Ag-coated tetrapod gold nanostars (Au@AgNSs) for acetamiprid determination in tea using SERS combined with microfluidics.

Acetamiprid is an organic and highly toxic compound. Despite being widely used as a pesticide agent on a large scale, acetamiprid poses numerous health risks to living organisms, particularly humans. Herein, a strategy for the detection of acetamiprid in tea employing surface-enhanced Raman scattering (SERS) technology incorporated with a microfluidic chip was developed. Significantly, a seed-mediated growth approach was utilized to engineer Ag-coated tetrapod gold nanostars (core-shell Au@AgNSs) with four sharp tips. The synthesized Au@AgNSs showed an enhancement factor of 7.2 × 106. Solid works was used to figure out the two-channel microfluidic chip featuring four circular split hybrid structures, and COMSOL (Software for Multiphysics Simulation) was utilized to model the fusion effect between the substrate (Au@AgNSs) and the sample (acetamiprid). For the first time, the core-shell Au@AgNSs and acetamiprid were fused in the microfluidic channel to facilitate the detection of acetamiprid using SERS. The outcomes pointed out that the standard curve correlation coefficient between SERS intensity (876 cm-1) and the concentration of acetamiprid in tea specimens was calculated as 0.991, while the limit of detection (LOD) was 0.048 ng mL-1, which is well below the minimum limit set by the European Union (10 ng mL-1). Thus, the developed technique combining SERS and microfluidics demonstrated high potential for the rapid and efficient detection of acetamiprid in tea.

Dual function of magnetic nanocomposites-based SERS lateral flow strip for simultaneous detection of aflatoxin B1 and zearalenone.

Aflatoxin B1 (AFB1) and zearalenone (ZEN) are two mycotoxins that often co-occur in corn. A surface-enhanced Raman scattering-based lateral flow immunoassay (SERS-LFIA) that can simultaneously detect AFB1 and ZEN in corn samples was developed employing the core-interlayer-satellite magnetic nanocomposites (Fe3O4@PEI/AuMBA@AgMBA) as dual-functional SERS tags. Under the optimal conditions, the detection ranges of AFB1 and ZEN in corn samples were 0.1-10 µg/kg and 4-400 µg/kg, respectively. Moreover, the test results for two mycotoxins in contaminated corn samples employing the suggested SERS-LFIA was in line with those of the HPLC technique. In view of its satisfactory sensitivity, accuracy, precision and short testing time (20 min), the developed system has a promising application prospect in the on-site simultaneous detection of AFB1 and ZEN.

Raman spectroscopy-based microfluidic platforms: A promising tool for detection of foodborne pathogens in food products.

Rapid and sensitive detection of foodborne pathogens in food products is paramount for ensuring food safety and public health. In the ongoing effort to tackle this issue, detection methods are continually researched and upgraded to achieve rapidity, sensitivity, portability, and cost-effectiveness. This review addresses the critical need for improved technique by focusing on Raman spectroscopy-based microfluidic platforms, which have shown potential in revolutionizing the field of foodborne pathogen analysis offering point-of-care diagnosis and multiplex detection. The key problem lies in the persistent threat of compromised food quality and public health due to inadequate pathogen detection. The review elucidates the various trapping strategies employed in a microfluidic platform, including optical trapping, electrical trapping, mechanical trapping, and acoustic trapping for the capture of microbial cells. Subsequently, the review delves into the key aspects of the application of microbial detection in food products, highlighting recent advances and challenges in the field. The integrated technique allows point-of-care application assessment, which is an attractive quality for in-line and real-time detection of foodborne pathogens. However, the application of the technique in food products is limited and requires further research to combat the complexity of the food matrix, reduced costs of production, and ensure real-time use for diverse pathogens. Ultimately, this review aims to propel advancements in microbial detection, thus promoting enhanced food safety through state-of-the-art technologies.

A film-like SERS aptasensor for sensitive detection of patulin based on GO@Au nanosheets.

