Large-area display textiles integrated with functional systems.

Displays are basic building blocks of modern electronics1,2. Integrating displays into textiles offers exciting opportunities for smart electronic textiles-the ultimate goal of wearable technology, poised to change the way in which we interact with electronic devices3-6. Display textiles serve to bridge human-machine interactions7-9, offering, for instance, a real-time communication tool for individuals with voice or speech difficulties. Electronic textiles capable of communicating10, sensing11,12 and supplying electricity13,14 have been reported previously. However, textiles with functional, large-area displays have not yet been achieved, because it is challenging to obtain small illuminating units that are both durable and easy to assemble over a wide area. Here we report a 6-metre-long, 25-centimetre-wide display textile containing 5 × 105 electroluminescent units spaced approximately 800 micrometres apart. Weaving conductive weft and luminescent warp fibres forms micrometre-scale electroluminescent units at the weft-warp contact points. The brightness between electroluminescent units deviates by less than 8 per cent and remains stable even when the textile is bent, stretched or pressed. Our display textile is flexible and breathable and withstands repeated machine-washing, making it suitable for practical applications. We show that an integrated textile system consisting of display, keyboard and power supply can serve as a communication tool, demonstrating the system's potential within the 'internet of things' in various areas, including healthcare. Our approach unifies the fabrication and function of electronic devices with textiles, and we expect that woven-fibre materials will shape the next generation of electronics.

Field-dependent deep learning enables high-throughput whole-cell 3D super-resolution imaging.

Single-molecule localization microscopy in a typical wide-field setup has been widely used for investigating subcellular structures with super resolution; however, field-dependent aberrations restrict the field of view (FOV) to only tens of micrometers. Here, we present a deep-learning method for precise localization of spatially variant point emitters (FD-DeepLoc) over a large FOV covering the full chip of a modern sCMOS camera. Using a graphic processing unit-based vectorial point spread function (PSF) fitter, we can fast and accurately model the spatially variant PSF of a high numerical aperture objective in the entire FOV. Combined with deformable mirror-based optimal PSF engineering, we demonstrate high-accuracy three-dimensional single-molecule localization microscopy over a volume of ~180 × 180 × 5 µm3, allowing us to image mitochondria and nuclear pore complexes in entire cells in a single imaging cycle without hardware scanning; a 100-fold increase in throughput compared to the state of the art.

Single-particle spectroscopy for functional nanomaterials.

Tremendous progress in nanotechnology has enabled advances in the use of luminescent nanomaterials in imaging, sensing and photonic devices. This translational process relies on controlling the photophysical properties of the building block, that is, single luminescent nanoparticles. In this Review, we highlight the importance of single-particle spectroscopy in revealing the diverse optical properties and functionalities of nanomaterials, and compare it with ensemble fluorescence spectroscopy. The information provided by this technique has guided materials science in tailoring the synthesis of nanomaterials to achieve optical uniformity and to develop novel applications. We discuss the opportunities and challenges that arise from pushing the resolution limit, integrating measurement and manipulation modalities, and establishing the relationship between the structure and functionality of single nanoparticles.

Spatiotemporally mapping temperature dynamics of lysosomes and mitochondria using cascade organelle-targeting upconversion nanoparticles.

The intracellular metabolism of organelles, like lysosomes and mitochondria, is highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of adenosine triphosphate (ATP) generation during active metabolism. Here, we developed temperature-sensitive LysoDots and MitoDots to monitor the in situ thermal dynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and low uncertainty of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the ion concentrations and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by ∼2 to 4 °C. Intriguingly, with chloroquine (CQ) treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed an ∼3 to 7 °C temperature increase and a thermal transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multimodality functional imaging of subcellular organelles and interactions with high spatial, temporal, and thermal dynamics resolutions.

Thermally Prolonged NIR-II Luminescence Lifetimes by Cross-Relaxation.

