Real-time intelligent classification of COVID-19 and thrombosis via massive image-based analysis of platelet aggregates.

Microvascular thrombosis is a typical symptom of COVID-19 and shows similarities to thrombosis. Using a microfluidic imaging flow cytometer, we measured the blood of 181 COVID-19 samples and 101 non-COVID-19 thrombosis samples, resulting in a total of 6.3 million bright-field images. We trained a convolutional neural network to distinguish single platelets, platelet aggregates, and white blood cells and performed classical image analysis for each subpopulation individually. Based on derived single-cell features for each population, we trained machine learning models for classification between COVID-19 and non-COVID-19 thrombosis, resulting in a patient testing accuracy of 75%. This result indicates that platelet formation differs between COVID-19 and non-COVID-19 thrombosis. All analysis steps were optimized for efficiency and implemented in an easy-to-use plugin for the image viewer napari, allowing the entire analysis to be performed within seconds on mid-range computers, which could be used for real-time diagnosis.

Long-term effects of Pfizer-BioNTech COVID-19 vaccinations on platelets.

There is a global concern about the safety of COVID-19 vaccines associated with platelet function. However, their long-term effects on overall platelet activity remain poorly understood. Here we address this problem by image-based single-cell profiling and temporal monitoring of circulating platelet aggregates in the blood of healthy human subjects, before and after they received multiple Pfizer-BioNTech (BNT162b2) vaccine doses over a time span of nearly 1 year. Results show no significant or persisting platelet aggregation trends following the vaccine doses, indicating that any effects of vaccinations on platelet turnover, platelet activation, platelet aggregation, and platelet-leukocyte interaction was insignificant.

Two Filters for Acquiring the Profiles from Images Obtained from Weak-Light Background, Fluorescence Microscope, Transmission Electron Microscope, and Near-Infrared Camera.

Extracting the profiles of images is critical because it can bring simplified description and draw special attention to particular areas in the images. In our work, we designed two filters via the exponential and hypotenuse functions for profile extraction. Their ability to extract the profiles from the images obtained from weak-light conditions, fluorescence microscopes, transmission electron microscopes, and near-infrared cameras is proven. Moreover, they can be used to extract the nesting structures in the images. Furthermore, their performance in extracting images degraded by Gaussian noise is evaluated. We used Gaussian white noise with a mean value of 0.9 to create very noisy images. These filters are effective for extracting the edge morphology in the noisy images. For the purpose of a comparative study, we used several well-known filters to process these noisy images, including the filter based on Gabor wavelet, the filter based on the watershed algorithm, and the matched filter, the performances of which in profile extraction are either comparable or not effective when dealing with extensively noisy images. Our filters have shown the potential for use in the field of pattern recognition and object tracking.

Glutathione Depletion-Induced Activation of Dimersomes for Potentiating the Ferroptosis and Immunotherapy of "Cold" Tumor.

The abundant glutathione (GSH) in "cold" tumors weakens ferroptosis therapy and the immune response. Inspired by lipids, we fabricated cinnamaldehyde dimers (CDC) into lipid-like materials to form dimersomes capable of depleting GSH and delivering therapeutics to potentiate the ferroptosis and immunotherapy of breast cancer. The dimersomes exhibited superior storage stability for over one year. After reaching the tumor, they quickly underwent breakage in the cytosol owing to the conjugation of hydrophilic GSH on CDC by Michael addition, which not only triggered the drug release and fluorescence switch "ON", but also led to the depletion of intracellular GSH. Ferroptosis was significantly enhanced after combination with sorafenib (SRF) and elicited a robust immune response in vivo by promoting the maturation of dendritic cells and the priming of CD8+ T cells. As a result, the CDC@SRF dimersomes cured breast cancer in all the mice after four doses of administration.

Far-field head-media optical interaction in heat-assisted magnetic recording.

We have used a plane wave expansion method to theoretically study the far-field head-media optical interaction in heat-assisted magnetic recording. For the Advanced Storage Technology Consortium media stack specifically, we notice the outstanding sensitivity related to the interlayer's optical thickness for media reflection and the magnetic layer's light absorption. With 10 nm interlayer thickness change, the recording layer absorption can be changed by more than 25%. The 2D results are found to correlate well with the full 3D model and magnetic recording tests on a flyable disc with different interlayer thickness.

