Elsevier最新文献

The polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl-PCBs) are worldwide contaminants, and they tend to accumulate in wide variety of matrices. Therefore, due to the highest accumulation rate and recalcitrancy, their precise quantification makes significant concern about their toxicological effects on both humans and organisms. The objective of the study is that using hydrogen carrier gas instead of helium in gas chromatography with triple quadrupole (GC-MS/MS) systems could contribute to improvements on the analysis of dl-PCBs and PCDD/Fs in environmental matrices. The study evaluates the performance of the analysis time under the desired chromatographic resolution criteria for PCDD/Fs analysis, monitoring the plausible mass spectrum/fragmentation ratio changes, and finally the quantification limits of the targeted most toxic persistent organic compound congeners. The main advantage of using H₂ carrier gas is that the analysis time was drastically reduced (∼2.5 times) along with improved resolution due to an increase in peak widths in ∼0.6-0.7 factor. This study emphasized that the resolution was remarkably affected by the hexa congeners of PCDD/Fs; nearly baseline separation was observed. However, the sensitivity was slightly reduced (∼6-7 fold), which affected the calibration starting concentrations (0.8-3.2 pg/μl). The acquired mass spectra indicated that the lower fragment enhancement was noticeable, particularly on higher chlorinated ones (hexa, hepta, and octa congeners). The calculated ortho-effect values (1-58) in this study are consistent with the previous results in the literature (1-66 and 1-83) and supports the conclusion about the observations of lower fragment enhancement. Despite non-detection of hydrogenation, there is a significant difference in the quant/qual ion ratios in the studied compounds between helium and hydrogen carrier gas. The finalized methodology was examined, and the performance of the hydroinert® ion source was assessed over a three-month analysis period with a real sample analysis (RSD ≤17.8 %). The results indicate that hydrogen is a potential and reliable GC-MS/MS carrier gas in dl-PCBs and PCDD/Fs for environmental matrices.

While numerous needle-based continuous glucose monitoring (CGM) devices have been available today, the insufficient enzyme immobilization on monitoring sensor severely limited the detection sensitivity of CGM devices. This manuscript describes here a high-sensitivity continuous glucose sensor (CGS) by engineering a porous 3D cellulose/carbon nanotube (CNT) network on the working electrode, which subcutaneously increases the detection enzyme capacity and thus significantly enhances the signal intensity and sensitivity. Furthermore, a tapered needle made of soft resin is engraved into three distinct microgrooves where the glucose oxidase (GOD)-modified working electrode, Pt-modified counter electrode, and Ag/AgCl-modified reference electrode are separately constructed inside the microgrooves. Moreover, a miniature potentiostat tailored for signal acquisition, processing, and transmission is engineered. After incorporated with a wireless circuit, the proposed CGS achieves continuous glucose monitoring in interstitial fluid with a surprising sensitivity of 9.15 μA/mM/cm², as well as maintaining functionality for a period of up to 9 days in live rats. This work provides the public a high-sensitivity continuous glucose monitoring device.

Brain metastases account for a significant number of cancer-related deaths with poor prognosis and limited treatment options. Current diagnostic methods have limitations in resolution, sensitivity, inability to differentiate between primary and metastatic brain tumors, and invasiveness. Liquid biopsy is a promising non-invasive alternative; however, current approaches have shown limited efficacy for diagnosing brain metastases due to biomarker instability and low levels of detectable tumor-specific biomarkers. This study introduces an innovative liquid biopsy technique using extracellular vesicles (EVs) as a biomarker for brain metastases, employing the Brain nanoMET sensor. The sensor was fabricated through an ultrashort femtosecond laser ablation process and provides excellent surface-enhanced Raman Scattering functionality. We developed an in vitro model of metastatic tumors to understand the tumor microenvironment and secretomes influencing brain metastases from breast and lung cancers. Molecular profiling of EVs derived from brain-seeking metastatic tumors revealed unique, brain-specific signatures, which were also validated in the peripheral circulation of brain metastasis patients. Compared to primary brain tumor EVs, we also observed an upregulation of PD-L1 marker in the metastatic EVs. A machine learning model trained on these EV molecular profiles achieved 97% sensitivity in differentiating metastatic brain cancer from primary brain cancer, with 94% accuracy in predicting the primary tissue of origin for breast metastasis and 100% accuracy for lung metastasis. The results from this pilot validation suggest that this technique holds significant potential for improving metastasis diagnosis and targeted treatment strategies for brain metastases, addressing a critical unmet need in neuro-oncology.

