Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans.

SARS-CoV-2 infection and mRNA vaccination induce robust CD4+ T cell responses that are critical for the development of protective immunity. Here, we evaluated spike-specific CD4+ T cells in the blood and draining lymph node (dLN) of human subjects following BNT162b2 mRNA vaccination using single-cell transcriptomics. We analyze multiple spike-specific CD4+ T cell clonotypes, including novel clonotypes we define here using Trex, a new deep learning-based reverse epitope mapping method integrating single-cell T cell receptor (TCR) sequencing and transcriptomics to predict antigen-specificity. Human dLN spike-specific T follicular helper cells (TFH) exhibited distinct phenotypes, including germinal center (GC)-TFH and IL-10+ TFH, that varied over time during the GC response. Paired TCR clonotype analysis revealed tissue-specific segregation of circulating and dLN clonotypes, despite numerous spike-specific clonotypes in each compartment. Analysis of a separate SARS-CoV-2 infection cohort revealed circulating spike-specific CD4+ T cell profiles distinct from those found following BNT162b2 vaccination. Our findings provide an atlas of human antigen-specific CD4+ T cell transcriptional phenotypes in the dLN and blood following vaccination or infection.

A Recognition-Molecule-Free Photoelectrochemical Sensor Based on Ti3C2/TiO2 Heterostructure for Monitoring of Dopamine.

Herein, a novel, recognition-molecule-free electrode based on Ti3C2/TiO2 composites was synthesized using Ti3C2 as the Ti source and TiO2 in situ formed by oxidation on the Ti3C2 surface for the selective detection of dopamine (DA). The TiO2 in situ formed by oxidation on the Ti3C2 surface not only increased the catalytically active surface for DA binding but also accelerated the carrier transfer due to the coupling between TiO2 and Ti3C2, resulting in a better photoelectric response than pure TiO2. Through a series of experimental conditions optimization, the photocurrent signals obtained by the MT100 electrode were proportional to the DA concentration from 0.125 to 400 µM, with a detection limit estimated at 0.045 µM. We also monitored DA in human blood serum samples using the MT100 electrode. The results showed good recovery, demonstrating the promising use of the sensor for the analysis of DA in real samples.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses and the development of vaccines aimed at the new variants1-4. SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells5-9. However, it remains unclear whether the additional doses induce germinal centre reactions whereby re-engaged B cells can further mature, and whether variant-derived vaccines can elicit responses to variant-specific epitopes. Here we show that boosting with an mRNA vaccine against the original monovalent SARS-CoV-2 mRNA vaccine or the bivalent B.1.351 and B.1.617.2 (Beta/Delta) mRNA vaccine induced robust spike-specific germinal centre B cell responses in humans. The germinal centre response persisted for at least eight weeks, leading to significantly more mutated antigen-specific bone marrow plasma cell and memory B cell compartments. Spike-binding monoclonal antibodies derived from memory B cells isolated from individuals boosted with either the original SARS-CoV-2 spike protein, bivalent Beta/Delta vaccine or a monovalent Omicron BA.1-based vaccine predominantly recognized the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted sorting approach, we isolated monoclonal antibodies that recognized the BA.1 spike protein but not the original SARS-CoV-2 spike protein from individuals who received the mRNA-1273.529 booster; these antibodies were less mutated and recognized novel epitopes within the spike protein, suggesting that they originated from naive B cells. Thus, SARS-CoV-2 booster immunizations in humans induce robust germinal centre B cell responses and can generate de novo B cell responses targeting variant-specific epitopes.

A label-free PEC aptasensor platform based on g-C3N4/BiVO4 heterojunction for tetracycline detection in food analysis.

A simple low-cost label-free photoelectrochemical (PEC) biosensing platform based on red blood cell shaped BiVO4 modified g-C3N4 was designed for tetracycline detection under room temperature. The prepared g-C3N4/BiVO4 heterojunction not only demonstrated a high surface area, excellent physicochemical stability and favorable PEC activity, but also can be employed as nanostructure support for aptamers to construct a visible-light-driven PEC aptasensor due to rich π-π accumulation sites. More importantly, the proposed PEC aptasensor showed a favorable linear toward tetracycline in the range from 5 × 10-9 to 2 × 10-7 M with a detection limit of 1.6 nM, which well covered the Food Standards Testing requirements. Practical food sample analysis further revealed the accuracy and feasibility of the g-C3N4/BiVO4 heterostructure based PEC platform. It is expected that such a label-free and cost-effective PEC strategy should act as a promising candidate for tetracycline determination in food quality control and supervision.

