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Tyrosinase (TYR) is as a well-known polyphenol oxidase and important biomarker of melanocytic lesions. Thus, developing powerful methods to determine TYR activity is of great value in the early diagnosis of skin disease. Direct surface-enhanced Raman scattering (SERS) detection of biomolecules is usually affected by non-specific interference and complicate structure of the analytes. It is a challenge to develop Raman-active molecules with specific recognition to analytes in complex media. Here, we report a novel colorimetric and surface-enhanced Raman scattering (SERS) dual-readout assay for the determination of TYR using commercially available and economical 4-mercaptophenyl boronic acid (4-MPBA) as a Raman-active and recognition molecule. 4-MPBA provides a unique interactive boronic acid group to the diol group of TYR substrate and exhibits good SERS signal. Also, the introduction of magnetic beads could promptly improve the anti-interference ability of dual-mode sensor. The TYR-incubated tyramine-modified magnetic beads could obviously change the concentration of 4-MPBA-AuNPs in the presence of O 2 and ascorbic acid, where the ultraviolet visible (UV–vis) absorption and SERS intensity were directly related to the concentration of TYR added. The dual-mode sensor had a rapid response to TYR within 1 min under optimized conditions and had high selectivity for TYR with a limit of detection at 0.001 U/mL. In addition, the dual-mode strategy showed promising prospects in the determination of TYR activity in serum samples and could be used to screen TYR inhibitors. [Display omitted] • Commercially available and economical 4-MPBA was used for Raman signal and recognition molecule. • We report a colorimetric and SERS dual-mode assay for tyrosinase (TYR). • A simple yet highly sensitive and selective method was used to detect TYR. • The TYR-incubated tyramine-MBs can rapidly react with 4-MPBA-AuNPs, resulting in an obvious change of color and SERS spectra. [ABSTRACT FROM AUTHOR]

Studies the multiphoton ionization of the hydrogen-bonded pyrrole-water clusters with a reflectron-time of flight mass spectrometer. Existence of a series of poly-pyrrole-water binary-mixed cluster ions; Results of the ab initio calculations of the structures, bond strengths, charge distributions and reaction energies of poly-pyrrole-water binary-mixed cluster ions.

The ion–molecule reaction is one of the most important pathways for the formation of new interstellar chemical species. Herein, infrared spectra of cationic binary clusters of acrylonitrile (AN) with methanethiol (CH3SH) and dimethyl sulfide (CH3SCH3) are measured and compared to those previous studies of AN and methanol (CH3OH) or dimethyl ether (CH3OCH3). The results suggest that the ion–molecular reactions of AN with CH3SH and CH3SCH3 only yield products with S...HN H-bonded or S∴N hemibond structures, rather than the cyclic products as observed in AN-CH3OH and AN-CH3OCH3 studied previously. The Michael addition-cyclization reaction between acrylonitrile and sulfur-containing molecules does not occur due to the weaker acidity of CH bonds in sulfur-containing molecules, which results from their weaker hyperconjugation effect compared to oxygen-containing molecules. The reduced propensity for the proton transfer from the CH bonds hinders the formation of the Michael addition-cyclization product that follows. [ABSTRACT FROM AUTHOR]

• Atomically precise Ag 152 nanoclusters (~2 nm) are introduced into 3D arrays structure. • Au nanoparticle (AuNP) with single particle size are prepared as AuNP monolayer film. • The ZnO-NC/Au/Ag 152 3D SERS substrate has high density of hot spots. • The ZnO-NC/Au/Ag 152 substrate exhibits the capability of ultra-sensitive detection. • The substrate can achieve rapid self-cleaning and recycling through photocatalysis. It is well known that the intensity and density of hot spots directly determine the surface-enhanced Raman scattering (SERS) performance of a substrate. In this work, we proposed a new strategy to improve the density of hot spots of a SERS substrate by innovatively introducing atomically precise Ag nanoclusters (Ag 152 (SCH 2 CH 2 Ph) 60 , ~2 nm). First, a 30 nm gold nanoparticle (AuNP) film in conjunction with hexagonal zinc oxide nanocone (ZnO-NC) arrays is prepared as a three-dimensional (3D) backbone; these ZnO-NC/AuNP arrays provide numerous anchors to facilitate the loading of Ag 152 nanoclusters, thereby further enhancing the intensity and density of hot spots on the entire substrate. In addition, the ultra-small particle size of the Ag 152 nanoclusters will not cover the original hot spots on the surface of AuNP film during deposition. Thus, the ZnO-NC/Au/Ag 152 3D SERS sensing platform shows the capability of ultra-sensitive detection, and the substrate results in an enhancement factor (EF) of up to 6.48 × 109. More importantly, the prepared substrate can act as an environmentally friendly sensing platform to achieve rapid self-cleaning and recycling through photocatalysis. The present work confirms the application prospects of novel metal nanoclusters in the field of SERS and photocatalysis. [ABSTRACT FROM AUTHOR]

