Gluconate Research Articles

Nanozyme-based Clusterphene for Enhanced Electrically Catalytic Cancer Therapy.

Nanozyme mediated catalytic therapy is an attractive strategy for cancer therapy. However, the nanozymes are tended to assemble into 3D architectures, resulting in poor catalytic efficiency for therapy. This study designs the assembly of nanozymes and natural enzymes into the layered structures featuring hexagonal pores as nanozyme clusterphene and investigates their catalytic therapy with the assistance of electric field. The nanozyme-based clusterphene consists of polyoxometalate (POM) and natural glucose oxidase (GOx), named POMG-based clusterphene, which facilitate multi-enzyme activities including peroxidase (POD), catalase (CAT), and glutathione oxidase (GPx). The highly ordered layers with hexagonal pores of POMG units significantly improve the peroxidase-like (POD-like) activity of the nanozyme and thus the sustained production of reactive oxygen species (ROS). At the same time, GOx can increase endogenous H2O2 and produce gluconic acid while consuming glucose, the nutrient of tumor cell growth. The results indicate that the POD-like activity of POMG-based clusterphene increase approximately sevenfold under electrical stimulation compared with Nd-substituted keggin type POM cluster (NdPW11). The experiments both in vitro and in vivo show that the proposed POMG-based clusterphene mediated cascade catalytic therapy is capable of efficient tumor inhibiting and preventing tumor proliferation in tumor-bearing mice model, promising as an excellent candidate for catalytic therapy.

Whole genome sequencing and characterization of Pantoea agglomerans DBM 3797, endophyte, isolated from fresh hop (Humulus lupulus L.).

This paper brings new information about the genome and phenotypic characteristics of Pantoea agglomerans strain DBM 3797, isolated from fresh Czech hop (Humulus lupulus) in the Saaz hop-growing region. Although P. agglomerans strains are frequently isolated from different materials, there are not usually thoroughly characterized even if they have versatile metabolism and those isolated from plants may have a considerable potential for application in agriculture as a support culture for plant growth. P. agglomerans DBM 3797 was cultured under aerobic and anaerobic conditions, its metabolites were analyzed by HPLC and it was tested for plant growth promotion abilities, such as phosphate solubilization, siderophore and indol-3-acetic acid productions. In addition, genomic DNA was extracted, sequenced and de novo assembly was performed. Further, genome annotation, pan-genome analysis and selected genome analyses, such as CRISPR arrays detection, antibiotic resistance and secondary metabolite genes identification were carried out. The typical appearance characteristics of the strain include the formation of symplasmata in submerged liquid culture and the formation of pale yellow colonies on agar. The genetic information of the strain (in total 4.8 Mb) is divided between a chromosome and two plasmids. The strain lacks any CRISPR-Cas system but is equipped with four restriction-modification systems. The phenotypic analysis focused on growth under both aerobic and anaerobic conditions, as well as traits associated with plant growth promotion. At both levels (genomic and phenotypic), the production of siderophores, indoleacetic acid-derived growth promoters, gluconic acid, and enzyme activities related to the degradation of complex organic compounds were found. Extracellular gluconic acid production under aerobic conditions (up to 8 g/l) is probably the result of glucose oxidation by the membrane-bound pyrroloquinoline quinone-dependent enzyme glucose dehydrogenase. The strain has a number of properties potentially beneficial to the hop plant and its closest relatives include the strains also isolated from the aerial parts of plants, yet its safety profile needs to be addressed in follow-up research.

