l-Cysteine-Tuned the Hierarchical Structure Based on Benzimidazole: Synthesis, Characterization, and Application in Ratiometric Electrochemiluminescence Immunoassay.

Efficient and robust electrochemiluminescence (ECL) emitters are crucial for enhancing the ECL immunosensor sensitivity. This study introduces a novel ECL emitter, CoBIM/Cys, featuring a hierarchical core-shell structure. The core of the structure is created through the swift coordination between the sulfhydryl and carboxyl groups of l-cysteine (l-Cys) and cobalt ions (Co2+), while the shell is constructed by sequentially coordinating benzimidazole (BIM) with Co2+. This design yields a greater specific surface area and a more intricate porous structure compared to CoBIM, markedly enhancing mass transfer and luminophore accessibility. Moreover, the l-Cys and Co2+ core introduces Co-S and Co-O catalytic sites, which improve the catalytic decomposition of H2O2, leading to an increased production of hydroperoxyl radicals (OOH•). This mechanism substantially amplifies the ECL performance. Leveraging the competitive interaction between isoluminol and BIM for OOH• during ECL emission, we developed a ratiometric immunosensor for cardiac troponin I (cTnI) detection. This immunosensor demonstrates a remarkably broad detection range (1 pg mL-1 to 10 ng mL-1), a low detection limit (0.4 pg mL-1), and exceptional reproducibility and specificity.

Detection of Cannabinoids in Oral Fluid Specimens as the Preferred Biological Matrix for a Point-of-Care Biosensor Diagnostic Device.

An increasing number of countries have started to decriminalize or legalize the consumption of cannabis for recreational and medical purposes. The active ingredients in cannabis, termed cannabinoids, affect multiple functions in the human body, including coordination, motor skills, memory, response time to external stimuli, and even judgment. Cannabinoids are a unique class of terpeno-phenolic compounds, with 120 molecules discovered so far. There are certain situations when people under the influence of cannabis may be a risk to themselves or the public safety. Over the past two decades, there has been a growing research interest in detecting cannabinoids from various biological matrices. There is a need to develop a rapid, accurate, and reliable method of detecting cannabinoids in oral fluid as it can reveal the recent intake in comparison with urine specimens, which only show a history of consumption. Significant improvements are continuously made in the analytical formats of various technologies, mainly concerning improving their sensitivity, miniaturization, and making them more user-friendly. Additionally, sample collection and pretreatment have been extensively studied, and specific devices for collecting oral fluid specimens have been perfected to allow rapid and effective sample collection. This review presents the recent findings regarding the use of oral fluid specimens as the preferred biological matrix for cannabinoid detection in a point-of-care biosensor diagnostic device. A critical review is presented, discussing the findings from a collection of review and research articles, as well as publicly available data from companies that manufacture oral fluid screening devices. Firstly, the various conventional methods used to detect cannabinoids in biological matrices are presented. Secondly, the detection of cannabinoids using point-of-care biosensors is discussed, emphasizing oral fluid specimens. This review presents the current pressing technological challenges and highlights the gaps where new technological solutions can be implemented.

Fine tuning of porphyrin based-paddlewheel framework by imidazole derivative to boost electrochemiluminescence performance.

Precise tuning the structure of catalytic center is of great importance for the construction of enhanced electrochemiluminescence (ECL) emitters and the development of ECL amplification strategies, which is a key factor in improving the sensitivity of biosensors. In this work, we report the enhanced ECL emitters based on the porphyrin-based paddlewheel framework (PPF) with axial coordinated imidazole-like ligands (PPF/X, X = 2-methylimidazole (MeIm), imidazole (Im), benzimidazole (BIM)). In this system, the electron-donating ability of the axial ligands is positively correlated to its coordination ability to the paddlewheel units and the catalytic ability of the axially coordinated paddlewheel units. In addition, the electrochemical and ECL behavior of PPF/X (X = MeIm, Im, BIM) with different axial coordinated ligands are explored.

Additive Manufacturing Applications in Biosensors Technologies.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the additive manufacturing applications in biosensor technologies with a particular emphasis on extrusion-based 3D printing modalities. We highlight the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis is placed on the approach by which the sensing molecules are introduced during the fabrication process. Finally, future perspectives are provided.

Micelle-Assisted Confined Coordination Spaces for Benzimidazole: Enhanced Electrochemiluminescence for Nitrite Determination.

