Deciphering Indirect Nitrite Reduction to Ammonia in High-Entropy Electrocatalysts Using In Situ Raman and X-ray Absorption Spectroscopies.

This research adopts a new method combining calcination and pulsed laser irradiation in liquids to induce a controlled phase transformation of Fe, Co, Ni, Cu, and Mn transition-metal-based high-entropy Prussian blue analogs into single-phase spinel high-entropy oxide and face-centered cubic high-entropy alloy (HEA). The synthesized HEA, characterized by its highly conductive nature and reactive surface, demonstrates exceptional performance in capturing low-level nitrite (NO2 -) in an electrolyte, which leads to its efficient conversion into ammonium (NH4 +) with a Faradaic efficiency of 79.77% and N selectivity of 61.49% at -0.8 V versus Ag/AgCl. In addition, the HEA exhibits remarkable durability in the continuous nitrite reduction reaction (NO2 -RR), converting 79.35% of the initial NO2 - into NH4 + with an impressive yield of 1101.48 µm h-1 cm-2. By employing advanced X-ray absorption and in situ electrochemical Raman techniques, this study provides insights into the indirect NO2 -RR, highlighting the versatility and efficacy of HEA in sustainable electrochemical applications.

3D Hierarchical MOF-Derived Defect-Rich NiFe Spinel Ferrite as a Highly Efficient Electrocatalyst for Oxygen Redox Reactions in Zinc-Air Batteries.

The strategy of defect engineering is increasingly recognized for its pivotal role in modulating the electronic structure, thereby significantly improving the electrocatalytic performance of materials. In this study, we present defect-enriched nickel and iron oxides as highly active and cost-effective electrocatalysts, denoted as Ni0.6Fe2.4O4@NC, derived from NiFe-based metal-organic frameworks (MOFs) for oxygen reduction reactions (ORR) and oxygen evolution reactions (OER). XANES and EXAFS confirm that the crystals have a distorted structure and metal vacancies. The cation defect-rich Ni0.6Fe2.4O4@NC electrocatalyst exhibits exceptional ORR and OER activities (ΔE = 0.68 V). Mechanistic pathways of electrochemical reactions are studied by DFT calculations. Furthermore, a rechargeable zinc-air battery (RZAB) using the Ni0.6Fe2.4O4@NC catalyst demonstrates a peak power density of 187 mW cm-2 and remarkable long-term cycling stability. The flexible solid-state ZAB using the Ni0.6Fe2.4O4@NC catalyst exhibits a power density of 66 mW cm-2. The proposed structural design strategy allows for the rational design of electronic delocalization of cation defect-rich NiFe spinel ferrite attached to ultrathin N-doped graphitic carbon sheets in order to enhance active site availability and facilitate mass and electron transport.

Streptomyces monashensis MSK03-mediated synthesis of gold nanoparticles: characterization and antibacterial activity.

Nanotechnology is a cutting-edge field with diverse applications, particularly in the utilization of gold nanoparticles (AuNPs) due to their stability and biocompatibility. AuNPs serve as pivotal components in medical applications, with a specific emphasis on their significant antibacterial efficacy. This study focuses on synthesizing AuNPs using the cell-free supernatant of Streptomyces monashensis MSK03, isolated from terrestrial soil in Thailand. The biosynthesis process involved utilizing the cell-free supernatant of S. monashensis MSK03 and hydrogen tetrachloroauric acid (HAuCl4) under controlled conditions of 37 °C and 200 rpm agitation. Characterization studies revealed spherical AuNPs with sizes ranging from 7.1 to 40.0 nm (average size: 23.2 ± 10.7 nm), as confirmed by TEM. UV-Vis spectroscopy indicated a localized surface plasmon resonance (LSPR) band at 545 nm, while XRD analysis confirmed a crystalline structure with characteristics of cubic lattice surfaces. The capping molecules on the surface of AuNPs carry a negative charge, indicated by a Zeta potential of -26.35 mV, and FTIR analysis identified functional groups involved in reduction and stabilization. XANES spectra further confirmed the successful reduction of Au3+ to Au0. Moreover, the synthesized AuNPs demonstrated antibacterial activity against drug-resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Interestingly, the AuNPs showed non-toxicity to Vero cell lines. These significant antibacterial properties of the produced nanoparticles mean they hold great promise as new antimicrobial treatments for tackling the increasing issue of antibiotic resistance.

