Chemical Nose Strategy with Metabolic Labeling and "Antibiotic-Responsive Spectrum" Enables Accurate and Rapid Pathogen Identification.

The worldwide antimicrobial resistance (AMR) dilemma urgently requires rapid and accurate pathogen phenotype discrimination and antibiotic resistance identification. The conventional protocols are either time-consuming or depend on expensive instrumentations. Herein, we demonstrate a metabolic-labeling-assisted chemical nose strategy for phenotyping classification and antibiotic resistance identification of pathogens based on the "antibiotic-responsive spectrum" of different pathogens. d-Amino acids with click handles were metabolically incorporated into the cell wall of pathogens for further clicking with dibenzocyclooctyne-functionalized upconversion nanoparticles (DBCO-UCNPs) in the presence/absence of six types of antibiotics, which generates seven-channel sensing responses. With the assistance of machine learning algorithms, eight types of pathogens, including three types of antibiotic-resistant bacteria, can be well classified and discriminated in terms of microbial taxonomies, Gram phenotypes, and antibiotic resistance. The present metabolic-labeling-assisted strategy exhibits good anti-interference capability and improved discrimination ability rooted in the unique sensing mechanism. Sensitive identification of pathogens with 100% accuracy from artificial urinary tract infection samples at a concentration as low as 105 CFU/mL was achieved. Pathogens outside of the training set can also be discriminated well. This clearly demonstrated the potential of the present strategy in the identification of unknown pathogens in clinical samples.

Modulating Visible-Light Driven NIR Lanthanide Polymer Photocatalysis for Amplification Detection of Exosomal Proteins and Cancer Diagnosis.

Near-infrared (NIR) luminescent lanthanide materials hold great promise for bioanalysis, as they have anti-interference properties. The approach of efficient luminescence is sensitization through a reasonable chromophore to overcome the obstacle of the aqueous phase. The involvement of the surfactant motif is an innovative strategy to arrange the amphiphilic groups to be regularly distributed near the polymer to form a closed sensitized space. Herein, a lanthanide polymer (TCPP-PEI70K-FITC@Yb/SDBS) is designed in which the meso-tetra(4-carboxyphenyl)porphine (TCPP) ligand serves as both a sensitizer and photocatalytic switch. The surfactant sodium dodecyl benzenesulfonate (SDBS) wraps the photosensitive polymers to form a hydrophobic layer, which augments the light-harvesting ability and expedites its photocatalysis. TCPP-PEI70K-FITC@Yb/SDBS is subsequently applied as an amplified photocatalysis toolbox for universally regulating the generation of reactive oxygen species (ROS). Boosting 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to produce blue products, a dual-mode biosensor is fabricated for improving the diagnosis of programmed death ligand-1-positive (PDL1) cancer exosomes. Exosomes were captured by Fe3O4 modified by the PDL1 aptamer, enabling replacement of alkaline phosphatase (ALP)-labeled multiple hybridized chains; then, the isolated ALP triggered a hydrolysis reaction to block the generation of oxTMB. Detection sensitivity improves by 1 order of magnitude through SDBS modulation, down to 104 particles/mL. The sensor performed well clinically in distinguishing cancer patients from healthy individuals, expanding physiological applications of near-infrared lanthanide luminescence.

Comparative transcriptome analysis reveals genes involved in trichome development and metabolism in tobacco.

BACKGROUND: The glandular trichomes of tobacco (Nicotiana tabacum) can efficiently produce secondary metabolites. They act as natural bioreactors, and their natural products function to protect plants against insect-pests and pathogens and are also components of industrial chemicals. To clarify the molecular mechanisms of tobacco glandular trichome development and secondary metabolic regulation, glandular trichomes and glandless trichomes, as well as other different developmental tissues, were used for RNA sequencing and analysis. RESULTS: By comparing glandless and glandular trichomes with other tissues, we obtained differentially expressed genes. They were obviously enriched in KEGG pathways, such as cutin, suberine, and wax biosynthesis, flavonoid and isoflavonoid biosynthesis, terpenoid biosynthesis, and plant-pathogen interaction. In particular, the expression levels of genes related to the terpenoid, flavonoid, and wax biosynthesis pathway mainly showed down-regulation in glandless trichomes, implying that they lack the capability to synthesize certain exudate compounds. Among the differentially expressed genes, 234 transcription factors were found, including AP2-ERFs, MYBs, bHLHs, WRKYs, Homeoboxes (HD-ZIP), and C2H2-ZFs. These transcription factor and genes that highly expressed in trichomes or specially expressed in GT or GLT. Following the overexpression of R2R3-MYB transcription factor Nitab4.5_0011760g0030.1 in tobacco, an increase in the number of branched glandular trichomes was observed. CONCLUSIONS: Our data provide comprehensive gene expression information at the transcriptional level and an understanding of the regulatory pathways involved in glandular trichome development and secondary metabolism.