Selective and sensitive detection of nitrite has important medical and biological implications. In the present work, to obtain an enhanced electrochemiluminescence (ECL) determination of nitrite, a novel nano-ECL emitter CoBIM/cetyltrimethylammonium bromide (CTAB) was prepared via a micelle-assisted, energy-saving, and ecofriendly method based on benzimidazole (BIM) and CTAB. Unlike conventional micelle assistance, the deprotonated BIM (BIM-) preferential placement was in the palisade layer of cationic CTAB-based micelles. Enriching the original CTAB micelle with BIM- disrupted its stability and resulted in the formation of considerably smaller BIM/CTAB-based micelles, providing a confined coordination environment for BIM- and Co2+. As a result, the growth of CoBIM/CTAB was also limited. Owing to the unusual nitration reaction between BIM and nitrite, the prepared CoBIM/CTAB was successfully applied as a novel ECL probe for the detection of nitrite with a wide linear range of 1-1500 µM and a low detection limit of 0.67 µM. This work also provides a promising ECL platform for ultrasensitive monitoring of nitrite and it was applied with sausages and pickled vegetables.

Post-synthetic modification-driven ZIF reconstruction and functionalization for efficient SARS-CoV-2 ECL detection.

The emergence of novel pathogens, as well as their frequent variants, raises the significance of developing superior and versatile sensing materials and techniques. Herein, a post-modified zeolitic imidazolate framework (pm-ZIF) was synthesized by using ZIF-67 as a parent MOF, and zinc(II) meso-tetra (4-carboxyphenyl) porphine (ZnTCPP) as a successive exchange ligand. Due to the preservation of the tetrahedral Co-N4 units from the ZIF precursor and the introduced porphyrin luminophores, this hybrid material pm-ZIF/P(Zn) enables the linear electrochemiluminescence (ECL) signal conversion of the target DNA concentration. An efficient biosensor that can be used to quantitatively detect SARS-CoV-2 was therefore constructed. The linear range of the sensor was 10-12-10-8 M, with a limit of detection (LOD) reaching 158 pM. Compared with the traditional amplification-based methods, the duration time of our method is significantly shortened and the quantitation of the SARS-Cov-2 RdRp gene can be completed within twenty minutes at room temperature.

3,3'-Diindolylmethane (DIM): A Potential Therapeutic Agent against Cariogenic Streptococcus mutans Biofilm.

Indole, a metabolite of the amino acid tryptophan, has been proven to act as a signal molecule in bacteria, acting in different aspects of biofilm formation. The oral biofilm is a type of biofilm that has consequences for human health. It is a complex, three-dimensional structure that develops on the surface of teeth via the attachment of primary microbial colonizers. Many oral infections are caused by an imbalance occurring in the microorganisms naturally found in oral biofilms and are considered major public health concerns. In this study, we test the effect of a natural bis-indole, 3,3'-Diindolylmethane (DIM), in mitigating the pathogenicity of the oral biofilm inhabiting bacterium Streptococcus mutans, a bacterium that is considered to be a principal etiological agent in dental caries. Our study found that DIM was able to attenuate S. mutans biofilm formation by 92%. Additionally, treatment with DIM lowered extracellular polymeric substance (EPS) production and decreased its durability significantly under acidic conditions. Therefore, the anti-biofilm and anti-virulence properties of DIM against S. mutans bacteria in an "oral setting" provides evidence for its usefulness in reducing biofilm formation and potentially for caries attenuation.

Conversations in the Gut: The Role of Quorum Sensing in Normobiosis.

An imbalance in gut microbiota, termed dysbiosis, has been shown to affect host health. Several factors, including dietary changes, have been reported to cause dysbiosis with its associated pathologies that include inflammatory bowel disease, cancer, obesity, depression, and autism. We recently demonstrated the inhibitory effects of artificial sweeteners on bacterial quorum sensing (QS) and proposed that QS inhibition may be one mechanism behind such dysbiosis. QS is a complex network of cell-cell communication that is mediated by small diffusible molecules known as autoinducers (AIs). Using AIs, bacteria interact with one another and coordinate their gene expression based on their population density for the benefit of the whole community or one group over another. Bacteria that cannot synthesize their own AIs secretly "listen" to the signals produced by other bacteria, a phenomenon known as "eavesdropping". AIs impact gut microbiota equilibrium by mediating intra- and interspecies interactions as well as interkingdom communication. In this review, we discuss the role of QS in normobiosis (the normal balance of bacteria in the gut) and how interference in QS causes gut microbial imbalance. First, we present a review of QS discovery and then highlight the various QS signaling molecules used by bacteria in the gut. We also explore strategies that promote gut bacterial activity via QS activation and provide prospects for the future.

Regulating the coordination capacity of ATMP using melamine: facile synthesis of cobalt phosphides as bifunctional electrocatalysts for the ORR and HER.

