Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring.

Bacillus Calmette-Guérin (BCG) vaccination induces a type of immune memory known as "trained immunity", characterized by the immunometabolic and epigenetic changes in innate immune cells. However, the molecular mechanism underlying the strategies for inducing and/or boosting trained immunity in alveolar macrophages remains unknown. Here, we found that mucosal vaccination with the recombinant strain rBCGPPE27 significantly augmented the trained immune response in mice, facilitating a superior protective response against Mycobacterium tuberculosis and non-related bacterial reinfection in mice when compared to BCG. Mucosal immunization with rBCGPPE27 enhanced innate cytokine production by alveolar macrophages associated with promoted glycolytic metabolism, typical of trained immunity. Deficiency of the mammalian target of rapamycin complex 2 and hexokinase 1 abolished the immunometabolic and epigenetic rewiring in mouse alveolar macrophages after mucosal rBCGPPE27 vaccination. Most noteworthy, utilizing rBCGPPE27's higher-up trained effects: The single mucosal immunization with rBCGPPE27-adjuvanted coronavirus disease (CoV-2) vaccine raised the rapid development of virus-specific immunoglobulin G antibodies, boosted pseudovirus neutralizing antibodies, and augmented T helper type 1-biased cytokine release by vaccine-specific T cells, compared to BCG/CoV-2 vaccine. These findings revealed that mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via reprogramming mTORC2- and HK-1-mediated aerobic glycolysis, providing new vaccine strategies for improving tuberculosis (TB) or coronavirus variant vaccinations, and targeting innate immunity via mucosal surfaces.

AGAT-PPIS: a novel protein-protein interaction site predictor based on augmented graph attention network with initial residual and identity mapping.

Identifying protein-protein interaction (PPI) site is an important step in understanding biological activity, apprehending pathological mechanism and designing novel drugs. Developing reliable computational methods for predicting PPI site as screening tools contributes to reduce lots of time and expensive costs for conventional experiments, but how to improve the accuracy is still challenging. We propose a PPI site predictor, called Augmented Graph Attention Network Protein-Protein Interacting Site (AGAT-PPIS), based on AGAT with initial residual and identity mapping, in which eight AGAT layers are connected to mine node embedding representation deeply. AGAT is our augmented version of graph attention network, with added edge features. Besides, extra node features and edge features are introduced to provide more structural information and increase the translation and rotation invariance of the model. On the benchmark test set, AGAT-PPIS significantly surpasses the state-of-the-art method by 8% in Accuracy, 17.1% in Precision, 11.8% in F1-score, 15.1% in Matthews Correlation Coefficient (MCC), 8.1% in Area Under the Receiver Operating Characteristic curve (AUROC), 14.5% in Area Under the Precision-Recall curve (AUPRC), respectively.

Pyroelectric-Effect-Assisted Near-Infrared-Driven Photoelectrochemical Biosensor Based on Exponential DNA Amplifier for MicroRNA Detection.

Although near-infrared responsive photoelectrochemical (PEC) biosensors have less damage to biological components compared to UV-visible light, they still reveal an inferior response due to the rapid recombination of photogenerated electron-hole. In this study, a near-infrared-driven PEC biosensor is fabricated for microRNA (miRNA) detection via integrating photoelectricity and pyroelectricity. Upon the introduction of target miRNA-21, the exponential DNA amplifier is triggered based on enzyme-assisted strand displacement amplification (SDA), releasing multiple Ag2S reporter probes to hybridize with capture probes immobilized on a CdS-2-mercaptobenzimidazole (2MBI)-modified photoelectrode. As a result, under the stimulation of NIR, the photoelectric conversion of Ag2S NPs generates the photocurrents. In addition, due to the strong hole acceptor ability of MBI, the pyroelectric effect of CdS-2MBI nanocomposites is enhanced, which generates highly pyroelectro-induced charge separation efficiency and induces the pyroelectric current benefited from the spontaneous polarization of CdS-2MBI caused by the temperature variation under the function of Ag2S nanoheaters. Impressively, this PEC biosensor has achieved the sensitive and selective determination of miRNA-21 with a detection limit as low as 54 fM. Overall, this NIR-driven PEC biosensor based on pyroelectric and photoelectric effects opens up a new horizon for bioanalysis and early disease diagnosis.

