Employing a magnetic chitosan/molybdenum disulfide nanocomposite for efficiently removing polycyclic aromatic hydrocarbons from milk samples.

This study aimed to develop a highly efficient nanocomposite composed of magnetic chitosan/molybdenum disulfide (CS/MoS2/Fe3O4) for the removal of three polycyclic aromatic hydrocarbons (PAHs)-pyrene, anthracene, and phenanthrene. Novelty was introduced through the innovative synthesis procedure and the utilization of magnetic properties for enhanced adsorption capabilities. Additionally, the greenness of chitosan as a sorbent component was emphasized, highlighting its biodegradability and low environmental impact compared to traditional sorbents. Factors influencing PAH adsorption, such as nanocomposite dosage, initial PAH concentration, pH, and contact time, were systematically investigated and optimized. The results revealed that optimal removal efficiencies were attained at an initial PAH concentration of 150 mg/L, a sorbent dose of 0.045 g, pH 6.0, and a contact time of 150 min. The pseudo-second-order kinetic model exhibited superior fitting to the experimental data, indicating an equilibrium time of approximately 150 min. Moreover, the equilibrium adsorption process followed the Freundlich isotherm model, with kf and n values exceeding 7.91 mg/g and 1.20, respectively. Remarkably, the maximum absorption capacities for phenanthrene, anthracene, and pyrene on the sorbent were determined as 217 mg/g, 204 mg/g, and 222 mg/g, respectively. These findings underscore the significant potential of the CS/MoS2/Fe3O4 nanocomposite for efficiently removing PAHs from milk and other dairy products, thereby contributing to improved food safety and public health.

Amyloid formation and depolymerization of tumor suppressor p16INK4a are regulated by a thiol-dependent redox mechanism.

The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16INK4a leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16INK4a is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond.

Allicin inhibits the growth of HONE-1 and HNE1 human nasopharyngeal carcinoma cells by inducing ferroptosis.

Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.

A Practical Guide to All-Atom and Coarse-Grained Molecular Dynamics Simulations Using Amber and Gromacs: A Case Study of Disulfide-Bond Impact on the Intrinsically Disordered Amyloid Beta.

Intrinsically disordered proteins (IDPs) pose challenges to conventional experimental techniques due to their large-scale conformational fluctuations and transient structural elements. This work presents computational methods for studying IDPs at various resolutions using the Amber and Gromacs packages with both all-atom (Amber ff19SB with the OPC water model) and coarse-grained (Martini 3 and SIRAH) approaches. The effectiveness of these methodologies is demonstrated by examining the monomeric form of amyloid-ß (Aß42), an IDP, with and without disulfide bonds at different resolutions. Our results clearly show that the addition of a disulfide bond decreases the ß-content of Aß42; however, it increases the tendency of the monomeric Aß42 to form fibril-like conformations, explaining the various aggregation rates observed in experiments. Moreover, analysis of the monomeric Aß42 compactness, secondary structure content, and comparison between calculated and experimental chemical shifts demonstrates that all three methods provide a reasonable choice to study IDPs; however, coarse-grained approaches may lack some atomistic details, such as secondary structure recognition, due to the simplifications used. In general, this study not only explains the role of disulfide bonds in Aß42 but also provides a step-by-step protocol for setting up, conducting, and analyzing molecular dynamics (MD) simulations, which is adaptable for studying other biomacromolecules, including folded and disordered proteins and peptides.

P-N Heterojunction formation: Metal Sulfide@Metal Oxide Chemiresistor for ppb H2S Detection from Exhaled Breath and Food Spoilage at Flexible Room Temperature.

The development of a portable, low-cost sensor capable of accurately detecting H2S gas in exhaled human breath at room temperature is highly anticipated in the fields of human health assessment and food spoilage evaluation. However, achieving outstanding gas sensing performance and applicability for flexible room-temperature operation with parts per billion H2S gas sensors still poses technical challenges. To address this issue, this study involves the in situ growth of MoS2 nanosheets on the surface of In2O3 fibers to construct a p-n heterojunction. The In2O3@MoS2-2 sensor exhibits a high response of 460.61 to 50 ppm of H2S gas at room temperature, which is 19.5 times higher than that of the pure In2O3 sensor and 322.1 times higher than that of pure MoS2. The In2O3@MoS2-2 also demonstrates a minimum detection limit of 3 ppb and maintains a stable response to H2S gas even after being bent 50 times at a 60° angle. These exceptional gas sensing properties are attributed to the increase in oxygen vacancies and chemisorbed oxygen on In2O3@MoS2-2 nanofibers as well as the formation of the p-n heterojunction, which modulates the heterojunction barrier. Furthermore, in this study, we successfully applied the In2O3@MoS2-2 sensor for oral disease and detection of food spoilage conditions, thereby providing new design insights for the development of portable exhaled gas sensors and gas sensors for evaluating food spoilage conditions at room temperature.

