Automated identification of pesticide mixtures via machine learning analysis of TLC-SERS spectra.

Identification of components in pesticide mixtures has been a major challenge in spectral analysis. In this paper, we assembled monolayer Ag nanoparticles on Thin-layer chromatography (TLC) plates to prepare TLC-Ag substrates with mixture separation and surface-enhanced Raman scattering (SERS) detection. Spectral scans were performed along the longitudinal direction of the TLC-Ag substrate to generate SERS spectra of all target analytes on the TLC plate. Convolutional neural network classification and spectral angle similarity machine learning algorithms were used to identify pesticide information from the TLC-SERS spectra. It was shown that the proposed automated spectral analysis method successfully classified five categories, including four pesticides (thiram, triadimefon, benzimidazole, thiamethoxam) as well as a blank TLC-Ag data control. The location of each pesticide on the TLC plate was determined by the intersection of the information curves of the two algorithms with 100 % accuracy. Therefore, this method is expected to help regulators understand the residues of mixed pesticides in agricultural products and reduce the potential risk of agricultural products to human health and the environment.

Interfacial Self-Assembly of Surfactant-Free Au Nanoparticles as a Clean Surface-Enhanced Raman Scattering Substrate for Quantitative Detection of As5+ in Combination with Convolutional Neural Networks.

Surface-enhanced Raman scattering (SERS) is a highly sensitive tool in the field of environmental testing. However, the detection and accurate quantification of weakly adsorbed molecules (such as heavy metal ions) remain a challenge. Herein, we combine clean SERS substrates capable of capturing heavy metal ions with convolutional neural network (CNN) algorithm models for quantitative detection of heavy metal ions in solution. The SERS substrate consists of surfactant-free Au nanoparticles (NPs) and l-cysteine molecules. As plasmonic nanobuilt blocks, surfactant-free Au NPs without physical or chemical barriers are more accessible to target molecules. The amino and carboxyl groups in the l-cysteine molecule can chelate As5+ ions. The CNN algorithm model is applied to quantify and predict the concentration of As5+ ions in samples. The results demonstrated that this strategy allows for fast and accurate prediction of As5+ ion concentrations, and the determination coefficient between the predicted and actual values is as high as 0.991.

Qualitative and quantitative detection and identification of two benzodiazepines based on SERS and convolutional neural network technology.

Drug abuse is a global social issue of concern. As the drug market expands, there is an urgent need for technological methods to rapidly detect drug abuse to meet the needs of different situations. Here, we present a strategy for the rapid identification of benzodiazepines (midazolam and diazepam) using surface-enhanced Raman scattering (SERS) combined with neural networks (CNN). The method uses a self-assembled silver nanoparticle paper-based SERS substrate for detection. Then, a SERS spectrum intelligent recognition model based on deep learning technology was constructed to realize the rapid and sensitive distinction between the two drugs. In this work, a total of 560 SERS spectra were collected, and the qualitative and quantitative identification of the two drugs in water and a beverage (Sprite) was realized by a trained convolutional neural network (CNN). The predicted concentrations for each scenario could reach 0.1-50 ppm (midazolam in water), 0.5-50 ppm (midazolam in water and diazepam in Sprite), and 5-150 ppm (diazepam in Sprite), with a strong coefficient of determination (R2) larger than 0.9662. The advantage of this method is that the neural network can extract data features from the entire SERS spectrum, which makes up for information loss when manually identifying the spectrum and selecting a limited number of characteristic peaks. This work clearly clarifies that the combination of SERS and deep learning technology has become an inevitable development trend, and also demonstrates the great potential of this strategy in the practical application of SERS.

Aligned Plasmonic Antenna and Upconversion Nanoparticles toward Polarization-Sensitive Narrowband Photodetection and Imaging at 1550 nm.

