Thiol Groups Research Articles

Thiol-containing hyperbranched polysiloxane for scavenging reactive oxygen species.

Unconventional luminescent polymers have attracted considerable attention in the biological field due to their intrinsic fluorescence properties and excellent biocompatibility. However, exploring the luminescent properties of thiol-containing polymers and the mechanism of their scavenging of ROS remains unclear. In this work, we synthesised three kinds of hyperbranched polysiloxanes (HE, HP, and HB) with terminal thiol groups containing different chain lengths by the polycondensation reaction. Surprisingly, HP exhibits longer-wavelength emission at 480 nm with a quantum yield of 12.23% compared to HE and HB. Experiments and density functional theory (DFT) calculations have revealed that the rigidity of the conformation is enhanced by substantial hydrogen bonds and through-space O⋯O interactions in the polymer structure. These interactions, combined with the rigid carbon chains, balance the flexibility of the Si-O-C chain segments, which emerges as a critical factor contributing to the superior fluorescence performance of HP. In addition, HP exhibits excellent biocompatibility and ROS scavenging ability with a scavenging capacity of up to 35.095%. This work provides a new fluorescent polymer for scavenging ROS for the treatment of ROS-related diseases.

Boosting the enzymatic activity of CxxC motif-containing PDI family members.

Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase (PDI) family and thus can be used to accelerate folding processes and increase the production of native proteins by minimal loading in comparison to glutathione.

Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.

Onopordopicrin from the Japanese Leaf Burdock Exerts Antiallergic Effects through the Inhibition of I Kappa B Kinase β

Onopordopicrin (OPP), found in burdock leaves and stems, exerts antiallergic properties whose mechanism remains elusive. We aimed to elucidate its mechanism using rat basophilic leukemia cells in vitro. Purified OPP demonstrated concentration‐dependent inhibition of degranulation after allergen or PMA/A23187 stimulation. OPP effectively suppressed TNF‐α and PGD2 releases. However, OPP did not suppress the increase in intracellular Ca2+ concentration after allergen stimulation. The α, β‐unsaturated carbonyl structure of OPP suggests potential electrophilic reactivity with polyfunctional thiol‐trapping agents, such as cysteine residues. Indeed, the degranulation‐inhibiting effect of OPP disappeared with the addition of cysteamine, which possesses a thiol group. I kappa B kinase β (IKKβ), which regulates degranulation in an NF‐κB‐independent manner, possesses a cysteine residue between the activation loop. Moreover, IKKβ plays an important role in TNF‐α and PGD2 production. OPP was found to reduce IKKβ activity in a concentration‐dependent manner. Together, our findings suggest that OPP exerts its antiallergic action via binding to cysteine residues in signal proteins such as IKKβ, thereby inhibiting their activation.

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 μM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Synthesis of a metal-organic framework Cu-Mi-UiO-66-based fluorescent nanoprobe for the simultaneous sensing and intracellular imaging of GSH and ATP.

This study reports a fluorescent nanoprobe operated in fluorescence turn-on mode for simultaneously sensing and imaging intracellular GSH and ATP. By using maleimide-derivatives as the ligand, the bimetallic nanoscale metal-organic framework (NMOF) Cu-Mi-UiO-66 has been synthesized for the first time using a straightforward one-step solvothermal approach, serving as a GSH recognition moiety. Subsequently, a Cy5-labeled ATP aptamer was assembled onto Cu-Mi-UiO-66 via strong coordination between phosphate and zirconium, π-π stacking and electrostatic adsorption to develop the dual-responsive fluorescence nanoprobe Cu-Mi-UiO-66/aptamer. Due to the photoinduced electron transfer (PET) effect between maleimide groups and the benzene ring of the ligand and the charge transfer between Cy5 and the Zr(IV)/Cu(II) bimetal center of the NMOF, the Cu-Mi-UiO-66/aptamer exhibits a fluorescence turn-off status. The Michael addition reaction between the thiol group of GSH and the maleimide on the NMOF skeleton results in turning on of the blue fluorescence of Cu-Mi-UiO-66. Meanwhile, upon specific interaction with ATP, the aptamer changes into internal loop structures and detaches from Cu-Mi-UiO-66, resulting in turning on of the red fluorescence of Cy5. The nanoprobe demonstrated an excellent sensing performance with a good linear range (GSH, 5.0-450.0 μM; ATP, 1.0-50.0 μM) and a low detection limit (GSH, 2.17 μM; ATP, 0.635 μM). More importantly, the Cu-Mi-UiO-66/aptamer exhibits good performance for tracing intracellular concentration variations of GSH and ATP in living HepG2 cells under different stimulations. This study highlights the potential of NMOFs for multiplexed analysis and provides a valuable tool for tumor microenvironment research and early cancer diagnosis.

