Human Serum Research Articles

Genomic Dissection of an Enteroaggregative Escherichia coli Strain Isolated from Bacteremia Reveals Insights into Its Hybrid Pathogenic Potential.

Escherichia coli is a frequent pathogen isolated from bloodstream infections. This study aimed to characterize the genetic features of EC092, an E. coli strain isolated from bacteremia that harbors enteroaggregative E. coli (EAEC) genetic markers, indicating its hybrid pathogenic potential. Whole-genome sequencing showed that EC092 belongs to phylogroup B1, ST278, and serotype O165:H4. Genes encoding virulence factors such as fimbriae, toxins, iron-uptake systems, autotransporter proteins (Pet, Pic, Sat, and SepA), and secretion systems were detected, as well as EAEC virulence genes (aggR, aatA, aaiC, and aap). EC092 was found to be closely related to the other EAEC prototype strains and highly similar in terms of virulence to three EAEC strains isolated from diarrhea. The genomic neighborhood of pet, pic, sat, sepA, and the EAEC virulence genes of EC092 and its three genetically related fecal EAEC strains showed an identical genomic organization and nucleotide sequences. Also, EC092 produced and secreted Pet, Pic, Sat, and SepA in the culture supernatant and resisted the bactericidal activity of normal human serum. Our results demonstrate that the strain EC092, isolated from bacteremia, is a hybrid pathogenic extraintestinal E. coli (ExPEC)/EAEC with virulence features that could mediate both extraintestinal and intestinal infections.

Genetic liability to human serum metabolites is causally linked to telomere length: insights from genome-wide Mendelian randomization and metabolic pathways analysis.

Telomere has been recognized as a biomarker of accelerating aging, and telomere length (TL) shortening is closely related to diverse chronic illnesses. Human serum metabolites have demonstrated close correlations with TL maintenance or shortening in observational studies. Nevertheless, little is known about the underlying pathological mechanisms, and Mendelian randomization (MR) analysis of serum metabolites may provide a more comprehensive understanding of the potential biological process. We employed a two-sample MR analysis method to assess the causal links between 486 serum metabolites and TL. We applied the inverse-variance weighted (IVW) approach as our primary analysis, and to assure the stability and robustness of our results, additional analysis methods including the weighted median, MR-Egger, and weighted mode were conducted. MR-Egger intercept test was utilized to detect the pleiotropy. Cochran's Q test was implemented to quantify the extent of heterogeneity. Furthermore, the pathway analysis was conducted to identify potential metabolic pathways. We identified 11 known blood metabolites associated with TL. Among these metabolites, four were lipid (taurocholate, dodecanedioate, 5,8-tetradecadienoate, and 15-methylpalmitate), one amino acid (levulinate (4-oxovaleate)), one carbohydrate (lactate), one nucleotide (pseudouridine), one energy (phosphate), and three xenobiotics (2-hydroxyacetaminophen sulfate, paraxanthine, and ergothioneine). The known protective metabolites included levulinate (4-oxovaleate), dodecanedioate, 5,8-tetradecadienoate, lactate, phosphate, paraxanthine, and ergothioneine. Multiple metabolic pathways have been identified as being implicated in the maintenance of telomere length. Our MR analysis provided suggestive evidence supporting the causal relationships between 11 identified blood metabolites and TL, necessitating further exploration to clarify the mechanisms by which these serum metabolites and metabolic pathways may affect the progression of telomeres.

Molecular and Energetic Descriptions of the Plasma Protein Adsorption onto the PVC Surface: Implications for Biocompatibility in Medical Devices.

