Search Results (93)

Sepsis is a life-threatening condition driven by a dysregulated host response to infection, with high mortality and few treatment options. Decades of failed drug development underscore the urgent need for therapies with novel mechanisms of action. Vimentin, an intermediate filament protein, acts as a network hub that senses and integrates cellular signals. Its involvement in key sepsis pathologies, including infection, hyperinflammation, immunosuppression, coagulopathy and metabolic dysregulation, positions it as a potential therapeutic target. This study evaluated the efficacy of ALD-R491, a novel small-molecule vimentin modulator, in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice received ALD-R491 prophylactically or therapeutically, alone or with ceftriaxone. The treatment significantly reduced serum levels of key biomarkers of sepsis, including C-reactive protein (CRP), lactate (Lac), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and dose-dependently improved the survival of septic mice. Organ-specific analysis confirmed the effects of ALD-R491 in mitigating hyperinflammation and multi-organ injury. The treatment reduced pulmonary edema and inflammation; preserved liver tissue architecture and improved hepatic function with lowered alanine aminotransferase/aspartate aminotransferase (ALT/AST); decreased kidney tubular damage; and improved renal function with lowered creatinine/blood urea nitrogen (BUN). These preclinical findings indicate that the vimentin-targeting agent ALD-R491 represents a promising therapeutic candidate for sepsis and merits further clinical investigation. Full article

In this study, blue fluorescence carbon dots of high quantum yield (42.96%) were successfully synthesized via a one-step hydrothermal method using Pueraria residues as the precursor and urea as the nitrogen source. The preparation process was simple, was environmentally friendly, and did not use toxic chemicals, with the resulting nitrogen-doped Pueraria carbon dots (N-PCDs) exhibiting excellent dispersibility, regular morphology and stable fluorescence performance. Moreover, fluorescence quenching could be induced through electron transfer between N-PCDs and hexavalent chromium (Cr(VI)) in water, which enabled the application of N-PCDs as a fluorescent probe for sensing Cr(VI) in water, with a limit of detection (LOD) and limit of quantitation (LOQ) of 0.078 μM and 0.26 μM, respectively. The effectiveness of the proposed fluorescent probe was also validated in various water matrices, achieving stable recovery rates ranging from 98.7% to 101.5%. Furthermore, experimental investigations and theoretical calculations through density functional theory (DFT) confirmed that the underlying reaction mechanism was photoinduced electron transfer (PET). Above all, this study not only demonstrated the potential of N-PCDs as sensitive probes to sense toxic elements in the environment, but also promotes the green and scalable production of high-value carbon-based products from waste biomass. Full article

Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), are crucial for physiological regulation and their imbalance poses severe health risks. Herein, we developed a pH-responsive liquid crystal (LC)-based sensing platform for detection of biothiols by doping 4-n-pentylbiphenyl-4-carboxylic acid (PBA) into 4-n-pentyl-4-cyanobiphenyl (5CB). Urease catalyzed urea hydrolysis to produce OH⁻, triggering the deprotonation of PBA, thereby inducing a vertical alignment of LC molecules at the interface corresponding to dark optical appearances. Heavy metal ions (e.g., Hg²⁺) could inhibit urease activity, under which condition LC presents bright optical images and LC molecules maintain a state of tilted arrangement. However, biothiols competitively bind to Hg²⁺, the activity of urease is maintained which enables the occurrence of urea hydrolysis. This case triggers LC molecules to align in a vertical orientation, resulting in bright optical images. This pH-driven reorientation of LCs provides a visual readout (bright-to-dark transition) correlated with biothiol concentration. The detection limits of Cys/Hcy and GSH for the PBA-doped LC platform are 0.1 μM and 0.5 μM, respectively. Overall, this study provides a simple, label-free and low-cost strategy that has a broad application prospect for the detection of biothiols. Full article