Attenuation of albumin glycation and oxidative stress by minerals and vitamins: An in vitro perspective of dual-purpose therapy.

Nonenzymatic glycation of proteins is accelerated in the context of elevated blood sugar levels in diabetes. Vitamin and mineral deficiencies are strongly linked to the onset and progression of diabetes. The antiglycation ability of various water- and fat-soluble vitamins, along with trace minerals like molybdenum (Mo), manganese (Mn), magnesium (Mg), chromium, etc., have been screened using Bovine Serum Albumin (BSA) as in vitro model. BSA was incubated with methylglyoxal (MGO) at 37°C for 48h, along with minerals and vitamins separately, along with controls and aminoguanidine (AG) as a standard to compare the efficacy of the minerals and vitamins. Further, their effects on renal cells' (HEK-293) antioxidant potential were examined. Antiglycation potential is measured by monitoring protein glycation markers, structural and functional modifications. Some minerals, Mo, Mn, and Mg, demonstrated comparable inhibition of protein-bound carbonyl content and ß-amyloid aggregation at maximal physiological concentrations. Mo and Mg protected the thiol group and free amino acids and preserved the antioxidant potential. Vitamin E, D, B1 and B3 revealed significant glycation inhibition and improved antioxidant potential in HEK-293 cells as assessed by estimating lipid peroxidation, SOD and glyoxalase activity. These results emphasize the glycation inhibitory potential of vitamins and minerals, indicating the use of these micronutrients in the prospect of the therapeutic outlook for diabetes management.

Engineering a hierarchically micro-/nanostructured Si@Au-based artificial enzyme with improved accessibility of active sites for enhanced catalysis.

The active site accessibility and high loading of gold nanoparticles (AuNPs) are key factors affecting the catalytic activity of supported AuNP-based catalysts. However, the preparation of supported AuNP-based catalysts with highly accessible active sites still remains a challenge. Herein, sphere-on-sphere (SoS) silica microspheres with a hierarchical structure, good dispersion and high surface density of thiol groups (10 SH nm-2) are prepared and used as a platform for the growth of high-density AuNPs. The obtained hierarchical Si@Au micro-/nanostructure consisting of 0.55 μm SoS silica microspheres and 7.3 nm AuNPs (SoS-0.55@Au-7.3) is found to show excellent peroxidase-mimicking activity (Km = 0.033 mM and Vmax = 34.6 × 10-8 M s-1) with merits of high stability and good reusability. Furthermore, the as-obtained SoS-0.55@Au-7.3-based system can sensitively detect hydrogen peroxide (H2O2) with a low detection limit of 1.6 μM and a wide linear range from 2.5 μM to 1.0 mM. The high catalytic activity, excellent stability and good reusability of SoS-0.55@Au-7.3 imply its great prospects in biosensing and biomedical analysis.

Photo-initiated thiol-ene reaction of multi-functional thiol and olefinic organosilicon compounds leading to porous polymers: Solution polymerization and photolithography

Photo-initiated thiol-ene reaction between multi-functional thiol compounds and unsaturated organosilicon compounds in ethanol/dimethyl sulfoxide mixed solvent successfully yielded porous polymers. The morphology of the porous polymer was formed by connected particles, whose diameters ranged from 1 to 6 μm. An increase in the number of thiol group of multi-functional thiol compounds decreased the particle size and increased the Young's modulus of the porous polymers. Porous polymers absorbed various organic solvents and showed high water repellency. Photolithography based on the thiol-ene reaction led to the patterning by the porous polymers.

