Proceedings of the National Academy of Sciences, 2019
Significance Recently, an exotic hyperuniform fluid state was found in a number of nonequilibrium... more Significance Recently, an exotic hyperuniform fluid state was found in a number of nonequilibrium systems, which shows the promise for fabrication of novel lifelike functional materials capable of self-healing and self-adapting. However, the general mechanism of fluidic hyperuniformity (HU) and its fundamental difference from equilibrium fluids remain unclear, which hinders the rational design of nonequilibrium hyperuniform fluids. In this work, we propose a nonequilibrium hard-sphere model of hyperuniform fluids and formulate a full hydrodynamic description based on the generalized Navier–Stokes equations. Our theory reveals the mechanism of fluidic HU in a simple and intuitive way, which is confirmed by simulating a realistic active spinner system.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2018
Objective— Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y 12 antagonist, such as c... more Objective— Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y 12 antagonist, such as clopidogrel, is the standard of care for acute coronary syndromes. However, the drugs have divergent effects on the formation of cAMP, an inhibitory second messenger. Thus, by inhibiting the synthesis of prostacyclin, acetylsalicylic acid reduces cAMP formation, whereas clopidogrel potentiates it. Therefore, with higher doses of acetylsalicylic acid, the potentiation of cAMP production by clopidogrel may be attenuated, which could limit the antithrombotic potential of the drug combination. The purpose of this study was to examine this possibility in vivo. Approach and Results— Mice were given oral acetylsalicylic acid at varying doses, oral clopidogrel (5 mg/kg body weight), or both. At doses of 0.15 and 0.6 mg/kg, acetylsalicylic acid inhibited arachidonic acid–induced platelet aggregation, but only 0.6 mg/kg acetylsalicylic acid, or higher, decreased the plasma levels of 6-keto-prostagl...
Designing and fabricating self-assembled open colloidal crystals have become one major direction ... more Designing and fabricating self-assembled open colloidal crystals have become one major direction in soft matter community because of many promising applications associated with open colloidal crystals. However, most of the...
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung can... more Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion were determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was significantly up-regulated in NSCLC tissues compared with normal samples. ZEB1-AS1 overexpression was significantly associated with advanced tumor, lymph node, and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, ZEB1-AS1 knockdown inhibited NSCLC cell proliferation and migration, and promoted cell apoptosis. In addition, a chr...
Potential relationship between serum soluble programmed cell death ligand 1 and prognosis of smal... more Potential relationship between serum soluble programmed cell death ligand 1 and prognosis of small cell lung cancer is not well explored. The aim of the study was to reveal the prognostic significance of serum soluble programmed cell death ligand 1 in patients with small cell lung cancer. A total of 250 small cell lung cancer patients and 250 controls were included. Research information was obtained from their medical records. Blood samples were collected on admission. Serum concentration of programmed cell death ligand 1 was measured using Enzyme-Linked Immunosorbent Assay. The patients underwent cisplatin-etoposide chemotherapy with a maximum of six cycles. Subsequently, they were followed-up for 12 months, and therapeutic response and cancer death were recorded. Serum concentration of programmed cell death ligand 1 was higher in the patients than in the controls on admission (P < 0.001). After chemotherapy, 112 patients had no response to this therapy. In the 12-month follow u...
Langmuir : the ACS journal of surfaces and colloids, Jan 18, 2017
The delivery and dissolution of poorly soluble drugs is challenging in the pharmaceutical industr... more The delivery and dissolution of poorly soluble drugs is challenging in the pharmaceutical industry. One way to significantly improve the delivery efficiency is to incorporate these hydrophobic small molecules into a colloidal polyelectrolyes(PE)-drug complex in their ionized states. Despite its huge application value, the general mechanism of PE collapse and complex formation in this system has not been well understood. In this work, by combining a mean-field theory with extensive molecular simulations, we unveil the phase behaviors of the system under dilute and salt-free conditions. We find that the complexation is a first-order-like phase transition triggered by the hydrophobic attraction between the drug molecules. Importantly, the valence ratio between the drug molecule and PE monomer plays a crucial role in determining the stability and morphology of the complex. Moreover, the sign of the zeta potential and the net charge of the complex are found to be inverted as the hydropho...