Achieving Cross Time-Domain Multiplexed Signal Cascade and Cancer Exosomes Identification by Bridging Long Lifetime Phosphor to NIR-II Lanthanide Energy Transfer.

Designing lanthanide luminescence lifetime sensors in the second near-infrared (NIR-II) window holds great potentials for physiological studies. However, the single lifetime signal is confined to one or two orders of magnitude of signal variation, which limits the sensitivity of lifetime probes. In this study, a lifetime cascade system, i.e., ZGO:Mn, Eu-DNA-1/TCPP-PEI70K @Yb-AptEpCAM , with a variety of signals (τm , τn , τµ , τm /τn and τm /τµ ) is constructed for exosome identification using time-domain multiplexing. The sensitized ligand TCPP acts as both target-modulated switch and a bridge for connecting long lifetime ZGO:Mn, Eu-DNA-1 emitter to lanthanide Yb3+ . This drives successive dual-path energy transfer and forms two D(donor) -A(acceptor) pairs. The lifetime variation is dominantly modulated by arranging TCPP as energy intermediate relay to covert milliseconds to nanoseconds to microseconds. It enables a broad lifetime range of six orders of magnitude. The presence of exosome specifically recognizes aptamers on TCPP-PEI70K @Yb-AptEpCAM to impede D-A pairs and reverse multiplexed response signals of the lifetime cascade system. The ratio lifetime signals τm /τn and τm /τµ achieve prominent exosome quantification and exosome type differentiation attributed to signal amplification. The cascade system relying on lifetime criteria can realize precise quantization and provide an effective strategy for subsequent physiological study.

Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis.

BACKGROUND: It is unclear how the efficacy of tezepelumab, approved for the treatment of type 2 high and low asthma, compares to the efficacy of other biologics for type 2-high asthma. OBJECTIVES: We sought to conduct an indirect comparison of tezepelumab to dupilumab, benralizumab, and mepolizumab in the treatment of eosinophilic asthma. METHODS: The investigators conducted a systematic review and Bayesian network meta-analyses. They identified randomized controlled trials indexed in PubMed, Embase, or Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 2000, and August 12, 2022. Outcomes included exacerbation rates, prebronchodilator FEV1, and the Asthma Control Questionnaire. RESULTS: Ten randomized controlled trials (n = 9201) met eligibility. Tezepelumab (relative risk: 0.63; 95% credible interval [CI]: 0.46-0.86) was associated with significantly lower exacerbation rates than benralizumab and larger improvements in FEV1 compared to mepolizumab (mean difference [MD]: 66; 95% CI: -33 to 170) and benralizumab (MD: 62; 95% CI: -22 to 150), though the 95% CI crossed the null value of 0. Mepolizumab improved the Asthma Control Questionnaire score the most, but this improvement was not significantly different from that of tezepelumab (tezepelumab vs mepolizumab; MD: 0.14; 95% CI: -0.10 to 0.38). For efficacy by clinically important thresholds, tezepelumab, mepolizumab, and dupilumab achieved a >99% probability of reducing exacerbation rates by ≥50% compared to placebo, but benralizumab had only a 66% probability of doing so. Tezepelumab and dupilumab had a probability of 1.00 of improving prebronchodilator FEV1 by ≥100 mL above placebo. Compared to mepolizumab, dupilumab had >90% chance for improving FEV1 by ≥50 mL, but none of the differences between biologics exceeded 100 mL. CONCLUSIONS: In individuals with eosinophilic asthma, tezepelumab and dupilumab were associated with greater improvements (although below clinical thresholds) in exacerbation rates and lung function than benralizumab or mepolizumab.

