Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Exploiting Dynamic Nonlinearity in Upconversion Nanoparticles for Super-Resolution Imaging.

Single-beam super-resolution microscopy, also known as superlinear microscopy, exploits the nonlinear response of fluorescent probes in confocal microscopy. The technique requires no complex purpose-built system, light field modulation, or beam shaping. Here, we present a strategy to enhance this technique's spatial resolution by modulating excitation intensity during image acquisition. This modulation induces dynamic optical nonlinearity in upconversion nanoparticles (UCNPs), resulting in variations of nonlinear fluorescence response in the obtained images. The higher orders of fluorescence response can be extracted with a proposed weighted finite difference imaging algorithm from raw fluorescence images to generate an image with higher resolution than superlinear microscopy images. We apply this approach to resolve single nanoparticles in a large area, improving the resolution to 132 nm. This work suggests a new scope for the development of dynamic nonlinear fluorescent probes in super-resolution nanoscopy.

Preselectable Optical Fingerprints of Heterogeneous Upconversion Nanoparticles.

The control in optical uniformity of single nanoparticles and tuning their diversity in multiple dimensions, dot to dot, holds the key to unlocking nanoscale applications. Here we report that the entire lifetime profile of the single upconversion nanoparticle (τ2 profile) can be resolved by confocal, wide-field, and super-resolution microscopy techniques. The advances in both spatial and temporal resolutions push the limit of optical multiplexing from microscale to nanoscale. We further demonstrate that the time-domain optical fingerprints can be created by utilizing nanophotonic upconversion schemes, including interfacial energy migration, concentration dependency, energy transfer, and isolation of surface quenchers. We exemplify that three multiple dimensions, including the excitation wavelength, emission color, and τ2 profile, can be built into the nanoscale derivative τ2-dots. Creating a vast library of individually preselectable nanotags opens up a new horizon for diverse applications, spanning from sub-diffraction-limit data storage to high-throughput single-molecule digital assays and super-resolution imaging.

Upconversion Nonlinear Structured Illumination Microscopy.

Video-rate super-resolution imaging through biological tissue can visualize and track biomolecule interplays and transportations inside cellular organisms. Structured illumination microscopy allows for wide-field super resolution observation of biological samples but is limited by the strong extinction of light by biological tissues, which restricts the imaging depth and degrades its imaging resolution. Here we report a photon upconversion scheme using lanthanide-doped nanoparticles for wide-field super-resolution imaging through the biological transparent window, featured by near-infrared and low-irradiance nonlinear structured illumination. We demonstrate that the 976 nm excitation and 800 nm upconverted emission can mitigate the aberration. We found that the nonlinear response of upconversion emissions from single nanoparticles can effectively generate the required high spatial frequency components in the Fourier domain. These strategies lead to a new modality in microscopy with a resolution below 131 nm, 1/7th of the excitation wavelength, and an imaging rate of 1 Hz.

Super-Resolution Mapping of Single Nanoparticles inside Tumor Spheroids.

Cancer spheroids have structural, functional, and physiological similarities to the tumor, and have become a low-cost in vitro model to study the physiological responses of single cells and therapeutic efficacy of drugs. However, the tiny spheroid, made of a cluster of high-density cells, is highly scattering and absorptive, which prevents light microscopy techniques to reach the depth inside spheroids with high resolution. Here, a method is reported for super-resolution mapping of single nanoparticles inside a spheroid. It first takes advantage of the self-healing property of a "nondiffractive" doughnut-shaped Bessel beam from a 980 nm diode laser as the excitation, and further employs the nonlinear response of the 800 nm emission from upconversion nanoparticles, so that both excitation and emission at the near-infrared can experience minimal loss through the spheroid. These strategies lead to the development of a new nanoscopy modality with a resolution of 37 nm, 1/26th of the excitation wavelength. This method enables mapping of single nanoparticles located 55 µm inside a spheroid, with a resolution of 98 nm. It suggests a solution to track single nanoparticles and monitor their release of drugs in 3D multicellar environments.

WITHDRAWN: GAS5 enhances natural killer cell-mediated killing by promoting ubiquitination of SESN2 in prostate cancer cells.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

HIF-1α induces immune escape of prostate cancer by regulating NCR1/NKp46 signaling through miR-224.

