Robust Luminescent Pyrene-Based Metal-Organic Framework Hydrogel as a pH-Responsive Fluorescence Emitter for Sensitive Immunoassay of Cardiac Troponin I.

Despite many luminescent advantages including outstanding absorption coefficient and high quantum yield, pyrene and its derivatives have been suffering from a dramatic aggregation-caused quenching (ACQ) effect. Although the dramatic ACQ effect of pyrene-based fluorophores has been restrained in pyrene-doped metal-organic frameworks (MOFs), the low loading of fluorescent (FL) units substantially impedes the improved luminescent behaviors. Herein, pyrene-based MOFs hydrogel was synthesized with a high loading of pyrene as the unique organic linker blocks instead of a dopant in MOFs. The gel matrix contributed to rigidifying the location of the FL emitters and achieving intensive FL emission and high luminescent stability and therefore efficiently overcoming the ACQ effect. Furthermore, the protonation of pyrene in the MOFs hydrogel remarkably decreased the luminescent intensity, which endowed the FL hydrogel with highly pH-responsive activity in the broad range (pH 4-10). Interestingly, glucose oxidase was immobilized into ZIF-8 as a highly efficient luminescent quencher, which contributed to catalyzing the form of gluconic acid and thus drastically quenching the FL signal of the MOFs hydrogel. Furthermore, the emitter-quencher pair of pyrene-based MOFs hydrogel and glucose oxidase was successfully employed to develop an ultrasensitive FL immunoassay platform for cardiac troponin I (as a model analyte). The limit of detection for cardiac troponin I was 5.2 pg/mL (3σ). The proof-of-principle study demonstrated the thrilling auxiliary effect of tailorable MOFs hydrogel on boosting the feasibility of aqueous insoluble FL chromophores for trace analysis.

Association Between High Sensitivity Troponin I and NTproBNP With Rejection and Graft Loss in Pediatric Heart Transplant Recipients.

BACKGROUND: Troponin I is a blood biomarker of cardiac injury and levels measured using a high-sensitivity assay after pediatric heart transplantation (HT) have not been described. We sought to assess the association between high-sensitivity troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NTproBNP) with treated acute rejection (AR) and graft loss in pediatric heart transplant (HT) recipients. METHODS: Serum was collected and banked from pediatric HT recipients prior to cardiac catheterization. Patients with samples drawn within 365 days post-HT were included and followed for up to 5 years. Generalized linear mixed-effect models examined the association between hsTnI and treated AR using a random intercept per patient. Cox proportional hazards models tested the association between maximal hsTnI and NT-proBNP and death/graft loss. RESULTS: HsTnI and NTproBNP values decline in the weeks following HT, after which these biomarkers stabilize. HsTnI was higher in AR versus no AR (6.2 vs. 3.5 ng/L, p < 0.001); doubling of hsTnI increased the odds of AR by 33% (p = 0.004). HsTnI showed moderate discrimination for AR with an AUC of 0.811 (95% CI 0.76, 0.87) and a NPV of 96.4% (95% CI 93.0, 98.1). Elevation in NT-proBNP was not associated with AR. In multivariable Cox modeling, a doubling of maximal NT-proBNP was associated with graft loss (HR 8.96, p = 0.014). CONCLUSIONS: In this pediatric HT cohort, HsTnI was moderately discriminative for AR and higher maximal NT-proBNP was associated with graft loss. HsTnI may add value in pediatric HT non-invasive AR surveillance, and elevated NTproBNP could suggest an increased risk of graft loss.

ST-Segment Alterations in the Electrocardiogram of Acute Pulmonary Thromboembolism: A Rabbit Model.

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-?), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-?, and TNI were significantly elevated, and these changes were statistically significant (P<0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-?, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P<0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE. Keywords: Animal model of pulmonary embolism, B-type natriuretic peptide, Electrocardiogram, Pulmonary thromboembolism, Troponin I, Tumor necrosis factor-alpha.

Significance of an Early Repeat Troponin Measurement Upon Presentation to the Hospital for Acute Heart Failure.