Two-Dimensional Multi-parameter Cytometry Platform for Single-Cell Analysis.

A 2D flow cytometry platform, known as CytoLM Plus, was developed for multi-parameter single-cell analysis. Single particles or cells after hydrodynamic alignment in a microfluidic unit undergo first-dimension fluorescence and side scattering dual-channel optical detection. They were thereafter immediately directed to ICP-MS by connecting the microfluidic unit with a high-efficiency nebulizer to facilitate the second-dimension ICP-MS detection. Flow cytometry measurements of fluorescent microspheres evaluated the performance of CytoLM Plus for optical detection. 6434 fluorescence bursts were observed with a valid signal proportion as high as 99.7%. After signal unification and gating analysis, 6067 sets of single-particle signals were obtained with 6.6 and 6.2% deviations for fluorescence burst area and height, respectively. This is fairly comparable with that achieved by a commercial flow cytometer. Afterward, CytoLM Plus was evaluated by 2D flow cytometry measurement of Ag+-incubated and AO-stained MCF-7 cells. A program for 2D single-cell signal unification was developed based on the algorithm of screening in lag time window. In the present case, a lag time window of -4.2 ± 0.09 s was determined by cross-correlation analysis and two-parameter optimization, which efficiently unified the concurrent single-cell signals from fluorescence, side scattering, and ICP-MS. A total of 495 sets of concurrent 2D signals were screened out, and the statistical analysis of these single-cell signals ensured 2D multi-parameter single-cell analysis and data elucidation.

Dean-Flow-Coupled Elasto-Inertial Focusing Accelerates Exosome Purification to Facilitate Single Vesicle Profiling.

Exosomes are recognized as noteworthy biomarkers playing unprecedented roles in intercellular communication and disease diagnosis and treatment. It is a prerequisite to obtain high-purity exosomes for the comprehension of exosome biochemistry and further illustration of their functionality/mechanisms. However, the isolation of nanoscale exosomes from endogenous proteins is particularly challenging for small-volume biological samples. Herein, a Dean-flow-coupled elasto-inertial microfluidic chip (DEIC) was developed. It consists of a spiral microchannel with dimensional confined concave structures and facilitates elasto-inertial separation of exosomes with lower protein contaminants from cell culture medium and human serum. The presence of 0.15% (w/v) poly-(oxyethylene) controls the elastic lift force acting on suspended nanoscale particles and makes it feasible for field-free purification of integrity exosomes with a 70.6% recovery and a 91.4% removal rate for proteins. As a proof of concept, the technique demonstrated the individual-vesicle-level biomarker (EpCAM and PD-L1) profiling in combination with simultaneous aptamer-mediated analysis to disclose the sensibility for immune response. Overall, DEIC enables the collection of high-purity exosomes and exhibits potential in integration with downstream analyses of exosomes.

Interaction of Cellular Uptake of Nanosilver and Metallothionein Stress Expression Elucidated by 2D Single-Cell Analyses Based on LIF and ICP-MS.

The exploration of cytology mechanisms of nanosilver uptake, toxicity, and detoxification has become an important issue due to its widespread applications. Previous studies have shown differences in the toxic response of mammalian cells to nanosilver. However, the analysis results based on cell populations ignore the impact of cell uptake heterogeneity on the expression of associated stress proteins and cellular physiological activities. In this respect, this work investigated the interaction between silver uptake and metallothionein (MT) expression in individual cells. In addition, we have also preliminarily elucidated the sensitivity variation to AgNPs by using five cell lines, e.g., LX-2, HepG-2, SK-HEP-1, Huh-7, and MDA-MB-231, by adopting a two-dimensional (2D) high-throughput single-cell analysis platform coupling laser-induced fluorescence (LIF) and inductively coupled plasma mass spectrometry (ICP-MS). We developed a 2D data analysis method for one-to-one unification of fluorescence-mass spectrometry signals corresponding to a specific single cell. It indicated that there is no obvious correlation between cellular silver uptake and cell size, and the low MT expression of cells is more sensitive to silver nanoparticles. For each cell line, significant heterogeneity in MT expression was observed. This provides important information for understanding the potential heterogeneous effects of nanosilver on mammalian biological systems. Overall, detoxified cells are more tolerant to nanosilver and normal cells are more tolerant than cancer cells.

