Solitary eosinophilic granulocytic sarcoma in a dog.

A 6-year-old male golden retriever presented with swelling of the left upper eyelid of 2 months duration, which did not improve following a course of antibiotics. Routine serum biochemistry, complete blood count and diagnostic imaging identified no clinically significant abnormalities. The mass was surgically excised, and histopathologic examination was performed. Eosinophilic granulocytic sarcoma (GS) was diagnosed based on the results of histopathology and immunohistochemistry. This is the first report of GS affecting the eyelid of a dog.

Maximizing Interlaminar Fracture Toughness in Bidirectional GFRP through Controlled CNT Heterogeneous Toughening.

"Interleaving" is widely used for interlaminar toughening of fiber-reinforced composites, and the structure of interleaving is one of the important factors affecting the toughening efficiency of laminates. Several experiments have demonstrated that compared to continuous and dense structures, toughening layers with structural heterogeneity can trigger multiple toughening mechanisms and have better toughening effects. On this basis, this work further investigates the application of heterogeneous toughening phases in interlaminar toughening of bidirectional GFRP. CNT was selected to construct toughening phases, which was introduced into the interlaminar of composites through efficient spraying methods. By controlling the amount of CNT, various structures of CNT toughening layers were obtained. The fracture toughness of modified laminates was tested, and their toughening mechanism was analyzed based on fracture surface observation. The results indicate that the optimal CNT usage (0.5 gsm) can increase the initial and extended values of interlayer fracture toughness by 136.0% and 82.0%, respectively. The solvent acetone sprayed with CNT can dissolve and re-precipitate a portion of the sizing agent on the surface of the fibers, which improves the bonding of the fibers to the resin. More importantly, larger discrete particles are formed between the layers, guiding the cracks to deflect in the orientation of the toughened layer. This generates additional energy dissipation and ultimately presents an optimal toughening effect.

Non-Woven Fabric Thermal-Conductive Triboelectric Nanogenerator via Compositing Zirconium Boride.

With the vigorous development of the Internet of Things, 5G technology, and artificial intelligence, flexible wearable sensors have received great attention. As a simple and low-cost power supply in wearable sensors, the triboelectric nanogenerator (TENG) has a wide range of applications in the field of flexible electronics. However, most polymers are thermally poor conductors (less than 0.1 W/(m·K)), resulting in insufficient heat dissipation performance and limiting the development of TENG. In this study, a high-performance non-woven fabric TENG with strong thermal conductivity (0.26 W/m·K) was achieved by introducing ZrB2 into the polyurethane (PU) matrix. The excellent output performance with an open circuit voltage (Voc) of 347.6 V, a short circuit current (Isc) of 3.61 µA, and an accumulated charge of 142.4 nC endows it with good sensitivity. The electrospun PU/ZrB2 composites exhibit excellent sensing performance to detect body movements in situ, such as pressing, clapping, running, and walking. Moreover, the generated power can light up 224 LED bulbs as a demonstration of self-powering ability.

Proximity-Enhanced Functional Imaging Analysis of Engineered Tumors.

Functional imaging (FI) techniques have revolutionized tumor imaging by providing information on specific tumor functions, such as glycometabolism. However, tumor cells lack unique molecular characteristics at the molecular level and metabolic pathways, resulting in limited metabolic differences compared to normal cells and increased background signals from FI. To address this limitation, we developed a novel imaging technique termed proximity-enhanced functional imaging (PEFI) for accurate visualization of tumors. By using "two adjacent chemically labeled glycoproteins" as output signals, we significantly enhance the metabolic differences between tumor and normal cells by PEFI, thereby reducing the background signals for analysis and improving the accuracy of tumor functional imaging. Our results demonstrate that PEFI can accurately identify tumors at the cellular, tissue, and animal level, and has potential value in clinical identification and analysis of tumor cells and tissues, as well as in the guidance of clinical tumor resection surgery.

Metal-organic framework integrated hydrogel bioreactor for smart detection of metal ions.

Bioreactors with environment responsiveness for smart detection has attracted widespread interest. Bioreactors that operate in liquid have excellent reaction speed and sensitivity, and those that operate at a solid interface have unique portability and stability. However, bioreactors that can simultaneously take advantage of both properties are still limited. Here, we developed a metal-organic framework (MOF) integrated hydrogel bioreactor that can accommodate both solid and liquid properties by using a hydrogel as a quasi-liquid medium. To enhance the stability and intelligence of the hydrogel bioreactor, we have opted for the utilization of europium metal-organic framework (Eu-MOF) as the optical output to withstand long-term storage challenges, and DNA as the highly programmable substance for intelligent target response. On this basis, smart detection of metal ions and biological micro-molecules have been achieved. Notably, this quasi-liquid hydrogel bioreactor has effectively tackled the intrinsic issues of inadequate dispersion stability of Eu-MOF in liquid systems and poor stability of DNA against environmental interference. Moreover, this MOF integrated hydrogel bioreactor has been applied to the construction of a portable hydrogel bioreactor, which enables platform-free and arrayed target detection via a smartphone, providing a new perspective for further promoting the application of quasi-liquid hydrogel bioreactors and intelligent nanobiological sensors.