This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchia... more This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway. A total of 27 BALB/c male mice were selected and divided into control, asthma and IL-4R groups. Ovalbumin-induced mouse asthma model was established. Maximal pulmonary resistance was recorded. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were conducted to observe the pathological changes in lung tissue. Optical microscope was used to detect numbers of total cells, mastocytes, eosinophils (EOS), neutrophils, and lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was adopted for the levels of immunoglobulin (IgE), IL-4, IL-5, IL-13 and interferon (IFN)-γ, flow cytometry for the percentages of IL-4(+) CD4(+), IFN-γ(+) CD4(+) and IFN-γ(+)/IL-4(+) in total thymus-derived (T) cells, qRT-PCR for the mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, suppressor of cytokine signaling (SOCS), inducible nitric oxide synthas...
Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigen... more Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour recurrence and therapy resistance of lung cancer will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we found that miR-520a-3p expression is downregulated in NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer). miR-520a-3p can inhibit proliferation and cancer stem cell phenotype in NSCLC and SCLC cells. Overexpressing miR-520a-3p can degrade HOXD8 mRNA in NSCLC cells, but its overexpression cannot suppress HOXD8 in SCLC cells. HOXD8 protein is upregulated in NSCLC tissues and its overexpression can promote proliferation, formation of cancer stem cells, migra...
Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression p... more Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined. We evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3'-untranslated region (3'-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth ...
On the basis of the coarse-grained model, we performed Brownian dynamics simulations to investiga... more On the basis of the coarse-grained model, we performed Brownian dynamics simulations to investigate behavior of the polyelectrolyte (PE)-macroion complexations in 1:1 and 3:1 salt contents. Our simulation results show that in 3:1 salt content there exists a critical salt concentration (CSC), which is determined by the charge stoichiometry, for the breakup of the PE-macroion complexations. Beyond the CSC concentration, an obvious depletion appears in the macroion-macroion and macroion-PE interactions, which is absent in 1:1 salt content. Both the mobilities of macroions and PEs increase monotonically with increasing the salt concentration in 1:1 and 3:1 salt contents. And the mobility in 3:1 salt content is always larger than that in corresponding 1:1 salt content, which is due to the fact that in 3:1 salt content the PE-macroion complexations are looser than those in 1:1 salt content. Moreover, we observed the collapse and re-expansion of PE chains with the increase of the salt concentration in the PEs-macroions systems of 3:1 salt content, which is due to the charge inversion of PE chains induced by the adsorption of trivalent cations. In addition, we also explored the effects of salt concentration and the length and charge density of PE chains. Our simulation results show that the effects of the length and charge density of PE chains in both salt contents on the radial distribution functions (RDFs) between macroions and between a macroion and a PE segment are similar to these in salt free solution basically. However, we observed an interesting phenomenon that the gyration radius of PE chains in the system of 3:1 salt content is not affected significantly by its charge density, while that in 1:1 salt content increases monotonically.
