Nonlocal Optical Response of Particle Plasmons in Single Gold Nanorods.

The investigation of particle plasmons in metal nanoparticles has predominantly relied on local optical response approximations. However, as the nanoparticle size approaches the average distance of electrons to the metal surface, mesoscopic effects such as size-dependent plasmon line width broadening and resonance energy blue shifts are expected to become observable. In this work, we compared the experimental spectral characteristics with simulated values obtained by using a generalized nonlocal optical response theory-based local analogue model. Our results show that the nonlocal plasmon damping effects in single nanoparticles are less pronounced than those observed in plasmon-coupled systems. Furthermore, our research demonstrates that single-particle dark-field spectroscopy is an effective tool for investigating the nonlocal optical response of particle plasmons in single nanoparticles. These results have important implications for the rational design of novel nanophotonic devices.

Multiple solution solving in plasmon sensing by deep learning: determination of layer refractive index and thickness in one experiment: comment.

In a recent Letter [Opt. Lett.46, 5667 (2021)10.1364/OL.444442], Du et al. proposed a deep learning method for determining the refractive index (n) and thickness (d) of the surface layer on nanoparticles in a single-particle plasmon sensing experiment. This comment highlights the methodological issues arising in that Letter.

Steering the Pathway of Plasmon-Enhanced Photoelectrochemical CO2 Reduction by Bridging Si and Au Nanoparticles through a TiO2 Interlayer.

Photoelectrochemical (PEC) conversion of CO2 in an aqueous medium into high-energy fuels is a creative strategy for storing solar energy and closing the anthropogenic carbon cycle. However, the rational design of catalytic architectures to selectively and efficiently produce a target product such as CO has remained a grand challenge. Herein, an efficient and selective Si photocathode for CO production is reported by utilizing a TiO2 interlayer to bridge the Au nanoparticles and n+ p-Si. The TiO2 interlayer can not only effectively protect and passivate Si surface, but can also exhibit outstanding synergies with Au nanoparticles to greatly promote CO2 reduction kinetics for CO production through stabilizing the key reaction intermediates. Specifically, the TiO2 layer and Au nanoparticles work concertedly to enhance the separation of localized surface plasmon resonance generated hot carriers, contributing to the improved activity and selectivity for CO production by utilizing the hot electrons generated in Au nanoparticles during PEC CO2 reduction. The optimized Au/TiO2 /n+ p-Si photocathode exhibits a Faradaic efficiency of 86% and a partial current density of -5.52 mA cm-2 at -0.8 VRHE for CO production, which represent state-of-the-art performance in this field. Such a plasmon-enhanced strategy may pave the way for the development of high-performance PEC photocathodes for energy-efficient CO2 utilization.

Observing Mesoscopic Nucleic Acid Capacitance Effect and Mismatch Impact via Graphene Transistors.

This work reports a molecular-scale capacitance effect of the double helical nucleic acid duplex structure for the first time. By quantitatively conducting large sample measurements of the electrostatic field effect using a type of high-accuracy graphene transistor biosensor, an unusual charge-transport behavior is observed in which the end-immobilized nucleic acid duplexes can store a part of ionization electrons like molecular capacitors, other than electric conductors. To elucidate this discovery, a cascaded capacitive network model is proposed as a novel equivalent circuit of nucleic acid duplexes, expanding the point-charge approximation model, by which the partial charge-transport observation is reasonably attributed to an electron-redistribution behavior within the capacitive network. Furthermore, it is experimentally confirmed that base-pair mismatches hinder the charge transport in double helical duplexes, and lead to directly identifiable alterations in electrostatic field effects. The bioelectronic principle of mismatch impact is also self-consistently explained by the newly proposed capacitive network model. The mesoscopic nucleic acid capacitance effect may enable a new kind of label-free nucleic acid analysis tool based on electronic transistor devices. The in situ and real-time nucleic acid detections for virus biomarkers, somatic mutations, and genome editing off-target may thus be predictable.

Revisiting the plasmon radiation damping of gold nanorods.

Noble metal nanoparticles have been utilized for a vast amount of optical applications. For applications that use metal nanoparticles as nanosensors and for optical labeling, higher radiative efficiency is preferred. To get a deeper knowledge about the radiation damping of noble metal nanoparticles, we used gold nanorods with different geometry factors (aspect ratios) as the model system to study. We investigated theoretically how the radiation damping of a nanorod depends on the material, and shape of the particle. Surprisingly, a simple analytical equation describes radiation damping very accurately and allows the disentanglement of the maximal radiation damping parameter for gold nanorods with resonance energy Eres around 1.81 eV (685 nm). We found very good agreement with theoretical predictions and experimental data obtained by single-particle spectroscopy. Our results and approaches may pave the way for designing and optimizing gold nanostructures with higher optical signal and better sensing performance.

