Semantic segmentation of microbial alterations based on SegFormer

IntroductionPrecise semantic segmentation of microbial alterations is paramount for their evaluation and treatment. This study focuses on harnessing the SegFormer segmentation model for precise semantic segmentation of strawberry diseases, aiming to improve disease detection accuracy under natural acquisition conditions.MethodsThree distinct Mix Transformer encoders - MiT-B0, MiT-B3, and MiT-B5 - were thoroughly analyzed to enhance disease detection, targeting diseases such as Angular leaf spot, Anthracnose rot, Blossom blight, Gray mold, Leaf spot, Powdery mildew on fruit, and Powdery mildew on leaves. The dataset consisted of 2,450 raw images, expanded to 4,574 augmented images. The Segment Anything Model integrated into the Roboflow annotation tool facilitated efficient annotation and dataset preparation.ResultsThe results reveal that MiT-B0 demonstrates balanced but slightly overfitting behavior, MiT-B3 adapts rapidly with consistent training and validation performance, and MiT-B5 offers efficient learning with occasional fluctuations, providing robust performance. MiT-B3 and MiT-B5 consistently outperformed MiT-B0 across disease types, with MiT-B5 achieving the most precise segmentation in general.DiscussionThe findings provide key insights for researchers to select the most suitable encoder for disease detection applications, propelling the field forward for further investigation. The success in strawberry disease analysis suggests potential for extending this approach to other crops and diseases, paving the way for future research and interdisciplinary collaboration

Synthesis, biological evaluation and molecular modeling study of thiadiazolo[3,2-a][1,3]diazepine analogues of HIE-124 as a new class of short acting hypnotics*

A new series of 6,7-dihydro-[1,3,4]thiadiazolo[3,2-a][1,3]diazepine analogues were synthesized, and biological evaluated. Compound GS-62 (33) exhibited potent in vivo short acting hypnotic activity with onset time, duration of sleep and therapeutic index of 6.4 ± 0.2, 94.8 ± 5.3 min, 6.62, respectively), in comparison to thiopental sodium (6). Compounds 33 did not show any sign of acute tolerance reported with the maintenance dose of 6. Meanwhile 33 potentiated the in vivo hypnotic effect of 6 in an equimolar amounts (0.06 mmol) combination showing an onset and duration of 7.5 ± 1.3, 62.5 ± 5.9 min, respectively. This combination allowed the use of lower doses of both drugs to avoid the undesirable side effects. Docking studies revealed favorable interactions and binding to BDZ binding site of the GABAA receptor especially with Arg87, Arg149, and Thr151 amino acid residues

Bioorganic & Medicinal Chemistry Letters

A new series of 2,3,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 28 and 61 proved to be active DHFR inhibitors with IC50 0.02 and 0.01 µM, respectively. Molecular modeling studies concluded that recognition with the key amino acid Phe34 is essential for binding and hence DHFR inhibition. Compounds 34, 56 and 66 showed broad spectrum antimicrobial activity comparable to Gentamicin and Ciprofloxacin. Compounds 40 and 64 showed broad spectrum antitumor activity toward several tumor cell lines and proved to be 10 fold more active than 5-FU, with GI50 MG-MID values of 2.2 and 2.4 µM, respectively

Synthesis, antimicrobial, anti-biofilm evaluation, and molecular modelling study of new chalcone linked amines derivatives

<p>A series of amide chalcones conjugated with different secondary amines were synthesised and characterised by different spectroscopic techniques ¹H NMR, ¹³C NMR, and ESI-MS. They were screened for <i>in vitro</i> antibacterial activity. Compounds <b>36</b>, <b>37</b>, <b>38</b>, <b>42</b>, and <b>44</b> are the most active among the synthesised series exhibiting MIC value of 2.0–10.0 µg/ml against different bacterial strains. Compound <b>36</b> was equipotent to the standard drug Ampicillin displaying MBC value of 2.0 µg/ml against the bacterial strain <i>Staphylococcus aureus.</i> The products were screened for anti-biofilm activity. Compounds <b>36</b>, <b>37</b>, and <b>38</b> exhibited promising anti-biofilm activity with IC₅₀ value ranges from 2.4 to 8.6 µg. Molecular modelling was performed suggesting parameters of signalling anti-biofilm mechanism. AspB327 HisB340 (arene–arene interaction) and IleB328 amino acid residues seemed of higher importance to inhibit c-di-GMP. Hydrophobicity may be crucial for activity. ADME calculations suggested that compounds <b>36</b>, <b>37</b>, and <b>38</b> could be used as good orally absorbed anti-biofilm agents.</p

Dihydrofolate reductase (DHFR) inhibition and molecular modeling study of some 6-bromo- or 6,8-dibromo-quinazolin-4(3H)-ones