Temperature regulates nonradiative processes in luminescent materials, fundamental to luminescence nanothermometry. However, elevated temperatures often suppress the radiative process, limiting the sensitivity of thermometers. Here, we introduce an approach to populating the excited state of lanthanides at elevated temperatures, resulting in a sizable lifetime lengthening and intensity increase of the near-infrared (NIR)-II emission. The key is to create a five-energy-level system and use a pair of lanthanides to leverage the cross-relaxation process. We observed the lifetime of NIR-II emission of Er3+ has been remarkably increased from 3.85 to 7.54 ms by codoping only 0.5 mol % Ce3+ at 20 °C and further increased to 7.80 ms when increasing the temperature to 40 °C. Moreover, this concept is universal across four ion pairs and remains stable within aqueous nanoparticles. Our findings emphasize the need to design energy transfer systems that overcome the constraint of thermal quenching, enabling efficient imaging and sensing.

Lanthanide-Complex-Enhanced Bioorthogonal Branched DNA Amplification.

Fluorescence in situ hybridization (FISH) is a widely used technique for detecting intracellular nucleic acids. However, its effectiveness in detecting low-copy nucleic acids is limited due to its low fluorescence intensity and background autofluorescence. To address these challenges, we present here an approach of lanthanide-complex-enhanced bioorthogonal-branched DNA amplification (LEBODA) with high sensitivity for in situ nuclear acid detection in single cells. The approach capitalizes on two levels of signal amplification. First, it utilizes click chemistry to directly link a substantial number of bridge probes to target-recognizing probes, providing an initial boost in signal intensity. Second, it incorporates high-density lanthanide complexes into each bridge probe, enabling secondary amplifications. Compared to the traditional "double Z" probes used in the RNAscope method, LEBODA exhibits 4 times the single enhancement for RNA detection signal with the click chemistry approach. Using SARS-CoV-2 pseudovirus-infected HeLa cells, we demonstrate the superiority in the detection of viral-infected cells in rare populations as low as 20% infectious rate. More encouragingly, the LEBODA approach can be adapted for DNA-FISH and single-molecule RNA-FISH, as well as other hybridization-based signal amplification methods. This adaptability broadens the potential applications of LEBODA in the sensitive detection of biomolecules, indicating promising prospects for future research and practical use.

Lanthanide Complex for Single-Molecule Fluorescent in Situ Hybridization and Background-Free Imaging.

Traditional single-molecule fluorescence in situ hybridization (smFISH) methods for RNA detection often face sensitivity challenges due to the low fluorescence intensity of the probe. Also, short-lived autofluorescence complicates obtaining clear signals from tissue sections. In response, we have developed an smFISH probe using highly grafted lanthanide complexes to address both concentration quenching and autofluorescence background. Our approach involves an oligo PCR incorporating azide-dUTP, enabling conjugation with lanthanide complexes. This method has proven to be stable, convenient, and cost-effective. Notably, for the mRNA detection in SKBR3 cells, the lanthanide probe group exhibited 2.5 times higher luminescence intensity and detected 3 times more signal points in cells compared with the Cy3 group. Furthermore, we successfully applied the probe to image HER2 mRNA molecules in breast cancer FFPE tissue sections, achieving a 2.7-fold improvement in sensitivity compared to Cy3-based probes. These results emphasize the potential of time-resolved smFISH as a highly sensitive method for nucleic acid detection, free of background fluorescence interference.

Posterior default mode network is associated with the social performance in male children with autism spectrum disorder: A dynamic causal modeling analysis based on triple-network model.

The triple-network model has been widely applied in neuropsychiatric disorders including autism spectrum disorder (ASD). However, the mechanism of causal regulations within the triple-network and their relations with symptoms of ASD remains unclear. 81 male ASD and 80 well matched typically developing control (TDC) were included in this study, recruited from Autism Brain Image Data Exchange-I datasets. Spatial reference-based independent component analysis was used to identify the anterior and posterior part of default-mode network (aDMN and pDMN), salience network (SN), and bilateral executive-control network (ECN) from resting-state functional magnetic resonance imaging data. Spectral dynamic causal model and parametric empirical Bayes with Bayesian model reduction/average were adopted to explore the effective connectivity (EC) within triple-network and the relationship between EC and autism diagnostic observation schedule (ADOS) scores. After adjusting for age and site effect, ASD and TDC groups both showed inhibition patterns. Compared with TDC, ASD group showed weaker self-inhibition in aDMN and pDMN, stronger inhibition in pDMN→aDMN, weaker inhibition in aDMN→LECN, pDMN→SN, LECN→SN, and LECN→RECN. Furthermore, negative relationships between ADOS scores and pDMN self-inhibition strength, as well as with the EC of pDMN→aDMN were observed in ASD group. The present study reveals imbalanced effective connections within triple-networks in ASD children. More attentions should be focused at the pDMN, which modulates the core symptoms of ASD and may serve as an important region for ASD diagnosis and the target region for ASD treatments.