Single-particle spectroscopic investigation on the scattering spectrum of Au@MoS2 core-shell nanosphere heterostructure.

Owing to the uniform shape of the nanospheres, the Au@MoS2 core-shell nanosphere heterostructure enables us to design nano-optoelectronic devices and nanosensors with highly tunable and reproducible optical properties. However, until now, at the single-particle level, there is still uncertainty as to how much the scattering characteristics depend on the particle size and the local environment. In this letter, we performed an in situ single-particle study of the scattering spectrum of the Au@MoS2 core-shell nanosphere heterostructure before and after coating with the MoS2 layer. Single-particle characterization confirms that the classic quasi-static approximation (QSA) theory can be used to predict the scattering spectra of Au@MoS2 core-shell nanoparticles. Moreover, we have found that the A and B-exciton absorption peaks do not rely on the local refractive index change, while the position of the particle plasmon resonances does. Such features can be used as an internal reference for sensing applications against measurement errors, such as defocusing the imaging. Our results show that Au@MoS2 core-shell nanoparticles have the potential to become one of the promising nanosensors in the field of single-particle sensing.

Intensity-Based Single Particle Plasmon Sensing.

Plasmon sensors respond to local changes of their surrounding environment with a shift in their resonance wavelength. This response is usually detected by measuring light scattering spectra to determine the resonance wavelength. However, single wavelength detection has become increasingly important because it simplifies the setup, increases speed, and improves statistics. Therefore, we investigated theoretically how the sensitivity toward such single wavelength scattering intensity changes depend on the material and shape of the plasmonic sensor. Surprisingly, simple equations describe this intensity sensitivity very accurately and allow us to distinguish the various contributions: Rayleigh scattering, dielectric contrast, plasmon shift, and frequency-dependent plasmon bulk damping. We find very good agreement of theoretical predictions and experimental data obtained by single particle spectroscopy.

Mapping Hot Electron Response of Individual Gold Nanocrystals on a TiO2 Photoanode.

Incorporating metal nanocrystals with semiconductor photoanodes significantly enhances the efficiency of the energy conversion in the visible range during water splitting due to the excitation of hot electrons. While extensively studied on ensemble samples, hot electron response of metal nanocrystals in a photoelectrochemical cell remains unexploited at the single-particle level. Herein, we systematically investigate hot electron response of individual single-crystalline gold nanocrystals (AuNCs) on a TiO2 photoanode during water splitting. We directly correlate the morphology of the AuNC and its plasmonic property to the efficiencies involving hot electrons with the help of single-particle dark-field microscopy and photocurrent mapping. Our results show that the efficiencies of individual AuNCs are dependent on a variety of factors including interface condition, applied bias, excitation power, incident angle, and AuNC size. Our research may shed light on optimizing the light-harvesting capability of metal/semiconductor photoanodes by providing insights into the photocatalytic processes.

Fully Solid-State Graphene Transistors with Striking Homogeneity and Sensitivity for the Practicalization of Single-Device Electronic Bioassays.

To break through a critical barrier in the practical application of graphene biosensors, namely, device-to-device performance inhomogeneity, this work presents a novel scenario employing a fully solid-state (FSS) transistor configuration. Herein, the graphene sensing unit is completely encapsulated by a high-κ solid dielectric material, which isolates the sensing unit from solution contaminants and thus homogeneously maintains the extraordinary carrier mobility of pristine graphene in batch-made devices. To create an interface sensitive to biomolecular interactions based on the FSS configuration, a metallic floating gate functionalized by conductive mercapto-phenyl molecular linkers is defined on the top-layer solid dielectric. As the solid dielectric layer beneath the metal floating gate enables a higher capacitive gating efficiency than the regular graphene-solution electrical double layer (EDL) interface, the overall transistor amplification gain is further enhanced. As a proof of principle, a label-free DNAzymatic bioassay of Pb2+ is conducted. Without the traditional one-by-one device normalization, an excellent concentration detection limit of 929.8 fM is achieved, which is almost 2 orders of magnitude lower than that in existing works. The FSS configuration allows enhanced sensitivity and homogeneity, thereby providing new developmental guidelines for graphene biosensors beyond the laboratory investigation stage. Additionally, it has the potential to be universally applicable for cost-efficient single-device bioassays.