Patulin (PAT) commonly contaminates fruits, posing a significant risk to human health. Therefore, a highly effective and sensitive approach in identifying PAT is warranted. Herein, a SERS aptasensor was constructed based on a two-dimensional film-like structure. GO@Au nanosheets modified with SH-cDNA were employed as capture probes, while core-shell Au@Ag nanoparticles modified with 4-MBA and SH-Apt were utilized as signal probes. Through the interaction between capture probes and signal probes, adjustable hotspots were formed, yielding a significant Raman signal. During sensing, the GO@Au-cDNA competitively attached to Au@AgNPs@MBA-Apt, resulting in an inverse relationship between PAT levels and SERS intensity. The acquired results exhibited linear responses to PAT within the range of 1-70 ng/mL, with a calculated limit of detection of 0.46 ng/mL. In addition, the SERS aptasensor exhibited satisfactory recoveries in apple samples, which aligned closely with HPLC. With high sensitivity and specificity, this method holds significant potential for PAT detection.

Anti-Pseudomonas aeruginosa activity of natural antimicrobial peptides when used alone or in combination with antibiotics.

The World Health Organization has recently published a list of 12 drug-resistant bacteria that posed a significant threat to human health, and Pseudomonas aeruginosa (P. aeruginosa) was among them. In China, P. aeruginosa is a common pathogen in hospital acquired pneumonia, accounting for 16.9-22.0%. It is a ubiquitous opportunistic pathogen that can infect individuals with weakened immune systems, leading to hospital-acquired acute and systemic infections. The excessive use of antibiotics has led to the development of various mechanisms in P. aeruginosa to resist conventional drugs. Thus, there is an emergence of multidrug-resistant strains, posing a major challenge to conventional antibiotics and therapeutic approaches. Antimicrobial peptides are an integral component of host defense and have been found in many living organisms. Most antimicrobial peptides are characterized by negligible host toxicity and low resistance rates, making them become promising for use as antimicrobial products. This review particularly focuses on summarizing the inhibitory activity of natural antimicrobial peptides against P. aeruginosa planktonic cells and biofilms, as well as the drug interactions when these peptides used in combination with conventional antibiotics. Moreover, the underlying mechanism of these antimicrobial peptides against P. aeruginosa strains was mainly related to destroy the membrane structure through interacting with LPS or increasing ROS levels, or targeting cellular components, leaded to cell lysis. Hopefully, this analysis will provide valuable experimental data on developing novel compounds to combat P. aeruginosa.

Safety and Tolerability of Low-Dose Radiation and Stereotactic Body Radiotherapy + Sintilimab for Treatment-Naïve Stage IV PD-L1+ Non-Small Cell Lung Cancer Patients.

PURPOSE: Low-dose radiotherapy (LDRT) may enhance the synergistic antitumor effect of combined immunotherapy and stereotactic body radiotherapy (SBRT). The safety and efficacy of this novel triple-combination therapy were evaluated for the first time as first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This prospective phase I study enrolled 29 patients and included a dose-escalation and dose-expansion phase. Patients received SBRT [30 Gray (Gy)/3f] to small lesions and LDRT (2 Gy/1f, 4 Gy/2f, or 10 Gy/5f) to a large lesion concurrently, followed by sintilimab (a programmed death-1 inhibitor). The primary endpoint was safety and tolerability; secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: No dose-limiting toxicities were observed during the dose-escalation phase; 4 Gy/2f was the recommended LDRT dose. Median follow-up was 15.6 months. Treatment-related adverse events (TRAE) occurred in 96.6% (28/29) of patients [grade ≥ 3; 20.7% (6/29)]; 2 patients (6.9%) discontinued due to TRAEs. Seven patients experienced pneumonitis (grade 2, n = 6; grade 3, n = 1). Immune-related adverse events were noted in 58.6% (17/29) of patients. In patients with tumor assessment (n = 28), ORR and confirmed ORR were 60.7% and 57.1%, respectively. Median PFS was 8.6 months (95% confidence interval, 3.7-16.5), and median OS was not reached. Exploratory analyses suggested both expanded and newly emerging T-cell receptor clonotypes were associated with better PFS. CONCLUSIONS: The findings indicate that the novel SBRT + LDRT + sintilimab therapy is safe and promising in patients with programmed death ligand-1-positive, driver gene-negative primary metastatic NSCLC.

