Self-Assembly-Based Nanoprobes for the Simultaneous Detection and Downregulation of HSP90α mRNA to Enhance Photothermal Therapy.

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α to reduce tumor heat tolerance. Moreover, another nanoprobe, Au-DNA3, can self-assemble with the Au-DNA1 nanoprobe after the detection to form Au aggregations to enhance PTT afterward for better efficiency. Simultaneously, such a design improves tissue penetration and tumor retention, thereby reducing the damage to the surrounding normal tissues. Both in vitro and in vivo experiments showed that the nanoprobes have excellent tumor diagnosis and cancer treatment capabilities, which is of great significance for clinical translational applications.

Simple yet effective analysis of waveguide mode symmetry: generalized eigenvalue approach based on Maxwell's equations.

Particular waveguide structures and refractive index distribution can lead to specified degeneracy of eigenmodes. To obtain an accurate understanding of this phenomenon, we propose a simple yet effective approach, i.e., generalized eigenvalue approach based on Maxwell's equations, for the analysis of waveguide mode symmetry. In this method, Maxwell's equations are reformulated into generalized eigenvalue problems. The waveguide eigenmodes are completely determined by the generalized eigenvalue problem given by two matrices (M, N), where M is 6 × 6 waveguide Hamiltonian and N is a constant singular matrix. Close examination shows that N usually commute with the corresponding matrix of a certain symmetry operation, thus the waveguide eigenmode symmetry is essentially determined by M, in contrast to the tedious and complex procedure given in the previous work [Opt. Express25, 29822 (2017)10.1364/OE.25.029822]. Based on this new approach, we discuss several symmetry operations and the corresponding symmetries including chiral, parity-time reversal, rotation symmetry, wherein the constraints of symmetry requirements on material parameters are derived in a much simpler way. In several waveguides with balanced gain and loss, anisotropy, and geometrical symmetry, the analysis of waveguide mode symmetry based on our simple yet effective approach is consistent with previous results, and shows perfect agreement with full-wave simulations.

RPSA distribution and expression in tissues and immune cells of pathogen-infected mice.

AIMS: 40S ribosomal protein SA (RPSA), a component of the small ribosomal subunit, is a high-affinity receptor of laminin that is widely expressed in cells and involves in many biological processes. However, it hasn't been reported which tissues and cells may be targeted by RPSA-mediated pathogen regulation. Therefore, in this study, a gram-positive bacterium Streptococcus suis Type 2 (SS2), gram-negative bacterium Actinobacillus pleuropneumoniae (A.pleuropneumoniae), and porcine circovirus Type 2 (PCV2) were used to infect ICR mice. METHODS AND RESULTS: The effects of infection with the three pathogens on expression levels of RPSA in mouse tissues and peripheral blood immune cells were analysed by immunohistochemistry and flow cytometry. The results suggested that the pathological changes in mice infected with SS2 were mainly manifested as congestion and inflammatory infiltration in the meninges, lungs, hearts and livers. The mice infected with A.pleuropneumoniae or PCV2 showed lung lesions and mild hepatocyte degeneration, respectively. In uninfected mice, RPSA protein was expressed to various degrees in all tissues except the spleen. After SS2 infection for 3 d, the expression of RPSA in the liver and brain increased, while decreased significantly in the heart and duodenum. These results were corroborated on examining the correlation between RPSA expression and the process of SS2 infection, except that there was no significant difference between the expression levels in the heart at 1 d and 3 d. After A.pleuropneumoniae and PCV2 infection for 3 d, the expression of RPSA decreased in the heart, and brain, respectively. Additionally, under physiological conditions, RPSA expression in CD4+ T cells, CD8+ T cells, neutrophils, and macrophages in the peripheral blood of mice was higher than that in B cells and NK cells. After SS2 infection for 3 d, RPSA expression increased significantly in CD4+ T cells and CD8+ T cells but decreased significantly in macrophages. The expression of RPSA after A.pleuropneumoniae and PCV2 infection were similar, and RPSA expression decreased only in macrophages. CONCLUSIONS: The results revealed that RPSA showed different expression levels in tissues and immune cells due to different pathogens causing disease courses, suggesting different target tissues and target cells in RPSA-mediated pathogenesis after infection, which supports the systematic study of the pathogenesis of RPSA in infectious diseases.

Advances in aptamer screening and aptasensors' detection of heavy metal ions.