Enhancing gluconic acid selectivity in catalytic oxidation: the synergetic effect of glucose-fructose mixtures and kinetic insights

Enhancing gluconic acid selectivity in catalytic oxidation: the synergetic effect of glucose-fructose mixtures and kinetic insights

Bacterial community structure and metabolites after ensiling paper mulberry mixed with corn or wheat straw

BackgroundIn this study, we aimed to address the low utilization of straw and poor fermentation quality of paper mulberry silage (under natural fermentation conditions). Straw was combined with paper mulberry for ensiling, and the fermentation characteristics, bacterial community, and metabolite composition of the mixed straw and paper mulberry silage were investigated. Four treatment groups were established: corn-straw treatment 2 (3:7 ratio of corn straw to paper mulberry), corn-straw treatment 3 (5:5 ratio of corn straw to paper mulberry), wheat-straw treatment 2 (3:7 ratio of wheat straw to paper mulberry), wheat-straw treatment 3 (5:5 ratio of wheat straw to paper mulberry), and a control group (ensiling of paper mulberry alone).ResultsThe control group demonstrated the highest pH and ammonia (AN) and acetic acid (AA) content compared with all the treatment groups. Corn-straw treatment 2 had the highest lactic acid content (54.70 g/kg dry weight) compared with the control and other treatment groups. The relative abundance of Enterobacter (7.085%) was the lowest in the control than in the other treatment groups (p < 0.05). The relative abundance of Enterococcus was higher in both the control and wheat-straw treatment 2 (22.03% and 21.29%, respectively) than in other treatment groups. The relative abundance of Lactococcus was highest in wheat-straw treatment 3 (15.83%) compared with the control and other treatment groups. Corn-straw treatments 2 and 3 demonstrated the same metabolite composition but were clearly different from the wheat-straw treatment 2, wheat-straw treatment 3, and the control. Diacetoxyscirpenol (DAS) belongs to the Fusarium metabolite type A trichothecenes, which were not detected in corn or wheat silage. DAS was downregulated in the wheat-straw treatment 3 and both corn-straw treatments compared with the control, which indicates that the addition of straw decreased mycotoxin production. Lactococcus was significantly and positively correlated with gluconic acid content (R2 = 0.5166).ConclusionOur results suggest that straw treatment can improve the nutritional value of paper mulberry silage by decreasing mycotoxin production, pH value, and AN content and increasing lactic acid production.

Manure derived hydrochar reduced phosphorus loss risk via an alteration of phosphorus fractions and diversified microbial community in rice paddy soil

Phosphorus (P) loss caused by the irrational use of manure organic fertilizer has become a worldwide environmental problem, which has caused a potential threat to water safety and intensified agricultural non-point source pollution. Hydrothermal carbonization is method with a low-energy consumption and high efficiency to deal with environmental problems. Application of pig manure-derived hydrochar (PMH) to soil exhibited potential of sustainable development compared with the pristine pig manure (PM). However, the effects of PMH on the distribution of P among the fractions/forms and the interaction between microorganisms and P forms and its relevance to the potential loss of P in paddy fields has not been clarified. Therefore, in this study, a soil column experiment was conducted using the untreated soil (control), and the PM, PMH1 (PMH derived at 180 °C), and PMH2 (PMH derived at 260 °C) treated soils (at the dose of 0.05 %) and rice was cultivated to investigate the effects of PM and PMH on the P fractions, mobilization, ad potential loss via the induced changes on soil microbial community after a complete growing season of rice. The trend of P utilization was evaluated by P speciation via continuous extraction and 31P NMR. The addition of PMH reduced the proportion of residual P in soil by 23.8–26.3 %, and increased the proportion of HCl-P and orthophosphate by 116.2–158.6 % and 6.1–6.8 % compared to PM. The abundance of gcd gene developed after the application of PMH2, which enhanced the mobile forms of soil P utilization via secreting gluconic acid. The network diagram analysis concluded that the changes in various P forms were mainly related to Proteobacteria, Bacteroides, Firmicutes and Acidobacteria. The results illustrated that PMH mitigate the potential risk of P loss more than PM by altering P fractions and affecting soil microbial community.