The rapid and accurate prediction of crop yield and the construction of optimal yield prediction models are important for guiding field-scale agronomic management practices in precision agriculture. This study selected the leaf area index (LAI) of winter wheat (Triticum aestivum L.) at four different stages, and collected canopy spectral information and extracted vegetation indexes through unmanned aerial vehicle (UAV) multi-spectral sensors to establish the yield prediction model under the condition of slow-release nitrogen fertilizer and proposed optimal fertilization strategies for sustainable yield increase in wheat. The prediction results were evaluated using random forest (RF), support vector machine (SVM) and back propagation neural network (BPNN) methods to select the optimal spectral index and establish yield prediction models. The results showed that LAI has a significantly positive correlation with yield across four growth stages of winter wheat, and the correlation coefficient at the anthesis stage reached 0.96 in 2018–2019 and 0.83 in 2019–2020. Therefore, yield prediction for winter wheat could be achieved through a remote sensing estimation of LAI at the anthesis stage. Six vegetation indexes calculated from UAV-derived reflectance data were modeled against LAI, demonstrating that the red-edge vegetation index (CI_{red edge}) achieved superior accuracy in estimating LAI for winter wheat yield prediction. RF, SVM and BPNN models were used to evaluate the accuracy and precision of CI_{red edge} in predicting yield, respectively. It was found that RF outperformed both SVM and BPNN in predicting yield accuracy. The CI_{red edge} of the anthesis stage was the best vegetation index and stage for estimating yield of winter wheat based on UAV remote sensing. Under different N application rates, both predicted and measured yields exhibited a consistent trend that followed the order of SRF (slow-release N fertilizer) > SRFU1 (mixed TU and SRF at a ratio of 2:8) > SRFU2 (mixed TU and SRF at a ratio of 3:7) > TU (traditional urea). The optimum N fertilizer rate and N fertilizer type for winter wheat in this study were 220 kg ha⁻¹ and SRF, respectively. The results of this study will provide significant technical support for regional crop growth monitoring and yield prediction. Full article

Gut-derived uremic toxins (UTs) contribute to cardiovascular disorders like atherosclerosis and cardiomyopathy in patients with chronic kidney disease (CKD), causing increased cardiovascular morbidity and mortality. The intermediate steps between higher concentrations of gut-derived UTs and organ damage caused by UTs are still insufficiently understood. Glycosaminoglycans (GAGs) as components of the extracellular matrix are known to interact with various ligands such as growth factors or receptors, thereby influencing (patho)physiological processes. We previously found that the UT inorganic phosphate (Pi) induces the synthesis and sulphation of the GAGs heparan sulphate and chondroitin sulphate in the rat vascular smooth muscle cell (VSMC) line A7r5 and in the human endothelial cell (EC) line EA.Hy926. The aim of this study was to investigate if other organic UTs modulate GAGs in vascular cells as well. We treated ex vivo cultures of rat aortic rings as well as primary rat VSMCs and human ECs with the UTs Pi, indoxylsulphate (IS), p-cresylsulphate (pCS), trimethylamine N-oxide (TMAO), and urea, and analyzed the samples by histological staining, qPCR, western blot, HPLC, and colorimetric assays. The UT treatment of aortic rings and cells increased contents of sulphated GAGs and hyaluronic acid. UT-treated cells contained higher amounts of 4S- and 6S-sulphated GAGs compared to controls. This was accompanied by altered expressions of genes and proteins relevant for GAG metabolism. Mechanistically, the effects of the UTs on GAGs involve the activation of the PI3K/Akt pathway and of the transcription factor NF-κB. In conclusion, the UT-induced remodeling of the cardiovascular matrix by upregulation of sulphated GAGs and hyaluronic acid in aortic tissue and vascular cells might be a missing link between gut-derived UT and pathophysiological alterations in the cardiovascular system in the sense of a gut–matrix axis. Full article