On-Chip Mirror Enhanced Multiphoton Upconversion Super-Resolution Microscopy.

Multiphoton upconversion super-resolution microscopy (MPUM) is a promising imaging modality, which can provide increased resolution and penetration depth by using nonlinear near-infrared emission light through the so-called transparent biological window. However, a high excitation power is needed to achieve emission saturation, which increases phototoxicity. Here, we present an approach to realize the nonlinear saturation emission under a low excitation power by a simply designed on-chip mirror. The interference of the local electromagnetic field can easily confine the point spread function to a specific area to increase the excitation efficiency, which enables emission saturation under a lower excitation power. With no additional complexity, the mirror assists to decrease the excitation power by 10-fold and facilities the achievement of a lateral resolution around 35 nm, 1/28th of the excitation wavelength, in imaging of a single nanoparticle on-chip. This method offers a simple solution for super-resolution enhancement by a predesigned on-chip device.

Metasurface-Controlled Photonic Rashba Effect for Upconversion Photoluminescence.

We demonstrate the effect of spin-momentum locking of upconversion photoluminescence emitted from rare-earth doped nanocrystals coupled to a phase-gradient dielectric metasurface. We observe different directionalities for left and right circular polarized light and associate this experimental observation with the photonic Rashba effect realized for upconverted photoluminescence that is manifested in the spin-dependent splitting of emitted light in the momentum space.

Carbon Free Radical (R⋠) Inactivates NF-κB for Radical Capping Therapy.

Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.

Ion Current Rectification Activity Induced by Boron Hydride Nanosheets to Enhance Magnesium Analgesia.

The low analgesic efficiency has limited magnesium used in analgesia. Here, we report boron hydride (BH) with ion current rectification activity can significantly improve the analgesic efficiency of magnesium, even higher than morphine. The synthesized injectable MgB2 composes of hexagonal boron sheets alternating with Mg2+. In pathological environment, while the intercalated Mg2+ will be exchanged by H+, the 2-dimensional borophene-analogue BH sheets will be formed to interact with the charged cations via the cation-pi interaction, synergistically leading to a sort of two-way dynamic modulation of sodium and potassium ion currents in neurons. By coordinating with the released Mg2+ to compete Ca2+, the threshold potential remarkably increases from the normal -35.9 mV to -5.9 mV, which significantly suppresses neuronal excitability, providing a potent analgesic effect. In three typical pain models , including CFA-induced inflammatory pain, PINP- or CCI-induced neuropathic pain, MgB2 demonstrates its analgesic efficiency approximately 2.23, 3.20, and 2.0 times higher than the clinical MgSO4, respectively. The development of MgB2 as analgesic drugs addresses the unmet medical need of pain relief without the risks of drug tolerance or addiction to opioids.

Thiolate DNAzymes on Gold Nanoparticles for Isothermal Amplification and Detection of Mesothelioma-derived Exosomal PD-L1 mRNA.

Catalytic DNAzymes have been used for isothermal amplification and rapid detection of nucleic acids, holding the potential for point-of-care testing applications. However, when Subzymes (universal substrate and DNAzyme) are tethered to the polystyrene magnetic microparticles via biotin-streptavidin bonds, the residual free Subzymes are often detached from the microparticle surface, which causes a significant degree of false positives. Here, we attached dithiol-modified Subzyme to gold nanoparticle and improved the limit of detection (LoD) by 200 times compared to that using magnetic microparticles. As a proof of concept, we applied our new method for the detection of exosomal programed cell-death ligand 1 (PD-L1) RNA. As the classical immune checkpoint, molecule PD-L1, found in small extracellular vesicles (sEVs, traditionally called exosomes), can reflect the antitumor immune response for predicting immunotherapy response. We achieved the LoD as low as 50 fM in detecting both the RNA homologous to the PD-L1 gene and exosomal PD-L1 RNAs extracted from epithelioid and nonepithelioid subtypes of mesothelioma cell lines, which only takes 8 min of reaction time. As the first application of isothermal DNAzymes for detecting exosomal PD-L1 RNA, this work suggests new point-of-care testing potentials toward clinical translations.