Protein adsorption on material surfaces plays a key role in the biocompatibility of medical devices. Therefore, understanding the complex interplay of physicochemical factors driving this kind of biofouling is paramount for advancing biomaterial design. In this study, we investigated the interaction of the most prominent plasma proteins with polyvinyl chloride (PVC) as one of the ubiquitous materials in medical devices. Through molecular docking, we identified human serum albumin (HSA) as a plasma protein with the highest affinity for adsorption onto the PVC surface with the binding energy of -25.9 kJ mol-1. Subsequently, utilizing triplicate molecular dynamics (MD) simulations (0.5 μs each), we quantitatively analyzed the interactions between HSA and PVC, probing potential structural changes in the protein upon adsorption. Our findings revealed that water-mediated hydrogen bonds and van der Waals forces are key contributors in stabilizing HSA onto the surface of PVC without significant alteration to its secondary and tertiary structures. The observed distribution of water molecules further highlights the importance of the hydration layer in facilitating and modulating protein-polymer interactions. We further evaluated the thermodynamic properties governing the adsorption process by calculating the potential of mean force (PMF) along the direction normal to the surface. The computed Gibbs free energy of adsorption at 300 K (-507.4 kJ/mol) indicated a thermodynamically favored and spontaneous process. Moreover, our investigations across different temperatures (290 to 310 K) consistently showed an enthalpy-driven adsorption process.

Studies of the interaction of graphene oxide (GO) with endothelial cells under static and flow conditions

Graphene oxide, due to its unique properties, has several potential applications in biomedicine, especially as a drug carrier. Despite emerging studies on its cytotoxicity and uptake into cells, there are still gaps in knowledge on this area. When analyzing the internalization of nanomaterials, many different factors must be considered, including particle size, surface modifications, and interactions with biological fluids that can change their properties. In the present study, we evaluated the effects of graphene oxide fractions in different sizes and samples incubated in human serum on endothelial cells (HUVECs). In addition, the study was conducted in both macroscale and microscale using Cell-on-a-Chip technology to better replicate in vivo conditions. Our findings indicate that samples incubated with serum reduce the efficiency of fraction uptake into cells. It was also observed that the uptake efficiency of graphene oxide (GO) fractions is higher in the microscale (in more real to in vivo environment) compared to the macroscale. Our research has shown that in order to determine the correct interaction of new materials into mammalian cells, it is necessary to take into account many different biochemical and physical factors.

Paper chip-based colorimetric biosensor for glucose by using CuFe2O4@GO as nanozyme

The development of nanomaterials with notable enzyme-like activity is of great significance to the field of bioanalysis. Herein, a nanomaterial composed of copper ferrite nanoparticles (CuFe2O4 NPs) and graphene oxide (GO) was successfully prepared (CuFe2O4@GO). The obtained CuFe2O4@GO was proved to have peroxidase-like (POD-like) activity, which could catalyze the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) to generate oxidized TMB (ox-TMB) in the presence of H2O2 with an obvious color change. On this basis, a colorimetric biosensor using a UV–vis spectrometer as readout and a paper chip-based colorimetric biosensor using a smartphone as readout was constructed for glucose detection, respectively, as glucose oxidase (GOD) could oxidize glucose to form H2O2. The UV–vis spectrometer-based approach exhibits a linear range of 0 to 1000 μM and a limit of detection (LOD) of 0.79 μM for glucose. The smartphone-based method shows a linear range of 0.1 to 50 mM and a LOD of 0.04 mM for glucose. Moreover, the fabricated colorimetric biosensors have good selectivity towards glucose and the sample matrixes cannot affect the detection of glucose. Finally, the concentration of glucose in human serum samples was successfully detected using two different ways, and the results are close to the clinical values. The proposed method embraces several good merits. Firstly, the colorimetric biosensors combining UV–vis spectrometer and smartphone offer precise results, which could effectively prevent the occurrence of false events. Secondly, paper-based microfluidic analytical device (μPAD) as analytical platform and smartphone as readout provides a versatile approach for constructing sensitive, cost-effective, and simple colorimetric biosensor for the visual monitoring of glucose. Lastly, except for glucose detection, this work also shows great application prospects for other small molecules detection that could generate H2O2.

Interaction between polydopamine-based IONPs and human serum albumin (HSA): a spectroscopic analysis with cytotoxicity impact

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe3O4@PDA). The Fe3O4@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA’s successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe3O4@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe3O4@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe3O4@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.