Upconversion NaYF4:Yb/Er-TiO2-Ti3C2 Heterostructure-Based Near-Infrared Light-Driven Photoelectrochemical Biosensor for Highly Sensitive and Selective d-Serine Detection.

A near-infrared (NIR) light-driven NaYF4:Yb/Er-TiO2-Ti3C2 (NYF-TiO2-Ti3C2) heterostructure-based photoelectrochemical (PEC) biosensing platform was constructed for highly sensitive d-serine (d-ser) detection. Accurate d-ser detection depends on the model biocatalyst, d-amino acid oxidase (DAAO), which converts d-ser into hydroxypyruvate and an equimolar concentration of hydrogen peroxide (H2O2) via an enzymatic reaction. The TiO2-Ti3C2 semiconductor and NaYF4:Yb/Er optical transducer formed a Schottky junction that provided an irreversible channel for electron transfer. Infrared light was converted into absorbable multiemission light, thereby effectively increasing light absorption. Simultaneously, the generated H2O2 rapidly scavenged photogenerated holes to separate electron-hole pairs, which amplified the photocurrent signal. Under optimal conditions, the NIR light-driven PEC biosensor exhibited an excellent PEC performance for d-ser detection, with a wide linear range of 2-1650 µmol L-1 and detection limit as low as 0.286 µmol L-1. Importantly, high detection reproducibility and accuracy were achieved using this strategy for analyzing human serum and rat cerebrospinal fluid (CSF) specimens. The admirable applicability of the NYF-TiO2-Ti3C2-based PEC biosensor for detecting d-ser may lead to further opportunities for detecting other disease-related biomarkers.

SARS-CoV-2 Omicron boosting induces de novo B cell response in humans.

The primary two-dose SARS-CoV-2 mRNA vaccine series are strongly immunogenic in humans, but the emergence of highly infectious variants necessitated additional doses of these vaccines and the development of new variant-derived ones 1-4 . SARS-CoV-2 booster immunizations in humans primarily recruit pre-existing memory B cells (MBCs) 5-9 . It remains unclear, however, whether the additional doses induce germinal centre (GC) reactions where reengaged B cells can further mature and whether variant-derived vaccines can elicit responses to novel epitopes specific to such variants. Here, we show that boosting with the original SARS- CoV-2 spike vaccine (mRNA-1273) or a B.1.351/B.1.617.2 (Beta/Delta) bivalent vaccine (mRNA-1273.213) induces robust spike-specific GC B cell responses in humans. The GC response persisted for at least eight weeks, leading to significantly more mutated antigen-specific MBC and bone marrow plasma cell compartments. Interrogation of MBC-derived spike-binding monoclonal antibodies (mAbs) isolated from individuals boosted with either mRNA-1273, mRNA-1273.213, or a monovalent Omicron BA.1-based vaccine (mRNA-1273.529) revealed a striking imprinting effect by the primary vaccination series, with all mAbs (n=769) recognizing the original SARS-CoV-2 spike protein. Nonetheless, using a more targeted approach, we isolated mAbs that recognized the spike protein of the SARS-CoV-2 Omicron (BA.1) but not the original SARS-CoV-2 spike from the mRNA-1273.529 boosted individuals. The latter mAbs were less mutated and recognized novel epitopes within the spike protein, suggesting a naïve B cell origin. Thus, SARS-CoV-2 boosting in humans induce robust GC B cell responses, and immunization with an antigenically distant spike can overcome the antigenic imprinting by the primary vaccination series.

Polydopamine-based molecularly imprinted electrochemical sensor for the highly selective determination of ecstasy components.

