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Background: Pre-hospital delay was a critical factor affecting stroke patients receiving intravenous thrombolytic therapy. The aim of this study was to explore the factors associated with pre-hospital delay and thrombolysis in China.Methods: Patient data were obtained from emergency department (ED), and the factors of patient pre-hospital delay were recorded through a well-designed form.Results: A total of 630 patients were eventually included in the study. 317 patients were admitted to the ED during the thrombolysis time window, and only 105 patients received intravenous thrombolytic therapy. In the univariate analysis, transportation (OR: 0.15; 95% CI: 0.44 - 0.518; p = 0.001), atrial fibrillation (OR: 0.555; 95% CI: 0.372-0.828; p = 0.004) and response of symptoms (OR: 0.002; 95% CI: 0.000-0.013; p = 0.000) were associated with early arrival. Speech disturbances (OR: 2.095; 95% CI: 1.294-3.391; p = 0.002), smoking (OR: 2.563; 95% CI: 1.527-4.304; p = 0.000), alcohol consumption (OR: 2.155; 95% CI: 1.159-4.005; p = 0.014) and referral presentation (OR: 2.837; 95% CI: 1.584-5.082; p = 0.000) were associated with thrombolysis. In the logistic regression analysis, direct visiting to the hospital after onset and rushing to emergency after onset were independent predictor of early arrival of AIS and intravenous thrombolytic.Conclusions: The pre-hospital delay of acute ischemic stroke in China was still serious. Strengthening the ability to identify stroke-related symptoms and establishing a mutual referral medical support service model between lower and upper hospitals may effectively shorten the pre-hospital delay of stroke patients. [ABSTRACT FROM AUTHOR]

Cao, X.; Li, X.; Yue, F., and Sun, H., 2020. Research and application of vibration measurement while drilling in the undersea coal mine. In: Yang, Y.; Mi, C.; Zhao, L., and Lam, S. (eds.), Global Topics and New Trends in Coastal Research: Port, Coastal and Ocean Engineering. Journal of Coastal Research, Special Issue No. 103, pp. 323–327. Coconut Creek (Florida), ISSN 0749-0208. In order to solve the problem of fine detection of complex geological structure in the mining process of undersea coal mine, the method of vibration measurement while drilling is put forward to realize the automatic and effective identification of lithology. In order to determine the feasibility of the method of vibration measurement while drilling on different engineering conditions, the time domain and frequency domain signals under different drilling conditions were analyzed. The various working conditions, such as static drill pipe, artificial drill pipe, rotated unbroken rock and rotated broken rock, were determined by the time domain signals collected from undersea coal mine. Combined with variance analysis, time-consuming analysis and high frequency signal in frequency domain in rock breaking time, the changes in frequency domain signals of different lithology during drilling and rock breaking are determined, thus determining the position of lithological changes during the drilling process. The method of vibration measurement while drilling provides technical guarantee for fine geological detection. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a novel pathogen in 2019. The virus is responsible for a severe acute respiratory syndrome outbreak, affecting the respiratory system of infected individuals. COVID-19 is a super amplifier of basic diseases, and the disease with basic diseases is often more serious. Controlling the spread of the COVID-19 pandemic relies heavily on the timely and accurate detection of the virus. To resolve the problem, a polyaniline functionalized NiFeP nanosheet array-based electrochemical immunosensor using Au/Cu2O nanocubes as a signal amplifier is fabricated for the detection of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP). Polyaniline (PANI) functionalized NiFeP nanosheet arrays are synthesized as an ideal sensing platform for the first time. PANI is coated on the surface of NiFeP by electropolymerization to enhance biocompatibility, beneficial for the efficient loading of the capture antibody (Ab1). Significantly, Au/Cu2O nanocubes possess excellent peroxidase-like activity and exhibit outstanding catalytic activity for the reduction of H2O2. Therefore, Au/Cu2O nanocubes combine with a labeled antibody (Ab2) through the Au–N bond to form labeled probes, which can effectively amplify current signals. Under optimal conditions, the immunosensor for the detection of SARS-CoV-2 NP shows a wide linear range of 10 fg mL−1–20 ng mL−1 and a low detection limit of 1.12 fg mL−1 (S/N = 3). It also exhibits desirable selectivity, repeatability, and stability. Meanwhile, the excellent analytical performance in human serum samples confirms the practicality of the PANI functionalized NiFeP nanosheet array-based immunosensor. The electrochemical immunosensor based on the Au/Cu2O nanocubes as a signal amplifier demonstrates great potential for application in the personalized point-of-care (POC) clinical diagnosis. [ABSTRACT FROM AUTHOR]

Detection of tumor biomarkers is of great significance for early diagnosis of cancer. Herein, we fabricated a novel lab-on-a chip surface-enhanced Raman scattering (SERS) (LoC-SERS) biosensing platform for highly sensitive and specific detection of thrombin and platelet-derived growth factor-B (PDGF-B) using aptamer recognition technology. This strategy relies on the specific aptamer recognition between SERS probes (Ag–Au core–shell nanorods (Ag–AuNRs) modified with Raman reporter molecules and detection aptamer) and SERS capture substrate (Au nanoflower (AuNF) substrates modified with capture aptamer), which significantly amplify the plasmonic coupling effect that allows the ultrasensitive and high specificity SERS detection. The limits of detection (LODs) are as low as 3.62 fM for thrombin and 2.86 fM for PDGF-B. Such LoC-SERS platform is further employed to simultaneously detect two types of gastric carcinoma-related with high sensitivity and specificity, which meanwhile exhibit robust capacity of resisting disturbance in practical samples. The results revealed that the present LoC-SERS platform displayed excellent analytical performance, including superior reproducibility, specificity, and sensitivity. Satisfactory results were obtained in real sample analysis with the LoC-SERS platform. [ABSTRACT FROM AUTHOR]

At the end of 2019, the novel coronavirus disease 2019 (COVID-19), a cluster of atypical pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been known as a highly contagious disease. Herein, we report the MXene/P–BiOCl/Ru(bpy) 3 2+ heterojunction composite to construct an electrochemiluminescence (ECL) immunosensor for SARS-CoV-2 nucleocapsid protein (CoVNP) determination. Two-dimensional (2D) material ultrathin phosphorus-doped bismuth oxychloride (P–BiOCl) is exploited and first applied in ECL. 2D architectures MXene not only act as "soft substrate" to improve the properties of P–BiOCl, but also synergistically work with P–BiOCl. Owing to the inimitable set of bulk and interfacial properties, intrinsic high electrochemical conductivity, hydrophilicity and good biocompatible of 2D/2D MXene/P–BiOCl/Ru(bpy) 3 2+, this as-exploited heterojunction composite is an efficient signal amplifier and co-reaction accelerator in the presence of tri-n-propylamine (TPA) as a coreactant. The proposed MXene/P–BiOCl/Ru(bpy) 3 2+-TPA system exhibits a high and stable ECL signal and achieves ECL emission quenching for "signal on-off" recognition of CoVNP. Fascinatingly, the constructed ECL biosensor towards CoVNP allows a wide linear concentration range from 1 fg/mL to 10 ng/mL and a low limit of detection (LOD) of 0.49 fg/mL (S /N = 3). Furthermore, this presented strategy sheds light on designing a highly efficient ECL nanostructure through the combination of 2D MXene architectures with 2D semiconductor materials in the field of nanomedicine. This ECL biosensor can successfully detect CoVNP in human serum, which can promote the prosperity and development of diagnostic methods of SARS-CoV-2. [Display omitted] • Two-dimensional (2D) material ultrathin P–BiOCl is exploited and first applied in ECL. • 2D architectures MXene act as "soft substrate" to improve the properties of P–BiOCl and synergistically work with P–BiOCl. • MXene/P–BiOCl/ Ru(bpy) 3 2+ is an efficient signal amplifier and co-reaction accelerator in the presence of TPA as a coreactant. • A "signal on-off" ECL biosensor MXene/P–BiOCl/ Ru(bpy) 3 2+/GCE can specifically recognize SARS-CoV-2 nucleocapsid protein. [ABSTRACT FROM AUTHOR]

