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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.

Accurate single-cell capture is a crucial step for single cell biological and chemical analysis. Conventional single-cell capturing often confront operational complexity, limited efficiency, cell damage, large scale but low accuracy, incompetence in the acquirement of nano-upgraded single-cell liquid. Flow cytometry has been widely used in large-scale single-cell detection, while precise single-cell isolation relies on both a precision operating platform and a microscope, which is not only extremely inefficient, but also not conducive to couple with modern analytical instruments. Herein, we develop a modular single-cell pipette (mSCP) microfluidic chip with high efficiency and strong applicability for accurate direct capture of single viable cell from cell suspensions into nanoliter droplets (30−1000 nL). The mSCP is used as a sampling platform for the detection of CdTe quantum dots in single cells with electrothermal atomic absorption spectrometry (ETAAS) for the first time. It also ensures precise single-cell sampling and detection by inductively coupled plasma mass spectrometry (ICP-MS).

The measurement of ultra-trace level of heavy metals in complex metrics is of great concern and challenge in life and environmental science. Herein, a novel thiol-functionalized covalent organic framework (COF) was prepared and achieved quantitative preconcentration of trace heavy metals in environmental water samples. The material was synthetized by two-step reactions, including a Schiff base reaction between 1,3,5-triformylphloroglucinol (Tp) and 2,5-divinyl-p-phenylenediamine (DvPa) to form preliminary COF (TpDvPa), and a thiol-ene “click” reaction between 1,2-ethanedithiol and the vinyl groups of TpDvPa to produce thiol-functionalized TpDvPa (TpDvPa-S-SH). By packing the material into a home-made SPE micro-column, and hyphenating the micro-column with inductively coupled plasma mass spectrometry (ICP-MS), trace level of Co2+, Ni2+ and Cd2+ in environmental waters could be successfully preconcentrated and measured, with LODs of 1.46, 1.38 and 0.10 ng L-1, respectively. The precisions were all less than 2.7%，with linear ranges extended from 5 to 1000 ng L-1. The proposed method was validated by the analysis of the certificated reference material (GBW08608), and measurement of Co2+, Ni2+ and Cd2+ in tap water, reservoir water, effluent of wastewater treatment plant and sea water, confirming the accuracy and feasibility of the method.

Aggregation-induced emission luminogens (AIEgens) exhibit efficient cytotoxic reactive oxygen species (ROS) generation capability and unique light-up features in the aggregated state, which have been well explored in image-guided photodynamic therapy (PDT). However, the limited penetration depth of light in tissue severely hinders AIEgens as a candidate for primary or adjunctive therapy for clinical applications. Coincidentally, microwaves (MWs) show a distinct advantage for deeper penetration depth in tissues than light. Herein, for the first time, we report AIEgen-mediated microwave dynamic therapy (MWDT) for cancer treatment. We found that two AIEgens (TPEPy-I and TPEPy-PF6) served as a new type of microwave (MW) sensitizers to produce ROS, including singlet oxygen (1O2), resulting in efficient destructions of cancer cells. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and live/dead assays reveal that the two AIEgens when activated by MW irradiation can effectively kill cancer cells with average IC-50 values of 2.73 and 3.22 μM, respectively. Overall, the ability of the two AIEgens to be activated by MW not only overcomes the limitations of conventional PDT, but also helps to improve existing MW ablation therapy by reducing the MW dose required to achieve the same therapeutic outcome, thus reducing the occurrence of side-effects of MW radiation., Graphical abstract Image 1, Highlights • For the first time, microwave-induced photodynamic therapy using AIEgens is reported. • The AIEgens showed significant cytotoxicity when excited by microwave toward HeLa cells. • AIEgens are promising candidates for image-guided microwave dynamic therapy. • This novel work opens a new door for AIEgens applications.

The efficient recognition of circulating tumor cells (CTCs) with an aptamer probe confers numerous benefits; however, the stability and binding affinity of aptamers are significantly hampered in real biological sample matrices. Inspired by the efficient preying mechanism by multiplex tubing feet and endoskeletons of sea urchins, we engineered a superefficient biomimetic single-CTC recognition platform by conjugating dual-multivalent-aptamers (DMAs) Sgc8 and SYL3C onto AuNPs to form a sea urchin-like nanoprobe (sea urchin-DMA-AuNPs). Aptamers Sgc8 and SYL3C selectively bind with the biomarker proteins PTK7 and EpCAM expressed on the surface of CTCs. CTCs were captured with 100% efficiency, followed by sorting on a specially designed multifunctional microfluidic configuration, integrating a single-CTC separation unit and a hydrodynamic filtrating purification unit. After sorting, background-free analysis of biomarker proteins in single CTCs was undertaken with inductively coupled plasma mass spectrometry by measuring the amount of 197Au isotope in sea urchin-DMA-AuNPs. With respect to a single-aptamer nanoprobe/-interface, the dual-aptamer nanoprobe improves the binding efficiency by more than 200% (Kd < 0.35 nM). The microchip facilitates the recognition of single CTCs with a sorting separation rate of 93.6% at a flow rate of 60 μL min-1, and it exhibits 73.8 ± 5.0% measurement efficiency for single CTCs. The present strategy ensures the manipulation and detection of a single CTC in 100 μL of whole blood within 1 h.