Structural and mechanistic insights into the interaction of the circadian transcription factor BMAL1 with the KIX domain of the CREB-binding protein.

The mammalian CLOCK:BMAL1 transcription factor complex and its coactivators CREB-binding protein (CBP)/p300 and mixed-lineage leukemia 1 (MLL1) critically regulate circadian transcription and chromatin modification. Circadian oscillations are regulated by interactions of BMAL1's C-terminal transactivation domain (TAD) with the KIX domain of CBP/p300 (activating) and with the clock protein CRY1 (repressing) as well as by the BMAL1 G-region preceding the TAD. Circadian acetylation of Lys537 within the G-region enhances repressive BMAL1-TAD-CRY1 interactions. Here, we characterized the interaction of the CBP-KIX domain with BMAL1 proteins, including the BMAL1-TAD, parts of the G-region, and Lys537 Tethering the small compound 1-10 in the MLL-binding pocket of the CBP-KIX domain weakened BMAL1 binding, and MLL1-bound KIX did not form a ternary complex with BMAL1, indicating that the MLL-binding pocket is important for KIX-BMAL1 interactions. Small-angle X-ray scattering (SAXS) models of BMAL1 and BMAL1:KIX complexes revealed that the N-terminal BMAL1 G-region including Lys537 forms elongated extensions emerging from the bulkier BMAL1-TAD:KIX core complex. Fitting high-resolution KIX domain structures into the SAXS-derived envelopes suggested that the G-region emerges near the MLL-binding pocket, further supporting a role of this pocket in BMAL1 binding. Additionally, mutations in the second CREB-pKID/c-Myb-binding pocket of the KIX domain moderately impacted BMAL1 binding. The BMAL1(K537Q) mutation mimicking Lys537 acetylation, however, did not affect the KIX-binding affinity, in contrast to its enhancing effect on CRY1 binding. Our results significantly advance the mechanistic understanding of the protein interaction networks controlling CLOCK:BMAL1- and CBP-dependent gene regulation in the mammalian circadian clock.

In situ monitoring of silver adsorption on assembled gold nanorods by surface-enhanced Raman scattering.

Self-assembly of metal nanocrystals is able to create a gap of sub-nanometer distance for concentrating incoming light by the strong coupling of surface plasmon resonance, known as a 'hot spot'. Although the plasmonic property of silver is better than other metals in the visible range, the superior Raman enhancement of silver compared to gold is still under debate. To provide direct evidence, in this work, we studied the silver adsorption on assembled gold nanorods (AuNRs) using in situ surface-enhanced Raman scattering (SERS) measurements. The self-assembled AuNR multimers were used as the SERS substrate, where the 4-mercaptophenol (MPh) molecules in our experiment played dual roles as both probe molecules for the Raman scattering and linking molecules for the AuNR assembly in a basic environment. Silver atoms were adsorbed on the surface of gold nanorod assemblies by reduction of Ag+ anions. The stability of the adsorbed silver was guaranteed by the basic environment. We monitored the SERS signal during the silver adsorption with a home-built in situ Raman spectroscope, which was synchronized by recording the UV-vis absorption spectra of the reaction solution to instantly quantify the plasmonic effect of the silver adsorption. Although a minor change was found in the plasmonic resonance wavelength or intensity, the measured SERS signal at specific modes faced a sudden increase by 2.1 folds during the silver adsorption. The finite element method (FEM) simulation confirmed that the silver adsorption corresponding to the plasmonic resonance variation gave little change to the electric field enhancement. We attributed the mode-specific enhancement mechanism of the adsorption of silver to the chemical enhancement from charge transfer (CT) for targeting molecules with a specific orientation. Our findings provided new insights to construct SERS substrates with higher enhancement factor (EF), which hopefully would encourage new applications in the field of surface-enhanced optical spectroscopies.

Efficacy and Safety of Ezetimibe in Combination with Atorvastatin for Acute Coronary Syndrome Patients Accompanied with Type 2 Diabetes: A Single-Center, Non-randomized Cohort Study.