A novel surface-enhanced Raman scattering and lateral flow assay (SERS–LFA) biosensor with multiple channels based on an aptamer has been proposed in this work. The developed biosensor was designed for the rapid, convenient, sensitive and specific detection of vascular endothelial growth factor (VEGF) and osteopontin (OPN) in several samples simultaneously. During the assay, VEGF and OPN were recognized by detection aptamers immobilized on cuprous oxide nanocubes (Cu2O NCs) and captured by capture aptamers to form a sandwich structure on the test lines. In this way, generous numbers of "hot spots" formed by the aggregation of Cu2O NCs remarkably enhanced the SERS signals of Raman reporters (NBA and 4-ATP). The detection limits were as low as 0.78 pg mL−1 for the VEGF and 0.86 pg mL−1 for OPN in the human serum within 15 min, respectively. Additionally, the biosensor possesses favorable specificity, reproducibility, uniformity and stability. In the clinical analysis of serum specimens, patients with cervical cancer can be differentiated from healthy volunteers. Consequently, the presented aptamer-based SERS–LFA biosensor with multiple channels provides a powerful tool for the early diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

In this work, a microfluidic chip using Au@SiO2 array–based highly active SERS substrates was developed for quantitative detection of squamous cell carcinoma antigen (SCCA) and carcinoembryonic antigen (CEA) associated with cervical cancer. The chip consisted of six functional units with pump-free design, enabling parallel detection of multiple samples in an automatic manner without external pumps and improving the portability. Ag nanocubes (AgNCs) were labeled with Raman reporters and coupled with antibodies (labeling) to prepare SERS tags, while the Au nanoparticle–modified SiO2 microsphere (Au@SiO2) array was conjugated with antibodies (coating) to generate the highly SERS-active capturing substrate. In the presence of target biomarkers, they were captured by SERS tags and capturing substrate, resulting in the formation of "sandwich" structures which were trapped in the detection chamber. As the immune reaction proceeded, a large number of "hot spots" were generated by the proximity of the Au@SiO2 array substrate and AgNCs, greatly amplifying SERS signals. With this chip, the limits of detection of the SCCA and CEA levels in human serum were estimated to be as low as 0.45 pg mL−1 and 0.36 pg mL−1, respectively. Furthermore, the good selectivity and reproducibility of this chip were confirmed. Finally, clinical serum samples were analyzed by this chip, and the outcomes were consistent with those of enzyme-linked immunosorbent assay (ELISA). Thus, the proposed microfluidic chip can be potentially applied for the clinical diagnosis of cervical cancer. [ABSTRACT FROM AUTHOR]

With the increasing influence of electromagnetic radiation on precision instruments and organisms, there is an urgent need for research on lightweight and high-strength electromagnetic wave absorbing materials. This study has probed into a new composite absorbing material based on reduced graphene oxide (rGO)-NiMnO3, where the like-core-shell NiMnO3 is anchored on the rGO nanosheets to significantly improve the electromagnetic wave dissipation ability of the composite material using the inter-component dipole polarization and interface polarization. At the same time, NiMnO3 can effectively adjust the impedance matching ratio of rGO so that electromagnetic waves can effectively enter the absorbing material. At a thickness of 3.73 mm, the maximum absorption strength of rGO-NiMnO3 reaches −61.4 dB at 6.6 GHz; at a thickness of 2.5 mm, the adequate absorption bandwidth is 10.04–18.00 GHz, achieving a full coverage for the Ku band. As a new option for preparing lightweight and broadband electromagnetic wave absorbing materials, rGO-NiMnO3 is an ideal material for electromagnetic wave protection. [ABSTRACT FROM AUTHOR]

Small G protein Ras induces the activation of apoptosis-related molecule mammalian Ste20-like kinase1 (MST1)/JNK signal pathway, which is involved in the regulation of tissue damage under pathological conditions such as ischemic stroke. Our previous study indicated that GTPase-activating protein for Ras (SynGAP), a negative regulator of Ras, could bind with postsynaptic density protein-93 (PSD-93) and Tat-SynGAP (670–685aa) small peptide to exhibit neuroprotective role. Here, we report that Tat-SynGAP (670–685aa) reduced cerebral edema at acute cerebral ischemia/reperfusion (I/R), improved integrity of blood-brain barrier, and decreased cortical and striatum neuronal injury. Mechanistically, Tat-SynGAP (670–685aa) not only inhibited the phosphorylation of MST1 and JNK and the cleavage of caspase-3, but also facilitated the expression of angiogenesis related molecules VEGF and Ang-1. In conclusion, Tat-SynGAP (670–685aa) reduces neuronal apoptosis and cerebral infarction volume and maintains vascular stability and blood-brain barrier integrity by inhibiting MST1/JNK signaling pathway. • Tat-SynGAP improves stroke recovery via inhibiting binding of PSD-93 and SynGAP. • Tat-SynGAP maintains vascular stability and blood-brain barrier integrity. • Tat-SynGAP performs neuroprotective effect by disturbing MST1/JNK signal pathway. [ABSTRACT FROM AUTHOR]

Research methods for DNA detection have been widely extended since the application of nanotechnology, but it remains a challenge to detect specific DNA sequences or low abundance genes in biological samples with accuracy and sensitivity. Herein, a novel biosensor is proposed for the analysis of target DNA in maize based on a high-density "hot spot" surface-enhanced Raman scattering (SERS) substrate and hybridization chain reaction (HCR) amplification strategy. Finite-difference time-domain (FDTD) simulation confirmed that the electromagnetic field enhancement at the gaps between the adjacent Au nanoflowers (AuNFs) was much richer than that around a single AuNF, indicating that the aggregated AuNFs had a good SERS signal amplification effect. Based on the high-density "hot spots" AuNF substrate, the HCR of biotin-hairpin DNA (bio-H1 and bio-H2) could be triggered by the existence of target DNA and a long double-stranded DNA (dsDNA) could be formed rapidly. Due to the biotin and streptavidin (SA) interaction, SERS probes prepared by modifying biotin-DNA-cyanine 5 (bio-DNA-Cy5) on the surface of Ag–Au core–shell nanorods (Ag–AuNRs) could be assembled along the dsDNA, causing significant signal enhancement. The developed biosensor displayed a significant sensitivity with a broad detection range covering from 0.01 to 1 × 104 fM, and the limit of detection (LOD) was as low as 6.31 aM. Moreover, SERS was applied to detect target DNA in maize extract to verify the feasibility of the detection strategy. This strategy could not only carry out the ultrasensitive detection of target DNA but also provide an informative supplement to the SERS biosensing platform. [ABSTRACT FROM AUTHOR]

Post‐synaptic density 93 (PSD‐93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD‐93 mediates the crosstalk between neurons and microglia in the post‐synaptic dense region remain elusive. CX3 chemokine ligand 1 (CX3CL1) is a chemokine specifically expressed in neurons while its receptor CX3CR1 is highly expressed in microglia. In this study, we examined the interaction of PSD‐93 and CX3CL1 in the crosstalk between neurons and microglia in acute ischemic stroke. We utilized male C57BL/6 mice to establish the middle cerebral artery occlusion model (MCAO) and designed a fusion small peptide Tat‐CX3CL1 (357‐395aa) to inhibit PSD‐93 and CX3CL1 interaction. The combination peaks of PSD‐93 and CX3CL1 at 6 hr after I/R were observed. The binding sites were located at the 420–535 amino acid sequence of PSD‐93 and 357–395 amino acid sequence of CX3CL1. Tat‐CX3CL1 (357‐395aa) could inhibit the interaction of PSD‐93 and CX3CL1 and inhibited the pro‐inflammatory cytokine IL‐1β and TNF‐α expression and provided neuroprotection following reperfusion. Together, these data suggest that PSD‐93 binds CX3CL1 to activate microglia and initiate neuroinflammation. Specific blockade of PSD‐93‐CX3CL1 interaction reduces I/R induced neuronal cell death, and provides a new therapeutic target for ischemic stroke. [ABSTRACT FROM AUTHOR]

The detection of dopamine is essential for the treatment and diagnosis of depression and other diseases. In this work, cobalt phosphide nanowire arrays grown on titanium mesh (CoP NWAs/TM) are prepared by two steps of hydrothermal and phosphating, and firstly used for the detection of dopamine. The electrochemical behavior of the CoP NWAs/TM was evaluated by amperometry and differential pulse voltammetry. Amperometric analysis reveals admirable parameters in neutral PBS: (a) a working potential of 0.30 V; (b) a wide linear range (1 μM ~ 3 mM); (c) a high sensitivity (3366 μA·mM−1·cm−2); (d) a low detection limit (3.56 × 10–4 mM). Moreover, the interference effect of the common interfering species and the stability were investigated. Further experiments show that the sensor could be successfully used to detect dopamine in human blood serum. Highly sensitive and selective dopamine sensor uses three-dimensional cobalt phosphide nanowire array, which is the first experiment to apply Co-based transition metal phosphides for dopamine detection. The sensor based on cobalt phosphide nanowire array-electrode could be successfully used to detect dopamine in human blood serum. [ABSTRACT FROM AUTHOR]