Due to the complexity of the synthetic process of cobalt phosphides (CoP), ongoing efforts concentrate on simplifying the preparation process of CoP. In this work, amino tris(methylene phosphonic acid) (ATMP, L1) and melamine (MA, L2) are assembled into two-dimensional (2D) organic nanostructures by hydrogen bonding and ionic interactions via a supramolecular assembly, which greatly weakens the coordination ability of L1 with Co2+. As the introduced L2 is rich in carbon and nitrogen, it allows the cobalt-organophosphate complex to be placed under a strongly reducing atmosphere during the high-temperature calcination process to achieve an in situ phosphating purpose. The resulting catalyst (N-CoP/NC) exhibits the sought-after enhanced oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) performance. For the ORR in 0.1 M KOH, an enhanced onset potential (0.908 V vs. RHE) and diffusion limiting current (6.280 mA cm-2) can be obtained, which is comparable to those of 20% Pt/C (0.911 V vs. RHE, 5.380 mA cm-2). For the HER in 0.5 M H2SO4, an overpotential of 150 mV is required to drive a current of 10 mA cm-2. Moreover, Density Functional Theory (DFT) calculations reveal the catalytic pathway of N-CoP/NC.

Schiff Base Complexes with Covalently Anchored Luminophores: Self-Enhanced Electrochemiluminescence Detection of Neomycin.

A novel electrochemiluminescence (ECL) amplification strategy was established aiming to overcome the inherent shortcomings of the current oxygen (O2) coreactant ECL systems. Macrocyclic Schiff base Fe complexes were rationally designed as a novel integrated ECL emitter by iminium linkage between N-(4-aminobutyl)-N-ethylisoluminol (ABEI) and 1,10-phenanthroline-2,9-dicarbaldehyde (PDL) and postmetalation of the macrocyclic Schiff base. Covalently combining luminophore ABEI with a catalytic center endowed the novel ECL emitter with both remarkable redox electrocatalytic properties and significantly enhanced ECL efficiency. The high content of ferrous iron and the dominantly active low-spin Fe state greatly contributed to the inherent catalytic activity for O2 activation. The rational modification of luminophore optimized the spatial distribution and simultaneously shortened the species transport distance of coreactant radicals generated in situ from dissolved O2, resulting in significantly self-enhanced ECL efficiency. Neomycin, which posed a growing threat to aquatic biodiversity and environmental safety, as the model antibiotic was successfully detected with a detection limit of 0.21 pM (S/N = 3), clarifying a promising application prospect of this new luminophore-embedded ECL amplification strategy in biological analysis and environmental monitoring.

Anti-Virulence Activity of 3,3'-Diindolylmethane (DIM): A Bioactive Cruciferous Phytochemical with Accelerated Wound Healing Benefits.

Antimicrobial resistance is among the top global health problems with antibacterial resistance currently representing the major threat both in terms of occurrence and complexity. One reason current treatments of bacterial diseases are ineffective is the occurrence of protective and resistant biofilm structures. Phytochemicals are currently being reviewed for newer anti-virulence agents. In the present study, we aimed to investigate the anti-virulence activity of 3,3'-diindolylmethane (DIM), a bioactive cruciferous phytochemical. Using a series of in vitro assays on major Gram-negative pathogens, including transcriptomic analysis, and in vivo porcine wound studies as well as in silico experiments, we show that DIM has anti-biofilm activity. Following DIM treatment, our findings show that biofilm formation of two of the most prioritized bacterial pathogens Acinetobacter baumannii and Pseudomonas aeruginosa was inhibited respectively by 65% and 70%. Combining the antibiotic tobramycin with DIM enabled a high inhibition (94%) of P. aeruginosa biofilm. A DIM-based formulation, evaluated for its wound-healing efficacy on P. aeruginosa-infected wounds, showed a reduction in its bacterial bioburden, and wound size. RNA-seq was used to evaluate the molecular mechanism underlying the bacterial response to DIM. The gene expression profile encompassed shifts in virulence and biofilm-associated genes. A network regulation analysis showed the downregulation of 14 virulence-associated super-regulators. Quantitative real-time PCR verified and supported the transcriptomic results. Molecular docking and interaction profiling indicate that DIM can be accommodated in the autoinducer- or DNA-binding pockets of the virulence regulators making multiple non-covalent interactions with the key residues that are involved in ligand binding. DIM treatment prevented biofilm formation and destroyed existing biofilm without affecting microbial death rates. This study provides evidence for bacterial virulence attenuation by DIM.

