Human Body Fluids Research Articles

Comprehensive evaluation of the impact of whole-genome bisulfite sequencing (WGBS) on the fragmentomic characteristics of plasma cell-free DNA

BackgroundCell-free DNA (cfDNA) is non-randomly fragmented in human body fluids. Analyzing such fragmentation patterns of cfDNA holds great promise for liquid biopsy. Whole-genome bisulfite sequencing (WGBS) is widely used for cfDNA methylation profiling. However, its applicability for studying fragmentomic characteristics remains largely unexplored. MethodsWe performed paired WGBS and whole-genome sequencing (WGS) on 66 peripheral plasma samples from 58 pregnant women. Then, we systematically compared the fragmentation patterns of cell-free nuclear DNA and mitochondrial DNA (mtDNA) sequenced from these two approaches. Additionally, we evaluated the extent of the size shortening in fetal-derived cfDNA and estimated the fetal DNA fraction in maternal plasma using both sequencing methods. ResultsCompared to WGS samples, WGBS samples demonstrated a significantly lower genome coverage and higher GC content in cfDNA. They also showed a significant decrease in the size of cell-free nuclear DNA, along with alterations in the end motif pattern that were specifically associated with CpG and “CC” sites. While there was a slight shift in the inferred nucleosome footprint from cfDNA coverages in WGBS samples, the cfDNA coverage patterns in CTCF and TSS regions remained highly consistent between these two sequencing methods. Both methods accurately reflected gene expression levels through their TSS coverages. Additionally, WGBS samples exhibited an increased abundance and longer length of mtDNA in plasma. Furthermore, we observed the size shortening of fetal cfDNA in plasma consistently, with a highly correlated fetal DNA fraction inferred by cfDNA coverage between WGBS and WGS samples (r = 0.996). However, the estimated fetal cfDNA fraction in WGBS samples was approximately 7 % lower than in WGS samples. ConclusionsWe confirmed that WGBS can introduce artificial breakages to cfDNA, leading to altered fragmentomic patterns in both nuclear and mitochondrial DNA. However, WGBS cfDNA remains suitable for analyzing certain cfDNA fragmentomic characteristics, such as coverage in genome regulation regions and the essential characteristics of fetal DNA in maternal plasma.

Circular RNA landscape in extracellular vesicles from human biofluids

BackgroundCircular RNAs (circRNAs) have emerged as a prominent class of covalently closed single-stranded RNA molecules that exhibit tissue-specific expression and potential as biomarkers in extracellular vesicles (EVs) derived from liquid biopsies. Still, their characteristics and applications in EVs remain to be unveiled.MethodsWe performed a comprehensive analysis of EV-derived circRNAs (EV-circRNAs) using transcriptomics data obtained from 1082 human body fluids, including plasma, urine, cerebrospinal fluid (CSF), and bile. Our validation strategy utilized RT-qPCR and RNA immunoprecipitation assays, complemented by computational techniques for analyzing EV-circRNA features and RNA-binding protein interactions.ResultsWe identified 136,327 EV-circRNAs from various human body fluids. Significantly, a considerable amount of circRNAs with a high back-splicing ratio are highly enriched in EVs compared to linear RNAs. Additionally, we discovered brain-specific circRNAs enriched in plasma EVs and cancer-associated EV-circRNAs linked to clinical outcomes. Moreover, we demonstrated that EV-circRNAs have the potential to serve as biomarkers for evaluating immunotherapy efficacy in non-small cell lung cancer (NSCLC). Importantly, we identified the involvement of RBPs, particularly YBX1, in the sorting mechanism of circRNAs into EVs.ConclusionsThis study unveils the extensive repertoire of EV-circRNAs across human biofluids, offering insights into their potential as disease biomarkers and their mechanistic roles within EVs. The identification of specific circRNAs and the elucidation of RBP-mediated sorting mechanisms open new avenues for the clinical application of EV-circRNAs in disease diagnostics and therapeutics.

