggressive attention in the photovoltaic field in light of the rapid increasing power conversion efficiency.However,their large-scale application and commercialization are limited by the toxicity issue of lead(Pb).Among all the lead-free perovskites,tin(Sn)-based perovskites have shown potential due to their low toxicity,ideal bandgap structure,high carrier mobility,and long hot carrier lifetime.Great progress of Sn-based PSCs has been realized in recent years,and the certified efficiency has now reached over 14%.Nevertheless,this record still falls far behind the theoretical calculations.This is likely due to the uncontrolled nucleation states and pronounced Sn(Ⅳ)vacancies.With insights into the methodologies resolving both issues,ligand engineering-assisted perovskite film fabrication dictates the state-of-the-art Sn-based PSCs.Herein,we summarize the role of ligand engineering during each state of film fabrication,ranging from the starting precursors to the ending fabricated bulks.The incorporation of ligands to suppress Sn~(2+)oxidation,passivate bulk defects,optimize crystal orientation,and improve stability is discussed,respectively.Finally,the remained challenges and perspectives toward advancing the performance of Sn-based PSCs are presented.We expect this review can draw a clear roadmap to facilitate Sn-based PSCs via ligand engineering.
基金supported by the National Natural Science Foundation of China (Nos. 21878221 and 21476166)the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 21621004)。
文摘Oriented ligand immobilization is one of the most effective strategies used in the design and construction of a high-capacity protein A chromatography. In this work, cysteine was introduced as anchoring sites by substituting a specific residue on Helix Ⅰ, Ⅱ, and at C-terminus of antibody binding domain Z from protein A, respectively, to investigate structural evolution and binding behavior of protein A ligands at liquid-solid interfaces. Among the three affinity dextran-coated Fe_(3)O_(4) magnetic nanoparticles(Fe_(3)O_(4)@Dx MNPs), affinity MNPs with the immobilized ligand via N11C on Helix Ⅰ(Fe_(3)O_(4)@Dx-Z_(1) MNPs) had the highest helical content, and MNPs with the immobilized ligand via G29C on Helix Ⅱ(Fe_(3)O_(4)@Dx-Z_(2) MNPs) had the lowest helical content at the same pHs. It was attributed to less electrostatic attraction of ligand to negatively charged surface on Fe_(3)O_(4)@Dx-Z_(1) MNPs because of less positive charged residues on Helix Ⅰ(K6) than Helix Ⅱ(R27/K35). Among the three affinity MNPs, moreover, the highest affinity to immunoglobulin G(IgG) binding was observed on Fe_(3)O_(4)@Dx-Z_(1) MNPs in isothermal titration calorimetry measurement, further validating greater structural integrity of the ligand on Fe_(3)O_(4)@Dx-Z_(1) MNPs. Finally,the study of IgG binding on MNPs and 96-well plates showed that anchoring sites for ligand immobilization had distinct influences on IgG binding and IgG-mediated antigen binding. This work illustrated that anchoring sites of the ligands had a striking significance for the molecular structure of the ligand at liquid-solid interfaces and raised an important implication for the design and optimization of protein A chromatography and protein A-based immunoassay analysis.
基金supported by National Key Research&Development Program of China (2022YFA1506200)the National Natural Science Foundations of China (22078007, 21627813, 21706009,22002085)+3 种基金Guangdong Basic and Applied Basic Research Foundation (2020A1515110832)the Fundamental Research Funds for the Central Universities (buctrc201921, JD2223)Innovative Achievement Commercialization Service-Platform of Industrial CatalysisChemistry and Chemical Engineering Guangdong Laboratory for a startup funding support(2111001)
文摘Bimetallic nanoparticles exhibit a synergistic effect that critically depends on their surface composition,but such promotion mechanisms become vague with varying surface compositions.Here,alumina supported Ag@Pd core–shell and PdAg alloy structure with controlled size and surface compositions were prepared to demonstrate synergetic mechanisms,particularly,ligand and strain effects on activity and ethylene selectivity for acetylene hydrogenation.The performance evaluation indicates that Ag@Pd catalysts with well-controlled Pd-shell thickness can effectively lower apparent activation energy and improve ethylene selectivity.Hydrogenation activity increases from 0.019 to 0.062 s^(-1) with decreasing Pd-shell thickness under mild conditions,which is 3–6 times higher than their alloyed and monometallic counterparts.Combined characterizations and density functional theory are conducted to reveal such shell-thickness-dependent performance.The ligand effect arising from Ag alloying in the interface of Ag@Pd2ML observes the strongest binding of acetylene,but it diminished sharply and the strain effect gets more prevailing with increasing shell thickness.The competition of ethylene desorption and deephydrogenation were also investigated to understand the selectivity governing factors,and the selectivity descriptor(0.5BE(C_(2)H_(4))–BE(H))was built to match the contribution of ligand and strain effect on the different surfaces of Pd-Ag bimetallic NPs.The exploration of synergetic mechanisms among bimetallic NPs with varied structure and surface compositions in this work can help us to deepen the understanding catalyst structure–activity relationship and provide a feasible way to optimize the overall catalytic performance.
