Human Serum Research Articles

Selective Clearance of Circulating Histones Based on Dodecapeptide-Grafted Copolymer Material for Sepsis Blood Purification.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.

Development of a simple estimation method of serum caffeine concentration using a point-of-care test kit for urinary caffeine.

Serum caffeine concentration is an indicator of caffeine intoxication; however, it is difficult to measure it in most emergency departments. We developed a simple estimation method using a point-of-care test kit for urinary caffeine. Caffeine-spiked human serum (100, 50, 25, and 10µg/mL) was diluted 10-, 20-, 50-, and 100-fold with phosphate-buffered saline and applied to the kit. After 5min incubation, the kit was scanned by a flatbed scanner and the membrane image was processed with ImageJ. When the 20-fold diluted serum was applied, serum samples with initial caffeine concentration ≤ 25 and ≥ 50µg/mL were caffeine-negative and -positive, respectively. When the 100-fold diluted serum was applied, none of the caffeine-spiked serum samples gave positive results. Therefore, we proposed the following test procedure: (i) 20-fold diluted serum was initially tested and (ii) 100-fold diluted serum was additionally tested when the initial result was caffeine positive. Using this procedure, caffeine concentration is expected to be classified into three levels: ≤ 25, > 25- ≤ 100, and > 100µg/mL, which almost correspond to no or mild, severe, and potentially fatal intoxication, respectively. The test procedure was validated using postmortem heart blood from two cases of fatal caffeine intoxication (caffeine concentration: 276 and 175µg/mL) and two cases of other intoxication. Our developed method using point-of-care urinary caffeine test kits enabled simple estimation of serum caffeine concentration.

Production of conductive microfibers based on Polybutylene adipate terephthalate and graphite using a 3D printed electrospinning system and their application as electrochemical dopamine sensor

The use of fibers has intensified in the application of technological and industrial devices and systems, due to their characteristics such as mechanical resistance, elasticity, and a wide range of morphological configurations. In this sense, conductive microfibers based on graphite powder (GP) and the polylactic acid/ Polybutylene adipate terephthalate polymeric blend were developed through the electrospinning technique using a new 3D printer automatized collector. The obtained microfibers were characterized and used in the manufacture of an electrochemical sensor for the determination of dopamine, which presented a linear range of 0.5 to 20 μmol L−1 with a limit of detection of 0.008 μmol L−1. The sensor was applied for the detection of dopamine in a human serum sample and had a recovery range of 85.5 to 101.0 %. Therefore, conductive microfibers manufactured by electrospinning have potential as a material for the development of electrochemical sensors.

Improving the Sensitivity of Protein Quantification by Immunoaffinity Liquid Chromatography─Triple Quadrupole Mass Spectrometry Using an Iterative Transition Summing Technique.

The desire to reach ever-diminishing lower limits of quantification (LLOQ) to probe changes in low abundance protein targets has led to enormous progress in sample preparation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) instrumentation. To maximize signal and reduce noise, many approaches have been employed, including specific immunoaffinity (IA) enrichment and reducing the LC flow to the nanoflow (nLC) level; however, additional sensitivity gains may still be required. Recently, a technique termed "echo summing" has been described for small-molecular-weight analytes on a triple quadrupole (QqQ) MS where multiple iterations of the same, single selected reaction monitoring (SRM) transition are collected, summed, and integrated, yielding significant analyte dependent signal-to-noise (S/N) improvements. Herein, the direct applicability of echo summing to protein quantification by sequential IA combined with nLC-MS/MS (IA-nLC-MS/MS) is described for a beta nerve growth factor (NGF) and a soluble asialoglycoprotein receptor (sASGPR) assay from human serum. Five iterations of echo summing outperformed traditional collection in relative average accuracy (-1.5 ± 7.7 vs -41.7 ± 10.7% bias) and precision (7.8 vs 18.4% coefficient of variation (CV)) of the low-end quality control (QC) sample (N = 4) for NGF and improved functional sensitivity of serially diluted serum QC samples (N = 5 each population) approximately 2-fold (1.96 and 2.00-fold) for two peptides of sASGPR. Echo summing also extended the minimum quantifiable QC level for sASGPR 4-fold lower. Similar gains are believed to be achievable for most protein IA-nLC-MS/MS assays.