Deciphering the Antibiofilm, Antibacterial, and Antioxidant Potential of Essential Oil from Indian Garlic and its Phytocompounds Against Foodborne Pathogens.

Garlic (Allium sativum L.), particularly its volatile essential oil, is widely recognized for medicinal properties. We have evaluated the efficacy of Indian Garlic Essential Oil (GEO) for antimicrobial and antibiofilm activity and its bioactive constituents. Allyl sulfur-rich compounds were identified as predominant phytochemicals in GEO, constituting 96.51% of total volatile oils, with 38% Diallyl trisulphide (DTS) as most abundant. GEO exhibited significant antibacterial activity against eleven bacteria, including three drug-resistant strains with minimum inhibitory concentrations (MICs) ranging from 78 to 1250 µg/mL. In bacterial growth kinetic assay GEO effectively inhibited growth of all tested strains at its ½ MIC. Antibiofilm activity was evident against two important human pathogens, S. aureus and P. aeruginosa. Mechanistic studies demonstrated that GEO disrupts bacterial cell membranes, leading to the release of nucleic acids, proteins, and reactive oxygen species. Additionally, GEO demonstrated potent antioxidant activity at IC50 31.18 mg/mL, while its isolated constituents, Diallyl disulphide (DDS) and Diallyl trisulphide (DTS), showed effective antibacterial activity ranging from 125 to 500 µg/mL and 250-1000 µg/mL respectively. Overall, GEO displayed promising antimicrobial and antibiofilm activity against enteric bacteria, suggesting its potential application in the food industry.

4-Ethylphenyl Sulfate Detection by an Electrochemical Sensor Based on a MoS2 Nanosheet-Modified Molecularly Imprinted Biopolymer.

One of the gut-derived uremic toxins 4-ethylphenyl sulfate (4-EPS) exhibits significantly elevated plasma levels in chronic kidney diseases and autism, and its early quantification in bodily fluids is important. Therefore, the development of rapid and sensitive technologies for 4-EPS detection is of significant importance for clinical diagnosis. In the current work, the synthesis of a molecularly imprinted biopolymer (MIBP) carrying 4-EPS specific cavities only using the biopolymer polydopamine (PDA) and molybdenum disulfide (MoS2) nanosheets has been reported. The fabricated electrode was prepared using screen-printed carbon electrodes on a polyvinyl chloride substrate. The synthesized material was characterized using several techniques, and electrochemical studies were performed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The DPV technique for the electrochemical sensing of 4-EPS using the fabricated sensor (PDA@MoS2-MIBP) determined a sensitivity of 0.012 µA/ng mL/cm2 and a limit of detection of 30 ng/mL in a broad linear range of 1-2200 ng/mL. Also, the interferent study was performed to evaluate the selectivity of the fabricated sensor along with the control and stability study. Moreover, the performance of the sensor was evaluated in the spiked urine sample, and a comparison was made with the data obtained by ultraperformance liquid chromatography-tandem mass spectroscopy.

High performance Pt-anchored MoS2based chemiresistive ascorbic acid sensor.

Ascorbic acid (AA), known as vitamin C, is a vital bioactive compound that plays a crucial role in several metabolic processes, including the synthesis of collagen and neurotransmitters, the removal of harmful free radicals, and the uptake of iron by cells in the human intestines. As a result, there is an absolute need for a highly selective, sensitive, and economically viable sensing platform for AA detection. Herein, we demonstrate a Pt-decorated MoS2for efficient detection of an AA biosensor. MoS2hollow rectangular structures were synthesized using an easy and inexpensive chemical vapor deposition approach to meet the increasing need for a reliable detection platform. The synthesized MoS2hollow rectangular structures are characterized through field effect scanning electron microscopy (FESEM), energy-dispersive spectroscopy elemental mapping, Raman spectroscopy, and x-ray photoelectron spectroscopy. We fabricate a chemiresistive biosensor based on Pt-decorated MoS2that measures AA with great precision and high sensitivity. The experiments were designed to evaluate the response of the Pt-decorated MoS2biosensor in the presence and absence of AA, and selectivity was evaluated for a variety of biomolecules, and it was observed to be very selective towards AA. The Pt-MoS2device had a higher response of 125% against 1 mM concentration of AA biomolecules, when compared to that of all other devices and 2.2 times higher than that of the pristine MoS2device. The outcomes of this study demonstrate the efficacy of Pt-decorated MoS2as a promising material for AA detection. This research contributes to the ongoing efforts to enhance our capabilities in monitoring and detecting AA, fostering advancements in environmental, biomedical, and industrial applications.