BACKGROUND: Higher cardiac troponin is associated with worse outcomes in patients with acute heart failure. The significance of repeat measurements over hours remains unclear. We assessed whether a repeat measurement and the Δ between measurements of high-sensitivity cardiac troponin I (hs-cTnI) were associated with outcomes in hypervolemic patients with acute heart failure without acute coronary syndrome. METHODS AND RESULTS: We analyzed 582 individuals from AKINESIS (Acute Kidney Injury Neutrophil Gelatinase-Associated Lipocalin Evaluation of Symptomatic Heart Failure Study) with hs-cTnI measured ≤12 hours from admission and repeated ≤6 hours thereafter. Associations between hs-cTnI levels and their Δ with short-term (death, intensive care unit admission, receipt of inotropes, or positive pressure ventilation during hospitalization) and long-term (death or heart failure readmission within 1 year) outcomes were assessed. The average age was 69±13 years, 62% were men, 65% were White, 46% had coronary artery disease, and 22% had chest pain. Median hs-cTnI levels were 27 (interquartile range [IQR], 13-62) ng/L initially and 28 (IQR, 14-68) ng/L subsequently, with a Δ of 0 [IQR, -2 to 4] ng/L over 3.4±1 hours. Only the second measurement was associated with short-term outcomes (odds ratio, 1.14 per 2-fold higher [95% CI, 1.02-1.28]). Both individual measurements and the Δ were associated with long-term outcomes (hazard ratios, 1.09, 1.12, and 1.16 for first, second, and Δ, respectively). Associated risk for the first and second measurements were not constant over the year but highest early after being measured and decreased over 1 year. CONCLUSIONS: Repeat measurements of hs-cTnI over hours can identify individuals with acute heart failure without acute coronary syndrome at risk for short- and long-term outcomes.

Genetic excision of the regulatory cardiac troponin I extension in high-heart rate mammal clades.

Mammalian cardiac troponin I (cTnI) contains a highly conserved amino-terminal extension harboring protein kinase A targets [serine-23 and -24 (Ser23/24)] that are phosphorylated during ß-adrenergic stimulation to defend diastolic filling by means of an increased cardiomyocyte relaxation rate. In this work, we show that the Ser23/24-encoding exon 3 of TNNI3 was pseudoexonized multiple times in shrews and moles to mimic Ser23/24 phosphorylation without adrenergic stimulation, facilitating the evolution of exceptionally high resting heart rates (~1000 beats per minute). We further reveal alternative exon 3 splicing in distantly related bat families and confirm that both cTnI splice variants are incorporated into cardiac myofibrils. Because exon 3 of human TNNI3 exhibits a relatively low splice strength score, our findings offer an evolutionarily informed strategy to excise this exon to improve diastolic function during heart failure.

Perioperative Change of High-Sensitive Cardiac Troponin I Concentration in Cats According to Three Different Anaesthesia Protocols.

BACKGROUND: Cardiac troponin I, a particular biomarker, is released into the bloodstream in response to myocardial injury. OBJECTIVES: To evaluate perioperative changes in high-sensitivity cardiac troponin I (hs-cTnI) concentration during ovariohysterectomy in cats undergoing three different anaesthesia protocols. METHODS:  Twenty-one female mixed-breed cats owned by clients aged (2.2 ± 0.7 years) and weight (3.2 ± 0.5 kg) were included in our study. The cats were divided into three groups: propofol-isoflurane (PI) group (n = 7), xylazine-ketamine (XK) group (n = 7) and xylazine-isoflurane (XI) group (n = 7). After pre-anaesthetic propofol (6 mg/kg IV) was administered to cats in Group PI, a mask was placed, and anaesthesia was maintained with 3.0% isoflurane in oxygen. Cats in Group XK underwent general anesthetization with xylazine hydrochloride (2 mg/kg IM) and, 10 min later, ketamine hydrochloride (10 mg/kg IM). Cats in Group XI were administered xylazine hydrochloride (2 mg/kg IM), and then anaesthesia (3.0% isoflurane and oxygen) was continued with a mask. Blood samples were collected from all cats; preoperatively and postoperatively at 0 and 12 h (Pre-, Post-0 h and Post-12 h, respectively). Serum hs-cTnI concentrations were measured with the Advia Centaur TnI-Ultra. RESULTS: In all 21 cats, hs-cTnI concentration increased at Post-0 h and 12 h measurement points compared to Pre-. In the XK group, hs-cTnI concentrations exhibited a significant increase at the Post-0 h (51.30 ng/L) and Post-12 h (157.70 ng/L) time points compared to Pre- (6.70 ng/L) (p < 0.05). CONCLUSIONS: The XK group increased the concentration of hs-cTnI more than other protocols. In the PI group, the increase in hs-cTnI concentrations at Post-0 and 12 h increased less than the other two groups (p < 0.05). The PI group was found to induce less myocardial damage.