This study reports the synthesis and characterization of two solvatochromic pentacyanoferrate(II) complexes. Their structural design incorporates ligands with flexible xylylene bridges and distinct heterocycles—one combining 4-dimethylaminopyridine (DMAP) with 4,4′-bipyridine, and the other isoquinoline with 4,4′-bipyridine. Their structural diversity enables the complexes to engage in a broad range of solvent–solute interactions, providing valuable insights into the behavior of solvents and media with regard to polarity, through sizable solvatochromic shifts. Their solvatochromism is examined using a set of nine solvents and solvent mixtures. The solvatochromic sensitivities to polarity changes, expressed through a variety of polarity parameters and functions, are determined. Moreover, using a set of four complementary linear solvation energy relationships (LSERs), the roles of solvent polarity, solute–solvent interactions and the molecular responsiveness of the two compounds to different media are investigated. Additionally, their dipole moments in the ground and MLCT-excited states are determined using a suitable model, namely that of Suppan and Tsiamis. As a step further, the polarity sensing aptitude of the two solvatochromic compounds is examined in aqueous urea solutions at varying urea concentrations. The solvatochromic sensitivity of the two compounds is compared with that of a model cyanoferrate(II) complex, Fe^II(CN)₂(phen)₂. The two compounds clearly surpass the sensitivity of Fe^II(CN)₂(phen)₂ with subtle solvent polarity changes induced by varying the urea concentration. An LSER describing and predicting the solvatochromic effects in aqueous urea is developed and tested. Full article

This study investigates the photoelectrochemical (PEC) performance of molybdenum-doped bismuth vanadate (Mo-doped BiVO₄) and its heterojunction with the BiOCl layer in glucose and urea sensing. Photoelectrochemical analyses, including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), revealed that the formation of a heterojunction enhanced charge carrier separation. The impact of the interaction between the surface of the photoanode and analytes on sensing performance was systematically evaluated. Among the tested configurations, Mo-doped BiVO₄ exhibited superior glucose sensing with a limit of detection (LOD) of 0.173 µM, while BiVO₄/BiOCl demonstrated an LOD of 2.474 µM. In the context of urea sensing, Mo-doped BiVO₄ demonstrated an LOD of 0.656 µM, while BiVO₄/BiOCl exhibited an LOD of 0.918 µM. Notably, despite the enhanced PEC activity observed in heterostructured samples, Mo-doped BiVO₄ exhibited superior sensing performance, attributable to good interaction with analytes. The photocurrent response trends—an increase with glucose concentration and a decrease with urea concentration—were attributed to oxidation and adsorption phenomena on the photoanode surface. These findings underscore the critical role of photoanode surface engineering in advancing PEC sensor technology, paving the way for more efficient environmental and biomedical applications. Full article

Electrochemical glucose sensors are vital for clinical diagnostics and the food industry, where accurate detection is essential. However, the limitations of glucose oxidase (GOx)-based sensors, such as complex preparation, high cost, and environmental sensitivity, highlight the need for non-enzymatic sensors that directly oxidize glucose at the electrode surface. In this study, a self-supporting hierarchical Cu/Fe₃O₄ nanosheet electrode was successfully fabricated by in situ growth on Ni Foam using a hydrothermal method, followed by annealing treatment. The Cu/Fe₃O₄ hierarchical nanosheet structure, with its large surface area, provides abundant active sites for electrocatalysis, while the strong interactions between Cu/Fe₃O₄ and Ni Foam enhance electron transfer efficiency. This novel electrode structure demonstrates exceptional electrochemical performance for non-enzymatic glucose sensing, with an ultrahigh sensitivity of 12.85 μA·μM⁻¹·cm⁻², a low detection limit of 0.71 μM, and a linear range extending up to 1 mM. Moreover, the Cu/Fe₃O₄/NF electrode exhibits excellent stability, a rapid response (~3 s), and good selectivity against interfering substances such as uric acid, ascorbic acid, H₂O₂, urea, and KCl. It also shows strong reliability in analyzing human serum samples. Therefore, Cu/Fe₃O₄/NF holds great promise as a non-enzymatic glucose sensor, and this work offers a valuable strategy for the design of advanced electrochemical electrodes. Full article

