BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

Nitrogen fertilization modulates rice phyllosphere functional genes and pathogens through fungal communities.

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Continuous age- and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease.

BACKGROUND: Alanine aminotransferase (ALT) is widely used to screen patients with hepatic diseases. However, the current reference ranges (< 50 U/L) were developed by laboratories and have not been validated in populations with a large number of healthy individuals. METHODS: This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare. We applied the least mean square algorithm to establish age- and sex-related reference percentiles of serum levels of transaminases. For validation, we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital. Using receiver operating characteristic curves, we determined age- and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases. RESULTS: This study revealed a significant correlation between serum transaminase levels and age and sex (P < 0.01). These transaminase levels exhibited age- and sex-specific patterns. Among individuals in the non-alcoholic fatty liver disease (NAFLD) cohort, elevated ALT levels displayed a positive association with clinical markers of disease severity, including homeostatic model assessment of insulin resistance, waist-hip ratio, and serum uric acid levels (P < 0.01). According to the receiver operating characteristic curves, ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity. CONCLUSIONS: This study provides age- and sex-specific reference ranges for ALT, aspartate aminotransferase, and γ-glutamyltransferase in Chinese children and adolescents, making it the largest population study to date. Furthermore, the study establishes a precise upper limit for ALT levels, facilitating their use in NAFLD screening. Video Abstract.

Self-adjuvant Astragalus polysaccharide-based nanovaccines for enhanced tumor immunotherapy: a novel delivery system candidate for tumor vaccines.

The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.19 kD; APSHMw, 135.67 kD) from Radix Astragali and made them self-assemble with OVA257-264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method. The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability. APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy. The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution. The FITC-OVA in APS-NVs could be effectively taken up by DCs, and APS-NVs could stimulate the maturation of DCs, improving the antigen cross-presentation efficiency in vitro. The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4. Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c. injection. Smaller APS-NVs could easily access the lymph nodes. Furthermore, APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells. In addition, APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group. The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region. Subsequently, the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs. Therefore, this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.

Electrical tuning of branched flow of light.

Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light.

Spinal TAOK2 contributes to neuropathic pain via cGAS-STING activation in rats.

Thousand and one amino acid kinase 2 (TAOK2) is a member of the mammalian sterile 20 kinase family and is implicated in neurodevelopmental disorders; however, its role in neuropathic pain remains unknown. Here, we found that TAOK2 was enriched and activated after chronic constriction injury (CCI) in the rat spinal dorsal horn. Meanwhile, cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling was also activated with hyperalgesia. Silencing TAOK2 reversed hyperalgesia and suppressed the activation of cGAS-STING signaling induced by CCI, while pharmacological activation of TAOK2 induced pain hypersensitivity and upregulation of cGAS-STING signaling in naive rats. Furthermore, pharmacological inhibition or gene silencing of cGAS-STING signaling attenuated CCI-induced hyperalgesia. Taken together, these data demonstrate that the activation of spinal TAOK2 contributes to CCI-induced hyperalgesia via cGAS-STING signaling activation, providing new molecular targets for the treatment of neuropathic pain.

Cs2 SnCl6 : To Emit or to Catalyze? Te4+ Ion Calls the Shots.

A low concentration of Te4+ doping is found to be capable of endowing the lead-free Cs2 SnCl6 perovskites with excellent photoluminescence quantum yield (PLQY), while further increasing Te4+ concentration leads to PLQY deterioration. The mechanism behind the improved PLQY is intensively studied and reported elsewhere. However, little work is conducted to understand the decreased PLQY at high doping levels and to explore its implications for non-PL-related applications. Here, it is demonstrated that the Te4+ -incorporated Cs2 SnCl6 can be promising candidate for efficient CO2 photocatalysis. An optimum photocatalytic performance is achieved when Te4+ concentration reaches as high as 50%, at which point significant PL quenching has occurred. Through a detailed spectral characterization, such concentration-dependent functionality is attributed to systematic changes in both electronic and local crystal structure, which allow a robust regulation of excitation energy relaxation channels. These findings expand the scope of available photocatalysts for CO2 reduction and also inform synthetic planning for the preparation of multifunctional Pb-free metal halide perovskites.

Scalable graphene sensor array for real-time toxins monitoring in flowing water.