Green synthesis of CoVS2-MOF@CMS nanocomposite electrode for sustainable approach towards eco-friendly energy storage and dopamine detection

Dopamine, a crucial brain chemical belonging to the catecholamine and phenethylamine chemical families, plays a vital role in promoting a healthy and happy life. Irregular dopamine release has been linked to various neurological disorders and depressive conditions. Therefore, conducting real-time, in vivo monitoring of dopamine levels is essential to gain a comprehensive understanding of its physiological functions. In this research, the hydrothermal technique was employed to synthesize copper‑molybdenum sulfide (Cu2MoS4 (CMS)). Further, we have reported the one-pot hydrothermal synthesis of CoVS2-MOF, using the bioactive chemical as fuel obtained from Euphorbia cognata Boiss. The specific capacity (Qs) of the sample CoVS2-MOF@CMS was calculated to be 820 Cg−1 at 3 mVs−1, a value expressively higher than that of the reference samples. Furthermore, in the supercapattery device, an outstanding Qs of 300 Cg−1 was achieved at 1.5 Ag−1, surpassing the previously observed values. The device demonstrated outstanding performance, including a coulombic efficiency of 89 %, a specific energy of 36.68 Whkg−1, and a power density (Pd) of 2218.53 Wkg−1. Moreover, the sensor typically yielded dopamine (DA) concentrations in human serum ranging from 100.8 % to 102.2 %. The utilization of the multifunctional CoVS2-MOF@CMS nanocomposite electrode material illustrates promising prospects for the fabrication of hybrid devices with applications in biomedical and energy harvesting fields.

Production, purification and formulation of nanoradiopharmaceutical with 211At: An emerging candidate for targeted alpha therapy

IntroductionAstatine-211 has attained significant interest in the recent times as a promising radioisotope for targeted alpha therapy (TAT) of cancer. In this study, we report the production of 211At via 209Bi (α, 2n) 211At reaction in a cyclotron and development of a facile radiochemical separation procedure to isolate 211At for formulation of nanoradiopharmaceuticals. MethodsNatural bismuth oxide target in pelletized form wrapped in Al foil was irradiated with 30 MeV α-beam in an AVF cyclotron. The irradiated target was dissolved in 2 M HNO3 followed by selective precipitation of Bi as Bi(OH)3 under alkaline condition. The radiochemically separated 211At was used for labeling cyclic RGD peptide conjugated gold nanoparticles (Au-RGD NPs) by surface adsorption. The radiochemical stability of 211At-Au-RGD NPs was evaluated in phosphate buffered saline (PBS) and human serum media. ResultsThe batch yield of 211At at the end of irradiation was ∼6 MBq.μA−1.h−1. After radiochemical separation, ∼80 % of 211At could be retrieved with >99.9 % radionuclidic purity. Au-RGD NPs (particle size 8.4±0.8 nm) could be labeled with 211At with >99 % radiolabeling yield. The radiolabeled nanoparticles retained their integrity in PBS and human serum media over a period of 21 h. ConclusionsThe present strategy simplifies 211At production in terms of purification and would increase affordable access to this radioisotope for TAT of cancer.

Cupric ion coordination-mediated molecularly imprinted electrochemical sensor for the recognition and ratiometric detection of lidocaine

Molecularly imprinted polymers (MIPs) have been widely used as artificial recognition elements in sensing applications. However, their electrochemical sensing performance is generally hampered by limited affinity and uncontrolled condition change. In this work, a novel MIP electrochemical sensor based on metal coordination interaction was prepared and used for the recognition and ratiometric detection of lidocaine (LC). The sensor was constructed by electrodepositing Cu-coordinated MIP on biomass carbon modified glassy carbon electrode. Herein, Cu2+ ions acted as anchor for the immobilization of LC during the synthesis process, enabling the orderly formation of molecular recognition sites. Reversely, the metal coordination between Cu2+ ions and LC molecules facilitated the recognition of LC. Moreover, the doped cupric ions in the polymer film could provide a reference signal for subsequent ratiometric strategy. Thus the resulting sensor exhibited high selectivity, sensitivity, satisfactory reproducibility, and anti-interference ability. Under the selected conditions, the peak current ratio of LC and cupric ion was linear to LC concentration in the range of 0.008–2.5 μmol L−1 (R2 = 0.9951), and the limit of detection was 1.9 nmol L−1 (S/N = 3). The practical feasibility of the sensor was evaluated by detecting human serum and pharmaceutical samples, and satisfactory outcomes were obtained.