• Proton transfer processes in gaseous clusters of Acrylonitrile (ALN) and acetonitrile (ATN) molecules. • Effect of conjugation and hyperconjugation. • The conjugation effect in ALN induces a high proton transfer barrier. • The hyperconjugation in the ATN molecule makes the proton transfer process a low-barrier or no-barrier process. Acrylonitrile (ALN) and acetonitrile (ATN) are two important interstellar molecules that contain nitrogen atoms. Herein, we explore the proton transfer processes occurring in gaseous clusters of ALN and ATN molecules with the aid of synchrotron vacuum ultraviolet radiation. We investigated the proton transfer phenomenon by use of time-of-flight mass spectrometry as well as theoretical calculations. We observe that the mass spectra of ALN and ATN clusters are apparently different from each other. In the mass spectrum of ALN clusters, the peaks related to un-protonated cluster cations are dominant. Unlike the ALN clusters, the protonated cluster cations are dominant in the mass spectrum of ATN clusters. These results are attributed to the different conjugate and hyperconjugate molecular structures in ALN and ATN, respectively. Theoretical calculations show that the conjugation effect between the π C=C orbital and π C≡N orbital in ALN induces a high proton transfer barrier that determines the dominant peaks of its non-protonated clusters cations. Conversely, the hyperconjugation between the σ Cα-H and π C≡N orbital in the ATN molecule determines that the proton transfer process in ATN is a low-barrier or even a no-barrier process. This favors the formation of protonated clusters. The present results reveal that ALN clusters are more aprotic than those consisting of ATN, and a relative high energy barrier is needed to surmount the proton transfer process of ALN clusters. This property of ALN makes it an appropriate candidate molecule to form the membrane alternative in the liquid methane lakes of Titan. ATN is not an appropriate candidate. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes irreversible damage to the joints. However, effective drugs exist that can stop disease progression, leading to intense interest in early detection and treatment monitoring to improve patient outcomes. Imaging approaches have the potential for early detection, but current methods lack sensitivity and/or are time-consuming and expensive. We examined potential routes for self-administration of molecular imaging agents in the form of subcutaneous and oral delivery of an integrin binding near-infrared (NIR) fluorescent imaging agent in an animal model of RA with the long-term goal of increasing safety and patient compliance for screening. NIR imaging has relatively low cost, uses non-ionizing radiation, and provides minimally invasive spatial and molecular information. This proof-of-principle study shows significant uptake of an IRDye800CW agent in inflamed joints of a collagen antibody induced arthritis (CAIA) mouse model compared to healthy joints, irrespective of the method of administration. The imaging results were extrapolated to clinical depths in silico using a 3D COMSOL model of NIR fluorescence imaging in a human hand to examine imaging feasability. With target to background concentration ratios greater than 5.5, which are achieved in the mouse model, these probes have the potential to identify arthritic joints following oral delivery at clinically relevant depths. [ABSTRACT FROM AUTHOR]