Single Cell Phenotypic Analysis for Cancer Stem Cell Identification by Dual-Isotope ICP-QMS.

Single cell phenotypic analysis is significant for clinical diagnosis, treatment, and prognosis of cancer. Accurate differentiation of cancer stem cell (CSC) subpopulations from a large number of cancer cells may become a cancer surveillance tool and provide important implications for the development of new CSC-targeted therapy strategies. Herein, we report a new approach based on dual-isotope inductively coupled plasma quadrupole mass spectrometry (ICP-QMS) for single cell phenotypic analysis. High-throughput single cell sampling was achieved by a spiral channel microfluidic chip for cell focusing and alignment, and single cell analysis was performed with time-resolved ICP-QMS by identifying the highly specific probes. This enables the monitoring of two surface protein markers (EpCAM and MUC1) of three cell types, i.e., HeLa, MCF-7, and HepG2, at single cell level. The analysis of breast cancer stem cells further confirmed its capability in distinguishing rare cell phenotypes. The present study provides promising possibilities for adopting ICP-QMS in biomedical investigations in terms of cell typing, stemness identification of tumor cells, and cell heterogeneity analysis.

Reactive Oxygen Species Triggered Oxidative Degradation of Polystyrene in the Gut of Superworms (Zophobas atratus Larvae).

Oxidative decomposition of polystyrene (PS) by insects has been previously demonstrated, yet little is known about the oxidation mechanism and its effect on the metabolism of plastics within the insect gut. Here, we demonstrate the generation of reactive oxygen species (ROS) in the gut of superworms (Zophobas atratus larvae) under different feeding trails, which in turn induced the oxidative decomposition of ingested PS. The ROS were commonly generated in the larva gut, and PS consumption resulted in a significant increase of ROS with a maximum ·OH of 51.2 µmol/kg, which was five times higher than in the bran feeding group. Importantly, scavenging of ROS significantly decreased the oxidative depolymerization of PS, indicating a vital role of ROS in effective PS degradation in the gut of superworms. Further investigation suggested that the oxidative depolymerization of PS was caused by the combinatorial effect of ROS and extracellular oxidases of gut microbes. These results demonstrate that ROS were extensively produced within the intestinal microenvironment of insect larvae, which greatly favored the digestion of ingested bio-refractory polymers. This work provides new insights into the underlying biochemical mechanisms of plastic degradation in the gut.

Lumi-HOF@Tb as Probes for Multiple Ratiometric Fluorescence and Chemiluminescence Sensing of α-Glucosidase.

The innovative assembly of luminescent hydrogen-bonded organic frameworks (HOFs) into multifunctional optical sensors is of great significance for developing advanced materials. Herein, we report a facile room-temperature synthesis strategy for the luminol HOF modified by Tb3+ (Lumi-HOF@Tb) and featuring sensitive chemiluminescence and fluorescence characteristics. Lumi-HOF@Tb is further pioneered as a dual-signal sensor for selective detection of α-glucosidase, a type of enzyme that plays a crucial role in the digestion of carbohydrates, and screening of its inhibitors. The sensor is constructed by combining the dual optical characteristics of luminol from the HOF and lanthanide ion assistance. From the hydrolysis of α-glucosidase and the 4-nitrophenyl-α-d-glucopyranoside (pNGP) substrate emerges the fluorescent luminol-p-nitrophenol (pNP) complex at 466 nm and changes the inner filter absorption to recover Tb3+ characteristic fluorescence at 546 nm; luminol also produces a chemiluminescence signal driven by H2O2 from additional glucose oxidase-catalyzed hydrolysis of α-d-glucose. Fluorescence and chemiluminescence assays for α-glucosidase activity have therefore been established and exhibit detection limits as low as 0.04 and 0.005 U L-1, respectively. This study not only presents the possibility of Ln3+-HOF-based sensors as intelligent optical materials by integration of fluorescence and chemiluminescence techniques but also demonstrates great potential for future applications in biosensing.

Insights into Surface Charge of Single Particles at the Orifice of a Nanopipette.