Biosensors Precision in Healthcare: A Scientific Odyssey

Biosensors have been the beacon of precision in the ever-evolving landscape of health care and offer a profound impact on diagnostics and patient care. These devices are designed to detect specific biological markers and convert then into measurable signals, seamlessly blending biology with cutting-edge technology. The diverse tapestry of biosensors encompass enzyme based sensors, immuno-assays, photo-biosensors, tissue-based sensors, DNA biosensors and nano-biosensors. Enzyme-based biosensors showcase unparalleled catalytic precision exemplified by glucose biosensors. Glucose oxidase serves as the biological catalyst and converts glucose into gluconic acid and hydrogen peroxide. Electrodes of the sensor then transduce this reaction into measurable signals which enables the precise quantification of glucose levels in diabetes management. Similarly, immunoassays rely on the specificity of antigen-antibody interactions. Most widely used immunoassay, Enzyme-linked immunosorbent assay (ELISA) exemplify this category, which finds applications in a number of diagnostics and provide a window into immunological responses and diseases such as HIV. Advancing the field of biosensing are the photobiosensors which utilize diverse technologies such as fluorescence resonance energy transfer (FRET) to illuminate biological processes. Genetically encoded biosensors that employ proteins like green fluorescent protein (GFP), enable non-invasive monitoring of cellular dynamics and offer real-time insights. Another cateogory, tissue-based biosensors converge the technology with the physiological environments. For instance, implantable glucose sensors that continuously monitor blood glucose concentrations and provide real-time data for personalized treatment approaches. At the core of precision diagnostics lie DNA biosensors such as DNA microarrays. They offer parallel analysis of gen expression, influencing decisions in cancer diagnostics and pharmacogenomics. Nanobiosensors, represented by nanoparticle-based sensors, navigate the nano-frontiers with exceptional sensitivity. For example, quantum dots exhibit unique optical properties for sensitive detection. Likewise, gold nanoparticles based biosensors enable real-time monitoring of drug release in drug delivery systems and emphasize their role in precision medicine. As biosensors advance, ethical considerations come to the forefront. Issues such as data privacy, consent, and equitable access to these technologies demand careful attention. It becomes imperative to ensure that biosensors are developed and deployed responsibly with a keen awareness of potential societal implications in navigating the ethical landscape. In the symphony of precision that biosensors bring to healthcare, their types and applications reflect not only technological prowess but also the ethical responsibility inherent in their development and deployment. As these devices continue to evolve, the healthcare landscape stands on the brink of a new era, where precision and ethics intertwine for the betterment of patient outcomes.

Oxidative fermentation of glucose and ethanol in designed media and cooked grape must by acetic acid bacteria

In this study, acetic acid bacteria strains were investigated for their ability to oxidize different carbon sources producing the corresponding oxidative products. Bacterial strains were cultivated in seven designed media and their acetification ability was assessed. The most performing strains were further tested to evaluate gluconic acid production in cooked grape must. Organic acids, sugars, and ethanol concentrations were assayed by high-pressure liquid chromatography. Overall, the findings showed high variability amongst strains of the same species, especially amongst Gluconobacter oxydans strains. However, strains ATCC 621H and DSM 3503T resulted to be the highest gluconic acid producers in all tested conditions. This study shows that grape must can be further valorized by selective fermentations for the production of gluconic based products.

Targeting and Microenvironment-Activated Nanoreactor for Diabetic Chronic Wound Healing via Multienzyme Cascade Reactions.

The development of cell-like nanoreactors with the ability to initiate biocatalytic cascades under special conditions holds tremendous potential for therapeutic applications. Herein, conformationally gated nanoreactors that respond to the acidic microenvironment of infected diabetic wounds were developed by cucur[8]bituril (CB[8])-based supramolecular assembly. The bioinspired nanoreactors exhibit not only self-regulated permeability and selectivity to control internal enzyme activities by substance exchange but also distinct binding specificities toward Gram-positive and Gram-negative bacteria via noncovalent modification with different ligands. The encapsulation of glucose oxidase (GOx), Fe3O4 nanozyme, and l-arginine (l-Arg) into the nanocarriers enables intelligent activation of multienzyme cascade reactions upon glucose (Glu) uptake to produce gluconic acid (GA) and hydrogen peroxide (H2O2), which is further converted into highly toxic hydroxyl radicals (·OH) for selective antibacterial activity. Moreover, acidic H2O2 promotes the oxidization of l-Arg, leading to the release of nitric oxide (NO). Consequently, this nanoreactor provides a multifunctional and synergistic platform for diabetic chronic wound healing by combining enzyme dynamic therapy with NO gas therapy to combat bacterial infections and inflammation under high blood Glu levels.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data

BackgroundLung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics.MethodsThe study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results.ResultsFinally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification.ConclusionWe developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.

