Publications by authors named "Yani Chen"

54 Publications

Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation.

J Exp Med 2021 Jun;218(6)

Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA.

Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite-infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.
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http://dx.doi.org/10.1084/jem.20202359DOI Listing
June 2021

Fatigue Performance and Stress Distribution of Endodontically Treated Premolars Restored with Direct Bulk-fill Resin Composites.

J Adhes Dent 2021 ;23(1):67-75

Purpose: To investigate the fatigue performance and stress distribution of endodontically treated maxillary premolars with occlusal (O), mesio-occlusal (MO), or mesio-occluso-distal (MOD) cavities filled directly with bulk-fill composite.

Materials And Methods: Besides the intact teeth (control group), sixty sound maxillary first premolars, standardized by size and morphology, were subjected to root canal treatment and randomly allocated to three groups throughout cavity preparations (O/MO/MOD). All cavities were restored with a bulk-fill composite (Tetric N-Ceram Bulk fill) and universal adhesive (Tetric N-Bond Universal) using etch-and-rinse mode. Half of the specimens of each group underwent 20,000 thermocycles (5°C-55°C). All specimens were subjected to a 50-N load perpendicular to their buccal bevels on the palatal cusps for 1,200,000 cycles. The survival curve and fracture mode were analyzed by log-rank and Fisher's exact tests, respectively. Finite element analysis (FEA) was conducted to simulate the working condition of premolars with O/MO/MOD cavities. The von Mises stress and the first principal stress were calculated for three FEA models.

Results: Premolars with O cavity restorations exhibited better stress distributions than did those with MO and MOD cavity restorations. Compared to the intact premolars, no significant difference was detected in the fatigue performance of O/MO/MOD restorations, regardless of whether they underwent thermocycling. Only one specimen presented unrestorable fracture, while the rest of the fractured premolars were restorable.

Conclusion: The cavity design of endodontic premolars restored with a bulk-fill composite has no influence on the stress distribution or fatigue survival, with a biomechanical performance similar to that of an intact tooth.
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http://dx.doi.org/10.3290/j.jad.b906631DOI Listing
February 2021

Nanoparticle Shaped Titanium Promotes Osteogenic Differentiation of Bone Mesenchymal Stem Cells Through Integrin/Integrin Linked Kinase/Glycogen Synthase Kinase-3 Axis.

J Biomed Nanotechnol 2020 Aug;16(8):1267-1275

Dental implantation is an important method in treating missing teeth, widely used in oral treatment. As regards to physical and mechanical properties, pure titanium (Ti) material has become the most common dental implant material for its high stability and biocompatibility, clinically. Cell-substrate interactions have vital contribution in regulating pertinent cell functions like adhesion, proliferation, and differentiation. Initiation of the signal cascades to modulate cells behavior can also relate to surface topography. Bone mesenchymal stem cells (BMSCs) primarily migrate and adhere to the surface of implant prosthesis in the process of cells adhesion. Moreover, it was verified that adhesion and differentiation ability of BMSCs is mainly determined by surface morphology of implant prosthesis. In this study, we employed nanoparticle cluster beam technique to establish a kind of nanoparticle surface modified Ti material to examine BMSCs' osteogenic differentiation. By examining osteospecific genes (osteocalcin, osteopontin and runx2) altered expressions, we found that nanoparticle modified Ti material can contribute to a higher up regulation of BMSCs osteogenic differentiation. During the process, ILK (integrin linked kinase) and Wnt/-catenin signaling were expressed differentially. Mechanistically, we demonstrated that nanoparticle shaped Ti material induced osteogenic differentiation of BMSCs can be impaired by inhibiting ILK or Wnt/-catenin signaling. Analyzation of the obtained results concludes that ILK-mediated activation of Wnt/-catenin signaling is principal for osteogenic differentiation of BMSCs, because of improved physical properties, nanoparticle modified Ti material are superior for cell attachment and osseointegration.
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http://dx.doi.org/10.1166/jbn.2020.2957DOI Listing
August 2020

Molecular Mechanism Underlying the Synergetic Effect of Jasmonate on Abscisic Acid Signaling during Seed Germination in Arabidopsis.

Plant Cell 2020 12 6;32(12):3846-3865. Epub 2020 Oct 6.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming 650091, China

Abscisic acid (ABA) is known to suppress seed germination and post-germinative growth of Arabidopsis (), and jasmonate (JA) enhances ABA function. However, the molecular mechanism underlying the crosstalk between the ABA and JA signaling pathways remains largely elusive. Here, we show that exogenous coronatine, a JA analog structurally similar to the active conjugate jasmonate-isoleucine, significantly enhances the delayed seed germination response to ABA. Disruption of the JA receptor CORONATINE INSENSITIVE1 or accumulation of the JA signaling repressor JASMONATE ZIM-DOMAIN (JAZ) reduced ABA signaling, while mutants enhanced ABA responses. Mechanistic investigations revealed that several JAZ repressors of JA signaling physically interact with ABSCISIC ACID INSENSITIVE3 (ABI3), a critical transcription factor that positively modulates ABA signaling, and that JAZ proteins repress the transcription of ABI3 and ABI5. Further genetic analyses showed that JA activates ABA signaling and requires functional ABI3 and ABI5. Overexpression of and simultaneously suppressed the ABA-insensitive phenotypes of the mutant and JAZ-accumulating () plants. Together, our results reveal a previously uncharacterized signaling module in which JAZ repressors of the JA pathway regulate the ABA-responsive ABI3 and ABI5 transcription factors to integrate JA and ABA signals during seed germination and post-germinative growth.
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http://dx.doi.org/10.1105/tpc.19.00838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721325PMC
December 2020

Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells.