Probiotic Characteristics of Lactiplantibacillus Plantarum N-1 and Its Cholesterol-Lowering Effect in Hypercholesterolemic Rats.

In this study, the probiotic potential and treatment effects of Lactiplantibacillus plantarum N-1 in hypercholesterolemic rats were investigated, and the possible regulatory mechanisms of lipid metabolism via short-chain fatty acids (SCFAs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase were elucidated. The strain N-1 displayed probiotic properties of antioxidant capacity, adhesion to Caco-2 cells, susceptibility to antibiotics in vitro. The results in animal study showed that the total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in serum and TC in liver declined significantly in both N-1 and simvastatin (Sta) treatment groups compared to the control (P < 0.05), and the extent of these decreases were similar between them. The expression of the HMG-CoA gene in the N-1 group was downregulated significantly by 31.18% compared to the control (P < 0.01), and the contents of butyrate and valerate in N-1 groups were significantly higher than those in both model and Sta group (P < 0.05). Thus, promoting the production of the intestinal SCFAs and inhibiting the expression of HMG-CoA reductase by L. plantarum N-1 may contribute to the improved lipid metabolism and thus lowering cholesterol level in rats. Our investigation indicated that L. plantarum N-1 has the potential to be developed into a functional food supplement for hypercholesterolemia treatment.

Rational Design of a Highly Dispersed Fe-N-C Nanosheet with 1,10-Phenanthroline-2,9-Dicarboxylic Acid as a Preorganized Ligand: Boosted Electrochemiluminescence Detection of Tetracycline.

In view of the shortcomings of the current coreactant electrochemiluminescence (ECL) and inspired by natural oxygen (O2) reduction metalloenzymes, a novel ECL amplification strategy was established. A pyrolytic iron- and nitrogen-doped (Fe-N-C) nanosheet rich in singly ionized oxygen vacancy (VO•) defects was rationally designed by destroying the highly saturated coordination with a preorganized ligand 1,10-phenanthroline-2,9-dicarboxylic acid (PDA). Extraordinary catalytic activity for O2 activation was obtained via screening a special pyrolysis temperature using spectroscopic and electrochemical methods. The high-spin ferric centers of highly dispersed FeC nanoclusters and abundant carbon and oxygen vacancy defects fully contributed to the inherent catalytic activity. ECL amplification was achieved by integrating the material with luminol to generate redox-active radicals in situ from dissolved O2 and simultaneously shorten the transferring distance of radicals. Tetracycline (TC), which posed a growing threat to aquatic biodiversity and environmental safety, as a model antibiotic was successfully detected with a detection limit of 3.88 nM (S/N = 3), clarifying a promising application prospect of this new effective ECL amplification strategy in biological analysis and environmental monitoring.

Multi-tailoring of a modified MOF-derived CuxO electrochemical transducer for enhanced hydrogen peroxide sensing.

Reasonable control of the redox states within the catalytic units together with the interconnection degrees of the substrate is of great significance in the modulation of a well-performing transducer. Herein, a novel carbon black (CB)-modified copper metal-organic framework nanomaterial (CB@Cu-MOF) prepared at room temperature was utilized as a precursor to synthesize mixed-valent copper-oxide composite catalysts (NC/CuxO-T). By tuning the carbonization process of the precursor at different temperatures (T = 100 °C, 200 °C, 300 °C and 400 °C), the different ratio configurations of the redox-alternated CuxO portions were successfully controlled with the simultaneous effective tailoring of the defect abundance in the N-doped carbon substrate. As a result, an optimized NC/CuxO-300 electrochemical H2O2 sensor was able to present a low detection limit (0.26 µM) and decent linear ranges (0.02-1.79 mM and 2.29-9.29 mM). Our strategy using easily available initial materials with mild preparation conditions is expected to promote the practical application of the star materials in laboratories.

Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing.

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria N-acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.

Postmodulation of the Metal-Organic Framework Precursor toward the Vacancy-Rich CuxO Transducer for Sensitivity Boost: Synthesis, Catalysis, and H2O2 Sensing.

Metal-organic frameworks (MOFs) act as versatile coordinators for the subsequent synthesis of high-performance catalysts by providing dispersed metal-ion distribution, initial coordination condition, dopant atom ratios, and so on. In this work, a crystalline MOF trans-[Cu(NO3)2(Him)4] was synthesized as the novel precursor of a redox-alternating CuxO electrochemical catalyst. Through simple temperature modulation, the gradual transformation toward a highly active nanocomposite was characterized to ascertain the signal enhancing mechanism in H2O2 reduction. Owing to the proprietary structure of the transducer material and its ensuing high activity, a proof-of-principle sensor was able to provide an amplified sensitivity of 2330 µA mM-1 cm-2. The facile one-pot preparation and intrinsic nonenzymatic nature also suggests its wide potentials in medical settings.

