Theoretical study on the lasing plasmon of a split ring for label-free detection of single molecules and single nanoparticles

This paper reports the plasmonic lasing of a split ring filled with gain material in water. The lasing mode（1500 nm）is far from the pump mode（980 nm）, which can depress the detection noise from the pump light. The laser intensities of the two modes simultaneously increase by more than 10^3 in amplitude, which can intensify the absorption efficiency of the pumping light and enhance the plasmonic lasing. The plasmonic lasing is a sensitive sensor. When a single protein nanoparticle（n = 1.5, r = 1.25 nm） is trapped in the gap of the split ring, the lasing spectrum moves by 0.031 nm, which is much larger than the detection limit of 10^-5 nm. Moreover, the lasing intensity is also very sensitive to the trapped nanoparticle. It reduces to less than 1/600 when a protein nanoparticle（n = 1.5, r = 1.25 nm） is trapped in the gap.

Preferable Orientations of Interacting C_(60) Molecules inside Single Wall Boron Nitride Nanotubes

This work focuses on the preferable orientation analysis of the hybrid system where the C60 molecules are encap- sulated inside the boron nitride nanotubes by using the two-molecule model. The low-energy state can be acquired in the contour map, which provides the visual information of the systematical van der Waals interaction potential for the C60 molecules adopting different orientations. Our results show that the C60 molecules exhibit the pre- ferred pentagon and hexagon orientations with the tube＇s diameter smaller and larger than 13.55A, respectively. The preferred two-bond orientation obtained in the single-molecule model is absent in this study, indicating that the intermolecular interaction of adjacent C60 molecules plays an important role in the orientational behaviors of this peapod structure.

Photon Statistical Properties of Single Terrylene Molecules in P-Terphenyl Crystals

We consider the photon emission statistical properties of a single molecule under pump-probe field driving, using the generating function method. The first- and second-order moments of statistical quantities are presented. Derived from the first-order moment, the line shapes are in good agreement with the experimental results. Derived from the second-order moment, Mandel＇s Q parameters show an obvious quantum effect of photon statistical distribution, i.e., the anti-bunching effect.

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Adjuvant postbiotic administration improves dental caries prognosis by restoring the oral microbiota

Conventional filling therapy fails to fundamentally reduce oral cariogenic bacteria.Thus,oral microbiota follow-up intervention after filling would be necessary for improving dental caries prognosis.We recruited 9 caries-free individuals,and 89 dental caries subjects(5 dropouts).Eighty-nine patients were randomized into three groups:caries(n=8;no treatment),control(n=40;filling),and postbiotics(n=41;filling and 14-day Probio-Eco®intervention).Salivary samples were collected at 0 day(after filling)and 14 days.Our results showed that the diversity of dental caries oral microbiota was significantly increased compared with healthy subjects,and filling could restore a healthier oral microbiota partially and temporarily.Thepostbiotics intervention keeps a low alpha-diversity.Co-occurrence network analysis showed that a more stable oral microbiota structure after postbiotics intervention.Taxonomic and functional annotation of the microbiota revealed that postbiotics co-treatment significantly:increased the relative abundance of Pseudomonas and P.reactans,decreased the relative abundance of Prevotella shahii,and enriched the energy metabolism-related pathways.BugBase-predicted phenotypes inferred to an oral microbiota with decreased potential pathogenic bacteria and increased oxidative stress-tolerant bacteria after postbiotics intervention.Collectively,it suggested that postbiotics co-treatment could be a promising strategy that restores the oral microecological balance for dental caries.

Interaction Study between DNA and Histone Proteins on Single-molecule Level using Atomic Force Microscopy

DNA and histone protein are important in the formation of nucleosomal arrays, which are the first packaging level of DNA into a more compact chromatin structure. To characterize the interactions of DNA and histone proteins, we reconstitute nucleosomes using lambda DNA and whole histone proteins by dialysis and perform direct atomic force microscopy （AFM） imaging. Compared with non-specific DNA and histone binding, nucleosomes are formed within the assembled “beads-on-a-string” nucleosomal array by dialysis. These observations facilitate the establishment of the molecular mechanisms of nucleosome and demonstrate the capability of AFM for protein-DNA interaction analysis.

π-Electron-Assisted Relaxation of Spin Excited States in Cobalt Phthalocyanine Molecules on Au（111） Surface

We present our investigation on the spin relaxation of cobalt phthalocyanine （CoPc） films on Au（111） （CoPc/Au（111）） surface using scanning tunneling microscopy and spectroscopy. The spin relaxation time derived from the linewidth of spin-flip inelastic electron tunneling spectroscopy is quantitatively analyzed according to the Korringa-like formula. We find that although this regime of the spin relaxation time calculation by just considering the exchange interaction between itinerant conduction electrons and localized d-shells （s-d exchange interaction） can successfully reproduce the experimental value of the adsorbed magnetic atom, it fails in our case of CoPc/Au（111）. Instead, we can obtain the relaxation time that is in good agreement with the experimental result by considering the fact that the 7c electrons in CoPc molecules are spin polarized, where the spin polarized 7c electrons extended at the Pc macrocycle may also scatter the conduction electrons in addition to the localized d spins. Our analyses indicate that the scattering by the π electrons provides an efficient spin relaxation channel in addition to the s-d interaction and thus leads to much short relaxation time in such a kind of molecular system on a metal substrate.