Impacts of Mg doping on the structural properties and degradation mechanisms of a Li and Mn rich layered oxide cathode for lithium-ion batteries.

The Li- and Mn-rich layered oxide cathode material class is a promising cathode material type for high energy density lithium-ion batteries. However, this cathode material type suffers from layer to spinel structural transition during electrochemical cycling, resulting in energy density losses during repeated cycling. Thus, improving structural stability is an essential key for developing this cathode material family. Elemental doping is a useful strategy to improve the structural properties of cathode materials. This work examines the influences of Mg doping on the structural characteristics and degradation mechanisms of a Li1.2Mn0.4Co0.4O2 cathode material. The results reveal that the prepared cathode materials are a composite, exhibiting phase separation of the Li2MnO3 and LiCoO2 components. Li2MnO3 and LiCoO2 domain sizes decreased as Mg content increased, altering the electrochemical mechanisms of the cathode materials. Moreover, Mg doping can retard phase transition, resulting in reduced structural degradation. Li1.2Mn0.36Mg0.04Co0.4O2 with optimal Mg doping demonstrated improved electrochemical performance. The current work provides deeper understanding about the roles of Mg doping on the structural characteristics and degradation mechanisms of Li-and Mn-rich layered oxide cathode materials, which is an insightful guideline for the future development of high energy density cathode materials for lithium-ion batteries.

Isolation and Identification of Bioactive Compounds from Streptomyces actinomycinicus PJ85 and Their In Vitro Antimicrobial Activities against Methicillin-Resistant Staphylococcus aureus.

Antibiotic-resistant strains are a global health-threatening problem. Drug-resistant microbes have compromised the control of infectious diseases. Therefore, the search for a novel class of antibiotic drugs is necessary. Streptomycetes have been described as the richest source of bioactive compounds, including antibiotics. This study was aimed to characterize the antibacterial compounds of Streptomyces sp. PJ85 isolated from dry dipterocarp forest soil in Northeast Thailand. The 16S rRNA gene sequence and phylogenetic analysis showed that PJ85 possessed a high similarity to Streptomyces actinomycinicus RCU-197T of 98.90%. The PJ85 strain was shown to produce antibacterial compounds that were active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The active compounds of PJ85 were extracted and purified using silica gel column chromatography. Two active antibacterial compounds, compound 1 and compound PJ85_F39, were purified and characterized with spectroscopy, including liquid chromatography and mass spectrometry (LC-MS). Compound 1 was identified as actinomycin D, and compound PJ85_F39 was identified as dihomo-γ-linolenic acid (DGLA). To the best of our knowledge, this is the first report of the purification and characterization of the antibacterial compounds of S. actinomycinicus.

Streptomyces chiangmaiensis SSUT88A mediated green synthesis of silver nanoparticles: characterization and evaluation of antibacterial action against clinical drug-resistant strains.

This study involved the characterization of AgNPs synthesized from soil isolate Streptomyces sp. SSUT88A and their antimicrobial activities. The strain SSUT88A revealed 98.8% similarity of the 16s rRNA gene to Streptomyces chiangmaiensis TA4-1T. The AgNPs were synthesized by mixing either intracellular or extracellular cell-free supernatant of strain SSUT88A with AgNO3. The synthesized AgNPs from intracellular cell-free supernatant and extracellular cell-free supernatant were designated as IS-AgNPs and ES-AgNPs, respectively. The IS-AgNPs showed maximum absorbance of UV-vis spectra at 418 nm, while ES-AgNPs revealed maximum absorbance at 422 nm. The TEM observation of synthesized AgNPs revealed a spherical shape with an average diameter of 13.57 nm for IS-AgNPs and 30.47 nm for ES-AgNPs. The XRD and XANES spectrum profile of both synthesized AgNPs exhibited similar spectrum energy, which corresponded to AgNPs. The IS-AgNPs revealed antimicrobial activity against clinical isolate drug-resistant bacteria (Acinetobacter baumannii, Escherichia coli 8465, Klebsiella pneumoniae 1617, and Pseudomonas aeruginosa N90PS), while ES-AgNPs had no antimicrobial activity. When compared to commercial AgNPs, IS-AgNPs exhibited antibacterial efficacy against all clinical isolate bacteria including A. baumannii, one of the most threatening multi-drug resistant strains, while commercial AgNPs did not. Thus, IS-AgNPs has potential to be further developed as an antimicrobial agent against drug-resistant bacteria.