Risk management for drinking water often requires continuous monitoring of various toxins in flowing water. While they can be readily integrated with existing water infrastructure, two-dimensional (2D) electronic sensors often suffer from device-to-device variations due to the lack of an effective strategy for identifying faulty devices from preselected uniform devices based on electronic properties alone, resulting in sensor inaccuracy and thus slowing down their real-world applications. Here, we report the combination of wet transfer, impedance and noise measurements, and machine learning to facilitate the scalable nanofabrication of graphene-based field-effect transistor (GFET) sensor arrays and the efficient identification of faulty devices. Our sensors were able to perform real-time detection of heavy-metal ions (lead and mercury) and E. coli bacteria simultaneously in flowing tap water. This study offers a reliable quality control protocol to increase the potential of electronic sensors for monitoring pollutants in flowing water.

Thoracic endovascular aortic repair of an anastomosis pseudoaneurysm after the Bentall procedure assisted by rapid ventricular pacing: A case report.

Background: Although commonly used for the treatment of descending aortic dissection, endovascular repair is challenging for ascending aortic pseudoaneurysms. Rapid ventricular pacing (RVP), a method that temporarily impedes cardiac output by stopping ventricular activity, heralds potential benefits for thoracic endovascular aortic repair (TEVAR) during precision landing. Recently, we successfully treated an anastomosis pseudoaneurysm after the Bentall procedure using TEVAR assisted by RVP. Case report: A 69-year-old male was admitted to our hospital with a ascending aortic anastomosis pseudoaneurysm. He had undergone a Bentall procedure and a coronary artery bypass grafting nine years prior. After extensive consultation, the decision was made to perform TEVAR with the assistance of RVP. After a covered stent graft was delivered to the precise location of the ascending aorta, RVP was performed at a frequency of 180 beats/min with a pacemaker. When a flattened arterial blood wave of <50 mmHg was observed, the stent graft was released precisely between the opening of the coronary graft and innominate artery. Angiography revealed the presence of an endoleak; therefore, a set of interlock coils were packed into the aneurysm. Subsequent angiography showed intact blood flow in the aorta, superior arch branches, and coronary graft vessels. The patient recovered uneventfully after the procedure. He was discharged six days later and was doing well at the eight-month follow-up. Conclusion: The case indicates that TEVAR assisted by RVP is a promising combination for ascending aortic pseudoaneurysm in selected patients.

Isolation, Purification, and Structural Characterization of Polysaccharides from Codonopsis pilosula and Their Anti-Tumor Bioactivity by Immunomodulation.

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP-43 and Encoding A Novel TMEFF1-339aa Protein.

Skeletal muscle atrophy is a common clinical feature of many acute and chronic conditions. Circular RNAs (circRNAs) are covalently closed RNA transcripts that are involved in various physiological and pathological processes, but their role in muscle atrophy remains unknown. Global circRNA expression profiling indicated that circRNAs are involved in the pathophysiological processes of muscle atrophy. circTmeff1 is identified as a potential circRNA candidate that influences muscle atrophy. It is further identified that circTmeff1 is highly expressed in multiple types of muscle atrophy in vivo and in vitro. Moreover, the overexpression of circTmeff1 triggers muscle atrophy in vitro and in vivo, while the knockdown of circTmeff1 expression rescues muscle atrophy in vitro and in vivo. In particular, the knockdown of circTmeff1 expression partially rescues muscle mass in mice during established atrophic settings. Mechanistically, circTmeff1 directly interacts with TAR DNA-binding protein 43 (TDP-43) and promotes aggregation of TDP-43 in mitochondria, which triggers the release of mitochondrial DNA (mtDNA) into cytosol and activation of the cyclic GMP-AMP synthase (cGAS)/ stimulator of interferon genes (STING) pathway. Unexpectedly, TMEFF1-339aa is identified as a novel protein encoded by circTmeff1 that mediates its pro-atrophic effects. Collectively, the inhibition of circTmeff1 represents a novel therapeutic approach for multiple types of skeletal muscle atrophy.

Ultrafast non-adiabatic dynamics of stilbene-based plant-derived sunscreens with cis-trans isomerization structures.