Versatile, reusable and highly sensitive SERS-based point-of-care testing microplatform for reliable ATP detection

The advancement in miniaturized Raman spectrometers, coupled with the single-molecule-level sensitivity and unique fingerprint identification capability of surface-enhanced Raman scattering (SERS), offers great potential for point-of-care testing (POCT). Despite this, accurately quantifying analyte molecules, particularly in complex samples with limited sample volumes, remains difficult. Herein, we present a versatile and reusable SERS microplatform for highly sensitive and reliable quantitative detection of adenosine triphosphate (ATP) in biological fluids. The platform utilizes gold-Prussian blue core-shell nanoparticles modified with polyethyleneimine (Au@PB@PEI NPs), embedded within gold nanoparticle-immobilized capillary-based silica monolithic materials. PB acts as an internal standard, while PEI enhances molecular capture. The periodic, bimodal porous structure of the silica monolithic materials provides uniform and abundant sites for nanoparticle attachment, facilitating rapid liquid permeation, intense SERS enhancement, and efficient enrichment. The platform regulates ATP capture and release through magnesium ions in the liquid phase, eliminating matrix interferences and enabling platform reuse. Integrating efficient molecular enrichment, separation, an interference-free internal standard, a liquid flow channel, and a detection chamber, our platform offers simplicity in operation, exceptional sensitivity and accuracy, and rapid analysis (∼10 min). Employing PB as an internal calibration standard, ratiometric Raman signals (I732/I2123) facilitate precise ATP quantification, achieving a remarkable limit of detection down to 0.62 pM. Furthermore, this platform has been proven to be highly reproducible and validated for ATP quantification in both mouse cerebrospinal fluid and human serum, underscoring its immense potential for POCT applications.

Aminophenylboronic acid-modified nitrogen-doped graphene quantum dots and their applications in lysine sensing based on interplaying fluorescent mechanisms.

Using nitrogen-doped graphene quantum dots (N-GQDs) and 3-aminophenylboronic acid (APBA), a novel fluorescence nanosensorwas developed. This nanosensor exhibits high selectivity and sensitivity for lysine detection. Its sensing mechanism involves the suppression of electron transfer from APBA to the N-GQDs unit, thereby inhibiting photoinduced electron transfer and initiating internal charge transfer. At an optimal pH of 7, the protonated α-amine and ε-amine groups of lysine interact with the amide and boronic acid moieties, respectively. This interaction results in a redshift of fluorescence, substantially enhancing the response signal. A linear response was observed within a concentration range 0.40-3.01μM, with the detection limit being 0.005μM. A similar linear range was also achieved for the determination of lysine in human serum. Density functional theory calculations correlating molecular orbits and geometries support UV-vis and fluorescence findings. Additionally, the nanosensor wassuccessfully applied to detect lysine in living cells and real samples, including milk and honey. For practical application, we construct a lysine-specific sensing platform using a commercial chip (TCS34725) that collects red, blue, and green signals, thereby facilitating the convenient use of the nanosensor. Overall, this study offers new perspectives on the development and application of fluorescent nanosensors for detecting individual amino acids.

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.

Cyclohexanediamine Triazole (CHDT) Functionalization Enables Labeling of Target Molecules with Al18F/68Ga/111In.

The Al18F-labeling approach offers a one-step access to radiofluorinated biomolecules by mimicking the labeling process for radiometals. Although these labeling conditions are considered to be mild compared to classic radiofluorinations, improvements of the chelating units have led to the discovery of (±)-H3RESCA, which allows Al18F-labeling already at ambient temperature. While the suitability of (±)-H3RESCA for functionalization and radiofluorination of proteins is well established, its use for small molecules or peptides is less explored. Herein, we advanced this acyclic pentadentate ligand by introducing an alkyne moiety for the late-stage functionalization of biomolecules via click chemistry. We show that in addition to Al18F-labeling, the cyclohexanediamine triazole (CHDT) moiety allows stable complexation of 68Ga and 111In. Three novel CHDT-functionalized PSMA inhibitors were synthesized and their Al18F-, 68Ga-, and 111In-labeled analogs were subjected to a detailed in vitro radiopharmacological characterization. Stability studies in vitro in human serum revealed among others a high kinetic inertness of all radiometal complexes. Furthermore, the Al18F-labeled PSMA ligands were characterized for their biodistribution in a LNCaP derived tumor xenograft mouse model by PET imaging. One radioligand, Al[18F]F-CHDT-PSMA-1, bearing a small azidoacetyl linker at the glutamate-urea-lysine motif, provided an in vivo performance comparable to that of [18F]PSMA-1007 but with even higher tumor-to-blood and tumor-to-muscle ratios at 120 min p.i. Overall, our results highlight the suitability of the novel CHDT moiety for functionalization and radiolabeling of small molecules or peptides with Al18F, 68Ga, and 111In and the triazole ring seems to entail favorable pharmacokinetic properties for molecular imaging purposes.