Lanthanide-doped upconversion nanoparticles (UCNPs) are rising as prospect nanomaterials for constructing polarization-sensitive narrowband near-infrared (NIR) photodetectors (PDs), which have attracted significant interest in astronomy, object identification, and remote sensing. However, polarized narrowband NIR photodetection and imaging based on UCNPs have yet to be realized. Herein, we demonstrate that NIR photodetection and imaging are capable of sensing polarized light as well as affording wavelength-selective detection at 1550 nm by integrating directional-Au@Ag nanorods (D-Au@Ag NRs) with NaYF4:Er3+@NaYF4 UCNPs. Monolayer and large-area D-Au@Ag NRs polarization-sensitive plasmonic antenna films are obtained, and the center of their localized surface plasmon resonance (LSPR) peak is located at around 1550 nm. Experimental and theoretical results reveal that D-Au@Ag NRs have a sharp localized LSPR peak with a dominant scattering cross section. The UCNPs coupled with D-Au@Ag NRs exhibit significantly enhanced and strongly polarization-dependent luminescence with a high degree of polarization (DOP) of 0.72. The first polarization-resolved UC narrowband PD at 1550 nm is achieved, which delivers a DOP of 0.63, a detectivity of 1.69 × 1010 Jones, and a responsivity of 0.32 A/W. Finally, we develop a polarized imaging system for 1550 nm with visual photoelectric detection based on the aforementioned PDs. Our work opens up possibilities for manipulating UC and developing next-generation polarization-sensitive narrowband infrared photodetection and imaging technology.

Machine Learning-Driven 3D Plasmonic Cavity-in-Cavity Surface-Enhanced Raman Scattering Platform with Triple Synergistic Enhancement Toward Label-Free Detection of Antibiotics in Milk.

The surface-enhanced Raman scattering (SERS) technique with ultrahigh sensitivity has gained attention to meet the increasing demands for food safety analysis. The integration of machine learning and SERS facilitates the practical applicability of sensing devices. In this study, a machine learning-driven 3D plasmonic cavity-in-cavity (CIC) SERS platform is proposed for sensitive and quantitative detection of antibiotics. The platform is prepared by transferring truncated concave nanocubes (NCs) to an obconical-shaped template surface. Owing to the triple synergistic enhancement effect, the highly ordered 3D CIC arrays improve the simulated electromagnetic field intensity and experimental SERS activity, demonstrating a 33.1-fold enhancement compared to a typical system consisting of Au NCs deposited on a flat substrate. The integration of machine learning and Raman spectroscopy eliminates subjective judgments on the concentration of detectors using a single feature peak and achieves accurate identification. The machine learning-driven CIC SERS platform is capable of detecting ampicillin traces in milk with a detection limit of 0.1 ppm, facilitating quantitative analysis of different concentrations of ampicillin. Therefore, the proposed platform has potential applications in food safety monitoring, health care, and environmental sampling.

Interfacial layer-by-layer self-assembly of PS nanospheres and Au@Ag nanorods for fabrication of broadband and sensitive SERS substrates.

Broadband surface-enhanced Raman scattering (SERS) substrates can achieve strong SERS enhancement at multiple excitation wavelengths, which is highly desirable in diverse fields. Here, a facile and reliable interfacial layer-by-layer self-assembly technique was proposed to construct broadband and sensitive Au@Ag nanorod (NR) monolayer film over nanosphere (MFON) substrate. The Au@Ag NR MFON substrate with ultra-broad spectrum from visible to near-infrared region was achieved by varying the shape of plasmonic nanoparticles, which exhibits excellent SERS activity at different excitation wavelengths. Besides, the size of Au@Ag NRs and polystyrene spheres, and the layer numbers of Au@Ag NR film were altered to optimize the sensitivity of SERS substrates. Notably, the SERS intensity of the optimally designed Au@Ag NR MFON substrate is 25-fold larger than that of Au@Ag NR monolayer film deposition on the plane Si wafer. Furthermore, the optimal Au@Ag NR MFON substrate presents excellent reproducibility and a much wider quantitative detection range, which enables a wide-linear-range analysis of thiram in grape juice by a portable Raman spectrometer. Therefore, we envision that this study opens a new avenue toward the design of ultra-sensitive and broadband SERS platforms with widespread applications.

[Comparative study on pros and cons of sequential high-flow nasal cannula and non-invasive positive pressure ventilation immediately following early extubated patients with severe respiratory failure due to acute exacerbations of chronic obstructive pulmonary disease].