Heavy metal pollution has become more and more serious with industrial development and resource exploitation. Because heavy metal ions are difficult to be biodegraded, they accumulate in the human body and cause serious threat to human health. However, the conventional methods to detect heavy metal ions are more strictly to the requirements by detection equipment, sample pretreatment, experimental environment, etc. Aptasensor has the advantages of strong specificity, high sensitivity and simple preparation to detect small molecules, which provides a new direction platform in the detection of heavy metal ions. This paper reviews the selection of aptamers as target for heavy metal ions since the 21th century and aptasensors application for detection of heavy metal ions that were reported in the past five years. Firstly, the selection methods for aptamers with high specificity and high affinity are introduced. Construction methods and research progress on sensor based aptamers as recognition element are also introduced systematically. Finally, the challenges and future opportunities of aptasensors in detecting heavy metal ions are discussed.

Structure and Performance Analysis of Signal Acquisition and Doppler Tracking in LEO Augmented GNSS Receiver.

Due to the low signal power, the Global Navigation Satellite System (GNSS) signal is vulnerable to interference and even cannot be captured or tracked in harsh environments. As an alternative, the Low Earth Orbit (LEO) satellite has been widely used in the navigation field due to the advantages of low cost and strong signals. It is becoming a significant component of the new combined navigation system with GNSS. The combination of an LEO Doppler signal and GNSS observables can improve the positioning accuracy and high-precision positioning convergence time of the GNSS receiver. However, the GNSS signal receiving capability cannot be improved from this data fusion level. We propose a novel assisted structure where GNSS signal acquisition and Doppler tracking are assisted by LEO Doppler positioning. The receiver uses the LEO signal to achieve Doppler positioning firstly. Then, the coarse position with the GNSS navigation messages received from LEO, as well as the estimated clock information, is used to assist in the acquisition and tracking of GNSS. In this way, the GNSS receiver's sensitivity can get the benefit from this integrated system. The paper presents the structure of the assisted receiver and analyzes the assisted GNSS signal acquisition and carrier tracking performance in detail. Simulation experiments of this assisted structure are carried out to verify its superiority of acquisition and tracking sensitivity in comparison with standalone GNSS receivers. Theoretical analysis and experimental results show that the proposed acquisition method can achieve 90% detection probability at a carrier-to-noise ratio (C/N0) of 15 dB-Hz, which is about 8 dB higher than the conventional acquisition method without assistance; the proposed tracking method can track weak signals of 5 dB-Hz, which is about 4 dB higher than the conventional method. Therefore, this novel LEO-assisted receiver has significantly improved weak signal acquisition and tracking sensitivity.

Arginine inhibits the malignant transformation induced by interferon-gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo.

Breast cancer is the most common female malignant tumors in the world. It seriously affects women's physical and mental health and the leading cause of cancer death among women. Our previous study demonstrated that diet-derived IFN-γ promoted the malignant transformation of primary bovine mammary epithelial cells by accelerating arginine depletion. The current study aimed to explore whether arginine addition could inhibit the degree of malignant transformation and its molecular mechanism. The results indicate that arginine addition could alleviate the malignant transformation of mammary epithelial cells induced by IFN-γ, including reducing cell proliferation, cell migration and colony formation, through the NF-κB-GCN2/eIF2α pathway. The in vivo experiments also consistently confirmed that arginine supplementation could significantly inhibit tumor growth in tumor-bearing mice. Furthermore, the investigation of the clinical data also revealed that the plasma or tissue from human breast cancer patients owned lower arginine level and higher IFN-γ level than that from patients with benign breast disease, showing IFN-γ may be a potential control target. Our findings demonstrate that arginine supplement could antagonize the malignant transformation of mammary epithelial cells induced by IFN-γ (nutritionally induced) both in vitro and in vivo, and IFN-γ was higher in breast cancer women. This might provide a novel strategy for the prevention and treatment of breast cancer regarding to nutrition.

Design and Performance Evaluation of a Dual Antenna Joint Carrier Tracking Loop.

In order to track the carrier phases of Global Navigation Satellite Systems (GNSS) signals in signal degraded environments, a dual antenna joint carrier tracking loop is proposed and evaluated. This proposed tracking loop processes inputs from two antennas, namely the master antenna and the slave antenna. The master antenna captures signals in open-sky environments, while the slave antenna capture signals in degraded environments. In this architecture, a Phase Lock Loop (PLL) is adopted as a master loop to track the carrier phase of the open-sky signals. The Doppler frequency estimated by this master loop is utilized to assist weak carrier tracking in the slave loop. As both antennas experience similar signal dynamics due to satellite motion and clock frequency variations, a much narrower loop bandwidth and possibly a longer coherent integration can be adopted to track the weak signals in slave channels, by utilizing the Doppler aid from master channels. PLL tracking performance is affected by the satellite/user dynamics, clock instability, and thermal noise. In this paper, their impacts on the proposed phase tracking loop are analyzed and verified by both simulation and field data. Theoretical analysis and experimental results show that the proposed loop structure can track degraded signals (i.e., 18 dB-Hz) with a very narrow loop bandwidth (i.e., 0.5 Hz) and a TCXO clock.

