High-Performance Graphene Flexible Sensors for Pulse Monitoring and Human-Machine Interaction.

Flexible sensors are of great interest due to their potential applications in human physiological signal monitoring, wearable devices, and healthcare. However, sensor devices employed for cardiovascular testing are normally bulky and expensive, which hamper wearability and point-of-care use. Herein, we report a simple method for preparing multifunctional flexible sensors using hydrazine hydrate (N2H4·H2O) as the reducing agent, graphene as the active material, and polyethylene (PE) tape as the encapsulation material. The flexible sensor produced with this method has a low detection limit of 100 mg, a fast response and recovery time of 40 and 20 ms, and shows no performance degradation even after up to 30,000 motion cycles. The sensors we have developed are capable of monitoring the pulse with relative accuracy, which presents an opportunity to replace bulky devices and normalize cardiovascular testing in the future. In order to further broaden the application field, the sensor is installed as a sensor array to recognize objects of different weights and shapes, showing that the sensor has excellent application potential in wearable artificial intelligence.

Thioproline-Based Oxidation Strategy for Direct Preparation of N-Terminal Thiazolidine-Containing Peptide Thioesters from Peptide Hydrazides.

We describe a simple and robust oxidation strategy for preparing N-terminal thiazolidine-containing peptide thioesters from peptide hydrazides. We find for the first time that l-thioproline can be used as a protective agent to prevent the nitrosation of N-terminal thiazolidine during peptide hydrazide oxidation. The thioproline-based oxidation strategy has been successfully applied to the chemical synthesis of CC chemokine ligand-2 (69aa) and omniligase-C (113aa), thereby demonstrating its utility in hydrazide-based native chemical ligation.

Fluorescent-based micellar incorporated hydrogel materials for selective determination of long-chain aldehydes.

A highly sensitive micelle-induced sensory has been developed for detection of long-chain aldehydes as potential biomarkers of respiratory cancers. The micelle-like sensor was fabricated through the partial self-assembly of CTAB and S2 surfactants, containing a fluorescent hydrazine-functionalized dye (Naph-NH2). In principle, long-chain aldehydes with amphiphilic character act as the induced-fit surfactants to form well-entrapped micellar particles, as well as react with Naph-NH2 to form hydrazone derivatives resulting in fluorescent enhancement. The limit of detection (LOD) of micellar Naph-NH2/CTAB/S2 platform was calculated to be ∼  64.09-80.98 µM for detection of long-chain aldehydes, which showed fluorescent imaging in lung cancer cells (A549). This micellar sensory probe demonstrated practical applicability for long-chain aldehyde sensing in human blood samples with an accepted percent recovery of ~ 94.02-102.4%. Beyond Naph-NH2/CTAB/S2 sensor, the milcellar hybrid sensor was successfully developed by incorporating a micelle-like platform with supramolecular gel regarding to carboxylate-based gelators (Gel1), which showed a tenfold improvement in sensitivity. Expectedly, the determination of long-chain aldehydes through these sensing platforms holds significant promise for point-of-care cancer diagnosis and therapy.

Cyanoacetohydrazide as a Novel Derivatization Agent for the Determination of UHPLC-HRMS Steroids in Urine.

The possibility of cyanoacetohydrazide usage as a novel derivatizing agent is demonstrated in the presented article, and a comparison with hydroxylamine as the most commonly used reagent is provided. Optimal conditions for steroid derivatization with cyanoacetohydrazide are provided. According to the collected data, the maximum yield of derivatives was observed at pH 2.8 within 70 min at 40 °C with 5 ng/mL limit of detection for all investigated analytes. It was shown that cyanoacetohydrazide derivatives produces both syn- and anti-forms as well as hydroxylamine, and their ratios were evaluated and shown in presented work. An efficiency enchantment from two to up to five times was achieved with a novel derivatization reagent. Its applicability for qualitative analysis of steroids in urine was presented at real samples. Additionally, the reproducible fragmentation of the derivatizing agent in collision-induced dissociation offers opportunities for simplified non-targeted steroidomic screening. Furthermore, cyanoacetohydrazide increases ionization efficiency in positive mode, which can eliminate the need for redundant high-resolution instrument runs required for both positive and negative mode analyses.