MORPHOLOGY EVOLUTION IN PTFE AS A FUNCTION OF MELT TIME AND TEMPERATURE——Ⅰ.HIGH MOLECULAR WEIGHT SINGLE-AND MULTI-MOLECULE FOLDED CHAIN SINGLE CRYSTALS AND BAND STRUCTURES

The effect of sintering dispersed dispersion and nano-emulsion particles of high molecular weightpolytetrafluoroethylene(PTFE)on a substrate as a function of“melt”time and temperature is described.Folded chain singlecrystals parallel to the substrate and as ribbons on-edge(with double striations),as well as bands,are produced for longersintering times;particle merger and diffusion of individual molecules,crystallizing as folded chain,single(or few)molecule,single crystals when“trapped”on the substrate by cooling occur for shorter sintering times.It is suggested the observedstructures develop with sintering time,in a mesomorphic melt.The structure of the nascent particles is also discussed.

A glass nanopore electrode for single molecule detection

We have developed a simple method for fabricating robust and low noise glass nanopore electrodes with pore size 10±5 nm to detect single molecules.β-Cyclodextrin was used as model compound for characterization.In 1.0 mol/L NaCl solution,the molecules generated current pulses of 2-5 pA with noise level less than 0.8 pA.A slide mode and a plug mode were suggested for the way ofβ-cyclodextrin single molecule moving into the glass nanopores.

Visualized SERS Imaging of Single Molecule by Ag/ Black Phosphorus Nanosheets

Single-molecule detection and imaging are of great value in chemical analysis,biomarker identification and other trace detection fields.However,the localization and visualization of single molecule are still quite a challenge.Here,we report a special-engineered nanostructure of Ag nanoparticles embedded in multi-layer black phosphorus nanosheets(Ag/BP-NS)synthesized by a unique photoreduction method as a surfaceenhanced Raman scattering(SERS)sensor.Such a SERS substrate features the lowest detection limit of 10^(–20) mol L^(−1) for R6G,which is due to the three synergistic resonance enhancement of molecular resonance,photoinduced charge transfer resonance and electromagnetic resonance.We propose a polarization-mapping strategy to realize the detection and visualization of single molecule.In addition,combined with machine learning,Ag/BP-NS substrates are capable of recognition of different tumor exosomes,which is meaningful for monitoring and early warning of the cancer.This work provides a reliable strategy for the detection of single molecule and a potential candidate for the practical bio-application of SERS technology.

Detailed investigation on single water molecule entering carbon nanotubes

The behavior of a water molecule entering carbon nanotubes （CNTs） is stud- ied. The Lennaxd-Jones potential function together with the continuum approximation is used to obtain the van der Waals interaction between a single-walled CNT （SWCNT） and a single water molecule. Three orientations are chosen for the water molecule as the center of mass is on the axis of nanotube. Extensive studies on the variations of force, energy, and velocity distributions axe performed by vaxying the nanotube radius and the orientations of the water molecule. The force and energy distributions are validated by those obtained from molecular dynamics （MD） simulations. The acceptance radius of the nanotube for sucking the water molecule inside is derived, in which the limit of the radius is specified so that the nanotube is favorable to absorb the water molecule. The velocities of a single water molecule entering CNTs axe calculated and the maximum entrance and the interior velocity for different orientations axe assigned and compared.

Improved data analysis method of single-molecule experiments based on probability optimization

To extract the dynamic parameters from single molecule manipulation experiments, usually lots of data at different forces need to be recorded. But the measuring time of a single molecule is limited due to breakage of the tether or degradation of the molecule. Here we propose a data analysis method based on probability maximizalion of the recorded time trace to extract the dynamic parameters from a single measurement. The feasibility of this method was verified by dealing with the simulation data of a two-state system. We also applied this method to estimate the parameters of DNA hairpin folding and unfolding dynamics measured by a magnetic tweezers experiment.

A versatile platform for single-molecule enzymology of restriction endonuclease

Enzymes are the major players for many biological processes.Fundamental studies of the enzymatic activity at the single-molecule level provides important information that is otherwise inaccessible at the ensemble level.Yet,these single-molecule experiments are technically di±cult and generally require complicated experimental design.Here,we develop a Holliday junction(HJ)-based platform to study the activity of restriction endonucleases at the single-molecule level using single-molecule FRET(sm-FRET).We show that the intrinsic dynamics of HJ can be used as the reporter for both the enzyme-binding and the substrate-release events.Thanks to the multiple-arms structure of HJ,the fluorophore-labeled arms can be different from the surface anchoring arm and the substrate arm.Therefore,it is possible to independently change the substrate arm to study different enzymes with similar functions.Such a design is extremely useful for the systematic study of enzymes from the same family or enzymes bearing different pathologic mutations.Moreover,this method can be easily extended to study other types of DNA-binding enzymes without too much modi fication of the design.We anticipate it can find broad applications in single-molecule enzymology.