An Intelligent DNA Nanoreactor for Easy-to-Read In Vivo Tumor Imaging and Precise Therapy.

Nanomaterial-based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent "always ON" or single-parameter responsive signal output, substantial off-target effects, and high cost. Therefore, achieving in vivo easy-to-read tumor imaging and precise therapy in a multi-parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the "AND" Boolean logic algorithm to address these issues. iDNR-mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers "AND" hydrogen peroxide (H2 O2 ). Therefore, intelligent temperature-based in vivo easy-to-read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.

Negative Enthalpy Variation Drives Rapid Recovery in Thermoplastic Elastomer.

The mechanism behind the resilience of polymeric materials, typically attributed to the well-established entropy elasticity, often ignores the contribution of enthalpy variation (ΔH), because it is based on the assumption of an ideal chain. However, this model does not fully account for the reduced resilience of thermoplastic polyurethane (TPU) during long-range deformation, which is mainly caused by the dynamics of physical crosslink networks. Such reduction is undesirable for long-range stretchable TPU considering its wide application range. Therefore, a negative ΔH effect is established in this work to facilitate instant recovery in long-range stretchable TPU, achieved by constructing a reversible interim interface via strain-induced phase separation. Consequently, the newly constructed dual soft segmental TPU shows resilience efficiency exceeding 95%, surpassing many synthetic high-performance TPUs with typical efficiencies below 80%, and comparable to biomaterials. Moreover, a remarkable hysteresis loop with a ratio exceeding 50%, makes it a viable candidate for applications such as artificial ligaments or buffer belts. The research also clarifies structural factors influencing resilience, including the symmetry of the dual soft segments and the content of hard segments, offering valuable insights for the design of highly resilient long-range stretchable elastomers.

Bile duct hamartoma in a dog.

An 11-year-old female Collie presented with a significantly increased abdominal circumference. Computed tomography of the abdomen revealed that the left lateral lobe of the liver contained a large mass, which was excised via laparotomy. Histologically, many small, dilated, cystic luminal structures were anastomosed and connected to a net-like structure. Immunohistochemistry revealed cytokeratin 19-immunopositive areas, representing bile duct structures in the cystic lumen. Based on these results, the tumour was diagnosed as a bile duct hamartoma. To our knowledge, this is the first report of a bile duct hamartoma in a dog.

Aptamer-based self-assembled nanomicelle enables efficient and targeted drug delivery.

Nucleic acid aptamer-based nanomicelles have great potential for nanomedicine and nanotechnology applications. However, amphiphilic aptamer micelles are known to be inherently unstable upon interaction with cell membranes in the physiological environment, thus potentially compromising their specific targeting against cancer cells. This flaw is addressed in the present work which reports a superstable micellar nanodelivery system as an amphiphilic copolymer self-assembled micelle composed of nucleic acid aptamer and polyvalent hydrophobic poly(maleic anhydride-alt-1-octadecene) (C18PMH). Using Ce6 as a drug model, these C18-aptamer micelles exhibit efficient tumor-targeting and -binding ability, facilitating the entry of Ce6 into targeted cells for photodynamic therapy. In addition, they can be loaded with other hydrophobic drugs and still demonstrate favorable therapeutic effects. As such, these C18-aptamer micelles can serve as a universal platform for loading multiple drugs, providing a safer and more effective solution for treating cancer.

Free-Standing CNT Film for Interlaminar Toughening: Insight into Infiltration and Thickness Effects.

Carbon fiber reinforced polymer composites have the advantages of being lightweight, having high strength and designability, and having been extensively used. However, the interlaminar toughness and delamination resistance of these composites are relatively poor due to their laminated structure and intrinsic brittleness of resin matrix. In this paper, commercialized free-standing carbon nanotube (CNT) films, drawn from CNT forests, were used to toughen the interlaminar interfaces of the composites. The effects of resin infiltration state and thickness of CNT films on the interlaminar toughening effect were systematically investigated. The results show that the pre-infiltration treatment of CNT films with acetone diluted epoxy resin solution can effectively improve the degree of resin infiltration. Compared with the samples containing untreated CNT film, the Mode I and Mode II interlaminar fracture toughness of the treated samples were significantly improved. The GIC reached a maximum of 1412.42 J/m2 at a CNT film thickness of 5 µm, which was about 61.38% higher than that of the baseline. At a CNT film thickness of 15 µm, the GIIC reached a maximum value of 983.73 J/m2, approximately 67.58% higher than that of the baseline. The corresponding toughening mechanisms were also systematically analyzed.

