Recombinant manufacturing of multispecies biolubricants.

Lubricin, a lubricating glycoprotein abundant in synovial fluid, forms a low-friction brush polymer interface in tissues exposed to sliding motion including joints, tendon sheaths, and the surface of the eye. Despite its therapeutic potential in diseases such as osteoarthritis and dry eye disease, there are few sources available. Through rational design, we developed a series of recombinant lubricin analogs that utilize the species-specific tissue-binding domains at the N- and C-termini to increase biocompatibility while replacing the central mucin domain with an engineered variant that retains the lubricating properties of native lubricin. In this study, we demonstrate the tissue binding capacity of our engineered lubricin product and its retention in the joint space of rats. Next, we present a new bioprocess chain that utilizes a human-derived cell line to produce O-glycosylation consistent with that of native lubricin and a purification strategy that capitalizes on the positively charged, hydrophobic N- and C-terminal domains. The bioprocess chain is demonstrated at 10 L scale in industry-standard equipment utilizing commonly available ion exchange, hydrophobic interaction and size exclusion chromatography resins. Finally, we confirmed the purity and lubricating properties of the recombinant biolubricant. The biomolecular engineering and bioprocessing strategies presented here are an effective means of lubricin production and could have broad applications to the study of mucins in general.

Immunoengineering can overcome the glycocalyx armour of cancer cells.

Cancer cell glycocalyx is a major line of defence against immune surveillance. However, how specific physical properties of the glycocalyx are regulated on a molecular level, contribute to immune evasion and may be overcome through immunoengineering must be resolved. Here we report how cancer-associated mucins and their glycosylation contribute to the nanoscale material thickness of the glycocalyx and consequently modulate the functional interactions with cytotoxic immune cells. Natural-killer-cell-mediated cytotoxicity is inversely correlated with the glycocalyx thickness of the target cells. Changes in glycocalyx thickness of approximately 10 nm can alter the susceptibility to immune cell attack. Enhanced stimulation of natural killer and T cells through equipment with chimeric antigen receptors can improve the cytotoxicity against mucin-bearing target cells. Alternatively, cytotoxicity can be enhanced through engineering effector cells to display glycocalyx-editing enzymes, including mucinases and sialidases. Together, our results motivate the development of immunoengineering strategies that overcome the glycocalyx armour of cancer cells.

Size-selective adhesion of calcium oxalate monohydrate crystals to lipid membranes.

The retention of calcium oxalate monohydrate (COM) crystals on cell membranes is pivotal in kidney stone formation. However, the mechanisms underlying COM attachment to neutral lipid membranes remain unclear. In this study, we demonstrate that COM exhibits size-selective adhesion to fluid lipid membranes composed of lipids with distinct sizes. Specifically, the (100) facet of COM induces the formation of new domains and establishes strong adhesion in the 18:1 (Δ9-Cis) PC (DOPC) membrane, while the (010) facet induces domains with strong adhesion in the 16:0-14:0 PC membrane. This selectivity is linked to the compatibility of the area per lipid in DOPC with the unit cell area of the (100) facet and the area per lipid in 16:0-14:0 PC with the (010) facet. Our Raman spectroscopic analyses reveal that the lipid acyl chains within these induced domains exhibit a higher degree of ordering compared to the typical fluid state of the membrane. This ordered structural alignment, combined with the lateral size-matching effect, suggests the potential formation of molecular arrays within the lipid bilayer that are in harmony with the lattice dimension of COM. To elucidate the strong adhesion between calcium oxalate and the phospholipid head group in the absence of a direct molecular structural correspondence, we propose that crystal water associated with COM can form hydrogen bonds with the phospholipid head group. Using structure visualization software, we demonstrate the feasibility of such hydrogen bonding networks. The formation of this network could serve to stabilize and enhance the attachment of COM to the lipid membrane. This mediation by water molecules offers a plausible explanation for the pronounced affinity at the interface.

Deciphering Oxygen-Independent Augmented Photodynamic Oncotherapy by Facilitating the Separation of Electron-Hole Pairs.