A Small Highly Sensitive Glucose Sensor Based on a Glucose Oxidase-Modified U-Shaped Microfiber.

Diabetes patients need to monitor blood glucose all year round. In this article, a novel scheme is proposed for blood glucose detection. The proposed sensor is based on a U-shaped microfiber prepared using hydrogen-oxygen flame-heating technology, and then 3-aminopropyltriethoxysilane (APTES) and glucose oxidase (GOD) are successively coated on the surface of the U-shaped microfiber via a coating technique. The glucose reacts with the GOD of the sensor surface to produce gluconic acid, which changes the effective refractive index and then shifts the interference wavelength. The structure and morphology of the sensor were characterized via scanning electron microscope (SEM) and confocal laser microscopy (CLM). The experimental results show that the sensitivity of the sensor is as high as 5.73 nm/(mg/mL). Compared with the glucose sensor composed of the same material, the sensitivity of the sensor increased by 329%. The proposed sensor has a broad application prospect in blood glucose detection of diabetic patients due to the advantages of miniaturization, high sensitivity, and good stability.

Sustainable cellobionic acid biosynthesis from starch via artificial in vitro synthetic enzymatic biosystem

Cellobionic acid (CBA), a kind of aldobionic acid, offers potential applications in the fields of pharmaceutical, cosmetic, food, and chemical industry. To tackle the high cost of the substrate cellobiose in CBA production using quinoprotein glucose dehydrogenase, this study developed a coenzyme-free and phosphate-balanced in vitro synthetic enzymatic biosystem (ivSEBS) to enable the sustainable CBA synthesis from cost-effective starch in one-pot via the CBA-synthesis module and gluconic acid-supply module. The metabolic fluxes of this artificial biosystem were strengthened using design−build−test−analysis strategy, which involved exquisite pathway design, meticulous enzyme selection, module validation and integration, and optimization of the key enzyme dosage. Under the optimized conditions, a remarkable concentration of 6.2 g/L CBA was achieved from initial 10 g/L maltodextrin with a starch-to-CBA molar conversion rate of 60 %. Taking into account that the biosystem simultaneously accumulated 3.6 g/L of gluconic acid, the maltodextrin utilization rate was calculated to be 93.3 %. Furthermore, a straightforward scaling-up process was performed to evaluate the industrial potential of this enzymatic biosystem, resulting in a yield of 21.2 g/L CBA from 50 g/L maltodextrin. This study presents an artificial ivSEBS for sustainable production of CBA from inexpensive starch, demonstrating an alternative paradigm for biomanufacturing of other aldobionic acids.

Designing Tough Hydrogel Shells for Glucose Sensing.

Conventional hydrogel microcapsules often suffer from inadequate mechanical stability, hindering their use. Here, water-cored double-network (DN) hydrogel shells are designed, formed by polyacrylamide and calcium alginate networks using triple-emulsion templates. These DN hydrogel shells offer robust mechanical stability, optical transparency, and a precisely-defined cut-off threshold. The feasibility of this platform is demonstrated through the development of a fluorometric glucose sensor. Glucose oxidase is enclosed within the water core, while a pH-responsive fluorescent dye is incorporated into the DN shells. Glucose diffuses into the core through the DN shells, where the glucose oxidase converts glucose into gluconic acid, leading to pH reduction and a subsequent decrease in fluorescence intensity of DN shells. Additionally, the pH-sensitive colorant dissolved in the medium enables visual pH assessment. Thus, glucose levels can be determined using both fluorometric and colorimetric methods. Notably, the DN shells exhibit exceptional stability, enduring intense mechanical stress and cycles of drying and rehydration without leakage. Moreover, the DN shells act as effective barriers, safeguarding glucose oxidase against proteolysis by large disruptive proteins, like pancreatin. This versatile DN shell platform extends beyond glucose oxidase encapsulation, serving as a foundation for various capsule sensors utilizing enzymes and heterogeneous catalysts.