Metal-polyDNA nanoparticles reconstruct osteoporotic microenvironment for enhanced osteoporosis treatment.

Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi4- generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

Biological effect abundance analysis of hemolytic pathogens based on engineered biomimetic sensor.

Conventional pathogen detection strategies based on the molecular structure or chemical characteristics of biomarkers can only provide the "physical abundance" of microorganisms, but cannot reflect the "biological effect abundance" in the true sense. To address this issue, we report an erythrocyte membrane-encapsulated biomimetic sensor cascaded with CRISPR-Cas12a (EMSCC). Taking hemolytic pathogens as the target model, we first constructed an erythrocyte membrane-encapsulated biomimetic sensor (EMS). Only hemolytic pathogens with biological effects can disrupt the erythrocyte membrane (EM), resulting in signal generation. Then the signal was amplified by cascading CRISPR-Cas12a, and more than 6.67 × 104-fold improvement in detection sensitivity compared to traditional erythrocyte hemolysis assay was achieved. Notably, compared with polymerase chain reaction (PCR) or enzyme linked immunosorbent assay (ELISA)-based quantification methods, EMSCC can sensitively respond to the pathogenicity change of pathogens. For the detection of simulated clinical samples based on EMSCC, we obtained an accuracy of 95% in 40 samples, demonstrating its potential clinical value.

Throwing and manipulating and cheating with a DNA nano-dice.

Artificial molecular machines have captured the imagination of researchers, given their clear potential to mimic and influence human life. Key to behavior simulation is to reproduce the specific properties of physical or abstract systems. Dice throwing, as a stochastic model, is commonly used for result judgment or plan decision in real life. In this perspective we utilize DNA cube framework for the design of a dice device at the nanoscale to reproduce probabilistic events in different situations: equal probability, high probability, and low probability. We first discuss the randomness of DNA cube, or dice, adsorbing on graphene oxide, or table, and then explore a series of events that change the probability through the way in which the energy released from entropy-driven strand displacement reactions or changes in intermolecular forces. As such, the DNA nano-dice system provides guideline and possibilities for the design, engineering, and quantification of behavioral probability simulation, a currently emerging area of molecular simulation research.

Paraganglioma of the Urinary Bladder in a Dog.

A 3-year-old male Bichon Frise developed lethargy, anorexia and haematuria. B-scan ultrasonography examination revealed a small, irregular, soft-textured mass in the bladder. Histopathologically, there was an incomplete fibrous pseudocapsule around the tumour tissue and although there was clear demarcation from the surrounding tissue, there was invasion of the capsule. Tumour cells proliferated in nests or cords of variable size, separated by fibrovascular tissue. The neoplastic cells were immunopositive for chromogranin A, synaptophysin and neuron-specific enolase, and electron microscopy revealed that they contained cytoplasmic secretory granules. On the basis of these findings, the tumour was diagnosed as a primary paraganglioma of the urinary bladder.

A colorimetric smartphone-based platform for pesticides detection using Fe-N/C single-atom nanozyme as oxidase mimetics.

In this study, a novel highly sensitive colorimetric platform has been designed for malathion assay based on Fe-N/C SAzyme. The as-synthesized SAzyme can directly oxidize 3,3´,5,5´-tetramethylbenzidine (TMB) to generate blue colored oxidized TMB. L-ascorbic acid-2-phosphate (AA2P), a substrate of acid phosphatase (ACP), could be hydrolyzed to AA, thereafter inhibit the oxidization reaction of TMB, leading to a conspicuous blue color fading. With the addition of malathion hindered the ACP activity and limited the AA production, resulting in the recovery of the catalytic activity of single-atom nanozyme. Under optimized operational conditions, a novel colorimetric assay has been designed for malathion detection with LOD of 0.42 nM. Besides, quantification of malathion in environmental and food samples was achieved based on the proposed strategy. In addition, the successfully integrated paper/smartphone sensor provided sensitive, and rapid, reliable detection of malathion with a LOD of 1 nM.

Computer-Aided Design of DNA Self-Limited Assembly for Relative Quantification of Membrane Proteins.

Immunofluorescence imaging of cells plays a vital role in biomedical research and clinical diagnosis. However, when it is applied to relative quantification of proteins, it suffers from insufficient fluorescence intensity or partial overexposure, resulting in inaccurate relative quantification. Herein, we report a computer-aided design of DNA self-limited assembly (CAD-SLA) technology and apply it for relative quantification of membrane proteins, a concept proposed for the first time. CAD-SLA can achieve exponential cascade signal amplification in one pot and terminate at any desired level. By conjugating CAD-SLA with immunofluorescence, in situ imaging of cell membrane proteins is achieved with a controllable amplification level. Besides, comprehensive fluorescence intensity information from fluorescent images can be obtained, accurately showing relative quantitative information. Slight protein expression differences previously indistinguishable by immunofluorescence or Western blotting can now be discriminated, making fluorescence imaging-based relative quantification a promising tool for membrane protein analysis. From the perspectives of both DNA self-assembly technology and immunofluorescence technology, this work has solved difficult problems and provided important reference for future development.