Developing Type-I photosensitizers provides an attractive approach to solve the dilemma of inadequate efficacy of photodynamic therapy (PDT) caused by the inherent oxygen consumption of traditional Type-II PDT and anoxic tumor microenvironment. The challenge for the exploration of Type-I PSs is to facilitate the electron transfer ability of photosensitization molecules for transforming oxygen or H2O to reactive oxygen species (ROS). Herein, we propose an electronic acceptor-triggered photoinduced electron transfer (a-PET) strategy promoting the separation of electron-hole pairs by marriage of two organic semiconducting molecules of a non-fullerene scaffold-based photosensitizer and a perylene diimide that significantly boost the Type-I PDT pathway to produce plentiful ROS, especially, inducing 3.5-fold and 2.5-fold amplification of hydroxyl (OH⋅) and superoxide (O2 -⋅) generation. Systematic mechanism exploration reveals that intermolecular electron transfer and intramolecular charge separation after photoirradiation generate a competent production of radical ion pairs that promote the Type-I PDT process by theoretical calculation and ultrafast femtosecond transient absorption (fs-TA) spectroscopy. By complementary tumor diagnosis with photoacoustic imaging and second near-infrared fluorescence imaging, this as-prepared nanoplatform exhibits fabulous photocytotoxicity in harsh hypoxic conditions and terrific cancer revoked abilities in living mice. We envision that this work will broaden the insight into high-efficiency Type-I PDT for cancer phototheranostics.

Recombinant Production of Glycoengineered Mucins in HEK293-F Cells.

Recombinant mucins are attractive polymeric building blocks for new biomaterials, biolubricants, and therapeutics. Advances in glycoengineered host cell systems now enable the recombinant production of mucins with tailored O-glycan side chains, offering new opportunities to tune the functionality of mucins and investigate the biology of specific O-glycan structures. Here, we provide a protocol for the scalable production of glycoengineered mucins and mucin-like glycoproteins in suspension-adapted HEK293-F cells. The protocol includes the preparation of engineered cell lines with homozygous knockout (KO) of glycosyltransferases using CRISPR/Cas9 and homology-directed repair (HDR) templates designed for efficient screening of clones. Strategies are provided for the stable introduction of mucin expression cassettes into the HEK293-F genome and the subsequent isolation of high-expressing cell populations. The high-titer production of recombinant mucins in conventional shaker flasks is described as an example production strategy using these cell lines.

Atomically Site Synergistic Effects of Dual-Atom Nanozyme Enhances Peroxidase-like Properties.

Pursuing effective and generalized strategies for modulating the electronic structures of atomically dispersed nanozymes with remarkable catalytic performance is exceptionally attractive yet challenging. Herein, we developed a facile "formamide condensation and carbonization" strategy to fabricate a library of single-atom (M1-NC; 6 types) and dual-atom (M1/M2-NC; 13 types) metal-nitrogen-carbon nanozymes (M = Fe, Co, Ni, Mn, Ru, Cu) to reveal peroxidase- (POD-) like activities. The Fe1Co1-NC dual-atom nanozyme with Fe1-N4/Co1-N4 coordination displayed the highest POD-like activity. Density functional theory (DFT) calculations revealed that the Co atom site synergistically affects the d-band center position of the Fe atom site and served as the second reaction center, which contributes to better POD-like activity. Finally, Fe1Co1 NC was shown to be effective in inhibiting tumor growth both in vitro and in vivo, suggesting that diatomic synergy is an effective strategy for developing artificial nanozymes as novel nanocatalytic therapeutics.

Photoinduced Electron Transfer Modulated Photoelectric Signal: Toward an Organic Small Molecule-Based Photoelectrochemical Platform for Formaldehyde Detection.

Photoelectrochemical (PEC) sensing has been rapidly evolving in recent years, while the introduction of small molecules with specific recognition functions into the sensing interface remains a nascent area of study. In this work, we reported a PEC biosensor for formaldehyde (FA) detection based on photoinduced electron transfer (PET)-gated electron injection between organic small molecules and inorganic semiconducting substrates. Specifically, an FA-responsive probe (NA-FA-COOH) and TiO2 nanoarrays were integrated to construct a PEC platform (NFC/TiO2) via a coordination bond. NFC served simultaneously as a target-specific recognition element and a modulator of photoinduced electron injection. Treatment of NFC/TiO2 by FA would suppress the intramolecular PET process, with the quenched photocurrent signal due to the changed carrier transfer pathway, thus establishing the PEC platform for FA based on effective PET modulation. The proposed PEC system exhibited high selectivity and sensitivity, with a low detection limit of 0.071 µM. This study presents a novel perspective on the use of organic small molecules with a PET effect for advanced PEC bioanalysis.

Microelectromechanical Microsystems-Supported Photothermal Immunoassay for Point-of-Care Testing of Aflatoxin B1 in Foodstuff.