Construction of durable antibacterial cellulose textiles through grafting dynamic disulfide-containing amino-compound and nanosilver deposition

Cotton textile is very comfortable to wear, and also provides an ideal environment for bacterial propagation, easily causing harm to human health. In order to address this issue, various antibacterial techniques are employed for cotton finishing. However, some processes are complex and involve the use of environmentally unfriendly chemicals. In this work, a durable and efficient antibacterial cotton fabric was prepared via grafting of an amino-compound containing dynamic disulfide bonds, and then in-situ deposition of silver nanoparticles (AgNPs). Briefly, the reactive α-lipoic acid-modified polyethyleneimine (mPEI) was introduced to the cotton fibers via thiol-ene click reaction. Subsequently, the amino groups and dynamically-generated sulfhydryl groups in the mPEI molecules were used to initiate the ultrafast reduction of silver ions without the participation of additional reductant, constructing a stable antibacterial layer on fiber surface. The results reveal that the amino and thiol groups of mPEI could form coordination bonds with the deposited silver nanoparticles, and the antibacterial ability of AgNP@cotton-g-mPEI fabric remains at a high level even after 20 washing cycles. After 30 min of contact with Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), the antibacterial rates against both bacteria reached 99.99 %. Meanwhile, the network matrix constructed by the recombination of the dynamic disulfide bonds in mPEI endows the cotton fabric with detectable wrinkle resistance and encouraging anti-ultraviolet effect. The present work provides a novel alternative for preparation of durable and efficient antibacterial textiles.

Synthesis and Thio-Functionalization of Metal Organic Frameworks of Isonicotinate Ligands and their Application for Fluorescein Removal from Aqueous Solution

Mechanochemical syntheses of four (4) know metal organic frameworks (MOFs) were obtained by grinding stoichiometric amounts of metal salts [Zn (II) and Cu (II)] and corresponding carboxylate ligands [Fumaric and Isonicotinic acids] in a mortar with a pestle. Also, Solvent-based syntheses of MOFs were carried out with the reaction of metal salts and each carboxylate ligand by mixing in the presence of solvents. The compounds were characterized by the comparison of melting point, elemental analysis, FT-IR spectroscopy and XRPD results with those of the free ligands and literature. The analytical and spectroscopic data of the compounds prepared via the two different methods gave the expected product.
 The presence of coordinatively unsaturated metal centers in the synthesized MOFs provides an accessible way to selectively functionalize them through coordination bonds. In this work, thiol-functionalization of MOFs were described by choosing six well known MOFs in which three (3) are Zn-based while the other three (3) are Cu-based MOF, by a facile coordination based postsynthetic strategy. The obtained thiol-functionalized MOFs were characterized by powder X-ray diffraction, CHN and infrared spectroscopy. The analytical and spectroscopic data of the unmodified and modified compound were different.
 A series of [Cu (Ina)2] samples stoichiometrically decorated with thiol groups has been prepared through coordination bonding of coordinatively unsaturated metal centers with –SH group in thioglycolic acid. [Cu (Ina)2]. H2O and [Cu(Ina)2]-TH were investigated for the adsorptive removal of fluorescein from aqueous solution. The parameters that affect the dye sorption such as contact time, solution pH, initial fluorescein concentration and temperature, have been investigated and optimized conditions determined at PH of 7.8. Dubinin–Radushkevich Equilibrium isotherm studies were used to evaluate the maximum sorption capacity of MOFs and experimental results showed that the removal efficiency decreases in the order of [Cu(Ina)2]-TH > [Cu(Ina)2].H2O both in adsorption rate and adsorption capacity. The Langmuir, Freundlich, Temkin and Dubinin Radushkevich models have been applied and the data correlate well with Dubinin Radushkevich model. The adsorption mechanism may be explained with a simple electrostatic interaction and π- π interaction. Finally, it can be suggested that modification of MOFs can be use to improve their adsorption capacity and rate, making them a better adsorbent to remove emerging dyes contaminants from waste water.

Therapeutic potentials of N-acetylcysteine immobilized polyrhodanine nanoparticles toward acetaminophen-induced acute hepatotoxicity in rat.