Catheter-Assisted Bioinspired Adhesive Magnetic Soft Millirobot for Drug Delivery.

Soft millirobots have evolved into various therapeutic applications in the medical field, including for vascular dredging, cell transportation, and drug delivery, owing to adaptability to their surroundings. However, most soft millirobots cannot quickly enter, retrieve, and maintain operations in their original locations after removing the external actuation field. This study introduces a soft magnetic millirobot for targeted medicine delivery that can be transported into the body through a catheter and anchored to the tissues. The millirobot has a bilayer adhesive body with a mussel-inspired hydrogel layer and an octopus-inspired magnetic structural layer. It completes entry and retrieval with the assistance of a medical catheter based on the difference between the adhesion of the hydrogel layer in air and water. The millirobot can operate in multiple modes of motion under external magnetic fields and underwater tissue adhesion after self-unfolding with the structural layer. The adaptability and recyclability of the millirobots are demonstrated using a stomach model. Combined with ultrasound (US) imaging, operational feasibility within organisms is shown in isolated small intestines. In addition, a highly efficient targeted drug delivery is confirmed using a fluorescence imaging system. Therefore, the proposed soft magnetic millirobots have significant potential for medical applications.

Engineering of Cerium Modified TiNb2O7 Nanoparticles For Low-Temperature Lithium-Ion Battery.

Although TiNb2O7 (TNO) with comparable operating potential and ideal theoretical capacity is considered to be the most ideal replacement for negative Li4Ti5O12 (LTO), the low ionic and electronic conductivity still limit its practical application as satisfactory anode for lithium-ion batteries (LIBs) with high-power density. Herein, TNO nanoparticles modified by Cerium (Ce) with outstanding electrochemical performance are synthesized. The successful introduction of Ce3+ in the lattice leads to increased interplanar spacing, refined grain size, more oxygen vacancy, and a smaller lithium diffusion barrier, which are conducive to improve conductivity of both Li+ and electrons. As a result, the modified TNO reaches high reversible capacity of 256.0 mA h g-1 at 100 mA g-1 after 100 cycles, and 183.0 mA h g-1 even under 3200 mA g-1. In particular, when the temperature drops to -20 °C, the cell undergoing 1500 cycles at a high current density of 500 mA g-1 can still reach 89.7 mA h g-1, corresponding to a capacity decay rate per cycle of only 0.033%. This work provides a new way to improve the electrochemical properties of alternative anodes for LIBs at extreme temperature.

Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

High-performance, large-area flexible SERS substrates prepared by reactive ion etching for molecular detection.

In the realm of molecular detection, the surface-enhanced Raman scattering (SERS) technique has garnered increasing attention due to its rapid detection, high sensitivity, and non-destructive characteristics. However, conventional rigid SERS substrates are either costly to fabricate and challenging to prepare over a large area, or they exhibit poor uniformity and repeatability, making them unsuitable for inspecting curved object surfaces. In this work, we present a flexible SERS substrate with high sensitivity as well as good uniformity and repeatability. First, the flexible polydimethylsiloxane (PDMS) substrate is manually formulated and cured. SiO2/Ag layer on the substrate can be obtained in a single process by using ion beam sputtering. Then, reactive ion etching is used to etch the upper SiO2layer of the film, which directly leads to the desired densely packed nanostructure. Finally, a layer of precious metal is deposited on the densely packed nanostructure by thermal evaporation. In our proposed system, the densely packed nanostructure obtained by etching the SiO2layer directly determines the SERS ability of the substrate. The bottom layer of silver mirror can reflect the penetrative incident light, the spacer layer of SiO2and the top layer of silver thin film can further localize the light in the system, which can realize the excellent absorption of Raman laser light, thus enhancing SERS ability. In the tests, the prepared substrates show excellent SERS performance in detecting crystalline violet with a detection limit of 10-11M. The development of this SERS substrate is anticipated to offer a highly effective and convenient method for molecular substance detection.