A surface-enhanced Raman scattering (SERS) method is described for the determination of microRNA that is associated with various forms of cancer. The substrate consists of functionalized gold-silver bimetallic structure, and the sensitivity is strongly enhanced by making use of a re-circulated enzymatic amplification system (REAS). Poly-dopamine acts as both a reductant and a protective of the substrates. It was employed to link the gold core and silver satellite. The unique "hot spots" consisting of a Au@PDA@Ag nanocomposite improve the Raman signal and sensitivity. The reductive feature of PDA can prevent the susceptible oxidation of metallic silver to maintain the high Raman activity. To improve the sensitivity of the assays, a re-circulated enzymatic amplification system was developed in which the nicking endonuclease triggers the nucleic acid reaction system to enter an amplified cycle. By integrating the bimetallic nanosubstrate and magnetic separation into the REAS, microRNA can be detected by SERS (best at the Raman band of 1586 cm−1) with a limit of detection as low as 0.2 fM. In our perception, the assay provides an exciting new avenue to study the expression of tumor genes. Thus, it holds vast promise in cancer diagnosis.Schematic presentation of the SERS method based on poly-dopamine mediated bimetallic SERS substrate and re-circulated enzymatic amplification. [ABSTRACT FROM AUTHOR]

Concrete with manufactured sand (MSC) requires adequate compressive properties, which may be caused by stone powder. This present study investigated the effect of different stone powder content (0%, 3%, 5%, 7%, 9% and 11%) on compressive properties of MSC. The properties of fresh MSC were evaluated by three tests, compressive strength, axial compressive strength and elastic modulus. Measure results showed that stone powder as part of fine aggregate replacement improved compressive properties of MSC. The content ranging from 5%–7% increased compressive strength. The content of 11% could greatly improve axial compressive strength. The elastic modulus had a slightly enhancement when the stone powder was within 9%. Predictive models were proposed for the prediction of long-term compressive strength of MSC. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to compare the outcomes of the two-stage induced membrane technique (IMT) and one-stage autografting in the treatment of aseptic atrophic nonunion in lower limb long bones. Methods: From January 2014 to January 2022, we reviewed all surgically treated long bone nonunion patients, including patients aged 18 years or older with atrophic nonunion, who were either treated with the two-stage induced membrane technique (IMT) or one-stage autografting. Outcome parameters interns of clinical, quality of life and healthcare burden were recorded and retrospectively analysed between the two treatment populations. The follow-up time was at least 1 year. Results: In total, 103 patients who met the criteria for aseptic atrophic nonunion were enrolled. Among them, 41 (39.8%) patients were treated with two-stage IMT, and 62 (60.2%) patients were treated with one-stage autologous bone grafting. The follow-up time was 12 to 68 months, with an average of 28.4 months. The bone healing rate was comparable in both groups (IMT: 92.7% vs. one-stage grafting: 91.9%, P = 0.089) at 12 months post-operation, and the bone healing Lane–Sandhu score was superior in the IMT group (mean: 8.68 vs. 7.81, P = 0.002). Meanwhile, the SF-12 scores of subjective physical component score (PCS) (mean: 21.36 vs. 49.64, P < 0.01) and mental health component score (MCS) (mean: 24.85 vs. 46.14, P < 0.01) significantly increased in the IMT group, as well as in the one-stage grafting group, and no statistically significant difference was found within groups. However, the total hospital stays (median: 8 days vs. 14 days, P < 0.01) and direct medical healthcare costs (median: ¥30,432 vs. ¥56,327, P < 0.05) were greater in the IMT group, while the complications (nonunion 8, infection 3, material failure 2, and donor site pain 6) were not significantly different between the two groups (17.1% vs. 19.4, P = 0.770). Conclusion: The data indicate that two-stage method of IMT serves as an alternative method in treating atrophic nonunion; however, it may not be a preferred option, in comprehensive considering patient clinical outcomes and healthcare burden. More evidence-based research is needed to further guide clinical decision-making. [ABSTRACT FROM AUTHOR]