In aptamer-based assay schemes, aptamer probes not labeled with biomarkers have to be eliminated before testing, which may lead to a tremendous waste of precious probes. We herein propose a microfluidics system integrating an aptamer concentration gradient generator (Apt-CGG) and a dual single-cell culturing array (D-SCA), termed Mi-Apt-SCA. This facilitates the precise construction of a nanoscale-gradient microenvironment and the high-throughput profiling of single-cell growth/phenotypesiin situ/iwith the minimal consumption of Apt-probe. Unlike previous snakelike mixers, the choreographed winding-ravined aptamer dual-spiral micromixer (Apt-WD-mixer) in Apt-CGG could allow thorough blending to generate linear concentration gradients of aptamer (quasi-non-Newtonian fluid) under the action of continuous fluidic wiggles and bidirectionaliDean/iflow. In contrast to other trap-like systems, the mild vortex allows single-cell growth in an ultra-tender fluidic microenvironment using triple-jarless single-cell culture capsules (TriJ-SCCs) in D-SCA (shear stress: 3.43 × 10sup-5/supdynes per cmsup2/sup). The minimum dosage of aptamer probe required for exploring PDL1 protein expression in two hepatoma cell lines is only one-900th of that required by conventional protocols. In addition, this approach facilitated the profiling of ITF-β/cisplatin-mediated single-cell/cell-cluster phenotypes.

It is unclear how the efficacy of tezepelumab, approved for the treatment of type 2 ("T2") high and low asthma, compares to the efficacy of other biologics for T2-high asthma.To conduct an indirect comparison of tezepelumab to dupilumab, benralizumab, and mepolizumab in the treatment of eosinophilic asthma.We conducted a systematic review and Bayesian network meta-analyses. We identified randomized controlled trials (RCTs) indexed in PubMed, Embase, or CENTRAL between January 1, 2000, and August 12, 2022. Outcomes included exacerbation rates, prebronchodilator Forced Expiratory Volume (FEV1), and the Asthma Control Questionnaire (ACQ). (PROSPERO CRD42021232084) RESULTS: Ten RCTs (n = 9201) met eligibility. Tezepelumab (relative risk 0.63, 95% credible intervals [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, CI -33 to 170) and benralizumab (MD, 62, CI -22 to 150), though the CI crossed the null value of 0. Mepolizumab improved ACQ the most but was not significantly different from tezepelumab (tezepelumab vs. mepolizumab, MD, 0.14, CI -0.10 to 0.38). For efficacy by clinically important thresholds, tezepelumab, mepolizumab, and dupilumab achieved a99% 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 had90% chance for improving FEV1 by ≥50 mL, but none of the differences between biologics exceeded 100 mL.In individuals with eosinophilic asthma, tezepelumab and dupilumab were associated with greater improvements in exacerbation rates and lung function than benralizumab or mepolizumab, although below clinical thresholds.

Iodine ion is one of the most indispensable anions in living organisms, particularly being an important substance for the synthesis of thyroid hormones. Curcumin is a yellow-orange polyphenol compound derived from the rhizome of Curcuma longa L., which has been commonly used as a spice and natural coloring agent, food additives, cosmetics as well as Chinese medicine. However, excess curcumin may cause DNA inactivation, lead to a decrease in intracellular ATP levels, and trigger the tissue necrosis. Therefore, quantitative detection of iodine and curcumin is of great significance in the fields of food and life sciences. Herein, we develop nitrogen-doped fluorescent carbon dots (NCDs) as a multi-mechanism detection for iodide and curcumin in actual complex biological and food samples, which was prepared by a one-step solid-phase synthesis using tartaric acid and urea as precursors without adding any other reagents. An assembled NCDs-Hg2+ fluorescence-enhanced sensor for the quantitative detection of I− was established based on a fluorescence “turn-off-on” mechanism in a linear range of 0.3–15 μM with a detection limit of 69.4 nM and successfully quantified trace amounts of I− in water samples and urine sample. Meanwhile, the as-synthesized NCDs also can be used as a fluorescent quenched sensor for curcumin detection based on the synergistic internal filtration effect (IFE) and static quenching, achieving a good linear range of 0.1–20 μM with a satisfactory detection limit of 29.8 nM. These results indicate that carbon dots are potential sensing materials for iodine and curcumin detection for the good of our health., Graphical abstract Image 1, Highlights • Facile synthesis of nitrogen-doped carbon dots with tartaric acid and urea as precursors without any additives. • High-sensitive determination of I− with assembled NCDs-Hg2+ fluorescence-enhanced sensor. • Fluorescence sensor for curcumin detection with good linear response, high specificity, and high sensitivity. • Successful applications for I− and curcumin in water, urine, and foods.