基金financially supported by the National Natural Science Foundation of China (Grants Nos.51772338,51972349,91963210 and U1801255).
文摘The design of efficient and robust non-precious metal electrocatalysts towards oxygen evolution reaction(OER)is of great value for developing green energy technologies.The in-situ formed high-valence(oxy)hydroxides species during the reconstruction process of pre-catalysts are recognized as the real contributing sites for OER.However,pre-catalysts generally undergo a slow and inadequate self-reconstruction.Herein,we reported a PO^(3-)_(4)optimized CoFe-based OER catalysts with amorphous structure,which enables a fast and deep reconstruction during the OER process.The amorphous structure induced by ligands PO^(3-)_(4)is prone to evolution and further form active species for OER.The electron interaction between metal sites can be modulated by electron-rich PO^(3-)_(4),which promotes generation of high active CoOOH.Simultaneously,the etching of PO^(3-)_(4)from the pre-catalysts during the catalytic process is in favor of accelerating the self-reconstruction.As a result,as-prepared precatalyst can generate high active CoOOH at a low potential of 1.4 V and achieve an in-depth reconstructed nanosheet structure with abundant OER active sites.Our work provides a promising design of pre-catalysts for realizing efficient catalysis of water oxidation.
基金supported by the National Natural Science Foundation of China(22072034,22001050,and 21873025)the China Postdoctoral Science Foundation(2020T130147,2020M681084,and 2022M710949)+1 种基金the Postdoctoral Foundation of Heilongjiang Province(LBH-Z19059)the Natural Science Foundation of Heilongjiang Youth Fund(YQ2021B002).
文摘Deep-level defects and random oriented configuration in perovskite crystallization process would cause the nonradiative recombination and further affect the performance of perovskite solar cells(PSCs).Herein,two metal-organic frameworks(MOFs)with tunable Lewis-base passivation sites have been constructed(Cd-Httb and Cd-Httb-BDC,Httb=5-(4-(1H-1,2,4-triazole-1-yl)benzyl)-1h-tetrazole,BDC=1,4-dicarboxybenzene)to eliminate deep-level defects and simultaneously as nanostructured heterogeneous nucleation seed to assist the growth of large-grained perovskite films.Compared with the control and Cd-Httb,Cd-Httb-BDC designed with mix-ligands strategy exhibited the enhanced inducted effect on the crystallization and nucleation of high-quality perovskite films during annealing process.Consequently,the resultant Cd-Httb-BDC-modified device achieved higher power conversion efficiency(PCE)(22.18%)than the control(20.89%)and Cd-Httb(21.56%).Meanwhile,the unencapsulated Cd-Httb-BDC-modified device still maintained 90%of initial PCE after 1500 h in ambient conditions and exhibited enhanced thermal stability(85℃ in N_(2) atmosphere).This work presented a successful example of mixligands strategy on construction of high-quality MOF-assisted perovskite films for high-efficient and stable PSCs.
基金supported by the National Key Research and Development Program of China(Nos.2021YFB3602703,2022YFB3606504,and 2022YFB3602903)National Natural Science Foundation of China(No.62122034)+3 种基金Guangdong University Key Laboratory for Advanced Quantum Dot Displays and Lighting(No.2017KSYS007)Shenzhen Key Laboratory for Advanced Quantum Dot Displays and Lighting(No.ZDSYS201707281632549)Shenzhen Science and Technology Program(No.JCYJ20220818100411025)Shenzhen Development and Reform Commission Project(No.XMHT20220114005)。
文摘The performance of inverted quantum-dot light-emitting diodes(QLEDs)based on solution-processed hole transport layers(HTLs)has been limited by the solvent-induced damage to the quantum dot(QD)layer during the spin-coating of the HTL.The lack of compatibility between the HTL’s solvent and the QD layer results in an uneven surface,which negatively impacts the overall device performance.In this work,we develop a novel method to solve this problem by modifying the QD film with 1,8-diaminooctane to improve the resistance of the QD layer for the HTL’s solvent.The uniform QD layer leads the inverted red QLED device to achieve a low turn-on voltage of 1.8 V,a high maximum luminance of 105500 cd/m2,and a remarkable maximum external quantum efficiency of 13.34%.This approach releases the considerable potential of HTL materials selection and offers a promising avenue for the development of high-performance inverted QLEDs.