There is a challenge to obtain an ultrasensitive and rapid approach to detect bacteria and identify resistance. As a powerful bioanalytical tool, surface-enhanced Raman scattering (SERS) in bacterial detection have attracted increasing attentions. Herein, we developed a SERS-active Au@Ag core-shell nanorod (Au@AgNR) tag platform for ultrasensitive bacteria detection and antibiotic-susceptibility testing (AST). The platform established that surface enhanced Raman scattered Rhodamine 6G (R6G) absorption at 1517 cm−1 had a good linearity (RI = 3865 + 193logC; R2 = 0.97) with logarithm of E. coli concentration over a range of 107–102 CFU (colony forming unit)/mL with limit of detection as low 102 CFU/mL. When E. coli was exposed to ampicillin at minimum inhibitory concentration (MIC, 4 μg/mL), Raman spectroscopy showed the obvious variation between ampicillin-susceptible E. coli (Amp−- E. coli) and the ampicillin-resistant E. coli (Amp+- E. coli). Combined with principal component analysis (PCA) statistical analysis, the Raman intensity variation mentioned above allows to obtain rapid antibiotic resistance testing (<3.5 h). In addition, E.coli spiked into blood from C57BL/6 mice can be identified clearly, indicating the potential for point-of-care diagnostics. Image 1 • Ultrasensitive and rapid approach to detect bacteria and identify resistance. • SERS nanotags can specifically anchor onto E.coli. • Raman intensity collected from the SERS nanotags bound E. coli is proportional to logarithm of E. coli concentration. • Combined with PCA, the Raman intensity statistical analysis allows to obtain rapid antibiotic resistance testing. [ABSTRACT FROM AUTHOR]

Ultrasensitive detection of specific biomarkers in clinical serum is helpful for early diagnosis of cervical cancer. In this paper, a surface-enhanced Raman scattering (SERS)-based immunoassay was developed for the simultaneous determination of squamous cell carcinoma antigen (SCCA) and osteopontin (OPN) in cervical cancer serum. Au-Ag nanoshuttles (Au-AgNSs) as SERS tags and hydrophobic filter paper-based Au nanoflowers (AuNFs) as capture substrate were constructed into a sandwich structure which served as an ultrasensitive SERS-based immunoassay platform. Finite difference time domain simulation confirmed that the electromagnetic field coupled between the AuNFs had a prominent SERS signal enhancement effect, which improved the detection sensitivity. SERS mapping showed that hexadecenyl succinic anhydride hydrophobic treatment could prevent the analyte from being quickly absorbed by the filter paper and increase the retention time to be more evenly distributed on the filter paper substrate. The immunoassay platform was verified to have good selectivity and reproducibility. With this method, the detection limits of SCCA and OPN in human serum were as low as 8.628 pg/mL and 4.388 pg/mL, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects; cervical intraepithelial neoplasia I (CINI), CINII, and CINIII; and cervical cancer patients were analyzed, and the reliability of the results was confirmed by enzyme-linked immunosorbent assay experiments. The constructed SERS-based immunoassay platform could be used as a clinical tool for early screening of cancers in the future. [ABSTRACT FROM AUTHOR]

Nanowires of copper(II)-based metal-organic frameworks (Cu-MOFs) of type Cu(II)(1,4-naphthalenedicarboxylic acid) (1,4-NDC) were deposited on the surface of a copper foam by immersion of Cu(OH)2 nanowires in a solution of 1,4-NDC. An electrochemical immunosensor for the prostate specific antigen (PSA) is obtained by using the nanowire arrays as a redox signal probe. The signal is generated by the conversion of Cu(I) and Cu(II) of Cu-MOFs nanowires. Cu(1,4-NDC) nanowires contain many uncoordinated carboxyl groups which can bind to the amino groups of the PSA antibody. When PSA antibody binds to PSA antigen during an immune response, the current signal will decrease due to the electrical insulation of PSA antigen. The decrease of current is directly proportional to the increase of PSA concentration. The immunosensor, best operated at a voltage of typically −0.08 V (vs. Ag/AgCl), has a low limit of detection (4.4 fg·mL−1) and a wide linear range (0.1 pg·mL−1 to 20 ng·mL−1). This meets the demands of clinical diagnosis (with values <4 ng·mL−1) in serum. The method was applied to the determination of PSA in spiked serum. [ABSTRACT FROM AUTHOR]

Enterocytozoon hepatopenaei (EHP) is a prevalent microsporidian pathogen responsible for hepatopancreatic microsporidiosis (HPM) in Litopenaeus vannamei. This infection not only leads to slowed growth in shrimp abut aslo inflicts substantial economic losses in the global aquaculture industry. However, the molecular mechanisms by which EHP influences the host during various infection stages remain unclear. This study employed comparative transcriptomics to examine the effects of EHP infection on Litopenaeus vannamei between early and late stage of infection groups. Utilizing transcriptomic approaches, we identified differentially expressed genes (DEGs) with notable biological significance through the COG, GO, KEGG, GSEA, and Mufzz time-series methodologies. The results reveal that EHP infection considerably influences host gene expression, with marked differences between early and late infection across distinct timeframes. Key processes such as detoxification, cell apoptosis, and lipid metabolism are pivotal during host-parasite interactions. Hexokinase and phosphatidic acid phosphatase emerge as key factors enabling invasion and sustained effects. Cytochrome P450 and glucose-6-phosphate dehydrogenase could facilitate infection progression. EHP significantly impacts growth, especially through ecdysteroids and 17β-estradiol dehydrogenase. By delineating stage-specific effects, we gain insights into interaction between EHP and Litopenaeus vannamei, showing how intracellular pathogens reprogram host defenses into mechanisms enabling long-term persistence. This study provides a deeper understanding of host-pathogen dynamics, emphasizing the interplay between detoxification, metabolism, immunity, apoptosis and growth regulation over the course of long-term symbiosis. As the duration of EHP infection increased, shrimp were subjected to changes in each of the main effects. PCA analysis was used to assess inter-sample group variability versus intra-sample group reproducibility. Venn diagrams of DEGs in Asn vs Asp, Jsn vs Jsp, Asn vs Jsn, and Asp vs Jsp. Distribution of KEGG pathway enrichment. The results of GSEA analysis for Asn vs Asp, Jsn vs Jsp groups. [Display omitted] • EHP infection influences host gene expression between early and late infection stages. • Detoxification, cell apoptosis and lipid metabolism are pivotal in host-parasite interactions. • Hexokinase and phosphatase enable invasion and prolonged effects through key roles. • Cytochrome P450 and G6PD facilitate infection progression. • EHP affects growth, particularly through ecdysteroids and 17β-HSD. [ABSTRACT FROM AUTHOR]

[Display omitted] • A competitive recognition binding strategy regarding the aptamer was designed. • An integrated SERS-enabled LoC system was fabricated for gastric cancer detection. • VEGF and PDGF-B in human serum was directedly quantified with an ultralow LOD. Multiplex detection of biomarkers is nontrivial for gastric cancer diagnosis. Herein, we presented a lab-on-a-chip surface-enhanced Raman scattering (LoC-SERS) sensing system for the detection of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-B (PDGF-B). The sensing system includes three parallel channels, each channel consists of two detection chambers, enabling the simultaneous analysis of multiple samples. The capillary structure provides self-driving power without the need of external pumps. The ordered gold nano-bipyramids (GNBPs) array in the detection chamber can form uniform and dense "hot spots", due to the homogeneous double-tip structure and narrow gaps, resulting in better SERS performance. During the analysis process, VEGF and PDGF-B in the serum can lead to the change of aptamer conformation. Raman reporter-labeled complementary DNA is shed from the aptamer due to competition of the target. The entire process only requires 20 min, which is rapid. By monitoring the changes in Raman intensity and fitting it with the logarithm of concentration, the correlation between the intensity and concentration can be clearly reflected as a mathematical relationship. The LoC-SERS sensing system has been verified to have excellent selectivity and reproducibility. Via the sensing system, the limits of detection (LOD) of VEGF and PDGF-B are as low as 0.342 pg/mL and 0.265 pg/mL in serum, respectively. In addition, the accuracy was verified through enzyme-linked immunosorbent assay (ELISA). Therefore, the proposed LoC-SERS sensing system has great potential for clinical detection of gastric cancer. [ABSTRACT FROM AUTHOR]