Application of Bacillus sp. protease in the fabrication of silver/silver chloride nanoparticles in solution and cotton gauze bandages.

Silver (Ag)/silver chloride (AgCl) nanoparticles have been used worldwide for their antimicrobial activity. Proteases play an important role in many physiological processes during wound healing. Therefore, the aim of this study was to fabricate silver-type nanoparticles exhibiting protease activity for medical applications such as wound healing and dressings. The Ag/AgCl nanoparticles were fabricated using Bacillus sp. protease and visible light activation. The size of the fabricated nanoparticles was estimated to be 35.29 ± 6.43 nm. The nanoparticles were coated on a cotton gauze bandage using immersion and ultrasonication. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed that the nanoparticles could be used to coat the gauze bandage. Synchrotron radiation X-ray tomographic microscopy indicated that coating with the nanoparticles did not destroy the packing of cotton fibers in the gauze bandage. The nanoparticles exhibited fibrinolytic and collagenolytic activities. Protease activity remained after the nanoparticle coating was applied to the gauze bandage. The nanoparticles were not absorbed on a gelatin agar plate after incubation at 37 °C for 18 H. These results suggest that the coated cotton gauze bandage may be safe for further use, and the nanoparticles may not be absorbed into animal or human skin.

Application of magnetic field to CO hydrogenation using a confined-space catalyst: effect on reactant gas diffusivity and reactivity.

An external magnetic field has recently been applied in reaction processes to promote movement and avoid agglomeration of magnetic particles, and also reduce the activation energy through improving the gas-solid contact. In this work, the effect of an external magnetic field on reactant gas diffusivity and reactivity in CO hydrogenation within a confined-space catalyst was investigated for the first time using a conventional reactor packed with a bimetallic 5Fe-5Co/ZSM-5 molecular sieve catalyst. The synergistic effect between magnetic field and limited mass transfer within zeolite cavities improved the mass transfer ability and reaction phenomena of the reactant molecules, leading to enhancement of catalytic activity with tailored reaction pathways. As a result, CO conversion and CH4 selectivity were increased by factors of 1.9 and 1.3 compared to those without a magnetic field. These synergistic interactions are able to provide an innovative challenge for green and sustainable chemical processes and separation processes by means of selective reactant and product mass transfer designed for selective catalytic conversion in the future.

A multiscale investigation elucidating the structural complexities and electrochemical properties of layered-layered composite cathode materials synthesized at low temperatures.

Layered-layered composite (xLi2MnO3·(1 -x) LiMO2, M = Mn, Ni, Co, and Fe) cathode materials have attracted much attention as cathodes for high energy density lithium ion batteries. However, these materials are structurally unstable resulting from complicated phase transformation mechanisms during cycling. Additionally, the complex structural characteristics and structural stability of these materials largely depend on their preparation methods. Studying the correlation between multiscale structural properties and preparation methods is important in the development of layered-layered composite cathode materials. In this work, 0.5Li2MnO3·0.5LiCoO2 composite materials were prepared with different heating and cooling rates with a maximum temperature of 600 °C. The structural properties of the 0.5Li2MnO3·0.5LiMO2 composite materials were investigated using combined in situ X-ray absorption spectroscopy (XAS), in situ X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and high resolution transmission electron microscopy (HRTEM) techniques. Heating and cooling rates have no significant effect on either the crystal or local atomic structures of the prepared samples. However, the microstructure was critically important for its impact on electrochemical properties.

Identification and characterization of a protease (EuRP-61) from Euphorbia resinifera latex.