Tuning assembled DNA nanoarchitecture into disassembled state to enhance accurate and ultrasensitive detection of KRAS G12D mutation

Cancer remains a formidable global health challenge, necessitating precise diagnostic tools. The KRAS gene, particularly the G12D mutation, holds pivotal clinical significance across various cancer subtypes. Existing DNA sensing techniques using single-stranded and double-stranded oligonucleotide probes are susceptible for enzymatic degradation, especially in complex biological samples like blood or serum. To address these challenges, we present an innovative approach that involves tuning assembled DNA nanoarchitecture into a disassembled state to accurate and ultrasensitive detection of the KRAS G12D mutation. Our method utilized a pair of multifunctional assembly hairpin probes to construct a DNA wire with both of a fluorophore labeled probe and a quencher labeled probe attached. Upon binding with the target DNA, the DNA wire undergoes gradual disassembly, separating all fluorophores from quenchers to significantly amplify fluorescence signals. This approach offers exceptional sensitivity and reaction kinetics, capable of detecting the KRAS G12D at femtomolar levels, and demonstrates outstanding specificity in discriminating single-base mutations. Furthermore, the DNA nanoarchitecture with well-demonstrated ability to nuclease resistance makes our method exhibits robustness in detecting KRAS G12D mutation in human serum samples. This innovative approach represents an advancement in cancer diagnostics, providing a promising tool for early disease diagnosis and biomedical study.

Toward the point-of-care testing of alkaline phosphatase in human serum

This work addresses challenges of simple but reliable determination of enzyme alkaline phosphatase (ALP) in μL-sized serum samples. The single-tube assay and plate-based immunoassay were developed by using a commercial glucose test strip (GTS) to transduce analytical signal from the ALP + glucose-6-phosphate (G6P) reaction. The glucose released from G6P contributed to the flow of anodic charge Q20s through GTS. The interferences from serum matrix including those from native glucose were eliminated by devising a signal ΔQ20s = Q20s (total) – Q20s (matrix). The ΔQ20s was proportional to ALP activity within a linear range of 7.4–720 IU L−1 for assay (R2, 0.995) and 10–300 IU L−1 for immunoassay (R2, 0.983), which far exceeded a normal clinical range for ALP in adult human serum (30–150 IU L−1). Both methods required no auxiliary enzymes or labels, and were accurate (93–99 % signal recovery) and precise (RSD ≤10%). The assay was a simpler option because it required only one 20-min incubation step to determine ALP. The immunoassay involved three steps but it was still less laborious (by ∼70%) than a traditional enzyme-linked immunosorbent assay (ELISA) of ALP due to the substitution of ELISA detection antibody with GTS. The GTS-G6P-based methods bring ALP testing closer to the point-of-care locations, which is important considering the growing role of ALP as a prophylactic, therapeutic, and anti-inflammatory agent, and a marker of human diseases.

Precise determination of human serum albumin levels in blood serum by a D-π-A based near-infrared fluorescent probe via TICT mechanism

Human serum albumin (HSA) levels in the body are crucial for the accurate diagnosis of various health issues, necessitating continuous monitoring and novel detection methods. This study focused on the development and synthesis of two novel D-π-A small molecule near-infrared fluorescent probes, PTPA-B and CPTPA-B. The probes demonstrated selective detection of HSA with a rapid response time of 1 min and high sensitivity, featuring limits of detection (LOD) of 0.102 μM and 1.702 μM. Under physiological conditions, the intrinsic fluorescence of these probes is minimal due to intramolecular charge transfer (TICT). Upon entering the hydrophobic cavity of HSA, the probes exhibit red fluorescence by inhibiting the TICT process. Additionally, the probes exhibited enhanced biocompatibility in living cells and enabled fluorescence imaging of L-02 live cells. Therefore, the PTPA-B fluorescent probe serves as an effective tool for serum detection, revealing its potential applications in live cell imaging and precise clinical diagnosis.