Electrophoretic Microplate Protein Identification Based on Gold Staining of Molybdenum Disulfide Hydrogels.

Numerous high-performance nanotechnologies have been developed, but their practical applications are largely restricted by the nanomaterials' low stabilities and high operation complexity in aqueous substrates. Herein, we develop a simple and high-reliability hydrogel-based nanotechnology based on the in situ formation of Au nanoparticles in molybdenum disulfide (MoS2)-doped agarose (MoS2/AG) hydrogels for electrophoresis-integrated microplate protein recognition. After the incubation of MoS2/AG hydrogels in HAuCl4 solutions, MoS2 nanosheets spontaneously reduce Au ions, and the hydrogels are remarkably stained with the color of as-synthetic plasmonic Au hybrid nanomaterials (Au staining). Proteins can precisely mediate the morphologies and optical properties of Au/MoS2 heterostructures in the hydrogels. Consequently, Au staining-based protein recognition is exhibited, and hydrogels ensure the comparable stabilities and sensitivities of protein analysis. In comparison to the fluorescence imaging and dye staining, enhanced sensitivity and recognition performances of proteins are implemented by Au staining. In Au staining, exfoliated MoS2 semiconductors directly guide the oriented growth of plasmonic Au nanostructures in the presence of formaldehyde, showing environment-friendly features. The Au-stained hydrogels merge the synthesis and recognition applications of plasmonic Au nanomaterials. Significantly, the one-step incubation of the electrophoretic hydrogels leads to high simplicity of operation, largely challenging those multiple-step Ag staining routes which were performed with high complexity and formaldehyde toxicity. Due to its toxic-free, simple, and sensitive merits, the Au staining integrated with electrophoresis-based separation and microplate-based high-throughput measurements exhibits highly promising and improved practicality of those developing nanotechnologies and largely facilitates in-depth understanding of biological information.

Chiral MoS2@BC fibrous membranes selectively promote peripheral nerve regeneration.

BACKGROUND: Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear. METHODS: In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months. RESULTS: These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group. CONCLUSION: We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.

A sensitive sandwich-type electrochemical aptasensing platform based on Ti3C2Tx/MoS2/MWCNT@rGONR composites for simultaneous detection of kanamycin and chloramphenicol in food samples.

A Ti3C2Tx/MoS2/MWCNT@rGONR nanocomposite was prepared for the first time for building a sensitive electrochemical aptasening platform to simultaneously detect kanamycin (Kana) and chloramphenicol (Cap). Owing to their accordion-like structure, rich surface groups, and high charge mobility, Ti3C2Tx/MoS2/MWCNT@rGONR composites provided a spacious covalent immobilization surface and a better electrochemical aptasensing platform. The aptamers of Kana and Cap used in sensors enhance the selectivity. Furthermore, TiP, an ion exchanger, was used for loading more different metal ions functioning as labels to form a sandwich-type sensor together with Ti3C2Tx/MoS2/MWCNT@rGONR, improving the electrochemical sensitivity and obtaining a highly distinguishable signal readout. Under the optimized conditions, the sensor has good detection limits of 0.135 nmol L-1 and 0.173 nmol L-1 for Kana and Cap, respectively, at the same linearity concentration of 0.5-2500 nmol L-1. Finally, it was successfully applied for detection in milk and fish meat, and the results were compared with the standard method HPLC, indicating its great potential for food safety monitoring.

Structure-activity relationships of the intramolecular disulphide bonds in LEAP2, an antimicrobial peptide from Acrossocheilus fasciatus.