Accurate identification of acutely toxic and low-fatality mycotoxins on a large scale in a quick and cheap manner is critical for reducing population mortality. Herein, a portable photothermal immunosensing platform supported by a microelectromechanical microsystem (MEMS) without enzyme involvement was reported for point-of-care testing of mycotoxins (in the case of aflatoxin B1, AFB1) in food based on the precise satellite structure of Au nanoparticles. The synthesized Au nanoparticles with a well-defined, graded satellite structure exhibited a significantly enhanced photothermal response and were coupled by AFB1 antibodies to form signal conversion probes by physisorption for further target-promoted competitive responses in microplates. In addition, a coin-sized miniature NIR camera device was constructed for temperature acquisition during target testing based on advanced MEMS fabrication technology to address the limitation of expensive signal acquisition components of current photothermal sensors. The proposed MEMS readout-based microphotothermal test method provides excellent AFB1 response in the range of 0.5-500 ng g-1 with detection limits as low as 0.27 ng g-1. In addition, the main reasons for the efficient photothermal transduction efficiency of Au with different graded structures were analyzed by finite element simulations, providing theoretical guidance for the development of new Au-based photothermal agents. In conclusion, the proposed portable micro-photothermal test system offers great potential for point-of-care diagnostics for residents, which will continue to facilitate immediate food safety identification in resource-limited regions.

Convergent Approaches to Delineate the Metabolic Regulation of Tumor Invasion by Hyaluronic Acid Biosynthesis.

Metastasis is the leading cause of breast cancer-related deaths and is often driven by invasion and cancer-stem like cells (CSCs). Both the CSC phenotype and invasion are associated with increased hyaluronic acid (HA) production. How these independent observations are connected, and which role metabolism plays in this process, remains unclear due to the lack of convergent approaches integrating engineered model systems, computational tools, and cancer biology. Using microfluidic invasion models, metabolomics, computational flux balance analysis, and bioinformatic analysis of patient data, the functional links between the stem-like, invasive, and metabolic phenotype of breast cancer cells as a function of HA biosynthesis are investigated. These results suggest that CSCs are more invasive than non-CSCs and that broad metabolic changes caused by overproduction of HA play a role in this process. Accordingly, overexpression of hyaluronic acid synthases (HAS) 2 or 3 induces a metabolic phenotype that promotes cancer cell stemness and invasion in vitro and upregulates a transcriptomic signature predictive of increased invasion and worse patient survival. This study suggests that HA overproduction leads to metabolic adaptations to satisfy the energy demands for 3D invasion of breast CSCs highlighting the importance of engineered model systems and multidisciplinary approaches in cancer research.

Point-of-Care Immunoassay Based on a Multipixel Dual-Channel Pressure Sensor Array with Visual Sensing Capability of Full-Color Switching and Reliable Electrical Signals.

The point-of-care (POC) method with affordability and portability for the sensitive detection of biological substances is an emerging topic in rapid disease screening and personalized medicine. In this work, we demonstrated a diverse responsive platform based on a dual-channel pressure sensor (DCPS). The DCPS had a multilayer flexible architecture consisting of a photonic hydrogel with chromatic transitions and a piezoresistive pressure sensor as the electrical data transmission unit, both of which had the property of pressure-induced mechanical stimulus feedback. By incorporating a platinum nanoparticles-labeled detection antibody (PtNPs-dAb) into the sandwich-type immunoreaction for the target carcinoembryonic antigen (CEA, as a model analyte), gas decomposition could be triggered by the addition of hydrogen peroxide (H2O2) to induce a significant increase under pressure in a closed chamber. Meanwhile, the DCPS enabled an accurate electrical signal output, and the photonic hydrogel converted spatiotemporal stimuli into eye-readable colorations with string brilliance. In this way, the target concentration could be quantificationally related to the electrical response and intuitively perceived through visible color alterations. Under optimal conditions, a sensitive determination of CEA was performed in a detectable range of 0.3-60 ng/mL with a limit of detection (LOD) of 0.13 ng/mL. In addition, the proposed protocol had satisfactory selectivity, accuracy, and reproducibility. Furthermore, an array-based immunoassay device was fabricated to conceptually validate its application potential in high-throughput biomedical detection and inspire a dual-signal POC diagnostic platform in a friendly way for resource-limited settings.

Dual-Signaling Photoelectrochemical Biosensor Based on Biocatalysis-Induced Vulcanization of Bi2MoO6 Nanosheets.