Biomed Res Int 2020 26;2020:5053975. Epub 2020 Jun 26.

Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an, 716000 Shannxi, China.

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC.
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http://dx.doi.org/10.1155/2020/5053975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336199PMC
April 2021

Probing the Ferromagnetism and Spin Wave Gap in VI by Helicity-Resolved Raman Spectroscopy.

Nano Lett 2020 Aug 8;20(8):6024-6031. Epub 2020 Jul 8.

Department of Physics, Southern University of Science and Technology, Shenzhen 518055, China.

Circularly polarized light carries light spin angular momentum, which may lead helicity-resolved Raman scattering to be sensitive to the electronic spin configuration in magnetic materials. Here, we demonstrate that all Raman modes in the 2D ferromagnet VI show different scattering intensities to left and right circularly polarized light at low temperatures, which gives direct evidence of the time-reversal symmetry breaking. By measuring the circular polarization of the dominant Raman mode with respect to the temperature and magnetic field, the ferromagnetic (FM) phase transition and hysteresis behavior can be clearly resolved. Besides the lattice excitations, quasielastic scattering is detected in the paramagnetic phase, and it gradually evolves into the acoustic magnon mode at 18.5 cm in the FM state, which gives the spin wave gap that results from large magnetic anisotropy. Our findings demonstrate that helicity-resolved Raman spectroscopy is an effective tool to directly probe the ferromagnetism in 2D magnets.
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http://dx.doi.org/10.1021/acs.nanolett.0c02029DOI Listing
August 2020

miR-30a-3p Targets MAD2L1 and Regulates Proliferation of Gastric Cancer Cells.

Onco Targets Ther 2019 19;12:11313-11324. Epub 2019 Dec 19.

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an, Shaanxi 716000, People's Republic of China.

Purpose: This study was done to investigate the inhibition effects of miR-30a-3p on mitotic arrest deficient 2 like 1 (MAD2L1) expression and the proliferation of gastric cancer cells.

Patients And Methods: Cluster analysis and the TCGA database were used to screen the key genes highly expressed in gastric cancer. Based on the LinkedOmics website, the correlation between the miR-30a-3p and the cell cycle-related target gene in gastric cancer was analyzed. The mRNA and protein expression levels were detected with the quantitative real-time PCR and Western blot analysis. The cell proliferation and cell cycle were also detected and analyzed.

Results: Bioinformatics analysis showed that MAD2L1 was highly expressed in tumor tissues compared with normal tissues. Compared with normal tissues, the miR-30a-3p was significantly decreased in the gastric cancer tissues. Moreover, MAD2L1 was significantly negatively correlated with the miR-30a-3p expression. Furthermore, over-expression of miR-30a-3p decreased the expression of MAD2L1 at the protein level, which inhibited the proliferation of AGS and BGC-823 gastric cancer cells. In addition, the cell cycles of AGS and BGC-823 cells were arrested at the G0/G1 phase.

Conclusion: MAD2L1 is a pro-oncogene which is up-regulated in gastric cancer. The miR-30a-3p can down-regulate the MAD2L1 expression, inhibiting the proliferation of gastric cancer cells and affect the cell cycle.
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http://dx.doi.org/10.2147/OTT.S222854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927793PMC
December 2019

MicroRNA-497-5p Induces Cell Cycle Arrest Of Cervical Cancer Cells In S Phase By Targeting CBX4.

Onco Targets Ther 2019 2;12:10535-10545. Epub 2019 Dec 2.

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an 716000, People's Republic of China.

Purpose: miR-497-5p can inhibit cervical cancer cell proliferation. However, the underlying mechanism remains to be elucidated.

Methods: Bioinformatics was used to analyze the target genes of miR-497-5p. qRT-PCR and Western blot were used to analyze mRNA and protein expression, respectively. Dual-luciferase reporter assay was used to analyze the direct binding between miR-497-5p and 3'-untranslated region of CBX4. Cell viability was measured with MTT assay. Flow cytometry was performed to detect cell cycle distribution.

Results: Here, using bioinformatics methods we firstly found that miR-497-5p regulated cervical carcinoma proliferation by targeting polycomb chromobox4 (CBX4). Expression of miR-497-5p in cervical carcinoma tissues was negatively correlated with CBX4. A binding region of miR-497-5p in 3'-untranslated region of CBX4 was predicted. Further experiments confirmed that miR-497-5p directly targeted CBX4. Besides, RNA interference of CBX4 inhibited cervical cancer cell proliferation, arrested cells at S phase and reduced the expression of CDK2 and Cyclin A2 proteins. The use of miR-497-5p inhibitor compromised CBX4 interference RNAs induced cycle arrest of cervical cancer cells. Cells co-transfected with miR-497-5p inhibitors and CBX4 interference RNAs had a higher proliferation rate than CBX4 inference RNA-transfected cells.

Conclusion: All together, the present study demonstrates that miR-497-5p inhibits cervical cancer cells proliferation by directly targeting CBX4.
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http://dx.doi.org/10.2147/OTT.S210059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910861PMC
December 2019

Scalable chemical synthesis of doped silicon nanowires for energy applications.

