Significant Activity Research Articles

The Mediterranean Zoanthid Parazoanthus axinellae as a Novel Source of Antimicrobial Compounds

Marine bioprospecting is a dynamic research field that explores the oceans and their biodiversity as noteworthy sources of new bioactive compounds. Anthozoans are marine animals belonging to the Cnidaria phylum characterized by highly specialized mechanosensory cells used both for defence against predators and prey capture. Here, high concentration of cnidocysts have been isolated from the Mediterranean zoanthid coral Parazoanthus axinellae (Schmidt, 1862) and their antimicrobial potential has been investigated. The cnidocyst extract exerted significant antibacterial activity against some human pathogens capable of developing resistance to conventional antibiotics such as Streptococcus agalactiae and Coccus sp., and against several Vibrio species, including some microbial strains for humans and farmed fish, such as Vibrio alginolyticus, Vibrio anguillarum, Vibrio fischeri, Vibrio harveyi, and Vibrio vulnificus. Results have been discussed in light of both the ecological aspects and biotechnological value of the cnidocyst extract in the nutritional, nutraceutical, and pharmaceutical fields.

Four unreported aporphine alkaloids with antifungal activities from Artabotrys hexapetalus

In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1–4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5–10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1–3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1–3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.

Antibacterial and antibiotic-modifying activity of the commercialized essential oil of Copaifera spp. Associated with LED lights against a Staphylococcus aureus strain

Copaiba oil is widely used in medicine due to its antibacterial, anti-inflammatory, healing, antiviral, antiseptic and analgesic properties. Thus, the main objective of the study is to evaluate the antibacterial activity and modifier of the antibiotic action of the commercialized essential oil of four species of Copaifera spp. in combination with Ampicillin and LED lights against the multidrug-resistant strain of S. aureus (SA 10). The essential oil was obtained commercially through the dōTERRA® company. The evaluation of the antibacterial and modulating activity was performed using the microdilution methodology in a 96-well plate, using blue 415 nm, red 620 nm and yellow 590 nm LEDs and Ampicillin at an initial concentration of 1.024 µg/mL. The experiments were carried out in triplicate and submitted to ANOVA statistical analysis, considering a significant value of p < 0,05. The essential oil of Copaifera spp. did not show antibacterial activity alone, but showed significant modifying activity when combined with Ampicillin in the absence of LED and with red LED. However, the yellow LED and the blue LED had no significant modulating effect. The results suggest the presence of an enzymatic mechanism of resistance, indicating relevance for the development of future scientific research, aiming to help in the treatment of lesions caused by multiresistant pathogens.

A New Biocontrol Agent Bacillus velezensis SF334 against Rubber Tree Fungal Leaf Anthracnose and Its Genome Analysis of Versatile Plant Probiotic Traits.

Natural rubber is an important national strategic and industrial raw material. The leaf anthracnose of rubber trees caused by the Colletotrichum species is one of the important factors restricting the yields of natural rubber. In this study, we isolated and identified strain Bacillus velezensis SF334, which exhibited significant antagonistic activity against both C. australisinense and C. siamense, the dominant species of Colletotrichum causing rubber tree leaf anthracnose in the Hainan province of China, from a pool of 223 bacterial strains. The cell suspensions of SF334 had a significant prevention effect for the leaf anthracnose of rubber trees, with an efficacy of 79.67% against C. siamense and 71.8% against C. australisinense. We demonstrated that SF334 can lead to the lysis of C. australisinense and C. siamense mycelia by causing mycelial expansion, resulting in mycelial rupture and subsequent death. B. velezensis SF334 also harbors some plant probiotic traits, such as secreting siderophore, protease, cellulase, pectinase, and the auxin of indole-3-acetic acid (IAA), and it has broad-spectrum antifungal activity against some important plant pathogenic fungi. The genome combined with comparative genomic analyses indicated that SF334 possesses most genes of the central metabolic and gene clusters of secondary metabolites in B. velezensis strains. To our knowledge, this is the first time a Bacillus velezensis strain has been reported as a promising biocontrol agent against the leaf anthracnose of rubber trees caused by C. siamense and C. australisinense. The results suggest that B. velezensis could be a potential candidate agent for the leaf anthracnose of rubber trees.