A semi-solid state electrochromic device with deep eutectic solvent gel as the electrolyte, Ethyl-viologen as the electrochromic compound, and K 4 Fe(CN) 6 as the electron donor was reported. Four kinds of silica were simply mixed with ethaline for preparing the gel electrolyte, and the hydrophilic ones were found to be capable of being used as the gelling agent. To enhance the electron transfer at the electrode/gel interface and keep the transparency of the electrode, tiny amount of Au was electrochemically deposited on the FTO electrode. The as-prepared electrochromic device shows a coloration time of ca. 60 s at −0.7 V with the coloration efficiency of 91 cm 2 /C, and a bleaching time of ca. 150 s at 0 V with the efficiency of 194 cm 2 /C. The reversible response of the electrochromic device up to 820 cycles with Δ T max > 60% was also demonstrated. [ABSTRACT FROM AUTHOR]

Serum analysis is crucial for favourable prognosis of gastric cancer (GC) and for improving patient survival rates. However, it remains a challenge to develop an effective strategy to accurately identify differences in gastric cancer before and after treatment to guide efficacy evaluation. In this study, we combined surface-enhanced Raman scattering (SERS) with principal component analysis (PCA)-two-layer nearest neighbour (TLNN) to propose a promising serum analytical platform for label-free detection of cisplatin-treated GC mice. A microarray chip fabricated from Au nano-hexagon (AuNH) substrates was employed to measure the SERS spectra of the serum of GC mice at different treatment stages, and then a model for recognition of SERS spectra was constructed using a PCA-TLNN algorithm. The results revealed that the microarray chip exhibited superior portability, SERS activity, stability, and uniformity. Through PCA-TLNN, the GC mice at different treatment stages were successfully segregated, and several key spectral features for distinguishing different treatment stages were captured. The established PCA-TLNN model achieved satisfactory results, with an accuracy of over 97.5%, a sensitivity of over 90%, and a specificity of over 96.7%. Label-free serum SERS in combination with multivariate analysis could serve as a potential technique for the clinical diagnosis and staging of treatments. [Display omitted] • The novel microarray chip can realize rapid, sensitive, label-free and high-throughput detection of SERS spectra of serum. • PCA-TLNN successfully differentiated the SERS spectra of serum from cisplatin-treated GC mice at different stages. • The most prominent spectral features for distinguishing different treatment stages. • were captured in PCs loading plots. • PCA-TLNN was superior to traditional multivariate algorithm in accuracy, sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Early and precise diagnosis of lung cancer is critical for a better prognosis. However, it is still a challenge to develop an effective strategy for early precisely diagnose and effective treatments. Here, we designed a label-free and highly accurate classification serum analytical platform for identifying mice with lung cancer. Specifically, the microarray chip integrated with Au nanostars (AuNSs) array was employed to measure the surface-enhanced Raman scattering (SERS) spectra of serum of tumor-bearing mice at different stages, and then a recognition model of SERS spectra was constructed using the principal component analysis (PCA)-representation coefficient-based k-nearest centroid neighbor (RCKNCN) algorithm. The microarray chip can realize rapid, sensitive, and high-throughput detection of SERS spectra of serum. RCKNCN based on the PCA-generated features successfully differentiated the SERS spectra of serum of tumor-bearing mice at different stages with a classification accuracy of 100%. The most prominent spectral features for distinguishing different stages were captured in PCs loading plots. This work not only provides a practical SERS chip for the application of SERS technology in cancer screening, but also provides a new idea for analyzing the feature of serum at the spectral level. [Display omitted] • A rapid, sensitive, label-free, high-throughput SERS microarray chip was developed. • Combining SERS with PCA-RCKNCN successfully differentiated the SERS spectra. • The most prominent spectral features of SERS spectra in PCs loading were captured. • PCA-RCKNCN was superior to traditional multivariate algorithm in accuracy. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is a major histologic category of lung cancer. In this paper, a new type of surface-enhanced Raman scattering (SERS) microfluidic chip proposed for the simultaneous and efficient detection of miR-92a and miR-339-3p, two microRNAs (miRNAs) related to NSCLC. In addition, the method was used to detect miR-92a and miR-339-3p in the serum of NSCLC clinical samples, and the results were consistent with the quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, this new SERS microfluidic chip is a very promising tool for detecting miRNA expression levels, which can help in the early diagnosis and prognosis of NSCLC. [Display omitted] • SERS effect of the Au-AgNBs array is excellent, which improves the sensitivity of SERS analysis. • The hydrophilic-treated SERS microfluidic chip combined with the hpDNA- functioned Au-AgNBs array eliminates the need for an external driver while improving detection efficiency. • The LOD of the SERS microfluidic chip reaches aM level, and the detection and analysis time is as low as 8 min. • The device can be used for the early diagnosis of non-small cell lung cancer to improve cancer survival rates. In this paper, a novel surface-enhanced Raman scattering (SERS) microfluidic chip is proposed for the simultaneous and efficient detection of miR-92a and miR-339-3p, two microRNAs (miRNAs) related to non-small cell lung cancer (NSCLC). The sample solution can flow along the microchannel into the reaction zone during the assay, driven by the capillary force generated by the comb-like structured channel. A one-step paired hybridization reaction with the corresponding hairpin DNA (hpDNA) on the hpDNA-functioned Au-Ag nanobowl (Au-AgNBs) array takes place when the target strand is present in the sample solution, amplifying the SERS signal. The detection limits of miR-92a and miR-339-3p in serum were 44.36 aM and 63.58 aM, respectively, using this method, with a detection and analysis time of only 8 min. The microfluidic chip showed good specificity, reproducibility, and stability. Finally, the method was used to detect miR-92a and miR-339-3p in the serum of NSCLC clinical samples, and the results were consistent with the quantitative real-time polymerase chain reaction (qRT-PCR). In conclusion, this new SERS microfluidic chip is a very promising tool for detecting miRNA expression levels, which can help in the early diagnosis and prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA), as one of the ideal target biomarker analytes, plays an essential role in biological processes; thus, the development of rapidly sensitive detection methods is imperative. Herein, we proposed a pump-free surface-enhanced Raman scatting (SERS) microfluidic chip for the rapid and ultrasensitive detection of miR-106b and miR-196b, laryngeal squamous cell carcinoma (LSCC)-related miRNAs. Ag–Au core-shell nanorods (Ag-AuNRs) were applied to prepare SERS tags by modifying Raman reporters and hairpin DNAs. The capture probes were synthesized by labeling hairpin DNAs onto the magnetic beads (MBs) surface. In the presence of targets, the catalytic hairpin assembly (CHA) reactions between SERS tags and capture probes could be triggered, causing the aggregation of Ag-AuNRs. The tiny magnets installed under the rectangular chamber could magnetically gather the CHA products, leading to the further aggregation of Ag-AuNRs. Thus, this strategy could achieve the double aggregation of Ag-AuNRs, resulting in the significant amplification of the SERS signal. The proposed strategy achieved simultaneous and sensitive detection of miR-106b and miR-196b, with limits of detection low to aM level. The whole detection process could be completed within 5 min. Moreover, this microfluidic chip exhibited excellent reproducibility, stability, and specificity. The high accuracy of this SERS microfluidic chip was proved by practical analysis in LSCC patients' serum. The results demonstrated that SERS could be a promising alternative clinical diagnosis tool and exhibited potential application for the dynamic monitoring of cancer staging. A pump-free SERS microfluidic chip coupling with CHA amplification is fabricated for the ultrasensitive and simultaneous detection of miR-106b and miR-196b. [Display omitted] • To our knowledge, this is the first report demonstrating pump-free SERS microfluidic chip coupling with catalytic hairpin assembly (CHA) reaction for detection of miR-106b and miR-196b simultaneously. • Dual signal amplification composed of CHA-induced powerful cycle amplification and the aggregation effect caused by MBs enables the ultrasensitive detection of miRNA, with the LODs low to aM level. • The entire detection process could be finished less than 5 min. • Excellent uniformity, stability, specificity and reproducibility of this pump-free SERS microfluidic chip are demonstrated. [ABSTRACT FROM AUTHOR]

Hydroquinone (HQ) and catechol (CC) are important chemical raw materials in the modern industry, unfortunately, which are also high toxic phenolic pollutants. So how to achieve highly sensitive and selective determination HQ and CC is the challenge we face. In the present work, we report a facile strategy to obtain nitrogen and phosphorous co-doped glucose-derived carbon coated CoP nanowires (G-CoP/N,P–C NWs), in which nitrilotriacetic acid (NTA) was as the chelating reagent, glucose was as carbon source, and the precursors were subsequently experienced carbonization and phosphorization process. G-CoP/N,P–C NWs can shorten the distance of the electron transport and expand the reaction area, showing the intriguing electronic conductivity and electrocatalytic abilities. An electrochemical phenolic sensor based on G-CoP/N,P–C NWs is fabricated. The as-prepared sensor showcases the good sensing performance for HQ and CC with comparative linearity ranges of 0.8–900 μM (HQ) and 0.6–800 μM (CC), low limits of detections (LODs) of 0.18 μM (S/N = 3) and 0.12 μM (S/N = 3) for HQ and CC, respectively. Notably, it also displays excellent practical application for the recognition of HQ and CC in the rain water, the tap water, the domestic wastewater and the lake water, which may be a promising candidate in environmental water monitoring and drinking water safety. [Display omitted] • The 2D nitrogen and phosphorous co-doped glucose-derived carbon coated CoP nanowires were synthesized and applied. • A sensitive sensor for hydroquinone (HQ) and catechol (CC) detection was exploited, using 2D G-CoP/N,P–C NWs for the first time. • The sensor exhibits lower LODs of 0.18 μM and 0.12 μM for HQ and CC, respectively. • The sensor shows excellent practical application for the recognition of HQ and CC in several actual samples. [ABSTRACT FROM AUTHOR]