Nanoscale 2019 Nov;11(46):22504-22514

Univ. Grenoble Alpes, CEA, CNRS, IRIG, SYMMES, 38000 Grenoble, France.

A versatile, low-cost and easily scalable synthesis method is presented for producing silicon nanowires (SiNWs) as a pure powder. It applies air-stable diphenylsilane as a Si source and gold nanoparticles as a catalyst and takes place in a sealed reactor at 420 °C (pressure <10 bar). Micron-sized NaCl particles, acting as a sacrificial support for the catalyst particles during NW growth, can simply be removed with water during purification. This process gives access to SiNWs of precisely controlled diameters in the range of 10 ± 3 nm with a high production yield per reactor volume (1 mg cm-3). The reaction was scaled up to 500 mg of SiNWs without altering the morphology or diameter. Adding diphenylphosphine results in SiNW n-type doping as confirmed by ESR spectroscopy and EDX analyses. The measured SiNW doping level closely follows the initial dopant concentration. Doping induces both an increase in diameter and a sharp increase of electrical conductivity for P concentrations >0.4%. When used in symmetric supercapacitor devices, 1% P-doped SiNWs exhibit an areal capacity of 0.25 mF cm-2 and retention of 80% of the initial capacitance after one million cycles, demonstrating excellent cycling stability of the SiNW electrodes in the presence of organic electrolytes.
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http://dx.doi.org/10.1039/c9nr03749gDOI Listing
November 2019

Matrine pre-treatment suppresses AGEs- induced HCSMCs fibrotic responses by regulating Poldip2/mTOR pathway.

Eur J Pharmacol 2019 Dec 18;865:172746. Epub 2019 Oct 18.

Department of Cardiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China. Electronic address:

The fibrotic response of vascular smooth muscle cells (VSMCs) takes responsibilities in atherosclerosis. Advanced glycation end products (AGEs) induce and promote the fibrotic responses of VSMCs. Matrine shows potent anti-fibrotic and cardio-protective effects. This study was aimed to investigate the underlying mechanisms of matrine's inhibitory effects on AGEs-induced VSMCs fibrotic responses. Cultured human coronary smooth muscle cells (HCSMCs) were pre-treated with matrine and exposed to AGEs. Specific siRNA was used to silence polymerase delta interacting protein 2 (Poldip2) expression. Sircol collagen assay was used to assess collagen content. Protein expression and phosphorylation levels were determined by Western blotting. Matrine pre-treatment significantly reduced collagen content, increased smooth muscle myosin heavy chain 11 (MYH11) and Poldip2 expression, decreased expressions of collagen I, β1-integrin, phsphoinositide-3-kinase (PI3K) and nuclear phosphorylated p70S6k, and reduced phosphorylation levels of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) in HCSMCs exposed to AGEs in a concentration dependent manner. Specific siRNA effectively silenced Poldip2 expression and impaired matrine's effect on collagen content, expressions of MYH11, collagen I, β1-integrin, PI3K, nuclear p-p70S6k and phosphorylation levels of Akt and mTOR in HCSMCs exposed to AGEs. Matrine suppresses AGEs- induced fibrotic responses in HCSMCs via regulating Poldip2/mTOR signaling pathway.
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http://dx.doi.org/10.1016/j.ejphar.2019.172746DOI Listing
December 2019

New Light on Molecule-Nanotube Hybrids.

Adv Mater 2019 Nov 25;31(48):e1902917. Epub 2019 Sep 25.

Univ. Grenoble Alpes, CNRS, Grenoble INP, Institut Néel, 38000, Grenoble, France.

Optoelectronics benefits from outstanding new nanomaterials that provide emission and detection in the visible and near-infrared range, photoswitches, two level systems for single photon emission, etc. Among these, carbon nanotubes are envisioned as game changers despite difficult handling and control over chirality burdening their use. However, recent breakthroughs on hybrid carbon nanotubes have established nanotubes as pioneers for a new family of building blocks for optics and quantum optics. Functionalization of carbon nanotubes with molecules or polymers not only preserves the nanotube properties from the environment, but also promotes new performance abilities to the resulting hybrids. Photoluminescence and Raman signals are enhanced in the hybrids, which questions the nature of the electronic coupling between nanotube and molecules. Furthermore, coupling to optical cavities dramatically enhances single photon emission, which operates up to room temperature. This new light on nanotube hybrids shows their potential to push optoelectronics a step forward.
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http://dx.doi.org/10.1002/adma.201902917DOI Listing
November 2019

Computational determination of binding modes of 2-acetoxyphenylhept-2-ynyl sulfide to cyclooxygenase-2.

J Biomol Struct Dyn 2020 Aug 16;38(12):3648-3658. Epub 2019 Sep 16.

Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

2-Acetoxyphenylhept-2-ynyl sulfide (APHS) is a potent covalent inhibitor with cyclooxygenase-2 (COX-2) selectivity. However, no crystal structure for APHS‒COX-2 complex has been reported. In this work, we have extensively studied the binding modes and interactions between APHS and COX-2. Molecular docking followed by MD simulations identified a stable and reactive binding mode, of which the calculated binding free energy was in good agreement with the experimental reports. Furthermore, binding modes of six analogs of APHS were also analyzed to study the effects on binding affinity of the triple bond, heteroatom and length of alkyl chain. The findings help to understand the action mechanisms of APHS and explain why it is more potent than the analogs, which might be useful in the design of new compounds with higher inhibitory activity to COX-2.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2019.1666033DOI Listing
August 2020

The effect of MTHFD2 on the proliferation and migration of colorectal cancer cell lines.