Purification, structural characterization, and bioactive properties of exopolysaccharides from Saccharomyces cerevisiae HD-01.

Exopolysaccharides (EPSs), which show excellent biological activities, like anti-tumor, immune regulation, and anti-oxidation activities, have gained widespread attention. In this study, an EPS-producing Saccharomyces cerevisiae HD-01 was identified based on 18S rDNA sequence analysis and an API 20C test. The purified HD-01 EPS was obtained by gel filtration chromatography. High-performance liquid chromatography (HPLC), gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR) revealed that it was a heteropolysaccharide composed of α-1 (38.3%), α-1, 2 (17.5%), α-1, 6 (14.8%)-linked mannose and α-1, 2, 3, 6 (24.3%), α-1 (3.3%), ß-1, 4 (1.8%)-linked glucose. Chemical composition and elemental analysis indicated the existence of sulfation modifications. A scanning electron microscope (SEM) and an atomic force microscope (AFM) revealed that it exhibited a flaky structure with thorn-like protrusions on the three-dimensional surface. X-ray diffraction (XRD) revealed that it was an amorphous non-crystalline substance. HD-01 EPS had great thermostability; probiotic properties; strong antioxidant properties to DPPH, ABTS, and hydroxyl; and good reducing power. The MTT, NO, and neutral red assays demonstrated that it had a great immunomodulatory effect on macrophages RAW264.7. All results suggested that the HD-01 EPS had the potential to be applied in the food and pharmaceutical fields.

Eutrophication constrains driving forces of dissolved organic carbon biodegradation in metropolitan lake systems.

Dissolved organic carbon (DOC) components can be highly variable in aquatic ecosystems, and play a pivotal role in the global carbon cycles. To comprehend potential effects of nutrient enrichment on portion of DOC biodegradability (%BDOC), we conducted an extensive investigation on 26 urban lakes in a major metropolitan area in subtropical China in a small gradient of trophic levels from mesotrophic to light and middle eutrophic. In addition to field measurements on lake ambient conditions and laboratory analysis of DOC characteristics, we conducted a 28-day temperature-controlled incubation experiment, in which %BDOC of lake waters was determined. In the mesotrophic waters, %BDOC ranged from 0.6 to 41.4 % (11.2 ± 8.9 %). The %BDOC levels spanned from 5.2 to 20.2 % (10.7 ± 4.0 %) in the light eutrophic waters, and the %BDOC ranged from 2.7 to 35.0 % (13.7 ± 8.4 %) in the middle eutrophic waters. We found a significant change in DOC chemical composition across the study lakes characterized by shifting of trophic levels. Although the experiment found significant changes in the factors that can influence %BDOC, a significant difference was not observed in %BDOC among the three trophic levels. The %BDOC was primarily influenced by the inherent DOC concentration and aromaticity, with eutrophication leading to the varied driving factors of %BDOC in lake systems. We show that most of the lake water DOC was stable. The findings indicate the intricate interplay between biological metabolism and nutrient availability governing %BDOC dynamics in urban lake ecosystems.

Michael Addition-Based Neoadjuvant for Enhanced Cancer Immunotherapy.

Cancer immunotherapy suffers from inefficient antigen presentation owing to the limited endocytosis of antigen by dendritic cells (DCs) and dysfunction of DCs in the immunosuppressive tumor microenvironment (ITME). Here, we revealed that cinnamaldehyde-grafted polyethylenimine (PC) held the potential to serve as a neoadjuvant to modulate the above processes and thus potentiate immune responses. The PC neoadjuvant could capture the tumor antigen generated during chemotherapy to enhance the crosstalk between the antigen and DCs. Then, it depleted the intracellular glutathione by the in situ Michael addition reaction, which not only activated the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) pathway to promote DCs maturation but also triggered the antigen release. As a result, it significantly augmented antigen presentation with a 46% ratio of DCs maturation and a 53% ratio of CD8+ T cell infiltration in low immunogenic murine breast cancer.

Potassium Ion-Assisted Self-Assembled MXene-K-CNT Composite as High-Quality Sulfur-Loaded Hosts for Lithium-Sulfur Batteries.

We successfully synthesized hybrid MXene-K-CNT composites composed of alkalized two-dimensional (2D) metal carbide and carbon nanotubes (CNTs), which were employed as host materials for lithium-sulfur (Li-S) battery cathodes. The unique three-dimensional (3D) intercalated structure through electrostatic interactions by K+ ions in conjunction with the scaffolding effect provided by CNTs effectively inhibited the self-stacking of MXene nanosheets, resulting in an enhanced specific surface area (SSA) and ion transport capability. Moreover, the addition of CNTs and in situ-grown TiO2 considerably improved the conductivity of the cathode material. K+ ion etching created a more hierarchical porous structure in MXene, which further enhanced the SSA. The 3D framework effectively confined S embedded between nanosheet layers and suppressed volume changes of the cathode composite during charging/discharging processes. This combination of CNTs and alkalized nanosheets functioned as a physical and chemical dual adsorption system for lithium polysulfides (LiPSs). When subjected to a high current at 1.0C, S@MXene-K-0.5CNT with S-loaded of 1.2 mg cm-2 had an initial capacity of 919.6 mAh g-1 and capacity decay rate of merely 0.052% per cycle after 1000 cycles. Moreover, S@MXene-K-0.5CNT maintained good cycling stability even at a high current of up to 5.0C. These impressive results highlight the potential of alkalized 2D MXene nanosheets intercalated with CNTs as highly promising cathode materials for Li-S batteries. The study findings also have prospects for the development of next-generation Li-S batteries with high energy density and prolonged lifespans.

Three filters for the enhancement of the images acquired from fluorescence microscope and weak-light-sources and the image compression.

Fluorescence images enhancement is important as it can provide more information for medical diagnosis. In this work, we design three simple yet useful filters based on the combinations of mathematical functions, which are proved to be effective in strengthening the images acquired from the fluorescence microscope. Using these filters, detailed objects can be found in the dark sections of the fluorescence images. In addition, these filters can be used to enhance the low-light image, which provide satisfactory visual information and marginal profile for the blurred objects in the image. Moreover, these filters have been used to enhance the image with high degradation by the Gaussian noise, where clear edge profile can be extracted. Finally, we have shown that these filters can be utilized for the image compression. Compression ratio can be obtained to be 0.9688. This study shows the making of the filters with dual functions for the image enhancement and the image compression. Our designed filters are showing the potentials in the field of biomedical imaging and pattern identification.

Image Enhancement via Special Functions and Its Application for Near Infrared Imaging.

Image enhancement is important given that it can be used to highlight the area of interest in the images. This article designs four filters via special function for realizing image enhancement. Firstly, a filter based on the exponential function is designed. When the value of the progression is even, the edge feature can be extracted. When the value of the progression is odd, sharp contrast can be obtained. Secondly, a filter is built using hyperbolic cosine and its inverse function, where a printmaking feature can be extracted. Thirdly, a filter is made via a hyperbolic secant function and its inverse. It can lead to the extraction of image edge. When the progression value is increasing, marginal effect can be found and the brightness is decreasing. Ripple morphology can be found. Fourthly, a filter is constructed through a hyperbolic sine function and its inverse, where marginal features can be extracted. Furthermore, these filters are useful for extracting the marginal features even when a high noise density of 0.9 is added to the original images. They are useful for highlighting the images acquired from near infrared imaging.

"Dominolike" Barriers Elimination with an Intratumoral Adenosine-Triphosphate-Supersensitive Nanogel to Enhance Cancer Chemoimmunotherapy.

Pathophysiological barriers in "cold" tumors seriously limit the clinical outcomes of chemoimmunotherapy. These barriers distribute in a spatial order in tumors, including immunosuppressive microenvironment, overexpressed chemokine receptors, and dense tumor mesenchyme, which require a sequential elimination in therapeutics. Herein, we reported a "dominolike" barriers elimination strategy by an intratumoral ATP supersensitive nanogel (denoted as BBLZ-945@PAC-PTX) for enhanced chemoimmunotherapy. Once it has reached the tumor site, BBLZ-945@PAC-PTX nanogel undergoes supersensitive collapse triggered by adenosine triphosphate (ATP) in perivascular regions and releases BLZ-945 conjugated albumin (BBLZ-945) to deplete tumor-associated macrophages (TAMs). Deeper spatial penetration of shrunk nanogel (PAC-PTX) could not only block CXCR4 on the cell membrane to decrease immunosuppressive cell recruitment but also internalize into tumor cells for tumor-killing and T cell priming. The strategy of "dominolike" barriers elimination in tumors enables immune cell infiltration for a potentiated immune response and offers a high-responsive treatment opinion for chemoimmunotherapy.