Spoilage Monitoring and Early Warning for Apples in Storage Using Gas Sensors and Chemometrics.

In the process of storage and cold chain logistics, apples are prone to physical bumps or microbial infection, which easily leads to spoilage in the micro-environment, resulting in widespread infection and serious post-harvest economic losses. Thus, development of methods for monitoring apple spoilage and providing early warning of spoilage has become the focus for post-harvest loss reduction. Thus, in this study, a spoilage monitoring and early warning system was developed by measuring volatile component production during apple spoilage combined with chemometric analysis. An apple spoilage monitoring prototype was designed to include a gas monitoring array capable of measuring volatile organic compounds, such as CO2, O2 and C2H4, integrated with the temperature and humidity sensor. The sensor information from a simulated apple warehouse was obtained by the prototype, and a multi-factor fusion early warning model of apple spoilage was established based on various modeling methods. Simulated annealing-partial least squares (SA-PLS) was the optimal model with the correlation coefficient of prediction set (Rp) and root mean square error of prediction (RMSEP) of 0.936 and 0.828, respectively. The real-time evaluation of the spoilage was successfully obtained by loading an optimal monitoring and warning model into the microcontroller. An apple remote monitoring and early warning platform was built to visualize the apple warehouse's sensors data and spoilage level. The results demonstrated that the prototype based on characteristic gas sensor array could effectively monitor and warn apple spoilage.

Determination of Dicofol in Tea Using Surface-Enhanced Raman Spectroscopy Coupled Chemometrics.

Dicofol is a highly toxic residual pesticide in tea, which seriously endangers human health. A method for detecting dicofol in tea by combining stoichiometry with surface-enhanced Raman spectroscopy (SERS) technology was proposed in this study. AuNPs were prepared, and silver shells were grown on the surface of AuNPs to obtain core-shell Au@AgNPs. Then, the core-shell Au@AgNPs were attached to the surface of a PDMS membrane by physical deposition to obtain a Au@AgNPs/PDMS substrate. The limit of detection (LOD) of this substrate for 4-ATP is as low as 0.28 × 10-11 mol/L, and the LOD of dicofol in tea is 0.32 ng/kg, showing high sensitivity. By comparing the modeling effects of preprocessing and variable selection algorithms, it is concluded that the modeling effect of Savitzky-Golay combined with competitive adaptive reweighted sampling-partial least squares regression is the best (Rp = 0.9964, RPD = 10.6145). SERS technology combined with stoichiometry is expected to rapidly detect dicofol in tea without labels.

Development of a Sensitive SERS Method for Label-Free Detection of Hexavalent Chromium in Tea Using Carbimazole Redox Reaction.

Tea plants absorb chromium-contaminated soil and water and accumulate in tea leaves. Hexavalent chromium (Cr6+) is a very toxic heavy metal; excessive intake of tea containing Cr6+ can cause serious harm to human health. A reliable and sensitive surface-enhanced Raman spectroscopy (SERS) method was developed using Au@Ag nanoparticles as an enhanced substrate for the determination of Cr6+ in tea. The Au@AgNPs coated with carbimazole showed a highly selective reaction to Cr6+ in tea samples through a redox reaction between Cr6+ and carbimazole. The Cr6+ in the contaminated tea sample reacted with methimazole-the hydrolysate of carbimazole-to form disulfide, which led to the decrease in the Raman intensity of the peak at 595 cm-1. The logarithm of the concentration of Cr6+ has a linear relationship with the Raman intensity at the characteristic peak and showed a limit of detection of 0.945 mg/kg for the tea sample. The carbimazole functionalized Au@AgNPs showed high selectivity in analyzing Cr6+ in tea samples, even in the presence of other metal ions. The SERS detection technique established in this study also showed comparable results with the standard ICP-MS method, indicating the applicability of the established technique in practical applications.