A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates.

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential via multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN 4a (MIC = 0.001 mM) exhibited a potent antifungal activity against Candida albicans, which is 13-fold higher than that of fluconazole. Furthermore, nitrofuryl HN 4a displayed low cytotoxicity, hemolysis and resistance, as well as a rapid fungicidal efficacy. Preliminary mechanistic investigations revealed that nitrofuryl HN 4a could inhibit lactate dehydrogenase to decrease metabolic activity and promote the accumulation of reactive oxygen species, leading to oxidative stress. Moreover, nitrofuryl HN 4a did not exhibit membrane-targeting ability; it could embed into DNA to block DNA replication but could not cleave DNA. These findings implied that HNs are promising as novel structural scaffolds of potential multitargeting broad-spectrum antifungal candidates for treating fungal infection.

Design, synthesis, and biological evaluation of 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamides as a potential EGR-1 inhibitor for targeted therapy of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterized by intense itching and frequent skin barrier dysfunctions. EGR-1 is a transcription factor that aggravates the pathogenesis of atopic dermatitis by promoting the production of various inflammatory cytokines. Three 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamides (IT21, IT23, and IT25) were identified as novel inhibitors of EGR-1 DNA-binding activity. In silico docking experiments were performed to elucidate the binding conditions of the EGR-1 zinc-finger (ZnF) DNA-binding domain. Electrophoretic mobility shift assays confirmed the targeted binding effect on the EGR-1 ZnF DNA-binding domain, leading to dose-dependent dissociation of the EGR-1-DNA complex. At the functional cellular level, IT21, IT23, and IT25 effectively reduced mRNA expression of TNFα-induced EGR-1-regulated inflammatory genes, particularly in HaCaT keratinocytes inflamed by TNFα. In the in vivo efficacy study, IT21, IT23, and IT25 demonstrated the potential to alleviate atopic dermatitis-like skin lesions in the ear skin of BALB/c mice. These findings suggest that targeting the EGR-1 ZnF DNA-binding domain with 2-(2-oxoindolin-3-ylidene)hydrazinecarbothioamide derivatives (IT21, IT23, and IT25) could serve as lead compounds for the development of potential therapeutic agents against inflammatory skin disorders, including atopic dermatitis.

Unveiling carcinogenic pollutant levels in environmental water samples through facile fabrication of gold nanoparticles on sulfur-doped graphitic carbon nitride.

Extensive utilization of pesticides and herbicides to boost agricultural production increased the environmental health risks, which can be mitigate with the aid of highly sensitive detection systems. In this study, an electrochemical sensor for monitoring the carcinogenic pesticides in the environmental samples has been developed based on sulfur-doped graphitic-carbon nitride-gold nanoparticles (SCN-AuNPs) nanohybrid. Thermal polycondensation of melamine with thiourea followed by solvent exfoliation via ultrasonication leads to SCN formation and electroless deposition of AuNPs on SCN leads to SCN-AuNPs nanohybrid synthesis. The chemical composition, S-doping, and the morphology of the nanohybrid were confirmed by various microscopic and spectroscopic tools. The as-synthesized nanohybrid was fabricated with glassy carbon (GC) electrode for determining the carcinogenic hydrazine (HZ) and atrazine (ATZ) in field water samples. The present sensor exhibited superior electrocatalytic activity than GC/SCN and GC/AuNPs electrodes due to the synergism between SCN and AuNPs and the amperometric studies showed the good linear range of detection of 20 nM-0.5 mM and 500 nM-0.5 mM with the limit of detection of 0.22 and 69 nM (S/N = 3) and excellent sensitivity of 1173.5 and 13.96 µA mM-1 cm-2 towards HZ and ATZ, respectively. Ultimately, the present sensor is exploited in environmental samples for monitoring HZ and ATZ and the obtained results are validated with high-performance liquid chromatography (HPLC) technique. The excellent recovery percentage and close agreement with the results of HPLC analysis proved the practicability of the present sensor. In addition, the as-prepared materials were utilized for the photocatalytic degradation of ATZ and the SCN-AuNPs nanohybrid exhibited higher photocatalytic activity with the removal efficiency of 93.6% at 90 min. Finally, the degradation mechanism was investigated and discussed.