3,4-Methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) are the main components of illicit stimulant drugs, also known as "ecstasy", which belong to psychoactive medicine and tend to be increasingly abused among drug addicts worldwide. Herein, an electrochemical sensor based on molecularly imprinted polydopamine (MIP@PDA) was developed to detect MDA and MDMA using differential pulse voltammetry (DPV). An MIP film on a Au electrode was synthesized via electrochemical polymerization with the safe chemical DA as the polymerization monomer and the uncontrolled pharmaceutical intermediate 3,4-methylenedioxyphenethylamine (MDPEA) as the template molecule, which can provide a great quantity of specific binding sites and expand the practical application of the sensor. Due to the superior affinity of MIP@PDA to the target, the proposed sensor displayed excellent analytical performance, with LODs of 37 nM and 54 nM for the determination of MDA and MDMA, respectively. Additionally, this sensor presented suitable selectivity, stability, reproducibility and detection ability in practical urine samples, which suggested that it is a promising candidate as a rapid diagnostic method in drug investigations.

Inhibition mechanism of melanin formation based on antioxidant scavenging of reactive oxygen species.

The production of reactive oxygen species (ROS) leads to the generation of oxidative stress, which will result in the excessive production and accumulation of melanin in the body and even the occurrence of some skin diseases. The intervention of antioxidants can slow down the rate of melanin formation to some extent. In order to explore the relationship between ROS, melanin and antioxidants, this work investigated the effects of antioxidants on melanin formation by the scavenging of ROS in vitro, where zebrafish were used as the model organism in in vivo experiments. The results showed that the inhibition order of natural antioxidants on melanin formation was GSH > AA > GA and PG > BHT > BHA for synthetic antioxidants. Between natural antioxidants and synthetic antioxidants, the former mainly have a strong scavenging ability on ˙OH and 1O2, while the latter have a strong scavenging ability on O2˙-. At the same time, the results in vivo showed that GSH and PG within a certain concentration not only did not affect the hatchability, survival rate and teratogenic rate of zebrafish embryos, but also can significantly inhibit melanin formation in zebrafish embryos. The results of this study have an important guiding significance for the dosage of antioxidants used in the cosmetics and food industries.

Novel strategy of natural antioxidant nutrition quality evaluation in food: Oxidation resistance mechanism and synergistic effects investigation.

Effective evaluation methods for assessing the nutritional quality of foods that eliminate free radicals (i.e., foods that are classified as antioxidants) have long attracted the attention of scientists and the populace. In this case, constructing a corresponding photoelectrochemical sensor that has the advantages of being intuitive, rapid, and capable of accurate assessment for global antioxidant capacity is of profound significance. In this study, a novel g-C3N4/NiS/TiO2 photoelectric sensitive platform was constructed and afforded the possibility of a synergistic/antagonistic effect for estimating intrinsic antioxidant ingredients in food. Further investigation revealed that the internal influences of the compound structure, such as the redox potential and type of groups on the molecular benzene ring should be the main internal reasons for antioxidant synergistic behaviors. The photochemical strategy of concern is expected to provide benefits for on-site foods nutrition assays that should become a guide for health care diets.

Oxidized titanium carbide MXene-enabled photoelectrochemical sensor for quantifying synergistic interaction of ascorbic acid based antioxidants system.

Antioxidants can protect organization from damage by scavenging of free radicals. When two kinds of antioxidants are consumed together, the total antioxidant capacity might be enhanced via synergistic interactions. Herein, we develop a simple, direct, and effective strategy to quantify the synergistic interaction between ascorbic acid (AA) and other different antioxidants by photoelectrochemical (PEC) technology. MXene Ti3C2-TiO2 composites fabricated via hydrogen peroxide oxidation were applied as sensing material for the antioxidants interaction study. Under excitation of 470 nm wavelength, the photogenerated electrons transfer from the conduction band of TiO2 nanoparticles to the Ti3C2 layers, and the holes in TiO2 can oxidize antioxidants, leading to an enhanced photocurrent as the detection signal. This PEC sensor exhibits a good linear range to AA concentrations from 12.48 to 521.33 µM as well as obvious antioxidants capability synergism. In particular, the photocurrents of AA + gallic acid (GA) and AA + chlorogenic acid (CHA) mixtures at 476.19 µM increase 1.95 and 2.35 times respectively comparing with the sum of photocurrents of AA and GA or CHA. It is found that the synergistic effect is mainly depending on the fact that AA with the low redox potential (0.246 V vs NHE) can reduce other antioxidants radical to promote regeneration, improving the overall antioxidant performance. Moreover, it is proved that the greater redox potential of antioxidants, the more obvious the synergistic effect. In addition, the sensor was used to real sample assay, which provides available information towards food nutrition analysis, health products design and quality inspection.