基金the financial support of the Training Program of the Major Research Plan of the National Natural Science Foundation of China(92061124)the National Natural Science Foundation of China(21975292,21978331,22068008,and 52101186)+3 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010167 and 2022A1515011196)the Guangzhou Key R&D Program/Plan Unveiled Flagship Project(20220602JBGS02)the Guangzhou Basic and Applied Basic Research Project(202201011449)the Research Fund Program of Guangdong Provincial Key Laboratory of Fuel Cell Technology(FC202220 and FC202216)。
文摘Colloidal synthesis of metal nanoclusters will inevitably lead to the blockage of catalytically active sites by organic ligands.Here,taking[Au_(25)(PET)_(18)]-(PET=2-phenylethanethiol)nanocluster as a model catalyst,this work reports a feasible procedure to achieve the controllably partial removal of thiolate ligands from unsupported[Au_(25)(PET)_(18)]-nanoclusters with the preservation of the core structure.This procedure shortens the processing duration by rapid heating and cooling on the basis of traditional annealing treatment,avoiding the reconfiguration or agglomeration of Au_(25)nanoclusters,where the degree of dethiolation can be regulated by the control of duration.This work finds that a moderate degree of dethiolation can expose the Au active sites while maintaining the suppression of the competing hydrogen evolution reaction.Consequently,the activity and selectivity towards CO formation in electrochemical CO_(2)reduction reaction of Au_(25)nanoclusters can be promoted.This work provides a new approach for the removal of thiolate ligands from atomically precise gold nanoclusters.
基金supported by the National Natural Science Foundation of China,Nos. 82071304 (to QXZ), 81671149 (to QXZ),and 81971179 (to XML)the Natural Science Foundation of Jiangsu Province,Nos. BK20191463 (to XML) and BK20161167 (to QXZ)。
文摘We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357–395 of C-X3-C motif chemokine ligand 1(CX3 CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3 CL1(comprising amino acids 357–395 of CX3 CL1) disrupts the interaction between postsynaptic density-93 and CX3 CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3 CL1(357–395 aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3 CL1. Furthermore, the a disintegrin and metalloprotease domain 17(ADAM17) inhibitor GW280264 x, which inhibits metalloprotease activity and prevents CX3 CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3 CL1 formation. Additionally, Tat-CX3 CL1(357–395 aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31–34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3 CL1(357–395 aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3 CL1(357–395 aa) is a potential therapeutic agent for ischemic stroke.
文摘Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.
文摘Cancer is one of the most prevalent diseases worldwide,which causes significant morbidity and mortality.Designing and developing a potential anti-cancer drug is an active field of research worldwide.Microorganisms have been considered a potential source of anti-cancer drugs.One such microbe-derived compound is surfactin,which shows potential anti-cancer activities.In this study,we evaluated the binding potential of surfactin with several cancer cell ligands via an in-silico approach.Hence,molecular docking studies were performed to test the binding potential of surfactin against four targets.The analyses revealed that surfactin from Bacillus sp.can bind with the targeted ligands(coenzyme A,D-leucine,glycerol,and(R)-3-hydroxytetradecanal)with significant affinity.Surfactin showed the highest binding affinity(-7.7 kcal mol-1)to coenzyme A among the targeted ligands.These results may be useful for developing anti-cancer drugs.Nevertheless,further experimental studies are needed to investigate the ligand binding capacity and anti-cancer potential of such surfactin-like molecules.