In this work, we investigated the potential UV protection mechanism of the natural compounds hydroxy resveratrol and pterostilbene by combining theoretical calculations and femtosecond transient absorption spectra (FTAS). The UV absorption spectra showed that the two compounds exhibited strong absorption properties and high photostability. We found two molecules will reach the S1 state or an even higher excited state after UV exposure and molecules in S1 will cross a lower energy barrier to reach the conical intersection. The adiabatic trans-cis isomerization process happened and finally return to the ground. Meanwhile, FTAS clarified the time scale of trans-cis isomerization of two molecules was âˆ¼ 10 ps, which also met the requirement of fast energy relaxation. This work also provides theoretical guidance for developing new sunscreen molecules from natural stilbene.

High-precision nanosecond detection of a gas absorption spectrum based on optical frequency comb time-frequency mapping.

There is an increasing demand for high-precision gas absorption spectroscopy in basic research and industrial applications, such as gas tracking and leak warning. In this Letter, a novel, to the best of our knowledge, high-precision and real-time gas detection method is proposed. A femtosecond optical frequency comb is used as the light source, and a broadening pulse containing a range of oscillation frequencies is formed after passing through a dispersive element and a Mach-Zehnder interferometer. Four absorption lines of H13C14N gas cells are measured at five different concentrations within a single pulse period. A single scan detection time of only 5 ns is obtained along with a coherence averaging accuracy of 0.0055 nm. High-precision and ultrafast detection of the gas absorption spectrum is accomplished while overcoming complexities related to the acquisition system and light source that are encountered in existing methods.

Topological Defect Guided Order Evolution across the Nematic-Smectic Phase Transition.

Topological defects usually emerge and vary during the phase transition of ordered systems. Their roles in thermodynamic order evolution keep being the frontier of modern condensed matter physics. Here, we study the generations of topological defects and their guidance on the order evolution during the phase transition of liquid crystals (LCs). With a given preset photopatterned alignment, two different types of topological defects are achieved depending on the thermodynamic process. Because of the memory effect of LC director field across the Nematic-Smectic (N-S) phase transition, a stable array of toric focal conic domains (TFCDs) and a frustrated one are generated in S phase, respectively. The frustrated one transfers to a metastable TFCD array with a smaller lattice constant, and further changes to a crossed-walls type N state due to the inheritance of orientational order. A free energy on temperature diagram and corresponding textures vividly describe the phase transition process and the roles of topological defects in the order evolution across the N-S phase transition. This Letter reveals the behaviors and mechanisms of topological defects on order evolution during phase transitions. It paves a way for investigating topological defect guided order evolution which is ubiquitous in soft matter and other ordered systems.

Identification of a novel small-molecule inhibitor of miR-29b attenuates muscle atrophy.

Muscle atrophy is debilitating and can be induced by several stressors. Unfortunately, there are no effective pharmacological treatment until now. MicroRNA (miR)-29b is an important target that we identified to be commonly involved in multiple types of muscle atrophy. Although sequence-specific inhibition of miR-29b has been developed, in this study, we report a novel small-molecule miR-29b inhibitor that targets miR-29b hairpin precursor (pre-miR-29b) (Targapremir-29b-066 [TGP-29b-066]) considering both its three-dimensional structure and the thermodynamics of interaction between pre-miR-29b and the small molecule. This novel small-molecule inhibitor has been demonstrated to attenuate muscle atrophy induced by angiotensin II (Ang II), dexamethasone (Dex), and tumor necrosis factor α (TNF-α) in C2C12 myotubes, as evidenced by increase in the diameter of myotube and decrease in the expression of Atrogin-1 and MuRF-1. Moreover, it can also attenuate Ang II-induced muscle atrophy in mice, as evidenced by a similar increase in the diameter of myotube, reduced Atrogin-1 and MuRF-1 expression, AKT-FOXO3A-mTOR signaling activation, and decreased apoptosis and autophagy. In summary, we experimentally identified and demonstrated a novel small-molecule inhibitor of miR-29b that could act as a potential therapeutic agent for muscle atrophy.

Insights into the Mechanism of Bipolar Electrodeposition of Au Films and Its Application in Visual Detection of Prostate Specific Antigens.