Research on the Corrosion Resistance and Cytotoxicity of Medical Forged Co-28Cr-6Mo Alloy

Co-Cr-Mo alloy as a human body implant material has a long history, because of its excellent corrosion resistance and biocompatibility, and is widely used in human hip joint materials. Co-Cr-Mo alloy in the human body is often in a passivation state; the formation of dense oxide film on the alloy surface prevents further corrosion of the alloy. The main component of the passivation film is the oxide of Cr, so a layer of oxide film formed by Cr on the surface of Co-Cr-Mo alloy is the reason for its good corrosion resistance. In biocompatibility, cytotoxicity is the first choice and necessary option for biological evaluation, and cytotoxicity can quickly detect the effect of materials on cells in a relatively short time. Therefore, this research conducted a comparative evaluation on the corrosion resistance and biocompatibility of forged Co-Cr-Mo alloys produced in domestic and foreign alloys in line with medical standards. Three simulated human body fluids and Princeton electrochemical station were selected for corrosion resistance experiments, and it was found that the corrosion resistance of four alloys in sodium citrate solution inside and outside China would be reduced. All the alloys exhibit secondary passivation behavior in Hanks solution, which improves the corrosion resistance of the alloys. According to the self-corrosion potential Ecorr analysis, the corrosion resistance of domestic B alloy is the best, while that of foreign R31537 alloy is poor. In the biocompatibility experiment, the biocompatibility of Co-Cr-Mo alloy was evaluated through the measurement of contact Angle and cytotoxicity reaction. The experimental results show that Co-Cr-Mo alloy is a hydrophilic material, and the contact Angle of foreign R31537 alloy is smaller, indicating that the surface of R31537 alloy is more suitable for cell adhesion and spreading. According to the qualitative and quantitative analysis of the cytotoxicity experiment, the toxic reaction grade of domestic A, B and R31537 alloy is grade 1, the toxic reaction grade of C alloy is grade 2, and C alloy has a slight toxic reaction.

A Nonfouling Electrochemical Biosensor for Protein Analysis in Complex Body Fluids Based on Multifunctional Peptide Conjugated with PEGlyated Phospholipid.

Developing antifouling biosensors capable of performing robustly in complex human body fluids is crucial for biomarker diagnosis and health monitoring. Herein, an antifouling and highly sensitive and stable biosensor was constructed through the self-assembly of the designed conjugates composed of a multifunctional peptide (MP) and PEGylated distearoylphosphatidylethanolamine (DSPE-PEG). The self-assembly capability of the DSPE-PEG-MP was demonstrated clearly through coarse-grained molecular dynamics simulation and transmission electron microscopy, and it can be effectively self-assembled onto the electrode surface modified with gold nanoparticles. The MP was designed to be antifouling and contained a peptide sequence that can specifically bind the target protein Annexin A1 (ANXA1), and the D-type amino acid composition of MP can enhance its resistance to enzymatic hydrolysis. The unique design of MP, in conjugation with the self-assembly capability of the PEGylated phospholipid DSPE-PEG, enabled the biosensor to exhibit excellent antifouling capability and stability in various complex human body fluids. The biosensor was capable of sensitively and selectively quantifying ANXA1 and achieved a limit of detection down to 0.12 pg mL-1. More importantly, the biosensor demonstrated satisfactory accuracy for ANXA1 detection in clinical serum samples, as verified by the enzyme linked immunosorbent assay (ELISA) kits. It is expected that various antifouling biosensors suitable for application in complex biological environments can be constructed by utilizing the strategy of designing similar DSPE-PEG-MP conjugates.