BACKGROUND: The liver-expressed antimicrobial peptide 2 (LEAP2) plays a pivotal role in the host's immune response against pathogenic microorganisms. Numerous such antimicrobial peptides have recently been shown to mitigate infection risk in fish, and studying those harboured by the economically important fish Acrossocheilus fasciatus is imperative for enhancing its immune responses against pathogenic microorganisms. In this study, we cloned and sequenced LEAP2 cDNA from A. fasciatus to examine its expression in immune tissues and investigate the structure-activity relationships of its intramolecular disulphide bonds. RESULTS: The predicted amino acid sequence of A. fasciatus LEAP2 was found to include a signal peptide, pro-domain, and mature peptide. Sequence analysis indicated that A. fasciatus LEAP2 is a member of the fish LEAP2A cluster and is closely related to Cyprinus carpio LEAP2A. A. fasciatus LEAP2 transcripts were expressed in various tissues, with the head kidney exhibiting the highest mRNA levels. Upon exposure to Aeromonas hydrophila infection, LEAP2 expression was significantly upregulated in the liver, head kidney, and spleen. A mature peptide of A. fasciatus LEAP2, consisting of two disulphide bonds (Af-LEAP2-cys), and a linear form of the LEAP2 mature peptide (Af-LEAP2) were chemically synthesised. The circular dichroism spectroscopy result shows differences between the secondary structures of Af-LEAP2 and Af-LEAP2-cys, with a lower proportion of alpha helix and a higher proportion of random coil in Af-LEAP2. Af-LEAP2 exhibited potent antimicrobial activity against most tested bacteria, including Acinetobacter guillouiae, Pseudomonas aeruginosa, Staphylococcus saprophyticus, and Staphylococcus warneri. In contrast, Af-LEAP2-cys demonstrated weak or no antibacterial activity against the tested bacteria. Af-LEAP2 had a disruptive effect on bacterial cell membrane integrity, whereas Af-LEAP2-cys did not exhibit this effect. Additionally, neither Af-LEAP2 nor Af-LEAP2-cys displayed any observable ability to hydrolyse the genomic DNA of P. aeruginosa. CONCLUSIONS: Our study provides clear evidence that linear LEAP2 exhibits better antibacterial activity than oxidised LEAP2, thereby confirming, for the first time, this phenomenon in fish.

Biofiltration of gaseous mixtures of dimethyl sulfide, dimethyl disulfide and dimethyl trisulfide: Effect of operational conditions and microbial analysis.

The efficient removal of volatile sulfur compounds (VSCs), such as dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS), is crucial due to their foul odor and corrosive potential in sewer systems. Biofilters (BFs) offer promise for VSCs removal, but face challenges related to pH control and changing conditions at full scale. Two BFs, operated under acidophilic conditions for 78 days, were evaluated for their performance at varying inlet concentrations and empty bed residence times (EBRTs). BF1, incorporating 4-6 mm marble limestone for pH control, outperformed BF2, which used NaHCO3 in the nutrient solution. BF1 displayed better resilience, maintained a stable pH of 4.6 ± 0.6, and achieved higher maximum elimination capacities (ECmax, 41 mg DMS m-3 h-1 (RE 38.3%), 146 mg DMDS m-3 h-1 (RE 83.1%), 47 mg DMTS m-3 h-1 (RE 93.1%)) at an EBRT of 56 s compared to BF2 (9 mg DMS m-3 h-1 (RE 7.1%), 9 mg DMDS m-3 h-1 (RE 4.8%) and 11 mg DMTS m-3 h-1 (RE 26.6%)). BF2 exhibited pH stratification and decreased performance after feeding interruptions. The biodegradability of VSCs followed the order DMTS > DMDS > DMS, and several microorganisms were identified contributing to VSCs degradation in BF1, including Bacillus (14%), Mycobacterium (11%), Acidiphilium (7%), and Acidobacterium (3%).

Utility of thiol/disulphide homeostasis as a biomarker for acute appendicitis: a systematic review and meta-analysis.

The aim of this study was to analyze the role of thiol/disulfide homeostasis (TDH) parameters as an indicator of oxidative stress in acute appendicitis (AA). PubMed, EMBASE, Web of Science, and Scopus databases were systematically searched. Studies reporting on TDH in AA (both complicated and uncomplicated cases) were included. The comparator group were healthy controls. The TDH domain was compared between the groups using anti-oxidant parameters, namely native thiol and total thiol levels, and native thiol/total thiol ratio; and oxidant parameters, namely disulfide level, disulfide/native thiol ratio, and disulfide/total thiol ratio. The statistical analysis was performed using a random-effects model. The methodological quality of the studies was assessed utilizing the Newcastle-Ottawa scale. Eleven studies with a total of 926 subjects, comprising 457 patients with uncomplicated appendicitis, 147 with complicated appendicitis, and 322 healthy controls were included. Our study demonstrated significantly increased oxidative stress in AA as compared to healthy controls in all TDH parameters and significantly lower total thiol levels in complicated AA as compared to uncomplicated AA. Due to a poor methodological quality in five out of eleven studies, future prospective studies with adequate power are essential to validate these observations and refine the diagnostic approaches to AA.