Exercise-Induced Cardiac Troponin I Elevation Is Associated With Regional Alterations in Left Ventricular Strain in High-Troponin Responders.

BACKGROUND: The implications of exercise-induced cardiac troponin elevation in healthy individuals are unclear. This study aimed to determine if individuals with a high exercise-induced cardiac troponin I (cTnI) response have alterations in myocardial function following high-intensity endurance exercise compared with normal-cTnI responders. METHODS AND RESULTS: Study individuals were recruited from previous participants in a 91-km mountain bike cycling race (the North Sea Race) and were classified as high- (n=34) or normal-cTnI responders (n=25) based on maximal cTnI values after the recruitment race. The present study exposed all participants to 2 prolonged high-intensity exercises: a combined lactate threshold and cardiopulmonary exercise test and repeated participation in the North Sea Race. Echocardiography was performed before, immediately after, and 24 hours following exercise. All study individuals (n=59) had normal coronary arteries, and were aged 51±10 years; 46 (74%) were men. There were no differences in baseline characteristics between the high- and normal-cTnI responders. Maximal cTnI levels 3 hours after exercise were significantly higher in the high- compared with normal-cTnI group (P<0.001-0.027). Following exercise, there were no differences in global ventricular function between the 2 groups. In contrast, high-cTnI responders had significantly lower regional strain in the anteroseptal segments following exercise, with more profound changes after the race. CONCLUSIONS: High-cTnI responders had lower anteroseptal segmental strain shortly after exercise than normal-cTnI responders. However, there were no permanent alterations in myocardial strain, indicating no short- or long-term adverse consequences of these exercise-induced alterations in myocardial function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

Copper(II)-Tannic Acid@Cu with In Situ Grown Gold Nanoparticles as a Bifunctional Matrix for Facile Construction of Label-Free and Ultrasensitive Electrochemical cTnI Immunosensor.

Sensitive detection of cardiac troponin I (cTnI) is of great significance in the diagnosis of a fatal acute myocardial infarction. A redox-active nanocomposite of copper(II)-tannic acid@Cu (CuTA@Cu) was herein prepared on the surface of a glassy carbon electrode by electrochemical deposition of metallic copper combined with a metal stripping strategy. Then, HAuCl4 was in situ reduced to gold nanoparticles (AuNPs) by strong reductive catechol groups in the TA ligand. The AuNPs/CuTA@Cu composite was further utilized as a bifunctional matrix for the immobilization of the cTnI antibody (anti-cTnI), producing an electrochemical immunosensor. Electrochemical tests show that the immunoreaction between anti-cTnI and target cTnI can cause a significant reduction of the electrochemical signal of CuTA@Cu. It can be attributed to the insulating characteristic of the immunocomplex and its barrier effect to the electrolyte ion diffusion. From the signal changes of CuTA@Cu, cTnI can be analyzed in a wide range from 10 fg mL-1 to 10 ng mL-1, with an ultralow detection limit of 0.65 fg mL-1. The spiked recovery assays show that the immunosensor is reliable for cTnI determination in human serum samples, demonstrating its promising application in the early clinical diagnosis of myocardial infarction.

Controlled labelling of tracer antibodies for time-resolved fluorescence-based immunoassays.