Physical-mechanical behavior of workable mortars with Perna perna mussel shell as fine aggregate

Cultivation of mussels stands as a significant economic activity in coastal regions Brazil. Often disregarded as waste, mussel shells (MS) possess properties that can be harnessed in the production of building materials. This study explores the utilization of large amounts of Perna perna MS as fine aggregates for the production of fluid mortars. Key parameters such as compressive strength, bulk density, water absorption and void ratio were evaluated. Specimens were prepared according to a full factorial design, with variations of MS content (%MS) (45 to 65 vol%) and water-to-cement (w/c) ratio (0.40 to 0.50). The resulting fluid mortars exhibited satisfactory strength, minimal segregation, and low void content with compactness at the aggregate-cement paste interface. The increase in %MS contributed to higher mortar bulk density but led to reduced void ratio, compressive strength, and workability. The incorporation of a superplasticizer (SP) significantly improved the matrix by enhancing the dispersion of cement particles, mitigating the adverse effects of reduced cementitious material, and enhancing strength. The influence of w/c on compressive strength was found to be 1.6 times greater than that for %MS, while its impact on void ratio was 0.5 times smaller. The full factorial model effectively predicted the mix design for MS-added mortars, yielding strengths ranging from 12 to 21 MPa and void ratios from 21 to 34%.

Discovery of an antitumor compound from xenorhabdus stockiae HN_xs01.

Xenorhabdus, known for its symbiotic relationship with Entomopathogenic nematodes (EPNs), belongs to the Enterobacteriaceae family. This dual-host symbiotic nematode exhibits pathogenic traits, rendering it a promising biocontrol agent against insects. Our prior investigations revealed that Xenorhabdus stockiae HN_xs01, isolated in our laboratory, demonstrates exceptional potential in halting bacterial growth and displaying anti-tumor activity. Subsequently, we separated and purified the supernatant of the HN_xs01 strain and obtained a new compound with significant inhibitory activity on tumor cells, which we named XNAE. Through LC-MS analysis, the mass-to-nucleus ratio of XNAE was determined to be 254.24. Our findings indicated that XNAE exerts a time- and dose-dependent inhibition on B16 and HeLa cells. After 24h, its IC50 for B16 and HeLa cells was 30.178µg/mL and 33.015µg/mL, respectively. Electron microscopy revealed conspicuous damage to subcellular structures, notably mitochondria and the cytoskeleton, resulting in a notable reduction in cell numbers among treated tumor cells. Interestingly, while XNAE exerted a more pronounced inhibitory effect on B16 cells compared to HeLa cells, it showed no discernible impact on HUVEC cells. Treatment of B16 cells with XNAE induced early apoptosis and led to cell cycle arrest in the G2 phase, as evidenced by flow cytometry analysis. The impressive capability of X. stockiae HN_xs01 in synthesizing bioactive secondary metabolites promises to significantly expand the reservoir of natural products. Further exploration to identify the bioactivity of these compounds holds the potential to shed light on their roles in bacteria-host interaction. Overall, these outcomes underscore the promising potential of XNAE as a bioactive compound for tumor treatment.

Novel sulfonamide-indolinone hybrids targeting mitochondrial respiration of breast cancer cells

Breast cancer (BC) still poses a threat worldwide which demands continuous efforts to present safer and efficacious treatment options via targeted therapy. Beside kinases’ aberrations as Aurora B kinase which controls cell division, BC adopts distinct metabolic profiles to meet its high energy demands. Accordingly, targeting both aurora B kinase and/or metabolic vulnerability presents a promising approach to tackle BC. Based on a previously reported indolinone-based Aurora B kinase inhibitor (III), and guided by structural modification and SAR investigation, we initially synthesized 11 sulfonamide-indolinone hybrids (5a-k), which showed differential antiproliferative activities against the NCI-60 cell line panel with BC cells displaying preferential sensitivity. Nonetheless, modest activity against Aurora B kinase (18–49% inhibition) was noted at 100 nM. Screening of a representative derivative (5d) against 17 kinases, which are overexpressed in BC, failed to show significant activity at 1 μM concentration, suggesting that kinase inhibitory activity only played a partial role in targeting BC. Bioinformatic analyses of genome-wide transcriptomics (RNA-sequencing), metabolomics, and CRISPR loss-of-function screens datasets suggested that indolinone-completely responsive BC cell lines (MCF7, MDA-MB-468, and T-47D) were more dependent on mitochondrial oxidative phosphorylation (OXPHOS) compared to partially responsive BC cell lines (MDA-MB-231, BT-549, and HS 578 T). An optimized derivative, TC11, obtained by molecular hybridization of 5d with sunitinib polar tail, manifested superior antiproliferative activity and was used for further investigations. Indeed, TC11 significantly reduced/impaired the mitochondrial respiration, as well as mitochondria-dependent ROS production of MCF7 cells. Furthermore, TC11 induced G0/G1 cell cycle arrest and apoptosis of MCF7 BC cells. Notably, anticancer doses of TC11 did not elicit cytotoxic effects on normal cardiomyoblasts and hepatocytes. Altogether, these findings emphasize the therapeutic potential of targeting the metabolic vulnerability of OXPHOS-dependent BC cells using TC11 and its related sulfonamide-indolinone hybrids. Further investigation is warranted to identify their precise/exact molecular target.