The key to improve the service effect of virtual digital human is the personality trait recognition technology of users. However, the complexity of Chinese and the sparsity of short texts limit the accuracy of personality trait recognition. Therefore, we applied emotional features to the research of personality trait recognition and constructed a deep learning model for Chinese corpus personality trait recognition to improve the accuracy of personality trait recognition. The model ( R-B e) extracted semantic features and embedded emotional features through RoBERTa-wwm-ext Chinese pre-training model, BiLSTM neural network, and attention mechanism. Some experiments were carried out using two Chinese datasets with different scenes. The comparative experiments and ablation experiments showed that the overall effect of the personality trait recognition model ( R-B e) is the best, and the Macro-F1 value reaches 75.3%, which is significantly better than the existing models. The results showed that emotional features can significantly improve the accuracy of multi-label personality trait classification in both Chinese daily life scenarios and online scenarios. The proposed model can integrate emotional features and Chinese semantic features to improve the accuracy of personality traits recognition. These findings support the development of personality trait recognition and the application of virtual digital human. [ABSTRACT FROM AUTHOR]

Undesired physiological instability of nanocarriers and premature drug leakage during blood circulation result in compromised therapeutic efficacy and severe side effects, which have significantly impeded the development of nanomedicine. Facile crosslinking of drug-loaded nanocarriers while keeping the potency of site-specific degradation and drug release has emerged as a viable strategy to overcome these drawbacks. Additionally, combination therapy has already shown advantages in inhibiting advanced tumors and life extension than single drug therapy. Herein, three kinds of diselenide-rich polymers were fabricated with distinct hydrophobic side chains. The component effect was interrogated to screen out PEG- b -PBSe diblock copolymer due to its favorable self-assembly controllability and high drug loading of camptothecin (CPT) and doxorubicin (DOX) that had synergistic antitumor property. Facile visible light-induced diselenide metathesis and regeneration was employed to crosslink nanocarriers for the first time. The dual drug-loaded crosslinked micelles (CPT/DOX-CCM) were stable in physiological conditions with minimal drug leakage, possessing extended blood circulation, whereas hand-in-hand dual drug release was significantly accelerated in tumor's redox microenvironments. In vitro cytotoxicity evaluation and in vivo tumor suppression with low dosage drugs further demonstrated the favorable potency of the redox-responsive nanoplatform in tumor combination chemotherapy. [ABSTRACT FROM AUTHOR]

Curcumin is a dietary spice and coloring agent widely used in food and herbal medicine. Herein, we visualized the distribution of curcumin in fresh Curcuma longa (turmeric) root sections using the state-of-the-art vacuum-ultraviolet (VUV, 118 nm) single photon-postionization mass spectrometric imaging method. Compared with other mass spectrometric imaging methods, the proposed method does not require any sample pre-treatment. The proposed approach could be more conducive to in situ detection of small molecules. The mass spectroscopic imaging (MSI) images of curcumin sections with a lateral resolution of 100 μm indicated that the concentrations of curcumin decreased from the phloem to the xylem of the root. We also show MS imaging of curcumin in the turmeric root at different maturity periods, revealing the transformation of this endogenous species. The result of quantitative analysis indicates that the total curcumin content of the mature turmeric root is estimated to be 3.43%, which is consistent with the previous report that the content of curcumin in the turmeric root is estimated between 3% and 5%. The report indicated that the proposed method of VUV single photon postionization MSI can be used to explore the metabolic process of plants, which is critical for herbal farming, harvest, and its ingredient extraction. [ABSTRACT FROM AUTHOR]

A novel ratiometric fluorescent probe HB‐2 based on benzothiazole for hypobromous acid (HBrO) was synthesized and studied. After HBrO was added to the CH3CN‐HEPES solution of the HB‐2, the probe cyclized to form a sulfimine bond, which increased the conjugated degree of the system. The fluorescence emission peak of the reaction system at 447 nm gradually decreased, while the newly generated emission peaks gradually increased at 580 nm. The ratio of the fluorescence intensity at the two wavelengths of 447 nm and 580 nm increased about 234 times. Moreover, it has successfully been used to stain and record microscopy images of 4T1 cells, and the presence of exogenous HBrO could be judged by the change of fluorescence intensity. [ABSTRACT FROM AUTHOR]