A serine protease designated as EuRP-61 was purified from Euphorbia resinifera latex. The N-terminal sequence of 15 amino acids of EuRP-61 supported the conclusion that the enzyme was a serine protease because its amino acid sequence had homology (between 50 and 70% identities) with the subtilisin-like proteases of other plants. EuRP-61 had a molecular weight estimated at 61 kDa analyzed by MALDI-TOF MS. The enzyme could cleave human fibrinogen with optimal conditions at pH 5.0 and 45 °C. The enzyme had a broad range of pH stability from 1 to 14 and tolerance to denaturation up to a temperature of approximately 65-66 °C. EuRP-61 hydrolyzed fibrinogen with a Michaelis constant (Km) of 4.95 ±â€¯0.1 µM; a maximal velocity (Vmax) of 578.1 ±â€¯11.81 ng min-1; and a catalytic efficiency (Vmax/Km) of 116.8 ±â€¯1 ng µM-1 min-1. EuRP-61was crystallized under the condition of sodium iodide (0.2 M), Bis-Tris propane (0.1 M, pH 8.5) and PEG3350 (20%) by the sitting-drop method. The crystal belonged to space group P212121, with unit cell dimension a = 109.91, b = 67.38 and c = 199.45 Šand diffracted X-ray to 2.53 Šresolution. The crystal structure of EuRP-61 will be explored further by special phase solving techniques.

Rate dependent structural transition and cycling stability of a lithium-rich layered oxide material.

Lithium-rich layered oxide materials, xLi2MnO3·(1 - x)LiMO2 (M = Mn, Fe, Co, Ni, etc.), are a promising candidate for use as cathode materials in the batteries of electric vehicles (EVs). This is due to their high energy density (∼900 W h kg-1), which is larger than those of the currently used commercial cathode materials. Moreover, EV technologies require lithium ion batteries with a high rate performance to achieve short charging times. The high rate property largely depends on the electrochemical properties of the electrodes in these batteries. However, the correlation between the cycling rate, structural stability and electrochemical properties of cathode materials is not clearly understood. In this work, the influence of cycling rate on structural transition behaviors and cycling stability of a 0.5Li2MnO3·0.5LiCoO2 composite-based material was investigated. The experimental results reveal that cycling rates significantly affect the activation of the Li2MnO3 component. A high cycling rate retards Li2MnO3 activation, leading to a smaller spinel phase transition and a higher cycling stability.

Roles of ZnO in Cu/Core-Shell Al-MCM-41 for NO Reduction by Selective Catalytic Reduction with NH3: The Effects of Metal Loading and Cu/ZnO Ratio.

Cu-ZnO/Al-MCM-41 catalysts were studied for NO x reduction. The total metal loading was varied as 3, 5, and 7 wt %, whereas the Cu-to-ZnO ratio was fixed at 1:1. Too high metal loading led to lower reducibility of Cu2+, as CuO and ZnO covers on the catalyst surface could partially block pores and hinder gas molecules to access the Cu2+ ions. Subsequently, Cu loading was fixed at 2.5 wt %, whereas ZnO content was varied as 0, 2.5, and 3.5 wt %. The results demonstrated that 2.5Cu-2.5ZnO catalyst exhibits the best catalytic activity, as it gave the average NO conversion of 87%.

Structural and Electrochemical Kinetic Properties of 0.5Li2MnO3∙0.5LiCoO2 Cathode Materials with Different Li2MnO3 Domain Sizes.

Lithium rich layered oxide xLi2MnO3∙(1-x)LiMO2 (M = Mn, Co, Ni, etc.) materials are promising cathode materials for next generation lithium ion batteries. However, the understanding of their electrochemical kinetic behaviors is limited. In this work, the phase separation behaviors and electrochemical kinetics of 0.5Li2MnO3∙0.5LiCoO2 materials with various Li2MnO3 domain sizes were studied. Despite having similar morphological, crystal and local atomic structures, materials with various Li2MnO3 domain sizes exhibited different phase separation behavior resulting in disparate lithium ion transport kinetics. For the first few cycles, the 0.5Li2MnO3∙0.5LiCoO2 material with a small Li2MnO3 domain size had higher lithium ion diffusion coefficients due to shorter diffusion path lengths. However, after extended cycles, the 0.5Li2MnO3∙0.5LiCoO2 material with larger Li2MnO3 domain size showed higher lithium ion diffusion coefficients, since the larger Li2MnO3 domain size could retard structural transitions. This leads to fewer structural rearrangements, reduced structural disorders and defects, which allows better lithium ion mobility in the material.

Isolation and characterization of a galactose-specific lectin (EantH) with antimicrobial activity from Euphorbia antiquorum L. latex.