BACKGROUND: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1α. METHODS: MiR-224 expression in lymphocytes and HIF-1α protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46+ NK cells was detected with flow cytometry. The IFN-γ level was examined by enzyme linked immunosorbent assay (ELISA). NK cells were tested for cytolytic activity with a Non-Radioactive Cytotoxicity Assay, and treated with oxygenglucose deprivation (OGD) for hypoxia simulation. Interaction between miR-224 and NCR1 was evaluated with dual luciferase reporter assay. RESULTS: MiR-224 was down-regulated in lymphocytes isolated from prostate cancer tissues (n = 10). Overexpression of miR-224 protected prostate cancer from NK cells. HIF-1α increased miR-224 to inhibit the killing capability of NK cells on prostate cancer. MiR-224 controlled the expression of NCR1. Overexpression of miR-224 protected prostate cancer from NK cells through NCR1/NKp46 signaling. Suppression of HIF-1α enhanced the cytotoxicity of NK cells on prostate cancer via miR-224/NCR1 pathway. CONCLUSION: HIF-1α inhibits NCR1/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells.

Optical Nonlinearity Enabled Super-Resolved Multiplexing Microscopy.

Optical multiplexing for nanoscale object recognition is of great significance within the intricate domains of biology, medicine, anti-counterfeiting, and microscopic imaging. Traditionally, the multiplexing dimensions of nanoscopy are limited to emission intensity, color, lifetime, and polarization. Here, a novel dimension, optical nonlinearity, is proposed for super-resolved multiplexing microscopy. This optical nonlinearity is attributable to the energy transitions between multiple energy levels of the doped lanthanide ions in upconversion nanoparticles (UCNPs), resulting in unique optical fingerprints for UCNPs with different compositions. A vortex beam is applied to transport the optical nonlinearity onto the imaging point-spread function (PSF), creating a robust super-resolved multiplexing imaging strategy for differentiating UCNPs with distinctive optical nonlinearities. The composition information of the nanoparticles can be retrieved with variations of the corresponding PSF in the obtained image. Four channels multiplexing super-resolved imaging with a single scanning, applying emission color and nonlinearity of two orthogonal imaging dimensions with a spatial resolution higher than 150 nm (1/6.5λ), are demonstrated. This work provides a new and orthogonal dimension - optical nonlinearity - to existing multiplexing dimensions, which shows great potential in bioimaging, anti-counterfeiting, microarray assays, deep tissue multiplexing detection, and high-density data storage.

Cryogenic Thermal Shock Effects on Optical Properties of Quantum Emitters in Hexagonal Boron Nitride.

Solid-state quantum emitters are vital building blocks for quantum information science and quantum technology. Among various types of solid-state emitters discovered to date, color centers in hexagonal boron nitride have garnered tremendous traction in recent years, thanks to their environmental robustness, high brightness, and room-temperature operation. Most recently, these quantum emitters have been employed for satellite-based quantum key distribution. One of the most important requirements to qualify these emitters for space-based applications is their optical stability against cryogenic thermal shock. Such an understanding has, however, remained elusive to date. Here, we report on the effects caused by such thermal shock that induces random, irreversible changes in the spectral characteristics of the quantum emitters. By employing a combination of structural characterizations and density functional calculations, we attribute the observed changes to lattice strain caused by cryogenic temperature shock. Our study sheds light on the stability of the quantum emitters under extreme conditions─similar to those countered in outer space.

Sensing performance of precisely ordered TiO2 nanowire gas sensors fabricated by electron-beam lithography.

In this study, electron beam lithography, rather than the most popular method, chemical synthesis, is used to construct periodical TiO(2) nanowires for a gas sensor with both robust and rapid performance. The effects of temperature on the sensing response and reaction time are analyzed at various operation temperatures ranging from 200 to 350 °C. At the optimized temperature of 300 °C, the proposed sensor repeatedly obtained a rise/recovery time (ΔR: 0.9 R(0) to 0.1 R(0)) of 3.2/17.5 s and a corresponding sensor response (ΔR/R(0)) of 21.7% at an ethanol injection mass quantity of 0.2 µg.

Association between oxidative balance score and kidney stone in United States adults: analysis from NHANES 2007-2018.

Purpose: To investigate the relationship between the Oxidative Balance Score (OBS) and kidney stone risk using NHANES 2007-2018 data, and to explore potential mechanisms and population-specific effects. Materials and methods: Data from the NHANES 2007-2018 were analyzed. OBS was calculated based on 16 dietary components and 4 lifestyle components. Multivariate logistic regression was employed to investigate the relationship between OBS and kidney stone. Further stratified analyses were conducted to examine the associations across different subgroups. Results: A total of 19,799 participants were included in the study. There was a consistent inverse association between OBS and the risk of kidney stones (OR = 0.97; 95% CI: 0.96-0.99). After dividing the participants into quartiles based on OBS, compared to the lowest quartile of OBS, the risk of kidney stones in the highest quartile of OBS was reduced by 33% (95% CI 0.50-0.89; p = 0.002). This association was consistent across both dietary and lifestyle OBS scores. The protective effect of OBS was notably pronounced among Non-Hispanic white and Other race groups, and among individuals with a higher level of education. However, the association was not significant among individuals with diabetes. Conclusion: A higher OBS, indicating a balance skewed towards antioxidants, is associated with a reduced risk of kidney stones, especially among specific population subgroups. These findings underscore the potential role of oxidative balance in kidney stone pathogenesis and highlight the importance of considering individual and population-specific factors in future research and preventive strategies.