Third vaccine boosters and anti-S-IgG levels: A comparison of homologous and heterologous responses and poor immunogenicity in hepatocellular carcinoma.

The immune response of patients with chronic liver disease tends to be lower after receiving their second coronavirus disease 2019 (COVID-19) vaccine dose, but the effect of a third vaccine dose on their immune response is currently unknown. We recruited 722 patients without previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from three hospitals. The patients received homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA-1273 vaccines, respectively. Serum IgG spike antibody levels were measured at a mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 (visit 2) months after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity. In both visits, the patients who received the MMM booster had higher anti-S-IgG levels than those who received the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti-S-IgG levels than the control group (761.6 vs. 1498.2 BAU/mL; p = 0.019) at visit 1. The anti-S-IgG levels decreased significantly at visit 2. The patients with significant antibody activity had a lower rate of liver cirrhosis with decompensation (0.7% decompensation vs. 8.0% non-decompensation and 91.3% non-liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC vs. 3.7% non-active HCC and 94.7% non-HCC, p < 0.001). Receiving the MMM booster regimen (OR = 10.67, 95% CI 5.20-21.91, p < 0.001) increased the odds of having significant antibody activity compared with the AZAZBNT booster regimen. Patients with active HCC had a reduced immune response to the third COVID-19 vaccine booster. These findings underscore the importance of booster vaccinations, especially in immunocompromised patients, with superior efficacy observed with the homologous mRNA-1273 regimen.

Synergistic Anticancer Activity of Plumbagin and Xanthohumol Combination on Pancreatic Cancer Models.

Among diverse cancers, pancreatic cancer is one of the most aggressive types due to inadequate diagnostic options and treatments available. Therefore, there is a necessity to use combination chemotherapy options to overcome the chemoresistance of pancreatic cancer cells. Plumbagin and xanthohumol, natural compounds isolated from the Plumbaginaceae family and Humulus lupulus, respectively, have been used to treat various cancers. In this study, we investigated the anticancer effects of a combination of plumbagin and xanthohumol on pancreatic cancer models, as well as the underlying mechanism. We have screened in vitro numerous plant-derived extracts and compounds and tested in vivo the most effective combination, plumbagin and xanthohumol, using a transgenic model of pancreatic cancer KPC (KrasLSL.G12D/+; p53R172H/+; PdxCretg/+). A significant synergistic anticancer activity of plumbagin and xanthohumol combinations on different pancreatic cancer cell lines was found. The combination treatment of plumbagin and xanthohumol influences the levels of B-cell lymphoma (BCL2), which are known to be associated with apoptosis in both cell lysates and tissues. More importantly, the survival of a transgenic mouse model of pancreatic cancer KPC treated with a combination of plumbagin and xanthohumol was significantly increased, and the effect on BCL2 levels has been confirmed. These results provide a foundation for a potential new treatment for pancreatic cancer based on plumbagin and xanthohumol combinations.

Optimization of the Reaction between 5-O-Caffeoylquinic Acid (5-CQA) and Tryptophan—Isolation of the Product and Its Evaluation as a Food Dye