OBJECTIVE: To explore the pros and cons of sequential high-flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) immediately following early extubated patients with severe respiratory failure (SRF) due to acute exacerbations of chronic obstructive pulmonary disease (AECOPD), so as to provide evidence for clinical selection of optimal scheme. METHODS: Consecutive AECOPD patients admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Xinjiang Medical University from January 2019 to September 2020 were screened for enrollment. Patients were between 40 years old and 85 years old with acute exacerbation of bronchial-pulmonary infection, who received endotracheal intubation mechanical ventilation (ETI-MV) as the initial respiratory support method. The pattern of synchronous intermittent mandatory ventilation (SIMV) was used in the study. The parameters were set as follows: tidal volume (VT) 8 mL/kg, support pressure 10-15 cmH2O (1 cmH2O = 0.098 kPa), positive end-expiratory pressure (PEEP) 4-6 cmH2O and the ratio of inspiratory to expiratory time 1.5-2.5:1. Under these conditions, the plateau pressure (Pplat) was maintained less than 30 cmH2O. The minimum fraction of inspired oxygen was adjusted to keep the pulse oxygen saturation no less than 0.92. When the pulmonary infection control window (PIC window) occurred, the subjects were extubated immediately and randomly divided into two groups, with one group receiving HFNC (called HFNC group), the other group receiving NIPPV (called NIPPV group). Patients with failed sequential HFNC or NIPPV underwent tracheal re-intubation. The rate of tracheal re-intubation within 7 days of extubation, complications (such as nose and face crush injury and gastric distension), in-hospital mortality, duration of ETI before PIC window, length of RICU stay and length of hospital stay were compared, respectively. RESULTS: Forty-four patients were enrolled in the study, 20 in the HFNC group and 24 in the NIPPV group. There was no significant difference in the duration of ETI before PIC window between HFNC and NIPPV groups (hours: 95.9±13.1 vs. 91.8±20.4, P > 0.05). The rate of tracheal re-intubation within 7 days in the HFNC group was significantly higher than that in the NIPPV group [35.0% (7/20) vs. 4.2 % (1/24), P < 0.05]. However, the incidence of complication in the HFNC group was significantly lower than that in the NIPPV group [0% (0/20) vs. 25.0% (6/24), P < 0.05]. Compared with the NIPPV group, the in-hospital mortality in the HFNC group was slightly higher [5.0% (1/20) vs. 4.2% (1/24)], the length of RICU stay (days: 19.5±10.8 vs. 15.5±7.2) and the length of hospital stay (days: 27.4±12.2 vs. 23.3±10.9) were slightly longer, without statistical differences (all P > 0.05). CONCLUSIONS: For early extubated patients with SRF due to AECOPD, the compliance of sequential HFNC increased and the complications decreased significantly, but the final effect may be worse than sequential NIPPV.

Tetragonal Superlattice of Elongated Rhombic Dodecahedra for Sensitive SERS Determination of Pesticide Residues in Fruit.

The self-assembly of plasmonic nanoparticles into highly ordered superlattices could pave the way toward novel nanomaterials for surface-enhanced Raman scattering (SERS). Here, we propose the formation of large-area superlattices of elongated rhombic dodecahedra in a vertical orientation via a controlled droplet evaporation process. Expectedly, the constant humidity of the experimental condition could control the evaporation speed of droplets and this procedure promotes the balance between driven depletion attraction and electrostatic repulsion in the system, leading to the generation of well-organized three-dimensional (3D) superlattices. The unique geometry of elongated rhombic dodecahedra could establish the tetragonal superlattices, which breaks the conventional hexagonal symmetry of gold nanorods. Specifically, the influence of the type and concentration of surfactants, the concentration of nanoparticles, and the amount of droplets on the preparation results were systematically investigated to find the optimal assembly parameters. Remarkably, such close-packed tetragonal arrays of vertically aligned elongated rhombic dodecahedra exhibit more excellent SERS performance compared with the traditional hexagonal superstructure of gold nanorods. Benefiting from the high sensitivity and reproducibility of elongated rhombic dodecahedron superlattices, their applications in the determination of pesticide residues in apple and grape peels were successfully demonstrated. As a result, this study may advance the production of innovative plasmonic nanomaterials for a broad range of fields.

Marangoni Effect-Driven Transfer and Compression at Three-Phase Interfaces for Highly Reproducible Nanoparticle Monolayers.