Perovskite photodetector-based single pixel color camera for artificial vision.

Narrowband red, green, blue self-filtering perovskite photodetectors and a broadband white photodetector are incorporated into a single pixel imaging camera to mimic the long-, medium-, and short-wavelength cone cells and rod cells in human visual system, leading to the demonstration of high-resolution color images in diffuse mode.

Population Control of Upconversion Energy Transfer for Stimulation Emission Depletion Nanoscopy.

Upconverting stimulated emission depletion microscopy (U-STED) is emerging as an effective approach for super-resolution imaging due to its significantly low depletion power and its ability to surpass the limitations of the square-root law and achieve higher resolution. Though the compelling performance, a trade-off between the spatial resolution and imaging quality in U-STED has been recognized in restricting the usability due to the low excitation power drove high depletion efficiency. Moreover, it is a burden to search for the right power relying on trial and error as the underpinning mechanism is unknown. Here, a method is proposed that can easily predict the ideal excitation power for high depletion efficiency with the assistance of the non-saturate excitation based on the dynamic cross-relaxation (CR) energy transfer of upconversion nanoparticles. This allows the authors to employ the rate equation model to simulate the populations of each relevant energy state of lanthanides and predict the ideal excitation power for high depletion efficiency. The authors demonstrate that the resolution of STED with the assistance of nonsaturated confocal super-resolution results can easily achieve the highest resolution of sub-40 nm, 1/24th of the excitation wavelengths. The finding on the CR effect provides opportunities for population control in realizing low-power high-resolution nanoscopy.

Power-Dependent Optimal Concentrations of Tm3+ and Yb3+ in Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles (UCNPs) have enabled a broad range of emerging nanophotonics and biophotonics applications. Here, we provide a quantitative guide to the optimum concentrations of Yb3+ sensitizer and Tm3+ emitter ions, highly dependent on the excitation power densities. To achieve this, we fabricate the inert-core@active-shell@inert-shell architecture to sandwich the same volume of the optically active section. Our results show that highly doped UCNPs enable an approximately 18-fold enhancement in brightness over that of conventional ones. Increasing the Tm3+ concentration improves the brightness by 6 times and increases the NIR/blue ratio by 11 times, while the increase of Yb3+ concentration enhances the brightness by 3 times and only slightly affects the NIR/blue ratio. Moreover, the optimal doping concentration of Tm3+ varies from 2% to 16%, which is highly dependent on the excitation power density ranging from 102 to 107 W/cm2. This work provides a guideline for designing bright UCNPs under different excitation conditions.

Lanthanide Ion Resonance-Driven Rayleigh Scattering of Nanoparticles for Dual-Modality Interferometric Scattering Microscopy.

Light scattering from nanoparticles is significant in nanoscale imaging, photon confinement. and biosensing. However, engineering the scattering spectrum, traditionally by modifying the geometric feature of particles, requires synthesis and fabrication with nanometre accuracy. Here it is reported that doping lanthanide ions can engineer the scattering properties of low-refractive-index nanoparticles. When the excitation wavelength matches the ion resonance frequency of lanthanide ions, the polarizability and the resulted scattering cross-section of nanoparticles are dramatically enhanced. It is demonstrated that these purposely engineered nanoparticles can be used for interferometric scattering (iSCAT) microscopy. Conceptually, a dual-modality iSCAT microscopy is further developed to identify different nanoparticle types in living HeLa cells. The work provides insight into engineering the scattering features by doping elements in nanomaterials, further inspiring exploration of the geometry-independent scattering modulation strategy.

First identification of two co-existing genome-wide significant sex quantitative trait loci (QTL) in red tilapia using integrative QTL mapping.