Modular DNAzymes-Hydrogel Membrane Carriers for Highly Sensitive Isothermal Cross-Cascade Detection of Pathogenic Bacteria Nucleic Acids.

The increasing prevalence of antimicrobial resistance has called for improved diagnostic testing of pathogenic bacteria. However, the development of rapid, cost-effective, and easy-to-use tests for bacterial infections remains a constant challenge. Here, we report a class of modular hydrogel membrane carriers incorporated with composite DNAzymes, which enable rapid and highly sensitive detection of pathogenic bacteria gene target analytes. We apply free radical polymerization to incorporate composite DNAzymes, consisting of an RNA substrate component and a DNAzyme component (e.g., 10-23 or 8-17 DNAzymes), into polyethylene glycol diacrylate polymer networks. Initiated by a nucleic acid target acting as an assembly facilitator, multicomponent DNAzymes are combined to cleave the RNA substrate component in the hydrogel carriers, which releases the DNAzyme component to cleave RNA reporter probes to generate fluorescence. We modulate the morphology, composition, and microporous structures of the DNAzyme carriers to achieve quantitative assay performance. We demonstrate a rapid and high-sensitivity detection of C. trachomatis gene target analytes as low as 50 fM in a short assay time of 25 min. The work represents a crucial step forward in the development of a generic, isothermal, and protein enzyme-free pathogenic bacteria testing platform technology.

Pixel-Level Classification of Five Histologic Patterns of Lung Adenocarcinoma.

Lung adenocarcinoma is the most common histologic type of lung cancer. The pixel-level labeling of histologic patterns of lung adenocarcinoma can assist pathologists in determining tumor grading with more details than normal classification. We manually annotated a dataset containing a total of 1000 patches (200 patches for each pattern) of 512 × 512 pixels and 420 patches (contains test sets) of 1024 × 1024 pixels according to the morphological features of the five histologic patterns of lung adenocarcinoma (lepidic, acinar, papillary, micropapillary, and solid). To generate an even large amount of data patches, we developed a data stitching strategy as a data augmentation for classification in model training. Stitched patches improve the Dice similarity coefficient (DSC) scores by 24.06% on the whole-slide image (WSI) with the solid pattern. We propose a WSI analysis framework for lung adenocarcinoma pathology, intelligently labeling lung adenocarcinoma histologic patterns at the pixel level. Our framework contains five branches of deep neural networks for segmenting each histologic pattern. We test our framework with 200 unclassified patches. The DSC scores of our results outpace comparing networks (U-Net, LinkNet, and FPN) by up to 10.78%. We also perform results on four WSIs with an overall accuracy of 99.6%, demonstrating that our network framework exhibits better accuracy and robustness in most cases.

Advances and challenges for fluorescence nanothermometry.

Fluorescent nanothermometers can probe changes in local temperature in living cells and in vivo and reveal fundamental insights into biological properties. This field has attracted global efforts in developing both temperature-responsive materials and detection procedures to achieve sub-degree temperature resolution in biosystems. Recent generations of nanothermometers show superior performance to earlier ones and also offer multifunctionality, enabling state-of-the-art functional imaging with improved spatial, temporal and temperature resolutions for monitoring the metabolism of intracellular organelles and internal organs. Although progress in this field has been rapid, it has not been without controversy, as recent studies have shown possible biased sensing during fluorescence-based detection. Here, we introduce the design principles and advances in fluorescence nanothermometry, highlight application achievements, discuss scenarios that may lead to biased sensing, analyze the challenges ahead in terms of both fundamental issues and practical implementations, and point to new directions for improving this interdisciplinary field.

Amplified stimulated emission in upconversion nanoparticles for super-resolution nanoscopy.