Enhanced anticorrosive, antimicrobial and biocompatible properties of AZ91D magnesium alloy by MAO-polycaprolactone-modified ZnO composite coating

Magnesium alloys are biodegradable metal implant materials that are prone to corrosion in human body fluids and are poor biocompatible as a consequence. Herein, we report the preparation of a ceramic layer on an AZ91D magnesium alloy using the micro-arc oxidation (MAO) technique, after which polycaprolactone/citric-acid-monohydrate-modified nano‑zinc oxide was composited on the ceramic layer using a sol–gel method. The MAO-polycaprolactone-modified ZnO composite coating exhibited superior corrosion resistance compared to magnesium alloy, and a higher electrochemical impedance in simulated body fluid (1.0397 × 107 vs. 8.444 × 102 Ω·cm2). Furthermore, data from immersion, antimicrobial, hemolysis, cell-viability, and-proliferation testing revealed that the composite coating is significantly more antimicrobial and biocompatible than the magnesium alloy. We conclude that such composite coatings have considerable potential for use in biomedical orthopedic-implant applications.

Investigation of the microstructural characteristics of laser-cladded Ti6Al4V titanium alloy and its corrosion behavior in simulated body fluid

Laser cladding technology has a wide range of potential industrial applications in the surface strengthening, repair and reuse of orthopedic implants. By employing this technique to conduct same-material surface restoration and enhancement on titanium alloys, it demonstrates significant developmental potential. However, the microstructure of laser additively manufactured titanium alloy differs significantly from that of traditional titanium alloys, which affects its corrosion resistance in human body fluids. To compare the corrosion resistance differences between the cladding layer and the substrate, this study investigates the microstructure of multi-pass laser cladding Ti6Al4V (TC4) titanium alloy and analyzes the corrosion morphology and corrosion products of the cladding layer in simulated body fluids (SBF). By comparing the electrochemical corrosion behavior of laser cladding with that of traditionally manufactured TC4, this research reveals the differences in corrosion resistance between the two titanium alloys. The research demonstrates that the microstructure of cladding primarily consists of prior-β grains and continuous grain boundary α phase, along with a complex basketweave structure composed of fine acicular α phase and lamellar α phase. Additionally, due to the complex thermal cycling process, the acicular α' colonies within the prior-β grains. These features enhance the cladding layer’s resistance to plastic deformation and increase microhardness, though with some uneven distribution. Interestingly, the TC4 cladding layer forms a porous passivation layer after corrosion, primarily composed of a TiO2 passivation film and deposits of hydroxyapatite and other phosphates. Due to the lower β-phase content, finer grains with higher energy states, and a greater proportion of high-angle grain boundaries (HAGBs) in the cladding layer, it exhibits higher electrochemical activity. As a result of these microstructural differences, the corrosion resistance of the TC4 cladding layer in SBF is inferior to that of TC4 manufactured using traditional techniques.

Investigating the Predictive Biomethods. of Hypertension (HTN) in Human Foetal Astrocytes (HFAs) using Modified Proteomic Methods

Background: Hypertension (HTN) is a major risk factor for Cerebrovascular and cardiovas-cular diseases, causing premature deaths. Hence, there is an urgent need for predictive bi-omarkers to detect HTN before its onset. Methods • Cell Culture Technique: Growth of HFAs, followed by conversion of normal (A2) HFAs intoreactive (A1) type, by using ATP solution. • Confocal Microscopy: Quantification of Glial Fibrillary Acidic Protein (GFAP) in A1 and A2 HFAs, by using antibody ab 7260 with AF 488. Proteomics Methos • Extraction of proteins from A1 and A2 HFAs, using Single-pot, Sol-id-phase-enhanced Sample Preparation (SP3) protocol. • Liquid Chromatography- Mass Spectrometry techniques for obtaining the lev-els of calcium-gated proteins in A1 and A2 cell-solutions. Results • Micrographs obtained by Leica Microsystem indicated thicker filaments in A1 HFAs compared to A2 HFAs. • Confocal results showed higher levels of GFAP in A1 HFAs (P> 0.05). • Proteomics data analysed by PEAKS software revealed that proteins, such as GFAP were higher in reactive HFAs. Conclusions: The results showed higher levels of GFAP in A1 HFAs. Therefore, early detection of GFAP in human body fluids could be a reliable predictive biomarker for HTN

