Bunching Effect In Single-molecule T4 Lysozyme Nonequilibrium Conformational Dynamics Under Enzymatic Reactions

The bunching effect, implying that conformational motion times tend to bunch in a finite and narrow time window, is observed and identified to be associated with substrate enzyme complex formation in T4 lysozyme conformational dynamics under enzymatic reactions. Using single-molecule fluorescence spectroscopy, we have probed T4 lysozyme conformational motions under the hydrolysis reaction of polysaccharide of E. coli 13 cell walls by monitoring the fluorescence resonant energy transfer (FRET) between a donor acceptor probe pair tethered to T4 lysozyme domains involving open close hinge-bending motions. On the basis of the single-molecule spectroscopic results, molecular dynamics simulation, and a random walk model analysis, multiple intermediate states have been estimated in the evolution of T4 lysozyme enzymatic reaction active complex formation (Chen, Y.; Hu, D.; Vorpagel, E. R.; Lu, H. P. Probing single-molecule T4 lysozyme conformational dynamics by intramolecular fluorescence energy transfer. J. Phys. Chem. B 2003, 107, 7947-7956). In this Article, we report progress on the analysis of the reported experimental results, and we have identified the bunching effect of the substrate enzyme active complex formation time in T4 lysozyme enzymatic reactions. We show that the bunching effect, a dynamic behavior observed for the catalytic hinge-bending conformational motions of T4 lysozyme, is a convoluted outcome of multiple consecutive Poisson rate processes that are defined by protein functional motions under substrate enzyme interactions; i.e., convoluted multiple Poisson rate processes give rise to the bunching effect in the enzymatic reaction dynamics. We suggest that the bunching effect is likely common in protein conformational dynamics involved in conformation-gated protein functions

Probing Single-molecule Interfacial Geminate Electron-cation Recombination Dynamics

Interfacial electron-cation recombination in zinc-tetra (4-carboxyphenyl) porphyrin (ZnTCPP)/TiO(2) nanoparticle system has been probed at the single-molecule level by recording and analyzing photon-to-photon pair times of the ZnTCPP fluorescence. We have. developed a novel approach to reveal the hidden single-molecule interfacial electron-cation recombination dynamics by analyzing the autocorrelation function and a proposed convoluted single-molecule interfacial electron-cation recombination model. Our results suggest that the fluctuations of the interfacial electron transfer (ET) reactivity modulate the ET cycles as well as the interfacial electron-cation recombination dynamics. On the basis of this model, the single-molecule electron-cation recombination time of ZnTCPP/-TiO(2) system is deduced to be at time scale of 10(-5) s. The autocorrelation of photon-to-photon pair times as well as the convoluted ET model has been further demonstrated by simulation and interpreted in terms of the interfacial ET reactivity fluctuation and blinking. Our approach not only can effectively probe the single-molecule interfacial electron-cation dynamics but also can be applied to other single-molecule ground-state regeneration dynamics occurring at interfaces and within condensed phases

Combined Single-molecule Photon-stamping Spectroscopy And Femtosecond Transient Absorption Spectroscopy Studies Of Interfacial Electron Transfer Dynamics

The inhomogeneous interfacial electron transfer (IET) dynamics of 9-phenyl-2,3,7-trihydroxy-6-fluorone (PF)-sensitized TiO2 nanoparticles (NPs) has been probed by a single-molecule photon-stamping technique as well as ensemble-averaged femtosecond transient absorption spectroscopy. The forward electron transfer (FET) time shows a broad distribution at the single-molecule level, indicating the inhomogeneous interactions and ET reactivity of the PF/TiO2 NP system. The broad distribution of the FET time is measured to be 0.4 ± 0.1 ps in the transient absorption and picoseconds to nanoseconds in the photon-stamping measurements. The charge recombination time, having a broad distribution at the single-molecule level, clearly shows a biexponential dynamic behavior in the transient absorption: a fast component of 3.0 ± 0.1 ps and a slow component of 11.5 ± 0.5 ns. We suggest that both strong and weak interactions between PF and TiO2 coexist, and we have proposed two mechanisms to interpret the observed IET dynamics. A single-molecule photon-stamping technique and ensemble-averaged transient absorption spectroscopy provide efficient “zoom-in” and “zoom-out” approaches for probing the IET dynamics. The physical nature of the observed multiexponential or stretched-exponential ET dynamics in the ensemble-averaged experiments, often associated with dynamic and static inhomogeneous ET dynamics, can be identified and analyzed by single-molecule spectroscopy measurements