Highly Efficient and Stable Binary Cross-Linkable/ Self-Assembled Organic Nonlinear Optical Molecular Glasses.

The development of electro-optical materials with high chromophore loading levels that possess ultrahigh electro-optic coefficients and high long term alignment stability is a challenging topic. Anthracene-maleimide Diels-Alder (DA) reaction and π-π interaction of Anthracene-pentafluorobenzene and benzene-pentafluorobenzene are developed for making highly efficient binary cross-linkable/self-assembled dendritic chromophores FZL1-FZL4. A covalently or non-covalently cross-linked network is formed by DA reaction or π-π interaction after electric field poling orientation, which greatly improves the long-term alignment stability of the materials. An electro-optic coefficient up to 266 pm V-1 and glass transition temperature as high as 178 °C are achieved in cross-linked film FZL1/FZL2, and 272-308 pm V-1 is achieved for self-assembled films FZL1/FZL4 and FZL3/FZL4 due to high chromophore density (3.09-4.02 × 1020 molecules cm-3 ). Long-term alignment stability tests show that after heating at 85 °C for over 500 h, 99.73% of the initial r33 value is maintained for poled crosslinked electro-optic films 1:1 FZL1/FZL2. The poled self-assembled electro-optic films 1:1 FZL1/FZL4 and 1:1 FZL3/FZL4 can still maintain more than 97.11% and 98.23%, respectively, of the original electro-optic coefficient after being placed at room temperature for 500 h. The excellent electro-optic coefficient and stability of the material indicate the practical application prospects of organic electro-optic materials.

Iontronic pressure sensor with high sensitivity over ultra-broad linear range enabled by laser-induced gradient micro-pyramids.

Despite the extensive developments of flexible capacitive pressure sensors, it is still elusive to simultaneously achieve excellent linearity over a broad pressure range, high sensitivity, and ultrahigh pressure resolution under large pressure preloads. Here, we present a programmable fabrication method for microstructures to integrate an ultrathin ionic layer. The resulting optimized sensor exhibits a sensitivity of 33.7 kPa-1 over a linear range of 1700 kPa, a detection limit of 0.36 Pa, and a pressure resolution of 0.00725% under the pressure of 2000 kPa. Taken together with rapid response/recovery and excellent repeatability, the sensor is applied to subtle pulse detection, interactive robotic hand, and ultrahigh-resolution smart weight scale/chair. The proposed fabrication approaches and design toolkit from this work can also be leveraged to easily tune the pressure sensor performance for varying target applications and open up opportunities to create other iontronic sensors.

Poly-antioxidants for enhanced anti-miR-155 delivery and synergistic therapy of metastatic breast cancer.

Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release. Notably, the poly-drug strategy could not only promote the tumoral accumulation of small molecular antioxidants but also enhance the transfection efficiency of anti-miR-155 owing to the hydrophobic property of TEMPOL. After synergistic treatment, the NF-κB pathway was significantly blocked, thereby generating strong anti-metastatic ability both in vitro and in vivo. The poly-antioxidant could be a new type of nanoplatform for highly efficient and safe miRNA delivery, which also provides a promising strategy for the synergistic treatment of metastatic breast cancer.

Multimodal Sensors with Decoupled Sensing Mechanisms.