Diabetes is a common chronic metabolic disease. The frequent fluctuation of glucose is the main cause of most diabetes complications, which in turn causes harm to the health of patients. Surface-enhanced Raman scattering (SERS) spectroscopy has attracted much attention in the rapid detection of glucose due to its unique molecular fingerprinting ability, ultra-high sensitivity and fast response. However, due to the low affinity between glucose and SERS substrate, poor signal, susceptibility to complex environmental interference, and poor stability of SERS detection, it is still a challenge for SERS to accurately and sensitively determine glucose in complex environments. In this work, we encapsulated 4-mercaptobutyronitrile (4-MBN) as an internal standard (IS) in Au@Ag NRs inside and then Au@4-MBN@Ag NRs, Leucomalachite Green (LMG), glucose oxidase (GOx) and horseradish peroxidase (HPR) were encapsulated in ZIF-8 to prepare a tandem enzyme catalytic ratiometric SERS sensor Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) for the detection of glucose in saliva. Because ZIF-8 enhanced the catalytic activity of the enzyme, the ability of glucose enrichment, and weakens the aggregation of Ag NRs. The internal standard signal molecule improves the accuracy and sensitivity of detection. The ratiometric Raman signal I 412 /I 2233 of glucose has a good linear relationship with the concentration in the range of 0.1–100 μM, and the limit of detection (LOD) could be down to 0.03 μM. At the same time, it has excellent selectivity, repeatability and accuracy. The recovery rate of glucose in saliva is 96.50%–105.56 %, which proves the feasibility of the method. The Au@4-MBN@Ag@LMG@ZIF-8(GOx, HPR) sensor prepared in this study showed excellent SERS performance, which was able to detect glucose quickly, sensitively and accurately. This work provides a new strategy for the design of enzyme-catalyzed SERS sensors. [Display omitted] • A novel ratiometric glucose SERS sensor was successfully prepared. • Au@4-MBN@Ag NR is individually encapsulated in ZIF-8 crystals to improve SERS signal stability. • As a stationary carrier, ZIF-8 can effectively prevent biological and chemical degradation. • Detection of ratiometric Raman improves the sensitivity and accuracy of detection. [ABSTRACT FROM AUTHOR]

Abstract: This work demonstrates that the sequence of a Ge co-implant with a B2H6 PLAD in the source/drain is very critical in order to improve advanced PMOS performance. Locating the Ge co-implant after the B2H6 PLAD resulted in higher total retained B dose and less implant damage. PMOS performance was significantly improved compared to B2H6 PLAD without the Ge co-implant or Ge co-implant before B2H6 PLAD. The Ge implant energy was optimized to locate the Ge peak around the B deposition layer/Si substrate interface for a better knocking effect and less implant damage. With the optimized Ge implant conditions the source/drain contact resistance and sheet resistance were significantly reduced, while the junction leakage current was not degraded. As a result, PMOS I ds improved by 12%, transconductance KL improved by 14%, and I OFF variation improved by 33% without significant change in mean I OFF. This process helps overcome technical challenges of B2H6 PLAD, providing a path for continued scaling of PMOS junction depth with improved device performance. [Copyright &y& Elsevier]