N-acetylcysteine (NAC) is a recommended drug for treating acetaminophen (APAP) intoxication. Due to NAC's low bioavailability, this study aimed to use polyrhodanine (PR) nanoparticles (NPs) as a drug carrier to improve the effectiveness of NAC. After preparation and characterization of NAC loaded on PR, 30 rats were randomly divided into five groups of six. The first group (control) received normal saline. Groups 2-5 were treated with normal saline, PR, NAC, and NAC loaded on PR, respectively. The treatments were started 4 h after oral administration of APAP (2000 mg kg-1 ). After 48 h, the animals were anesthetized, and liver function indices and oxidative stress were measured in tissue and serum samples. The APAP administration can increase aminotransferases and alkaline phosphatase enzymes in serum, decreasing the total antioxidant capacity and thiol groups and increasing lipid peroxidation in liver tissue. Administration of PR-NAC could effectively improve the level of serum-hepatic enzymes, total antioxidant capacity and thiol groups, lipid peroxidation, and pathological changes in liver tissue in animals poisoned with APAP. PR-NAC has a significant therapeutic effect on preventing acute hepatotoxicity caused by APAP, and its effectiveness can be associated with an improvement in the oxidant/antioxidant balance of liver tissue.

Attenuation of protein arginine dimethylation via S-nitrosylation of protein arginine methyltransferase 1

Upregulation of nitric oxide (NO) production contributes to the pathogenesis of numerous diseases via S-nitrosylation, a post-translational modification of proteins. This process occurs due to the oxidative reaction between NO and a cysteine thiol group; however, the extent of this reaction remains unknown. S-Nitrosylation of PRMT1, a major asymmetric arginine methyltransferase of histones and numerous RNA metabolic proteins, was induced by NO donor treatment. We found that nitrosative stress leads to S-nitrosylation of cysteine 119, located near the active site, and attenuates the enzymatic activity of PRMT1. Interestingly, RNA sequencing analysis revealed similarities in the changes in expression elicited by NO and PRMT1 inhibitors or knockdown. A comprehensive search for PRMT1 substrates using the proximity-dependent biotin identification method highlighted many known and new substrates, including RNA-metabolizing enzymes. To validate this result, we selected the RNA helicase DDX3 and demonstrated that arginine methylation of DDX3 is induced by PRMT1 and attenuated by NO treatment. Our results suggest the existence of a novel regulatory system associated with transcription and RNA metabolism via protein S-nitrosylation.

Bioconjugation and Reaction-Induced Tumor Therapy via Alkynamide-Based Thiol-Yne Click Reaction.

Ferroptosis is associated with the occurrence and development of many diseases, which is the result of an imbalance in cellular metabolism and oxidation-reduction balance. Therefore, it is an effective therapeutic strategy that simultaneously regulating the intracellular oxidation-reduction system. Herein, a click reaction of alkynylamide with thiol groups in the presence of amine or in PBS (pH = 7.4) is developed, which can react efficiently with thiol substances, such as cysteine (Cys), glutathione (GSH), and bovine serum albumin (BSA). Notably, MBTB-PA, an aggregation-induced emission (AIE) photosensitizer with an alkynylamide unit, is synthesized and its intracellular behavior is visualized in situ by fluorescence imaging, demonstrating its excellent ability to target the endoplasmic reticulum. Furthermore, MBTB-PA reacted with proteins in tumor cells, consumed reducing substances, and triggered intracellular oxidative stress, resulting in cell death. Based on this reaction therapy strategy, click reaction is combined with photodynamic therapy to achieve effective killing of tumor cells by simultaneously raising the intracellular oxidative state and reducing the reductive state. This work not only develops an application of click reaction of alkynamide with thiol in bioconjugation and anti-tumor therapy, but also provides feasible ideas for organic reactions in the exploration of organisms.

The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors.