The dynamic behaviors of particles in various physical fields are related to the physicochemical properties of particles. Herein, we focus on the relationship between surface charge and dynamic behaviors of particles at the orifice of a nanopipette. We interestingly find that angle θ, a parameter related to the asymmetric degree of current spike, exhibits a strong relationship with surface charge of the particles. Both theoretical derivation and finite element simulation validate this relationship and thus could be used for quantifying the surface charge of single particles. Moreover, the gold and silica nanoparticles with the same size but different surface charges could be well distinguished and identified based on this relationship. This study not only gives a comprehensive understanding on the dynamic behaviors of particles outside the nanopipette but also opens a new way for investigating the surface charge of single particles.

Cryogenic Laser Ablation in a Rapid Cooling Chamber Ensures Excellent Elemental Imaging in Fresh Biological Tissues.

Laser ablation inductively coupled plasma mass spectrometry imaging of biologically significant targets largely relies on maintaining the original structures of samples. The temperature regulation capability of the ablation cell is crucial. Herein, a rapid cooling cryogenic sample cell (RCCSC) was developed. In the RCCSC chamber, the temperature reduces to -20 °C in 4 min with a minimum 10 h variation of ±0.1 °C at -26 °C. Improvements on the precision were achieved for the elements of interest in NIST 612 and spiked agarose gel under cryogenic conditions. The limits of detection improved by up to 1.57, 1.70, 3.26, and 1.33 fold for 63Cu, 66Zn, 57Fe, and 140Ce in agarose gel, respectively, were obtained under cryogenic conditions compared with those at room temperature. In a time period of testing (10 h), the cryogenic ablation maintains the native state of biological tissues with a high water content to ensure better elemental imaging by reducing thermal effects in ablation and suppressing evaporation of water. The rapid cooling cryogenic ablation significantly improves elemental imaging, as demonstrated by the imaging of various elements in coriander leaves. The present study may provide further insights into elemental distributions in fresh biological samples.

Nomogram to predict hemorrhagic transformation for acute ischemic stroke in Western China: a retrospective analysis.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is the most alarming complication of acute ischemic stroke. We aimed to identify risk factors for HT in Chinese patients and attempted to develop a nomogram to predict individual cases. METHODS: A retrospective study was used to collect the demographic and clinical characteristics of ischemic stroke patients at the Second Affiliated Hospital of Chongqing Medical University (development cohort) and Chongqing Sanbo Changan Hospital (validation cohort) from October 2013 to August 2020. Univariate analysis and multivariate analysis were used to identify the risk factors of patients in the development cohort. The nomogram was generated, and internal validation was performed. We used the area under the receiver-operating characteristic curve (AUC-ROC) to assess the discrimination and used the Hosmer-Lemeshow test to calibrate the model. To further verify the predictability and accuracy of the model, we performed an external validation of the patients in the validation cohort. RESULTS: A total of 570 patients were used to generate the nomogram. After univariate analysis and multivariate logistic regression, the remaining 7 variables (diabetes mellitus, atrial fibrillation, total cholesterol, fibrous protein, cerebral infarction area, NIHSS score and onset-to-treatment) were independent predictors of HT and used to compose the nomogram. The area under the receiver-operating characteristic curve of the model was 0.889 (95% CI, 0.841-0.938), and the calibration was good (P = 0.487 for the Hosmer-Lemeshow test). The model was validated externally with an AUC-ROC value of 0.832 (95% CI, 0.727-0.938). CONCLUSIONS: The nomogram prediction model in this study has good predictive ability, accuracy and discrimination, which can improve the diagnostic efficiency of HT in patients with acute ischemic stroke.

hsa_circ_0119412 overexpression promotes cervical cancer progression by targeting miR-217 to upregulate anterior gradient 2.