Sialon–ZrN powders were synthesized from low-grade bauxite using a zirconite additive by carbothermal reduction nitridation (CRN). The as-synthesized Sialon–ZrN powders were subsequently used as SiC-based free-fired refractories. Their phase compositions and microstructures of the powders were determined using X-ray diffraction and scanning electron microscopy. The physical properties and blast furnace (BF) slag resistance of the SiC–Sialon–ZrN free-fired refractories were also studied. The results show that the low-grade bauxite and zirconite powders were transformed to β-Sialon and ZrN by the CRN process at 1600°C. The phenolic resin provided a strongly bonded interface between the Sialon–ZrN matrix and SiC particles and thus enhanced their combined strength after drying at 150°C. The strength increased as the temperature was elevated from 1000°C to 1500°C. As the ZrN content increased, the slag erosion rate of the SiC–Sialon–ZrN free-fired refractories initially decreased and then increased after being heated at 1500°C. The presence of ZrO2 in the slag (oxidized from ZrN) revealed that the ZrO2 did not react with other oxides in the BF slag to form low melting point phases. This may play a crucial role in its BF slag erosion resistance. The corrosion mechanism of the BF slag towards the as-prepared SiC–Sialon–ZrN free-fired refractories was determined to be oxidation-erosion-dissolution-penetration. [ABSTRACT FROM AUTHOR]

In this article, for the first time, a novel, label-free and inherent electroactive redox biosensor based on ultrathin Au-Pt nanowire-decorated thionine/reduced graphene oxide (AuPtNWs/THI/rGO) is developed for carcinoembryonic antigen (CEA) detection. Ultrathin AuPtNWs are prepared by a one-pot synthesis method without the use of any stabilizer or template. The AuPtNWs/THI/rGO composites are obtained by the THI/rGO composites surface functionalized with -NH2 group employed as a support for loading ultrathin AuPtNWs by coordination. The AuPtNWs/THI/rGO composites not only favor the immobilization of antibody but also facilitate the electron transfer. It is found that the resultant AuPtNWs/THI/rGO composites can be designed to act as a sensitive label-free electrochemical immunosensor for CEA determination. Under the optimized conditions, the linear range of the proposed immunosensor is estimated to be from 50 fg·mL−1 to 100 ng·mL−1 (R= 0.998) and the detection limit is estimated to be 6 fg·mL−1 at a signal-to-noise ratio of 3, respectively. The prepared immunosensor for detection of CEA shows high sensitivity, reproducibility and stability. Our study demonstrates that the proposed immunosensor has also been used to determine CEA successfully in diluted blood samples. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel L-Cysteine self-assembled gold nanoparticles modified indium tin oxide electrode (ITO/Au/L-Cys) was obtained through a facile two step. • Comparing to bare Au, ITO/Au/L-Cys displays a highly sensitive and selective behavior for DA in the interference of UA. • ITO/Au/L-Cys exhibits an excellent electrocatalytic activity towards DA with the linear range of 2 μM ∼ 400 μM and a limit of detection reaches up to 0.6 μM. A novel L-Cysteine self-assembled gold nanoparticles modified indium tin oxide electrode (ITO/Au/L-Cys) was fabricated by facile steps of electro-deposition and immersion in solution. The as-prepared ITO/Au/L-Cys electrode is investigated as a potential electrochemical sensor for dopamine (DA) in the interference of Uric Acid (UA). It combines the catalytic advantages of the Au(1 1 1)-like nanoparticles array with self-assembled L-Cysteine. The biosensor displays a highly sensitive and selective behavior for DA in the present of UA. The peak currents response to DA is linear with their concentrations in the range of 2 μM ∼ 400 μM. In addition, a limit of detection reaches up to 0.6 μM (S/N = 3). Consequently, the high sensitivity, stability and excellent biocompatibility of ITO/Au/L-Cys electrode made it as a promising DA sensor. [ABSTRACT FROM AUTHOR]

• A novel bimetallic heterostructure ITO/AuNPs/PtNPs was synthesized by a facile two-step electrodeposition. • ITO/AuNPs/PtNPs exhibits an excellent activity than ITO/PtNPs for direct methanol fuel cells. • The heterostructure of ITO/AuNPs/PtNPs has synergetic effect for methanol oxidation. • ITO/AuNPs/PtNPs delivers operational durability with the jf/jb ratio of ~2.0. [Display omitted] The stability of Pt-based catalyst for methanol oxidation reaction (MOR) is the main hot topic to the commercial applications of direct methanol fuel cells (DMFCs) at present. In this article, a novel bimetallic heterostructure Pt-Au nanoparticles array catalyst on Indium Tin Oxide (ITO/AuNPs/PtNPs) for direct methanol fuel cells was synthesized through a facile two-step electrodeposition. Compared to ITO/PtNPs electrode, ITO/AuNPs/PtNPs delivers excellent activity and operational durability towards MOR. The turn over number (TON) of the as-prepared ITO/AuNPs/PtNPs is estimated as ~2.4 times higher than value of ITO/PtNPs at 0.06 V. The ability of resistance to CO poisoning for ITO/AuNPs/PtNPs is also evaluated, the I f /I b ratio of ITO/AuNPs/PtNPs and ITO/PtNPs is 2.0, 1.2, respectively. The enhanced properties of ITO/AuNPs/PtNPs for activity and durability can be ascribed to a high specific surface area, which could effectively promote the oxidation of methanol on Pt. Furthermore, Au can also greatly promote the transformation from CO-likes to CO 2 on Pt sites. The synergetic effects provide a guarantee for highly efficient methanol oxidation for ITO/AuNPs/PtNPs. [ABSTRACT FROM AUTHOR]

Accurate quantification of multiple miRNAs biomarkers in body fluid is still a challenge for early screening of cancer. Herein, by catalytic hairpin assembly as a signal amplification strategy, we designed a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) strip for ultrasensitive detection of miR-21 and miR-196a-5p in non-small cell lung cancer (NSCLC) urine on a single test (T) line. 4-mercaptobenzoic acid or 5,5′-dithiobis-2-nitrobenzoic acid as Raman molecules was labeled and two hairpin DNA sequence was modified gold nanocages (GNCs) were designed as two SERS tags. Through target miRNA-triggered catalytic hairpin assembly (CHA), the double-stranded DNAs (H1–H2 complex) formed by SERS tags and the related hairpin-structured DNA sequence 2 (H2) were immobilized on a single T line of SERS-LFA strip. This generated abundant "hot spots" because of the formation of numerous H1–H2 complex thus facilitated the SERS measurement. Through this method, two kinds of miRNAs were analyzed, resulting in limits of detection of 2.08 pM and 3.31 pM for miR-21 in PBS buffer and human urine, 1.77 pM and 2.18 pM for miR-196a-5p in PBS buffer and human urine. Significantly, the SERS-LFA strip exhibited high specificity and good repeatability toward miRNAs. The whole detection time was only 30 min, which means that the high detection efficiency of the strip. The clinical feasibility of the proposed method was also evaluated by detecting the levels of miR-21 and miR-196a-5p in urine samples from NSCLC patients and healthy subjects. The developed SERS-LFA strip has wide application prospect in biomedical research, drug development and early clinical diagnosis. A novel surface-enhanced Raman scattering-lateral flow assay strip in combination with catalytic hairpin assembly was developed for rapid, sensitive, and simultaneous detection of multiple non-small cell lung cancer-related miRNAs on a single test line. [Display omitted] • A simultaneous detection of multiple cancer biomarkers by catalytic hairpin assembly-based SERS-LFA strip on a single test line with high sensitivity and accuracy is proposed. • GNCs, as a kind of novel nanomaterial, can be prepared on a large scale and has good SERS reinforcement effect. • Catalytic hairpin assembly-based SERS-LFA strip shows favorable performance in clinical test, which can achieve the LODs as low as 3.31 pM (miR-21) and 2.18 pM (miR-196a-5p) in human urine. [ABSTRACT FROM AUTHOR]