Circ-SATB2 (hsa_circ_0008928) and miR-150-5p are regulators of TRIM66 in the regulation of NSCLC cell growth and metastasis of NSCLC cells via the ceRNA pathway.

Circular RNA (circRNA) was an important modulator and potential molecular target of nonsmall cell lung cancer (NSCLC). CircSATB2 was reported to be upregulated in NSCLC. However, the role and mechanism of circSATB2 in NSCLC progression remain to be illustrated. The RNA and protein expression was detected by quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry assay. Cell counting kit-8, cell colony formation, and 5-ethynyl-2'-deoxyuridine assays were applied to assess cell growth. The migrated and invaded cells were examined by transwell assay. Flow cytometry was performed to measure apoptotic cells. The interaction among circSATB2, microRNA-150-5p (miR-150-5p), and tripartite motif-containing protein 66 (TRIM66) was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. An in vivo experiment was conducted to investigate the effect of circSATB2 on tumor growth. CircSATB2 expression was highly expressed in NSCLC tissues and cell lines. CircSATB2 and TRIM66 silencing both suppressed NSCLC cell growth, migration, and invasion whereas promoted NSCLC cell apoptosis. CircSATB2 acted as a molecular sponge for miR-150-5p, and miR-150-5p interacted with the 3' untranslated region (3'UTR) of TRIM66. Moreover, circSATB2 knockdown-induced effects were partly reversed by TRIM66 overexpression in NSCLC cells. Besides, cirSATB2 expression was negatively correlated with miR-150-5p level and positively correlated with TRIM66 level in NSCLC tumor tissues. CircSATB2 knockdown blocked xenograft tumor growth in vivo. In summary, this study verified that circSATB2 stimulated NSCLC cell malignant behaviors by miR-150-5p/TRIM66 pathway, providing a possible circRNA-targeted therapy for NSCLC.

The multifaceted role of macrophage mitophagy in SiO2-induced pulmonary fibrosis: A brief review.

Prolonged exposure to environments with high concentrations of crystalline silica (CS) can lead to silicosis. Macrophages play a crucial role in the pathogenesis of silicosis. In the process of silicosis, silica (SiO2) invades alveolar macrophages (AMs) and induces mitophagy which usually exists in three states: normal, excessive, and/or deficiency. Different mitophagy states lead to corresponding toxic responses, including successful macrophage repair, injury, necrosis, apoptosis, and even pulmonary fibrosis. This is a complex process accompanied by various cytokines. Unfortunately, the details have not been fully systematically summarized. Therefore, it is necessary to elucidate the role of macrophage mitophagy in SiO2-induced pulmonary fibrosis by systematic analysis on the literature reports. In this review, we first summarized the current data on the macrophage mitophagy in the development of SiO2-induced pulmonary fibrosis. Then, we introduce the molecular mechanism on how SiO2-induced mitophagy causes pulmonary fibrosis. Finally, we focus on introducing new therapies based on newly developed mitophagy-inducing strategies. We conclude that macrophage mitophagy plays a multifaceted role in the progression of SiO2-induced pulmonary fibrosis, and reprogramming the macrophage mitophagy state accordingly may be a potential means of preventing and treating pulmonary fibrosis.

A neural network model to screen feature genes for pancreatic cancer.