Expression and prognosis of ADAMTS18 in different tumors.

ADAMTS18 has been identified as an orphan member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of Zn-dependent secreted metalloproteinases since 2002. Despite the recent breakthroughs in tumor biology of ADAMTS18, there is no literature systematically discussing the relationship between ADAMTS18 and cancer. In this review, we will summarize the expression pattern and prognostic value of ADAMTS18 in various cancers. In addition, we will highlight the biological functions of ADAMTS18 in the tumor microenvironment, including the regulation of cell proliferation signals, death patterns, invasion, and migration, which influence cancer progression.

Learning Heterogeneous Relation Graph and Value Regularization Policy for Visual Navigation.

The goal of visual navigation is steering an agent to find a given target object with current observation. It is crucial to learn an informative visual representation and robust navigation policy in this task. Aiming to promote these two parts, we propose three complementary techniques, heterogeneous relation graph (HRG), a value regularized navigation policy (VRP), and gradient-based meta learning (ML). HRG integrates object relationships, including object semantic closeness and spatial directions, e.g., a knife is usually co-occurrence with bowl semantically or located at the left of the fork spatially. It improves visual representation learning. Both VRP and gradient-based ML improve robust navigation policy, regulating this process of the agent to escape from the deadlock states such as being stuck or looping. Specifically, gradient-based ML is a type of supervision method used in policy network training, which eliminates the gap between the seen and unseen environment distributions. In this process, VRP maximizes the transformation of the mutual information between visual observation and navigation policy, thus improving more informed navigation decisions. Our framework shows superior performance over the current state-of-the-art (SOTA) in terms of success rate and success weighted by length (SPL). Our HRG outperforms the Visual Genome knowledge graph on cross-scene generalization with ≈ 56% and ≈ 39% improvement on Hits@ 5* (proportion of correct entities ranked in top 5) and MRR * (mean reciprocal rank), respectively. Our code and HRG datasets will be made publicly available in the scientific community.

Efficient and accurate numerical-projection of electromagnetic multipoles for scattering objects.

In this paper, we develop an efficient and accurate procedure of electromagnetic multipole decomposition by using the Lebedev and Gaussian quadrature methods to perform the numerical integration. Firstly, we briefly review the principles of multipole decomposition, highlighting two numerical projection methods including surface and volume integration. Secondly, we discuss the Lebedev and Gaussian quadrature methods, provide a detailed recipe to select the quadrature points and the corresponding weighting factor, and illustrate the integration accuracy and numerical efficiency (that is, with very few sampling points) using a unit sphere surface and regular tetrahedron. In the demonstrations of an isotropic dielectric nanosphere, a symmetric scatterer, and an anisotropic nanosphere, we perform multipole decomposition and validate our numerical projection procedure. The obtained results from our procedure are all consistent with those from Mie theory, symmetry constraints, and finite element simulations.

Ultrasensitive Electrochemical Aptasensing of Malathion Based on Hydroxylated Black Phosphorus/Poly-L-Lysine Composite.

A highly sensitive unlabeled electrochemical aptasensor based on hydroxylated black phosphorus/poly-L-lysine (hBP/PLL) composite is introduced herein for the detection of malathion. Poly-L-lysine (PLL) with adhesion and coating properties adhere to the surface of the nanosheets by noncovalent interactions with underlying hydroxylated black phosphorus nanosheets (hBP) to produce the hBP/PLL composite. The as-synthesized hBP/PLL composite bonded to Au nanoparticles (Au NPs) firmly by assembling and using them as a substrate for the aptamer with high specificity as a probe to fabricate the sensor. Under optimal conditions, the linear range of the electrochemical aptasensor was 0.1 pM~1 µM, and the detection limit was 2.805 fM. The electrochemical aptasensor has great selectivity, a low detection limit, and anti-interference, which has potential application prospects in the field of rapid trace detection of pesticide residues.

Selection and electrochemical-sensor application of an DNA-aptamer for methyl parathion detection.