Fe-MOGs-based enzyme mimetic and its mediated electrochemiluminescence for in situ detection of H2O2 released from Hela cells.

Enzyme mimetics have attracted wide interest due to their inherent enzyme-like activity and unique physicochemical properties, as well as promising applications in disease diagnosis, treatment and monitoring. Inspired by the attributes of nonheme iron enzymes, synthetic models were designed to mimic their capability and investigate the catalytic mechanisms. Herein, metal-organic gels (Fe-MOGs) with horseradish peroxidase (HRP) like Fe-NX structure were successfully synthesized though the coordination between iron and 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) and exhibited excellent peroxidase-like activity. Its structure-activity relationship and the in-situ electrochemiluminescence (ECL) detection of H2O2 secreted by Hela cells were further investigated. The highly dispersed Fe-NX active sites inside Fe-MOGs were able to catalyze the decomposition of H2O2 into large amounts of reactive oxygen species (ROS) via a Fenton-like reaction under a low overpotential. Due to the accumulation of ROS free radicals, the luminol ECL emission was significantly amplified. A proof-of-concept biosensor was constructed with a detection limit as low as 2.2 nM and a wide linear range from 0.01 to 40 µM. As a novel metal organic gels based enzyme mimetic, Fe-MOGs show great promises in early cancer detection and pathological process monitoring.

Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing.

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein's productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

Cigarette smoke toxicity modes of action estimated by a bioluminescent bioreporter bacterial panel.

Cigarette smoking is considered to be a risk factor for several chronic diseases and even premature death. However, despite the importance of this detrimental habit, little seems known in terms of the overall toxicity potential of its ingredients in humans. In this study, a panel of genetically modified bioluminescent bioreporter bacteria was used to evaluate its usefulness in estimating the cigarette smoke's complex molecular mixture on a bacterial toxicity-bioreporter panel, both filtered or unfiltered. This work enabled to confirm the usefulness of cigarette filters, with better protection found in higher priced brands despite both having genotoxic and cytotoxic attributes. Quorum sensing interference was also shown, which may explain why cigarette smokers are at greater risk for pulmonary infections. Moreover, the findings of this study support the fact that the filter is a dominating contributor to reducing the harm caused by cigarette smoke. Increased efforts should be conducted to reduce the harmful effects of cigarette smoke, via increasingly effective filters. To conclude, the panel of bioreporter bacteria was found to be useful in the evaluation of the general effect of the toxic mixture found in cigarette smoke and therefore has the potential to be used in cigarette research, helping researchers pinpoint the reduction of toxicity when working with filter improvement.

Blood biomarkers to detect new-onset atrial fibrillation and cardioembolism in ischemic stroke patients.

BACKGROUND: Accumulating data suggest blood biomarkers could inform stroke etiology. OBJECTIVE: The purpose of this study was to investigate the performance of multiple blood biomarkers in elucidating stroke etiology with a focus on new-onset atrial fibrillation (AF) and cardioembolism. METHODS: Between January and December 2017, information on clinical and laboratory parameters and stroke characteristics was prospectively collected from ischemic stroke patients recruited from the National University Hospital, Singapore. Multiple blood biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], d-dimer, S100ß, neuron-specific enolase, vitamin D, cortisol, interleukin-6, insulin, uric acid, and albumin) were measured in plasma. These variables were compared with stroke etiology and the risk of new-onset AF and cardioembolism using multivariable regression methods. RESULTS: Of the 515 ischemic stroke patients (mean age 61 years; 71% men), 44 (8.5%) were diagnosed with new-onset AF, and 75 (14.5%) had cardioembolism. The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 3 biomarkers (NT-proBNP ≥294 pg/mL; S100ß ≥64 pg/mL; cortisol ≥471 nmol/l) identified patients with new-onset AF (negative predictive value [NPV] 90%; positive predictive value [PPV] 73%; area under curve [AUC] 85%). The combination of 2 laboratory parameters (total cholesterol ≤169 mg/dL; triglycerides ≤44.5 mg/dL) and 2 biomarkers (NT-proBNP ≥507 pg/mL; S100ß ≥65 pg/mL) identified those with cardioembolism (NPV 86%; PPV 78%; AUC 87%). Adding clinical predictors did not improve the performance of these models. CONCLUSION: Blood biomarkers could identify patients with increased likelihood of cardioembolism and direct the search for occult AF.