Onco Targets Ther 2019 12;12:6361-6370. Epub 2019 Aug 12.

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an 716000, People's Republic of China.

Purpose: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a tetramethylfolate dehydrogenase enzyme involved in folate metabolism. The aim of this study is to determine the effect of MTHFD2 on the proliferation and metastasis of colorectal cancer (CRC).

Patients And Methods: MTHFD2 was silenced or overexpressed in CRC cells. qRT-PCR and Western blotting were used to analyze mRNA and protein expression, respectively. The MTT assay and colony forming assay were used to detect cell proliferation and colony formation ability. The cycle and apoptosis changes were detected by flow cytometry. Transwell experiments were used to analyze the migration ability of CRC cells.

Results: The expression of MTHFD2 in 31 kinds of cancers was analyzed by bioinformatics, and MTHFD2 was found highly expressed in various cancer cells including CRC cells. Silencing the expression of MTHFD2 resulted in inhibition of the proliferation of CRC cells, weakening of the migration ability, blocking of the cell cycle in G0/G1-S phase, and promotion of the apoptosis of CRC cells. On the contrary, overexpression of MTHFD2 in CRC cells resulted in enhancement of the proliferation and migration ability, promotion of cell cycle progression and inhibition of cell apoptosis.

Conclusion: MTHFD2 is positively related with colorectal cancer and the MTHFD2 gene is a tumor promoting gene in CRC cells.
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http://dx.doi.org/10.2147/OTT.S210800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697661PMC
August 2019

Matrine Suppresses Reactive Oxygen Species (ROS)-Mediated MKKs/p38-Induced Inflammation in Oxidized Low-Density Lipoprotein (ox-LDL)-Stimulated Macrophages.

Med Sci Monit 2019 Jun 3;25:4130-4136. Epub 2019 Jun 3.

Department of Cardiology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China (mainland).

BACKGROUND The objective of this study was to study the anti-inflammatory effect and possibly involved molecular mechanisms of matrine on oxidized low-density lipoprotein (ox-LDL)-exposed macrophages. MATERIAL AND METHODS Cultured human macrophages (THP-1 cell line) were exposed to ox-LDL at final concentrations of 0, 25, 50, and 100 μg/mL. Several cells were then treated with matrine at serial diluted concentrations. 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA) staining was used to evaluate reactive oxygen species (ROS) production; a colorimetric method was used to determine the cellular antioxidant capacity; production of pro-inflammatory cytokines interleukin (IL)18 and tumor necrosis factor (TNF)alpha were determined by enzyme-linked immunosorbent assay (ELISA); and immunoblot assay was used to assess the relative protein phosphorylation and expression. RESULTS ox-LDL exposure significantly elevated intracellular ROS level and supernatant IL18 and TNFalpha concentrations, but impaired total antioxidant capacity (TAC) of macrophages. The relative phosphorylations of MAPK kinase kinases (MKK)6, MKK3, and p38 mitogen-activated protein kinases (MAPK) were increased by ox-LDL exposure. The expression levels of IL18 and TNFalpha were also increased in ox-LDL-treated macrophages. The matrine treatment reduced intracellular ROS level and supernatant IL18 and TNFalpha concentrations and increased TAC in a concentration- dependent manner. The relative phosphorylations of MKK6, MKK3, and p38 MAPK were reduced after matrine administration. Moreover, the expression levels of IL18 and TNFalpha were also decreased by matrine treatment, in a concentration-dependent manner. CONCLUSIONS ox-LDL increases inflammatory response in macrophages by activating the ROS-mediated MKKs/p38 MAPK-induced inflammatory signaling pathway. Matrine suppresses ox-LDL-induced inflammatory by inhibiting the MKKs/p38 MAPK signaling pathway.
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http://dx.doi.org/10.12659/MSM.917151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561390PMC
June 2019

Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A.

PLoS Negl Trop Dis 2019 05 20;13(5):e0007247. Epub 2019 May 20.

Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, United States of America.

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp. are usually introduced by sand flies into the dermis of mammalian hosts in the presence of bacteria from either the host skin, sand fly gut or both. We hypothesized that bacteria at the dermal inoculation site of Leishmania major will influence the severity of infection that ensues. A C57BL/6 mouse ear model of single or coinfection with Leishmania major, Staphylococcus aureus, or both showed that single pathogen infections caused localized lesions that peaked after 2-3 days for S. aureus and 3 weeks for L. major infection, but that coinfection produced lesions that were two-fold larger than single infection throughout 4 weeks after coinfection. Coinfection increased S. aureus burdens over 7 days, whereas L. major burdens (3, 7, 28 days) were the same in singly and coinfected ears. Inflammatory lesions throughout the first 4 weeks of coinfection had more neutrophils than did singly infected lesions, and the recruited neutrophils from early (day 1) lesions had similar phagocytic and NADPH oxidase capacities. However, most neutrophils were apoptotic, and transcription of immunomodulatory genes that promote efferocytosis was not upregulated, suggesting that the increased numbers of neutrophils may, in part, reflect defective clearance and resolution of the inflammatory response. In addition, the presence of more IL-17A-producing γδ and non-γδ T cells in early lesions (1-7 days), and L. major antigen-responsive Th17 cells after 28 days of coinfection, with a corresponding increase in IL-1β, may recruit more naïve neutrophils into the inflammatory site. Neutralization studies suggest that IL-17A contributed to an enhanced inflammatory response, whereas IL-1β has an important role in controlling bacterial replication. Taken together, these data suggest that coinfection of L. major infection with S. aureus exacerbates disease, both by promoting more inflammation and neutrophil recruitment and by increasing neutrophil apoptosis and delaying resolution of the inflammatory response. These data illustrate the profound impact that coinfecting microorganisms can exert on inflammatory lesion pathology and host adaptive immune responses.
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http://dx.doi.org/10.1371/journal.pntd.0007247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527190PMC
May 2019

Effect of mGluR7 on proliferation of human embryonic neural stem cells.