A magnetic-assisted photoelectrochemical (PEC) and colorimetric (CL) dual-modal biosensing platform with high precision was established to monitor prostate-specific antigen (PSA) based on Bi2MoO6 nanosheets (BMO) by coupling the aptamer-guided hybridization chain reaction (HCR) with the hydrolysate-induced vulcanization reaction of Bi2MoO6 nanosheets. Upon addition of PSA, trigger DNA (tDNA) was released by the interaction between the target analyte and the aptamer and then further hybridized with anchor DNA (aDNA) conjugated on magnetic beads (MBs). The as-released tDNA initiated the target-assisted HCR in the presence of two alternating hairpin sequences (Bio-H1 and Bio-H2) to produce nicked long double-stranded DNA on the surface of MBs, where numerous alkaline phosphatase (ALP) enzymes could assemble with MBs through the biotin-avidin reaction, resulting in the hydrolysis of sodium thiophosphate (TP) to H2S. The as-produced H2S reacted with BMO to form vulcanized BMO (BMO-S), thus leading to obvious enhanced PEC performance under visible light with the color change from light yellow to brown. Having optimized the test conditions, the magnetic-assisted biosensing system holds a good quantitative diagnosis sensitivity area in a range of 5.0 pg mL-1-100 ng mL-1 with a calculated detection limit down to 3.5 pg mL-1. Meanwhile, a visual colorimetric assay on basis of the change in the color of the materials was also realized. Given the exceptional performance of the constructed biosensor, it may possess great promise as an advanced bioanalytical tool for practical applications.

Luminescent Composite Carbon/SiO2 Structures: Synthesis and Applications.

Luminescent carbon nanostructures (CNSs) have attracted great interest from the scientific community due to their photoluminescent properties, structural features, low toxicity, and a great variety of possible applications. Unfortunately, a few problems hinder their further development. These include the difficulties of separating a mixture of nanostructures after synthesis and the dependence of their properties on the environment and the aggregate state. The application of a silica matrix to obtain luminescent composite particles minimizes these problems and improves optical properties, reduces photoluminescence quenching, and leads to wider applications. We describe two methods for the formation of silica composites containing CNSs: inclusion of CNSs into silica particles and their grafting onto the silica surface. Moreover, we present approaches to the synthesis of multifunctional particles. They combine the unique properties of silica and fluorescent CNSs, as well as magnetic, photosensitizing, and luminescent properties via the combination of functional nanoparticles such as iron oxide nanoparticles, titanium dioxide nanoparticles, quantum dots (QDs), and gold nanoclusters (AuNCs). Lastly, we discuss the advantages and challenges of these structures and their applications. The novelty of this review involves the detailed description of the approaches for the silica application as a matrix for the CNSs. This will support researchers in solving fundamental and applied problems of this type of carbon-based nanoobjects.

Photoelectrochemical bioanalysis of microRNA on yolk-in-shell Au@CdS based on the catalytic hairpin assembly-mediated CRISPR-Cas12a system.

This work reports on the proof-of-concept of a photoelectrochemical (PEC) biosensor with a horseradish peroxidase-single stranded DNA-encoded magnetic bead (MB-ssDNA-HRP) signal probe cleaved by the catalytic hairpin assembly (CHA)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a system for the quantification of microRNA (miR-21) by using yolk-in-shell Au@CdS as a photoactive material.

Contactless Photoelectrochemical Biosensor Based on the Ultraviolet-Assisted Gas Sensing Interface of Three-Dimensional SnS2 Nanosheets: From Mechanism Reveal to Practical Application.

This work reports a contactless photoelectrochemical biosensor based on an ultraviolet-assisted gas sensor (UV-AGS) with a homemade three-dimensional (3D)-SnS2 nanosheet-functionalized interdigitated electrode. After rigorous examination, it was found that the gas responsiveness accelerated and the sensitivity increased using the UV irradiation strategy. The effects of the interlayer structure and the Schottky heterojunction on the gas-sensitive response of O2 and NH3 under UV irradiation were further investigated theoretically by 3D electrostatic field simulations and first-principles density functional theory to reveal the mechanism. Finally, a UV-AGS device was developed to quantify the blood ammonia bioassay in a small-volume whole blood sample by alkalizing blood to release gas-phase ammonia with a linear range of 25-5000 µM with a limit of detection (LOD) of 29.5 µM. The device also enables a rapid immunoassay of human cardiac troponin I (cTnI) with a linear range of 0.4-25.6 ng/mL and an LOD of 0.37 ng/mL using a urease-labeled antibody as the immune recognition molecule. Both analyses showed satisfying specificity and stability, suggesting that the device can be applied to practical assays and is of great potential to increase the value of gas-sensitive sensors in chemical biosensing.