Objectives: The dihydrofolate reductase (DHFR) inhibitory activity of 6-bromo- and 6,8-dibromo-quinazolin-4(3H)-ones (7–25) were studied to define the structural features and requirements that enhance selectivity and specificity for the proper binding to the enzyme active site. Methods: Compounds 7–25 were tested for their in vitro DHFR inhibition. As an application of the use of DHFR inhibitors, in vitro antitumor activity using disease-oriented human cell lines assay was performed. Key findings: Compounds 19, 20, and 22 showed remarkable DHFR inhibitory activity, inhibitory concentration (IC50 0.6, 0.2, and 0.1 μM, respectively). Compounds 12, 17, 18, 20, and 24 proved to be broad spectrum antitumor with median IC50 values of 0.6, 0.6, 0.5, 0.6, and 0.7 μM, respectively. Molecular docking study results revealed that the active DHFR inhibitors 22 and 20 bind to DHFR with similar amino acid residues as methotrexate, especially Arg 28. Conclusions: The mono-bromo series proved to be more active than the di-bromo counterparts and the 3-(2-hydrazinyl-acetyl)- is more active than its 3-(acetohydrazide) isoster. The investigated compounds could be used as template model for further optimization

Synthesis, biological evaluation and molecular modeling study of some new thiazolodiazepine analogs as CNS active agents

New derivatives of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 3), were synthesized as continuation to our previous patented efforts. Compounds 15 and 20 showed marginal hypnotic potency compared to 3. Compounds 15 (0.78 mmol/kg) and 20 (0.39 mmol/kg) showed remarkable 100% protection against PTZ induced convulsions with two and four fold increase in activity than sodium valproate (1.38 mmol/kg), respectively. Molecular modeling studies showed hydrogen bonding interaction between 15 and Thr56 residues at the binding site of GABA . Superposition, flexible alignment and surface mapping of 15, 20 and diazepam supports their biological resemblance where ADMET study suggested that those compounds could be used as oral anticonvulsants

Nonclassical antifolates, part 5. Benzodiazepine analogs as a new class of DHFR inhibitors: Synthesis, antitumor testing and molecular modeling study

A new series of tetrahydro-quinazoline and tetrahydro-1H-dibenzo[b,e][1,4]diazepine analogs were synthesized and tested for their DHFR inhibition and in vitro antitumor activity. Compound 35 showed a remarkable DHFR inhibitory potency (IC50, 0.004 mM) which is twenty fold more active than metho- trexate (MTX). Compounds 17 and 23 proved to be fifteen fold more active than the known antitumor 5- FU, with MG-MID GI50, TGI, and LC50 values of 1.5, 46.8, 93.3 and 1.4, 17.4, 93.3 mM, respectively. Com- puter modeling studies allowed the identification that methoxy and methyl substituents, the p-system of the chalcone core, the nitrogen atoms, on the dibenzodiazepine ring as pharmacophoric features essential for activity. These mark points could be used as template model for further future optimization

Nonclassical antifolates, part 4. 5-(2-Aminothiazol-4-yl)-4-phenyl-4H1,2,4-triazole-3-thiols as a new class of DHFR inhibitors: Synthesis, biological evaluation and molecular modeling study

A new series of compounds possessing 5-(2-aminothiazol-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol skeleton was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, antitumor and schistosomicidal activities. Four active compounds were allocated, the antibacterial 22 (comparable to gentamicin and ciprofloxacin), the schistosomicidal 29 (comparable to praziquantel), the DHFR inhibitor 34 (IC 0.03 mM, 2.7 fold more active than MTX), and the antitumor 36 (comparable to doxorubicin). Molecular modeling studies concluded that recognition with key amino acid Leu4 and Val1 is essential for DHFR binding. Flexible alignment and surface mapping revealed that the obtained model could be useful for the development of new class of DHFR inhibitors

Ameliorative effects of vitamins-loaded flavoured nanophytosomes fortified with star anise volatile oil against CsA-Induced liver and kidney injury in rats: Application in functional ice cream

This study investigated the effect of flavoured nanophytosomes loaded with vitamins A, E, D, B complex, folic acid, and C, as well as zinc on the immunosuppressive cyclosporin A (CsA)-induced liver and kidney injury in male rats. The vitamins flavoured nanophytosomes (VFnPs) were characterized in terms of particle size, zeta potential, encapsulation efficiency. Ice cream was flavoured with star anise volatile oil to mask the VFnPs' flavour and unacceptable taste. The study found that treatment with CsA alone resulted in increased (P > 0.05) levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, while the levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1β, and TLR4 decreased (P > 0.05). However, the group that received CsA simultaneously with VFnPs showed a significant (P > 0.05) decrease in the levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, and increased (P > 0.05) levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1β, and TLR4. The increase in the ratio of VFnPs had little effect on the physiochemical and sensory evaluation of the ice cream. Finally, the study suggests that VFnPs could potentially protect against CsA-induced liver and kidney injury and serve as a promising natural therapy for treating such conditions