The need for eco-friendly, cost-effective, and scalable methods to synthesize carbon quantum dots (CQDs) remains a critical goal in nanotechnology. In this work, nitrogen-doped carbon quantum dots (N-CQDs) were successfully synthesized using cellulose nanocrystals (CNCs) derived from microcrystalline cellulose (MCC) and urea through a rapid one-step microwave-assisted method. The use of renewable cellulose as a precursor aligns with sustainable practices, offering a pathway to transform agricultural waste into valuable nanomaterials. Characterized by TEM, XRD, Raman, XPS, and PL spectroscopy, the N-CQDs demonstrated outstanding optical properties, including strong excitation-dependent fluorescence with an emission maximum at 420 nm. The N-CQDs exhibited exceptional selectivity and sensitivity toward Fe³⁺, achieving a detection limit of 75 nM. Additionally, the pH-dependent fluorescence and stability in diverse conditions highlight the N-CQDs’ versatility in environmental monitoring. This study establishes a foundation for using agricultural waste to produce high-performance nanostructures for sensing applications, advancing green nanotechnology and environmental solutions. Full article

Detecting urea is crucial for diagnosing related health conditions and ensuring timely medical intervention. The addition of machine learning (ML) technologies has completely changed the field of biochemical sensing, providing enhanced accuracy and reliability. In the present work, an ML-assisted screen-printed, flexible, electrochemical, non-enzymatic biosensor was proposed to quantify urea concentrations. For the detection of urea, the biosensor was modified with a multi-walled carbon nanotube-zinc oxide (MWCNT-ZnO) nanocomposite functionalized with copper oxide (CuO) micro-flowers (MFs). Further, the CuO-MFs were synthesized using a standard sol-gel approach, and the obtained particles were subjected to various characterization techniques, including X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and Fourier transform infrared (FTIR) spectroscopy. The sensor’s performance for urea detection was evaluated by assessing the dependence of peak currents on analyte concentration using cyclic voltammetry (CV) at different scan rates of 50, 75, and 100 mV/s. The designed non-enzymatic biosensor showed an acceptable linear range of operation of 0.5–8 mM, and the limit of detection (LoD) observed was 78.479 nM, which is well aligned with the urea concentration found in human blood and exhibits a good sensitivity of 117.98 mA mM⁻¹ cm⁻². Additionally, different regression-based ML models were applied to determine CV parameters to predict urea concentrations experimentally. ML significantly improves the accuracy and reliability of screen-printed biosensors, enabling accurate predictions of urea levels. Finally, the combination of ML and biosensor design emphasizes not only the high sensitivity and accuracy of the sensor but also its potential for complex non-enzymatic urea detection applications. Future advancements in accurate biochemical sensing technologies are made possible by this strong and dependable methodology. Full article

Human urine and its detection are of interest in forensic studies in numerous contexts. Both crystalline urea and 1.0 M solutions of urea, as synthetic analog endmember components of human urine, were investigated as a proof-of-concept study to determine if detailed lab spectroscopy would be viable. Urea was reliably detected on Ottawa sand at concentrations of approximately 3.2% in dried experiments. Urea was detectable after 1 week of solution evaporation under lab conditions, at 9.65 wt.% 1 M solution. This investigation successfully establishes urea as a material of interest for reflective spectroscopy and hyperspectral remote sensing/image spectroscopy on a wide range of spatial scales, from specific centimeter-scale areas in a crime scene to searching large outdoor regions > 1 km². In addition, this investigation is relevant to improving the monitoring of human trafficking, status and condition of refugee camps, and monitoring sewage. Full article

Herein, we present a novel approach to quantify ferritin based on the integration of an Enzyme-Linked Immunosorbent Assay (ELISA) protocol on a Graphene Field-Effect Transistor (gFET) for bioelectronic immunosensing. The G-ELISA strategy takes advantage of the gFET inherent capability of detecting pH changes for the amplification of ferritin detection using urease as a reporter enzyme, which catalyzes the hydrolysis of urea generating a local pH increment. A portable field-effect transistor reader and electrolyte-gated gFET arrangement are employed, enabling their operation in aqueous conditions at low potentials, which is crucial for effective biological sample detection. The graphene surface is functionalized with monoclonal anti-ferritin antibodies, along with an antifouling agent, to enhance the assay specificity and sensitivity. Markedly, G-ELISA exhibits outstanding sensing performance, reaching a lower limit of detection (LOD) and higher sensitivity in ferritin quantification than unamplified gFETs. Additionally, they offer rapid detection, capable of measuring ferritin concentrations in approximately 50 min. Because of the capacity of transistor miniaturization, our innovative G-ELISA approach holds promise for the portable bioelectronic detection of multiple biomarkers using a small amount of the sample, which would be a great advancement in point–of–care testing. Full article