Glutathione (GSH) plays important roles in various physiological processes, thus highly sensitive assay of GSH and timely warning of its variation at trace level in complex biological matrixes is of great significance. However, this is challenging due to the coexisting reductive biomolecules and dynamic change of GSH levels in responding to various stimuli which remain largely unexploited. Herein, we report a dual mode protocol for the assay of GSH based on nanoconjugate g-C

Chromium plays an irreplaceable role in the life system. The exploration of chromium is beneficial to reveal its physiological or pathological processes. In this study, a novel method was established for determination of chromium in gels by matrix-matched external standard method-laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The relative standard deviation of chromium signal intensity during ablation standard were less than 16% (n = 300), the correlation coefficient (R2) of LA-ICP-MS quantitative calibration curve was 0.9805, and the detection limit was 2.22 µg/g. The MCF-7 cells were used as an in vitro cell model, and two kinds of polyacrylamide gel electrophoresis (PAGE) method were used to separate the protein extract after chromium incubation. And then, the electrophoresis bands obtained by two electrophoresis methods were ablated respectively by LA-ICP-MS with line scan mode, and the weak chromium-containing protein bands were obtained in electrophoresis band. Finally, the LA-ICP-MS was used to measure and image the chromium in individual cell, and it was found that the cell element distribution map overlapped well with the cell contour map under the laser microscope.

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.

A nanoscale MOF-199 was synthesized in a simple and fast way by mixing btc triethylammonium and copper nitrate solution at room temperature and characterized by scanning electron microscopy, transm...

Terbium doped graphitic carbon nitride (g-C3N4:Tb) gives rise to two exceptional emissions at λex/λem = 290/490 nm and 290/546 nm, with extremely narrow peak widths of FWHM 200 nm. The modification of g-C3N4:Tb with HOOC-PEG-COOH provides a ratiometric fluorescent probe which ensures highly sensitive detection of alkaline phosphatase (ALP) activity based on the inner filter effect (IFE).

A series of zwitterionic poly(sulfobetaine methacrylate)s (PSBMAs) with various N-substituents, including n-alkyl, cyclohexyl, 2-hydroxyethyl, and phenyl, was synthesized in order to elucidate the ...

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.

Flow injection chromatography (FIC) or sequential injection chromatography (SIC) is a low-pressure liquid chromatography technique that uses flow injection or sequential injection hardware. Due to the constraints of this hardware, the separation resolution is low; often no more than 3–5 components are resolved. We have recently demonstrated the excellent resolving power of narrow open tubular (OT) columns for various biomolecules, and only moderate elution pressures are needed to carry out these separations. In this paper, we incorporate a narrow OT column with FIC and construct an FIC system using a pressure chamber and two injection valves to implement gradient elution. The resultant system not only improves the resolution but also reduces the system cost. When we use the system to separate peptides from trypsin-digested cytochrome C, we can resolve dozens of peptides (with resolutions of 0.5 or greater) at a speed of 12 samples per hour. When we use this system to separate a mixture containing 3 amino acids, we can base-line resolve these compounds at a speed of 1800 sample per hour.

Single-cell analysis facilitates perception into the most essential processes in life's mysteries. While it is highly challenging to quantify them at the single-cell level, where precise single-cell sampling is the prerequisite. Herein, a real-time single-cell quantitative platform was established for high-throughput droplet-free single-cell sampling into time-resolved (TRA) ICP-MS and real-time quantification of intracellular target elements. The concentrated cells (2 × 106 cells mL-1) were spontaneously and orderly aligned in a spiral microchannel with 104 periodic dimensional confined micropillars. The quantification is conducted simultaneously by internal standard inducing from another branch channel in the chip. The flow-rate-independent feature of single-cell focusing into an aligned stream within a wide range of fluidic velocities (100-800 μL min-1) facilitates high-throughput, oil-free, single-cell introduction into TRA-ICP-MS. The system was used for real-time exploration of intracellular antagonism of Cu2+ against Cd2+. an obvious antagonistic effect was observed for the MCF-7 cell by culturing for 3, 6, 9, and 12 h with 100 μg L-1 Cd2+ and 100 μg L-1 Cu2+, and a rivalry rate of 12.8% was achieved at 12 h. At identical experimental conditions, however, limited antagonistic effect was encountered for a bEnd3 cell within the same incubation time period, with a rivalry rate of 4.81%. On the contrary, an antagonistic effect was not observed for the HepG2 cell by culturing for 6 h, while an obvious antagonistic effect was found by further culturing to 12 h, with a rivalry rate of 10.43%. For all three cell lines, significant heterogeneity was observed among individual cells.