Monitoring collagen denaturation is crucial for diagnosing collagen-related diseases such as tumors and fibrosis. Herein, we have developed specific probes to detect denatured collagen (d-Col) and collagen I (Col I), utilizing peptide probes with sequences (GOP)₁₀ and HVWMQAP, targeting at d-Col and Col I, respectively. These peptides were conjugated with 1,10-phenanthroline-5-carboxylic Acid (Phen), forming Phen-Ahx-(GOP)₁₀ and Phen-Ahx-HVWMQAP. Phen acts as both an antenna sensitizer and a chelator, coordinating with Terbium (III) and Europium (III) ions via its nitrogen atom, facilitating fluorescent emission in green and red, respectively. The investigation demonstrated that Tb³⁺ interacts with three (GOP)₁₀ peptide units through Phen, while Eu³⁺ connects with four units of Ahx-HVWMQAP peptides. Additionally, it is important to note that the structure of the peptides remains unchanged after chelating with the lanthanide ions, maintaining their integrity throughout the process. These probes have effectively demonstrated their ability to bind to specific collagen types with selectivity, enabling accurate identification of their presence. The excellent binding of these probes is due to the branched structure of the formed lanthanide-peptide complexes. A dose-dependent linear association was observed in the binding of Eu-[Phen-Ahx-HVWMQAP]₄ to Col I, with concentration levels ranging from 0.5 to 100 μM and a minimal detectable concentration of 0.113 μM. We anticipate that our developed probes will improve understanding of collagen remodeling and provide opportunities for the diagnosis of collagen-associated diseases.

The label-free detection and analysis of cancer cells using portable biosensing devices is crucial and promising. In this study, a novel reusable biosensing platform with a microfluidic-like based on terahertz plasmonic metasurfaces utilizing graphene integrated with an all-silicon groove for detecting liquid live cancer cells was developed. The proposed biosensor platform stands out because it can differentiate between the concentrations of three types of cancer cells by monitoring changes in resonance intensity and phase difference. The minimum concentration for identification was reduced to as low as 5 × 10⁴ cells/mL. We effectively constructed two-dimensional optical intensity cards using continuous wavelet transforms, which presented a more accurate approach for the recognition and determination of the three types of cancer cells. Our proposed biosensors show great potential for the determination and recognition of label-free cancer cells in aqueous environments as alternatives to non-immune biosensing technology.

Ambient ionization mass spectrometry (AIMS) allows rapid analysis of targets, while its overall selectivity is somewhat limited due to the lack of chromatographic separation. Recently, magnetic blade spray (MBS) has enhanced AIMS by incorporating immunomagnetic beads instead of the traditional coated blade spray (CBS) coating, thereby improving selectivity and sensitivity by targeted analyte detection and reducing background interference. In this study, an aptamer-functionalized and nucleic acid dye (GelRed)-loaded MS probe (AGMP) was developed and employed with MBS-based miniature mass spectrometer. Specifically, AGMP was assembled using aptamer-functionalized magnetic nanoparticles loaded with GelRed as mass tags for highly sensitive analysis of endoglin (CD105). For the preparation of AGMP, the CD105 binding aptamer of End-A2 was first selected through three rounds of capillary electrophoresis (CE)-SELEX with an optimal affinity of 62.3 pM. After optimizing the critical parameters that affected adsorption, desorption, and ionization efficiency, this method displayed satisfactory sensitivity with detection and quantitation limits of 0.2 and 1 ng/mL, respectively, as well as reliable recoveries of 90.1-106.8 % with relative standard deviations of 1.6-5.4 %. Besides, the method effectively mitigated the matrix effects with a slope deviation of 10.03 %, and exhibited good selectivity and environmental friendliness. Furthermore, this AGMP-based MBS strategy was successfully applied for CD105 detection in serum samples, demonstrating its potential for sensitive and on-site biomolecule analysis in complex matrices.

The liver plays a pivotal role in numerous critical physiological processes, functioning as the body's metabolic and detoxification center. Chronic liver disease can precipitate more severe health complications. The onset and progression of liver disease are often characterized by abnormal concentrations of ONOO^-, a highly reactive species whose direct capture and detection in physiological environments pose significant challenges. This work presents an innovative fluorescent probe NAP-ONOO derived from 1,8-naphthalimide, specifically engineered to dynamically monitor fluctuations of ONOO^- levels during liver injury. Due to its high biocompatibility, NAP-ONOO enabled to observe varying degrees of ONOO^- up-regulation across models of liver inflammatory injury, alcohol-induced damage, and drug-induced hepatotoxicity in cellular systems as well as in zebrafish and mice models. These findings highlight the potential of NAP-ONOO for identifying and detecting the liver injury biomarker ONOO^-. Furthermore, NAP-ONOO serves as potent tool for the identification of liver injuries, drug screening, and cellular imaging analyses, thereby promising avenues for future research endeavors.