Protein glycosylation inhibitory effects and mechanisms of phloretin and phlorizin

The anti-glycation potential and mechanism of phloretin and phlorizin were investigated in the study. In the methylglyoxal (MGO)-human serum albumin (HSA) glycosylation system, the inhibition against fluorescent advanced glycosylation end products (AGEs) was more than 60% at 960 μM phloretin and phlorizin. They decreased carbonylation and oxidative damage of protein, protected thiol groups and secondary structure of protein and inhibited protein aggregates. Treated with 1.37 mM phloretin or phlorizin, O2−· scavenging was more than 80%, and 1 mM phloretin or phlorizin chelated 60.08% or 28.11% of Fe2+, respectively. Analysis of HPLC and LC-QqQ-MS shown phloretin captured MGO by forming adducts with MGO, with capture rates of 92.67% within 24 h. The capture rate of phlorizin to MGO was 56.40%. The anti-glycosylation mechanisms of them could include the structural protection of HSA, capture of MGO, O2−· and ·OH scavenging and chelation of Fe2+. These findings may provide a theoretical basis for the application of phloretin and phlorizin as novel anti-glycosylation agents.

A comprehensive insight from molecular docking and dynamics with clinical investigation on the impact of direct oral anticoagulants on atheroprotective protein in atrial fibrillation

BackgroundDirect oral anticoagulants (DOACs) have high potency against their therapeutic target and are widely used in the treatment of atrial fibrillation (AF). Most DOACs are often claimed to have adverse effects due to off-target inhibition of essential proteins. Human serum paraoxonase 1 (PON1), one of the essential proteins, known for its anti-inflammatory and antioxidant properties, could be affected by DOACs. Thus, a comparative evaluation of DOACs and their effect on PON1 protein will aid in recommending the most effective DOACs for AF treatment. This study aimed to assess the impact of DOACs on PON1 through a combination of computational and experimental analyses.MethodsWe focus on apixaban, dabigatran, and rivaroxaban, the most recommended DOACs in AF treatment, for their impact on PON1 through molecular docking and molecular dynamics (MD) simulation to elucidate the binding affinity and drug-protein structural stability. This investigation revealed the most influential DOACs on the PON1 protein. Then experimental validation was performed in DOAC-treated AF participants (n = 42; 19 treated with dabigatran and 23 treated with rivaroxaban) compared to a healthy control group (n = 22) through gene expression analysis in peripheral blood mononuclear cells (PBMC) and serum enzyme concentration.ResultsOur computational investigation showed rivaroxaban (−4.24 kcal/mol) exhibited a lower affinity against the PON1 protein compared to apixaban (−5.97 kcal/mol) and dabigatran (−9.03 kcal/mol) through molecular docking. Dabigatran holds complex interactions with PON1 at GLU53, TYR197, SER193, and ASP269 by forming hydrogen bonds. Additionally, MD simulation revealed that dabigatran disrupts PON1 stability, which may contribute functional changes. Further experimental validation revealed a significant down-regulation (p < 0.05) of PON1 gene expression in PBMC and decreased serum PON1 enzyme concentration on DOAC treatment. Rivaroxaban as about 48% has inhibitory percentage and dabigatran as about 75% of inhibitory percentage compared to healthy control.ConclusionOverall, our computational and experimental results clearly show the higher inhibitory effect of dabigatran than rivaroxaban. Hence, rivaroxaban will be a better drug candidate for improving the outcome of AF.

A sandwich-type photoelectrochemical biosensor based on anthocyanin-sensitized ZnO/P5FIn heterojunction for the sensitive detection of CYFRA21-1.

. A sandwich-type photoelectrochemical (PEC) immunosensor based on a ZnO/poly(5-formylindole) (P5FIn)/anthocyanin heterostructure was developed to achieve sensitive background-free detection ofthe tumor marker CYFRA21-1. ZnO with good photovoltaic properties is combined with narrow bandgap P5FIn to form a p-n type heterojunction. This structure reduces the electron-hole pair recombination, thereby enhancing the photocurrent response of the composite. Anthocyanidins are environmentally friendly natural compounds with excellent antioxidant, redox properties, and remarkable electrochemical activity. After sensitization by anthocyanins, the absorption and utilization of visible light in the composites are enhanced, further improving the PEC luminescence efficiency of the materials. Additionally, boron nitride quantum dots (BN QDs) are combined with Ab2 via polydopamine (PDA) as a secondary antibody marker, enhancing its sensitivity. The biosensor exhibited a linear detection range of 0.001-100ngmL-1 with a limit of detection (LOD) of 0.00033ngmL-1. Furthermore, this biosensor demonstrates excellent selectivity, reproducibility, and stability, as well as successful results in analyzingactual human serum samples. This approach provides a feasible method for tumor marker detection.