Interfacial self-assembly is a powerful technology for preparing large scale nanoparticle monolayers, but fabrication of highly repeatable large scale nanoparticle monolayers remains a challenge. Here we develop an oil/water/oil (O/W/O) three-phase system based on the Marangoni effect to fabricate highly reproducible nanoparticle monolayers. Nanoparticles could be easily transferred and compressed from the lower O/W interface to the upper O/W interface due to the interfacial tension gradient. The O/W/O system can be constructed using different kinds of organic solvents. Through this approach, good uniformity and reproducibility of the nanoparticle monolayers could be guaranteed even using a wide range of nanoparticle concentrations. Furthermore, this strategy is generally applicable to various nanoparticles with different sizes, shapes, components, and surface ligands, which offers a facile and general approach to functional nanodevices.

Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice.

BACKGROUND AND AIMS: Chronic intermittent hypoxia (CIH) exposure causes atherosclerosis, although the underlying mechanisms are poorly understood. This study defines the role of endothelial intrinsic NF-κB signaling in the atherogenic response to CIH. METHODS: We created ApoE-ECI-κBmt mice that are deficient in the apolipoprotein E gene (ApoE-/-) and overexpress an I-κBα mutant (I-κBmt) selectively in endothelial cells. ApoE-/- and ApoE-ECI-κBmt mice were fed a normal chow diet (NCD) or high cholesterol diet (HCD) and exposed to sham or CIH, and atherosclerotic lesions were quantified. RESULTS: CIH exposure activated NF-κB in aortas, and induced the expression of endothelial-specific and NF-κB-dependent genes, E-selectin and vascular cell adhesion molecule (VCAM)-1, in the aortas and hearts. Endothelial I-κBmt overexpression in ApoE-ECI-κBmt mice significantly inhibited CIH-induced NF-κB activity, and suppressed E-selectin and VCAM-1 expressions, confirming endothelial NF-κB inhibition in ApoE-ECI-κBmt mice. ApoE-/- mice, on NCD, developed mild atherosclerotic lesions spontaneously, and developed advanced and larger areas of atherosclerotic plaques when exposed to CIH. ApoE-/- mice also developed advanced atherosclerotic lesions when fed an HCD alone. The HCD-induced atherosclerotic plaques became more advanced, and plaque area was doubled in mice exposed to HCD + CIH. Endothelial I-κBmt overexpression in ApoE-ECI-κBmt mice attenuated spontaneously developed atherosclerotic lesions, abrogated CIH-induced atherosclerosis and mitigated CIH-mediated facilitation of HCD-induced atherosclerosis. CONCLUSIONS: These results suggest that endothelial intrinsic NF-kB signaling may play a pivotal role in CIH-induced atherosclerosis.

Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.

Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.

The function of hematopoietic stem cells is altered by both genetic and inflammatory factors in lupus mice.

Hematopoietic stem cells (HSCs) are protected in a metabolically dormant state within the bone marrow stem cell niche. Inflammation has been shown to disrupt HSC dormancy and cause multiple functional changes. Here, we investigated whether HSC functions were altered in systemic lupus erythematosus (SLE)-prone mice and whether this contributed to clinical manifestations of SLE. We found that HSCs were significantly expanded in lupus mice. The increase in HSC cellularity was caused by both genetic lupus risk factors and inflammatory cytokines in lupus mice. In addition, the inflammatory conditions of lupus led to HSC mobilization and lineage-biased hematopoiesis. Strikingly, these functionally altered HSCs possessed robust self-renewal capacity and exhibited repopulating advantages over wild-type HSCs. A single-nucleotide polymorphism in the cdkn2c gene encoding p18(INK4c) within a SLE susceptibility locus was found to account for reduced p18(INK4c) expression and the increase in HSC self-renewal capacity in lupus mice. Lupus HSCs with enhanced self-renewal capacity and resistance to stress may compete out transplanted healthy HSCs, thereby leading to relapses after HSC transplantation.

Chronic intermittent hypoxia exposure induces atherosclerosis in ApoE knockout mice: role of NF-κB p50.