3D-QSAR-Directed Synthesis of Halogenated Coumarin-3-Hydrazide Derivatives: Unveiling Their Potential as SDHI Antifungal Agents.

The pursuit of new succinate dehydrogenase (SDH) inhibitors is a leading edge in fungicide research and development. The use of 3D quantitative structure-activity relationship (3D-QSAR) models significantly enhances the development of compounds with potent antifungal properties. In this study, we leveraged the natural product coumarin as a molecular scaffold to synthesize 74 novel 3-coumarin hydrazide derivatives. Notably, compounds 4ap (0.28 µg/mL), 6ae (0.32 µg/mL), and 6ah (0.48 µg/mL) exhibited exceptional in vitro effectiveness against Rhizoctonia solani, outperforming the commonly used fungicide boscalid (0.52 µg/mL). Furthermore, compounds 4ak (0.88 µg/mL), 6ae (0.61 µg/mL), 6ah (0.65 µg/mL), and 6ak (1.11 µg/mL) showed significant activity against Colletotrichum orbiculare, surpassing both the SDHI fungicide boscalid (43.45 µg/mL) and the broad-spectrum fungicide carbendazim (2.15 µg/mL). Molecular docking studies and SDH enzyme assays indicate that compound 4ah may serve as a promising SDHI fungicide. Our ongoing research aims to refine this 3D-QSAR model further, enhance molecular design, and conduct additional bioactivity assays.

A dual-color ESIPT-based probe for simultaneous detection of hydrogen sulfide and hydrazine.

Hydrogen sulfide (H2S) and hydrazine (N2H4) are toxic compounds in environmental and living systems, and hydrogen sulfide is also an important signaling molecule. However, in the absence of dual-color probes capable of detecting both H2S and N2H4, the ability to monitor the crosstalk of these substances is restricted. Herein, we developed an ESIPT-based dual-response fluorescent probe (BDM-DNP) for H2S and N2H4 detection via dually responsive sites. The BDM-DNP possessed absorbing strength in the detection of H2S and N2H4, with a large Stokes shift (156 nm for H2S and 108 nm for N2H4), high selectivity and sensitivity, and good biocompatibility. Furthermore, BDM-DNP can be utilized for the detection of hydrogen sulfide and hydrazine in actual soil, and gaseous H2S and N2H4 in environmental systems. Notably, BDM-DNP can detect H2S and N2H4 in living cells for disease diagnosis and treatment evaluation.

Ferroheme/Ferriheme Directly Involved in the Synthesis and Decomposition of Hydrazine as an Electron Carrier during Anammox.

Anammox bacteria performed the reaction of NH4+ and NO with hydrazine synthase to produce N2H4, followed by the decomposition of N2H4 with hydrazine dehydrogenase to generate N2. Ferroheme/ferriheme, which serves as the active center of both hydrazine synthase and hydrazine dehydrogenase, is thought to play a crucial role in the synthesis and decomposition of N2H4 during Anammox due to its high redox activity. However, this has yet to be proven and the exact mechanisms by which ferroheme/ferriheme is involved in the Anammox process remain unclear. In this study, abiotic and biological assays confirmed that ferroheme participated in NH4+ and NO reactions to generate N2H4 and ferriheme, and the produced N2H4 reacted with ferriheme to generate N2 and ferroheme. In other words, the ferroheme/ferriheme cycle drove the continuous reaction between NH4+ and NO. Raman, ultraviolet-visible spectroscopy, and X-ray absorption fine structure spectroscopy confirmed that ferroheme/ferriheme is involved in the synthesis and decomposition of N2H4 via the core FeII/FeIII cycle. The mechanism of ferroheme/ferriheme participation in the synthesis and decomposition of N2H4 was proposed by density functional theory calculations. These findings revealed for the first time the heme electron transfer mechanisms, which are of great significance for deepening the understanding of Anammox.

Turn-on Coumarin Precursor: From Hydrazine Sensor to Covalent Inhibition and Fluorescence Detection of Rabbit Muscle Aldolase.