To investigate the effect of Al content on the microstructure evolution and properties of Al x CoCrFeNi 2.1 high-entropy alloys, the Al x CoCrFeNi 2.1 high-entropy alloys (=0.5, 0.8, 1.0, 1.2 and 1.5) were prepared by vacuum arc melting. The results show that all the designed alloys are composed of single face-centered cubic (FCC) and ordered body-centered cubic (B2) phases. With the increase of Al content, the volume fraction of FCC phase decreases while that of B2 phase increases. In addition, the increasing Al content leads to the sequential increase of the hardness and yield strength of the alloys, while both the plasticity and compressive strength decrease. And the corresponding wear rate decreases from 312.9 × 10−5 mm2 N−1 to 55.3 × 10−5 mm2 N−1. It is revealed that the wear mechanism transforms from initially dominant abrasive wear with adhesive wear as a supplement to the mechanism dominated by adhesive wear with abrasive wear as a supplement, and finally to the oxidation wear plus abrasive wear. The experimental results show that the Al 1.2 CoCrFeNi 2.1 alloy has the most excellent comprehensive performance, with an average hardness of 441 HV, compression ratio of 36.4%, compressive strength of 2618 MPa and wear rate of 68.0 × 10−5 mm2 N−1. [Display omitted] • Clarifying the role of Al element in microstructure and properties of eutectic HEAs. • Elucidating the wear mechanism in Al x CoCrFeNi 2.1 high-entropy alloys. • Finding the Al 1.2 CoCrFeNi 2.1 alloy with the most excellent comprehensive performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • β-CD /Ni-MOFs composite nanomaterials have been applied to sensors for the first time, and have good stability and accuracy in human serum and dopamine hydrochloride injection samples. Dopamine (DA) is an important neurotransmitter in human's brain, which has direct connection to diseases like Parkinson's disease, schizophrenia, etc. Therefore, the sensitive and rapid quantitative detection of DA is essential for medical diagnosis and disease prevention. To construct a novel electrochemical sensor for DA detection, nickel-based metal–organic frameworks (Ni–MOF) were synthesized through a hydrothermal method and combined with β-cyclodextrin. Under optimal experimental conditions, the sensor exhibited a wide linear detection range (0.7–310.2 μM) and a low detection limit (0.227 μM). Furthermore, the sensor exhibited satisfactory stability and accuracy in an electrochemical study involving human serum and dopamine hydrochloride injection samples containing DA, and the redox mechanism of the sensor was elucidated. Overall, this study presents a novel electrochemical sensor based on cyclodextrins and MOFs for DA detection. [ABSTRACT FROM AUTHOR]

• A NIR-II FRET platform is established using lanthanide downshifting nanoparticles. • This NIR-II FRET platform exhibits extraordinary anti-interference in whole blood. • This NIR-II FRET platform enables a maximum FRET efficiency as high as 92.2%. • This NIR-II FRET platform can realize highly sensitive detection in whole blood. Förster or fluorescence resonance energy transfer (FRET) enables to probe biomolecular interactions, thus playing a vital role in bioassays. However, conventional FRET platforms suffer from limited sensitivity due to the low FRET efficiency and poor anti-interference of existing FRET pairs. Here we report a NIR-II (1000–1700 nm) FRET platform with extremely high FRET efficiency and exceptional anti-interference capability. This NIR-II FRET platform is established based on a pair of lanthanides downshifting nanoparticles (DSNPs) by employing Nd3+ doped DSNPs as an energy donor and Yb3+ doped DSNPs as an energy acceptor. The maximum FRET efficiency of this well-engineered NIR-II FRET platform reaches up to 92.2%, which is much higher than most commonly used ones. Owing to the all-NIR advantage (λ ex = 808 nm, λ em = 1064 nm), this highly efficient NIR-II FRET platform exhibits extraordinary anti-interference in whole blood, and thus enabling background-free homogeneous detection of SARS-CoV-2 neutralizing antibodies in clinical whole blood sample with high sensitivity (limit of detection = 0.5 μg/mL) and specificity. This work opens up new opportunities for realizing highly sensitive detection of various biomarkers in biological samples with severe background interference. [ABSTRACT FROM AUTHOR]