A production platform for disulfide-bonded peptides in the periplasm of Escherichia coli.

BACKGROUND: Recombinant peptide production in Escherichia coli provides a sustainable alternative to environmentally harmful and size-limited chemical synthesis. However, in-vivo production of disulfide-bonded peptides at high yields remains challenging, due to degradation by host proteases/peptidases and the necessity of translocation into the periplasmic space for disulfide bond formation. RESULTS: In this study, we established an expression system for efficient and soluble production of disulfide-bonded peptides in the periplasm of E. coli. We chose model peptides with varying complexity (size, structure, number of disulfide bonds), namely parathyroid hormone 1-84, somatostatin 1-28, plectasin, and bovine pancreatic trypsin inhibitor (aprotinin). All peptides were expressed without and with the N-terminal, low molecular weight CASPON™ tag (4.1 kDa), with the expression cassette being integrated into the host genome. During BioLector™ cultivations at microliter scale, we found that most of our model peptides can only be sufficiently expressed in combination with the CASPON™ tag, otherwise expression was only weak or undetectable on SDS-PAGE. Undesired degradation by host proteases/peptidases was evident even with the CASPON™ tag. Therefore, we investigated whether degradation happened before or after translocation by expressing the peptides in combination with either a co- or post-translational signal sequence. Our results suggest that degradation predominantly happened after the translocation, as degradation fragments appeared to be identical independent of the signal sequence, and expression was not enhanced with the co-translational signal sequence. Lastly, we expressed all CASPON™-tagged peptides in two industry-relevant host strains during C-limited fed-batch cultivations in bioreactors. We found that the process performance was highly dependent on the peptide-host-combination. The titers that were reached varied between 0.6-2.6 g L-1, and exceeded previously published data in E. coli. Moreover, all peptides were shown by mass spectrometry to be expressed to completion, including full formation of disulfide bonds. CONCLUSION: In this work, we demonstrated the potential of the CASPON™ technology as a highly efficient platform for the production of soluble peptides in the periplasm of E. coli. The titers we show here are unprecedented whenever parathyroid hormone, somatostatin, plectasin or bovine pancreatic trypsin inhibitor were produced in E. coli, thus making our proposed upstream platform favorable over previously published approaches and chemical synthesis.

Intramolecular Disulfide Bridges in Voltage-Dependent Anion Channel 2 (VDAC2) Protein from Rattus norvegicus Revealed by High-Resolution Mass Spectrometry.

Voltage-Dependent Anion Channel isoforms (VDAC1, VDAC2, and VDAC3) are relevant components of the outer mitochondrial membrane (OMM) and play a crucial role in regulation of metabolism and in survival pathways. As major players in the regulation of cellular metabolism and apoptosis, VDACs can be considered at the crossroads between two broad families of pathologies, namely, cancer and neurodegeneration, the former being associated with elevated glycolytic rate and suppression of apoptosis in cancer cells, the latter characterized by mitochondrial dysfunction and increased cell death. Recently, we reported the characterization of the oxidation pattern of methionine and cysteines in rat and human VDACs showing that each cysteine in these proteins is present with a preferred oxidation state, ranging from the reduced to the trioxidized form, and such an oxidation state is remarkably conserved between rat and human VDACs. However, the presence and localization of disulfide bonds in VDACs, a key point for their structural characterization, have so far remained undetermined. Herein we have investigated by nanoUHPLC/High-Resolution nanoESI-MS/MS the position of intramolecular disulfide bonds in rat VDAC2 (rVDAC2), a protein that contains 11 cysteines. To this purpose, extraction, purification, and enzymatic digestions were carried out at slightly acidic or neutral pH in order to minimize disulfide bond interchange. The presence of six disulfide bridges was unequivocally determined, including a disulfide bridge linking the two adjacent cysteines 4 and 5, a disulfide bridge linking cysteines 9 and 14, and the alternative disulfide bridges between cysteines 48, 77, and 104. A disulfide bond, which is very resistant to reduction, between cysteines 134 and 139 was also detected. In addition to the previous findings, these results significantly extend the characterization of the oxidation state of cysteines in rVDAC2 and show that it is highly complex and presents unusual features. Data are available via ProteomeXchange with the identifier PXD044041.