We present the construction of an organic electrochemical transistor (OECT) based on poly(3,4-ethylendioxythiophene, PEDOT) and polyallylamine (PAH) and its evaluation as a bioelectronic platform for urease integration and urea sensing. The OECT channel was fabricated in a one-step procedure using chemical polymerization. Then, urease was immobilized on the surface by electrostatic interaction of the negatively charged enzyme at neutral pH with the positively charged surface of PEDOH-PAH channels. The real-time monitoring of the urease adsorption process was achieved by registering the changes on the drain–source current of the OECT upon continuous scan of the gate potential during enzyme deposition with high sensitivity. On the other hand, integrating urease enabled urea sensing through the transistor response changes resulting from local pH variation as a consequence of enzymatic catalysis. The response of direct enzyme adsorption is compared with layer-by-layer integration using polyethylenimine. Integrating a polyelectrolyte over the adsorbed enzyme resulted in a more stable response, allowing for the sensing of urine even from diluted urine samples. These results demonstrate the potential of integrating enzymes into the active channels of OECTs for the development of biosensors based on local pH changes. Full article

Background: Remote dielectric sensing (ReDS) systems can estimate the amount of lung fluid non-invasively and easily without expert techniques. The correlation between the elevated ReDS value and other modalities that estimate pulmonary congestion has been validated. The clinical implications of lower ReDS values, which may indicate hypovolemia, remain unknown. Methods: A total of 138 patients who were hospitalized for various cardiovascular-related problems and underwent ReDS value measurements at the index discharge in a blinded manner to the attending clinicians were eligible for inclusion. Patients with ReDS values > 30%, indicating the presence of pulmonary congestion, were excluded. The prognostic impact of lower ReDS values on all-cause readmission after index discharge was evaluated. Results: A total of 97 patients were included. The median age was 78 years, and 48 were men. The median ReDS value at index discharge was 26% (23%, 27%). A lower ReDS value correlated with smaller inferior vena cava maximum diameters (r = 0.46, p < 0.001) and higher blood urea nitrogen/creatinine ratios (r = −0.35, p < 0.001). A lower ReDS value (≤25%) was associated with a risk of all-cause readmissions with an unadjusted hazard ratio of 2.68 (95% confidence interval 1.09–6.59, p = 0.031) and an adjusted hazard ratio of 2.30 (95% confidence interval 0.92–5.78, p = 0.076). Its calculated cutoff of 25% significantly stratified the cumulative incidence of the primary outcome (36% versus 17%, p = 0.038). Conclusions: A lower ReDS value may indicate hypovolemia and be associated with the risk of all-cause readmission in patients hospitalized for cardiovascular diseases. Full article

We investigated the impact of surface treatments on Si-based electrolyte-gated transistors (EGTs) for detecting urea. Three types of EGTs were fabricated with distinct gate electrodes (Ag, Au, Pt) using a top-down method. These EGTs exhibited exceptional intrinsic electrical properties, including a low subthreshold swing of 80 mV/dec, a high on/off current ratio of 10⁶, and negligible hysteresis. Three surface treatment methods ((3-amino-propyl) triethoxysilane (APTES) and glutaraldehyde (GA), 11-mercaptoundecanoic acid (11-MUA), 3-mercaptopropionic acid (3-MPA)) were individually applied to the EGTs with different gate electrodes (Ag, Au, Pt). Gold nanoparticle binding tests were performed to validate the surface functionalization. We compared their detection performance of urea and found that APTES and GA exhibited the most superior detection characteristics, followed by 11-MUA and 3-MPA, regardless of the gate metal. APTES and GA, with the highest pKa among the three surface treatment methods, did not compromise the activity of urease, making it the most suitable surface treatment method for urea sensing. Full article