Pressure-Based Immunoassays with Versatile Electronic Sensors for Carcinoembryonic Antigen Detection.

Pressure-based immunoassays have been studied for point-of-care testing for which increasing the sensitivity is still a challenge. In this study, we described an enhanced pressure-based immunoassay with a versatile electronic sensor for the sensitive biological analysis. The versatile electronic sensor had multifunctional sensing capabilities with temperature and pressure recording. Magnetic bead-modified capture antibody and platinum nanoparticle-labeled detection antibody were used as the biorecognition element of the target carcinoembryonic antigen (CEA) (as a model analyte) and would form a sandwich-type immune complex with CEA. After simple magnetic separation, this complex was transferred into the detection chamber, which contained both hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB). With the catalytic ability of PtNPs, the "H2O2-TMB-PtNPs" system was catalyzed to generate a large amount of oxygen (O2) and photothermal agent of oxidizer TMB (ox-TMB). Meanwhile, in a sealed chamber, further irradiation with an 808 nm near-infrared laser led to a triple-step signal amplification strategy of pressure increase, temperature increase, and gas thermal expansion to receive a strong electrical signal through the electronic sensor in real time. Thus, the amplified electrical signal from the electronic sensor could reveal the target concentration. In addition, we also verified that the synergistic system with two physical quantities had a lower limit of detection and a wider detection range compared to the detection system with a single physical quantity. In general, this immunoassay not only helped in exploring an effective signal amplification pathway but also offered an opportunity for the development of versatile electronic sensors in point-of-care settings.

A polypyrrole-polydimethylsiloxane sponge-based compressible capacitance sensor with molecular recognition for point-of-care immunoassay.

A highly compressible and all-solid-state polydimethylsiloxane (PDMS) sponge-based flexible capacitance sensor modified with polypyrrole (PPy) was designed as the signal readout for the sensitive immunoassay of prostate-specific antigen (PSA). This system mainly consisted of a compressible capacitance sensor, immunoreaction protocol and gas delivery channel. The capacitance sensor was connected to a single microplate by a syringe, whereas the immunoreaction was carried out in the microplate. The conjugated catalase with the detection antibody via biotin-streptavidin interaction could trigger gas generation to cause a pressure change, thus resulting in the increase in the capacitance of the PPy-PDMS sponge observed with an LCR-6100 digital bridge capacitance meter. By coupling with the capacitance sensor, the capacitance change could be monitored in real time to achieve portable detection of PSA. Under the optimal conditions, the compressible supercapacitor PPy-PDMS sponge showed great electrochemical performance and remained stable under compressive strains. The capacitance increased with increasing target PSA concentration within a dynamic working range of 0.1-50 ng mL-1 at a detection limit of 57 pg mL-1. Moreover, acceptable reproducibility, precision and high specificity were obtained from PSA analysis, and were in good accordance with the commercial PSA ELISA kit.

Distance-dependent visual fluorescence immunoassay on CdTe quantum dot-impregnated paper through silver ion-exchange reaction.

A paper-based visual fluorescence immunoassay is presented for the detection of matrix metalloproteinase-7 (MMP7) that is related to renal cancer. The method is based on the distance-dependent fluorescence quenching of CdTe quantum dots (QDs) on a nitrocellulose membrane by Ag+ following a sandwich-type immunoreaction on microtiter wells using silver nanoparticle (AgNP)-labeled secondary antibody- and primary antibody-coated microtiter wells. The silver nanoparticles captured in the well are dissolved with HNO3, while the quenching effect of QDs is based on silver ion-exchange reaction under 365-nm excitation light irradiation. Increasing concentration of released Ag+, thus higher concentration of the protein, leads to an increased distance of quenching on the nitrocellulose membrane. The paper-based immunoassay by combination of AgNP-assisted ion-exchange reaction with QD gives good distance-dependent responses and allows the detection of MMP7 at a concentration as low as 7.3 pg mL-1. The coefficients of variation are less than 6.9% and 12.4% for intra-assay and inter-assay, respectively. High specificity and long-term stability are achieved during the assay. Importantly, the testing of human serum samples using our strategy shows well-matched results with commercial human MMP7 ELISA kits. Graphical abstract A distance-dependent visual immunoassay is developed for the determination of serum matrix metalloproteinase-7 on CdTe quantum dot-impregnated paper with silver ion-exchange reaction.