Medicine (Baltimore) 2019 Mar;98(9):e14683

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an, P. R. China.

This study is to investigate the effect of metabotropic glutamate receptor 7 (mGluR7) on the proliferation of human embryonic neural stem cells (NSCs) and its molecular mechanism.Human embryonic NSCs were isolated. The pCMV2-GV146-GFP-mGluR7 plasmid was transfected to over-express mGluR7 while mGluR7 siRNA was transfected to knockdown mGluR7. MTT assay was used to analyze cell proliferation. Flow cytometry was used to detect cell cycle and apoptosis. Protein and mRNA levels were analyzed by Western blot and RT-qPCR, respectively.The viability of human NSCs and the diameter of neurospheres after 24 hours, 48 hours, and 72 hours of transfection significantly increased by mGluR7 overexpression whereas significantly decreased by mGluR7 knockdown. Ki-67 expression was up-regulated by mGluR7 overexpression whereas down-regulated by mGluR7 siRNA, indicating a promotive effect of mGluR7 on NSC proliferation. After mGluR7 overexpression, G1/G0 phase cell ratio dropped significantly compared with control group, while the S phase cell ratio increased. mGluR7 silencing arrested human NSCs at G1/G0 phase. After 48 hours of transfection, there was a decrease of apoptosis by mGluR7 overexpression, while mGluR7 silencing induced apoptosis of human NSCs. Additionally, overexpression of mGluR7 up-regulated the expression of p-serine/threonine kinase (AKT), cyclin D1, and cyclin-dependent kinase 2 (CDK2). The mGluR7 knockdown had opposite effects. Similarly, mGluR7 down-regulated the expression of Caspase-3/9, while the mGluR7 knockdown promoted this.mGluR7 can promote the proliferation of human embryonic cortical NSCs in vitro. This effect may be mediated by promoting cell cycle progression, inhibiting cell apoptosis, activating the AKT signaling pathway, and inhibiting the Caspase-3/9 signaling pathway.
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http://dx.doi.org/10.1097/MD.0000000000014683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831331PMC
March 2019

Molecular insight into chymotrypsin inhibitor 2 resisting proteolytic degradation.

Phys Chem Chem Phys 2019 Feb;21(9):5049-5058

Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Chymotrypsin inhibitor 2 (CI2) is a special serine protease inhibitor which can resist hydrolysis for several days with a rapid equilibrium between the Michaelis complex and acyl-enzyme intermediate. The energies and conformational changes for subtilisin-catalyzed proteolysis of CI2 were examined in this paper for the first time by employing pseudo bond ab initio QM/MM MD simulations. In the acylation reaction, a low-barrier hydrogen bond between His64 and Asp32 in the transition state together with the lack of covalent backbone constraints makes the peptide bonds of CI2 break more easily than in other serine protease inhibitors. After acyl-enzyme formation, molecular dynamics simulations showed that the access of hydrolytic water to the active site requires partial dissociation of the leaving group. However, retention of the leaving group mainly by the intra- and inter-molecular H-bonding networks hinders the access of water and retards the deacylation reaction. Instead of the dissociation constant of inhibitors, we suggest employing the free energy at the acyl-enzyme state to predict the relative hydrolysis rates of CI2 mutants, which are testified by the experimental relative hydrolysis rates.
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http://dx.doi.org/10.1039/c8cp07784cDOI Listing
February 2019

Effect and mechanism of mGluR6 on the biological function of rat embryonic neural stem cells.

Biosci Biotechnol Biochem 2019 Jun 10;83(6):1027-1034. Epub 2019 Feb 10.

a Department of Clinical Medicine , Medical College of Yan'an University , Yan'an , P.R. China.

Here, we investigated the effects and molecular mechanisms of metabotropic glutamate receptor 6 (mGluR6) on rat embryonic neural stem cells (NSCs). Overexpression of mGluR6 significantly promoted the proliferation of NSCs and increased the diameter of neutrospheres after treatment for 24 h, 48 h and 72 h. Overexpression of mGluR6 promoted G1 to S phase transition, with significantly decreased cell ratio in G1/G0 phase but significantly increased cell ratio in S phase. Additionally, mGluR6 overexpression for 48 h decreased the early and late apoptosis significantly. Moreover, overexpression of mGluR6 significantly increased the expression of p-ERK1/2, Cyclin D1 and CDK2, while the expression of p-p38 was significantly decreased. On the contrary, these effects of mGluR6 overexpression were reversed by mGluR6 knockdown. In conclusion, mGluR6 promotes the proliferation of NSCs by activation of ERK1/2-Cyclin D1/CDK2 signaling pathway and inhibits the apoptosis of NSCs by blockage of the p38 MAPK signaling pathway.
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http://dx.doi.org/10.1080/09168451.2019.1578639DOI Listing
June 2019

RNA inhibitors of nuclear proteins responsible for multiple organ dysfunction syndrome.