Dual-layers Raman reporter-tagged Au@Ag combined with core-satellite assemblies for SERS detection of Zearalenone.

Zearalenone (ZEN) is a prevalent mycotoxin identified in corn. A SERS-based immunosensor by constructing core-satellite assemblies was developed for ZEN detection. ZEN monoclonal antibody modified gold nanostars (AuNSs) were fabricated as the capture probe (core). The Raman signal probes (satellites) utilized ZEN antigen linked to the core-shell structures loaded with two layers of Raman reporter molecules (AuMBA@AgMBANPs). The coupling between AuNSs and AuMBA@AgMBANPs can produce a poweful electromagnetic field, thus considerably amplifying the Raman signal. The detection range of ZEN for corn samples under the optimal conditions was 5 âˆ¼ 400 µg/kg with a LOD of 3 µg/kg, which completely satisfying the requirement of maximum residual level (60 µg/kg). Moreover, the proposed SERS method was consistent with the HPLC-FLD method for the detection of ZEN in naturally contaminated corn samples (90.58% ∼ 105.29%). Conclusively, fabricated immunosensor with exceptional sensitivity and specificity broaden the application of SERS in mycotoxin detection.

Time to abandon CAR-T monotherapy for solid tumors.

In recent decades, chimeric antigen receptor T (CAR-T) cell therapy has achieved dramatic success in patients with hematological malignancies. However, CAR-T cell therapy failed to effectively treat solid tumors as a monotherapy. By summarizing the challenges of CAR-T cell monotherapy for solid tumors and analyzing the underlying mechanisms of combinatorial strategies to counteract these hurdles, we found that complementary therapeutics are needed to improve the scant and transient responses of CAR-T cell monotherapy in solid tumors. Further data, especially data from multicenter clinical trials regarding efficacy, toxicity, and predictive biomarkers are required before the CAR-T combination therapy can be translated into clinical settings.

Switchable aptamer-fueled colorimetric sensing toward agricultural fipronil exposure sensitized with affiliative metal-organic framework.

Persistent usage of pesticides in agriculture has posed serious damage to overall ecosystem and human health, and thereby it is imperative to develop sensitive and efficient tools to evaluate residual pesticides in food and environmental setting. Herein, we reported a switchable colorimetric probe toward fipronil residue sensitized with aptamer-fueled catalytic activity of affiliative ZIF-8. Innovatively, it was found that the attached aptamer preferred to adsorb 3,3',5,5'-tetramethylbenzidine (TMB) rather than 2,2-azinobis (3-ethylbenzothiazo-line-6-sulfonic acid) (ABTS), greatly promoting catalytic oxidation of ZIF-8 toward TMB for further improving sensitivity. Aiding with smartphone-based image acquisition, fipronil-responsive discoloration degree was converted into the ratio of green and blue (G/B) with limit of detection as low as 0.036 µM (0.016 µg·g-1). Moreover, it allowed for fipronil analysis in water, soil and vegetable samples with good recovery between 87 % and 110 %, verifying extension application prospect of the aptamer-fueled colorimetry for on-field pesticide evaluation in food safety supervision.

Novel mesoporous silica surface loaded gold nanocomposites SERS aptasensor for sensitive detection of zearalenone.