Hydrazine, a highly toxic compound, demands sensitive and selective detection methods. Building upon our previous studies with pre-coumarin OFF-ON sensors for fluoride anions, we extended our strategy to hydrazine sensing by adapting phenol protecting groups (propionate, levulinate, and γ-bromobutanoate) to our pre-coumarin scaffold. These probes reacted with hydrazine, yielding a fluorescent signal with low micromolar limits of detection. Mechanistic studies revealed that hydrazine deprotection may be outperformed by a retro-Knoevenagel reaction, where hydrazine acts as a nucleophile and a base yielding a fluorescent diimide compound (6,6'-((1E,1'E)-hydrazine-1,2diylidenebis(methaneylylidene))bis(3(diethylamino)phenol, 7). Additionally, our pre-coumarins unexpectedly reacted with primary amines, generating a fluorescent signal corresponding to phenol deprotection followed by cyclization and coumarin formation. The potential of compound 3 as a theranostic Turn-On coumarin precursor was also explored. We propose that its reaction with ALDOA produced a γ-lactam, blocking the catalytic nucleophilic amine in the enzyme's binding site. The cleavage of the ester group in compound 3 induced the formation of fluorescent coumarin 4. This fluorescent signal was proportional to ALDOA concentration, demonstrating the potential of compound 3 for future theranostic studies in vivo.

Development of new steroid-based hydrazide and (thio)semicarbazone compounds with anticancer properties.

Most breast and prostate cancers are caused by abnormal production or action of steroidal hormones. Hormonal drugs based on steroid scaffolds represent a significant class of chemotherapeutics that are routinely used in chemotherapy. In this study, the synthesis of new 17a-homo lactone and 17α-(pyridine-2-ylmethyl) androstane derivatives with hydrazide and semicarbazone motifs is presented. All compounds were screened for their effect on cell viability against a panel of five cancer cell lines and one healthy cell line. Two compounds showed significant cytotoxicity against cancer cells, with low toxicity against healthy cells. The relative binding affinities of compounds for the ligand-binding domains of estrogen receptor α, estrogen receptor ß, androgen receptor and glucocorticoid receptor were tested using a fluorescence screen in yeast. Potential for inhibition of aldo-keto reductase 1C3 and 1C4 activity was measured in vitro. Experimental results are analyzed in the context of molecular docking simulations. Our results could help guide design of steroid compounds with improved anticancer properties against androgen- and estrogen-dependent cancers.

Design, Synthesis, and 3D-QASR of 2-Ar-1,2,3-triazole Derivatives Containing Hydrazide as Potential Fungicides.

A series of novel 2-Ar-1,2,3-triazole derivatives were designed and synthesized based on our previously discovered active compound 6d against Rhizoctonia solani. Most of these compounds exhibited good antifungal activity against R. solani at a concentration of 25 µg/mL. Based on the results of biological activity, we established a three-dimensional quantitative structure-activity relationship (3D-QSAR) model that guided the synthesis of compound 7y. Compound 7y exhibited superior activity against R. solani (EC50 = 0.47 µg/mL) compared to the positive controls hymexazol (EC50 = 12.80 µg/mL) and tebuconazole (EC50 = 0.87 µg/mL). Furthermore, compound 7y demonstrated better protective activity than the aforementioned two commercial fungicides in both detached leaf assays and greenhouse experiments, achieving 56.21% and 65.75% protective efficacy, respectively, at a concentration of 100 µg/mL. The ergosterol content was determined and molecular docking was performed to explore the mechanism of these active molecules. DFT calculation and MEP analysis were performed to illustrate the results of this study. These results suggest that compound 7y could serve as a novel 2-Ar-1,2,3-triazole lead compound for controlling R. solani.

Design, Synthesis, and Antifungal Evaluation of Diverse Heterocyclic Hydrazide Derivatives as Potential Succinate Dehydrogenase Inhibitors.