Multifunctional sodium alginate-based self-healing edible cross-linked coating for banana preservation

Edible coating plays an important role in preventing fruit rot and prolonging the shelf life of fruit. However, a large amount of water will accumulate on the surface of the fruit through respiratory metabolism during storage, leading to the dissolution of the coating. Therefore, it is important to develop water-resistant coatings to extend the shelf life of bananas. In this work, gluconolactone (GDL) was used to slowly generate gluconic acid, which protonated the amino groups of the whey protein isolate (WPI) and enhanced the electrostatic interaction between WPI and sodium alginate (SA) to form a cross-linked composite coating. The introduction of WPI increased the water contact angle value of the films from 47.1° to 102.1°. The composite coating exhibited excellent mechanical properties, water resistance, UV shielding self-healing, and gas-selective transmission. The experiment of banana preservation proved that the composite coating could effectively slow down the water loss of bananas, retard the ripening and browning, and extend the shelf life of bananas for 6 days at 25 °C and 50% RH. Therefore, this multifunctional coating has important reference value for the design of self-healing coating, and shows good potential in the preservation of perishable fruits.

Pd-Bi-Based Catalysts for Selective Oxidation of Glucose into Gluconic Acid: The Role of Local Environment of Nanoparticles in Dependence of Their Composition

Palladium–bismuth nanomaterials are used in various chemical applications such detectors, electrodes, and catalysts. Pd-Bi catalysts are attracting widespread interest because these catalysts enable the production of valuable products quickly and efficiently, and are environmentally friendly. However, the composition of the catalyst can have a significant impact on its catalytic performance. In this work, we identified a correlation between the composition of the catalyst and its efficiency in converting glucose into sodium gluconate. It was found that the conversion decreases with increasing bismuth content. The most active catalyst was the 0.35Bi:Pd sample with a lower bismuth content (glucose conversion of 57%). TEM, SEM, EXAFS, and XANES methods were used to describe, in detail, the surface properties of the xBi:Pd/Al2O3 catalyst samples. The increase in particle size with increasing bismuth content, observed in the TEM micrographs, was associated with the low melting point of bismuth (271 °C). The SEM method showed that palladium and bismuth particles were uniformly distributed over the surface of the support in close proximity to each other, which allowed us to conclude that an alloy of non-stoichiometric composition was formed. The EXAFS and XANES methods established that bismuth was located on the surface of the nanoparticle predominantly in an oxidized state.

Improving glucose oxidase catalysis in Aspergillus niger via Vitreoscilla hemoglobin fusion protein.

Oxygen is crucial for converting glucose to gluconic acid catalyzed by glucose oxidase (Gox). However, industrial gluconic acid production faces oxygen supply limitations. To enhance Gox efficiency, Vitreoscilla hemoglobin (VHb) has been considered as an efficient oxygen transfer carrier. This study identified GoxA, a specific isoform of Gox in the industrial gluconic acid-producing strain of Aspergillus niger. Various forms of VHb expression in A. niger were tested to improve GoxA's catalytic efficiency. Surprisingly, the expression of free VHb, both intracellularly and extracellularly, did not promote gluconic acid production during shake flask fermentation. Then, five fusion proteins were constructed by linking Gox and VHb using various methods. Among these, VHb-GS1-GoxA, where VHb's C-terminus connected to GoxA's N-terminus via the flexible linker GS1, demonstrated a significantly higher Kcat/Km value (96% higher) than GoxA. Unfortunately, the expression of VHb-GS1-GoxA in A. niger was limited, resulting in a low gluconic acid production of 3.0 g/L. To overcome the low expression problem, single- and dual-strain systems were designed with tools of SpyCatcher/SpyTag and SnoopCatcher/SnoopTag. In these systems, Gox and VHb were separately expressed and then self-assembled into complex proteins. Impressively, the single-strain system outperformed the GoxA overexpression strain S1971, resulting in 23% and 9% higher gluconic acid production under 0.6 vvm and 1.2 vvm aeration conditions in the bioreactor fermentation, respectively. The successful construction of Gox and VHb fusion or complex proteins, as proposed in this study, presents promising approaches to enhance Gox catalytic efficiency and lower aerodynamic costs in gluconic acid production. KEY POINTS: • Overexpressing free VHb in A. niger did not improve the catalytic efficiency of Gox • The VHb-GS1-GoxA showed an increased Kcat/Km value by 96% than GoxA • The single-strain system worked better in the gluconic acid bioreactor fermentation.