Bridged triphenylamine-based fluorescent probe for selective and direct detection of HSA in urine

Human serum albumin (HSA) serves as a crucial indicator for therapeutic monitoring and biomedical diagnosis. In this study, a near infrared (NIR) fluorescent probe, termed BTPA, characterized a donor-π-acceptor (D-π-A) structure based on bridged triphenylamine (TPA) was developed. BTPA exhibited outstanding sensitivity and selectivity towards HSA among various analysts, with a remarkable 50-fold fluorescence enhancement with a significant Stokes shift (∼190 nm) and a wide linear detection range of 0–20 μM of HSA. Especially, BTPA displayed selectivity for discrimination of HSA from BSA. Job’s Plot analysis suggested a 1:1 stoichiometry for the formation of the BTPA-HSA complex. Displacement assays and molecular docking demonstrated that BTPA binds to subdomain IB of HSA which could effectively avoid interference from most drugs. Besides, BTPA have good biocompatibility and could detect of exogenous HSA with a relatively low fluorescence background. For practical applications, BTPA was tested for detecting HSA levels in human urine without any pretreatment, showing detection capability in the range of 0–10 μM with a fast response (<30 s), a limit of detection (LOD) of 0.12 μM and good recoveries (81.7–92.9 %), highlighting the high performance of bridged triphenylamine-based probe BTPA.

Ischemia-modified albumin: is it a promising marker in acute coronary syndrome?

BackgroundAcute coronary syndrome (ACS) is a type of coronary heart disease (CHD), which is responsible for one-third of total deaths in people older than 35 years. Even though cardiac troponin is the gold standard for myocardial necrosis it is blind for ischemia without necrosis. Studies demonstrate that Ischaemia Modified Albumin (IMA) is more sensitive in diagnosing ischemic chest pain compared to cardiac troponin T and electrocardiogram, and its combination with these tests significantly increases the sensitivity for diagnosing unstable angina, non-ST-elevation myocardial infarction (NSTEMI), or ST-elevation myocardial infarction (STEMI), with high positive and negative predictive values, making it a valuable tool for ruling out ACS in patients with inconclusive diagnoses in the emergency department.MethodsThis prospective cohort study, conducted at the Teaching Hospital, Peradeniya, Sri Lanka, from 2015 to 2019, investigated ischemia-modified albumin (IMA) levels in 330 acute coronary syndrome (ACS) patients. Excluding those with various chronic conditions and those on specific medications, serum IMA was analyzed using a colorimetric assay based on cobalt (II) binding to human serum albumin affected by myocardial ischemia. Serum IMA levels were measured, and statistical analyses, including non-parametric tests and correlation analyses, were conducted to evaluate the association between IMA levels and various demographic and clinical factors.ResultsIMA concentrations were found to be non-normally distributed, with an average concentration of 0.252 ± 0.123 AU. No overall significant gender-based difference in IMA levels was observed, though within the younger age group (< 59 years), males exhibited higher IMA concentrations than females. Significant gender differences were observed in the younger age group, with males showing higher IMA levels than females (p = 0.033). No significant differences in IMA levels were found across different ethnicities (p = 0.217) or BMI categories (p = 0.056). A significant increase in IMA levels was noted in ACS patients compared to control subjects (p < 0.001). Correlation analysis revealed significant associations between IMA levels and total cholesterol (r = 0.262, p = 0.009) and low-density lipoprotein (LDL) levels (r = 0.280, p = 0.006). Notably, a significant gender difference in IMA levels was found in obese patients, suggesting physiological differences in response to obesity. The study also revealed higher IMA concentrations in NSTEMI and STEMI patients compared to those with unstable angina.ConclusionThe study confirms elevated IMA levels in ACS patients, supporting its diagnostic potential. It reveals demographic influences, such as higher IMA levels in younger males and significant gender-specific differences in obese patients. Personalized approaches considering demographics and lipid management are essential for ACS risk reduction and IMA’s role in management.