Molecularly imprinted photo-electrochemical sensor for hemoglobin detection based on titanium dioxide nanotube arrays loaded with CdS quantum dots.

A novel molecularly imprinted photo-electrochemical sensor based on CdS/TiO2 nanocomposites was constructed for precisely detection of hemoglobin under visible light irradiation. CdS quantum dots were decorated on the surface of TiO2 nanorod arrays to form a heterojunction, which could enhance the charge-transfer efficiency for visible light and further increase the photo-generated current of the sensor. The molecularly imprinted polymer film assembled by dopamine monomer had achieved excellent performance for specifically binding with human hemoglobin. The hemoglobin bound on the sensor could catalyze the oxidation reaction of 4-chloro-1-naphthol by H2O2, generating insoluble product on the sensor surface and triggering an obviously decrease on photocurrent. The molecularly imprinted photo-electrochemical sensor exhibited excellent sensitivity, selectivity and stability for the detection of human hemoglobin. The sensor had a linear range from 0.01 to 100 ng mL-1 with a detection limit of 0.53 pg/mL (S/N = 3). Furthermore, the sensor was successfully applied on the analysis of human hemoglobin in the urine samples.

Carbon Nitride Quantum Dots Enhancing the Anodic Electrochemiluminescence of Ruthenium(II) Tris(2,2'-bipyridyl) via Inhibiting the Oxygen Evolution Reaction.

Although electrochemiluminescence (ECL) has been developed significantly in the past few decades, ECL efficiency in aqueous solutions remains quite low. Determination of the energy losses and development of new ECL-enhancing strategies are still of great value. In this work, we discovered a detrimental nonradiation relaxation pathway by a concurrent oxygen evolution reaction (OER) process in a well-known ruthenium(II) tris(2,2'-bipyridyl) (Ru(bpy)32+) aqueous ECL system due to similar surface-sensitive characteristics, and for the first time, a chemical strategy was developed by which carbon nitride quantum dots (CNQDs) could inhibit the surface OER process, alleviate the energy losses by nonradiation relaxation, and enhance the anodic ECL of Ru(bpy)32+. In the Ru(bpy)32+/CNQD system, CNQDs could enhance the anodic ECL of Ru(bpy)32+ in a nitrogen stream (10-fold) and ambient air (161-fold). The luminous and nitrogen-rich CNQDs were also confirmed not to serve as ECL luminophores, anodic coreactants, or donor/acceptors in ECL. The coreactant-free Ru(bpy)32+/CNQD system possesses several advantages over the common coreactant ECL system, such as low dosage (100 µg/mL CNQDs), favorable regeneration capacity, etc. As an example, ECL on-off detection of dopamine utilizing the Ru(bpy)32+/CNQD system was also developed to show prospects in ECL sensing. Besides, CNQDs were introduced into the classical Ru(bpy)32+/C2O42- coreactant ECL system, leading to suppressed OER and improved ECL signal. Overall, the proposed new ECL-enhancing strategy is promising for applicable ECL sensing, could be extended to other ECL luminophores with high oxidation potential, and enables an in-depth understanding of the ECL process and mechanism.

MoS2/ZnO-Heterostructures-Based Label-Free, Visible-Light-Excited Photoelectrochemical Sensor for Sensitive and Selective Determination of Synthetic Antioxidant Propyl Gallate.

Propyl gallate (PG) as one of the important synthetic antioxidants is widely used in the prevention of oxidative deterioration of oils during processing and storage. Determination of PG has received extensive concern because of its possible toxic effects on human health. Herein, we report a photoelectrochemical (PEC) sensor based on ZnO nanorods and MoS2 flakes with a vertically constructed p-n heterojunction. In this system, the n-type ZnO and p-type MoS2 heterostructures exhibited much better optoelectronic behaviors than their individual materials. Under an open circuit potential (zero potential) and visible light excitation (470 nm), the PEC sensor exhibited extraordinary response for PG determination, as well as excellent anti-inference properties and good reproducibility. The PEC sensor showed a wide linear range from 1.25 × 10-7 to 1.47 × 10-3 mol L-1 with a detection limit as low as 1.2 × 10-8 mol L-1. MoS2/ZnO heterostructure with proper band level between MoS2 and ZnO could make the photogenerated electrons and holes separated more easily, which eventually results in great improvement of sensitivity. On the other hand, formation of a five membered chelating ring structure of Zn(II) with adjacent oxygen atoms of PG played significant roles for selective detection of PG. Moreover, the PEC sensor was successfully used for PG analysis in different samples of edible oils. It demonstrated the ability and reliability of the MoS2/ZnO-based PEC sensor for PG detection in real samples, which is beneficial for food quality monitoring and reducing the risk of overuse of PG in foods.