Histone deacetylase inhibitors (HDACi) are part of a growing class of epigenetic therapies used for the treatment of cancer. Although HDACis are effective in the treatment of T-cell lymphomas, treatment of solid tumors with this class of drugs has not been successful. Overexpression of the multidrug resistance protein P-glycoprotein (P-gp), encoded by ABCB1, is known to confer resistance to the HDACi romidepsin in vitro, yet increased ABCB1 expression has not been associated with resistance in patients, suggesting that other mechanisms of resistance arise in the clinic. To identify alternative mechanisms of resistance to romidepsin, we selected MCF-7 breast cancer cells with romidepsin in the presence of the P-gp inhibitor verapamil to reduce the likelihood of P-gp-mediated resistance. The resulting cell line, MCF-7 DpVp300, does not express P-gp and was found to be selectively resistant to romidepsin but not to other HDACis such as belinostat, panobinostat, or vorinostat. RNA-sequencing analysis revealed upregulation of the mRNA coding for the putative methyltransferase, METTL7A, whose paralog, METTL7B, was previously shown to methylate thiol groups on hydrogen sulfide and captopril. As romidepsin has a thiol as the zinc-binding moiety, we hypothesized that METTL7A could inactivate romidepsin and other thiol-based HDACis via methylation of the thiol group. We demonstrate that expression of METTL7A or METTL7B confers resistance to thiol-based HDACis and that both enzymes are capable of methylating thiol-containing HDACis. We thus propose that METTL7A and METTL7B confer resistance to thiol-based HDACis by methylating and inactivating the zinc-binding thiol.

Tailoring ultrafiltration membranes with chemically modified human hair waste for improved permeability and antifouling performance

Human hair, a pervasive waste product, has the potential to pose environmental challenges due to its widespread accumulation. Therefore, exploring of alternatives that repurpose this waste into a valuable raw material aligns with the principles of the circular economy. This study introduces a novel protocol for crafting biohybrid ultrafiltration (UF) membranes with tailored charges, enhanced hydrophilicity, and notable attributes of high flux, rejection rate, and resistance to fouling. These membranes have been engineered by combining sulfonated poly(ethersulfone) (SPES) with chemically modified human hair (HH) filler, referred to as HH-SO3-NH2, utilizing the non-solvent induced phase separation (NIPS) approach. The preparation of HH-SO3-NH2 involved converting of oxidized thiol groups within human hair to sulfonic acid. Subsequently, 1 and 3 wt percent of HH-SO3-NH2 were integrated into the SPES matrix to formulate the biohybrid membranes. After incorporating HH-SO3-NH2, the biohybrid membranes changed in mechanical properties, porosity, and surface morphology, resulting in increased hydrophilicity. The pure water flux exhibited a systematic rise with higher HH-SO3-NH2 content-specifically, the hybrid membrane with 3 wt% HH-SO3-NH2 achieved a water flux of 239 L m−2 h−1 at 1 bar feed pressure, representing a 1.5-fold increase compared to the bare membrane's 175 L m−2 h−1 flux. The anti-fouling performance was assessed using humic acid (HA) and the hybrid membranes demonstrated removal efficiency of HA exceeding 99% without compromising rejection rates.

A Two-Step Surface Modification Methodology for the Advanced Protection of a Stone Surface.

The biodeterioration of the natural surface on monuments, historical buildings, and even public claddings brings to the attention of researchers and historians the issues of conservation and protection. Natural stones undergo changes in their appearance, being subjected to deterioration due to climatic variations and the destructive action of biological systems interfering with and living on them, leading to ongoing challenges in the protection of the exposed surfaces. Nanotechnology, through silver nanoparticles with strong antimicrobial effects, can provide solutions for protecting natural surfaces using specific coupling agents tailored to each substrate. In this work, surfaces of two common types of natural stone, frequently encountered in landscaping and finishing works, were modified using siloxane coupling agents with thiol groups. Through these agents, silver nanoparticles (AgNPs) were fixed, exhibiting distinct characteristics, and subjected to antimicrobial analysis. This study presents a comparative analysis of the efficiency of coupling agents that can be applied to a natural surface with porous structures, when combined with laboratory-obtained silver nanoparticles, in reducing the formation of microbial biofilms, which are a main trigger for stone biodeterioration.