Litmus-Body: A Molecularly Targeted Sensor for Cell-Surface pH Measurements.

Precise pH measurements in the immediate environment of receptors is essential for elucidating the mechanisms through which local pH changes associated with diseased phenotypes manifest into aberrant receptor function. However, current pH sensors lack the ability to localize and target specific receptor molecules required to make these measurements. Herein we present the Litmus-body, our recombinant protein-based pH sensor, which through fusion to an anti-IgG nanobody is capable of piggybacking on IgG antibodies for molecular targeting to specific proteins on the cell surface. By normalizing a pH-dependent green fluorescent protein to a long Stokes shift red fluorophore or fluorescent protein, we readily report pH independent of sensor concentration using a single 488 nm excitation. Our Litmus-body showed excellent responsiveness in solution, with a greater than 50-fold change across the regime of physiological pH. The sensor was further validated for use on live cells and shown to be specific to the protein of interest. In complex with our Litmus-body, cetuximab therapeutic antibody retained its functionality in binding and inhibiting ligand interaction of its target epidermal growth factor receptor (EGFR), triggering receptor-mediated endocytosis that allowed tracking of local pH from the cell surface through the endocytic pathway.

Alterations in Gut Microbiota of Gestational Diabetes Patients During the First Trimester of Pregnancy.

Background: Dysbiosis of human gut microbiota is associated with a wide range of metabolic disorders, including gestational diabetes mellitus (GDM). Yet whether gut microbiota dysbiosis participates in the etiology of GDM remains largely unknown. Objectives: Our study was initiated to determine whether the alternations in gut microbial composition during early pregnancy linked to the later development of GDM, and explore the feasibility of microbial biomarkers for the early prediction of GDM. Study design: This nested case-control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Gut microbiota profiles of 98 subjects with GDM and 98 matched healthy controls during the early pregnancy (10-15 weeks) were assessed via 16S rRNA gene amplicon sequencing of V4 region. The data set was randomly split into a discovery set and a validation set, the former was used to analyze the differences between GDM cases and controls in gut microbial composition and functional annotation, and to establish an early identification model of GDM, then the performance of the model was verified by the external validation set. Results: Bioinformatic analyses revealed changes to gut microbial composition with significant differences in relative abundance between the groups. Specifically, Eisenbergiella, Tyzzerella 4, and Lachnospiraceae NK4A136 were enriched in the GDM group, whereas Parabacteroides, Megasphaera, Eubacterium eligens group, etc. remained dominant in the controls. Correlation analysis revealed that GDM-enriched genera Eisenbergiella and Tyzzerella 4 were positively correlated with fasting blood glucose levels, while three control-enriched genera (Parabacteroides, Parasutterella, and Ruminococcaceae UCG 002) were the opposite. Further, GDM functional annotation modules revealed enrichment of modules for sphingolipid metabolism, starch and sucrose metabolism, etc., while lysine biosynthesis and nitrogen metabolism were reduced. Finally, five genera and two clinical indices were included in the linear discriminant analysis model for the prediction of GDM; the areas under receiver operating characteristic curves of the training and validation sets were 0.736 (95% confidence interval: 0.663-0.808) and 0.696 (0.575-0.818), respectively. Conclusions: Gut bacterial dysbiosis in early pregnancy was found to be associated with the later development of GDM, and gut microbiota-targeted biomarkers might be utilized as potential predictors of GDM.

Self-Powered Temperature Sensor with Seebeck Effect Transduction for Photothermal-Thermoelectric Coupled Immunoassay.

A self-powered temperature sensor based on Seebeck effect transduction was designed for photothermal-thermoelectric coupled immunoassay of α-fetoprotein (AFP). In this system, glucose oxidase (GOx)-conjugated detection antibody was first captured onto the microplate by target-induced sandwich-type immunoreaction. Thereafter, the as-generated hydrogen peroxide via the GOx-glucose system oxidized 3,3',5,5'-tetrametylbenzidine (TMB) into photothermal product oxidized TMB (ox-TMB). Under near-infrared (NIR) laser irradiation, the temperature change of ox-TMB was read out in an electrical signal by the flexible thermoelectric module in a 3D-printed integrated detection device. Under optimal conditions, the photothermal-thermoelectric coupled immunoassay exhibited a limit of detection of 0.39 ng mL-1 AFP over a dynamic linear range from 0.5 to 60 ng mL-1. Impressively, such a strategy presented herein offers tremendous potentials for applying many other high-efficiency thermoelectric materials in ultrasensitive biosensors.