Nat Commun 2019 01 10;10(1):116. Epub 2019 Jan 10.

Internal Medicine, University of Iowa, Iowa City, IA, 52242, USA.

The development of multiple organ dysfunction syndrome (MODS) following infection or tissue injury is associated with increased patient morbidity and mortality. Extensive cellular injury results in the release of nuclear proteins, of which histones are the most abundant, into the circulation. Circulating histones are implicated as essential mediators of MODS. Available anti-histone therapies have failed in clinical trials due to off-target effects such as bleeding and toxicity. Here, we describe a therapeutic strategy for MODS based on the neutralization of histones by chemically stabilized nucleic acid bio-drugs (aptamers). Systematic evolution of ligands by exponential enrichment technology identified aptamers that selectively bind those histones responsible for MODS and do not bind to serum proteins. We demonstrate the efficacy of histone-specific aptamers in human cells and in a murine model of MODS. These aptamers could have a significant therapeutic benefit in the treatment of multiple diverse clinical conditions associated with MODS.
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http://dx.doi.org/10.1038/s41467-018-08030-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328615PMC
January 2019

Proteomic Screening for Serum Biomarkers for Cervical Cancer and Their Clinical Significance.

Med Sci Monit 2019 Jan 9;25:288-297. Epub 2019 Jan 9.

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an, Shaanxi, China (mainland).

BACKGROUND The present study aimed to determine serum markers for cervical cancer (CC) and to provide valuable references for clinical diagnosis and treatment. MATERIAL AND METHODS Serum samples were collected from age-matched healthy control women, and from female CC patients before and after surgery. Serum biomarkers were selected by comparing serum peptides profiles among the 3 groups by magnetic bead-based weak cation - exchange chromatography fractionation combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Probable serum biomarkers for cervical cancer were then further identified by liquid chromatography-electrospray ionization-tandem mass spectrometry system and the identified proteins were verified by enzyme-linked immunosorbent assay (ELISA). RESULTS Three peptide biomarkers were identified for distinguishing CC patients from normal individuals, and distinguishing preoperative CC patients from postoperative CC patients. Of these 3 identified protein peptide regions, 2 peptide regions - TKT (Peak 2, 2435.63 m/z, 499-524) and FGA (Peak 4, 2761.79 m/z, 603-629) - were identified as upregulated markers, and peptide region of APOA1 (Peak 9, 2575.3 m/z, 245-260) was identified as a downregulated biomarker in preoperative CC patients compared with healthy women. CONCLUSIONS The present study provides a new method for identifying potential serum biomarkers for CC patients.
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http://dx.doi.org/10.12659/MSM.911478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338008PMC
January 2019

Gene regulatory divergence between locally adapted ecotypes in their native habitats.

Mol Ecol 2018 11 5;27(21):4174-4188. Epub 2018 Oct 5.

Department of Plant Biology, Michigan State University, East Lansing, Michigan.

Local adaptation is a key driver of ecological specialization and the formation of new species. Despite its importance, the evolution of gene regulatory divergence among locally adapted populations is poorly understood, especially how that divergence manifests in nature. Here, we evaluate gene expression divergence and allele-specific gene expression responses for locally adapted coastal perennial and inland annual accessions of the yellow monkeyflower, Mimulus guttatus, in a field reciprocal transplant experiment. Overall, 6765 (73%) of surveyed genes were differentially expressed between coastal and inland habitats, while 7213 (77%) were differentially expressed between the coastal perennial and inland annual accessions. Cis-regulatory variation was pervasive, affecting 79% (5532) of differentially expressed genes. We detected trans effects for 52% (3611) of differentially expressed genes. Expression plasticity of alleles across habitats (G × E interactions) appears to be relatively common (affecting 18% of transcripts) and could minimize fitness trade-offs at loci that contribute to local adaptation. We also found evidence that at least one chromosomal inversion may act as supergene by holding together haplotypes of differentially expressed genes, but this pattern depends on habitat context. Our results highlight multiple key patterns regarding the relationship between gene expression and the evolution of locally adapted populations.
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http://dx.doi.org/10.1111/mec.14852DOI Listing
November 2018

Composition Engineering in Two-Dimensional Pb-Sn-Alloyed Perovskites for Efficient and Stable Solar Cells.

ACS Appl Mater Interfaces 2018 Jun 13;10(25):21343-21348. Epub 2018 Jun 13.

Department of Materials Science , Fudan University , 200433 Shanghai , China.

Environmentally friendly tin (Sn)-based metallic halide perovskites suffer from oxidation and morphological issues. Here, we demonstrate the composition engineering of Pb-Sn-alloyed two-dimensional (2D) Ruddlesden-Popper perovskites, (BA)(MA)PbSn I, for efficient and stable solar cell applications. Smooth thin films with high surface coverage are readily formed without using any additive owing to the self-assembly characteristic of 2D perovskites. It is found that Sn plays a significant role in improving the crystallization and crystal orientation while narrowing the bandgap of Pb-Sn 2D perovskites. Photophysical studies further reveal that the optimal Sn ratio (25 mol %) based sample exhibits both minimized trap density and weakened quantum confinement for efficient charge separation. Consequently, the optimized (BA)(MA)PbSnI-based solar cells yield the best power conversion efficiency close to 6% with suppressed hysteresis.
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http://dx.doi.org/10.1021/acsami.8b06256DOI Listing
June 2018

Phase Engineering in Quasi-2D Ruddlesden-Popper Perovskites.

