Rational design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety.

In this paper, a series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety were constructed. The synthetic compounds were characterized by 1H NMR, 13C NMR, HRMS, and single crystal diffraction. The antimicrobial activities of title compounds against fungi (Pyricutaria oryzae Cav., Phomopsis sp., Botryosphaeria dothidea, cucumber Botrytis cinerea, tobacco Botrytis cinerea, blueberry Botrytis cinerea) and bacteria (Xanthomonas oryzae pv. oryzicola, Xoc; Xanthomonas axonopodis pv. citri, Xac) revealed these compounds possessed excellent antibacterial activity through mycelial growth rate method and turbidity method, respectively. Among them, compounds 7a, 7d, 7g, 7k, 7l, and 7n had the antibacterial inhibition rate of 90.68, 97.86, 93.61, 97.70, 97.26, and 92.34%, respectively. The EC50 values of 7a, 7d, 7g, 7k, 7l, and 7n were 58.31, 48.76, 58.50, 40.11, 38.15, and 46.99 µg/mL, separately, superior to that of positive control pesticide thiodiazole copper (104.26 µg/mL). The molecular docking simulation of compound 7l and glutathione s-transferase also confirmed its good activity. The in vivo bioassay toward Xac infected citrus leaves was also performed to evaluate the potential of compounds as efficient antibacterial reagent. Further study of antibacterial mechanism was also carried out, including extracellular polysaccharide production, permeability of bacterial membrane, and scanning electron microscope observations. The excellent antibacterial activities of these compounds provided a strong support for its application for preventing and control plant diseases.

Discovery of Novel Compounds for Combating Rising Severity of Plant Diseases Caused by Fungi and Viruses.

In recent years, the severity of plant diseases caused by plant pathogenic fungi and viruses has been on the rise. However, there is a limited availability of pesticide chemicals in the market for effectively controlling both fungal and viral infections. To solve this problem, a series of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment were synthesized. Among them, compound 6s exhibited remarkable in vivo protection activity against tobacco mosaic virus, demonstrating the superior 50% effective concentration (EC50) value of 0.42 µM, outperforming ningnanmycin (0.60 µM). Meanwhile, compound 6s exhibited remarkable antifungal activity against Botrytis cinerea Pers. in postharvest blueberry in vitro, with an EC50 value of 0.011 µM, surpassing the inhibition rate of Pyrimethanil (0.262 µM). Additionally, compound 6s also demonstrated remarkable curative and protection activities against blueberry fruit gray mold in vivo, with control efficiencies of 54.2 and 60.4% at 200 µg/mL concentration, respectively, which were comparable to those of Pyrimethanil (49.3 and 63.9%, respectively). Scanning electron microscopy showed that the compound 6s-treated hyphae of B. cinerea Pers. in postharvest blueberry became abnormally collapsed and shriveled. Furthermore, the molecular docking simulation demonstrated that compound 6s formed hydrogen bonds with SER-17, ARG-43, and SER-39 of succinate dehydrogenase (SDH), providing a possible explanation for the mechanism of action between the target compounds and SDH. This study represents the first report on the antiviral and antifungal activities of novel pyrimidine derivatives containing a 1,3,4-oxadiazole thioether fragment.

An improved transformer network for skin cancer classification.

BACKGROUND: Use of artificial intelligence to identify dermoscopic images has brought major breakthroughs in recent years to the early diagnosis and early treatment of skin cancer, the incidence of which is increasing year by year worldwide and poses a great threat to human health. Achievements have been made in the research of skin cancer image classification by using the deep backbone of the convolutional neural network (CNN). This approach, however, only extracts the features of small objects in the image, and cannot locate the important parts. OBJECTIVES: As a result, researchers of the paper turn to vision transformers (VIT) which has demonstrated powerful performance in traditional classification tasks. The self-attention is to improve the value of important features and suppress the features that cause noise. Specifically, an improved transformer network named SkinTrans is proposed. INNOVATIONS: To verify its efficiency, a three step procedure is followed. Firstly, a VIT network is established to verify the effectiveness of SkinTrans in skin cancer classification. Then multi-scale and overlapping sliding windows are used to serialize the image and multi-scale patch embedding is carried out which pay more attention to multi-scale features. Finally, contrastive learning is used which makes the similar data of skin cancer encode similarly so that the encoding results of different data are as different as possible. MAIN RESULTS: The experiment is carried out based on two datasets, namely (1) HAM10000: a large dataset of multi-source dermatoscopic images of common skin cancers; (2)A clinical dataset of skin cancer collected by dermoscopy. The model proposed has achieved 94.3% accuracy on HAM10000 and 94.1% accuracy on our datasets, which verifies the efficiency of SkinTrans. CONCLUSIONS: The transformer network has not only achieved good results in natural language but also achieved ideal results in the field of vision, which also lays a good foundation for skin cancer classification based on multimodal data. This paper is convinced that it will be of interest to dermatologists, clinical researchers, computer scientists and researchers in other related fields, and provide greater convenience for patients.