18Ni300-based cladding layers with micro/nano WC additives were fabricated via plasma transferred arc welding (PTA) technology. This work investigates the influence of WC grain size on microstructure evolution and wear performance. The comparative investigation of the microstructure results indicates that the nano-WC particle-reinforced 18Ni300 coating sample shows more fine grains and nanoparticles. These nanoprecipitates are Ni 3 Mo and WC, which are uniformly distributed in the martensite matrix. The in-situ precipitation forms Ni 3 Mo precipitates in the maraging matrix, which is triggered by the intrinsic heat treatment effect of PTA. The hardness of the 5 wt% nano-WC/18Ni300 composite exhibits the highest value (395.8 ± 10.7HV0.3), which is 12.41 % higher than that of the original 18Ni300 coating (352.1 ± 12.1HV0.3). Meanwhile, the nano-WC-reinforced 18Ni300 coating shows the highest wear resistance, which is approximately 2.5 times higher than the original 18Ni300 cladding layer. It could be concluded that the refining and strengthening effects of nano-WC addition on the microstructure and wear resistance of the 18Ni300 coating were superior to those of micro-WC. Molecular dynamics simulation results indicate that melting begins at the surface of nano-WC and then proceeds to the solid core as the temperature rises from 300 K to the melting point. Meanwhile, the nano-WC particles have a more sensitive diffusion tendency with the matrix than the micro-WC particles. This diffusion of the surface atoms can generate solid bonding with the surrounding atoms in their matrix and promote the agglomeration and in situ precipitation of Ni 3 Mo, finally synergistically improving the wear resistance of the nano-WC-reinforced composite. • A novel electrostatic self-assembly method is used to prepare the nano-WC surface-modified 18Ni300 powder. • The 5 % nano-WC reinforced 18Ni300 PTA coating has the highest hardness and wear resistance. • In-situ precipitation of Ni 3 Mo within the nano-WC/18Ni300 composites promotes the wear properties enhancement. [ABSTRACT FROM AUTHOR]

The p53 gene is a known cancer marker. We report a novel protocol for the SERS tandem strategy to detect the p53 gene with high sensitivity. Herein, the click reaction between azide and alkyne was catalyzed by utilizing copper oxide nanoparticles (CuONPs), which were enriched by a T-DNA-triggered hybridization chain reaction (HCR). The T-DNA signal was amplified by establishing the correlation between the T-DNA signal and the concentration of CuONPs in a nonenzymatic isothermal environment. In contrast to other Raman reporters, we used alkynyl compounds as Raman reporters, which showed excellent characteristics in the Raman-silent region (1800–2800 cm−1). Therefore, the highly sensitive and highly selective SERS signals could be obtained in complex biological matrices. Due to utilizing multistep amplification strategies, including the nanoparticle-modified HCR polymer and "click" reaction, the limit of detection (LOD) and the limit of quantification (LOQ) of this sensor could be as low as 0.0174 pM and 0.0583 pM, respectively. The accuracy of the strategy expressed as the RSD was in the range of 3.14%–6.21%. The results indicated that the constructed sensor has excellent performance for the detection of the p53 gene in serum samples in a low concentration range, which suggests that the proposed enzyme-free SERS analytical sensor has good clinical application prospects. [Display omitted] ● We report a novel SERS sensor to detect the p53 gene. ● The ability to use the sensor at normal temperatures without enzyme-mediated amplification increases the ability to adapt to environmental conditions as well as the selectivity. ● The Raman signal of the alkyne lies in the Raman silent region, which is different from other Raman reporters; thus, it is easier to distinguish from the background signal in the biological environment. ● Universally, the strategy of altering the raw hairpin chain of HCR according to the target sequence is suitable for the detection of other biomarkers at low concentrations. [ABSTRACT FROM AUTHOR]

High-throughput cardiotoxicity assessment is important for large-scale preclinical screening in novel drug development. To improve the efficiency of drug development and avoid drug-induced cardiotoxicity, there is a huge demand to explore the automatic and intelligent drug assessment platforms for preclinical cardiotoxicity investigations. In this work, we proposed an automatic and intelligent strategy that combined automatic feature extraction and multi-labeled neural network (MLNN) to process cardiomyocytes mechanical beating signals detected by an interdigital electrode biosensor for the assessment of drug-induced cardiotoxicity. Taking advantages of artificial neural network, our work not only classified different drugs inducing different cardiotoxicities but also predicted drug concentrations representing severity of cardiotoxicity. This has not been achieved by conventional strategies like principal component analysis and visualized heatmap. MLNN analysis showed high accuracy (up to 96%) and large AUC (more than 98%) for classification of different drug-induced cardiotoxicities. There was a high correlation (over 0.90) between concentrations reported by MLNN and experimentally treated concentrations of various drugs, demonstrating great capacity of our intelligent strategy to predict the severity of drug-induced cardiotoxicity. This new intelligent bio-signal processing algorithm is a promising method for identification and classification of drug-induced cardiotoxicity in cardiological and pharmaceutical applications. [ABSTRACT FROM AUTHOR]