An aptamer-based electrochemical sensor for methyl parathion (MP) detection is herein reported. The modified magnetic beads-systematic evolution of ligands by enrichment (MB-SELEX) was used to select the MP aptamer. After 14 rounds of selection, the aptamer (MPapta-6) with high affinity for MP was obtained, and its dissociation constant (Kd) was 39.66 ± 14.73 µM. Using the MPapta-6, the ultra-sensitive electrochemical sensor based on PLL-BP and AuNPs was constructed. The linear range of MP was 1-105 pM and detection limit (LOD) was as low as 0.49 pM. In addition, the application of the sensor in water samples was verified, and the recovery rate was 96.6%-103.5%. The results from this study showed that this strategy could be applied in practical detection.

A simple, rapid and low-cost qPCR assay for evaluating the severity of exosomal PD-L1-mediated T cell exhaustion in blood samples.

A novel dual-aptamer activated proximity-induced qPCR assay was developed for the quantitative analysis of exosomal PD-L1 on T cell-exosome complexes in blood samples.

Label-Free Aptasensor for Detection of Fipronil Based on Black Phosphorus Nanosheets.

A label-free fipronil aptasensor was built based on Polylysine-black phosphorus nanosheets composition (PLL-BPNSs) and Au nanoparticles (AuNPs). A PLL-BP modified glassy carbon electrode (GCE) was fabricated by combining BP NSs and PLL, which included a considerable quantity of -NH2. Au nanoparticles (AuNPs) were placed onto the GCE, and PLL-BPNSs bonded to Au NPs firmly by assembling. The thiolated primers were then added and fixed using an S-Au bond, and competitive binding of the fipronil aptamer was utilized for fipronil quantitative assessment. The sensor's performance was evaluated using differential pulse voltammetry (DPV) method. The linear equation is ΔI (µA) = 13.04 logC + 22.35, while linear correlation coefficient R2 is 0.998, and detection limit is 74 pg/mL (0.17 nM) when the concentration of fipronil is 0.1 ng/mL-10 µg/mL. This aptasensor can apply to quantitative detection of fipronil.

Real-time in situ monitoring of Lon and Caspase-3 for assessing the state of cardiomyocytes under hypoxic conditions via a novel Au-Se fluorescent nanoprobe.

Myocardial dysfunction caused by cardiomyocyte apoptosis under ischemic and hypoxic conditions is the pathological basis of most cardiovascular diseases. Current diagnosis of myocardial dysfunction still focuses on the symptomatic stage, usually after the occurrence of the irreversible remodelling and functional impairment. Thus, early stage identification of the apoptotic cardiomyocytes induced by hypoxia is highly significant for preventing the onset and delaying the progression of myocardial dysfunction. Herein, a novel Au-Se nanoprobe with strong anti-interference capability was developed for simultaneous real-time in situ monitoring the expression of Lon protease (Lon) and Caspase-3 with high-fidelity in living cardiomyocytes. As Lon upregulation plays a major role in the initiation of hypoxia-induced apoptosis and Caspase-3 is a marker protein for apoptosis, the nanoprobe has been successfully applied for imaging the activation of Lon-Caspase-3 apoptotic signalling pathway and assessing the state of cardiomyocytes under hypoxic conditions. Furthermore, combining with mitochondrial H2O2 probe-MitoPY1, the nanoprobe was also used to confirm the synergistic effect of Lon and ROS on hypoxia-induced apoptosis of cardiomyocytes and evaluate the function of ROS scavenger on attenuating such apoptosis. This work proposed a promising strategy for early diagnosis, prevention and treatment of hypoxic-ischemic myocardial dysfunction.

Tricolor imaging of MMPs to investigate the promoting roles of inflammation on invasion and migration of tumor cells.

The expression levels of matrix metalloproteinases (MMPs) are closely related to the degree of inflammation which facilitates tumor cells' invasion and migration. A tricolor fluorescence nanoprobe based on high-fidelity gold-selenium (Au-Se) nanoplatform was designed and constructed for simultaneously imaging matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-7 (MMP-7) and matrix metalloproteinase-9 (MMP-9) to thoroughly investigate the tumor cells' invasion and migration behaviors under inflammation environment. The nanoprobe was assembled by attaching Au NPs with three different peptide substrates respectively labeled with fluorescein isothiocyanate (FITC), 5-carboxytetramethylrhodamine (5-TAMRA) and cyanine 5 (Cy5) via the Au-Se bond. The nanoprobe can specifically respond to MMP-2/7/9, thereby triggering the fluorophores' fluorescence that quenched previously by fluorescence resonance energy transfer (FRET) to realize the MMP-2/7/9's visualization in biological systems. Moreover, as the inflammation stimulated by different concentrations lipopolysaccharide (LPS), the expression of MMP-2/7/9 in SMMC-7721 cells was observed to be significantly enhanced by confocal laser scanning microscope (CLSM) imaging, and inflammation was further proved to intensify SMMC-7721 cells' invasion and migration by transwell invasion and migration experiments. Therefore, the nanoprobe can be used to monitor biomarkers to provide a visual system for the degree of invasion and migration of tumor cells in an inflammatory environment, and also offer a new strategy for the study of the correlation between various active biomacromolecules and specific intracellular pathways in cells.