Verification of TRI3 Acetylation of Trichodermol to Trichodermin in the Plant Endophyte Trichoderma taxi.

Trichodermin, a trichothecene first isolated in Trichoderma species, is a sesquiterpenoid antibiotic that exhibits significant inhibitory activity to the growth of many pathogenic fungi such as Candida albicans, Rhizoctonia solani, and Botrytis cinerea by inhibiting the peptidyl transferase involved in eukaryotic protein synthesis. Trichodermin has also been shown to selectively induce cell apoptosis in several cancer cell lines and thus can act as a potential lead compound for developing anticancer therapeutics. The biosynthetic pathway of trichodermin in Trichoderma has been identified, and most of the involved genes have been functionally characterized. An exception is TRI3, which encodes a putative acetyltransferase. Here, we report the identification of a gene cluster that contains seven genes expectedly involved in trichodermin biosynthesis (TRI3, TRI4, TRI6, TRI10, TRI11, TRI12, and TRI14) in the trichodermin-producing endophytic fungus Trichoderma taxi. As in Trichoderma brevicompactum, TRI5 is not included in the cluster. Functional analysis provides evidence that TRI3 acetylates trichodermol, the immediate precursor, to trichodermin. Disruption of TRI3 gene eliminated the inhibition to R. solani by T. taxi culture filtrates and significantly reduced the production of trichodermin but not of trichodermol. Both the inhibitory activity and the trichodermin production were restored when native TRI3 gene was reintroduced into the disruption mutant. Furthermore, a His-tag-purified TRI3 protein, expressed in Escherichia coli, was able to convert trichodermol to trichodermin in the presence of acetyl-CoA. The disruption of TRI3 also resulted in lowered expression of both the upstream biosynthesis TRI genes and the regulator genes. Our data demonstrate that T. taxi TRI3 encodes an acetyltransferase that catalyzes the esterification of the C-4 oxygen atom on trichodermol and thus plays an essential role in trichodermin biosynthesis in this fungus.

Isolation of an acidic polysaccharide from the flowers of Leucosceptrum canum Smith and its immunomodulatory activity evaluation.

A water-soluble polysaccharide (LCP-05) was isolated from the flowers of Leucosceptrum canum Smith. LCP-05 was an acidic polysaccharide with a molecular weight of approximately 8.9 kDa. Monosaccharide composition analysis indicated that LCP-05 was composed of Man, Rha, GlcA, GalA, Glc, Gal and Ara in a molar ratio of 0.83:1.68:0.33:2.15:1.00:1.45:1.22. The framework of LCP-05 was speculated to be a branched rhamnogalacturonan with the backbone consisting of α-1,2,4-linked Rhap and α-1,4-linked GalAp, and bearing branches at the O-4 position of the Rha residues. The side chains are terminated primarily with the Araf and Glcp residues. LCP-05 was found to be able to significantly induce the production of NO, IL-6, and TNF-α in RAW 264.7 cells, and to induce RAW 264.7 cell's suppressive effect on both cell growth and cell migration of 4 T1 mammary breast cancer cells.

Investigation of roles of divalent cations in Shewanella oneidensis pellicle formation reveals unique impacts of insoluble iron.

BACKGROUND: Bacteria adopt a variety of lifestyles in their natural habitats and can alternate among different lifestyles in response to environmental changes. At high cell densities, bacteria can form extracellular matrix encased cell population on submerged tangible surfaces (biofilms), or at the air-liquid interface (pellicles). Compared to biofilm, pellicle lifestyle allows for better oxygen access, but is metabolically more costly to maintain. Further understanding of pellicle formation and environmental cues that influence cellular choices between these lifestyles will definitely improve our appreciation of bacterial interaction with their environments. METHODS: Shewanella oneidensis cells were cultured in 24-well plates with supplementation of varied divalent cations, and pellicles formed under such conditions were evaluated. Mutants defective in respiration of divalent cations were used to further characterize and confirm unique impacts of iron. RESULTS AND CONCLUSIONS: Small amount of Fe(2+) was essential for pellicle formation, but presence of over-abundant iron (0.3mM Fe(2+) or Fe(3+)) led to pellicle disassociation without impairing growth. Such impacts were found due to S. oneidensis-mediated formation of insoluble alternative electron acceptors (i.e., Fe3O4) under physiologically relevant conditions. Furthermore, we demonstrated that cells preferred a lifestyle of forming biofilm and respiring on such insoluble electron acceptors under tested conditions, even to living in pellicles. GENERAL SIGNIFICANCE: Our finding suggests that bacterial lifestyle choice involves balanced evaluation of multiple aspects of environmental conditions, and yet-to-be-characterized signaling mechanism is very likely underlying such processes.