Lanthanide-doped glasses and crystals are attractive for laser applications because the metastable energy levels of the trivalent lanthanide ions facilitate the establishment of population inversion and amplified stimulated emission at relatively low pump power. At the nanometre scale, lanthanide-doped upconversion nanoparticles (UCNPs) can now be made with precisely controlled phase, dimension and doping level. When excited in the near-infrared, these UCNPs emit stable, bright visible luminescence at a variety of selectable wavelengths, with single-nanoparticle sensitivity, which makes them suitable for advanced luminescence microscopy applications. Here we show that UCNPs doped with high concentrations of thulium ions (Tm3+), excited at a wavelength of 980 nanometres, can readily establish a population inversion on their intermediate metastable 3H4 level: the reduced inter-emitter distance at high Tm3+ doping concentration leads to intense cross-relaxation, inducing a photon-avalanche-like effect that rapidly populates the metastable 3H4 level, resulting in population inversion relative to the 3H6 ground level within a single nanoparticle. As a result, illumination by a laser at 808 nanometres, matching the upconversion band of the 3H4 → 3H6 transition, can trigger amplified stimulated emission to discharge the 3H4 intermediate level, so that the upconversion pathway to generate blue luminescence can be optically inhibited. We harness these properties to realize low-power super-resolution stimulated emission depletion (STED) microscopy and achieve nanometre-scale optical resolution (nanoscopy), imaging single UCNPs; the resolution is 28 nanometres, that is, 1/36th of the wavelength. These engineered nanocrystals offer saturation intensity two orders of magnitude lower than those of fluorescent probes currently employed in stimulated emission depletion microscopy, suggesting a new way of alleviating the square-root law that typically limits the resolution that can be practically achieved by such techniques.

Single Small Extracellular Vesicle (sEV) Quantification by Upconversion Nanoparticles.

Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 106 EVs/mL, which was nearly 3 orders of magnitude lower than the standard enzyme-linked immunosorbent assay (ELISA). Its specificity was validated by the difference between EpCAM-positive and EpCAM-negative sEVs. The accuracy of the UCNP-based single-sEV assay was benchmarked with immunomagnetic-beads flow cytometry, showing a high correlation (R2> 0.99). The platform is suitable for evaluating the heterogeneous antigen expression of sEV and can be easily adapted for biomarker discoveries and disease diagnosis.

High Spatial and Temporal Resolution NIR-IIb Gastrointestinal Imaging in Mice.

Conventional biomedical imaging modalities, including endoscopy, X-rays, and magnetic resonance, are invasive and insufficient in spatial and temporal resolutions for gastrointestinal (GI) tract imaging to guide prognosis and therapy. Here we report a noninvasive method based on lanthanide-doped nanocrystals with ∼1530 nm fluorescence in the near-infrared-IIb window (NIR-IIb, 1500-1700 nm). The rational design of nanocrystals have led to an absolute quantum yield (QY) up to 48.6%. Further benefiting from the minimized scattering through the NIR-IIb window, we enhanced the spatial resolution to ∼1 mm in GI tract imaging, which is ∼3 times higher compared with the near-infrared-IIa (NIR-IIa, 1000-1500 nm) method. The approach also realized a high temporal resolution of 8 frames per second; thus the moment of mice intestinal peristalsis can be captured. Furthermore, with a light-sheet imaging system, we demonstrated a three-dimensional (3D) imaging on the GI tract. Moreover, we successfully translated these advances to diagnose inflammatory bowel disease.

Heterostructures with Built-in Electric Fields for Long-lasting Chemodynamic Therapy.

Sustained signal activation by hydroxyl radicals (⋅OH) has great significance, especially for tumor treatment, but remains challenging. Here, a built-in electric field (BIEF)-driven strategy was proposed for sustainable generation of ⋅OH, thereby achieving long-lasting chemodynamic therapy (LCDT). As a proof of concept, a novel Janus-like Fe@Fe3 O4 -Cu2 O heterogeneous catalyst was designed and synthesized, in which the BIEF induced the transfer of electrons in the Fe core to the surface, reducing ≡Cu2+ to ≡Cu+ , thus achieving continuous Fenton-like reactions and ⋅OH release for over 18 h, which is approximately 12 times longer than that of Fe3 O4 -Cu2 O and 72 times longer than that of Cu2 O nanoparticles. In vitro and in vivo antitumor results indicated that sustained ⋅OH levels led to persistent extracellular regulated protein kinases (ERK) signal activation and irreparable oxidative damage to tumor cells, which promoted irreversible tumor apoptosis. Importantly, this strategy provides ideas for developing long-acting nanoplatforms for various applications.