The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear. The present investigation conducted in vitro - in vivo extrapolation to predict the potential risks. Our data indicated that miconazole potently inhibited phenytoin hydroxylation in both pooled human liver microsomes (HLMs) and recombinant cytochrome P450 2C9 (CYP2C9) with the K i values of 125 ± 7 nM and 30 ± 2 nM, respectively. Quantitative prediction of DDI risk suggests that, beside intravenous administration or swallowed tablet, combination of phenytoin and miconazole high dose oral gel or buccal tablet may also result in a clinically significant increase of phenytoin AUC (>53%) by the inhibition of miconazole against phenytoin hydroxylation, consequently a higher frequency of adverse events, while the coadministration of miconazole vaginal formulation and phenytoin will be safe. [Display omitted] • Miconazole was a potent inhibitor of phenytoin hydroxylation catalyzed by CYP2C9. • Miconazole high dose oral gel or buccal tablet may trigger off phenytoin toxicity. • Miconazole vaginal gel or low dose oral gel cannot lead to phenytoin toxicity. [ABSTRACT FROM AUTHOR]

Procalcitonion (PCT) have been proved to be disease-related markers of premature rupture of membranes (PROM) in serum of patients. Therefore, the profiling technology of rapid and sensitive is crucial for detecting the level of PCT in human serum, which is of great significance for early diagnosis and treatment of PROM. In this work, the surface-enhanced Raman scattering (SERS) detection platform combined with double antibody sandwich method was used to quantitatively detect PCT in serum of patients with PROM. A highly sensitive, uniform, and reliable SERS substrate was fabricated by assembling Ag nanowires (AgNWs) on the hydrophobic filter paper treated with alkyl ketene dimer (AKD). Then hollow Au nanocages (HAuNCs) with SERS activity were synthesized facilely. The SERS immunoassay system consists of SERS tags and capturing substrate. HAuNCs labled anti-PCT (labeling) were used as SERS tags. Filter paper modified with AgNWs and anti-PCT (coating) was used as capturing substrate. When the SERS immunoassay system were used to directly detect PCT antigen, Raman intensity at different PCT antigen concentrations (1 pg/mL-1 μg/mL) was linearly related to the logarithm of PCT antigen concentration. By establishing a calibration curve within a certain range, it can be concluded that the detection limits of PBS and human serum were as low as 2.86 pg/mL and 3.74 pg/mL respectively. Serum samples from PROM patients were detected by SERS, and the results were consistent with those of the enzyme-linked immunosorbent assay (ELISA). Furthermore, The high reproducibility and homogeneity of SERS immunoassay were confirmed. Above results demonstrated the feasibility and great potential for developing this new SERS immunosensor into a clinical tool for sensitive analysis of biomarkers in human serum. [ABSTRACT FROM AUTHOR]

Early diagnosis of drug-induced kidney injury (DIKI) is essential for clinical treatment and intervention. However, developing a reliable method to trace kidney injury origins through retrospective studies remains a challenge. In this study, we designed ordered fried-bun-shaped Au nanocone arrays (FBS NCAs) to create microarray chips as a surface-enhanced Raman scattering (SERS) analysis platform. Subsequently, the principal component analysis (PCA)-two-layer nearest neighbor (TLNN) model was constructed to identify and analyze the SERS spectra of exosomes from renal injury induced by cisplatin and gentamycin. The established PCA-TLNN model successfully differentiated the SERS spectra of exosomes from renal injury at different stages and causes, capturing the most significant spectral features for distinguishing these variations. For the SERS spectra of exosomes from renal injury at different induction times, the accuracy of PCA-TLNN reached 97.8% (cisplatin) and 93.3% (gentamicin). For the SERS spectra of exosomes from renal injury caused by different agents, the accuracy of PCA-TLNN reached 100% (7 days) and 96.7% (14 days). This study demonstrates that the combination of label-free exosome SERS and machine learning could serve as an innovative strategy for medical diagnosis and therapeutic intervention.

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this work, based on Fe 3 O 4 @AuNPs and double amplified signal Off-On strategy, a simple and sensitive SERS microfluidic chip was constructed to detect microRNA associated with non-small cell lung cancer (NSCLC). Fe 3 O 4 @AuNPs have two advantages of SERS enhanced and magnetic adsorption, the introduction of microfluidic chip can realize double amplification of SERS signal. First, the binding of complementary ssDNA and hpDNA moved the Raman signaling molecule away from Fe 3 O 4 @AuNPs, at which point the signal was turned off. Second, in the presence of the target microRNA, they were captured by complementary ssDNA and bound to them. HpDNA restored the hairpin conformation, the Raman signaling molecule moved closer to Fe 3 O 4 @AuNPs. At this time, the signal was turned on and strong Raman signal was generated. And last, through the magnetic component of SERS microfluidic chip, Fe 3 O 4 @AuNPs could be enriched to realize the secondary enhancement of SERS signal. In this way, the proposed SERS microfluidic chip can detect microRNA with high sensitivity and specificity. The corresponding detection of limit (LOD) for miR-21 versus miR-125b was 6.38 aM and 7.94 aM, respectively. This SERS microfluidic chip was promising in the field of early detection of NSCLC., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2024 Optica Publishing Group.)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged as a novel pathogen in 2019. The virus is responsible for a severe acute respiratory syndrome outbreak, affecting the respiratory system of infected individuals. COVID-19 is a super amplifier of basic diseases, and the disease with basic diseases is often more serious. Controlling the spread of the COVID-19 pandemic relies heavily on the timely and accurate detection of the virus. To resolve the problem, a polyaniline functionalized NiFeP nanosheet array-based electrochemical immunosensor using Au/Cu 2 O nanocubes as a signal amplifier is fabricated for the detection of SARS-CoV-2 nucleocapsid protein (SARS-CoV-2 NP). Polyaniline (PANI) functionalized NiFeP nanosheet arrays are synthesized as an ideal sensing platform for the first time. PANI is coated on the surface of NiFeP by electropolymerization to enhance biocompatibility, beneficial for the efficient loading of the capture antibody (Ab 1 ). Significantly, Au/Cu 2 O nanocubes possess excellent peroxidase-like activity and exhibit outstanding catalytic activity for the reduction of H 2 O 2 . Therefore, Au/Cu 2 O nanocubes combine with a labeled antibody (Ab 2 ) through the Au-N bond to form labeled probes, which can effectively amplify current signals. Under optimal conditions, the immunosensor for the detection of SARS-CoV-2 NP shows a wide linear range of 10 fg mL -1 -20 ng mL -1 and a low detection limit of 1.12 fg mL -1 (S/N = 3). It also exhibits desirable selectivity, repeatability, and stability. Meanwhile, the excellent analytical performance in human serum samples confirms the practicality of the PANI functionalized NiFeP nanosheet array-based immunosensor. The electrochemical immunosensor based on the Au/Cu 2 O nanocubes as a signal amplifier demonstrates great potential for application in the personalized point-of-care (POC) clinical diagnosis.

Purpose: Circulating tumor DNA (ctDNA) is more representative and accurate than biopsy and is also conducive to dynamic monitoring, facilitating accurate diagnosis and prognosis of glioma. Therefore, the present study aimed to establish and validate a novel amplified method for the detection of IDH1 R132H and BRAF V600E, which were associated with the genetic diagnosis of glioma., Patients and Methods: A dual-signal amplification method based on magnetic aggregation and catalytic hairpin assembly (CHA) was constructed for the simultaneous detection of ctDNAs. When target ctDNAs are present, the CHA reaction is initiated and leads to the assembly of Au-Ag nanoshuttles (Au-Ag NSs) onto magnetic beads (MBs). Further enrichment of MBs under an external magnetic field facilitated the dual-signal amplification of SERS., Results: The limit of detection (LOD) for IDH1 R132H and BRAF V600E in serum was as low as 6.01 aM and 5.48 aM. The reproducibility and selectivity of the proposed SERS analysis platform was satisfactory. Finally, the platform was applied to quantify IDH1 R132H and BRAF V600E in the serum of subcutaneous-tumor‑bearing nude mice, and the results obtained by SERS were consistent with those from quantitative real-time polymerase chain reaction (qRT-PCR)., Conclusion: The present study showed that the dual-signal amplification method is a simple and ultrasensitive strategy for gliomas-associated ctDNAs detection, which is crucial for early diagnosis and dynamic monitoring., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wang et al.)