Mycotoxin contamination is a severe threat to global food security, thus fast and effective detection of mycotoxins is of great significance. Herein, mesoporous silica surface loaded gold nanocomposites (MSN-Rh6G-AuNPs) were prepared as surface-enhanced Raman scattering (SERS) substrate, and the SERS aptasensor (MSN-Rh6G-AuNPs@apt) was further obtained by aptamer functionalization which can realize the quantitative and sensitive detection of zearalenone (ZEN). The small nanogaps between AuNPs made MSN-Rh6G-AuNPs present strong SERS performance under excitation light irradiation, while the aptamer performed the functions of ZEN recognition and Raman signal masking. The acquired results revealed that the SERS intensity at 1508 cm-1 had a good linear relationship with ZEN concentration of 3-200 ng/mL and the limit of detection (LOD) was calculated to be 0.0064 ng/mL. In addition, the designed SERS aptasensor was successfully applied to the detection of ZEN in corn, indicating great potential in practical implications.

Rapid and sensitive detection of zearalenone in corn using SERS-based lateral flow immunosensor.

Zearalenone (ZEN) is a universal mycotoxin contaminant in corn and its products. A surface-enhanced Raman scattering (SERS) based test strip was proposed for the detection of ZEN, which had the advantages of simplicity, rapidity, and high sensitivity. Core-shell Au@AgNPs with embedded reporter molecules (4-MBA) were synthesized as SERS nanoprobe, which exhibited excellent SERS signals and high stability. The detection range of ZEN for corn samples was 10-1000 µg/kg with the limit of detection (LOD) of 3.6 µg/kg, which is far below the recommended tolerable level (60 µg/kg). More importantly, the SERS method was verified by HPLC in the application on corn samples contaminated with ZEN, and the coincidence rates were in the range of 86.06%-111.23%, suggesting a high accuracy of the SERS assay. Therefore, the SERS-based test strip with an analysis time of less than 15 min is a promising tool for accurate and rapid detection of ZEN-field contamination.

Lung Cancer Stem Cell Markers as Therapeutic Targets: An Update on Signaling Pathways and Therapies.

Cancer stem cells, a relatively small group of self-renewing cancer cells, were first isolated from acute myeloid leukemia. These cells can play a crucial role in tumor metastasis, relapse, and therapy resistance. The cancer stem cell theory may be applied to lung cancer and explain the inefficiency of traditional treatments and eventual recurrence. However, because of the unclear accuracy and illusive biological function of cancer stem cells, some researchers remain cautious about this theory. Despite the ongoing controversy, cancer stem cells are still being investigated, and their biomarkers are being discovered for application in cancer diagnosis, targeted therapy, and prognosis prediction. Potential lung cancer stem cell markers mainly include surface biomarkers such as CD44, CD133, epithelial cell adhesion molecule, and ATP-binding cassette subfamily G member 2, along with intracellular biomarkers such as aldehyde dehydrogenase, sex-determining region Y-box 2, NANOG, and octamer-binding transcription factor 4. These markers have different structures and functions but are closely associated with the stem potential and uncontrollable proliferation of tumor cells. The aberrant activation of major signaling pathways, such as Notch, Hedgehog, and Wnt, may be associated with the expression and regulation of certain lung cancer stem cell markers, thus leading to lung cancer stem cell maintenance, chemotherapy resistance, and cancer promotion. Treatments targeting lung cancer stem cell markers, including antibody drugs, nanoparticle drugs, chimeric antigen receptor T-cell therapy, and other natural or synthetic specific inhibitors, may provide new hope for patients who are resistant to conventional lung cancer therapies. This review provides comprehensive and updated data on lung cancer stem cell markers with regard to their structures, functions, signaling pathways, and promising therapeutic target approaches, aiming to elucidate potential new therapies for lung cancer.

Green reduction of silver nanoparticles for cadmium detection in food using surface-enhanced Raman spectroscopy coupled multivariate calibration.