Deterministic Generation of Quantum State Transfer Between Spatially Separated Single Molecule Magnets

We propose a new scheme for realizing deterministic quantum state transfer （QST） between two spatially separated single molecule magnets （SMMs） with the framework of cavity quantum eleetrodynamics （QED）. In the present scheme, two SMMs are trapped in two spatially separated optical cavities coupled by an optical fiber. Through strictly numerically simulating, we demonstrate that our scheme is robust with respect to the SMMs＇ spontaneous decay and fiber loss under the conditions of dispersive SMMs-field interaction and strong coupling of cavity fiber. In addition, we also discuss the influence of photon leakage out of cavities and show that our proposal is good enough to demonstrate the generation of QST with high fidelity utilizing the current experimental technology. The present investigation provides research opportunities for realizing QST between solid-state qubits and may result in a substantial impact on the progress of solid-state-based quantum communications network.

Real-Time analysis of exosome secretion of single cells with single molecule imaging

The exosome-mediated response can promote or restrain the diseases by regulating the intracellular pathways,making the exosome become an effective marker for diagnosis and therapeutic control at the single-cell level.However,real-time analysis is hard to be achieved with traditional approaches because the exosomes usually need to be enriched by ultracentrifugation for a measurable signal-to-noise ratio.Recently developed label-free single-molecule imaging approaches may become an real-time quantitative tool for the analysis of single exosomes and related secretion behaviors of single living cells owing to their extreme sensitivity.

Combination of Micro-fluidic Chip with Fluorescence Correlation Spectroscopy for Single Molecule Detection

A single molecule detection technique was developed by the combination of a single channel poly （dimethylsiloxane）/glass micro-fluidic chip and fluorescence correlation spectroscopy （FCS）. This method was successfully used to determine the proportion of two model components in the mixture containing fluorescein and the rhodamine-green succinimidyl ester.

Magnetic anisotropy in 5d transition metal-porphyrin molecules

Single molecule magnets(SMMs) with large magnetic anisotropy energy(MAE) have great potential applications in magnetic recording.Using the first-principles calculations,we investigate the MAE of 5 d transition metal-porphyrin-based SMMs by using the PBE and PBE+U with different U values,respectively.The results indicate that W-P,Re-P,Os-P,and Ir-P possess the considerably large MAE among 5 d TM-P SMMs.Furthermore,the MAE of 5 d TM-P can be facilely manipulated by tensile strain.The reduction of the absolute value of MAE for Ir-P molecule caused by tensile strain makes it easier to implement the writing operation.The decreasing of the occupation number of minority-spin channels of Ir-d_(x^(2)-y^(2)) orbital leads the MAE to decrease when the tensile strain increases.

Single Molecule FRET Study of DNAG Quadruplex

The DNA G quadruplex formed by the human telomeric sequence is a potential target for novel anticancer drugs. We have investigated an intramolecular DNA G quadruplex using single molecule fluorescence resonance energy transfer and shown that individual folded quadruplexes can be identified. The mean proximity ratio measured at the single molecule level was consistent with ensemble measurement

Supramolecular organization of the sperm plasma membrane during maturation and capacitation

Aim： In the present study, a variety of high resolution microscopy techniques were used to visualize the organization and motion of lipids and proteins in the sperm＇s plasma membrane. We have addressed questions such as the presence of diffusion barriers, confinement of molecules to specific surface domains, polarized diffusion and the role of cholesterol in regulating lipid rafts and signal transduction during capacitation. Methods： Atomic force microscopy identified a novel region （EqSS） within the equatorial segment of bovine, porcine and ovine spermatozoa that was enriched in constitutively phosphorylated proteins. The EqSS was assembled during epididymal maturation. Fluorescence imaging techniques were then used to follow molecular diffusion on the sperm head. Results： Single lipid molecules were freely exchangeable throughout the plasma membrane and showed no evidence for confinement within domains. Large lipid aggregates, however, did not cross over the boundary between the post-acrosome and equatorial segment suggesting the presence of a molecular filter between these two domains. Conclusion： A small reduction in membrane cholesterol enlarges or increases lipid rafts concomitant with phosphorylation of intracellular proteins. Excessive removal of cholesterol, however, disorganizes rafts with a cessation of phosphorylation. These techniques are forcing a revision of long-held views on how lipids and proteins in sperm membranes are assembled into larger complexes that mediate recognition and fusion with the egg. （Asian JAndrol 2007 July; 9： 438-444）

Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators

Single-molecule detection is one of the fundamental challenges of modern biology.Such experiments often use labels that can be expensive,difficult to produce,and for small analytes,might perturb the molecular events being studied.Analyte size plays an important role in determining detectability.Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius,and 15.5 kDa molecules are detected in aqueous solution,thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell.Our results,covering several orders of magnitude of particle radius(100 nm to 2 nm),agree with the‘reactive’model prediction for the frequency shift of the resonator upon particle binding.This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle.We anticipate that our results will enable many applications,including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.