All the time, pancreatic cancer is a problem worldwide because of its high degree of malignancy and increased mortality. Neural network model analysis is an efficient and accurate machine learning method that can quickly and accurately predict disease feature genes. The aim of our research was to build a neural network model that would help screen out feature genes for pancreatic cancer diagnosis and prediction of prognosis. Our study confirmed that the neural network model is a reliable way to predict feature genes of pancreatic cancer, and immune cells infiltrating play an essential role in the development of pancreatic cancer, especially neutrophils. ANO1, AHNAK2, and ADAM9 were eventually identified as feature genes of pancreatic cancer, helping to diagnose and predict prognosis. Neural network model analysis provides us with a new idea for finding new intervention targets for pancreatic cancer.

Plasma Electrochemistry for Carbon-Carbon Bond Formation via Pinacol Coupling.

The formation of carbon-carbon bonds by pinacol coupling of aldehydes and ketones requires a large negative reduction potential, often realized with a stoichiometric reducing reagent. Here, we use solvated electrons generated via a plasma-liquid process. Parametric studies with methyl-4-formylbenzoate reveal that selectivity over the competing reduction to the alcohol requires careful control over mass transport. The generality is demonstrated with benzaldehydes, benzyl ketones, and furfural. A reaction-diffusion model explains the observed kinetics, and ab initio calculations provide insight into the mechanism. This study opens the possibility of a metal-free, electrically-powered, sustainable method for reductive organic reactions.

Syntheses, Structures, and Magnetic Properties of Three Cyano-Bridged FeII-MoIII Single-Molecule Magnets.

Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.

Molecular insights into nitrogen constraint for niche partitioning and physiological adaptation of coastal Synechococcus assemblages.

Coastal nitrogen input has substantially increased due to human activity. However, much remains unknown about the nitrogen-driven patterns and the underlying genetic basis of coastal picoplankton. To investigate the response and mechanisms of picoplankton induced by nitrogen variation, we conducted in-situ investigations using high-throughput sequencing in the Bohai Sea and performed laboratory nitrogen simulation experiments accompanied by physiological, genomic, and transcriptomic analyses, with Synechococcus as a representative. The results of in-situ investigation revealed that Synechococcus clades I, III, WPC1, and VI of subcluster 5.1 (S5.1) are prevalent in strait areas characterized by robust water exchange with the North Yellow Sea, while clades II, VIII, and IX of S5.1, as well as subcluster 5.2 (S5.2) and subcluster 5.3 (S5.3) are more abundant in central and bay areas experiencing elevated nitrate and nitrite loads. The laboratory experiments further confirmed that inorganic nitrogen is a crucial determinant of diversity and niche partitioning of Synechococcus lineages. Besides, the raising inorganic nitrogen concentration within the current in-situ range (0.1-10 µmol L-1) enhances photosynthesis and carbon fixation of Synechococcus, however further escalation of inorganic nitrogen (100 µmol L-1) may hinder these processes instead. The phenomenon could be associated with the differential expression of genes in metabolic pathways regulating nitrogen metabolism, photosynthetic system II, and photosynthesis-antenna proteins in response to nitrogen concentration and type variation. These findings expand our understanding of the impact of macronutrient variation resulting from human activities on marine picoplankton and biogeochemical cycles.

Zinc deficiency compromises the maturational competence of porcine oocyte by inducing mitophagy and apoptosis.