POLYETHYLENE TEREPHTHALATE (PET) COATED WITH CHITOSAN AND CYCLOSPORINE A LAYERS AS A POTENTIAL STENT MATERIAL AND DRUG-DELIVERY SYSTEM

The aim of this paper was to design, prepare and characterise chitosan (Ch) and cyclosporine A (CsA) mixed films deposited on a plasma-activated polyethylene terephthalate (PET) polymer surface to be used as a cover for implantable blood vessel stents. The PET polymer coated with Ch and CsA layers was immersed in simulated body fluid (SBF) to examine how the obtained layers can behave in the environment of human body fluids. Time-of-flight secondary ion mass spectrometry was employed to determine the chemical composition of the deposited films and to analyse the spatial distribution of molecules on the PET surface. The results showed the controlled release of CsA from the chitosan matrix. It can be concluded that the modification of the PET polymer with layers of chitosan and CsA has great application potential in the tissue engineering as a biocompatible stent of blood vessels with therapeutic properties.

Metabolic landscaping of extracellular vesicles from body fluids by phosphatidylserine imprinted polymer enrichment and mass spectrometry analysis

Extracellular vesicles (EVs) are emerging as new source of biomarkers discovery in liquid biopsy due to their stabilization in body fluids, protected by phospholipid bilayers. However, the metabolomics study of EVs is very little reported due to the lack of efficient and high-throughput isolation methods for clinical samples. In this study, phosphatidylserine imprinted polymers were employed for rapid and efficient EVs isolation from five human body fluids, including plasma, urine, amniotic fluid, cerebrospinal fluid, and saliva. The isolated EVs were subsequently analyzed for metabolomic studies by high-resolution mass spectrometry. Metabolic landscaping was conducted between the body fluids and their EVs, indicating EVs contain a large number of metabolites that are completely specific to the body fluid source. Finally, quantitative metabolomic analysis of EVs was carried out with plasma samples of hepatocellular carcinoma. Several differentially expressed exosomal metabolites were revealed including the upregulation of sphingosine (d18:1), taurochenodeoxycholic acid (TCDCA), pipecolic acid (PA), and 4-hydroxynonenal (4-HNE) and down-regulation of piperine, caffeine, and indole. We believe the proposed methodology will provide a deeper understanding of the molecular composition and functions of EVs as an alternative source for biomarker discovery.

Application of Response Surface Methodology Experimental Design to Optimize Tribological Lubrication Characteristics

Total Knee Replacement (TKR) has become a standard operation for patients with joint disorders. Despite the fact that the number of procedures is increasing all the time, the short service life of implants remains a persistent concern for researchers. Understanding lubrication may aid in explaining tribological processes that lead to replacements that last well into the third decade of service. Likewise, wear and friction in total knee replacement (TKR) components are among the most common causes of implant failure. As a result, this study will evaluate the feasibility of using the polymer Poly Lactic Acid (PLA) for cartilage replacement in Total Knee Replacement (TKR) using plant-based oils as lubricants. Furthermore, the modifier will be added to plant-based oils as an additive to make them analogous to human bodily fluids. The present paper is applying the Box-Behnken design to optimize the performance and mechanical responses of bio-lubricants toward Poly Lactic Acid (PLA) as a tibial insert for cartilage replacement in Total Knee Replacement (TKR). The main objective of this paper is to develop an optimized method for the selection of plant-based oil parameters using Response Surface Methodology (RSM). A three-level three-factor Box-Behnken design (BBD) was used to investigate the interactions between the essential factors comprising load (45 kg to 90 kg), speed (60 rpm, 90 rpm and 360 rpm), and concentration (0ml, 5ml and 10ml) of bio-lubricants to accomplish the indicated prospect of using polymer for cartilage replacement. Canola oil, castor oil, and sunflower seed oil are considered vegetable oils, whereas Hyaluronic Acid (HA) is the friction modifier. The parameters are used to create a Box-Behnken design for predicting lubricant anti-wear qualities stated in terms of coefficient of friction, wear rate and frictional force as determined by the pin-on-disk experimental procedure. As a result, the optimization using RSM successfully interpreted the experimental data, according to the analysis of variance, with coefficients of determination of R2 = 0.91 and adjusted R2 = 0.77. The Coefficient of Friction (CoF) and wear rate were investigated following tribological testing. Castor oil had a lower coefficient of friction than canola and sunflower seed oil, according to the findings. In terms of friction reduction, castor oil surpasses canola and sunflower seed oil.

Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics

BackgroundCancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx. MethodsSpatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx. ResultsDistinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs. ConclusionsThese findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.

Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC-MS/MS using standard addition method.

An analytical method was developed for determining ropivacaine and its main metabolite, 3-hydroxyropivacaine in biomedical samples using gas chromatography-tandem mass spectrometry (GC-MS/MS). Then, this established method was applied to investigate the distribution of ropivacaine and its metabolite in human fluids and solid tissues obtained from an authentic case ropivacaine involved. The fluid sample was added acetonitrile, and solid tissue was homogenized using a freezer mill and then added into acetonitrile. Then, an internal standard solution was added to the mixtures. The mixture was centrifuged at 12,000 × g for 5min, and the upper layer of acetonitrile was transferred to magnesium sulfate and octadecyl silica (C18) gel for cleaning up the sample. After centrifugation, the upper layer was then evaporated to dryness with nitrogen, and dissolved with methanol, then injected into the GC-MS/MS system. The coefficients of determination (r2) of constructed calibration curves were all greater than 0.999. The limits of detection for ropivacaine and 3-hydroxyropivacaine in target samples were 15ng/mL and 10ng/mL, respectively. The recovery rates of ropivacaine and 3-hydroxyropivacaine ranged from 97.6% to 103% and from 96.5% to 104%, respectively. The inter-day precision values of ropivacaine and 3-hydroxyropivacaine were not greater than 6.25% and 7.98%, respectively, and the inter-day trueness values were not greater than 6.90% and 8.33%, respectively; the intra-day precision and trueness values of ropivacaine and 3-hydroxyropivacaine were not greater than 3.20%, 6.78%, 7.84% and 8.99%, respectively. GC-MS/MS method for simultaneous detection and quantification of ropivacaine and 3-hydroxyropivacaine in biological samples was successfully developed. The method could also be applied to samples obtained from an authentic case; their distribution among tested fluids and solid tissues were also measured. This is the first report on the distribution of ropivacaine and its major metabolite 3-hydroxyropivacaine in a human case.

Postmortem-Derived Exosomal MicroRNA 486-5p as Potential Biomarkers for Ischemic Heart Disease Diagnosis.

Exosomes are nanovesicles 30-150 nm in diameter released extracellularly. Those isolated from human body fluids reflect the characteristics of their cells or tissues of origin. Exosomes carry extensive biological information from their parent cells and have significant potential as biomarkers for disease diagnosis and prognosis. However, there are limited studies utilizing exosomes in postmortem diagnostics. In this study, we extended our initial research which identified the presence and established detection methodologies for exosomes in postmortem fluids. We analyzed exosomal miRNA extracted from plasma and pericardial fluid samples of a control group (n = 13) and subjects with acute myocardial infarction (AMI; n = 24). We employed next-generation sequencing (NGS) to investigate whether this miRNA could serve as biomarkers for coronary atherosclerosis leading to acute myocardial infarction. Our analysis revealed 29 miRNAs that were differentially expressed in the AMI group compared to the control group. Among these, five miRNAs exhibited more than a twofold increase in expression across all samples from the AMI group. Specifically, miR-486-5p levels were significantly elevated in patients with high-grade (type VI or above) atherosclerotic plaques, as per the American Heart Association criteria, highlighting its potential as a predictive biomarker for coronary atherosclerosis progression. Our results indicate that postmortem-derived exosomal microRNAs can serve as potential biomarkers for various human diseases, including cardiovascular disorders. This finding has profound implications for forensic diagnostics, a field critically lacking diagnostic markers.