Probing Single-molecule Interfacial Electron Transfer Dynamics Of Porphyrin On Tio2 Nanoparticles

Single-molecule interfacial electron transfer (ET) dynamics has been studied by using single-molecule fluorescence spectroscopy and microscopic imaging. For a single-molecule zinc-tetra (4-carboxyphenyl) porphyrin (ZnTCPP)/TiO2 nanoparticle system, the single-molecule fluorescence trajectories show strong fluctuation and blinking between bright and dark states. The intermittency and fluctuation of the single-molecule fluorescence are attributed to the variation of the reactivity of interfacial electron transfer. The nonexponential autocorrelation function and the power-law distribution of the probability density of dark times imply the dynamic and static inhomogeneities of the interfacial ET dynamics. On the basis of the power-law analysis, the variation of single-molecule interfacial ET reactivity is analyzed as a fluctuation according to the Levy statistics

Aqueous extract of Aconitum carmichaelii Debeaux attenuates sepsis-induced acute lung injury via regulation of TLR4/NF-ΚB pathway

Purpose: To investigate the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced acute lung injury (ALI), as well as explore the underlying mechanism of action. Methods: C57BL/6 mice were treated with AEACD by gavage (4.0 g/kg/day) for 5 days before cecal ligation and puncture (CLP) challenge. After 24 h, the pathological morphology of lung tissue and the biochemical parameters in bronchoalveolar lavage fluid (BALF) were determined by H&E staining and enzyme-linked immunosorbent assay (ELISA). Furthermore, the total protein content and lactate dehydrogenase (LDH) level of BALF, as well as the oxidative biomarkers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)) were evaluated in the lung homogenates by ELISA assay. The levels of pro-inflammatory cytokines, TNFα, IL-1β, and IL-6, in lung tissue were measured by qRT-PCR or ELISA. Finally, key proteins in Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in lung tissue were evaluated by western blot. Results: CLP challenge induced abnormal changes in the histological structures of lung tissue, lung wet-to-dry weight (W/D) ratio, protein content and LDH levels of BALF, which were remarkably reversed by AEACD. In addition, AEACD decreased MDA levels, and increased GSH levels and SOD activity in the lung tissue of CLP–treated mice (p < 0.05). Furthermore, AEACD attenuated the CLP challengeinduced upregulation of TNFα, IL-1β, and IL-6. Finally, AEACD inactivated TLR4/NF-κB pathway by upregulating IκBα and downregulating TLR4 and phosphorylated-p65 levels. Conclusion: AEACD administration protects mice against sepsis-induced ALI through the regulation of oxidative stress and inflammatory responses in lung tissues. The underlying mechanism occurs by inhibiting TLR4/NF-κB signaling pathway. Keywords: Aconitum carmichaelii Debeaux, Acute lung injury, Sepsis, TLR4, NF-κ

Probing Ground-state Single-electron Self-exchange Across A Molecule-metal Interface

We have probed single-molecule redox reaction dynamics of hemin (chloride) adsorbed on Ag nanoparticle surfaces by single-molecule surface-enhanced Raman spectroscopy (SMSERS) combined with spectroelectrochemistry. Redox reaction at the molecule/Ag interface is identified and probed by the prominent fluctuations of the Raman frequency of a specific vibrational mode, nu(4), which is a typical marker of the redox state of the iron center in a hemin molecule. On the basis of the autocorrelation and cross-correlation analysis of the single-molecule Raman spectral trajectories and the control measurements of single-molecule spectroelectochemistry and electrochemical STM, we suggest that the single-molecule redox reaction dynamics at the hemin Ag interface is primarily driven by thermal fluctuations. The spontaneous fluctuation dynamics of the single-molecule redox reaction is measured under no external electric potential across the molecule metal interfaces, which provides a novel and unique approach to characterize the interfacial electron transfer at the molecule metal interfaces. Our demonstrated approaches are powerful for obtaining molecular coupling and dynamics involved in interfacial electron transfer processes. The new information obtained is critical for a further understanding, design, and manipulation of the charge transfer processes at the molecule metal interface or metal-molecule-metal junctions, which are fundamental elements in single-molecule electronics, catalysis, and solar energy conversion