J Phys Chem Lett 2018 May 7;9(10):2627-2631. Epub 2018 May 7.

Department of Materials Science , Fudan University , Shanghai 200433 , China.

Quasi-2D Ruddlesden-Popper (RP) halide perovskites have drawn intensive research interest because they possess superior ambient stability while retaining excellent device performance as compared to their pure 2D or 3D counterparts. By phase engineering strategy, quasi-2D perovskites can fall into three types-large- n 2D perovskite, 2D:3D mixed perovskite, and 3D/2D bilayer perovskite. This Perspective discusses the modulation of phase composition, hierarchical distribution, and crystal orientation in quasi-2D perovskites, aiming to uncover the correlation between morphological structure, band alignment, and charge recombination. A perspective of phase engineering in 2D RP-type perovskite materials is then given toward the concurrent stability and device efficiency.
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http://dx.doi.org/10.1021/acs.jpclett.8b00840DOI Listing
May 2018

2D Ruddlesden-Popper Perovskites for Optoelectronics.

Adv Mater 2018 Jan 13;30(2). Epub 2017 Oct 13.

Department of Materials Science, Fudan University, Shanghai, 200433, China.

Conventional 3D organic-inorganic halide perovskites have recently undergone unprecedented rapid development. Yet, their inherent instabilities over moisture, light, and heat remain a crucial challenge prior to the realization of commercialization. By contrast, the emerging 2D Ruddlesden-Popper-type perovskites have recently attracted increasing attention owing to their great environmental stability. However, the research of 2D perovskites is just in their infancy. In comparison to 3D analogues, they are natural quantum wells with a much larger exciton binding energy. Moreover, their inner structural, dielectric, optical, and excitonic properties remain to be largely explored, limiting further applications. This review begins with an introduction to 2D perovskites, along with a detailed comparison to 3D counterparts. Then, a discussion of the organic spacer cation engineering of 2D perovskites is presented. Next, quasi-2D perovskites that fall between 3D and 2D perovskites are reviewed and compared. The unique excitonic properties, electron-phonon coupling, and polarons of 2D perovskites are then be revealed. A range of their (opto)electronic applications is highlighted in each section. Finally, a summary is given, and the strategies toward structural design, growth control, and photophysics studies of 2D perovskites for high-performance electronic devices are rationalized.
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http://dx.doi.org/10.1002/adma.201703487DOI Listing
January 2018

An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis.

J Immunol 2017 10 20;199(8):2823-2833. Epub 2017 Sep 20.

Interdisciplinary Program in Molecular and Cellular Biology, University of Iowa, Iowa City, IA 52242;

The role of the nucleotide-binding domain and leucine-rich repeat containing receptor NLRP10 in disease is incompletely understood. Using three mouse strains lacking the gene encoding NLRP10, only one of which had a coincidental mutation in DOCK8, we documented a role for NLRP10 as a suppressor of the cutaneous inflammatory response to infection. There was no evidence that the enhanced local inflammation was due to enhanced inflammasome activity. NLRP10/DOCK8-deficient mice harbored lower parasite burdens at the cutaneous site of inoculation compared with wild-type controls, whereas NLRP10-deficient mice and controls had similar parasite loads, suggesting that DOCK8 promotes local growth of parasites in the skin, whereas NLRP10 does not. NLRP10-deficient mice developed vigorous adaptive immune responses, indicating that there was not a global defect in the development of Ag-specific cytokine production. Bone marrow chimeras showed that the anti-inflammatory role of NLRP10 was mediated by NLRP10 expressed in resident cells in the skin rather than by bone marrow-derived cells. These data suggest a novel role for NLRP10 in the resolution of local inflammatory responses during infection.
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http://dx.doi.org/10.4049/jimmunol.1500832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679237PMC
October 2017

Insights into charge carrier dynamics in organo-metal halide perovskites: from neat films to solar cells.

Chem Soc Rev 2017 Oct;46(19):5714-5729

Department of Materials Science, Fudan University, Shanghai 200433, China.

Organo-metal halide perovskites have recently obtained world-wide attention as promising solar cell materials. They have broad and strong light absorption along with excellent carrier transport properties which partially explain their record power conversion efficiencies above 22%. However, the basic understanding of the underlying physical mechanisms is still limited and there remain large discrepancies among reported transport characteristics of perovskite materials. Notably, the carrier mobility of perovskite samples either in thin films or within solar cells obtained using different techniques can vary by up to 7-8 orders of magnitude. This tutorial review aims to offer insights into the scope, advantages, limitations and latest developments of the techniques that have been applied for studying charge carrier dynamics in perovskites. We summarize a comprehensive set of measurements including (1) time-resolved laser spectroscopies (transient absorption, time-resolved photoluminescence, terahertz spectroscopy and microwave conductivity); (2) electrical transient techniques (charge extraction by linearly increasing voltage and time-of-flight); and (3) steady-state methods (field-effect transistor, Hall effect and space charge limited current). Firstly, the basics of the above measurements are described. We then comparatively summarize the charge carrier characteristics of perovskite-based neat films, bilayer films and solar cells. Finally, we compare the different approaches in evaluating the key parameters of transport dynamics and unravel the reasons for the large discrepancies among these methods. We anticipate that this tutorial review will serve as the entry point for understanding the experimental results from the above techniques and provide insights into charge carrier dynamics in perovskite materials and devices.
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http://dx.doi.org/10.1039/c6cs00942eDOI Listing
October 2017

MECP2 expression in gastric cancer and its correlation with clinical pathological parameters.