Tracer antibodies, which are labelled with fluorescent or other type of reporter molecules, are widely employed in diagnostic immunoassays. Time-resolved fluorescence immunoassay (TRFIA), recognized as one of the most sensitive immunoassay techniques, utilizes tracers labelled with lanthanide ion (Ln) chelates. The conventional approach for conjugating isothiocyanate (ITC) Ln-chelates to antibodies involves random chemical targeting of the primary amino group of Lys residues, requiring typically overnight exposure to an elevated pH of 9-9.3 and leading to heterogeneity. Moreover, efforts to enhance the sensitivity of the assays by introducing a higher number of Ln-chelates per tracer antibody are associated with an elevated risk of targeting critical amino acid residues in the binding site, compromising the binding properties of the antibody. Herein, we report a method to precisely label recombinant antibodies with a defined number of Ln-chelates in a well-controlled manner by employing the SpyTag/SpyCatcher protein ligation technology. We demonstrate the functionality of the method with a full-length recombinant antibody (IgG) as well as an antibody fragment by producing site-specifically labelled antibodies for TRFIA for cardiac troponin I (cTnI) detection with a significant improvement in assay sensitivity compared to that with conventionally labelled tracer antibodies. Overall, our data clearly illustrates the benefits of the site-specific labelling strategy for generating high-performing tracer antibodies for TRF immunoassays.

[Clinical analysis of maternal autoantibody-mediated complete left bundle branch block in 9 children].

Objective: To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies. Methods: A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results: Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) µg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions: Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Influence of Anticoagulants on the Dissociation of Cardiac Troponin Complex in Blood Samples.

Immunodetection of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT) in blood samples is widely used for the diagnosis of acute myocardial infarction. The cardiac troponin complex (ITC-complex), comprising cTnI, cTnT, and troponin C (TnC), makes up a large portion of troponins released into the bloodstream after the necrosis of cardiomyocytes. However, the stability of the ITC-complex has not been fully investigated. This study aimed to investigate the stability of the ITC-complex in blood samples. A native ITC-complex was incubated in buffer solutions, serum, and citrate, heparin, or EDTA plasma at various temperatures. Western blotting and gel filtration were performed, and troponins were detected using specific monoclonal antibodies. The ITC-complex dissociated at 37 °C in buffers with or without anticoagulants, in citrate, heparin, and EDTA plasmas, and in serum, into a binary cTnI-TnC complex (IC-complex) and free cTnT. In plasma containing heparin and EDTA, the IC-complex further dissociated into free TnC and cTnI. No dissociation was found at 4 °C or at room temperature (RT) in all matrices within 24 h except for EDTA plasma. After incubation at 37 °C in EDTA plasma and serum, dissociation was accompanied by proteolytic degradation of both cTnI and cTnT. The presence of anti-troponin autoantibodies in the sample impeded dissociation of the ITC-complex. The ITC-complex dissociates in vitro to form the IC-complex and free cTnT at 37 °C but is mostly stable at 4 °C or RT. Further dissociation of the IC-complex occurs at 37 °C in plasmas containing heparin and EDTA.

Acute Myocardial Injury in Spontaneous Intracerebral Hemorrhage: A Secondary Observational Analysis of the FAST Trial.

BACKGROUND: Acute myocardial injury is associated with poor outcomes in patients with acute ischemic stroke, but its prognostic significance in patients with spontaneous intracerebral hemorrhage remains unclear. We investigated whether acute myocardial injury and the direction of the cardiac troponin I (cTnI) change (rising versus falling) affect post-intracerebral hemorrhage outcomes. METHODS AND RESULTS: We re-analyzed the FAST (Factor-Seven-for-Acute-Hemorrhagic-Stroke) trial. Acute myocardial injury was defined as at least 1 cTnI value above the upper reference limit with a rise/fall of >20%. Logistic regression tested for associations (1) between acute myocardial injury (presence versus absence) and poor outcome (modified Rankin Scale 4-6) and mortality at 15 and 90 days; (2) among 3 groups (rising versus falling versus no acute myocardial injury) and outcomes. Among the 841 FAST participants, 785 patients were included. Acute myocardial injury was detected in 29% (n=227); 170 had rising cTnI. At 15 and 90 days, respectively, those with acute myocardial injury had higher odds of poor outcome (adjusted odds ratio) ([aOR] 2.3 [95% CI, 1.3-3.9]); and adjusted odds ratio 2.5 [95% CI, 1.6-3.9];, and higher odds of mortality (adjusted odds ratio 2.4 [95% CI, 1.4-4.3]; and adjusted odds ratio 2.2 [CI, 1.3-3.6]) than patients without. There was no interaction between FAST group assignment and myocardial injury, and associations between myocardial injury and outcomes were consistent across group assignments. Rising cTnI was associated with the highest risk of poor outcomes and mortality. CONCLUSIONS: In this secondary analysis of the FAST trial, acute myocardial injury was common and associated with poor outcomes. The direction of the cTnI change might provide additional risk stratification after intracerebral hemorrhage.