A harmonized occupational biomonitoring approach

Biomonitoring has been widely used in assessing exposures in both occupational and public health complementing chemical risk assessments because it measures the concentrations of chemical substances in human body fluids (e.g., urine and blood). Biomonitoring considers all routes and sources of exposure. An occupational biomonitoring guidance document has been elaborated (OECD Occupational Biomonitoring Guidance) within the OECD framework and specifically, the Working Parties on Exposure and Hazard Assessment by scientific experts from 40 institutes and organizations representing 15 countries. The guidance provides practical information for assessing chemical exposures in occupational settings including the three common routes of exposure: inhalation, skin absorption and ingestion due to hand to mouth contact. The elaborated stepwise approach for conducting biomonitoring is tailored for occupational health professionals, scientists, risk assessors, and regulators. It includes methods for selecting appropriate biomarkers, devising sampling strategies, and assessing laboratories for validated analytical methods for the biomarker of interest, and ensuring timely feedback of results. Furthermore, it describes procedures for setting up efficient biomonitoring programs based on the Similar Exposure Group (SEG) approaches. Derived health-based human exposure biomarker assessment values called Occupational Biomonitoring Levels (OBLs) are proposed for use in occupational exposure and risk assessment. It also helps with the interpretation of biomonitoring results routinely collected and procedures for communicating biomonitoring results at individual, collective, and workplace levels. Ethical considerations associated with biomonitoring are also discussed. The ultimate goal of this biomonitoring approach is to promote harmonized application and interpretation of biomarkers as well as evidence-based occupational risk management measures.

Dual-Modal Aptasensor for Sensitive Detection of Non-Small Cell Lung Cancer Exosomes Utilizing Two-Dimensional Nanopaper Co@g-C3N4@PB.

Nonsmall cell lung cancer (NSCLC), due to its lack of early symptoms, has become one of the leading causes of cancer-related deaths globally. Exosomes, small membrane vesicles secreted by cells, are widely present in human bodily fluids. In the bodily fluids of NSCLC patients, the quantity of extracellular vesicles is double that of healthy individuals, suggesting their potential as biomarkers for screening NSCLC. This study designed a dual-modal aptasensor that integrated excellent sensitivity in electrochemical detection and portability in fluorescence detection into one device. AuNPs were functionalized with exosome-capturing probes containing thiol-modified CD63 aptamers, which were immobilized on screen-printed gold electrodes. On the other hand, the carboxylated CD63 aptamer was immobilized on the surface of PB-modified g-C3N4 loaded with Co-SANs particles (Co@g-C3N4@PB). By combining these components, a sandwich structure (AuNPs/Apt1/Exo/Apt2- Co@g-C3N4@PB) was constructed, forming a probe for specific exosome recognition. First, the samples were preliminarily assessed for their positive or negative status under a fluorescence inverted microscope. Subsequently, a more in-depth quantitative analysis was conducted on suspected positive samples using electrochemical or fluorescence analysis methods. The detection limits for electrochemical analysis and fluorescence analysis were 66.68 and 33.5particles/mL, respectively. In the analysis of clinical serum exosome samples, the developed dual-modal aptasensor effectively distinguished serum specimens from those of NSCLC patients and healthy volunteers. This highlighted the inspection capability of the dual-modal adapter sensor, especially in point-of-care testing, making it a highly suitable tool for clinical applications.