Plant pathogenic fungi pose a significant threat to agricultural production, necessitating the development of new and more effective fungicides. The ring replacement strategy has emerged as a highly successful approach in molecular design. In this study, we employed the ring replacement strategy to successfully design and synthesize 32 novel hydrazide derivatives containing diverse heterocycles, such as thiazole, isoxazole, pyrazole, thiadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, thiophene, pyridine, and pyrazine. Their antifungal activities were evaluated in vitro and in vivo. Bioassay results revealed that most of the title compounds displayed remarkable antifungal activities in vitro against four tested phytopathogenic fungi, including Fusarium graminearum, Botrytis cinerea, Sclerotinia sclerotiorum, and Rhizoctonia solani. Especially, compound 5aa displayed a broad spectrum of antifungal activity against F. graminearum, B. cinerea, S. sclerotiorum, and R. solani, with the corresponding EC50 values of 0.12, 4.48, 0.33, and 0.15 µg/mL, respectively. In the antifungal growth assay, compound 5aa displayed a protection efficacy of 75.5% against Fusarium head blight (FHB) at a concentration of 200 µg/mL. In another in vivo antifungal activity evaluation, compound 5aa exhibited a noteworthy protective efficacy of 92.0% against rape Sclerotinia rot (RSR) at a concentration of 100 µg/mL, which was comparable to the positive control tebuconazole (97.5%). The existing results suggest that compound 5aa has a broad-spectrum antifungal activity. Electron microscopy observations showed that compound 5aa might cause mycelial abnormalities and organelle damage in F. graminearum. Moreover, in the in vitro enzyme assay, we found that the target compounds 5aa, 5ab, and 5ca displayed significant inhibitory effects toward succinate dehydrogenase, with the corresponding IC50 values of 1.62, 1.74, and 1.96 µM, respectively, which were superior to that of boscalid (IC50 = 2.38 µM). Additionally, molecular docking and molecular dynamics simulation results revealed that compounds 5aa, 5ab, and 5ca have the capacity to bind in the active pocket of succinate dehydrogenase (SDH), establishing hydrogen-bonding interactions with neighboring amino acid residues.

Development of an Analytical Method for Unsaturated Disaccharides from Heparan Sulfate Using Dansylhydrazine Derivatization and High-Performance Liquid Chromatography with Fluorescence Detection.

Glycosaminoglycans (GAGs), such as heparan sulfate (HS), play essential roles in living organisms. Understanding the functionality of HS and its involvement in disease progression necessitates the sensitive and quantitative detection of HS-derived unsaturated disaccharides. Conventionally, fluorescence derivatization precedes the HPLC analysis of these disaccharides. However, the presence of excess unreacted derivatization reagents can inhibit rapid and sensitive analysis in chromatographic determinations. In this study, we describe analytical methods that use dansylhydrazine as a derivatization agent for the detection and determination of HS-derived unsaturated disaccharides using HPLC. In addition, we have developed a straightforward method for removing excess unreacted reagent using a MonoSpin NH2 column. This method may be employed to remove excess pre-labeling reagents, thereby facilitating the analysis of HS-derived unsaturated disaccharides with satisfactory reproducibility.

Leveraging Hydrazide as Protection for Carboxylic Acid: Suppression of Aspartimide Formation during Fmoc Solid-Phase Peptide Synthesis.

Despite numerous optimizations in peptide synthesis, the formation of aspartimide remains a significant side reaction that needs to be addressed. Herein, we introduce an approach that utilizes hydrazide as a carboxylic-acid-protecting group to reduce the formation of aspartimide. The aspartic acid hydrazide effectively suppressed the formation of aspartimide, even under microwave conditions, and was readily converted to native aspartic acid using CuSO4 in an aqueous medium.

Naphthalimide functionalized metal-organic framework for rapid and nanomolar level detection of hydrazine and anti-hypertensive drug nicardipine.

The increasing utilization of hydrazine and its derivatives across diverse sectors highlights the pressing need for efficient detection methods to safeguard human health and the environment. Likewise, nicardipine, a widely used medication for heart diseases, necessitates accurate sensing techniques for clinical research and therapeutic monitoring. Here, we propose a novel approach using a naphthalimide-functionalized Zr-MOF as a fluorometric probe capable of detecting both hydrazine and nicardipine in aqueous medium. Our designed probe exhibited a significant 31-fold increase in fluorescence intensity upon interaction with hydrazine. At the same time, nicardipine induced 86% fluorescence quenching with an exceptionally rapid response time (100 s for hydrazine and 5 s for nicardipine). The designed probe has the ability to detect both analytes at nanomolar concentrations (LOD for hydrazine is 1.11 nM while that for nicardipine is 9.6 nM). Investigation across various wastewater samples and pH conditions further validated its practical utility. The mechanism behind fluorometric sensing of nicardipine was thoroughly investigated using modern instrumentation. Our study presents a versatile and effective approach for detecting hydrazine and nicardipine, addressing crucial needs in both industrial and biomedical contexts.