On the basis of the discretely charged sphere model of lysozyme, the release behavior of lysozyme... more On the basis of the discretely charged sphere model of lysozyme, the release behavior of lysozyme from the branched polyelectrolyte-lysozyme complexation is investigated by adding salt and changing the pH values of the solution. It is found that, with the increase of the salt ionic strength of the solution, the lysozymes are gradually released from the oppositely charged polyelectrolyte as a result of the screening of electrostatic attraction between the two ionic species by adding the salt. Interestingly, there exists a critical salt ionic strength at which all proteins are released from the branched polyelectrolyte, and the polyelectrolyte-protein complexation is broken completely. Beyond the critical value, the increase of the salt ionic strength causes self-association of the proteins released from the branched polyelectrolyte-protein complexation. The self-association of the protein is detrimental in biological systems. By calculating the second virial coefficient, we found that the optimal salt content for the dispersion of proteins coincides with the critical ionic strength, because the second virial coefficient reaches its maximum at the critical ionic strength. Similarly, increasing the pH value of the solution can also release the lysozymes from the polyelectrolyte, because the increase of pH value of the solution changes the charge distribution and net charge of the lysozyme, weakens the attraction between lysozymes mediated by polyelectrolyte, and finally leads to the dissolution of the complexation of branched polyelectrolyte with lysozymes in strong alkaline solution. In addition, by exploring the effect of architecture of the polyelectrolyte on the release behavior of proteins, we found that it is more difficult to release proteins from the branched polyelectrolyte than from the linear polyelectrolyte.
Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New M... more Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008
Proceedings of the National Academy of Sciences, 2019
Significance Recently, an exotic hyperuniform fluid state was found in a number of nonequilibrium... more Significance Recently, an exotic hyperuniform fluid state was found in a number of nonequilibrium systems, which shows the promise for fabrication of novel lifelike functional materials capable of self-healing and self-adapting. However, the general mechanism of fluidic hyperuniformity (HU) and its fundamental difference from equilibrium fluids remain unclear, which hinders the rational design of nonequilibrium hyperuniform fluids. In this work, we propose a nonequilibrium hard-sphere model of hyperuniform fluids and formulate a full hydrodynamic description based on the generalized Navier–Stokes equations. Our theory reveals the mechanism of fluidic HU in a simple and intuitive way, which is confirmed by simulating a realistic active spinner system.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2018
Objective— Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y 12 antagonist, such as c... more Objective— Dual-antiplatelet therapy with acetylsalicylic acid and a P2Y 12 antagonist, such as clopidogrel, is the standard of care for acute coronary syndromes. However, the drugs have divergent effects on the formation of cAMP, an inhibitory second messenger. Thus, by inhibiting the synthesis of prostacyclin, acetylsalicylic acid reduces cAMP formation, whereas clopidogrel potentiates it. Therefore, with higher doses of acetylsalicylic acid, the potentiation of cAMP production by clopidogrel may be attenuated, which could limit the antithrombotic potential of the drug combination. The purpose of this study was to examine this possibility in vivo. Approach and Results— Mice were given oral acetylsalicylic acid at varying doses, oral clopidogrel (5 mg/kg body weight), or both. At doses of 0.15 and 0.6 mg/kg, acetylsalicylic acid inhibited arachidonic acid–induced platelet aggregation, but only 0.6 mg/kg acetylsalicylic acid, or higher, decreased the plasma levels of 6-keto-prostagl...
Designing and fabricating self-assembled open colloidal crystals have become one major direction ... more Designing and fabricating self-assembled open colloidal crystals have become one major direction in soft matter community because of many promising applications associated with open colloidal crystals. However, most of the...
Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung can... more Long non-coding RNAs (lncRNAs) have been reported to play a vital role in non-small-cell lung cancer (NSCLC). ZEB1-AS1 overexpression predicts a poor prognosis in osteosarcoma and colorectal cancers. In the current study, we determined the clinical significance and prognostic value of ZEB1-AS1 in patients with NSCLC. The expression of ZEB1-AS1 and inhibitor of differentiation-1 (ID1) was measured using qRT-PCR and Western blot. Cell growth, migration, and invasion were determined using colony formation assays, Transwell assay, and flow cytometry, respectively. Tumor growth was determined with a xenograft model. ZEB1-AS1 was significantly up-regulated in NSCLC tissues compared with normal samples. ZEB1-AS1 overexpression was significantly associated with advanced tumor, lymph node, and metastases (TNM) stage and tumor size, as well as poorer overall survival. Moreover, ZEB1-AS1 knockdown inhibited NSCLC cell proliferation and migration, and promoted cell apoptosis. In addition, a chr...