Breathable and Skin-Mountable Strain Sensor with Tunable Stretchability, Sensitivity, and Linearity via Surface Strain Delocalization for Versatile Skin Activities' Recognition.

Metal film/elastomer-based strain sensors usually exhibit small rupture strain (<5%) because of the strain localization and necking effect of the metal film under tension. To achieve both high stretchability and wide linear region is still challenging for metal film-based strain sensors. Here, we propose a low-cost yet effective strategy for fabricating ultrathin, breathable, and skin-mountable strain sensors with high sensitivity (gauge factor from 7.2 to 474.8), high stretchability (up to 140%), and good linearity by regulating the surface strain delocalization in the metal film on elastomer substrate. On the basis of this phenomenon of strain delocalization, the sensitivity and linearity are further enhanced based on a novel diffraction-induced Au film with gradient thickness. Meanwhile, by means of the strain redistribution and Poisson effect, a novel biaxial strain sensor is designed for recognition of complex human motion. On the basis of the enhanced stretchability, linearity, skin-mountable, and breathable properties, the low-cost metal film-based strain sensors can be broadened as disposable wearables for human motion detection, emotional expression recognition, human interaction, and virtual reality.

Mediating physicochemical properties and paclitaxel release of pH-responsive H-type multiblock copolymer self-assembly nanomicelles through epoxidation.

pH-Sensitive H-type multiblock copolymers, namely, poly(methacrylic acid)2-block-epoxidized hydroxyl-terminated polybutadiene-block-poly(methacrylic acid)2 (PMAA2-b-epoHTPB-b-PMAA2), were synthesized by atom-transfer radical polymerization and subsequent in situ epoxidation by peracetic acid and characterized by 1H NMR, FT-IR and SEC techniques. The impact of epoxidation on the physicochemical and biomedical properties of copolymer self-assembly micelle nanoparticles was investigated by fluorescence spectrometry, DLS, TEM and an MTT assay. The experimental results indicated that epoxidation resulted in the formation of more stable copolymer micelle nanoparticles with a lower critical micelle concentration, smaller micelle size, and higher loading capacity and encapsulation efficiency of drugs than those without epoxidation. In particular, epoxidized copolymer micelle nanoparticles exhibited reasonable pH sensitivity at a pH of 5.3-5.6. The hydrophobic anticancer drug paclitaxel (PTX) displayed faster release rates from epoxidized nanomicelles than from unepoxidized nanomicelles in a PBS solution of a pH of 4.8-6.6, whereas in PBS of a pH of 7.4 smaller amounts of PTX were released from epoxidized nanomicelles than from unepoxidized nanomicelles. Epoxidized copolymer nanomicelles were reasonably biodegradable after the drug was released, and their degradation rate was faster than that of their unepoxidized counterparts. An MTT assay was performed to determine the biocompatibility of epoxidized copolymer micelle nanoparticles and the anticancer activities of PTX-loaded nanomicelles, which were important for applications in the therapy of cancers as a controlled-release drug carrier.

Prevalence of Antibodies against Neospora caninum in Père David's Deer ( Elaphurus davidianus ) in Beijing, China.

Neospora caninum is an apicomplexan protozoan and causes neuromuscular disorders in canids and abortions in cattle worldwide. We screened sera samples from 49 free-ranging Père David's deer ( Elaphurus davidianus ) in a nature reserve in Beijing, China, for antibodies against N. caninum using indirect fluorescence antibody tests and western blot tests. Antibodies were found in 27% of the deer. Western blot analysis revealed antibody reactivity against immunodominant N. caninum antigens of 16, 25, and 37 kDa in size together with other visible bands.