Nanoreactor based on single-atom nanoenzymes promotes ferroptosis for cancer immunotherapy

Immunotherapy is a promising mainstream approach in anti-tumor therapy. It boasts advantages such as durable responses and lower side effects. However, there are still some limitations to be addressed. Current cancer immunotherapy has shown low response rates due to inadequate immunogenicity of certain tumor cells. To address these challenges, an acid-specific nanoreactor was developed, designed to induce immunogenicity by triggering ferroptosis in tumor cells. The nanoreactor integrates glucose oxidase (GOx) with a single-atom nanoenzyme (SAE), which exhibits high peroxidase (POD)-like activity in the acidic tumor microenvironment (TME). This specific acid-sensitivity transforms endogenous hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH). GOx enhances the POD-like SAE activity in the nanoreactor by metabolizing glucose in tumor cells, producing gluconic acid and H2O2. This nanoreactor induces high levels of oxidative stress within tumor cells through the synergistic action of SAE and GOx, leading to depletion of GSH and subsequently triggering ferroptosis. The resulting nanoreactor-induced ferroptosis leads to immunogenic cell death (ICD) and significantly recruits T lymphocyte infiltration in tumor tissues. This study was designed with the concept of triggering ferroptosis-dependent ICD mechanism in bladder cancer cells, and developed an acid-specific nanoreactor to enhance the immunotherapy efficacy for bladder cancer, which introduces a novel approach for immunotherapy of bladder cancer.

Glucose-responsive soluble microneedle prepared with “Gelatin - hydroxyethylcellulose ethoxylate complex coacervate” for the transdermal drug delivery

A glucose-responsive “complex coacervate” based drug delivery system has tremendous potential to improve the quality of life and health. Polyquaternium-10, a cationic cellulose derivative offers a potential solution for creating a soluble, painless microneedle patch capable of responding to glucose levels and loaded with the enzyme glucose oxidase (GOx). The gelatin at pH 7.4 forms complex coacervate with polyquaternium at the ratio of 7:3 respectively. As the pH decreases to the isoelectric point of gelatin, the coacervate disassembles and enhances the release of the payload. Microneedles MNs were fabricated in a pyramid shape, containing complex coacervate improved the mechanical strength of MNs, enhancing penetration capability. The incorporation of GOx into the microneedles enabled glucose-responsive behavior. In vitro experiments with artificial skin demonstrated decreased pH within the buffer medium due to the generation of gluconic acid in the presence of GOx. This pH shift triggered enhanced drug release, especially under hyperglycemic conditions, making the system a valuable tool for regulating transdermal drug delivery. In summary, this innovative glucose-responsive drug delivery system based on complex coacervate of gelatin and polyquaternium combines pH-sensitive drug release, mechanical reinforcement, and real-time glucose monitoring, making it a promising solution for improving transdermal drug delivery.

Novel dual-responsive hydrogel composed of polyacrylamide/Fe-MOF/zinc finger peptide for construction of electrochemical sensing platform