Smartphone-Based Pure DNAzyme Hydrogel Platform for Visible and Portable Colorimetric Detection of Cell-Free DNA.

Cell-free DNA (cfDNA), as a tumor marker, is of great importance for the diagnosis of cancer and targeted therapy. However, the need for huge analytical instruments for cfDNA analysis has restricted its practical applications, especially in rural areas and third-world countries. Herein, a portable and visual smartphone-based DNAzyme hydrogel platform is developed for cfDNA detection. The target cfDNA triggers rolling circle amplification to produce a G-quadruplex-comprised DNA hydrogel with an horseradish peroxidase (HRP)-like catalytic function, which further catalyzes the chromogenic substrate to generate a visible output signal. Notably, the naked-eye detection of cfDNA can be realized by the macroscale visibility and catalytic ability of the DNA hydrogel. The linear range of the DNAzyme hydrogel platform for cfDNA detection is 0.1 pM-1500 nM with a detection limit of 0.042 pM. Moreover, this platform is exploited for the detection of cfDNA in spiked human serum with favorable sensitivity and recovery. Therefore, the DNAzyme hydrogel platform provides highly promising potential for testing other nucleic acid biomarkers.

Magnetism-Controllable Catalytic Activity of DNAzyme.

Controllable regulation of enzyme activity is an important prerequisite for the in-depth application of enzymes, especially in today's intelligent era. However, irreversible regulation and cumbersome operation make this goal difficult to achieve. Here, by adopting magnetism and a harmless, noncontact, and time- and space-controllable physical element, we developed a system that could conveniently and reversibly regulate the activity of DNAzyme. In this system, the strands of the DNAzyme could be stretched or folded by applying or removing a magnetic field. Thereby, the conformation-dependent endonuclease activity of the DNAzyme could be facilely switched between an "OFF" and "ON" state. This system provides a reusable platform for the control of enzyme catalytic activity through magnetism, which provides guidance for further application in some related scientific research, especially the regulation of the activity of conformation-dependent polymers (DNAzymes, aptamers, and peptides).

Cubic DNA nanocage-based three-dimensional molecular beacon for accurate detection of exosomal miRNAs in confined spaces.

In situ nondestructive bioanalysis of targets in nanoscale confined space, e.g. exosomes, poses a high challenge to analytical technologies, especially to molecular fluorescent probes, because it is required to enter the confined space to recognize the target, and maintain independent and stable signal output. The unexpected fluorescence quenching and fluorescence resonance energy transfer (FRET) caused by high-frequency Brownian motion and collision in confined space are the main limiting factors. Herein, we constructed a well-defined and programmable cubic DNA nanocage-based three-dimensional molecular beacon (ncMB), which successfully broke through the above dilemma, and realized the detection of miRNA in exosomes. Specifically, steric hindrance and electrostatic repulsion derived from the unique three-dimensional structure of ncMB result in a barrier between fluorescent probes, thus eliminating unexpected fluorescence quenching during single exosomal miRNA detection and unexpected FRET during dual exosomal miRNA detection. Benefiting from the excellent anti-fluorescence and anti-FRET performance of ncMB, compared with traditional molecular beacons (MB), the detected fluorescence signal in exosomes can be improved by an order of magnitude. Moreover, ncMB is proven to have powerful programmability and anti-interference capability. Overall, it is believed that the ncMB can eliminate the signal distortion that was usually associated with commonly used MB, especially in the confined space. The ncMB is considered as a powerful and versatile tool for accurate in situ signal output in exosomes and maybe other confined spaces.

Computer-aided design of reversible hybridization chain reaction (CAD-HCR) enables multiplexed single-cell spatial proteomics imaging.

In situ spatial proteomics analysis of a single cell has not been achieved yet, mainly because of insufficient throughput and sensitivity of current techniques. Recent progress on immuno-nucleic acid amplification technology presents tremendous opportunities to address this issue. Here, we report an innovative hybridization chain reaction (HCR) technique that involves computer-aided design (CAD) and reversible assembly. CAD enables highly multiplexed HCR with a sequence database that can work in parallel, while reversible assembly enables the switching of HCR between a working state and a resting state. Thus, CAD-HCR has been successfully adopted for single-cell spatial proteomics analysis. The fluorescence signal of CAD-HCR is comparable with conventional immunofluorescence, and it is positively correlated with the abundance of target proteins, which is beneficial for the visualization of proteins. The method developed here expands the toolbox of single-cell analysis and proteomics studies, as well as the performance and application of HCR.