Synthesis of Yolk-Shell CoNi2S4 Spheres Modified Flexible Carbon Cloth Electrode for Highly Sensitive Detection of Neurotransmitter Dopamine

Dopamine (DA) is a neurotransmitter that is connected with transitory information in the mammalian central nervous system; changes in its concentration in the body are directly related to mental activity. The absence and/or low level of DA can cause symptoms of several disorders, including Parkinson’s and schizophrenia. As a result, detecting DA in patients is critical for regulating body function. Many efforts have been made to build electrochemical sensing devices to detect DA in human body or biological fluids due to its inherent advantages of high sensitivity, speed, simplicity, and affordability. However, surface modification with nanomaterials, polymers, pretreatments, or simple functionalization are required to improve the performance of these sensing electrodes. Further, exploration of earth-abundant electro-catalysts with high activity and stability is also important for the development of highly selective and sensitive electrochemical sensing interfaces. With these considerations in mind, our study describes the construction of yolk-shell CoNi2S4 spheres modified flexible carbon cloth (CC) electrode for the sensitive detection of DA. The synthesized material's surface and morphological study were examined, and the successful synthesis was confirmed. The yolk-shell CoNi2S4 spheres shown good electrochemical sensing performance towards DA detection due to their unique surface morphology with large specific surface area and synergistic effects. In comparison to unmodified CC, the yolk-shell CoNi2S4 spheres modified CC demonstrated a low detection limit (5.1 nM), great sensitivity, and a wide linear range (0.01 – 5.2 µM). The detection selectivity was also tested in the presence of a high quantity of the common interference ascorbic acid. Selectivity, stability, and repeatability have also been demonstrated to be satisfactory. Furthermore, the fabricated sensor’s flexibility endows it with significant potential in the fabrication of wearable and soft electronics for human healthcare monitoring.

Antifouling and antimicrobial wearable electrochemical sweat sensors for accurate dopamine monitoring based on amyloid albumin composite hydrogels

Wearable electrochemical sweat sensors are potentially promising for health monitoring in a continuous and non-invasive mode with high sensitivity. However, due to the complexity of sweat composition and the growth of skin bacteria, the wearable sweat sensors may gradually lose their sensitivity or even fail over time. To deal with this issue, herein, we proposed a new strategy to construct wearable sweat sensors with antifouling and antimicrobial capabilities. Amyloid albumin hydrogels (ABSAG) were doped with two-dimensional (2D) nanomaterial MXene and CeO2 nanorods to obtain the antifouling and antimicrobial amyloid albumin composite hydrogels (ABSACG, CeO2/MXene/ABSAG), and the wearable sensors were prepared by modifying flexible screen-printed electrodes with the ABSACG. Within this sensing system, the hydrophilic ABSAG possesses strong hydration capability, and it can form a hydration layer on the electrode surface to resist biofouling in sweat. The 2D nanomaterial MXene dispersed in the hydrogel endows the hydrogel with good conductivity and electrocatalytic capability, while the doping of CeO2 nanorods further improves the electrocatalytic performance of the hydrogel and also provides excellent antimicrobial capability. The designed wearable electrochemical sensors based on the ABSACG demonstrated satisfying antifouling and antimicrobial abilities, and they were capable of detecting dopamine accurately in human sweat. It is expected that wearable sensors utilizing the antifouling and antimicrobial ABSACG may find practical applications in human body fluids analysis and health monitoring.

Nanoengineered Nonenzymatic Paper-Based Fluorescent Platform for Pre-Dilution-Free and Visual Real-Time Home Monitoring of Urea for Early Warning of Abnormal Nitrogen-Based Unhealthy Issues.

Distorted urea levels indicate several liver, kidney, or metabolic diseases; however, traditional clinical urea detection relies on urease-based methods enslaved to well-known limitations of high-price, unstable properties, complicated sample pretreatment and analysis procedures, and difficult visual real-time monitoring. Herein, nonenzymatic paper-based fluorescent materials (UFP-BP) are strategically integrated with an on-demand fluorescent-sensor (UFP) self-aggregated nanoparticle on commercial filter paper for pre-dilution-free and visual real-time urea monitoring. The UFP is synthesized and self-aggregated into the fluorescent nanoparticles for selective urea recognition. Then, the nanoparticles are interstitially loaded on filter paper to nanoengineer the UFP-BP, achieving selective quantitative urea detection in the normal concentration range (10-1000mm). UFP and UFP-BP can successfully monitor urea levels in real rat urine, artificial simulants, and milk. The proposed sensing platform, integrated with smartphones, offers accurate, quantitative, nonenzymatic, noninvasive, pre-dilution-free, on-site, rapid, low-cost, easy-to-operate, real-time visual urea detection in food samples and human body fluids. The designed sensing system can provide early warnings of abnormal nitrogen-based health issues.