Patients with type 2 diabetes (T2DM) and hyperlipidemia are with high risk of myocardial infarction (MI) or coronary death events. The combined use of ezetimibe and atorvastatin could improve treatment efficacy and safety. To explore the efficacy and safety of ezetimibe in combination with atorvastatin for the treatment of patients with T2DM and acute coronary syndrome (ACS). This was a non-randomized cohort study of 95 consecutive, treatment-naïve patients with T2DM and ACS treated at the Quanzhou First Hospital of Fujian Province between February 2014 and March 2016. According to the treatment strategy they selected, the patients were categorized into the atorvastatin (n = 46) and atorvastatin + ezetimibe (n = 49) groups. The patients were followed up at 2 weeks and 12 months. The primary endpoints included the incidence of adverse cardiovascular events and changed in blood lipids and high-sensitivity C-reactive protein (hs-CRP). At 12 months, serum total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels were significantly lower, and high-density lipoprotein cholesterol (HDL-C) levels were significantly higher in the atorvastatin + ezetimibe (EZ) group than in the atorvastatin group (all p < 0.05). The LDL-C control rate at 12 months was significantly higher in the atorvastatin + EZ group compared with the atorvastatin group (p = 0.006). Seven patients in the atorvastatin group were re-hospitalized for angina pectoris, while only one patient in the atorvastatin + EZ group was re-hospitalized for angina pectoris (p = 0.02). The efficacy of atorvastatin + EZ in treating T2DM patients accompanied with ACS was significantly higher than using atorvastatin alone. This combined strategy has good safety profile, and could be recommended for clinical application.

Conformational Dynamics of a Single Protein Monitored for 24 h at Video Rate.

We use plasmon rulers to follow the conformational dynamics of a single protein for up to 24 h at a video rate. The plasmon ruler consists of two gold nanospheres connected by a single protein linker. In our experiment, we follow the dynamics of the molecular chaperone heat shock protein 90 (Hsp90), which is known to show "open" and "closed" conformations. Our measurements confirm the previously known conformational dynamics with transition times in the second to minute time scale and reveals new dynamics on the time scale of minutes to hours. Plasmon rulers thus extend the observation bandwidth 3-4 orders of magnitude with respect to single-molecule fluorescence resonance energy transfer and enable the study of molecular dynamics with unprecedented precision.

Plasmonic Nanosensors Reveal a Height Dependence of MinDE Protein Oscillations on Membrane Features.

Single-particle plasmon spectroscopy has become a standard technique to detect and quantify the presence of unlabeled macromolecules. Here, we extend this method to determine their exact distance from the plasmon sensors with sub-nanometer resolution by systematically varying the sensing range into the surrounding by adjusting the size of the plasmonic nanoparticles. We improved current single-particle plasmon spectroscopy to record continuously for hours the scattering spectra of thousands of nanoparticles of different sizes simultaneously with 1.8 s time resolution. We apply this technique to study the interaction dynamics of bacterial Min proteins with supported lipid membranes of different composition. Our experiments reveal a surprisingly flexible operating mode of the Min proteins: In the presence of cardiolipin and membrane curvature induced by nanoparticles, the protein oscillation occurs on top of a stationary MinD patch. Our results reveal the need to consider membrane composition and local curvature as important parameters to quantitatively understand the Min protein system and could be extrapolated to other macromolecular systems. Our label-free method is generally easily implementable and well suited to measure distances of interacting biological macromolecules.

Multiplexed immunosensing of cancer biomarkers on a split-float-gate graphene transistor microfluidic biochip.

This work reports the development of a novel microfluidic biosensor using a graphene field-effect transistor (GFET) design for the parallel label-free analysis of multiple biomarkers. Overcoming the persistent challenge of constructing µm2-sized FET sensitive interfaces that incorporate multiple receptors, we implement a split-float-gate structure that enables the manipulation of multiplexed biochemical functionalization using microfluidic channels. Immunoaffinity biosensing experiments are conducted using the mixture samples containing three liver cancer biomarkers, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), and parathyroid hormone (PTH). The results demonstrate the capability of our label-free biochip to quantitatively detect multiple target biomarkers simultaneously by observing the kinetics in 10 minutes, with the detection limit levels in the nanomolar range. This microfluidic biosensor provides a valuable analytical tool for rapid multi-target biosensing, which can be potentially utilized for domiciliary tests of cancer screening and prognosis, obviating the need for sophisticated instruments and professional operations in hospitals.

Perivascular epithelioid cell tumors of the liver misdiagnosed as hepatocellular carcinoma: Three case reports.

