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The mechanical transplanting of over aged seedlings (OAS) of rice poses several challenges, including seedling mortality and a significant delay in the greening period, which severely restrict yield. The causes of these issues remain unknown. Through theoretical analysis, mechanical tests, bench tests, and growth experiments were conducted to explore the reasons for seedling mortality and the significant delay in the greening period from the perspectives of seedlings, transplanting machines, and post-transplant growth. The results indicated that OAS transplanting causes combined root and stem injuries. For 40-day-old seedlings, the energy required for stem elasto-plastic deformation ranged from 1.37 to 7.19 N mm. Within this deformation range, the stem sustains internal injury but is not considered as injured seedling. The main factors influencing stem injury were the stem's major axis length and elastic modulus, whereas root injury was primarily affected by root diameter. Root and stem injuries significantly inhibited seedling growth, as demonstrated by significant structural changes in the stem 3 days post-transplantation, along with partial seedling mortality. New roots emerged only 9 days post-transplantation, and the heart leaf growth rate and SPAD value at 12 days were only 49% and 77% those of uninjured transplanted seedlings, respectively. Based on these findings, it was concluded that the seedling mortality and significant delay in the greening period observed in OAS transplantation are due to inhibited nutrient absorption and transport, caused by stem elasto-plastic deformation and weakened root vitality. These results may serve as a basis for improving transplanting machine design and optimising rice cultivation practices. • Transplant injuries in over aged seedlings (OAS) stem from root and stem injury. • Elasto-plastic stem deformation causes internal injury, which is difficult to detect. • Stem major axis length and elastic modulus are key factors influencing stem injury. • Root diameter is the key factor influencing root injury. • Stem deformation and weak root vitality cause transplant mortality in OAS. [ABSTRACT FROM AUTHOR]

Heavy metal (HM) pollution is a threat to ecosystem balance and food security. Cadmium (Cd) is particularly hazardous to humans and accumulates in agricultural soils due to industrial activities and natural sources. Even if Cd adversely affects plant growth and vital functions, few studies have investigated its effects on durum wheat, an important staple crop. Therefore, this study aimed to understand the morphological alteration induced by Cd during the germination phase of durum wheat (Triticum durum L.) seeds to evaluate the tolerance of three cultivars (Karim, Nachit, and Louiza) to Cd stress. The experiment involved germinating wheat seeds in nine concentrations of Cd (0, 0.125, 0.25, 0.375, 0.5, 0.675, 0.75, 0.875, 1 g/L) where germination rate, biomass production, shoot and root length, vigor index, growth inhibition, and tolerance indices were assessed. The different treatments were arranged using a completely randomized design. The results showed that Cd negatively affected wheat germination. The minimum effect of Cd on germination percentage was recorded at 0.125 g/L of Cd for Nachit and Louiza, and at 0.25 g/L of Cd for Karim, while the maximum inhibition was noticed starting at 0.625, 0.875, and 0.625 g/L of Cd for Karim, Nachit, and Louiza, respectively. The negative effect of Cd on shoot and root length was more pronounced during seedling development than during germination. Cd had a greater effect on root length than on shoot length, with Louiza being the most affected cultivar. However, Cd had no significant effect on fresh and dry weight. Our research reveals that the presence of Cd pollution has a substantial impact on the initial growth stages of durum wheat with differential responses of the studied cultivars when exposed to Cd stress. These alterations in seedlings' performances strongly emphasize the importance of evaluating Cd's effects on plant development and fitness. This underscores the significance of this aspect not only for ensuring the health of our crops but also for safeguarding food quality in the presence of HM pollution. [ABSTRACT FROM AUTHOR]

Human babesiosis is a malaria‐like, tick‐borne infectious disease with a global distribution. Babesiosis is caused by intraerythrocytic, apicomplexan parasites of the genus Babesia. In the United States, human babesiosis is caused by Babesia microti and Babesia duncani. Current treatment for babesiosis includes either the combination of atovaquone and azithromycin or the combination of clindamycin and quinine. However, the side effects of these agents and the resistance posed by these parasites call for alternative approaches for treating human babesiosis. Proteases play several roles in the context of parasitic lifestyle and regulate basic biological processes including cell death, cell progression, and cell migration. Using the SYBR Green‐1 assay, we screened a protease inhibitor library that consisted of 160 compounds against B. duncani in vitro and identified 13 preliminary hits. Dose response assays of hit compounds against B. duncani and B. microti under in vitro conditions identified five effective inhibitors against parasite growth. Of these compounds, we chose ixazomib, a proteasome inhibitor as a potential drug for animal studies based on its lower IC50 and a higher therapeutic index in comparison with other compounds. Our results suggest that Babesia proteasome may be an important drug target and that developing this class of drugs may be important to combat human babesiosis. [ABSTRACT FROM AUTHOR]