Multiplexed detection of Parkinson's disease (PD) biomarkers is of great significance for early diagnosis and personalized treatment. In this study, we fabricated a robust surface-enhanced Raman scattering-enabled lab-on-a-chip (LoC-SERS) platform for simultaneous quantification of α-synuclein, phosphorylated tau protein 181, osteopontin, and osteocalcin. Herein, the antibody-DNA conjugate was designed to introduce the catalytic hairpin self-assembly (CHA) amplification into the protein detection. Au nano-stars (AuNSs) modified with Raman reporter molecules and hairpin-structure DNA 1 were applied as the SERS nanotags. Au-coated silicon nanocone array (Au/SiNCA) fabricated based on the maskless plasma etching-prepared high-density Si nanocone array (SiNCA) and surface ion sputtering was used as the capture substrate after the modification of hairpin-structure DNA 2. Benefitting from the antibody-DNA conjugate-induced CHA amplification, numerous AuNSs can be connected to the Au/SiNCA surface, which significantly amplify the plasmonic coupling effect for ultrasensitive SERS detection, and the limit of detection was less than the pg/mL level. The application of highly uniform Au/SiNCA and antibody-DNA conjugate endows the LoC-SERS platform excellent analytical performance, including superior reproducibility, satisfactory universality, and high sensitivity. In addition, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model was established, and satisfactory results were obtained in real sample analysis with the LoC-SERS platform, which may be enlightening for exploiting protein biomarkers in PD monitoring.

In this study, we apply catalytic hairpin assembly (CHA) as the signal amplification strategy for the quantification of carcinoembryonic antigen (CEA) and cytokeratin fragment antigen 21-1 (CYFRA21-1) with a surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) as the carrier. Herein, antibody-DNA conjugates are designed to assist the application of CHA amplification in protein detection. In the presence of protein biomarkers, antibody-DNA conjugates can specifically bind to the target proteins, forming the antigen@antibody-DNA conjugates. The terminal free part of the DNA on the conjugates can trigger the CHA events to connect SERS nanotags to capture nanoprobes. Then, micro-magnet can gather the CHA products in a rectangular chamber, resulting in the aggregation of SERS nanotags, which can ultimately generate abundant "hot spots" for SERS signal enhancement. Using this strategy, CEA and CYFRA21-1 can be successfully determined with a limit of detection (LOD) as low as pg mL -1 , much lower than recently reported methods. Meanwhile, a non-small cell lung cancer (NSCLC)-xenografted mouse model was established, and SERS was applied to analyze the expression level of CEA and CYFRA21-1 in tumorigenesis and development. The comparison between SERS results and those of the ELISA method demonstrated a high degree of consistency, suggesting that the proposed CHA-assisted LoC-SERS device has satisfying accuracy. Thus, introducing the CHA strategy via the design of antibody-DNA conjugates opens new gates to ultra-sensitive and specific SERS detection of protein biomarkers.

Circulating tumor DNA (ctDNA) is an ideal biomarker for cancer diagnosis based on liquid biopsy, so there is an urgent need for developing an efficient, rapid, and ultrasensitive detection method to meet clinical needs. In this paper, a novel surface-enhanced Raman scattering (SERS) microfluidic chip combined with a catalytic hairpin assembly (CHA) was proposed to detect two non-small cell lung cancer (NSCLC)-related ctDNA (TP53 and PIK3CA-Q546K) simultaneously. The chip consists of six channels for parallel detection. In the reaction region, the CHA reaction between HP 1 of the SERS probe and HP 2 of the capture substrate was triggered by ctDNAs to form HP 1 -HP 2 duplexes. As the reaction proceeds, more and more SERS probes are captured on the substrate. The gathered reaction products continuously form a lot of hot spots, which greatly enhance the SERS signal. This reaction was completed within 5 minutes. Through this method, the detection limits of TP53 and PIK3CA-Q546K in human serum were as low as 2.26 aM and 2.34 aM, respectively. The microfluidic chip also exhibited high specificity, reproducibility and stability. The clinical feasibility of the SERS microfluidic chip was verified by analyzing the serum samples of healthy subjects and NSCLC patients. The reliability of the experimental results was verified by the qRT-PCR test. The constructed SERS-based analytical micro-platform has great potential in dynamic monitoring of cancer staging and could be used as a clinical tool for early cancer screening.

Circulating tumour DNA (ctDNA) has emerged as an ideal biomarker for the early diagnosis and prognosis of gastric cancer (GC). In this work, a pump-free, high-throughput microfluidic chip coupled with catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) as the signal cascade amplification strategy (CHA-HCR) was developed for surface-enhanced Raman scattering (SERS) assays of PIK3CA E542K and TP53 (two GC-related ctDNAs). The chip consisted of six parallel functional units, enabling the simultaneous analysis of multiple samples. The pump-free design and hydrophilic treatment with polyethylene glycol (PEG) realized the automatic flow of reaction solutions in microchannels, eliminating the dependence on external heavy-duty pumps and significantly improving portability. In the reaction region of the chip, products generated by target-triggered CHA initiated the HCR, forming long nicked double-stranded DNA (dsDNA) on the Au nanobowl (AuNB) array surface, to which numerous SERS probes (Raman reporters and hairpin DNA-modified Cu 2 O octahedra) were attached. This CHA-HCR strategy generated numerous active "hot spots" around the Cu 2 O octahedra and AuNB surface, significantly enhancing the SERS signal intensity. Using this chip, an ultralow limit of detection (LOD) for PIK3CA E542K (1.26 aM) and TP53 (2.04 aM) was achieved, and the whole process was completed within 13 min. Finally, a tumour-bearing mouse model was established, and ctDNA levels in mouse serum at different stages were determined. To verify the experimental accuracy, the gold-standard qRT-PCR assay was utilized, and the results showed a high degree of consistency. Thus, this rapid, sensitive and cost-effective SERS microfluidic chip has potential as an ideal detection platform for ctDNA monitoring., (© 2022. The Author(s).)

Circulating tumour DNAs (ctDNAs) have been reported to be associated with real-time information of progression; however, an accurate and sensitive method has not been established. Herein, a novel dual-signal amplification strategy based on a pump-free surface-enhanced Raman scattering (SERS) microfluidic chip and a catalytic hairpin assembly (CHA) technique was developed for the dynamic monitoring of BRAF V600E and KRAS G12V, which are two non-small cell lung cancer (NSCLC)-related ctDNAs. In the presence of targets, CHA reactions can be triggered between two hairpin DNAs, fixing Pd-Au core-shell nanorods (Pd-AuNRs) onto the magnetic beads (MBs) surface. Thereafter, the composite structures can assemble under the action of magnet, enabling dual-amplification of SERS signal. Using this strategy, the limit of detection (LOD) was low (i.e. at the aM level) in serum. Furthermore, the entire chip-based analysis process could be completed within 5 min, eliminating manual incubation and heavy-duty injection pumps. The selectivity, reproducibility and uniformity of the proposed pump-free SERS microfluidic chip were satisfactory. This superior analysis strategy was finally applied to quantify BRAF V600E and KRAS G12V in tumour-bearing nude mice serum, the results of which corresponded with those of real-time polymerase chain reaction. Overall, this study provides a promising alternative tool for the dynamic monitoring of ctDNA expression level which can benefit the clinical diagnosis of NSCLC., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The evaluation of tumor biomarkers in blood specimens is vital for patients with cervical lesions. Herein, an ultrasensitive surface enhanced Raman scattering (SERS) platform was proposed for simultaneous detection of cervical-lesion-related serum biomarkers. Raman reporter labeled Au-Ag nanoshells (Au-AgNSs) acted as SERS tags and an Au-Ag nanobox (Au-AgNB) array substrate prepared by the oil-water interface self-assembly method was used as a capture substrate. This single-layer Au-AgNB array substrate was proved to have exceptional uniformity by atomic force microscopy and SERS mapping. Numerous "hot spots" and specific adsorption surfaces offered by the Au-AgNB array substrate were confirmed by the finite difference time domain method, which could generate a SERS signal in electromagnetic enhancement. Binding of antigens between antibodies on Au-AgNSs and the Au-AgNB array substrate led to the formation of a sandwich-structure by the two metal nanostructures. Consequently, an ultralow detection limit of 6 pg mL -1 for squamous cell carcinoma antigen (SCCA) and 5 pg mL -1 for survivin in a wide linear logarithmic range of 10 pg mL -1 to 10 μg mL -1 was acquired. High selectivity and reproducibility with relative standard deviations of 7.701% and 6.943% were detected. Furthermore, the simultaneous detection of the two biomarkers in practical specimens was conducted, and the results were consistent with those of the enzyme-linked immunosorbent assay. This platform exhibited good robustness in the rapid and sensitive detection of SCCA and survivin, which could be a promising tool in early clinical diagnosis for different grades of cervical lesions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we proposed a novel biosensor based on a high-density "hot spot" Au@SiO 2 array substrate and rolling circle amplification (RCA) strategy for the ultrasensitive detection of CpG methyltransferase (M.SssI) activity. In the presence of M.SssI, the RCA process can be triggered, causing the augmentation of the single-stranded DNA (ssDNA) at the tail of the double-stranded DNA (dsDNA), and the ssDNA can be hybridized with numerous DNA probes labeled with Raman reporters in the next steps. Afterwards, the resultant ssDNA can be modified to the Au@SiO 2 array substrate with the SERS enhancement factor of 7.49 × 10 6 . The substrate was synthesized by using a monolayer SiO 2 array to pick up the Au nanoparticle (AuNP) array and finite-difference time-domain (FDTD) simulation showed its excellent SERS effect. Particularly, the developed biosensor displayed a significant sensitivity with a broad detection range covering from 0.005 to 50 U mL -1 , and the limits of detection (LODs) in PBS buffer and human serum were 2.37 × 10 -4 U mL -1 and 2.51 × 10 -4 U mL -1 , respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects and breast cancer, prostate cancer, gastric cancer and cervical cancer patients were analyzed, and the reliability of the results was also confirmed by western blot (WB) experiments. Taking advantage of these merits, the proposed biosensor can be a very promising alternative tool for the detection of M.SssI activity, which is of vital importance in the early detection and prevention of tumors.