BACKGROUND: Mounting evidence summarizes that circRNA is closely implicated in the development of numerous cancers. Our study aimed to investigate the role of circ_0119412 whose function was not explored in cervical cancer. METHODS: RT-qPCR analysis was utilized for the expression analysis of circ_0119412, miR-217, and anterior gradient 2 (AGR2). CCK-8 assay, transwell assay, and MTT assay were employed to assess cell proliferation, migration, and adhesion, respectively. Animal study was performed to check the role of circ_0119412 in vivo. Bioinformatics analysis was applied to predict the downstream targets of circ_0119412. RIP assay was utilized to examine miRNAs potentially bound by circ_0119412. The interplays between miR-217 and circ_0119412 or AGR2 were validated by dual-luciferase reporter assay. RESULTS: circ_0119412 expression was highly enhanced in cervical tumor tissues and cancer cells. circ_0119412 overexpression aggravated cervical cancer cell proliferation, migration, and adhesion, and its overexpression was also conducive to tumor formation and growth in animal models. AGR2 was upregulated in cervical cancer by the public bioinformatics data. circ_0119412 bound to miR-217, and miR-217 bound to AGR 3'UTR. The promoting effects of circ_0119412 overexpression on cancer cell malignant phenotypes were reversed by miR-217 enrichment. In addition, increased expression of miR-217 suppressed AGR2 expression, thus weakening the functional effects of AGR2. CONCLUSION: circ_0119412 functioned as an oncogenic driver to promote the malignant development of cervical cancer by targeting the miR-217/AGR2 pathway.

Disentanglement Dynamics in Nonequilibrium Environments.

We theoretically study the non-Markovian disentanglement dynamics of a two-qubit system coupled to nonequilibrium environments with nonstationary and non-Markovian random telegraph noise statistical properties. The reduced density matrix of the two-qubit system can be expressed as the Kraus representation in terms of the tensor products of the single qubit Kraus operators. We derive the relation between the entanglement and nonlocality of the two-qubit system which are both closely associated with the decoherence function. We identify the threshold values of the decoherence function to ensure the existences of the concurrence and nonlocal quantum correlations for an arbitrary evolution time when the two-qubit system is initially prepared in the composite Bell states and the Werner states, respectively. It is shown that the environmental nonequilibrium feature can suppress the disentanglement dynamics and reduce the entanglement revivals in non-Markovian dynamics regime. In addition, the environmental nonequilibrium feature can enhance the nonlocality of the two-qubit system. Moreover, the entanglement sudden death and rebirth phenomena and the transition between quantum and classical nonlocalities closely depend on the parameters of the initial states and the environmental parameters in nonequilibrium environments.

The Impact of Human Papillomavirus Infection on Skin Cancer: A Population-Based Cohort Study.

BACKGROUND: This study investigated the correlation between a history of human papillomavirus (HPV) infection and skin cancer risk. MATERIALS AND METHODS: The study cohort comprised 26,919 patients with newly diagnosed HPV infection between 2000 and 2012; with the use of computer-generated numbers, patients without previous HPV infection were randomly selected as the comparison cohort. The patients in the HPV infection cohort were matched to comparison individuals at a 1:4 ratio by demographic characteristics and comorbidities. All study individuals were followed up until they developed skin cancer, withdrew from the National Health Insurance program, were lost to follow-up, or until the end of 2013. The primary outcome was subsequent skin cancer development. Cox proportional hazards regression analysis was used to analyze the risk of skin cancer with hazard ratios (HRs) and 95% confidence intervals (CIs) between the HPV and control cohort. RESULTS: The adjusted HR of skin cancer for patients with HPV relative to controls was 2.45 after adjusting sex, age and comorbidities. (95% CI, 1.44-4.18, p < .01). The subgroup analysis indicated that a patient with HPV infection had a significantly greater risk of skin cancer if they were aged >40 years. Notably, a risk of skin cancer was found in the group diagnosed with HPV within the first 5 years after the index date (adjusted HR, 3.12; with 95% CI, 1.58-5.54). Sensitivity analysis by propensity score, matching with balanced sex, age, and comorbidities, showed consistent results. CONCLUSION: A history of HPV infection is associated with the development of subsequent skin cancer in Taiwanese subjects, and the risk wanes 5 years later. IMPLICATIONS FOR PRACTICE: In this Taiwan nationwide cohort study, there was a 2.45-fold increased risk of developing new-onset skin cancers for patients with incident human papillomavirus (HPV) infection, compared with the matched controls. Furthermore, the risk was noticeably significant among patients aged >40 years. A prominent risk of skin cancers was found in the group diagnosed with HPV within the first 5 years after the index date in this study. The results of this analysis may raise consensus on the effect of HPV infection on the risk of skin cancers. Clinicians are encouraged to implement prudently on the differential diagnosis of skin cancers and HPV prevention and treatment, especially in older patients.