Herein, for the first time, we report copper-cysteamine (Cu-Cy) nanoparticles having Cu1+ instead of Cu2+ as an efficient heterogeneous Fenton-like catalyst for highly selective cancer treatment. I...

Alkaline phosphatase (ALP) plays critical roles in signal transmission and cell growth/apoptosis. Its abnormal level in serum/cell is tightly related to diseases, thus, serum and cellular ALP detection is of great significance for disease diagnosis. Herein, a novel approach for ALP assay based on a satellite-nanostructure is developed by conjugating lanthanide upconversion nanoparticles (UCNPs) with silver nanoclusters (AgNCs) through DNA bridging. UCNPs serve as the cores to conjugate with DNA fragments, followed by assembly of AgNCs as the satellites on UCNPs surface through the AgNCs-cytosine affinity, to produce the satellite-nanostructure of UCNPs@DNA-AgNCs. The presence of ALP converts phosphate groups into hydroxyl groups at DNA helix, weakening the coordination of DNA with UCNPs. As a result, the satellite AgNC labeling on DNA fragments strips off the UCNP surface. Silver is quantified by measuring isotope 107Ag with ICP-MS, which further derives the content of ALP by correlation to the number of AgNCs. A linear calibration range is obtained in 0.005-120 U/L with a detection limit of 1.8 mU/L. The distinct advantage of this strategy, on one hand, is the substrate-free feature that eliminates the intermediate process of substrate reaction, where the substrate activity decrease and its instability may significantly deteriorate the sensitivity. On the other hand, ALP triggers the production of a large number of AgNCs resulting in substantial amplification on ICP-MS signal to give a favorable sensitivity. This is the first attempt for ALP detection by inductively coupled plasma mass spectrometry.

Mercury speciation is of significant importance in environmental and biological analysis because its toxicity and metabolic behavior in the human body differ among species. Nanomaterial-assisted optical sensors are widely used for mercury ion detection but rarely applied in mercury speciation analysis. In this work, we develop a novel colorimetric sensing strategy for mercury speciation based on mercury-stimulated peroxidase mimetic activity of gold nanoparticles with the assistance of different reductants. In the presence of a weak reductant, only inorganic mercury can be reduced to Hg0, whereas both inorganic mercury and organic mercury can be reduced to Hg0 in the presence of a strong reductant. Due to the high affinity between Hg and Au, Hg0 deposits on the AuNP surface in the form of a Au-Hg amalgam, leading to a remarkable enhancement of peroxidase mimetic activity of gold nanoparticles. On the basis of this effect, inorganic mercury and total mercury can be detected by using 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate. The limits of detection for inorganic mercury and total mercury are 1.9 and 0.9 nM within 5-100 nM, respectively. The selectivity of this sensing system is high due to the specificity of Au-Hg interaction. Its practical applications are further demonstrated by organic mercury analysis in a fish sample and mercury speciation in a human hair sample.

The preparation of silver nanoparticles (AgNPs) with microbe or plant tissues as bio-template offers green approach, while it suffers from low harvest and purification is needed. Herein, we propose a facile protocol for one-pot preparation of AgNPs using M13 phage as bio-template by simply mixing AgNO3 solution with alkali M13 phage. In the obtained AgNPs-M13 phage composite, Cr(III) selectively coordinates with the amino residues on phage surface and leads to the aggregation of AgNPs through the bridging of M13 phages. This makes it feasible for colorimetric sensing of Cr(III) by measuring the absorbance ratio of AgNPs at 600 and 405 nm, which provides a LOD of 14 nmol/L. The composite also showed favorable bactericidal activity for both Gram-positive and Gram-negative bacteria, making it a promising candidate as antibacterial film in chromium-containing dental alloys and meanwhile serve as a sensing probe for monitoring the corrosion of the dental alloys.

A novel sensor array based on a (+)AuNP/AuNC nanocomposite was constructed for the selective discrimination of 10 types of Gram-negative bacteria (including 3 types of antibiotic-resistant strains) at a low concentration level of OD600 = 0.015. By recognizing the triple optical patterns of Gram-negative bacteria with the assistance of LDA, the sensor array is able to group the bacteria with respect to their species to each other.

ICP-MS is powerful in evaluating elemental species at the single-cell level, where high throughput/efficiency/precision are the keys for achieving statistically significant information based on massive data. We report an ultrahigh-throughput single-cell sampling system, consisting of a 3D spiral-helix tubing array to facilitate single-cell focusing into an orderly flow by inertial lift force and