Red tilapia ( Oreochromis spp .) is one of the most popular fish in China due to its bright red appearance, fast growth rate, and strong adaptability. Understanding the sex determination mechanisms is of vital importance for the selection of all-male lines to increase aquacultural production of red tilapia. In this research, the genetic architecture for sex from four mapping populations ( n=1 090) of red tilapia was analyzed by quantitative trait loci (QTL)-seq, linkage-based QTL mapping, and linkage disequilibrium (LD)-based genome-wide association studies. Two genome-wide significant QTL intervals associated with sex were identified on ChrLG1 (22.4-23.9 Mb) and ChrLG23 (32.0-35.9 Mb), respectively. The QTL on ChrLG1 was detected in family 1 (FAM1), FAM2, and FAM4, and the other QTL on ChrLG23 was detected in FAM3 and FAM4. Four microsatellite markers located within the QTL were successfully developed for marker-assisted selection. Interestingly, three ( lpp, sox14, and amh) of the 12 candidate genes located near or on the two QTL intervals were abundantly expressed in males, while the remaining genes were more highly expressed in females. Seven genes ( scly, ube3a, lpp, gpr17, oca2, cog4, and atp10a) were significantly differentially expressed between the male and female groups. Furthermore, LD block analysis suggested that a cluster of genes on ChrLG23 may participate in regulating sex development in red tilapia. Our study provides important information on the genetic architecture of sex in red tilapia and should facilitate further exploration of sex determination mechanisms in this species.

Heterochromatic Nonlinear Optical Responses in Upconversion Nanoparticles for Super-Resolution Nanoscopy.

Point spread function (PSF) engineering by an emitter's response can code higher-spatial-frequency information of an image for microscopy to achieve super-resolution. However, complexed excitation optics or repetitive scans are needed, which explains the issues of low speed, poor stability, and operational complexity associated with the current laser scanning microscopy approaches. Here, the diverse emission responses of upconversion nanoparticles (UCNPs) are reported for super-resolution nanoscopy to improve the imaging quality and speed. The method only needs a doughnut-shaped scanning excitation beam at an appropriate power density. By collecting the four-photon emission of single UCNPs, the high-frequency information of a super-resolution image can be resolved through the doughnut-emission PSF. Meanwhile, the two-photon state of the same nanoparticle is oversaturated, so that the complementary lower-frequency information of the super-resolution image can be simultaneously collected by the Gaussian-like emission PSF. This leads to a method of Fourier-domain heterochromatic fusion, which allows the extended capability of the engineered PSFs to cover both low- and high-frequency information to yield optimized image quality. This approach achieves a spatial resolution of 40 nm, 1/24th of the excitation wavelength. This work suggests a new scope for developing nonlinear multi-color emitting probes in super-resolution nanoscopy.

Multiplexed structured illumination super-resolution imaging with lifetime-engineered upconversion nanoparticles.

The emerging optical multiplexing within nanoscale shows super-capacity in encoding information by using lifetime fingerprints from luminescent nanoparticles. However, the optical diffraction limit compromises the decoding accuracy and throughput of the nanoparticles during conventional widefield imaging. This, in turn, challenges the quality of nanoparticles to afford the modulated excitation condition and further retain the multiplexed optical fingerprints for super-resolution multiplexing. Here we report a tailor-made multiplexed super-resolution imaging method using the lifetime-engineered upconversion nanoparticles. We demonstrate that the nanoparticles are bright, uniform, and stable under structured illumination, which supports a lateral resolution of 185 nm, less than 1/4th of the excitation wavelength. We further develop a deep learning algorithm to coordinate with super-resolution images for more accurate decoding compared to a numeric algorithm. We demonstrate a three-channel super-resolution imaging based optical multiplexing with decoding accuracies above 93% for each channel and larger than 60% accuracy for potential seven-channel multiplexing. The improved resolution provides high throughput by resolving the particles within the diffraction-limited spots, which enables higher multiplexing capacity in space. This lifetime multiplexing super-resolution method opens a new horizon for handling the growing amount of information content, disease source, and security risk in modern society.

Six-photon upconverted excitation energy lock-in for ultraviolet-C enhancement.

Photon upconversion of near-infrared (NIR) irradiation into ultraviolet-C (UVC) emission offers many exciting opportunities for drug release in deep tissues, photodynamic therapy, solid-state lasing, energy storage, and photocatalysis. However, NIR-to-UVC upconversion remains a daunting challenge due to low quantum efficiency. Here, we report an unusual six-photon upconversion process in Gd3+/Tm3+-codoped nanoparticles following a heterogeneous core-multishell architecture. This design efficiently suppresses energy consumption induced by interior energy traps, maximizes cascade sensitizations of the NIR excitation, and promotes upconverted UVC emission from high-lying excited states. We realized the intense six-photon-upconverted UV emissions at 253 nm under 808 nm excitation. This work provides insight into mechanistic understanding of the upconversion process within the heterogeneous architecture, while offering exciting opportunities for developing nanoscale UVC emitters that can be remotely controlled through deep tissues upon NIR illumination.

Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy.

Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic-co-glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine's distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery.