Sensitive Peroxide Research Articles

Mitochondria as multifaceted regulators of ferroptosis

AbstractMitochondria are well known to be “energy factories” of the cell as they provide intracellular ATP via oxidative phosphorylation. Interestingly, they also function as a “cellular suicidal weapon store” by acting as a key mediator of various forms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. Ferroptosis, distinct from the other types of regulated cell death, is characterized by iron-dependent lipid peroxidation and subsequent plasma membrane rupture. Growing evidence suggests that an impaired ferroptotic response is implicated in various diseases and pathological conditions, and this impaired response is associated with dramatic changes in mitochondrial morphology and function. Mitochondria are the center of iron metabolism and energy production, leading to altered lipid peroxidation sensitivity. Although a growing number of studies have explored the inextricable link between mitochondria and ferroptosis, the role of this organelle in regulating ferroptosis remains unclear. Here, we review recent advances in our understanding of the role of mitochondria in ferroptosis and summarize the characteristics of this novel iron-based cellular suicide weapon and its arsenal. We also discuss the importance of ferroptosis in pathophysiology, including the need for further understanding of the relationship between mitochondria and ferroptosis to identify combinatorial targets that are essential for the development of successful drug discovery.

Ferroptosis Patterns Predicting Prognosis and Drug Resistance in Acute Lymphoblastic Leukemia

Background: Most acute lymphoblastic leukemia (ALL) patients are treated with chemotherapy as primary care. Although treatment response is usually positive, resistance and relapse often occur through unclear mechanisms. Ferroptosis is an iron-dependent form of regulating cell death associated with cancer. The characteristics of ferroptosis in ALL are still uncertain. This study aimed to explore the effect of ferroptosis on drug resistance and prognosis, and the potential of ferroptosis-based treatment in ALL. Methods: We comprehensively evaluated the ferroptosis levels of 480 ALLs from the TARGET and GEO database, and 99 ALLs from our clinic based on 487 ferroptosis-related specific genes (FRGs) downloaded from FerrDb database. The ferroptosis score (FS) was constructed to quantify the ferroptosis levels of individuals using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. We then assessed the transcription profile of 99 ALLs in our clinic according to the minimal residual diseased (MRD) level, and the integrated metabolic analysis and RNA sequencing in drug-resistant and sensitive ALL cell lines. The biological function of solute carrier family 7 member 11 (SLC7A11), one of FRGs, on cell growth, lipid peroxidation, and drug sensitivity were further examined in ALL cell lines Nalm-6, Jurkat, and their corresponding drug-resistant cells Nalm-6/ADR and Jurkat/ADR. Results: At first, we identified that FRGs have prevalent genetic alteration in ALL, most for missense mutation of driver genes. In addition, the heterogeneous expression of the FRGs in normal and ALL samples indicated the involvement of FRGs expression in ALL development. Subsequently, we identified two distinct ferroptosis phenotypes in ALL with significantly different prognoses. We then developed a risk model termed FS to evaluate ferroptosis levels of ALL patients based on differential expression genes between the two ferroptosis phenotypes. Compared with the low-FS group, the high-FS group was characterized by higher estimated IC50 in the many chemotherapy drugs with an unfavorable prognosis, which was validated by our clinical data. Furtherly, SLC7A11 was identified as a key regulator of ferroptosis-related drug resistance in ALL. Clinically, SLC7A11 was selected out with the highest log |FC| in the MRDHigh(>1%) group in comparison with MRDlow(＜0.01%) group. The abundance of SLC7A11 was strongly correlated with relapsed/refractory disease. Overexpression of SLC7A11 and reduction of ferroptosis were observed in the drug-resistant cells. The SLC7A11-specific classic ferroptosis inducer erastin and shRNA both decreased cellular glutamine uptake, increased cellular lipid peroxidation, enhanced the sensitivity of chemotherapeutic with synergism, and led to deceleration of cell proliferation via glutamate metabolism in the oxidative phosphorylation pathway. Conclusions: Ferroptosis score could be a prognostic indicator for ALL progression and chemotherapy resistance. SLC7A11 functioned as an extracellular glutamine transporter, promoting ALL resistance through reprogramming glutamine metabolism of ALL, while rendering ALL cells insensitive to chemotherapy. Ferroptosis-based therapies employing agents to target SLC7A11 offered substantial therapeutic improvements over conventional chemotherapy for ALL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Capacitance-Based Biosensor for the Measurement of Total Loss of L-Amino Acids in Human Serum during Hemodialysis.

In this paper, we present a biosensor based on a gold nanoparticle (AuNP)-modified Pt electrode with an adjusted membrane containing cross-linked L-amino acid oxidase for the detection and quantification of total L-amino acids. The designed biosensor was tested and characterized using the capacitance-based principle, capacitance measurements after electrode polarization, disconnection from the circuit, and addition of the respective amount of the analyte. The method was implemented using the capacitive and catalytic properties of the Pt/AuNP electrode; nanostructures were able to store electric charge while at the same time catalyzing the oxidation of the redox reaction intermediate H2O2. In this way, the Pt/AuNP layer was charged after the addition of analytes, allowing for much more accurate measurements for samples with low amino acid concentrations. The combined biosensor electrode with the capacitance-based measurement method resulted in high sensitivity and a low limit of detection (LOD) for hydrogen peroxide (4.15 μC/μM and 0.86 μM, respectively) and high sensitivity, a low LOD, and a wide linear range for L-amino acids (0.73 μC/μM, 5.5 μM and 25-1500 μM, respectively). The designed biosensor was applied to measure the relative loss of amino acids in patients undergoing renal replacement therapy by analyzing amino acid levels in diluted serum samples before and after entering/leaving the hemodialysis apparatus. In general, the designed biosensor in conjunction with the proposed capacitance-based method was clinically tested and could also be applied for the detection of other analytes using analyte-specific oxidases.

Novel and highly stable strategy for the development of microfluidic enzymatic assays based on the immobilization of horseradish peroxidase (HRP) into cotton threads

The use of biological components in the development of new methods of analysis and point-of-care (POC) devices is an ever-expanding theme in analytical chemistry research, due to the immense potential for early diagnosis of diseases and monitoring of biomarkers. In the present work, the evaluation of an electrochemical microfluidic device based on the immobilization of horseradish peroxidase (HRP) enzyme into chemically treated cotton threads is described. This bioreactor was used as a channel for the build of the microfluidic device, which has allowed to use of a non-modified screen-printed electrode (SPE) as an amperometric detector. Cotton threads were treated using citric acid, and the immobilization of HRP has been performed by EDC/NHS crosslinking, connecting amine groups of the enzymes to carboxylic acids in the cellulosic structure. For the analytical evaluation, an amperometric assay for hydrogen peroxide detection was performed after the injection of H2O2 and hydroquinone (HQN) concomitantly. The enzymatic reaction consumes H2O2 leading to the formation of O-quinone, which is readily reducible at non-modified SPE. Several experimental parameters related to enzyme immobilization have been investigated and under the best set of conditions, a good analytical performance was obtained. In addition, the threads were freezer-stored and, after 12 weeks, 84% of hydrogen peroxide sensitivity was maintained, which is very reasonable for enzyme-based systems and still offers good analytical precision. Therefore, a simple and inexpensive microfluidic system was reported by crosslinking carboxylic groups to amine-containing macromolecules, suggesting a new platform for many other protein-based assays.

ZccE is a Novel P-type ATPase That ProtectsStreptococcus mutansAgainst Zinc Intoxication.

Zinc is a trace metal that is essential to all forms of life, but that becomes toxic at high concentrations. Because it has both antimicrobial and anti-inflammatory properties and low toxicity to mammalian cells, zinc has been used as a therapeutic agent for centuries to treat a variety of infectious and non-infectious conditions. While the usefulness of zinc-based therapies in caries prevention is controversial, zinc is incorporated into toothpaste and mouthwash formulations to prevent gingivitis and halitosis. Despite this widespread use of zinc in oral healthcare, the mechanisms that allow Streptococcus mutans, a keystone pathogen in dental caries and prevalent etiological agent of infective endocarditis, to overcome zinc toxicity are largely unknown. Here, we discovered that S. mutans is inherently more tolerant to high zinc stress than all other species of streptococci tested, including commensal streptococci associated with oral health. Using a transcriptome approach, we uncovered several potential strategies utilized by S. mutans to overcome zinc toxicity. Among them, we identified a previously uncharacterized P-type ATPase transporter and cognate transcriptional regulator, which we named ZccE and ZccR respectively, as responsible for the remarkable high zinc tolerance of S. mutans. In addition to zinc, we found that ZccE, which was found to be unique to S. mutans strains, mediates tolerance to at least three additional metal ions, namely cadmium, cobalt, and copper. Loss of the ability to maintain zinc homeostasis when exposed to high zinc stress severely disturbed zinc:manganese ratios, leading to heightened peroxide sensitivity that was alleviated by manganese supplementation. Finally, we showed that the ability of the ΔzccE strain to stably colonize the rat tooth surface after topical zinc treatment was significantly impaired, providing proof of concept that ZccE and ZccR are suitable targets for the development of antimicrobial therapies specifically tailored to kill S. mutans.

C. elegans ribosomal protein S3 protects against H2O2-induced DNA damage and suppresses spontaneous mutations in yeast

Carcinogenicity and cytotoxicity are severe consequences of DNA damage. Base Excision Repair (BER) is a conserved DNA repair pathway that replaces many damaged bases caused by oxidation. Aberrations in BER are associated with carcinogenesis, neurodegeneration, and aging. The nematode C. elegans is an attractive model system for studying BER. However, in this organism, the complete pathway is not fully delineated. To further explore the BER process in C. elegans, we used affinity tag chromatography and mass spectrometry to identify the interactome of uracil DNA glycosylase-1 (CeUNG-1), an enzyme that acts during the first step of the BER pathway. Our analysis identified that CeUNG-1 is associated with the 40 S ribosomal protein S3 (CeRPS-3), homologs of which have been shown to process 8-oxoguanine and abasic site lesions in other organisms. We report a strong in silico association between CeUNG-1 and CeRPS-3 and confirmed this interaction using the yeast two-hybrid system. Downregulation of the Cerps-3 gene reduced the viability of wild-type worms upon exposure to the chemical oxidant hydrogen peroxide. Further analysis shows that Cerps-3 knockdown significantly sensitized the AP endonuclease APN-1-deficient strain, apn-1, but to a lesser extent exo-3, to the lethal effects of hydrogen peroxide. A cross-species complementation experiment reveals that the expression of CeRPS-3 rescued the hydrogen peroxide sensitivity, and suppressed the high mutation frequency of the yeast AP endonuclease-deficient strain lacking Apn1 and Apn2. We propose that CeRPS-3 may function as an auxiliary DNA repair enzyme in C. elegans to process oxidative DNA lesions.

A sensitive hydrogen peroxide biosensor based on a new electron mediator 1-aminoethoxy-5-ethylphenazine dioctyl sulfosuccinate

Hydrogen peroxide (H2O2) plays a vital role in the fields of pharmaceutical production and biomedicine. The level of H2O2 in cells directly affects the growth and apoptosis of cells, so the development of H2O2 detection technology is very important. In this paper, a new type of electron mediator, 1-aminoethoxy-5-ethylphenazine dioctyl sulfosuccinate (aePEDS) was designed and synthesized and a biosensor based on a glass carbon (GC)/aePEDS/ horseradish peroxidase (HRP) modified electrode for the detection of H2O2 was developed. H2O2 was detected by the biosensor at a low working potential of 0.11 V (vs. Ag/AgCl), avoiding interference from other electroactive substances. Under optimal conditions, the limit of detection was 0.2 μM and the sensitivity was 0.001 μA/mM. The developed sensor was used to evaluate the activity of antitumor drugs by detecting the level of hydrogen peroxide in the cell culture medium after drug stimulation of lung cancer cells. Compared with the hydrogen peroxide kit method, the constructed electrochemical biosensor can more sensitively and accurately reflect the impact of the change of hydrogen peroxide content on cells after drug stimulation and is a more promising method for cell detection and screening of drug activity.

The Asparagine Hydroxylase FIH: A Unique Oxygen Sensor.

Significance: Limited oxygen availability (hypoxia) commonly occurs in a range of physiological and pathophysiological conditions, including embryonic development, physical exercise, inflammation, and ischemia. It is thus vital for cells and tissues to monitor their local oxygen availability to be able to adjust in case the oxygen supply is decreased. The cellular oxygen sensor factor inhibiting hypoxia-inducible factor (FIH) is the only known asparagine hydroxylase with hypoxia sensitivity. FIH uniquely combines oxygen and peroxide sensitivity, serving as an oxygen and oxidant sensor. Recent Advances: FIH was first discovered in the hypoxia-inducible factor (HIF) pathway as a modulator of HIF transactivation activity. Several other FIH substrates have now been identified outside the HIF pathway. Moreover, FIH enzymatic activity is highly promiscuous and not limited to asparagine hydroxylation. This includes the FIH-mediated catalysis of an oxygen-dependent stable (likely covalent) bond formation between FIH and selected substrate proteins (called oxomers [oxygen-dependent stable protein oligomers]). Critical Issues: The (patho-)physiological function of FIH is only beginning to be understood and appears to be complex. Selective pharmacologic inhibition of FIH over other oxygen sensors is possible, opening new avenues for therapeutic targeting of hypoxia-associated diseases, increasing the interest in its (patho-)physiological relevance. Future Directions: The contribution of FIH enzymatic activity to disease development and progression should be analyzed in more detail, including the assessment of underlying molecular mechanisms and relevant FIH substrate proteins. Also, the molecular mechanism(s) involved in the physiological functions of FIH remain(s) to be determined. Furthermore, the therapeutic potential of recently developed FIH-selective pharmacologic inhibitors will need detailed assessment. Antioxid. Redox Signal. 37, 913-935.

Antibacterial Effects of Bacteriocin PLNC8 against Helicobacter pylori and Its Potential Mechanism of Action.

Helicobacter pylori (H. pylori) is a bacterium that can cause a variety of gastric diseases. Most bacteriocins have gained popularity due to their non-toxic effects on cells and antibacterial effects against a wide range of pathogenic bacteria. In this study, the chemical synthesis of the bipeptide bacteriocin PLNC8 was used to investigate its possible action mechanism against H. pylori ZJC03 in vitro. Results showed that PLNC8 had significant anti-H. pylori ZJC03 potential, which resulted in a significant reduction in urease activity and a minimum inhibitory concentration (MIC) of 80 μM. PLNC8 inhibited the growth of H. pylori ZJC03, disrupting its structure as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, PLNC8 decreased the ATP level and hydrogen peroxide sensitivity of H. pylori ZJC03. In conclusion, PLNC8 disrupts the ability of H. pylori ZJC03 to alter the host environment, providing a new avenue for the prevention and control of H. pylori infection, providing a theoretical foundation for further elucidation of its regulatory mechanism.

Insight into OTFT Sensors Using Confocal Fluorescence Microscopy.

Confocal fluorescence microscopy provides a means to map charge carrier density within the semiconductor layer in an active organic thin film transistor (OTFT). This method exploits the inverse relationship between charge carrier density and photoluminescence (PL) intensity in OTFTs, originating from exciton quenching following exciton-charge energy transfer. This work demonstrates that confocal microscopy can be a simple yet effective approach to gain insight into doping and de-doping processes in OTFT sensors. Specifically, the mechanisms of hydrogen peroxide sensitivity are studied in low-voltage hygroscopic insulator field effect transistors (HIFETs). While the sensitivity of HIFETs to hydrogen peroxide is well known, the underlying mechanisms remain poorly understood. Using confocal microscopy, new light is shed on these mechanisms. Two distinct doping processes are discerned: one that occurs throughout the semiconductor film, independent of applied voltages; and a stronger doping effect occurring near the source electrode, when acting as an anode with respect to a negatively polarized drain electrode. These insights offer important guidance to future studies and the optimization of HIFET-based sensors. More importantly, the methods reported here are broadly applicable to the study of a range of OTFT-based sensors. This work demonstrates that confocal microscopy can be an effective research tool in this field.

Highly Sensitive Amperometric Detection of Hydrogen Peroxide in Saliva Based on N-Doped Graphene Nanoribbons and MnO2 Modified Carbon Paste Electrodes.

Four different graphene-based nanomaterials (htGO, N-htGO, htGONR, and N-htGONR) were synthesized, characterized, and used as a modifier of carbon paste electrode (CPE) in order to produce a reliable, precise, and highly sensitive non-enzymatic amperometric hydrogen peroxide sensor for complex matrices. CPE, with their robustness, reliability, and ease of modification, present a convenient starting point for the development of new sensors. Modification of CPE was optimized by systematically changing the type and concentration of materials in the modifier and studying the prepared electrode surface by cyclic voltammetry. N-htGONR in combination with manganese dioxide (1:1 ratio) proved to be the most appropriate material for detection of hydrogen peroxide in pharmaceutical and saliva matrices. The developed sensor exhibited a wide linear range (1.0–300 µM) and an excellent limit of detection (0.08 µM) and reproducibility, as well as high sensitivity and stability. The sensor was successfully applied to real sample analysis, where the recovery values for a commercially obtained pharmaceutical product were between 94.3% and 98.0%. Saliva samples of a user of the pharmaceutical product were also successfully analyzed.

Structural Engineering of Hollow Microflower-like CuS@C Hybrids as Versatile Electrochemical Sensing Platform for Highly Sensitive Hydrogen Peroxide and Hydrazine Detection.

Designing metal sulfides with unique configurations and exploring their electrochemical activities for hydrogen peroxide (H2O2) and hydrazine (N2H4) is challenging and desirable for various fields. Herein, hollow microflower-like CuS@C hybrids were successfully assembled and further exploited as a versatile electrochemical sensing platform for H2O2 reduction and N2H4 oxidation, of which the elaborate strategies make the perfect formation of hollow architecture, providing considerable electrocatalytic sites and fast charge transfer rate, while the appropriate introduction polydopamine-derived carbon skeleton facilitates the electronic conductivity and boosts structural robustness, thus generating wide linear range (0.05-14 and 0.01-10 mM), low detection limit (0.22 μM and 0.07 μM), and a rather low overpotential (-0.15 and -0.05 V) toward H2O2 and N2H4, as well as good selectivity, excellent reproducibility, and admirable long-term stability. It should be highlighted that the operating potentials can compare favorably with those of some reported H2O2 and N2H4 sensors based on noble metals. In addition, good recoveries and acceptable relative standard deviations (RSDs) attained in serum and water samples fully verify the accuracy and anti-interference capability of our proposed sensor systems. These results not only elucidate an effective structural nanoengineering strategy for electroanalytical science but also advance the rational utilization of H2O2 and N2H4 in practicability.

Highly Sensitive Hydrogen Peroxide Biosensor Based on Tobacco Peroxidase Immobilized on p‐Phenylenediamine Diazonium Cation Grafted Carbon Nanotubes: Preventing Fenton‐like Inactivation at Negative Potential

AbstractHerein, we present a novel electrode platform for H2O2 detection based on the immobilization of recombinant Tobacco Peroxidase (r‐TOP) onto graphite electrodes (G) modified with p‐phenylenediamine (p‐PD) diazonium cation grafted multi‐walled carbon nanotubes (MWCNTs). The employment of both p‐phenylenediamine moieties and covalent cross‐linking by using glutaraldehyde allowed us to enhance the sensitivity, stability, and selectivity toward H2O2 detection, as well as preventing enzyme inactivation due to the electro‐Fenton reaction. This reaction continuously produces hydroxyl radicals, whose high and unselective reactivity is likely to reduce drastically the operating life of the biosensor. The protection against the electro‐Fenton reaction is mainly ascribed to a beneficial enzyme immobilization leading to a correct orientation achieved through cross‐linking the enzyme in combination with interaction between the uncoupled ‐NH2 groups (mainly uncharged at pH 7, considering a pKa of 4.6) available on the electrode surface and the enzyme. In particular, the electrode based on the r‐TOP/p‐PD/MWCNTs/G platform showed a lower limit of detection of 1.8 μM H2O2, an extended linear range between 6 and 900 μM H2O2, as well as a significant increase in sensitivity (63.1±0.1 μA mM−1 cm−2) compared with previous work based on TOP. Finally, the r‐TOP/p‐PD/MWCNTs/G electrode was tested in several H2O2 spiked food samples as a screening analytical method for the detection of H2O2.

A promising sensitive electrochemiluminescence hydrogen peroxide sensor based on incorporated CuO nanostructures on 3-D Ni foam

A promising sensitive electrochemiluminescence hydrogen peroxide sensor based on incorporated CuO nanostructures on 3-D Ni foam

Brain-implantable multifunctional probe for simultaneous detection of glutamate and GABA neurotransmitters

Glutamate (GLU) and gamma-aminobutyric acid (GABA) are neurotransmitters (NTs) with an essential role in signal transmission in the brain. Brain disorders, such as epilepsy, Alzheimer's and Parkinson's diseases, and traumatic brain injury can be linked to imbalances in the GLU-GABA homeostasis that occurs in sub-second to seconds time frames. Current measurement techniques can detect these two NT concentrations simultaneously only in vitro. The present work reports on the fabrication of a silicon multifunctional biosensor microarray probe for sub-second simultaneous GLU-GABA detection in real-time, with excellent analyte sensitivity and selectivity and in vivo capabilities. The novel Si probes feature four surface-functionalized platinum ultramicroelectrodes (UMEs) for simultaneous amperometric detection of GLU and GABA with a sentinel, and a built-in microfluidic channel for the introduction of neurochemicals in the proximity of the UMEs. The microchannel also allows functioning of an On-Demand In-situ Calibrator that runs in-situ biosensor calibration. The probe exhibited excellent robustness at insertion in agarose-gel brain-tissue-mimicking test, and remarkably high hydrogen peroxide sensitivity (a by-product of GLU-GABA enzyme biosensor) with values on the order of 5000 nA μM -1 cm -2 and maximum sensitivities of 204±15 nA μM -1 cm -2 and 37±7 nA μM -1 cm -2 for GLU and GABA, respectively. Furthermore, the limit of detection of the biosensors reached as low as 7 nM, 165 nM and 750 nM for H 2 O 2, GLU and GABA, respectively and a temporal resolution of hundreds of milliseconds during in vivo studies using freely moving rats.

Synthesis of Fe3O4@MIL-101(Fe) for a Novel Electrochemistry Detection of Citric Acid

Introduction Urolithiasis is one of the most common diseases in the urinary system with very high incidence worldwide. In recent studies, citric acid (CA) has been considered as a biomarker of urolithiasis due to its vital suppression role in urinary stone formation. The detection of CA in urine is of great significance for early screening and prognostic monitoring of urolithiasis. However, most analytical methods for detecting CA are complicated and require expensive equipment.In the present study[1, 2], MIL-101(Fe) and Fe3O4 were used for electrochemical detection of CA, based on the reaction of Fe(Ⅲ) and CA. Following these ideas, the electrodes modified with Fe3O4@MIL-101(Fe) nanoparticles were fabricated and investigated for whether they were able to detect CA and improve the sensitivity. Method Synthesis of Fe3O4@MIL-101(Fe) nanoparticles(Figure1. A): The Fe3O4@MIL-101(Fe) core-shell nanoparticles were synthesized according to previous literatures[3, 4]. Specifically, 3.6 g NaAC and 0.87 g FeCl3 were dissolved in 75 mL ethylene glycol under ultrasound for 30 minutes. The mixture was transferred to a Teflon-lined autoclave chamber and heated at 200 °C for 16 h, then naturally cooled to room temperature. The obtained magnetic nanoparticles were collected with a magnet and washed with ethanol for three times. 350 mg above nanoparticles was dissolved to 75mL ethanol with 0.58mM Mercapto acetic acid (MAA), and gently stirred for 24h under nitrogen protection. The steps of self-assembly cycle were as follows. Firstly, 100 mg Fe3O4-MAA was dispersed in 10mM FeCl3, shaked for 1 minute and left for 15 minutes, then washed with ethanol for three times. Next, the nanoparticles was re-dispersed in 10 mM benzene-1,3,5-tricarboxylic acid, kept for 30 min at 70 °C with stripping, and then washed with ethanol for three times. After repeating this cycle 31 times, the synthesized core-shell nanoparticles were dried at 75 °C. Fabrication of the Fe3O4@MIL-101(Fe) /GCE: The GCE working electrode was polished with 1.0, 0.3, and 0.05 μm Al2O3 substance and sonicated with an ethyl alcohol and water solution for 5 min respectively then dried under a N2 stream. For the modification, the synthesized Fe3O4@MIL-101(Fe) core-shell nanoparticles was dissolved in ultrapure water and the final concentration was 1.0 mg/mL. After sonicating for 1 hour, 7 µL of the suspension was dripped onto the surface of the GCE and dried at room temperature. Detection of CA: Electrochemical analyses were carried out using differential pulse voltammetry (DPV) measurements in 0.01M KCl solution with different concentration of CA at pH 7.0. All experiments were performed at room temperature with a three-electrode system: Ag/AgCl (3 M KCl) electrode and platinum wire were used as a reference electrode and counter electrode, respectively, and applying in a potential range of 0 to 0.60 V, with an amplitude of 0.025 V and pulse period of 0.5 s. Results and Conclusions Characterization of Fe3O4@MIL-101(Fe): TEM images of as-prepared nanoparticles is shown in Figure 1. B. The Fe3O4@MIL-101(Fe) had spherical morphology and the core–shell structures which indicated the formation of MIL-101(Fe) layer on the Fe3O4 nanoparticles.. The dark core was the Fe3O4 with a diameter of about 348 nm, and the relatively bright outer layer was the MIL-101(Fe) with the thickness of 246 nm. The detection of CA: The DPVs of Fe3O4@MIL-101(Fe) /GCE in the 0.1M KCl with or without 100 mg/L CA are shown in Figure 1. C. In the presence of CA, a current peak was obtained in 0.324V. This could be explained due to the reaction of Fe3+ ions in Fe3O4@MIL-101(Fe) with CA. The performance of the Fe3O4@MIL-101(Fe) /GCE in different concentrations of CA solutions were monitored by DPV, and the corresponding ΔCurrent( ) are shown in Figure 1.D. The resulting calibration is presented in the Figure 1. E, which was linear over the concentration range of 40 to 100 mg/L and 100-500 mg/L CA, with the linear regression equations of Y = 0.0004*X +0.004 (R2 = 0.9956) and Y = 0.00016*X + 0.03773 (R2 = 0.9766), respectively. Based on three times the background noise, the modified electrode provided a limit of detection of 31 mg/L. References Valizadeh, H., J. Tashkhourian, and A.J.M.A. Abbaspour, A carbon paste electrode modified with a metal-organic framework of type MIL-101 (Fe) for voltammetric determination of citric acid. 2019. 186(7): p. 455. Guivar, J.A.R., et al., Preparation and characterization of cetyltrimethylammonium bromide (CTAB)-stabilized Fe3O4 nanoparticles for electrochemistry detection of citric acid. 2015. 755: p. 158-166. Chen, Y., et al., Facile preparation of core–shell magnetic metal–organic framework nanoparticles for the selective capture of phosphopeptides. 2015. 7(30): p. 16338-16347. Salman, F., A. Zengin, and H.Ç.J.I. Kazici, Synthesis and characterization of Fe 3 O 4-supported metal–organic framework MIL-101 (Fe) for a highly selective and sensitive hydrogen peroxide electrochemical sensor. 2020. 26(10): p. 5221-5232. Figure 1

Amphiphilic block versus random copolymer nanoparticles with reactive oxygen species responsiveness as berberine vehicles

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized via reversible addition–fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1–158.6 and 126.3–187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (H2O2) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to H2O2 than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%–9.1% and 7.3%–8.9%, respectively. The BBR release can be controlled in an H2O2 medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to H2O2 were higher over 48 h. The BBR cumulative release amount in the H2O2 medium for the block and random copolymer nanoparticles was 62.2%–70.2% and 68.6%–80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the H2O2 responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.

Fabrication of label-free and eco-friendly ROS optical sensor with potent antioxidant properties for sensitive hydrogen peroxide detection in human plasma

Herein, biogenic silver nanoparticles, Cafi-AgNPs was produced based on Cassia fistula-phenolic-rich extract (Cafi) only, without any toxic chemical reagent or organic solvent. Cafi bioactives were characterized using UHPLC-ESI-QTOF-MS/MS analysis. The as-synthesized nanoparticles were characterized using physico-chemical techniques including UV–vis, TEM, SEM, EDX, FTIR, DLS, Zeta potential, XRD, TGA and DGA. In addition, their antioxidant properties and cytocompatibility on erythrocytes and HEK-293 cells were examined. Results show that Cafi mediated the successful synthesis of stable well-dispersed AgNPs. Cafi-AgNPs demonstrated potent reducing and radical scavenging activities against ABTS˙+, DPPH˙ and NO˙. Furthermore, Cafi-AgNPs was compatible with human erythrocytes and HEK-293 cells. Based on the superior surface plasmonic and biological attributes of Cafi-AgNPs, its potential in H2O2 sensing was evaluated. The proposed sensor demonstrated satisfactory analytical performances with linearity of 10–200 μM, detection limit of 3.0 μM for H2O2, and was successfully applied in the detection of H2O2 in human plasma.

Carbon Assimilation, Isotope Discrimination, Proline and Lipid Peroxidation Contribution to Barley (Hordeum vulgare) Salinity Tolerance.

Barley (Hordeum vulgare L.) exhibits great adaptability to salt tolerance in marginal environments because of its great genetic diversity. Differences in main biochemical, physiological, and molecular processes, which could explain the different tolerance to soil salinity of 16 barley varieties, were examined during a two-year field experiment. The study was conducted in a saline soil with an electrical conductivity ranging from 7.3 to 11.5 dS/m. During the experiment, a number of different physiological and biochemical characteristics were evaluated when barley was at the two- to three-nodes growing stage (BBCH code 32–33). The results indicated that there were significant (p < 0.001) effects due to varieties for tolerance to salinity. Carbon isotopes discrimination was higher by 11.8% to 16.0% in salt tolerant varieties than that in the sensitive ones. Additionally, in the tolerant varieties, assimilation rates of CO2 and proline concentration were 200% and up to 67% higher than the sensitive varieties, respectively. However, in sensitive varieties, hydrogen peroxide and lipid peroxidation were enhanced, indicating an increased lipid peroxidation. The expression of the genes Hsdr4, HvA1, and HvTX1 did not differ among barley varieties tested. This study suggests that the increased carbon isotopes discrimination, increased proline concentration (play an osmolyte source role), and decreased lipid peroxidation are traits that are associated with barley tolerance to soil salinity. Moreover, our findings that proline improves salt tolerance by up-regulating stress-protective enzymes and reducing oxidation of lipid membranes will encourage our hypothesis that there are specific mechanisms that can be co-related with the salt sensitivity or the tolerance of barley. Therefore, further research is needed to ensure the tolerance mechanisms that exclude NaCl in salt tolerant barley varieties and diminish accumulation of lipid peroxides through adaptive plant responses.

A highly sensitive hydrazine and hydrogen peroxide non-enzymatic sensor based on CuO nanoplatelets

CuO nanoplatelets were synthesized via a controllable hydrothermal process. Their structure and morphology were characterized by X-ray diffraction (XRD), Raman spectroscopy, and transmission electron microscopy (TEM). The sensing activity of the CuO nanoplatelets towards the detection of hydrazine and H2O2 was investigated in a 0.1 M NaOH solution using cyclic voltammetry and amperometry. The proposed sensor exhibits a very high sensitivity: 2412 μA.mM− 1.cm− 2 for the detection of hydrazine and 1790 µA.mM− 1.cm− 2 for H2O2. The linear ranges were 0–1200 µM and 0–1800 µM, and the detection limits were 100 nM and 300 nM for hydrazine and hydrogen peroxide, respectively. Additionally, good recovery of the analyte in real water samples confirms the reliability of the prepared sensor in practical applications. The proposed sensor also showed a high selectivity. The enhanced electrocatalytic performance of the CuO nanoplatelets might be ascribed to the thin dispersed nanoplatelets which provide highly exposed active sites. These promising results could open the route for potential applications of the CuO nanoplatelet sensor in various fields such as environmental detection, industrial applications and food analyses.