Design, synthesis and identification of novel molecular hybrids based on naphthoquinone aromatic hydrazides as potential trypanocide and leishmanicidal agents.

In pursuit of potential agents to treat Chagas disease and leishmaniasis, we report the design, synthesis, and identification novel naphthoquinone hydrazide-based molecular hybrids. The compounds were subjected to in vitro trypanocide and leishmanicidal activities. N'-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-3,5-dimethoxybenzohydrazide (13) showed the best performance against Trypanosoma cruzi (IC50 1.83 µM) and Leishmania amazonensis (IC50 9.65 µM). 4-Bromo-N'-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide (16) exhibited leishmanicidal activity (IC50 12.16 µM). Regarding trypanocide activity, compound 13 was low cytotoxic to LLC-MK2 cells (SI = 95.28). Furthermore, through molecular modeling studies, the cysteine proteases cruzain, rhodesain and CPB2.8 were identified as the potential biological targets.

Discovery of a Bacterial Hydrazine Transferase That Constructs the N-Aminolactam Pharmacophore in Albofungin Biosynthesis.

Structural motifs containing nitrogen-nitrogen (N-N) bonds are prevalent in a large number of clinical drugs and bioactive natural products. Hydrazine (N2H4) serves as a widely utilized building block for the preparation of these N-N-containing molecules in organic synthesis. Despite its common use in chemical processes, no enzyme has been identified to catalyze the incorporation of free hydrazine in natural product biosynthesis. Here, we report that a hydrazine transferase catalyzes the condensation of N2H4 and an aromatic polyketide pathway intermediate, leading to the formation of a rare N-aminolactam pharmacophore in the biosynthesis of broad-spectrum antibiotic albofungin. These results expand the current knowledge on the biosynthetic mechanism for natural products with N-N units and should facilitate future development of biocatalysts for the production of N-N-containing chemicals.

Trypanosoma cruzi killing and immune response boosting by novel phenoxyhydrazine-thiazole against Chagas disease.

Trypanosoma cruzi (T. cruzi) causes Chagas, which is a neglected tropical disease (NTD). WHO estimates that 6 to 7 million people are infected worldwide. Current treatment is done with benznidazole (BZN), which is very toxic and effective only in the acute phase of the disease. In this work, we designed, synthesized, and characterized thirteen new phenoxyhydrazine-thiazole compounds and applied molecular docking and in vitro methods to investigate cell cytotoxicity, trypanocide activity, nitric oxide (NO) production, cell death, and immunomodulation. We observed a higher predicted affinity of the compounds for the squalene synthase and 14-alpha demethylase enzymes of T. cruzi. Moreover, the compounds displayed a higher predicted affinity for human TLR2 and TLR4, were mildly toxic in vitro for most mammalian cell types tested, and LIZ531 (IC50 2.8 µM) was highly toxic for epimastigotes, LIZ311 (IC50 8.6 µM) for trypomastigotes, and LIZ331 (IC50 1.9 µM) for amastigotes. We observed that LIZ311 (IC50 2.5 µM), LIZ431 (IC50 4.1 µM) and LIZ531 (IC50 5 µM) induced 200 µg/mL of NO and JM14 induced NO production in three different concentrations tested. The compound LIZ331 induced the production of TNF and IL-6. LIZ311 induced the secretion of TNF, IFNγ, IL-2, IL-4, IL-10, and IL-17, cell death by apoptosis, decreased acidic compartment formation, and induced changes in the mitochondrial membrane potential. Taken together, LIZ311 is a promising anti-T. cruzi compound is not toxic to mammalian cells and has increased antiparasitic activity and immunomodulatory properties.