Reconstruction of nano-flares based on Au-Se bonds for high-fidelity detection of RNA in living cells.

We have, for the first time, developed a Au-Se-DNA nanoprobe by upgrading the conventional Au-S bonds of nano-flares to more stable Au-Se bonds for high-fidelity imaging of target RNAs in living cells. The design concept is potentially introduced into various Au-DNA nanosensors that offer wide application prospects in research and clinical practice.

A Novel Strategy for Liquid Exfoliation of Ultrathin Black Phosphorus Nanosheets.

As an emerging two-dimensional layered material, black phosphorus nanosheets show unparalleled optical and electronic properties. Although black phosphorus nanosheets have attracted much attention in the photoelectric field, their applications in biomedical field were still limited due to their poor biocompatibility of current synthesis strategies. Herein, we propose a novel synthetic strategy for black phosphorus nanosheets that rely on Tween 20-assisted liquid exfoliation and post-processing in deoxygenated water. Microscopic and spectroscopic analysis suggested that the produced black phosphorus nanosheets dispersions exhibited good stability and higher yield compared with other currently prepared methods. Because of their ultrahigh exfoliation efficiency, the black phosphorus flakes present few-layer and even monolayer, which are thinner than the most dispersions of black phosphorus. Thus, this method enables mass-production of high-quality few-layer black phosphorus with high biocompatibility, and has the potential to be directly used in the biological field.

Recent Progress in Black Phosphorus Sensors.

Black phosphorus (BP) is a new two-dimensional material with many unique properties, such as great biocompatibility, excellent surface activity, high carrier mobility, and tunable bandgap. Black phosphorus has been particularly attractive in sensor. However, black phosphorus isolated by traditional methods is easily oxidized and degraded by air, with poor stability, which limits its application as sensors. The modification and functionalization of black phosphorus enhance the stability, sensitivity, selectivity and biocompatibility of its application in sensor. This review describes recent progresses in sensor based on black phosphorus (2016-2020). Firstly, the structure and properties, synthesis methods, modification and functionalization of black phosphorus are briefly described. Then, the advancements in designing of various sensors based on black phosphorus are systematically provided, with a specific focus on electrochemical sensors, electrochemiluminescence sensors and photoelectrochemical sensors. Finally, latest challenges and further opportunities for developing new sensors with black phosphorus nanomaterial are discussed.

Ribosomal Protein SA-Positive Neutrophil Elicits Stronger Phagocytosis and Neutrophil Extracellular Trap Formation and Subdues Pro-Inflammatory Cytokine Secretion Against Streptococcus suis Serotype 2 Infection.

Streptococcus suis serotype 2 (SS2), an important zoonotic pathogen that causes septicemia, arthritis, and irreversible meningitis in pigs and humans, can be transmitted to humans from pigs. S. suis causes huge economic losses to the swine industry and poses a serious threat to public health. Previously, we found that the brain tissues of mice with SS2-induced meningitis showed disrupted structural integrity and significantly enhanced polymorphonuclear neutrophil (PMN) infiltration. We showed that the brain tissues of SS2-infected mice had increased ribosomal protein SA (RPSA)-positive PMN counts. However, the inflammatory responses of RPSA+ PMNs to SS2 and their effects on the blood-brain barrier (BBB) remain unclear. Therefore, in studying the pathogenesis of SS2-induced meningitis, it is essential that we explore the functions of RPSA+ PMNs and their effects on the BBB. Herein, using flow cytometry and immunofluorescence microscopy analyses, we found that RPSA expression enhances PMN-induced phagocytosis and PMN-induced formation of neutrophil extracellular traps (NETs), which facilitate further elimination of bacteria. PMN surface expression of RPSA also alleviates local inflammation and tissue injuries by inhibiting secretion of the pro-inflammatory cytokines, TNF-α and IL-6. Moreover, the single-cell BBB model showed that RPSA disrupts BBB integrity by downregulating expression of tight junction-associated membrane proteins on PMNs. Taken together, our data suggest that PMN-surface expression of RPSA is a double-edged sword. RPSA+ PMN owns a stronger ability of bacterial cleaning and weakens inflammatory cytokines release which are useful to anti-infection, but does hurt BBB. Partly, RPSA+ PMN may be extremely useful to control the infection as a therapeutic cellular population, following novel insights into the special PMN population.