文摘N-11-azaartemisinins potentially active against Plasmodium falciparum are designed by combining molecular electrostatic potential (MEP), ligand-receptor interaction, and models built with supervised machine learning methods (PCA, HCA, KNN, SIMCA, and SDA). The optimization of molecular structures was performed using the B3LYP/6-31G* approach. MEP maps and ligand-receptor interactions were used to investigate key structural features required for biological activities and likely interactions between N-11-azaartemisinins and heme, respectively. The supervised machine learning methods allowed the separation of the investigated compounds into two classes: cha and cla, with the properties ε<sub>LUMO+1</sub> (one level above lowest unoccupied molecular orbital energy), d(C<sub>6</sub>-C<sub>5</sub>) (distance between C<sub>6</sub> and C<sub>5</sub> atoms in ligands), and TSA (total surface area) responsible for the classification. The insights extracted from the investigation developed and the chemical intuition enabled the design of sixteen new N-11-azaartemisinins (prediction set), moreover, models built with supervised machine learning methods were applied to this prediction set. The result of this application showed twelve new promising N-11-azaartemisinins for synthesis and biological evaluation.
基金supported by the National Institute of Health under Grant#R01EY027749-01A1,#R24EY028764-01A1,#R21EY027065-02,#R41EY027665-01A1 to LW,and#P30-EY014801The American Diabetes Association under Grant#1-18-IBS-172 to LW+1 种基金An institutional grant from Research to Prevent BlindnessThe National Natural Science Foundation of China under Grant#81573112 and#81373030 to WWD.
文摘Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells(LECs)were treated with or without PM2.5.Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity.Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs.Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding.Many other ligands showed no change in binding activity.For example,apolipoprotein E(ApoE),Notch2,and growth arrest-specific 6(Gas6)represent ligands with increased,decreased,or unchanged binding activity,respectively.Both ApoE and Gas6 are phagocytosis ligands,suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5.Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors,as quantified by ligand binding activity.This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.
基金National Science and Technology Major Project,No. 2017ZX10201201 and No. 2017ZX10202202Liaoning Province Natural Science Foundation,No. 20180550096。
文摘BACKGROUND The exact regulation network of programmed death 1(PD-1), programmed death ligand 1(PD-L1), and programmed death ligand 2(PD-L2) signaling in immune escape is largely unknown. We aimed to describe the gene expression profiles related to PD-1 as well as its ligands PD-L1 and PD-L2, thus deciphering their possible biological processes in hepatocellular carcinoma(HCC).AIM To find the possible mechanism of function of PD-1, PD-L1, and PD-L2 in HCC.METHODS Based on the expression data of HCC from The Cancer Genome Atlas, the PD-1/PD-L1/PD-L2 related genes were screened by weighted correlation network analysis method and the biological processes of certain genes were enriched. Relation of PD1/PD-L1/PD-L2 with immune infiltration and checkpoints was investigated by co-expression analysis. The roles of PD-1/PD-L1/PD-L2 in determination of clinical outcome were also analyzed.RESULTS Mutations of calcium voltage-gated channel subunit alpha1 E, catenin beta 1, ryanodine receptor 2, tumor suppressor protein p53, and Titin altered PD-1/PDL1/PD-L2 expression profiles in HCC. PD-1, PD-L1, and PD-L2 related genes were mainly enriched in biological procedures of T cell activation, cell adhesion, and other important lymphocyte effects. In addition, PD-1/PD-L1/PD-L2 was related with immune infiltration of CD8 T cells, cytotoxic lymphocytes,fibroblasts, and myeloid dendritic cells. Immune checkpoints of CTLA4, CD27, CD80, CD86, and CD28 were significantly related to the PD-1/PD-L1/PD-L2 axis. Clinically, PD-1 and PD-L2 expression was correlated with recurrence(P = 0.005 for both), but there was no significant correlation between their expression and HCC patient survival.CONCLUSION Mutations of key genes influence PD-1, PD-L1, and PD-L2 expression. PD-1, PDL1, and PD-L2 related genes participate in T cell activation, cell adhesion, and other important lymphocyte effects. The finding that PD-1/PD-L1/PD-L2 is related to immune infiltration and other immune checkpoints would expand our understanding of promising anti-PD-1 immunotherapy.
基金Supported by CAMS Innovation Fund for Medical Science(CIFMS),No.CAMS-2016-I2M-3-025Beijing Hope Run Special Fund of Cancer Foundation of China,No.LC2020L05.
文摘In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.
基金Supported by The Key Project of Science and Technology of Zhejiang Province, No. 2009C14017the National Natural Science Foundation of China, No. 81071959 and No. 81101837+1 种基金the Zhejiang Provincial Medical and Healthy Science Foundation of China, No. 2013KYA100 and No. 2009B043the Public Welfare Technology Research Project of Zhejiang Province, No. 2010C34001
文摘AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms. METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique. RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm 3 vs 1115.1 ± 223.8 mm 3 , P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed. CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.