Simultaneous Spectroscopic And Topographic Near-field Imaging Of Tio2 Single Surface States And Interfacial Electronic Coupling

We have probed single surface states and the involved interfacial charge transfer coupling on the TiO2 surface using confocal as well as tip-enhanced near-field topographic-spectroscopic imaging analysis on a niobium-doped rutile TiO2(110) surface. The confocal images excited with a radially polarized donut mode render ring-shaped excitation patterns typical for quantum systems with two perpendicular transition dipole moments. The tip-enhanced near-field optical images of single surface states are visualized by the strong exciton plasmon-polariton coupling localized at the subdomain boundaries with a spatial resolution of similar to 15 nm (far beyond the optical diffraction limit). We suggest that the abundant surface states in the doped TiO2 generate excitons under laser excitation which are strongly coupled to the surface plasmon polaritons of the Au tip. Moreover, the interfacial electronic molecule-substrate coupling has been characterized by probing the molecule-perturbed surface states distribution and the associated specific Raman vibrational modes. The imaging and characterization of the surface states and their distributions on TiO2 surfaces at nanoscale are critically relevant to a deep understanding of interfacial electron transfer dynamics and energetics involving in solar energy conversion, photocatalysis, and mechanistic understanding of surface-enhanced Raman scattering spectroscopy

An overall and dose-response meta-analysis of red blood cell distribution width and CVD outcomes

Red blood cell distribution width (RDW) is the coefficient of variation of red blood cell size, considered to be associated with cardiovascular disease (CVD). This study aimed to comprehensively synthesize previous studies on RDW and CVD outcomes through an overall and dose-response meta-analysis. PubMed, Embase and Web of Science were searched systematically for English and Chinese language publications up to November 30, 2015. We extracted data from publications matching our inclusion criteria for calculating pooled hazard ratio (HR), which was used to assess prognostic impact of RDW on CVD. Twenty-seven articles, consisting of 28 studies and 102,689 participants (mean age 63.9 years, 63,703 males/36,846 females, 2,140 gender-unmentioned subjects) were included in the present meta-analysis. The pooled HRs are 1.12 (95% CI = 1.09–1.15) for the association of all-cause mortality (ACM) per 1% increase of RDW, 1.12(95% CI = 1.08–1.17) for major adverse cardiac events (MACEs) per 1% increase of RDW. A dose-response curve relating RDW increase to its effect on CVD outcomes was established (pcurve \u3c 0.001). For every 1-unit increase of RDW, there is an increased risk of occurrence of ACM (pooled HR = 1.03, 95% CI = 1.02–1.04) and MACEs (pooled HR = 1.04, 95% CI = 1.01–1.06). This study indicates RDW may be a prognostic indicator for CVD outcomes

Align before Search: Aligning Ads Image to Text for Accurate Cross-Modal Sponsored Search

Cross-Modal sponsored search displays multi-modal advertisements (ads) when consumers look for desired products by natural language queries in search engines. Since multi-modal ads bring complementary details for query-ads matching, the ability to align ads-specific information in both images and texts is crucial for accurate and flexible sponsored search. Conventional research mainly studies from the view of modeling the implicit correlations between images and texts for query-ads matching, ignoring the alignment of detailed product information and resulting in suboptimal search performance.In this work, we propose a simple alignment network for explicitly mapping fine-grained visual parts in ads images to the corresponding text, which leverages the co-occurrence structure consistency between vision and language spaces without requiring expensive labeled training data. Moreover, we propose a novel model for cross-modal sponsored search that effectively conducts the cross-modal alignment and query-ads matching in two separate processes. In this way, the model matches the multi-modal input in the same language space, resulting in a superior performance with merely half of the training data. Our model outperforms the state-of-the-art models by 2.57% on a large commercial dataset. Besides sponsored search, our alignment method is applicable for general cross-modal search. We study a typical cross-modal retrieval task on the MSCOCO dataset, which achieves consistent performance improvement and proves the generalization ability of our method. Our code is available at https://github.com/Pter61/AlignCMSS