Highly sensitive and multimodal sensors have recently emerged for a wide range of applications, including epidermal electronics, robotics, health-monitoring devices and human-machine interfaces. However, cross-sensitivity prevents accurate measurements of the target input signals when a multiple of them are simultaneously present. Therefore, the selection of the multifunctional materials and the design of the sensor structures play a significant role in multimodal sensors with decoupled sensing mechanisms. Hence, this review article introduces varying methods to decouple different input signals for realizing truly multimodal sensors. Early efforts explore different outputs to distinguish the corresponding input signals applied to the sensor in sequence. Next, this study discusses the methods for the suppression of the interference, signal correction, and various decoupling strategies based on different outputs to simultaneously detect multiple inputs. The recent insights into the materials' properties, structure effects, and sensing mechanisms in recognition of different input signals are highlighted. The presence of the various decoupling methods also helps avoid the use of complicated signal processing steps and allows multimodal sensors with high accuracy for applications in bioelectronics, robotics, and human-machine interfaces. Finally, current challenges and potential opportunities are discussed in order to motivate future technological breakthroughs.

Macrophage targeted triptolide micelles capable of cGAS-STING pathway inhibition for rheumatoid arthritis treatment.

The abundant M1 macrophages in the joint synovium were the main factors that exacerbate rheumatoid arthritis (RA) by secreting various types of inflammatory cytokines. Here, we note that cGAS-STING, an important pro-inflammatory pathway, was significantly up-regulated in RA, enabling it be the potential target for RA therapy. Therefore, in this work, we developed M1 macrophages targeted micelles capable of cGAS-STING pathway inhibition for the smart treatment of RA. The folic acid (FA) and lauric acid (LA) were modified on dextran to obtain an amphiphilic polymer (FDL). Then, FDL was subsequently applied to encapsulate triptolide (TP) to form FDL@TP nanomicelles. The FDL@TP could target the joint and enhance the cell uptake of TP by M1 macrophages (overexpressing folate receptor-ß), which also reduced the side effects of TP on normal tissues. In M1 macrophages, the released TP, acted as an anti-inflammatory and immunosuppressant, obviously down-regulated the expressions of cGAS and STING protein, and thus reduced the secretion of TNF-α, IL-1ß and IL-6. Importantly, compared with the same dose of free TP, FDL@TP could significantly enhance the anti-inflammatory effect. Therefore, FDL@TP nanomicelles were believed to be superior candidates for the clinical treatment of RA.

Multi-Role Surface Modification of Single-Crystalline Nickel-Rich Lithium Nickel Cobalt Manganese Oxides Cathodes with WO3 to Improve Performance for Lithium-Ion Batteries.

Compared with the polycrystalline system, the single-crystalline ternary cathode material has better cycle stability because the only primary particles without grain boundaries effectively alleviate the formation of micro/nanocracks and retain better structural integrity. Therefore, it has received extensive research attention. There is no consistent result whether tungsten oxide acts as doping and/or coating from the surface modification of the polycrystalline system. Meanwhile, there is no report on the surface modification of the single-crystalline system by tungsten oxide. In this paper, multirole surface modification of single-crystalline nickel-rich ternary cathode material LiNi0.6Co0.2Mn0.2O2 by WO3 is studied by a simple method of adding WO3 followed by calcination. The results show that with the change in the amount of WO3 added, single-crystalline nickel-rich ternary cathode material can be separately doped, separately coated, and both doped and coated. Either doping or coating effectively enhances the structural stability, reduces the polarization of the material, and improves the lithium-ion diffusion kinetics, thus improving the cycle stability and rate performance of the battery. Interestingly, both doping and coating (for SC-NCM622-0.5%WO3) do not show a more excellent synergistic effect, while the single coating (for SC-NCM622-1.0%WO3) after eliminating the rock-salt phase layer performs the most excellent modification effect.

Pore forming-mediated intracellular protein delivery for enhanced cancer immunotherapy.

Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8+ T cells to form pores on the tumor cells' plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8+ T cell-mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer. Notably, three courses of laser irradiation induced efficient cell apoptosis and immune activation, resulting in a notable therapeutic efficacy that 75% of the tumors were ablated without relapse.

Deep subwavelength waveguiding and focusing based on designer surface plasmons.

We experimentally demonstrate focusing and guiding electromagnetic (EM) waves in a designer surface plasmonic waveguide with deep subwavelength mode cross section. Our experiments show that a metal grating with suitable parameters, functioning as a designer surface plasmonic waveguide, can support deep subwavelength surface modes and the width of the modes can be squeezed also into deep subwavelength by tapering the width of the waveguide. The results provide a new insight into deep subwavelength waveguiding and focusing.