High-efficiency electrochemiluminescence of host-guest ligand-assembled gold nanoclusters preoxidated for ultrasensitive biosensing of protein

Herein, host–guest ligand-assembled gold nanoclusters (AuNCs) with highly efficient electrochemiluminescence (ECL) as an emitter and a programable tripedal deoxyribonucleic acid (DNA) walker with a well-regulated DNA track as the signal amplifier were used to develop an ultrasensitive biosensing platform for determining soluble urokinase-type plasminogen activator receptor (suPAR) related to chronic kidney disease. Notably, the host–guest ligand-assembled AuNCs with 6-aza-2-thiothymine (ATT) as the ligand and guanidine butyric acid (Gba) as the model (Gba/ATT-AuNCs) exhibited a strong and stable ECL signal under preoxidation, 25.6 times higher than that of traditional ATT-protected AuNCs (ATT-AuNCs). This is because of the dual-enhancement ECL mechanism of the suppression of nonradiative transitions by host–guest recognition and the improvement of the electrochemical redox rate by preoxidation. Furthermore, the trace target protein suPAR could be efficiently converted into a tripedal DNA walker to walk along a well-regulated square DNA orbit with high movement efficiency and low background signal, thereby considerably improving detection sensitivity. Thus, the established ECL sensing platform achieved the ultrasensitive detection of suPAR with a linear range from 10 fg/mL to 10 ng/mL and a limit of detection of 3.15 fg/mL, whose detection sensitivity was five orders of magnitude higher than that of the gold-standard enzyme-linked immunosorbent assay with the lowest detection concentration of 1 ng/mL. This strategy provides a novel enhanced ECL mode of AuNCs for constructing a sensitive biosensing platform and is expected to be extended to the trace detection of other protein markers in human body fluids for disease diagnosis.

A novel disposable ultrasensitive sensor based on nanosized ceria uniformly loaded carbon nanofiber nanoceramic film wrapped on pencil graphite rods for electrocatalytic monitoring of a tyrosine kinase inhibitor capmatinib

For the first time, we introduce a novel disposable and ultrasensitive sensing electrode made up of nanosized ceria uniformly loaded carbon nanofibers (CeNPs@CNF) sol-gel nanoceramic film (CF) wrapped on eco-friendly and inexpensive pencil graphite rods (PGRs) to explore their electro-catalytic detection of the anticancer drug capmatinib (CMB). The as-prepared CeNPs@CNF hybrid nanocomposite was described by XRD, SEM, TEM, HRTEM, and EDX analysis. The CV study clearly demonstrated that, the disposable CeNPs@CNF-CF/PGRE sensor exhibited excellent redox activities in the ideal probe [Fe(CN)6]3-/4-. Due to the outstanding electrochemical properties, larger electrochemically active surface area, and tremendous electro-catalytic activity of CeNPs@CNF, the reduction current of CMB on the CeNPs@CNF-CF/PGRE sensor is considerably higher than that of bare PGRE. The detection conditions, such as supporting electrolyte, pH of the buffer solution, amount of modifier, adsorption potential, and time, were studied and optimized. The sensing platform demonstrated high sensitivity (1.2 μA nM−1 cm−2), an ultralow detection limit (0.6 nM), and a wide linear range of 2.0 nM–400 nM of CMB compared to the bare PGRE. Additionally, the CeNPs@CNF-CF/PGRE sensor showed high selectivity, stability, and simple operation, which provided a promising alternative tool for fast detection of CMB in human body fluids with good recoveries.