A homodimeric 75 kDa lectin with hemagglutination activity (HA) was purified from the crude latex of Euphorbia antiquorum L. by two types of chromatography, on cation exchange (HiTrap SP FF) and hydrophobic HiTrap Phenyl FF (high sub) columns. The purified protein was designated EantH, and is classified as a galactose-specific thermostable lectin. The HA of EantH was stable at pH values of 5-9 and temperature 5-65 °C. The lectin had bacteriostatic action on the Gram-positive bacteria Staphylococcus aureus and S. epidermidis, with a minimum inhibitory concentration (MIC) of 2000 µg/ml and on a Gram-negative bacterium Samonella typhimurium, with a MIC of 1000 µg/ml. EantH inhibited the growth of Propionibacterium acnes and Streptococcus agalactiae with MIC of 125 µg/ml and 250 µg/ml, respectively. EantH killed P. acnes and S. agalactiae with a minimum microbicidal concentration (MMC) of 1000 µg/ml and 2000 µg/ml, respectively. Scanning electron microscopy indicated that binding of EantH to the carbohydrates in the cell walls of P. acnes and S. typhimurium drastically altered the bacterial cells, and led to inhibition of growth and/or cell death. The antimicrobial activity of EantH could be neutralized by d­galactose, indicating that its bactericidal action involves binding to galactose in the cell wall.

Eucalyptus ash alters secondary protein conformation of human grey hair and facilitates anthocyanin dyeing.

Wood ashes infused with water have been traditionally used as hair cosmetics, but little or no research has examined the effects of ash on human hair. This study investigated the effect of eucalyptus ash on the structure and morphology of excised human grey hair and its potential use as a pretreatment in natural hair dyeing using anthocyanins extracted from purple cops of Zea mays. Tensile characteristics and surface morphology of ash-pretreated hair was monitored by texture analysis, scanning electron microscopy and atomic force microscopy. The biochemical characteristics of ash-treated hair were analyzed by synchrotron radiation-FTIR and sulfur K-edge X-ray absorption near edge. Dyeing with anthocyanins was analyzed by Lab color scale and adsorption of anthocyanins. Ash-treated hair was elastically and plastically deformed with microscopic alterations to the ridges of the cuticle cells, similar to ammonia-treated hair. The ash extract significantly changed the relative proportion of alpha-helices in the cuticle and cortex layers (p < 0.05), but did not affect the interaction of S-bonds with neighboring atoms (p > 0.05). Ash-treated hair showed significantly enhanced adsorption of anthocyanins (p < 0.05) which changed the color of the grey hair. The alteration of secondary proteins in the cuticle and cortex layers of the grey hair by ash extract pre-treatment, enhanced anthocyanin adsorption. The eucalyptus ash could potentially be useful as a natural hair dyeing pre-treatment.

Topical oral wound healing potential of anthocyanin complex: animal and clinical studies.

AIM: An anthocyanin complex (AC), combined Zea mays and Clitoria ternatea extracts, was evaluated for topical oral wound healing in rats and a clinical trial in orthodontic patients. METHODS/RESULTS: AC enhanced anthocyanin permeation in vitro. In rats, 10% w/w of AC in a mucoadhesive gel (AG) reduced erythema and sizes of oral wounds after topical applications at higher extent than its placebo gel. Acute orthodontic wounds in 68 volunteers were randomly assigned to topically receive either AG or placebo gel and double-blind assessed. Wound size reduction and wound closure enhancement were obvious in AG-treated group on day 3 (p < 0.05). CONCLUSION: At 10% w/w, AC promoted wound closure and possessed a potential in healing stimulation of acute oral wounds.

Topical Niosome Gel Containing an Anthocyanin Complex: a Potential Oral Wound Healing in Rats.