Current animal models of chronic intermittent hypoxia (CIH)-induced atherosclerosis have limitations. Mechanisms of CIH-induced atherosclerosis are poorly understood. This study tested new mouse models of CIH-induced atherosclerosis and defined the role of NF-κB p50 in CIH-induced atherosclerosis. Mice deficient in apolipoprotein E (ApoE-KO) or in both ApoE and p50 genes (ApoE-p50-DKO) were exposed to sham or CIH. Atherosclerotic lesions on aortic preparations were analyzed. CIH exposure caused atherosclerosis in ApoE-KO mice fed a normal chow diet and with no preexisting atherosclerotic condition in an exposure time-dependent manner. CIH caused more pronounced atherosclerotic lesions in ApoE-p50-DKO mice on a normal chow diet without preexisting atherosclerosis. ApoE-KO and ApoE-p50-DKO mice exposed to CIH for 30 and 9 weeks, respectively, displayed similar areas of atherosclerotic lesions on cross sections of aortic root. P50 gene deletion in ApoE-p50-DKO mice significantly augmented CIH-induced serum levels of tumor necrosis factor-α and IL-6, aortic tumor necrosis factor-α, and inducible nitric oxide synthase expression and aortic infiltration of Mac3-positive macrophages. CIH caused a greater elevation in serum cholesterol level in ApoE-p50-DKO than in ApoE-KO mice. CIH down-regulated hepatic low-density lipoprotein receptor and HMG-CoA reductase expression in ApoE-p50-DKO but not in ApoE-KO mice. We found two new mouse models that are useful for studying mechanisms and pathways of CIH-induced atherosclerosis. We showed that NF-κB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia.

Growth-factor receptor-bound protein-2 (Grb2) signaling in B cells controls lymphoid follicle organization and germinal center reaction.

Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form germinal centers in the spleen after antigen stimulation. Furthermore, mutant mice exhibit defects in splenic architecture resembling that observed in B-cell-specific lymphotoxin-ß-deficient mice, including disruption of marginal zone and follicular dendritic cell networks. We find that grb2(-/-) B cells are defective in lymphotoxin-ß expression. Although lymphotoxin can be up-regulated by chemokine CXCL13 and CD40 ligand stimulation in wild-type B cells, elevation of lymphotoxin expression in grb2(-/-) B cells is only induced by anti-CD40 but not by CXCL13. Our results thus define Grb2 as a nonredundant regulator that controls lymphoid follicle organization and germinal center reaction. Loss of Grb2 has no effect on B-cell chemotaxis to CXCL13, indicating that Grb2 executes this function by connecting the CXCR5 signaling pathway to lymphotoxin expression but not to chemotaxis.

Kelch repeat proteins control yeast PKA activity in response to nutrient availability.

Regulation of protein kinase A (PKA) by binding of cAMP to the regulatory subunit and the resulting release of the active catalytic subunit is a very well established mechanism of kinase activation. We have shown recently that PKA in budding yeast is also subject to an additional level of regulation that that modulates its activity in response to nutrient availability. Nutrient regulation of PKA activity requires a pair of proteins, Gpb1 and Gpb2, that contain several kelch repeats, a sequence motif that predicts that they fold into a ß-propeller structure. The regulatory process mediated by Gpb1 and Gpb2 causes an increase in the stability and phosphorylation of the PKA regulatory subunit Bcy1 in response to low extracellular glucose concentrations. Phosphorylation of serine-145 of Bcy1 controls its stability, and other phosphorylation events at the cluster of serines at positions 74-84 correlate with changes in nutrient availability. Here we present data consistent with a model in which the effects of Gpb1 and Gpb2 on Bcy1 are an indirect consequence of their primary effects on the PKA catalytic subunits.

MiRNA profile in esophageal squamous cell carcinoma: downregulation of miR-143 and miR-145.

AIM: To investigate the expression profile of miRNA in esophageal squamous cell carcinoma (ESCC). METHODS: The expression profile of miRNA in ESCC tissues was analyzed by miRNA microarray. The expression levels of miR-143 and miR-145 in 86 ESCC patients were determined by real-time polymerase chain reaction (PCR) using TaqMan assay. The mobility effect was estimated by wound-healing using esophageal carcinoma cells transfected with miRNA expression plasmids. RESULTS: A set of miRNAs was found to be deregulated in the ESCC tissues, and the expression levels of miR-143 and -145 were significantly decreased in most of the ESCC tissues examined. Both miR-143 and miR-145 expression correlated with tumor invasion depth. The transfection of human esophageal carcinoma cells with miR-143 and miR-145 expression plasmids resulted in a greater inhibition of cell mobility, however, the protein level of the previously reported target of miR-145, FSCN1, did not show any significant downregulation. CONCLUSION: These findings suggest that the deregulation of miRNAs plays an important role in the progression of ESCC. Both miR-143 and miR-145 might act as anti-oncomirs common to ESCC.