Novel Dielectric Barrier Discharge Trap for Arsenic Introduced by Electrothermal Vaporization: Possible Mechanism and Its Application.

In this work, a novel integrated dielectric barrier discharge (IDBD) reactor coupled to an electrothermal vaporizer (ETV) was established for arsenic determination. It is for the first time gas-phase enrichment (GPE) was fulfilled based on the hyphenation of ETV and DBD. The mechanisms of evolution of arsenic atomic and molecular species during vaporization, transportation, trapping, and release processes were investigated via X-ray photoelectron spectroscopy (XPS) and other approaches. Tentative mechanisms were deduced as follows: the newly designed DBD atomizer (DBDA) tube upstream to the air inlet fulfills the atomization of arsenic nanoparticles in vaporized aerosol, leading to free arsenic atoms that are indispensable for forming arsenic oxides; the DBD trap (DBDT) tube traps arsenic oxides under an O2-domininating atmosphere and then releases arsenic atoms under H2-dominating atmospheres. In essence, this process is a physical-chemical process rather than an electrostatic particle deposition. Such a trap and release sequence separates matrix interference and enhances analytical sensitivity. Under the optimized conditions, the method detection limit (LOD) was 0.04 mg/kg and the relative standard deviations (RSDs) were within 6% for As standard solution and real seafood samples, indicating adequate analytical sensitivity and precision. The mean spiked recoveries for laver, kelp, and Undaria pinnatifida samples were 95-110%, and the results of the certified reference materials (CRMs) were consistent with certified values. This ETV-DBD preconcentration scheme is easy and green and has low cost for As analysis in seafood samples. DBD was proved a novel ETV transportation enhancement and preconcentration technique for arsenic, revealing its potential in rapid arsenic analysis based on direct solid sampling ETV instrumentation.

ICP-MS and Photothermal Dual-Readout Assay for Ultrasensitive and Point-of-Care Detection of Pancreatic Cancer Exosomes.

Pancreatic cancer is known to have a high mortality rate, and its early diagnosis remains challenging due to the occult location of the pancreas. Exosomes derived from pancreatic cancer cells specifically express glypican-1, which may provide a liquid biopsy opportunity for the early diagnosis of pancreatic cancer. Herein, an inductively coupled plasma mass spectrometry (ICP-MS) and photothermal dual-readout platform was proposed for the ultrasensitive and point-of-care analysis of pancreatic cancer exosomes. In our design, exosomes were specifically captured by the sandwich immunoassay, and simultaneously, alkaline phosphatase was introduced in a low-background manner. The alkaline phosphatase triggered the hydrolysis of l-ascorbic acid 2-phosphate to produce ascorbic acid, followed by the etching of Fe3O4@MnO2 nanoflowers. As a result, the Mn2+ generated by etching stripped off the Fe3O4 and was quantified using ICP-MS. Meanwhile, the reduced Fe3O4@MnO2 was applied for the photothermal assay by oxidizing dopamine with MnO2. The protocol exhibits a detection limit down to 19.1 particles mL-1, which is the most sensitive protocol reported so far. To our knowledge, this is the first endeavor for exosome quantification using ICP-MS and photothermal methods. The developed dual-readout platform not only is capable of distinguishing pancreatic cancer patients from healthy people, but also shows excellent discernibility of individual differences at low concentrations of exosomes. This dual-readout assay is a promising platform for the ultrasensitive and point-of-care detection of exosomes in liquid biopsy-based early cancer diagnosis.

Label-Free Resistance Cytometry at the Orifice of a Nanopipette.

Development of new principles and techniques at the single-cell level is significantly important since cells as basic units of living organisms always bear large heterogeneity. Herein, we demonstrate a new electrochemical principle for single-cell analysis based on an ion current blockage at the orifice of a nanopipette, defined as resistance cytometry. The amplitude and the frequency of ion current transients show strong dependence on the size and the concentration of cells, which could be used for in situ cell sizing and counting. This technique shows good ability to detect the size change of RBCs under stimulations of different pH and osmotic pressure values. More importantly, the as-presented resistance cytometry can distinguish lymphoma blood cells from normal blood cells for patient blood samples. The as-presented resistance cytometry is label-free, non-invasive, and non-destructive, which not only opens new opportunities for single-cell analysis but also provides a new platform for cell-related medical diagnostic technologies.