An innovative surface-enhanced Raman spectroscopy and lateral flow assay (SERS-LFA) biosensor combined with aptamer recognition had been developed for the convenient, rapid, sensitive and accurate detection of thrombin and platelet-derived growth factor-BB (PDGF-BB) associated with prostate cancer simultaneously. During the biosensor operation, thrombin and PDGF-BB in the sample were recognized and combined by thiol-modified aptamers immobilized on Au-Ag hollow nanoparticles (Au-Ag HNPs) surface and biotinylated aptamers immobilized on the test lines of the biosensor. Thus, thrombin and PDGF-BB were simultaneously captured between detection aptamers and capture aptamers in a sandwich structure. Finite difference time domain simulation confirmed that 'hot spots' appeared at the gaps of Au-Ag HNPs dimer in the enhanced electromagnetic field compared to that of a single Au-Ag HNP, indicating that the aggregated Au-Ag HNPs owned a good SERS signal amplification effect. The detection limits of thrombin and PDGF-BB in human plasma were as low as 4.837 pg ml -1 and 3.802 pg ml -1 , respectively. Moreover, the accuracy of the biosensor which was applied to detect thrombin and PDGF-BB in prostate cancer plasma had been verified. This designed biosensor had broad application prospects in the clinical diagnosis of prostate cancer., (© 2021 IOP Publishing Ltd.)

The highly sensitive and reliable detection, imaging, and monitoring of changes of intracellular caspase-3 are critical for understanding the cell apoptosis and studying the progression of caspase-3-related cervical cancer. Herein, we present a novel surface-enhanced Raman scattering (SERS) probe for the detection of caspase-3 during cervical cancer cell apoptosis, composed of Au nanoboxes modified with Nile blue A as a Raman reporter and a caspase-3-specified peptide as a molecular cross-linker. In the presence of caspase-3, the substrate peptides can be cleaved and the changed surface charge of the Au nanoboxes results in the Au nanoboxes-NBA-peptide assembling to form aggregates and a great enhancement of SERS signal. The finite-difference time-domain simulation showed that hot spots mainly located in the nanogaps of the aggregated Au nanoboxes, which in theory proved the rationality of this signal amplification method. The SERS probes exhibited excellent reproducibility and selectivity toward caspase-3. A detection limit of 0.127 fM was obtained for caspase-3, with a dynamic range from 1 fM to 1 nM. MTT assay demonstrated that the probes had no obvious cytotoxicity within a certain concentration range. HeLa cells were treated with doxorubicin to induce long-term apoptosis. Upon cellular uptake of these probes, the spatiotemporal dynamics of caspase-3 in apoptotic cells could be real-time monitored using SERS. The activity of caspase-3 increased with the prolongation of apoptosis time. The SERS results were in accordance with that of western blotting assay. This kind of probe can offer great potential for the determination of enzymatic activities in the physiological processes of cells.

A CoNi-based metal-organic framework (CoNi-MOF) nanosheet array is synthesized by the treatment of a CoNi layered double hydroxide nanosheet array on Ni foam with 3,5-diaminobenzoic acid. The CoNi-MOF nanosheet array with amino and carboxyl groups can be used to capture the human chorionic gonadotropin (HCG) primary antibody (HCG Ab1). Nile Blue decorated ZnNi-MOF (NB@ZnNi-MOF) spheres immobilized with HCG secondary antibodies (HCG Ab2) are used for signal amplification. When HCG exists in an analytical sample, a sandwich structure is formed and an electrochemical signal is produced. The analytical signal generated during the detection is caused by the conversion of Co(ii) and Co(iii) in the CoNi-MOF nanosheet array. The Nile Blue of the NB@ZnNi-MOF sphere, as a kind of redox-active species, is responsible for the electrochemical signal amplification in the immunosensor. On the basis of the above advantages, the HCG immunosensor exhibits a lower limit of detection (1.85 × 10-3 mIU mL-1) and a wide linear range from 0.005 mIU mL-1 to 250 mIU mL-1. Additionally, this immunosensor is used to quantitatively detect HCG in human blood serum and shows good correlations with the standard enzyme-linked immunosorbent assay (ELISA), providing a high value on clinical diagnosis.

Cytochrome c (Cyt c) is a biomarker of early apoptosis that plays a critical role in the diagnosis and therapy of non-small cell lung cancer (NSCLC). In this work, we proposed a novel surface-enhanced Raman scattering (SERS)-based biosensor to implement the ultrasensitive detection of Cyt c in the serum of NSCLC patients. The SERS-supporting substrates based on hydrophobic filter paper were composed of gold nanourchins (GNUs) surface-functionalized with the Cyt c aptamer and the cyanine 5-labeled complementary DNA. In the existence of Cyt c, it could specifically bind to its aptamer, which leads to the detachment of complementary strands modified with Cy5 and the great weakness of SERS signal. The finite-difference time domain (FDTD) simulation showed that the excellent SERS performance of GNUs aggregation was strongly dependent on a large number of "hot spots" at the tips and between the nanogaps of aggregated GNUs. Alkyl ketene dimer (AKD) was used to make the filter paper modify its property from hydrophilic to hydrophobic, which consequently increased the density of GNUs and extended the retention time of the analyte. SERS biosensors based on hydrophobic paper exhibited prominent reproducibility and selectivity. The detection limit of Cyt c in PBS was 1.148 pg/mL, while the detection limit in human serum was 1.79 pg/mL. Moreover, the analysis of the serum samples of healthy subjects and NSCLC patients confirmed the feasibility of its clinical application. The results were consistent with enzyme-linked immunosorbent assay results. This method can be a powerful strategy for quantitative detection of extracellular Cyt c, and it is expected that the SERS-based biosensors could be applied in the practical clinical diagnoses of NSCLC., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

The diamondback moth Plutella xylostella is a major destructive pest of Brassica worldwide. P. xylostella has evolved resistance to nearly all commercial insecticides used for its control, including the most recent chemical class, diamide insecticides. Several studies show that the G4946E and I4790M mutations of ryanodine receptor (RyR) are strongly associated with diamide resistance in insects. While the pivotal functional role of G4946E in conferring diamide resistance phenotype has confirmed by several studies in different species, no direct evidence has unambiguously confirmed the functional significance of the single I4790M mutation in diamide resistance. Here, we successfully constructed a knockin homozygous strain (I4790M-KI) of P. xylostella using CRISPR/Cas9 coupled with homology directed repair approach to introduce I4790M into RyR. When compared with the background susceptible IPP-S strain, the manipulated I4790M-KI strain exhibited moderate resistance to the phthalic acid diamide flubendiamide (40.5-fold) and low resistance to anthranilic diamides chlorantraniliprole (6.0-fold) and cyantraniliprole (7.7-fold), with no changes to the toxicities of indoxacarb and β-cypermethrin. Furthermore, the acquired flubendiamide resistance was inherited in an autosomally recessive mode and significantly linked with the I4790M mutation of RyR in this I4790M-KI strain. Our findings provide in vivo functional evidence for the causality of I4790M mutation of PxRyR with moderate levels of resistance to flubendiamide in P. xylostella, and support the hypothesis that the diamide classes have different interactions with RyRs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)