Responsive hydrogels have received much attention for improving the detection performance of electrochemical sensors because of their special responsiveness. However, current responsive hydrogels generally suffer from long response times, ranging from tens of minutes to several hours. This situation severely limits the detection performance and practical application of electrochemical sensors. Here, an electrochemical sensing platform was constructed by employing dual-responsive polyacrylamide/zinc finger peptide/Fe-MOF hydrogel (PZFH) as the silent layer, sodium alginate-Ni2+-graphene oxide hydrogel as the signal layer. GOx@ZIF-8, as the immunoprobe, catalyzed glucose to H2O2 and gluconic acid, resulting in the cleavage of immunoprobe as the pH decreased and subsequent release of Zn2+ ions. During the process of Fe-MOF converting from Fe3+ to Fe2+, free radicals were generated and used to destroy the structure of the PZFH. Cysteine and histidine in the zinc finger peptide can specifically bind to Zn2+ to create many pores in PZFH, exposing the signal layer. These synergistic effects rapidly decreased the impedance of PZFH and increased the electrochemical signal of Ni2+. The electrochemical sensing platform was used to detect pro-gastrin-releasing peptide with response times as short as 7 min of PZFH, a wide linear range from 100 ng mL−1 to 100 fg mL−1, and an ultra-low limit of detection of 14.24 fg mL−1 (S/N = 3). This strategy will provide a paradigm for designing electrochemical sensors.

Metabolic Assessment in Non-Dialysis Patients with Chronic Kidney Disease.

The aim of this study was to investigate the changes of different metabolites in the body fluids of non-dialysis patients with chronic kidney disease (CKD) using a metabolomics approach. The goal was to identify early biomarkers of CKD progression through metabolic pathway analysis. Plasma samples from 47 patients with stages 1-4 CKD not requiring dialysis and 30 healthy controls were analyzed by liquid chromatography-mass spectrometry (LC-MS). Using multivariate data analysis, specifically a partially orthogonal least squares discriminant analysis model (OPLS-DA), we investigated metabolic differences between different stages of CKD. The sensitivity and specificity of the analysis were evaluated using the Area Under Curve (AUC) method. Furthermore, the metabolic pathways were analyzed using the Met PA database. Plasma samples from CKD patients and controls were successfully differentiated using an OPLS-DA model. Initially, twenty-five compounds were identified as potential plasma metabolic markers for distinguishing CKD patients from healthy controls. Among these, six compounds (ADMA, D-Ornithine, Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid) were found to be associated with CKD progression It has been found to be associated with the progression of CKD. Changes in metabolic pathways associated with CKD progression include arginine and ornithine metabolism, tryptophan metabolism, and the pentose phosphate pathway. By analyzing the metabolic pathways of different metabolites, we have identified the significant impact of CKD progression. The main metabolic pathways involved are Arginine and Ornithine metabolism, Tryptophan metabolism, and Pentose phosphate pathway. ADMA, D-Ornithine, L-Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid could serve as potential early biomarkers for CKD progression. These findings have important implications for the early intervention and treatment of CKD, as well as for further research into the underlying mechanisms of its pathogenesis.

A multimodal therapy for infected diabetic wounds based on glucose-responsive nanocomposite-integrated microneedles.

Diabetic wounds in a state of high glucose are refractory to treatment and healing, especially if they are infected with bacteria. Herein, a novel nanocomposite (CIP/GOx@ZIF-8) was synthesized by loading ciprofloxacin hydrochloride (CIP) and glucose oxidase (GOx) into zeolitic imidazole framework-8 (ZIF-8) that exhibited good glucose sensitivity and catalytic activity. The high glucose in diabetic wounds could be decomposed into hydrogen peroxide (H2O2) and gluconic acid via the catalysis of GOx, which further destroyed CIP/GOx@ZIF-8 to release Zn2+ and cargos. The combination of glucose starvation, Zn2+, H2O2 and CIP could elevate the antibacterial effect and reduce bacterial resistance. Subsequently, the nanocomposite was fabricated into dissolving microneedles (CIP/GOx@ZIF-8 MNs) using polyvinylpyrrolidone (PVP). The microneedles exhibited good mechanical strength, puncture performance, dissolving performance, glucose responsiveness, antibacterial performance and biocompatibility. For in vivo wound healing, CIP/GOx@ZIF-8 MNs with good biosafety facilitated neovascularization and collagen deposition as well as reduced inflammation, and the wounds were almost healed after treatment. This multimodal therapeutic strategy is created to provide a unique treatment for infected diabetic wounds.