Fabrication of Glucose Fluorescent Aptasensor Based on CdTe Quantum Dots.

Diabetes is a chronic metabolic disease characterized by high blood glucose (or blood sugar) levels, which harms the heart, blood vessels, eyes, kidneys, and nerves over time. So, it is crucial to regularly control glucose concentration in biological fluids to check its targets, reduce unpleasant symptoms of high and low blood sugar, and avoid long-term diabetes complications. This study developed a simple, rapid, sensitive, and cost-effective fluorescence system for glucose determination. The fluorescent Aptasensor was fabricated using cadmium telluride quantum dots (CdTe QDs) modified with thioglycolic acid and functionalized with thiol-glucose-aptamer through ligand exchange. The thiol-glucose-aptamer interacted directly with CdTe QDs, increasing fluorescence intensity. However, it decreased when the target molecules of glucose were introduced. The structural and morphological characteristics of the Aptasensor were confirmed by various analytical methods such as UV-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), energy dispersive x-ray spectroscopy (EDX), transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS). According to the typical Stern-Volmer equation, the relationship between fluorescent quenching and target concentration was linear with a detection limit (LOD) of 0.13 ± 1.95 × 10-11 mol L-1 and a relative standard deviation (RSD) of 1.05%. The Aptasensor demonstrated high specificity towards the target and stability over 28 days. Furthermore, it detected glucose in human serum and urine with a recovery rate of up to 99.74%. The results indicate that the fluorescent Aptasensor could be valuable in developing robust sensing technology for low-concentrated analytes.

Integrating high mannose-binding aptamer and CRISPR/Cas12a machinery for the remote detection of cell surface high mannose

High mannose is overexpressed on the cell surface during carcinogenesis; however, there are currently no efficient techniques for its detection. Herein, we propose an assay called RADAR (remote high mannose detection on cell surface with CRISPR) for the quantification of high mannose, leveraging the integration of high mannose-binding aptamer and CRISPR technique. The high mannose-binding aptamer is hybridized with a locker, which is released upon specific binding to high mannose. The released locker then activates CRISPR/Cas12a to produce a fluorescence signal. The "remote" concept in RADAR refers to the recognition of high mannose occurring on the cell surface, while signal generation takes place in a solution separate from the target. This feature makes RADAR suitable for the detection of suspended bio-samples without the need for sophisticated imaging. RADAR can detect high mannose Man9 with a limit of detection of 2.5 nM, distinguish cancer cells from non-cancerous cells, and profile high mannose level in human serum for potential non-small cell lung cancer (NSCLC) diagnosis. This work represents the first attempt to integrate CRISPR technology into the aptasensing of high mannose, which may serve as a synthetic biology-enabled tool in glycochemistry and glycobiology.

A ratiometric nanoplatform for fluorimetric and visual detection of Cu2+ and biothiols based on Eu MOFs and carbon dots

Herein, a ratiometric nanoplatform was established for fluorimetric and visual detection of Cu2+ and biothiols based on europium-based metal–organic frameworks (Eu MOFs) and carbon dots (CDs). Fluorescent Eu MOFs with red emission was facilely prepared via the coordination of Eu3+ with tetracycline (TC) and 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (Hepes). However, with addition of Cu2+, the fluorescence of Eu MOFs significantly decreased due to higher affinity of Cu2+ with TC, whereas the green fluorescence of CDs was not influenced by Cu2+, which served as an internal standard of the sensing platform. Interestingly, after introducing biothiols, the stronger coordination between Cu2+ and the sulfydryl of biothiols induced the release of TC to coordinate with Eu3+, thus recovering the fluorescence of Eu MOFs. The ratio changes of these two emissions accompanying by the distinct color variations of the solution under a 365 nm ultraviolet lamp could be used as output signals for fluorimetric and visual detection of Cu2+ and biothiols. The nanoplatform exhibited excellent sensing performance with limit detection as low as 0.57 μM for Cu2+, 0.54 μM for glutathione, 0.14 μM for homocyeteine and 0.42 µM for cysteine, respectively. In addition, it was successfully applied to detecting Cu2+ in environment water samples and biothiols in human serum samples, suggesting great potential for Cu2+ and biothiols determination in environmental and biological samples.