Zinc, an essential trace mineral, plays a pivotal role in cell proliferation, maintenance of redox homeostasis, apoptosis, and aging. Serum zinc concentrations are reduced in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanism of the effects of zinc deficiency on the female reproductive system, especially oocyte quality, has not been fully elucidated. Thus, we established an in vitro experimental model by adding N,N,N',N'-Tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) into the culture medium, and to determine the potential regulatory function of zinc during porcine oocytes maturation. In the present study, we found that zinc deficiency caused aberrant meiotic progress, accompanied by the disrupted cytoskeleton structure in porcine oocytes. Zinc deficiency impaired mitochondrial function and dynamics, leading to the increase of reactive oxygen species (ROS) and acetylation level of the antioxidative enzyme superoxide dismutase 2 (SOD2), eventually induced the occurrence of oxidative stress and early apoptosis. Moreover, zinc deficiency perturbed cytosolic Ca2+ homeostasis, lipid droplets formation, demonstrating the aberrant mitochondrial function in porcine oocytes. Importantly, we found that zinc deficiency in porcine oocytes induced the occurrence of mitophagy by activating the PTEN-induced kinase 1/Parkin signaling pathway. Collectively, our findings demonstrated that zinc was a critical trace mineral for maintaining oocyte quality by regulating mitochondrial function and autophagy in porcine oocytes.

ADAMTS13 inhibits H2O2-induced human venous endothelial cell injury to attenuate deep-vein thrombosis by blocking the p38/ERK signaling pathway.

Deep vein thrombosis (DVT) is a common complication in hematologic malignancies and immunologic disorders. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), a plasma metalloprotease that cleaves von Willebrand factor, acts as a critical regulator in normal hemostasis. This study was aimed to explore the role of ADAMTS13 in endothelial cell injury during DVT and the possible mechanism. First, human umbilical vein endothelial cells (HUVECs) were exposed to hydrogen peroxide (H2O2). Then, the mRNA and protein expressions of ADAMTS13 were evaluated with the reverse transcription-quantitative polymerase chain reaction and western blot. After treatment with recombinant ADAMTS13 (rADAMTS13; rA13), the viability and apoptosis of H2O2-induced HUVECs were assessed by cell counting kit-8 assay and terminal-deoxynucleoitidyl transferase-mediated nick end labeling staining. In addition, the levels of prostaglandin F1-alpha, endothelin-1, and reactive oxygen species were detected using the enzyme-linked immunosorbent assay and dichloro-dihydro-fluorescein diacetate assay. The expressions of proteins related to p38/extracellular signal-regulated kinase (ERK) signaling pathway were estimated with the western blot. Then, p79350 (p38 agonist) was used to pretreat cells to analyze the regulatory effects of rA13 on p38/ERK signaling in H2O2-induced HUVEC injury. The results revealed that ADAMTS13 expression was significantly downregulated in H2O2-induced HUVECs. The reduced viability and increased apoptosis of HUVECs induced by H2O2 were revived by ADAMTS13. ADAMTS13 also suppressed the oxidative stress in HUVECs after H2O2 treatment. Besides, ADAMTS13 was found to block p38/ERK signaling pathway, and p79350 reversed the impacts of ADAMTS13 on the damage of HUVECs induced by H2O2. To sum up, ADAMTS13 could alleviate H2O2-induced HUVEC injury through the inhibition of p38/ERK signaling pathway.

High-Density Functional Near-Infrared Spectroscopy and Machine Learning for Visual Perception Quantification.