Intracardiac ultrasound-guided transseptal puncture in horses: Outcome, follow-up, and perioperative anticoagulant treatment.

BACKGROUND: Cardiac catheterizations in horses are mainly performed in the right heart, as access to the left heart traditionally requires an arterial approach. Transseptal puncture (TSP) has been adapted for horses but data on follow-up and closure of the iatrogenic atrial septal defect (iASD) are lacking. HYPOTHESIS/OBJECTIVES: To perform TSP and assess postoperative complications and iASD closure over a minimum of 4 weeks. ANIMALS: Eleven healthy adult horses. METHODS: Transseptal puncture was performed under general anesthesia. Serum cardiac troponin I concentrations were measured before and after puncture. Weekly, iASD closure was monitored using transthoracic and intracardiac echocardiography. Relationship between activated clotting time and anti-factor Xa activity during postoperative enoxaparin treatment was assessed in vitro and in vivo. RESULTS: Transseptal puncture was successfully achieved in all horses within a median duration of 22 (range, 10-104) minutes. Balloon dilatation of the puncture site for sheath advancement was needed in 4 horses. Atrial arrhythmias occurred in 9/11 horses, including atrial premature depolarizations (N = 1), atrial tachycardia (N = 5), and fibrillation (N = 3). Serum cardiac troponin I concentrations increased after TSP, but remained under the reference value in 10/11 horses. Median time to iASD closure was 14 (1-35) days. Activated clotting time correlated with anti-factor Xa activity in vitro but not in vivo. CONCLUSIONS AND CLINICAL IMPORTANCE: Transseptal puncture was successfully performed in all horses. The technique was safe and spontaneous iASD closure occurred in all horses. Clinical application of TSP will allow characterization and treatment of left-sided arrhythmias in horses.

Perioperative changes in plasma cardiac troponin I concentration during mitral valvuloplasty for severe mitral regurgitation in dogs.

Background: Mitral valvuloplasty (MVP) is a surgical procedure for treating severe mitral regurgitation in dogs. Although MVP is considered highly invasive, the extent of myocardial injury, postoperative complications, and recovery has not been evaluated. Aim: This study examined the degree of MVP invasiveness, the extent of myocardial damage, postoperative complications, cardiomyocyte recovery, and timing of hospital discharge. Methods: Cardiac troponin I (cTnI) was used to investigate the myocardial damage caused by cardiac arrest associated with a surgical approach to the myocardium in 13 patients with MVP and five controls with patent ductus arteriosus (PDA) who underwent similar anesthesia and thoracotomy. Results: The level of cTnI peaked 1 day after surgery and was significantly higher in the MVP group (median, 19.90 ng/ml) than in the control group (median, 1.50 ng/ml p < 0.001). At day 7, the cTnI level was significantly higher in the MVP group (1.9 ng/ml) than in the control group (0.1 ng/ml) (p < 0.001), and recovery to the preoperative level took 10 days in the MVP group but returned to the preoperative level at day 7 in the control group. Although the mean arterial pressure of cardiopulmonary bypass (CPB) at the time of use was 42.92 mmHg, the peak cTnI levels in the two patients who exhibited a temporary decrease of 20 mmHg or less (46.03 ng/ml) were significantly higher than in the other 11 patients (19.70 ng/ml) (p < 0.05). Preoperative cTnI levels were correlated with the severity of postoperative complications (P = 0.03, F = 0.71). Conclusion: The results showed that MVP caused temporary greater myocardial tissue damage than thoracotomy, but postoperative recovery was smoother. A high preoperative cTnI level requires relatively more careful postoperative management, and measuring the level of cTnI over time after surgery can provide information about the extent of myocardial damage and recovery from surgery and help determine the time of discharge.

Minimal effects after a massive intravenous terbutaline overdose in a child.