Anthocyanins from dietary sources showing potential benefits as anti-inflammatory in oral lesions were developed as an anthocyanin complex (AC), comprised of extracts of Zea mays (CC) and Clitoria ternatea (CT), and formulated into a niosome gel to prove its topical oral wound healing in vitro and in vivo investigations. The AC formed nano-sized clusters of crystalline-like aggregates, occurring through both intra- and inter-molecular interactions, resulting in delivery depots of anthocyanins, following encapsulation in niosomes and incorporation into a mucoadhesive gel. In vitro permeation of anthocyanins was improved by complexation and further enhanced by encapsulation in niosomes. Collagen production in human gingival fibroblasts was promoted by AC and AC niosomes, but not CC or CT. The in vivo wound healing properties of AC gel (1 and 10%), AC niosome gel (1 and 10%), fluocinolone acetonide gel, and placebo gel were investigated for incisional wounds in the buccal cavities of Wistar rats. AC gel and AC niosome gel both reduced wound sizes after 3 days. AC niosome gel (10%) gave the highest reduction in wound sizes after day 3 (compared to fluocinolone acetonide gel, p < 0.05), and resulted in 100% wound healing by day 5. Histological observations of cross-sectioned wound tissues revealed the adverse effects of fluocinolone gel and wound healing potential of AC niosome gel. Topical application of AC niosome gel exhibited an anti-inflammatory effect and promoted oral wound closure in rats, possibly due to the improved mucosal permeability and presence of delivery depots of AC in the niosome gel.

Fabrication of silver chloride nanoparticles using a plant serine protease in combination with photoactivation and investigation of their biological activities.

Recently, the development of "green" methods for fabrication of silver nanoparticles (Ag-NPs) has been emphasized, in view of their environmental safety, feasibility, and low cost. In this study, a serine protease, EuP-82 from Euphorbia cf. lactea latex, was used to fabricate silver chloride nanoparticles (AgCl-NPs) in phosphate-buffered saline (pH 7.2), under the influence of visible light. The fabricated nanoparticles had a maximal surface plasmon resonance absorption peak at 435 nm. The size of the AgCl-NPs, estimated by scanning electron microscopy, was 57 ± 14.7 nm. Energy dispersive X-ray spectroscopy, X-ray absorption spectroscopy, and X-ray diffraction analysis confirmed that the fabricated Ag-NPs were of the AgCl type. The fabricated nanoparticles had antioxidant activity, scavenging DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals with IC50 of 204 ± 1.8 µg/mL. The fabricated AgCl-NPs had broad-spectrum in vitro antimicrobial activities, acting against the Gram-positive bacteria Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), and Bacillus cereus, and the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. AgCl-NPs also showed antifungal activity against Candida albicans and C. tropicalis. In addition, AgCl-NPs showed antiprotozoal activity against Giardia lamblia, with IC50 202 ± 2.1 µg/mL. Based on the biological activities of the fabricated AgCl-NPs, they have the potential for widespread application in medicine and industry.

Li2MnO3 domain size and current rate dependence on the electrochemical properties of 0.5Li2MnO3·0.5LiCoO2 cathode material.

Layered-layered composite oxides of the form xLi2MnO3·(1-x) LiMO2 (M = Mn, Co, Ni) have received much attention as candidate cathode materials for lithium ion batteries due to their high specific capacity (>250mAh/g) and wide operating voltage range of 2.0-4.8 V. However, the cathode materials of this class generally exhibit large capacity fade upon cycling and poor rate performance caused by structural transformations. Since electrochemical properties of the cathode materials are strongly dependent on their structural characteristics, the roles of these components in 0.5Li2MnO3·0.5LiCoO2 cathode material was the focus of this work. In this work, the influences of Li2MnO3 domain size and current rate on electrochemical properties of 0.5Li2MnO3·0.5LiCoO2 cathodes were studied. Experimental results obtained showed that a large domain size provided higher cycling stability. Furthermore, fast cycling rate was also found to help reduce possible structural changes from layered structure to spinel structure that takes place in continuous cycling.

Intranasal melatonin nanoniosomes: pharmacokinetic, pharmacodynamics and toxicity studies.

AIM: Intranasal melatonin encapsulated in nanosized niosomes was preclinically evaluated. METHODOLOGY: A formula of melatonin niosomes (MN) was selected through physicochemical and cytotoxic data for pharmacokinetic, pharmacodynamics and toxicity studies in male Wistar rats. RESULTS: Intranasal MN was bioequivalent to intravenous injection of melatonin, providing therapeutic level doses. Acute and subchronic toxicity screening showed no abnormal signs, symptoms or hematological effects in any animals. Transient nasal irritations with no inflammation were observed with intranasal MN, leading it to be categorized as relatively harmless. CONCLUSION: The intranasal MN could deliver melatonin to the brain to induce sleep and provide delayed systemic circulation, relative to intravenous injection and also distribute to peripheral tissue.