Au particles are commonly used for deposition on the surface of a bipolar electrode (BPE) in order to amplify electrochemical and electrochemiluminescence (ECL) signal because of their excellent conductivity, biocompatibility, and large surface area. In this work, a closed BPE device was fabricated and Au particles were deposited on the two poles of a BPE via bipolar deposition. Results indicated that the electrochemical stability of Au film on the anode part of the BPE and the reduction of AuCl4- to Au on the cathode part of the BPE depended on the conductivity of the solution. The prepared Au-Au BPE exhibited a remarkable amplification effect on the ECL signal. Then, a specific sensing interface was constructed on one pole of the BPE for the visual detection of prostate-specific antigens (PSA) based on sandwich-type immunoreactions between primary PSA antibodies (Ab1) on the electrode surface, PSA, and SiO2 nanoparticles labeled secondary PSA antibodies (SiO2-Ab2). The designed biosensor exhibited a good linear relationship for the ECL detection of PSA in the range of 1 × 10-6 to 1 × 10-10 g/mL with a correlation coefficient of 0.9866; the limit of detection (LOD) was 1.5 × 10-11 g/mL. Additionally, the biosensor can realize the electrochemical imaging of PSA by regulating the electrochemical oxidation of the Au anode with the immunoreactions on the cathode part of BPE. Therefore, the small, portable and highly sensitive biosensors have great potential for on-site detection.

[Analysis on Contamination Characteristics, Pollution Source Identification and Ecological Risk Assessment of Polycyclic Aromatic Hydrocarbons of Groundwater in a Large Coking Plant Site of Province].

Polycyclic aromatic hydrocarbons (PAHs), as a highly toxic persistent organic pollutant, are commonly found in soil and water environments. In recent years, the pollution of PAHs in groundwater has attracted wide attention from scientists. To study the pollution characteristics and sources of polycyclic aromatic hydrocarbon in groundwater of the coking site, 16 PAHs priorly controlled by the US EPA were analyzed and discussed. In this study, we identified the contamination characteristics of PAHs in groundwater, analyzed the pollution sources of PAHs, and evaluated the ecological risk of PAHs in the coking site by combining statistical techniques, the positive matrix factorization (PMF) model, and risk quotient (RQ) methods. The results indicated that the total detection rate of PAHs in groundwater of the coking plant was 46.7%. The concentrations of PAHs in groundwater of the coking plant ranged from below the detection limit to 444.9 µg·L-1, with the average value of 1.88 µg·L-1. The concentration of PAHs in the groundwater of different production workshops was significantly different. The most polluted workshop was in the tar-refining area, and the concentration of 16 PAHs was 444.9 µg·L-1. Based on the PMF model, we identified the two primary contamination sources of PAHs in groundwater of the coking plant:① oil combustion and ② coal and biomass combustion and oil leakage. The contribution ratios of the two sources to PAHs of groundwater were 38.6% and 61.4%, respectively. The results of the ecological risk assessment indicated that Σ16PAHs in groundwater of the coking plant had high ecological risk, and the ecological risk of single PAHs in 53.4% of the groundwater sampling site was at a high ecological risk level. In conclusion, it is urgent to carry out the treatment and restoration of the groundwater environment in the coking plant site.

Novel electrochemiluminescence biosensor of fumonisin B1 detection using MWCNTs-PDMS flexible bipolar electrode.

A novel portable and disposable bipolar electrode (BPE)-electrochemiluminescence (ECL) device was fabricated for fumonisin B1 (FB1) detection. BPE was fabricated by using MWCNTs and polydimethylsiloxane (PDMS) due to their excellent electrical conductivity and good mechanical stiffness. After the deposition of Au NPs on the cathode of BPE, the ECL signal could be improved 89-fold. Then a specific aptamer-based sensing strategy was constructed by grafting capture DNA on Au surface, followed by hybridizing with aptamer. Meanwhile, an excellent catalyst, Ag NPs was labeled on aptamer to activate oxygen reduction reaction, leading to a 13.8-fold enhancement in ECL signal at the anode of BPE. Under the optimal conditions, the biosensor exhibited a wide linear range of 0.10 pg/mL to 10 ng/mL for FB1 detection. Meanwhile, it demonstrated satisfactory recoveries for real sample detection with good selectivity, making it to be a convenient and sensitive device for mycotoxin assay.

Design, Synthesis, Antifungal Activity, and Molecular Docking of Streptochlorin Derivatives Containing the Nitrile Group.

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium, as well as a broad antifungal spectrum in primary screening at the concentration of 50 µg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.