The food industry is seeking a stable, non-toxic red dye as a substitute for synthetic pigments. This can result from the reaction between 5-O-Caffeoylquinic acid (5-CQA) and tryptophan (TRP). This study explores the reaction kinetics under ultrasound conditions and investigates reaction parameters, such as pH, temperature, and reactants’ concentrations, to accelerate the reaction. At the end of the reaction, the solution was either spray-dried or acidified to isolate the pigment, which was evaluated for its potential as a food dye. Using ultrasound at 40 °C led to a significant acceleration of the reaction that was completed in 8.5 h, marking a 300% improvement compared to literature. The caffeic acid, and not the quinic acid, moiety of 5-CQA seems to be partly responsible for the formation of the red pigment. The pH had a profound impact on the reaction rate, with an optimal value of pH = 9.5. Increased TRP concentrations led to increased reaction rates, while higher 5-CQA concentrations led to significant deviations from redness (a* value). The pigment, lacking significant antimicrobial activity, exhibited remarkable thermal stability (pH 3–9), delaying food oxidation and color deterioration. The results indicate that the reaction can be significantly accelerated by ultrasound, which will be useful for the scale-up of the process and giving the produced pigment the potential for use as an alternative to artificial coloring.

Isolation of Endophytic Fungi from Adhatoda vasica and Assessing its Antibacterial Efficacy and Cytotoxic Impact on the A549 Cancer Cells

The current study investigated the anti-bacterial and anti-cancer properties of endophytic fungi obtained from medicinal plant Adhatoda vasica. We isolated and identified the endophytic fungi Humicola fuscoatra. by examining their morphological characteristics and microscopic structures. We then extracted their secondary metabolites using ethyl acetate. The ethyl acetate extracts of the fungus H. fuscoatra have shown promising effectiveness against human pathogens, including Klebsiella pneumoniae, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. A strain of H. fuscoatra exhibited significant antibacterial activity. In addition, we have assessed the effects of ethyl acetate extracts from the fungus H. fuscoatra on the growth of the human lung cancer cell line A549 in vitro assays. Using ethyl acetate extracts from the fungus H. fuscoatra effectively suppressed the growth, survival, migration, and invasion of cancer cells. In this paper we studied in detail the identification of isolated endophytic fungi H. fuscoatra from Adhatoda vasica and characterized its active metabolite compounds. The ethyl acetate-extracted secondary metabolites from the fungal culture supernatant were analyzed using gas chromatography and mass spectrometry, which detected the presence of Hexadecanoic Acid, Hexadecane, Heptadecane, Octadecane, Octadecanoic acid, phytochemicals. The results suggest that the endophytic fungus H. fuscoatra found in medicinal plants has the potential to produce bioactive compounds. They could also be used as a biocontrol agent against bacterial pathogens and for therapeutic purposes in the A549 lung cancer cell line.

Uncovering Potentially Therapeutic Phytochemicals, In silico Analysis, and Biological Assessment of South-Chinese Red Dragon Fruit (Hylocereus polyrhizus).

Red dragon fruit is gaining popularity globally due to its nutritional value and bioactive components. The study aimed to assess the phytochemical, nutritional composition, antioxidant, antibacterial, and cytotoxic properties of extracts from the South Chinese red dragon fruit peel, flesh, and seeds. Extract fractions with increasing polarity (ethyl acetate<acetone<ethanol<methanol) were prepared. Significant amounts of nutritional components (minerals, protein, sugars, vitamins, fatty acids) were found in all parts of the fruit. The ethanol (ET) and methanol (MT) fractions of all the extracts exhibited significant antioxidant activity, with EC50 values ranging from 3.25-8.30μg/mL. The flesh MT and ET extract fractions demonstrated substantial inhibitory effects, with MIC50 ranging 73.62-98.85μg/mL, against several multidrug-resistant bacteria. Cytotoxicity assays revealed no adverse effects of the crude extract fractions on human keratinocytes (HaCaT) cells (from adult human skin). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analyses unveiled a wide array of compounds with known and unknown antibacterial and antioxidant activities. Thereafter, pharmacological property screening and molecular docking were performed. The results identified four active compounds, baicalein, quercetin, morin, and isorhamnetin, which demonstrated strong binding affinity with the selected target proteins and complied with most of the pharmacological parameters. In conclusion, this study provides essential information on the key nutrients present in the peel, flesh, and seeds of the red dragon fruit from Southern-China. Furthermore, it highlights the potential of ET and MT fractions, which contain compounds with promising antibacterial properties.

Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143

Seven new indole-diterpenoids, penpaxilloids A–E (1–5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8–27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1–b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Utilizing Sentinel-2 Satellite Imagery for LULC and NDVI Change Dynamics for Gelephu, Bhutan

Gelephu, located in the Himalayan region, has undergone significant development activities due to its suitable topography and geographic location. This has led to rapid urbanization in recent years. Assessing land use land cover (LULC) dynamics and Normalized Difference Vegetation Index (NDVI) can provide important information about urbanization trends and changes in vegetation health, respectively. The use of Geographic Information Systems (GIS) and Remote Sensing (RS) techniques based on various satellite products offers a unique opportunity to analyze these changes at a local scale. Exploring Bhutan’s mandate to maintain 60% forest cover and analyzing LULC transitions and vegetation changes using Sentinel-2 satellite imagery at 10 m resolution can provide important insights into potential future impacts. To examine these, we first performed LULC mapping for Gelephu for 2016 and 2023 using a Random Forest (RF) classifier and identified LULC changes. Second, the study assessed the dynamics of vegetation change within the study area by analysing the NDVI for the same period. Furthermore, the study also characterized the resulting LULC change for Gelephu Thromde, a sub-administrative municipal entity, as a result of the notable intensity of the infrastructure development activities. The current study used a framework to collect Sentinel-2 satellite data, which was then used for pre-and post-processing to create LULC and NDVI maps. The classification model achieved high accuracy, with an area under the curve (AUC) of up to 0.89. The corresponding LULC and NDVI statistics were analysed to determine the current status of the LULC and vegetation indices, respectively. The LULC change analysis reveals urban growth of 5.65% and 15.05% for Gelephu and Gelephu Thromde, respectively. The NDVI assessment shows significant deterioration in vegetation health with a 75.11% loss of healthy vegetation in Gelephu between 2016 and 2023. The results serve as a basis for strategy adaption required to examine the environmental protection and sustainable development management, and the policy interventions to minimize and balance the ecosystem, taking into account urban landscape.

Evaluation of the anti-cancer efficacy of lipid nanoparticles containing siRNA against HPV16 E6/E7 combined with cisplatin in a xenograft model of cervical cancer.

To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.

Study on antimicrobial activity of sturgeon skin mucus polypeptides (Rational Design, Self-Assembly and Application)

Despite the favorable biocompatibility of natural antimicrobial peptides (AMPs), their scarcity limits their practical application. Through rational design, the activity of AMPs can be enhanced to expand their application. In this study, we selected a natural sturgeon epidermal mucus peptide, AP-16 (APATPAAPALLPLWLL), as the model molecule and studied its conformational regulation and antimicrobial activity through amino acid substitutions and N-terminal lipidation. The structural and morphological transitions of the peptide self-assemblies were investigated using circular dichroism and transmission electron microscopy. Following amino acid substitution, the conformation of AL-16 (AKATKAAKALLKLWLL) did not change. Following N-terminal alkylation, the C8-AL-16 and C12-AL-16 conformations changed from random coil to β-sheet or α-helix, and the self-assembly changed from nanofibers to nanospheres. AL-16, C8-AL-16, and C8-AL-16 presented significant antimicrobial activity against Pseudomonas and Shewanella at low concentrations. N-terminal alkylation effectively extended the shelf life of Litopenaeus vannamei. These results support the application of natural AMPs.

Bioactivity and Sublethal Effects of Ageratina adenophora (Asteraceae) on Bactrocera dorsalis (Diptera: Tephritidae)

Abstract Local fruit orchards have incurred heavy losses due to invasive insects, including the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), in Guizhou Province, China. In our efforts to manage this invasive pest, a laboratory study was conducted to evaluate the response of adult B. dorsalis to an extract of Ageratina adenophora (Spreng.) R.M. King &amp; H. Rob (Gunneridae: Asteraceae). We evaluated the contact toxicity and oviposition-deterrent activity of the extract on adult B. dorsalis, as well as the sublethal effects on survival and reproduction. We found that the A. adenophora extract has significant insecticidal activity, with the 24-h median lethal concentration (LC50) for adults being 26.014 mg/ml. The extract of A. adenophora also showed oviposition inhibition. A residual deterrent effect (28.16%) was evident up to 5 d after treatment. Exposure to the LC25 concentration of the A. adenophora extract caused significant differences in preoviposition and fecundity, decreased adult longevity in the F0 generation, and decreased egg and pupa survival in the F1 generation. The levels of carboxylesterase enzyme activity in adults treated with the extract were significantly lower than those in the untreated controls at 12 h and 24 h. This latter phenomenon could perhaps be an adaptive response to the extract that might reduce its toxic effects in B. dorsalis.

Unveiling the Anticancer Mechanism of Echinops davuricus: Isolation and Evaluation of AKR1B10 Inhibitors.