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.

A thermodynamic investigation into protein–excipient interactions involving different grades of polysorbate 20 and 80

AbstractDeveloping stable biopharmaceutical formulations is of paramount importance and is typically achieved by incorporating surfactants as stabilising agents, such as polysorbate 20 and 80. However, little is known about the effect surfactant grade has on formulation stability. This study evaluates the effect of regular grade and Super-refined™ polysorbates 20 and 80 and their interaction with model proteins, namely β-lactoglobulin (β-Ig), human serum albumin (HSA) and immunoglobulin gamma (IgG), using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). ITC results indicated that all four polysorbates underwent binding interactions with β-Ig and HSA, yet no interaction was observed with IgG this is postulated to be a consequence of differences in secondary structure composition. Surfactant binding to β-Ig occurred at ratios of ~ 3:2 regardless of the surfactant used with dissociation constants ranging from 284 to 388 µM, whereas HSA bound at ratios of ~ 3:1 and dissociation constants ranging from 429 to 653 µM. Changes in enthalpy were larger for the surfactant interactions with HSA compared with β-Ig implying the former produced a greater binding interaction than the latter. DSC facilitated measurement of the temperature of unfolding of each protein with the presence of each polysorbate where results further confirmed interactions had occurred for β-Ig and HSA with an increased unfolding temperature between 4 and 6 K implying improved protein stability, yet again, no interaction was observed with IgG. This study thermodynamically characterised the role of polysorbates in protein stabilisation for biopharmaceutical formulations.

Preliminary exploration of the clinical warning value of ischemic modified albumin in the development of pre-eclampsia

Objective: To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity. Methods: A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE. Results: (1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference (F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant (F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure (r=0.279), mean arterial pressure (r=0.212), and urinary protein quantification (r=0.277), while the severe PE manifestations negatively correlated include HSA levels (r=-0.644) and newborn birth weight (r=-0.305), all of which were significantly correlated (P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95%CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95%CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions: The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

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.

Multi-walled carbon nanotubes functionalized with a new Schiff base containing phenylboronic acid residues: applicationtothe development of a bienzymatic glucose biosensor using a response surface methodology approach.

Aninnovative supramolecular architectureis reportedfor bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at - 0.050V in the presence of 5.0 × 10-4M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT-SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0mgmL-1 and 1.50mgmL-1, respectively, while the optimum interaction time was 3.0min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 102 µA dL mg-1 ((44 ± 4) × 102 µA M-1), a linear range between 0.06mg dL-1 and 21.6mg dL-1 (3.1µM-1.2mM) (R2 = 0.9991),and detection and quantification limits of 0.02mg dL-1 (1.0µM) and 0.06mg dL-1 (3.1µM), respectively. The reproducibility for five sensors prepared with the same MWCNT-SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT-SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples.

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.

Novel Self-Powered Biosensor Based on Au Nanoparticles @ Pd Nanorings and Catalytic Hairpin Assembly for Ultrasensitive miRNA-21 Assay.

An ultrasensitive self-powered biosensor is constructed for miRNA-21 detection based on Au nanoparticles @ Pd nanorings (Au NPs@Pd NRs) and catalytic hairpin assembly (CHA). The Au NPs@Pd NRs possess excellent electrical conductivity to improve the electron transfer rate and show good elimination of byproduct H2O2 to assist glucose oxidase (GOD) to catalyze glucose; CHA is used as an amplification strategy to effectively enhance the sensitivity of the biosensor. To further amplify the output signal, a capacitor is integrated into the self-powered biosensor. With multiple signal amplification strategies, the self-powered biosensor possesses a linear range of 0.1-10-4 fM and a lower limit of detection (LOD) of 0.032 fM (S/N = 3). In addition, the as-prepared self-powered biosensor displays potential applicability in the assay toward miRNA-21 in human serum samples.

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.