A 22-kg female in early childhood with a history of reactive airway disease presented to a paediatric emergency department with acute shortness of breath, tachypnoea and wheezing. Despite treatment with albuterol and corticosteroids, her bronchospasm persisted, prompting the administration of terbutaline. The patient received 220 mcg (10 mcg/kg) terbutaline intravenously, followed immediately by an inadvertent supratherapeutic intravenous dose of 10 000 mcg (454.5 mcg/kg). The patient's laboratory results obtained minutes after the medication error were notable for: potassium, 3.1 mmol/L, lactate, 2.6 mmol/L and troponin I, 0.30 ng/mL (normal <0.03 ng/mL). Over the next 48 hours, serial serum troponin values decreased. The patient was discharged home approximately 72 hours after the initial presentation and she remained well based on follow-up calls over the next several months. Given the timing and trend of troponin concentrations, we do not believe the terbutaline overdose to be responsible for the myocardial injury.

A Fluorescent Lateral Flow Immunoassay for the Detection of Skeletal Muscle Troponin I in Serum for Muscle Injury Monitoring at the Point of Care.

Exercise-induced muscle injury is one of the most common types of sports injuries. Skeletal muscle troponin I (skTnI) serves as an ideal biomarker in assessing such injuries, facilitating timely detection and evaluation. In this study, we develop a fluorescent sandwich lateral flow immunoassay (LFIA) combined with a desktop analyzer for rapid detection of skTnI. Through optimizing the reaction system, the assay achieves a satisfying detection performance, reaching a limit of detection (LOD) of 0.5 ng/mL with a turnaround time of 15 min. The proposed detection platform offers portability, ease of use, and high sensitivity, which facilitates the monitoring of exercise-induced muscle injuries at the point of care. This feature is particularly advantageous for end users, enabling timely detection of sports-related injuries and ultimately enhancing prognosis and sports life.

An Electrochemical Biosensor for the Detection of Pulmonary Embolism and Myocardial Infarction.

Due to the clinical similarities between pulmonary embolism (PE) and myocardial infarction (MI), physicians often encounter challenges in promptly distinguishing between them, potentially missing the critical window for the correct emergency response. This paper presents a biosensor, termed the PEMI biosensor, which is designed for the identification and quantitative detection of pulmonary embolism or myocardial infarction. The surface of the working electrode of the PEMI biosensor was modified with graphene oxide and silk fibroin to immobilize the mixture of antibodies. Linear sweep voltammetry was employed to measure the current-to-potential mapping of analytes, with the calculated curvature serving as a judgment index. Experimental results showed that the curvature exhibited a linear correlation with the concentration of antigen FVIII, and a linear inverse correlation with the concentration of antigen cTnI. Given that FVIII and cTnI coexist in humans, the upper and lower limits were determined from the curvatures of a set of normal concentrations of FVIII and cTnI. An analyte with a curvature exceeding the upper limit can be identified as pulmonary embolism, while a curvature falling below the lower limit indicates myocardial infarction. Additionally, the further the curvature deviates from the upper or lower limits, the more severe the condition. The PEMI biosensor can serve as an effective detection platform for physicians.

Cardiac troponin I directly binds and inhibits mitochondrial ATP synthase with a noncanonical role in the post-ischemic heart.

Cardiac troponin I (cTnI) is a key regulator of cardiomyocyte contraction. However, its role in mitochondria is unknown. Here we show that cTnI localized to mitochondria in the heart, inhibited mitochondrial functions when stably expressed in noncardiac cells and increased the opening of the mitochondrial permeability transition pore under oxidative stress. Direct, specific and saturable binding of cTnI to F1FO-ATP synthase was demonstrated in vitro using immune-captured ATP synthase and in cells using proximity ligation assay. cTnI binding doubled ATPase activity, whereas skeletal troponin I and several human pathogenic cTnI variants associated with familial hypertrophic cardiomyopathy did not. A rationally designed peptide, P888, inhibited cTnI binding to ATP synthase, inhibited cTnI-induced increase in ATPase activity in vitro and reduced cardiac injury following transient ischemia in vivo. We suggest that cTnI-bound ATP synthase results in lower ATP levels, and releasing this interaction during cardiac ischemia-reperfusion may increase the reservoir of functional mitochondria to reduce cardiac injury.