The main application scenario for wearable sensors involves the generation of data and monitoring metrics. fNIRS (functional near-infrared spectroscopy) allows the nonintrusive monitoring of human visual perception. The quantification of visual perception by fNIRS facilitates applications in engineering-related fields. This study designed a set of experimental procedures to effectively induce visible alterations and to quantify visual perception in conjunction with the acquisition of Hbt (total hemoglobin), Hb (hemoglobin), and HbO2 (oxygenated hemoglobin) data obtained from HfNIRS (high-density functional near-infrared spectroscopy). Volunteers completed the visual task separately in response to different visible changes in the simulated scene. HfNIRS recorded the changes in Hbt, Hb, and HbO2 during the study, the time point of the visual difference, and the time point of the task change. This study consisted of one simulated scene, two visual variations, and four visual tasks. The simulation scene featured a car driving location. The visible change suggested that the brightness and saturation of the car operator interface would change. The visual task represented the completion of the layout, color, design, and information questions answered in response to the visible change. This study collected data from 29 volunteers. The volunteers completed the visual task separately in response to different visual changes in the same simulated scene. HfNIRS recorded the changes in Hbt, Hb, and HbO2 during the study, the time point of the visible difference, and the time point of the task change. The data analysis methods in this study comprised a combination of channel dimensionality reduction, feature extraction, task classification, and score correlation. Channel downscaling: This study used the data of 15 channels in HfNIRS to calculate the mutual information between different channels to set a threshold, and to retain the data of the channels that were higher than those of the mutual information. Feature extraction: The statistics derived from the visual task, including time, mean, median, variance, extreme variance, kurtosis, bias, information entropy, and approximate entropy were computed. Task classification: This study used the KNN (K-Nearest Neighbors) algorithm to classify different visual tasks and to calculate the accuracy, precision, recall, and F1 scores. Scoring correlation: This study matched the visual task scores with the fluctuations of Hbt, Hb, and HbO2 and observed the changes in Hbt, Hb, and HbO2 under different scoring levels. Mutual information was used to downscale the channels, and seven channels were retained for analysis under each visual task. The average accuracy was 96.3% ± 1.99%; the samples that correctly classified the visual task accounted for 96.3% of the total; and the classification accuracy was high. By analyzing the correlation between the scores on different visual tasks and the fluctuations of Hbt, Hb, and HbO2, it was found that the higher the score, the more obvious, significant, and higher the fluctuations of Hbt, Hb, and HbO2. Experiments found that changes in visual perception triggered changes in Hbt, Hb, and HbO2. HfNIRS combined with Hbt, Hb, and HbO2 recorded by machine learning algorithms can effectively quantify visual perception. However, the related research in this paper still needs to be further refined, and the mathematical relationship between HfNIRS and visual perception needs to be further explored to realize the quantitative study of subjective and objective visual perception supported by the mathematical relationship.

Multi-Scene Mask Detection Based on Multi-Scale Residual and Complementary Attention Mechanism.

Vast amounts of monitoring data can be obtained through various optical sensors, and mask detection based on deep learning integrates neural science into a variety of applications in everyday life. However, mask detection poses technical challenges such as small targets, complex scenes, and occlusions, which necessitate high accuracy and robustness in multi-scene target detection networks. Considering that multi-scale features can increase the receptive field and attention mechanism can improve the detection effect of small targets, we propose the YOLO-MSM network based on the multi-scale residual (MSR) block, multi-scale residual cascaded channel-spatial attention (MSR-CCSA) block, enhanced residual CCSA (ER-CCSA) block, and enhanced residual PCSA (ER-PCSA) block. Considering the performance and parameters, we use YOLOv5 as the baseline network. Firstly, for the MSR block, we construct hierarchical residual connections in the residual blocks to extract multi-scale features and obtain finer features. Secondly, to realize the joint attention function of channel and space, both the CCSA block and PCSA block are adopted. In addition, we construct a new dataset named Multi-Scene-Mask, which contains various scenes, crowd densities, and mask types. Experiments on the dataset show that YOLO-MSM achieves an average precision of 97.51%, showing better performance than other detection networks. Compared with the baseline network, the mAP value of YOLO-MSM is increased by 3.46%. Moreover, we propose a module generalization improvement strategy (GIS) by training YOLO-MSM on the dataset augmented with white Gaussian addition noise to improve the generalization ability of the network. The test results verify that GIS can greatly improve the generalization of the network and YOLO-MSM has stronger generalization ability than the baseline.

Biometric Photoelectrochemical-Visual Multimodal Biosensor Based on 3D Hollow HCdS@Au Nanospheres Coupled with Target-Induced Ion Exchange Reaction for Antigen Detection.