Cadmium (Cd) causes pervasive harm on human health as a poisonous heavy metal. This study proposed a surface-enhanced Raman spectroscopy (SERS) approach using sodium alginate (SA) as green reductant in combination with edge enrichment and chemometrics to build label-free Cd quantitative models. The silver nanoparticles synthesized by SA had good dispersion and enhancement factor (3.48 × 105). The optimal detection system was established by optimizing the concentration of specific molecules (trimercaptotriazine) and the droplet volume of measured liquid. Partial least squares models based on preprocessing methods and selection algorithms were compared. The results indicated that the model combined with first-order derivative preprocessing and competitive adaptive reweighted sampling algorithms achieved the best performance (Rp = 0.9989, RMSEP = 1.6225) with the limit of detection of 2.36 × 10-5 µg L-1 in food. The SERS approach combined with edge enrichment and chemometrics holds promise for rapid and label-free determination of Cd in food.

Intelligent evaluation of taste constituents and polyphenols-to-amino acids ratio in matcha tea powder using near infrared spectroscopy.

Matcha tea is rich in taste and bioactive constituents, quality evaluation of matcha tea is important to ensure flavor and efficacy. Near-infrared spectroscopy (NIR) in combination with variable selection algorithms was proposed as a fast and non-destructive method for the quality evaluation of matcha tea. Total polyphenols (TP), free amino acids (FAA), and polyphenols-to-amino acids ratio (TP/FAA) were assessed as the taste quality indicators. Successive projections algorithm (SPA), genetic algorithm (GA), and simulated annealing (SA) were subsequently developed from the synergy interval partial least squares (SiPLS). The overall results revealed that SiPLS-SPA and SiPLS-SA models combined with NIR exhibited higher predictive capabilities for the effective determination of TP, FAA and TP/FAA with correlation coefficient in the prediction set (Rp) of Rp > 0.97, Rp > 0.98 and Rp > 0.98 respectively. Therefore, this simple and efficient technique could be practically exploited for tea quality control assessment.

The Dynamic Alternation of Local and Systemic Tumor Immune Microenvironment During Concurrent Chemoradiotherapy of Cervical Cancer: A Prospective Clinical Trial.

PURPOSE: This work assessed local and systemic alternations of the tumor immune microenvironment during concurrent chemoradiation therapy (CCRT) of local advanced cervical cancer to estimate the optimal timing for immune therapy in relation to CCRT. METHODS AND MATERIALS: In this single-center prospective clinical trial, 55 patients with stage IIA through IVA cervical cancer were enrolled between December 2016 and November 2017. The median follow-up was 32.1 months. All patients received cisplatin concurrently with external beam radiation therapy combined with high-dose-rate brachytherapy. Tumor tissues and peripheral blood mononuclear cells (PBMCs) were collected before, during and after CCRT. We analyzed the changes in lymphocyte subpopulations, programmed death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, and the T cell receptor (TCR) repertoire that occurred throughout CCRT. RESULTS: The frequencies of CD4+ and PD-1+ T cells in PBMCs decreased after the start of CCRT, whereas that of inhibitory regulatory T cells increased. In the tumor tissues, CCRT decreased the numbers of CD4+ and CD8+ T cells and reduced the median percentage of positive cells expressing PD-L1 from 78.1% to 49.8%. As indicated by the numbers of unique clones, the TCRs of PBMCs exhibited greater diversity before CCRT than after CCRT. Greater TCR diversity in PBMCs before CCRT was associated with superior 30-month progression-free survival (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04-0.39; P = .001) and overall survival (HR, 0.17; 95% CI, 0.04-0.68; P = .004). CONCLUSIONS: CCRT for cervical cancer altered the tumor immune microenvironment by reducing CD4+ and CD8+ T lymphocyte populations, PD-1/PD-L1 expression, and TCR diversity. Higher TCR diversity in PBMCs before CCRT resulted in better survival and prognosis, indicating that CCRT might inhibit immune activation. Our results suggest that it might be more effective to administer immune checkpoint inhibitors before CCRT of cervical cancer rather than during or after CCRT.

Publisher Correction: Safety and feasibility of CRISPR-edited T cells in patients with refractory non-small-cell lung cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.