BACKGROUND: Hepatic perivascular epithelioid cell neoplasms (PEComas) are rare. Diagnostic and treatment experience with hepatic PEComa remains insufficient. CASE SUMMARY: Three hepatic PEComa cases are reported in this paper: One case of primary malignant hepatic PEComa, one case of benign hepatic PEComa, and one case of hepatic PEComa with an ovarian mature cystic teratoma. During preoperative imaging and pathological assessment of intraoperative frozen samples, patients were diagnosed with hepatocellular carcinoma (HCC), while postoperative pathology and immunohistochemistry subsequently revealed hepatic PEComa. Patients with hepatic PEComa which is misdiagnosed as HCC often require a wider surgical resection. It is easy to mistake them for distant metastases of hepatic PEComa and misdiagnosed as HCC, especially when it's combined with tumors in other organs. Three patients eventually underwent partial hepatectomy. After 1-4 years of follow-up, none of the patients experienced recurrence or metastases. CONCLUSION: A clear preoperative diagnosis of hepatic PEComa can reduce the scope of resection and prevent unnecessary injuries during surgery.

Impact of shift work on irritable bowel syndrome and functional dyspepsia: A meta-analysis.

BACKGROUND: The possible association between shift work with irritable bowel syndrome (IBS) and functional dyspepsia (FD) remains controversial. The purpose of the study is to conduct a meta-analysis to explore the potential association between shift work with IBS/FD. METHODS: We searched relevant observational studies on Medline (PubMed) and Embase until June 30, 2021. Two different investigators extracted data and assessed the quality of each study independently. The meta-analysis was used to evaluate the pooled odds risk (OR) between shift work and IBS/FD. RESULTS: Eight studies were included ultimately. Shift workers were more likely to suffer from IBS. The OR of shift work was 1.81 (95% confidence interval 1.42; 2.32) with low heterogeneity (P < .05, I2 = 0%) for IBS. However, no evidence of the association was observed between shift work and the risk of FD. The OR of shift work was 0.87 (95% confidence interval 0.62; 1.23) (P > .05) for FD. CONCLUSIONS: There was a positive association between shift work and IBS. The prevalence of IBS was 81% higher among shift workers than among non-shift workers. Shift work was probably a risk factor for IBS. The low heterogeneity supports the reliability of the results. However, there was no significant association between shift work and FD. The strength of the evidence was limited and further prospective cohort studies were needed.

Multiplexed detection of heavy metal ions by single plasmonic nanosensors.

Detection of multiple analytes simultaneously in small liquid samples with high efficiency and precision is highly important to the fields like water quality monitoring. In this letter, we present a multiplexed nanosensors with position-encoded aptamer functionalized gold nanorods for heavy metal ions detection. The individual gold nanorods respond specifically to two different heavy metal ions (Pb2+ and Hg2+) with a spectral shift in the scattering spectrum. We used a home-built spectral imaging dark-field microscope to measure the response of thousands of single plasmonic nanosensors with relatively high time resolution and precision. To explore the performance and limit of detection (LOD) of our nanosensor and setup, we recorded the concentration-dependent response of our position-encoded nanosensors with a series of mixture solutions that contain different concentrations of Hg2+ and Pb2+ ions. The LOD levels of our system are around 5 nM for Pb2+ ions and 1 nM for Hg2+ ions. Our method and results demostrate the nanomolar sensitivity and the potential to detect more different heavy metal ions.

Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice.

Objective: Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, is a promising drug for nonalcoholic fatty liver disease (NAFLD); however, it can cause liver injury, especially at high doses. Here, we investigated the role of FXR in the high-dose OCA-induced hepatoxicity in the condition of the NAFLD mouse model. Methods: Wild-type (WT) mice and FXR-/- mice were administered with over-dose OCA (0.40%) and high-dose OCA (0.16%), in a high-fat diet. RNA-seq on liver samples of mice fed with high-dose OCA was performed to dig out the prominent biological events contributing to hepatic fibrosis. Results: Over-dose OCA induced liver injury and shortened survival in WT mice, but not FXR-/- mice. High-dose OCA caused hepatic stellate cell activation and liver fibrosis in the presence of FXR. Furthermore, high-dose OCA induced cholesterol accumulation in livers via the upregulation of genes involved in cholesterol acquisition and downregulation of genes regulating cholesterol degradation in liver, leading to the production of interleukin -1ß and an FXR-mediated inflammatory response. Conclusion: The high-dose OCA induced FXR-dependent hepatic injury via cholesterol accumulation and interleukin -1ß pathway in the NAFLD mice.