Three-dimensional (3D) hollow photoactive nanomaterials can enhance light capture due to the light scattering benefiting from the unique hollow nanostructures, which contributes to the decrease in energy loss and the electron-hole recombination during the process of photoelectric conversion. Herein, a 3D hollow HCdS@Au nanosphere synthesized by the templated-assisted method and photodeposition is employed to construct a multimodal sensing platform by combining the photoelectrochemical (PEC) biosensor with colorimetric analysis and photothermal imaging. In the presence of target carcinoembryonic antigen (CEA), a sandwich structure is formed on magnetic beads based on the dual-aptamer recognition, followed by the initiation of rolling circle amplification (RCA) to bind numerous CuO-DNA probes. Upon stimulation by chlorhydric acidic, a large number of Cu2+ is released from CuO, which could interact with yellow HCdS@Au on electrode to produce dark CuS by ion exchange. As a result, with increased CEA level, the photocurrent is weakened and the color of electrode interface is changed from yellow to dark, which thus facilitates the PEC and colorimetric detection of CEA. Simultaneously, the formed CuS with highly photothermal effect can achieve qualitative visual analysis of CEA using a portable infrared thermal imager. This work exhibits an excellent performance for sensitive and selective detection of CEA in the dynamic working range from 0.015 to 2.4 ng/mL with a detection limit as low as 3.5 pg/mL. Moreover, the proposed PEC biosensor is successfully applied to CEA determination in human serum, which holds great promise in accurate analysis of biomarkers and early diagnosis of diseases in the clinic.

Suspended 3D metallic dimers with sub-10 nm gap for high-sensitive SERS detection.

The suspended metallic nanostructures with tiny gaps have certain advantages in surface-enhanced Raman scattering (SERS) due to the coaction of the tiny metallic nanogaps and the substrate-decoupled electromagnetism resonant modes. In this study, we used the lithographic HSQ/PMMA electron-beam bilayer resist exposure combined with a deposition-induced nanogap-narrowing process to define elevated suspended metallic nanodimers with tiny gaps for surface-enhanced Raman spectroscopy detection. By adjusting the deposited metal thickness, the metallic dimers with sub-10 nm gaps can be reliably obtained. These dimers with tunable nanogaps successfully served as excellent SERS substrates, exhibiting remarkable high-sensitivity detection ability for crystal violet molecules. Systematic experiments and simulations were conducted to explain the origin of the improved SERS performance. The results showed that the 3D elevated suspended metallic dimers could achieve a higher SERS enhancement factor than the metallic dimers on HSQ pillars and a common Si substrate, demonstrating that this kind of suspended metallic dimer is a promising route for high-sensitive SERS detection and other plasmonic applications.

CircSamd4: A novel biomarker for predicting vascular calcification.

BACKGROUND: Vascular calcification (VC) is usually associated with cardiovascular diseases (CVDs), which are one of the main causes of mortality in the world. This study aimed to analyze the expression of circular RNAs (circRNAs) in patients with VC and to evaluate biomarkers for the diagnosis of VC. METHODS: Calcified human aortic endothelial cells (HAECs) and the calcification in mouse aorta were detected by qRT-PCR. Subsequently, this was verified in the plasma of patients with coronary artery calcification (CAC). The plasma of 40 patients in the control group and 31 patients in the calcified group were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect the level of circSamd4a in the blood. The diagnostic value was evaluated by logistic regression analysis and the working characteristics of subjects. RESULTS: In the HAECs, the qRT-PCR showed a significant decrease in the level of circSamd4a expression in the calcification group compared to the control group (p < 0.05). The calcified mouse aorta showed the same trend for circSamd4a expression, wherein the difference was statistically significant (p < 0.05); the expression of circSamd4a was significantly downregulated in the plasma of patients with VC (p < 0.01). The receiver operating characteristic (ROC) curves of circSamd4a in patients with VC and control group showed that the area under the curve (AUC) was 0.81 (95% CI: 0.707-0.913; p < 0.001). CONCLUSION: CircSamd4a showed a stable downward trend in different specimens, and had significant advantages as a biomarker for diagnosis of VC.