Potential relationship between serum soluble programmed cell death ligand 1 and prognosis of smal... more Potential relationship between serum soluble programmed cell death ligand 1 and prognosis of small cell lung cancer is not well explored. The aim of the study was to reveal the prognostic significance of serum soluble programmed cell death ligand 1 in patients with small cell lung cancer. A total of 250 small cell lung cancer patients and 250 controls were included. Research information was obtained from their medical records. Blood samples were collected on admission. Serum concentration of programmed cell death ligand 1 was measured using Enzyme-Linked Immunosorbent Assay. The patients underwent cisplatin-etoposide chemotherapy with a maximum of six cycles. Subsequently, they were followed-up for 12 months, and therapeutic response and cancer death were recorded. Serum concentration of programmed cell death ligand 1 was higher in the patients than in the controls on admission (P < 0.001). After chemotherapy, 112 patients had no response to this therapy. In the 12-month follow u...
Langmuir : the ACS journal of surfaces and colloids, Jan 18, 2017
The delivery and dissolution of poorly soluble drugs is challenging in the pharmaceutical industr... more The delivery and dissolution of poorly soluble drugs is challenging in the pharmaceutical industry. One way to significantly improve the delivery efficiency is to incorporate these hydrophobic small molecules into a colloidal polyelectrolyes(PE)-drug complex in their ionized states. Despite its huge application value, the general mechanism of PE collapse and complex formation in this system has not been well understood. In this work, by combining a mean-field theory with extensive molecular simulations, we unveil the phase behaviors of the system under dilute and salt-free conditions. We find that the complexation is a first-order-like phase transition triggered by the hydrophobic attraction between the drug molecules. Importantly, the valence ratio between the drug molecule and PE monomer plays a crucial role in determining the stability and morphology of the complex. Moreover, the sign of the zeta potential and the net charge of the complex are found to be inverted as the hydropho...
This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchia... more This study aims to explore the mechanisms of how IL-4R suppresses airway inflammation in bronchial asthma by inhibiting the IL-4/STAT6 pathway. A total of 27 BALB/c male mice were selected and divided into control, asthma and IL-4R groups. Ovalbumin-induced mouse asthma model was established. Maximal pulmonary resistance was recorded. Hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining were conducted to observe the pathological changes in lung tissue. Optical microscope was used to detect numbers of total cells, mastocytes, eosinophils (EOS), neutrophils, and lymphocytes. Enzyme-linked immunosorbent assay (ELISA) was adopted for the levels of immunoglobulin (IgE), IL-4, IL-5, IL-13 and interferon (IFN)-γ, flow cytometry for the percentages of IL-4(+) CD4(+), IFN-γ(+) CD4(+) and IFN-γ(+)/IL-4(+) in total thymus-derived (T) cells, qRT-PCR for the mRNA expressions of IL-4, IL-5, IL-13, STAT6, pSTAT6, suppressor of cytokine signaling (SOCS), inducible nitric oxide synthas...
Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigen... more Formation of cancer stem cells (CSCs) and increased cells proliferation are involved in tumorigenesis, tumour recurrence and therapy resistance and microRNA is essential for the development of the biological traits of CSCs and the increased cells proliferation. Studying molecular mechanism of tumorigenesis, tumour recurrence and therapy resistance of lung cancer will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we found that miR-520a-3p expression is downregulated in NSCLC (non-small cell lung cancer) and SCLC (small cell lung cancer). miR-520a-3p can inhibit proliferation and cancer stem cell phenotype in NSCLC and SCLC cells. Overexpressing miR-520a-3p can degrade HOXD8 mRNA in NSCLC cells, but its overexpression cannot suppress HOXD8 in SCLC cells. HOXD8 protein is upregulated in NSCLC tissues and its overexpression can promote proliferation, formation of cancer stem cells, migra...
Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression p... more Accumulating evidence has emphasized causative links between aberrant microRNA (miR) expression patterns and cancer development. Abnormally expressed miRNA-98 (miR-98) was found in certain types of human cancers. The biological roles of miR-98 in lung cancer, however, remain largely undefined. We evaluated the expression of miR-98 in normal lung tissues, lung cancer tissues, normal human bronchial epithelial cells, and lung cancer cells using quantitative real-time polymerase chain reaction. Effect of miR-98 on proliferation of lung cancer cells was investigated using MTT assay and colony formation assay. Transwell assay was used to assess the effects of miR-98 on migration and invasion of lung cancer cells. Whether miR-98 targets the 3'-untranslated region (3'-UTR) of integrin β3 (ITGB3) coding gene ITGB3 mRNA was ascertained using luciferase reporter assay. Finally, we transplanted miR-98 expressing A549 cells into nude mice to observe the effect of miR-98 on tumor growth ...
On the basis of the coarse-grained model, we performed Brownian dynamics simulations to investiga... more On the basis of the coarse-grained model, we performed Brownian dynamics simulations to investigate behavior of the polyelectrolyte (PE)-macroion complexations in 1:1 and 3:1 salt contents. Our simulation results show that in 3:1 salt content there exists a critical salt concentration (CSC), which is determined by the charge stoichiometry, for the breakup of the PE-macroion complexations. Beyond the CSC concentration, an obvious depletion appears in the macroion-macroion and macroion-PE interactions, which is absent in 1:1 salt content. Both the mobilities of macroions and PEs increase monotonically with increasing the salt concentration in 1:1 and 3:1 salt contents. And the mobility in 3:1 salt content is always larger than that in corresponding 1:1 salt content, which is due to the fact that in 3:1 salt content the PE-macroion complexations are looser than those in 1:1 salt content. Moreover, we observed the collapse and re-expansion of PE chains with the increase of the salt concentration in the PEs-macroions systems of 3:1 salt content, which is due to the charge inversion of PE chains induced by the adsorption of trivalent cations. In addition, we also explored the effects of salt concentration and the length and charge density of PE chains. Our simulation results show that the effects of the length and charge density of PE chains in both salt contents on the radial distribution functions (RDFs) between macroions and between a macroion and a PE segment are similar to these in salt free solution basically. However, we observed an interesting phenomenon that the gyration radius of PE chains in the system of 3:1 salt content is not affected significantly by its charge density, while that in 1:1 salt content increases monotonically.
On the basis of the discretely charged sphere model of lysozyme, the release behavior of lysozyme... more On the basis of the discretely charged sphere model of lysozyme, the release behavior of lysozyme from the branched polyelectrolyte-lysozyme complexation is investigated by adding salt and changing the pH values of the solution. It is found that, with the increase of the salt ionic strength of the solution, the lysozymes are gradually released from the oppositely charged polyelectrolyte as a result of the screening of electrostatic attraction between the two ionic species by adding the salt. Interestingly, there exists a critical salt ionic strength at which all proteins are released from the branched polyelectrolyte, and the polyelectrolyte-protein complexation is broken completely. Beyond the critical value, the increase of the salt ionic strength causes self-association of the proteins released from the branched polyelectrolyte-protein complexation. The self-association of the protein is detrimental in biological systems. By calculating the second virial coefficient, we found that the optimal salt content for the dispersion of proteins coincides with the critical ionic strength, because the second virial coefficient reaches its maximum at the critical ionic strength. Similarly, increasing the pH value of the solution can also release the lysozymes from the polyelectrolyte, because the increase of pH value of the solution changes the charge distribution and net charge of the lysozyme, weakens the attraction between lysozymes mediated by polyelectrolyte, and finally leads to the dissolution of the complexation of branched polyelectrolyte with lysozymes in strong alkaline solution. In addition, by exploring the effect of architecture of the polyelectrolyte on the release behavior of proteins, we found that it is more difficult to release proteins from the branched polyelectrolyte than from the linear polyelectrolyte.
Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New M... more Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008
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