Nongenetic Precise Neuromodulation and Spatiotemporal Neuroprotection for Epilepsy Therapy via Rationally Designed Multifunctional Nanotransducer.

The precise modulation of electrical activity in specific neuronal populations is paramount for rectifying abnormal neurological functions and is a critical element in the therapeutic arsenal for neurological disorders. However, achieving a balance between minimal invasiveness and robust neuroprotection poses a considerable challenge. Herein, we present a nanoneuromodulation strategy integrating neuroprotective features to effectively address epilepsy with minimal invasiveness and enable wireless functionality. Strategically engineered nanotransducer, adorned with platinum (Pt) decoration with titanium disulfide (TiS2) (TiS2/Pt), enables precise modulation of neuronal electrical activity in vitro and in vivo, ensuring exceptional temporal fidelity under millisecond-precision near-infrared (NIR) light pulses irradiation. Concurrently, TiS2/Pt showcase a pronounced enhancement in enzyme-mimicking activity, offering a robust defense against oxidative neurological injury in vitro. Nanotransducer-enabled wireless neuromodulation with biocatalytic neuroprotective capacity is highly effective in alleviating epileptic high-frequency neural activity and diminishing oxidative stress levels, thereby restoring redox equilibrium. This integrated therapeutic approach reduces the severity of epilepsy, demonstrating minimal invasiveness and obviating the requirements for genetic manipulation and optical fiber implantation, while providing an alternative avenue for neurological disorder treatment.

Molybdenum disulfide nanosheets based non-oxygen-dependent and heat-initiated free radical nanogenerator with antimicrobial peptides for antimicrobial, biofilm ablation and wound healing.

Chronic refractory wounds caused by multidrug-resistant (MDR) bacterial and biofilm infections are a substantial threat to human health, which presents a persistent challenge in managing clinical wound care. We here synthesized a composite nanosheet AIPH/AMP/MoS2, which can potentially be used for combined therapy because of the photothermal effect induced by MoS2, its ability to deliver antimicrobial peptides, and its ability to generate alkyl free radicals independent of oxygen. The synthesized nanosheets exhibited 61 % near-infrared (NIR) photothermal conversion efficiency, marked photothermal stability and free radical generating ability. The minimal inhibitory concentrations (MICs) of the composite nanosheets against MDR Escherichia coli (MDR E. coli) and MDR Staphylococcus aureus (MDR S. aureus) were approximately 38 µg/mL and 30 µg/mL, respectively. The composite nanosheets (150 µg/mL) effectively ablated >85 % of the bacterial biofilm under 808-nm NIR irradiation for 6 min. In the wound model experiment, approximately 90 % of the wound healed after the 4-day treatment with the composite nanosheets. The hemolysis experiment, mouse embryonic fibroblast (MEFs) cytotoxicity experiment, and mouse wound healing experiment all unveiled the excellent biocompatibility of the composite nanosheets. According to the transcriptome analysis, the composite nanosheets primarily exerted a synergistic therapeutic effect by disrupting the cellular membrane function of S. aureus and inhibiting quorum sensing mediated by the two-component system. Thus, the synthesized composite nanosheets exhibit remarkable antibacterial and biofilm ablation properties and therefore can be used to improve wound healing in chronic biofilm infections.

The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis.

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.

The Disulfide Bond-Mediated Cyclization of Oral Peptides.

'Structure determines function' is a consensus in the current biological community, but the structural characteristics corresponding to a certain function have always been a hot field of scientific exploration. A peptide is a bio-active molecule that is between the size of an antibody and a small molecule. Still, the gastrointestinal barrier and the physicochemical properties of peptides have always limited the oral administration of peptides. Therefore, we analyze the main ways oral peptide conversion strategies of peptide modification and permeation enhancers. Based on our analysis of the structure of natural oral peptides, which can be absorbed through the gastrointestinal tract, we believe that the design strategy of natural stapled peptides based on disulfide bonds is good for oral peptide design. This cannot only be used to identify anti-gastrointestinal digestive structural proteins in nature but also provide a solid structural foundation for the construction of new oral peptide drugs.