Five compounds (1-5), one long-chain fatty acid (1), two thiophenes (2 and 3), one alkaloid (4), and one phenyl ester (5), were isolated from the aerial part of Echinops davuricus. The structures of the products were established by performing detailed nuclear magnetic resonance (NMR) analysis, and the structure of compound 1 was determined via high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR. Compounds 1, 4, and 5 were isolated from Echinops davuricus for the first time. Based on network pharmacology methods, AKR1B10 was selected as a key anticancer target. Compounds 1 and 5 exhibited significant AKR1B10 inhibitory activities, with IC50 values of 156.0±1.00 and 146.2±1.50 nM, respectively, with epalrestat used as the positive control (81.09±0.61 nM). Additionally, the interactions between the active compounds and AKR1B10 were evaluated via molecular docking. Ultimately, the GO and KEGG enrichment analysis indicated that the key signaling pathways associated with the active compounds may be related to the PI3K-Akt, MAPK, apoptotic, cellular senescence, and TNF signaling pathways and the human diseases corresponding to the targets are cancer. Our study reveals for the first time the anticancer properties of Echinops davuricus and provides a comprehensive understanding of its application in traditional medicine.

Computational integration for antifungal 1,2,4-triazole inhibitors design: QSAR, molecular docking, molecular dynamics simulations, ADME/Tox, and retrosynthesis studies

Fungal infections are a growing public health problem worldwide. Despite the availability of several medicines, their efficacy is still constrained by fungal resistance. This research conducted the 2D/3D-QSAR analysis on twenty-nine triazole molecules previously evaluated for their antifungal activity. The HQSAR/B-H, CoMFA and CoMSIA models were built using twenty-three molecules in the training set. They show high Q2 values (0.646, 0.564 and 0.561, respectively) and important R2 values (0.764, 0.805 and 0.787, respectively). The predictive capacity of the established models was validated by external validation; they performed well. The contour maps derived from the HQSAR/B-H, CoMFA and CoMSIA models provide more detail to identify favorable and unfavorable groupings impacting the activity. Then, 4 proposed new triazole molecules with significant antifungal activity were suggested. In addition, the molecular docking results showed good binding energies and interactions of the proposed inhibitors in the active site of the receptor studied. The molecular dynamics and MM/PBSA methods confirmed and validated the molecular docking results. The new triazole molecules were evaluated for their oral bioavailability and toxicity using ADME/Tox properties. Finally, the retrosynthesis method created a synthetic pathway for the candidate inhibitor Z1.

EARTHQUAKE SWARMS AS EVIDENCE OF VOLCANO-TECTONIC PROCESSES OF THE SLOWEST SPREADING GAKKEL RIDGE IN THE ARCTIC

Based on the data from the Arctic regional seismic stations, the article presents the results of studying the swarm seismicity of the Gakkel Mid-Ocean Ridge, located in the Arctic Ocean. The active spreading processes of ultraslow ridges with spreading rates of less than 20 mm/yr, which include the Gakkel Ridge, are still poorly understood as compared to the MOR in the Atlantic and Pacific oceans, with spreading rates of more than 25 mm/yr. In 2012–2022, there were identified eight swarms: one within the western volcanic segment of the ridge, others – in the eastern volcanic segment. No earthquake swarms were recorded in the central amagmatic segment of the ridge; the recording therein covers primarily single earthquakes and aftershock sequences. Spatially identified swarms are confied to some volcanic centers revealed earlier from the geological and geophysical data during complex expeditions. The ridge segment at coordinates ∼85…∼93° E is characterized by the most intense manifestations of volcanic processes. The spatial distribution of swarms may also indicate potential presence of volcanic structures that have not yet been identified from the geological, geophysical and geomorphological data. In the temporal domain, there can be preliminarily distinguished a 5-year swarm activation cycle, which, however, requires additional verification over a longer time interval. The swarm seismicity of the slowest spreading Gakkel Ridge cannot be described by a simple model of volcanism and magma intrusion into a symmetrical rift; it is rather a result of a complex interaction between diking and faulting with magma transport along the faults with potentially significant seismic activities. There can probably be suggested a regular combination of the processes of volcanic activation and seismotectonic destruction, which is especially pronounced in the locations of transverse faults. The results described in this article expand our understanding of the manifestation of volcano-tectonic processes occurring within the slowest speading Gakkel Mid-Ocean Ridge.