Medicine (Baltimore) 2017 Aug;96(31):e7691

Department of Clinical Medicine, Medical College of Yan'an University, Yan'an, Shanxi, P. R. China.

This study is to investigate the expression of methyl CpG binding protein 2 (MECP2) in gastric cancer (GC) and its clinical significance.Expression of MECP2 was analyzed in 69 cases of GC tissues and 12 paracancerous tissues, either by qRT-PCR at the mRNA level or by Western blot and immunochemistry at the protein level. The correlation of MECP2 expression with clinicopathological parameters was analyzed in the 69 GC patients, and validated in data from the TCGA database. The effect of MECP2 expression on survival was also investigated.MECP2 was significantly increased at both mRNA and protein levels in GC compared with paracancerous tissues. MECP2 positive expression was significantly correlated with the TNM stages, histological types, and lymph node metastasis status, but was not correlated with sex or age. Significantly shorter overall survival and disease-free survival was observed in MECP2 positive GC cases compared with the MECP2 negative cases. Univariate and multivariate analyses showed that gender, histological type, lymph node metastasis, and MECP2 expression were independent prognostic factors of GC.The dysregulated expression of MECP2 in GC and its correlation to clinicopathological parameters indicate that MECP2 may regulate the development of GC.
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http://dx.doi.org/10.1097/MD.0000000000007691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626154PMC
August 2017

Thermal transport in monolayer InSe.

J Phys Condens Matter 2017 Aug 23;29(33):335702. Epub 2017 Jun 23.

Institute for Advanced Study, Shenzhen University, Shenzhen 518060, People's Republic of China. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, People's Republic of China.

Two-dimensional InSe, a recently synthesized semiconductor having a moderate band gap, has gained attention due to its ultra high mobility and high photo-responsivity. In this work, we calculate the lattice thermal conductivity (κ) of monolayer InSe by solving the phonon Boltzmann transport equation (BTE) with first-principles calculated inter atomic force constants. κ of monolayer InSe is isotropic and found to be around 27.6 W m [Formula: see text] at room temperature along the in-plane direction. The size dependence of κ shows the size effect can persist up to 20 μm. Further, κ can be reduced to half by tuning the sample size to 300 nm. This low value suggests that κ might be a limiting factor for emerging nanoelectronic applications of monolayer InSe.
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http://dx.doi.org/10.1088/1361-648X/aa7b63DOI Listing
August 2017

Triple-cation mixed-halide perovskites: towards efficient, annealing-free and air-stable solar cells enabled by Pb(SCN) additive.

Sci Rep 2017 04 6;7:46193. Epub 2017 Apr 6.

Department of Materials Science, Fudan University, Shanghai 200433, China.

Organo-metal halide perovskites have suffered undesirably from structural and thermal instabilities. Moreover, thermal annealing is often indispensable to the crystallization of perovskites and removal of residual solvents, which is unsuitable for scalable fabrication of flexible solar modules. Herein, we demonstrate the non-thermal annealing fabrication of a novel type of air-stable triple-cation mixed-halide perovskites, FAMACsPb(IBr) (FMC) by incorporation of Pb(SCN) additive. It is found that adding Pb(SCN) functions the same as thermal annealing process by not only improving the crystallinity and optical absorption of perovskites, but also hindering the formation of morphological defects and non-radiative recombination. Furthermore, such Pb(SCN)-treated FMC unannealed films present micrometer-sized crystal grains and remarkably high moisture stability. Planar solar cells built upon these unannealed films exhibit a high PCE of 14.09% with significantly suppressed hysteresis phenomenon compared to those of thermal annealing. The corresponding room-temperature fabricated flexible solar cell shows an impressive PCE of 10.55%. This work offers a new avenue to low-temperature fabrication of air-stable, flexible and high-efficiency perovskite solar cells.
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http://dx.doi.org/10.1038/srep46193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382775PMC
April 2017

Light Control of Charge Transfer and Excitonic Transitions in a Carbon Nanotube/Porphyrin Hybrid.

Adv Mater 2017 May 17;29(18). Epub 2017 Mar 17.

Institut Néel, CNRS, BP 166, Grenoble Cedex 9, 38042, Grenoble, France.

Carbon nanotube-chromophore hybrids are promising building blocks in order to obtain a controlled electro-optical transduction effect at the single nano-object level. In this work, a strong spectral selectivity of the electronic and the phononic response of a chromophore-coated single nanotube transistor is observed for which standard photogating cannot account. This paper investigates how light irradiation strongly modifies the coupling between molecules and nanotube within the hybrid by means of combined Raman diffusion and electron transport measurements. Moreover, a nonconventional Raman enhancement effect is observed when light irradiation is on the absorption range of the grafted molecule. Finally, this paper shows how the dynamics of single electron tunneling in the device at low temperature is strongly modified by molecular photoexcitation. Both effects will be discussed in terms of photoinduced excitons coupled to electronic levels.
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http://dx.doi.org/10.1002/adma.201605745DOI Listing
May 2017