Hemin/G-quadruplex and AuNPs-MoS2 based novel dual signal amplification strategy for ultrasensitively sandwich-type electrochemical thrombin aptasensor

In this work, a novel sandwich-type electrochemical aptasensor based on the dual signal amplification strategy of hemin/G-quadruplex and AuNPs-MoS2 was designed and constructed, which realized the highly sensitive and specific detection of thrombin (TB). In this aptasensor, the 15-mer TB-binding aptamer (TBA-1) modified with thiol group was immobilized on the surface of AuNPs modified glassy carbon electrode (AuNPs/GCE) as capturing elements. Another thiol-modified 29-mer TB-binding aptamer (TBA-2) sequence containing G-quadruplex structure for hemin immobilization was designed. The formed hemin/G-quadruplex/TBA-2 sequence was further combined to the AuNPs decorated flower-like molybdenum disulfide (AuNPs-MoS2) composite surface via Au-S bonds, acting the role of reporter probe. In presence of the target TB, the sandwich-type electrochemical aptamer detection system could be formed properly. With the assistance of the dual signal amplification of AuNPs-MoS2 and hemin/G-quadruplex toward H2O2 reduction, the sandwich-type electrochemical aptasensor was successfully constructed for sensitive detection of TB. The results demonstrate that the fabricated aptasensor displays a wide linear range of 1.0 × 10−6 ∼ 10.0 nM with a low detection limit of 0.34 fM. This proposed aptasensor shows potential application in the detection of TB content in real biological samples with high sensitivity, selectivity, and reliability.

Loss of cardiac mitochondrial complex I persulfidation impairs NAD+ homeostasis in aging

Protein persulfidation is a significant post-translational modification that involves addition of a sulfur atom to the cysteine thiol group and is facilitated by sulfide species. Persulfidation targets reactive cysteine residues within proteins, influencing their structure and/or function across various biological systems. This modification is evolutionarily conserved and plays a crucial role in preventing irreversible cysteine overoxidation, a process that becomes prominent with aging. While, persulfidation decreases with age, its levels in the aged heart and the functional implications of such a reduction in cardiac metabolism remain unknown. Here we interrogated the cardiac persulfydome in wild-type adult mice and age-matched mice lacking the two sulfide generating enzymes, namely cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). Our findings revealed that cardiac persulfidated proteins in wild type hearts are less abundant compared to those in other organs, with a primary involvement in mitochondrial metabolic processes. We further focused on one specific target, NDUFB7, which undergoes persulfidation by both CSE and 3MST derived sulfide species. In particular, persulfidation of cysteines C80 and C90 in NDUFB7 protects the protein from overoxidation and maintains the complex I activity in cardiomyocytes. As the heart ages, the levels of CSE and 3MST in cardiomyocytes decline, leading to reduced NDUFB7 persulfidation and increased cardiac NADH/NAD+ ratio. Collectively, our data provide compelling evidence for a direct link between cardiac persulfidation and mitochondrial complex I activity, which is compromised in aging.

Homogeneous fluorescence immunoassay based on AuNPs quenching dendritic silica assembled with multicolor QDs for the simultaneous determination of four mycotoxins in cereals

In this work, a novel homogeneous fluorescence immunoassay for the simultaneous detection of ochratoxin A (OTA), aflatoxin B1 (AFB1), fumonisins B1 (FB1), and zearalenone (ZEN) in cereal samples is established. Here, amino groups and thiol groups are grafted onto the surface of dendritic mesoporous silica nanoparticles (DMSNs) to improve loading rate and fluorescence preservation rate of quantum dots (QDs), enabling enrichment and amplification of fluorescence signals. In this test system, the fluorescence of the signal probe (DMSNs@QDs@Ab) is quenched by AuNPs, and then the presence of the targets makes the fluorescence of the signal probes recover. The correlation between the recovered fluorescence value and mycotoxin concentration is applied to achieve quantitative detecting mycotoxins. This assay displays good linear correlation in range of 0.01–100 μg L-1, with the limit of detection (LOD) of 0.0001 μg L-1 for OTA, 0.0008 μg L-1 for AFB1, 0.001 μg L-1 for FB1, and 0.0006 μg L-1 for ZEN, respectively. The proposed assay is applied to detect multiple mycotoxins in contaminated cereal samples and the test results is confirmed by liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Avail of silica with high loading capacity for assembling multicolor QDs to achieve simultaneous multi-signal output, a simple and efficient homogeneous fluorescence immunoassay is proposed for the first time. This multiplex test strategy provides a good idea for simultaneous, rapid, and sensitive detection of multiple hazardous substances in food and environment samples.