Black root rot (BRR) and Verticillium wilt of cotton are caused by soilborne Berkeleyomyces rouxiae and Verticillium dahliae, respectively, and can individually cause yield loss of a 10–50% in New South Wales (NSW). Both diseases were first detected in a northern valley of NSW but are now present across the state. 'Come Clean Go Clean' is a widely practiced biosecurity measure used to minimize the risk of further introducing the pathogens from one field to another by restricting the movement of soil-contaminated farm equipment and machinery. We rely on cleaning agents to effectively wash down and decontaminate the equipment and machinery. In this study, we examined 12 locally available, commercial disinfectants for their efficacy against B. rouxiae and V. dahliae reproductive structures with and without soil contamination of 10% (w/v). We found a significant interaction between pathogens, disinfectants, and soil amendment (p < 0.01). The germination of B. rouxiae chlamydospores and endoconidia in both the presence and absence of soil contamination was completely suppressed even after a short 10 sec exposure to 70% ethanol and 25% bleach. Both 70% ethanol and bleach were highly lethal at 10 sec exposures in similar assays against V. dahliae microsclerotia and conidia. Some other commercial products were able to reduce the germination rate significantly but did not completely kill microsclerotia and conidia even after 30 min of exposure. The lethal effect against B. rouxiae and V. dahliae warrants further exploration of both 70% ethanol and bleach to improve their field applications. Additionally, the efficacy of most tested commercial disinfectants was time-dependent; however, this is not recommended on the labels for their effectiveness. This study provides an additional integrated disease management option aiming to limit the spread of the pathogens. [ABSTRACT FROM AUTHOR]

Heavy metal Cd2+ can easily be accumulated by fungi, causing significant stress, with the fungal cell membrane being one of the primary targets. However, the understanding of the mechanisms behind this stress remains limited. This study investigated the changes in membrane lipid molecules of Pleurotus ostreatus mycelia under Cd2+ stress and the antagonistic effect of Ca2+ on this stress. Cd2+ in the growth media significantly inhibited mycelial growth, with increasing intensity at higher concentrations. The addition of Ca2+ mitigated this Cd2+-induced growth inhibition. Lipidomic analysis showed that Cd2+ reduced membrane lipid content and altered lipid composition, while Ca2+ counteracted these changes. The effects of both Cd2+ and Ca2+ on lipids are dose dependent and phosphatidylethanolamine appeared most affected. Cd2+ also caused a phosphatidylcholine/phosphatidylethanolamine ratio increase at high concentrations, but Ca2+ helped maintain normal levels. The acyl chain length and unsaturation of lipids remained unaffected, suggesting Cd2+ doesn't alter acyl chain structure of lipids. These findings suggest that Cd2+ may affect the growth of mycelia by inhibiting the synthesis of membrane lipids, particular the synthesis of phosphatidylethanolamine, providing novel insights into the mechanisms of Cd2+ stress in fungi and the role of Ca2+ in mitigating the stress. • Cd2+ in growth media inhibits mycelial growth, with stronger effects at higher concentrations. • Ca2+ mitigates Cd2+-induced growth inhibition in mycelium in a dose-dependent manner. • Cd2+ reduces membrane lipids and alters lipid composition, while Ca2+ counteracts the changes. • Phosphatidylethanolamine is most affected, the acyl chains of eight classes remain unaffected. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a multidrug-resistant pathogen known for chronic infections, mainly due to biofilm formation. This study aimed to explore the potential repurposing of 5-fluorouracil (5-FU), an anticancer drug, to treat P. aeruginosa infections. Firstly, we investigated the inhibitory effects of 5-FU on bacterial growth using the microdilution method. Secondly, the impact of 5-FU on biofilm formation and disassembly was assessed via biofilm biomass measurements with the crystal violet staining method and confocal microscopy analyses. Lastly, the potential synergy between 5-FU and the antibiotics gentamicin and meropenem was evaluated using a checkerboard assay. Results revealed that 5-FU inhibited bacterial growth in a dose-dependent manner, with 100% inhibition observed at concentrations of 25 µg/mL and higher. Also, 70% and 100% reductions in biofilm biomass were demonstrated at concentrations of 12 and 100 µg/mL, respectively. Controversy, these higher concentrations unexpectedly increased biofilm biomass in pre-formed biofilms. Synergistic interactions were observed between 5-FU and gentamicin in both growth inhibition (FICI 0.31) and biofilm inhibition (ZIP 14.1), while no synergy was found with meropenem. These findings highlight the potential of 5-FU as an adjunctive therapy for P. aeruginosa infections, especially in combination with gentamicin. However, further research is required to address 5-FU limitations against mature biofilms. [ABSTRACT FROM AUTHOR]

Pharmaceuticals can directly inhibit the growth of gut bacteria, but the degree to which such interactions manifest in complex community settings is an open question. Here, we compared the effects of 30 drugs on a 32-species synthetic community with their effects on each community member in isolation. While most individual drug-species interactions remained the same in the community context, communal behaviors emerged in 26% of all tested cases. Cross-protection during which drug-sensitive species were protected in community was 6 times more frequent than cross-sensitization, the converse phenomenon. Cross-protection decreased and cross-sensitization increased at higher drug concentrations, suggesting that the resilience of microbial communities can collapse when perturbations get stronger. By metabolically profiling drug-treated communities, we showed that both drug biotransformation and bioaccumulation contribute mechanistically to communal protection. As a proof of principle, we molecularly dissected a prominent case: species expressing specific nitroreductases degraded niclosamide, thereby protecting both themselves and sensitive community members. [Display omitted] • Bacteria can be protected from and sensitized to drugs in a community context • Cross-protection and community resilience dissipate at high drug concentrations • Drug biotransformation and bioaccumulation can partially explain communal protection • Enzyme specificity and expression dictate detoxification of nitroaromatic drugs A comparison of the effects of pharmaceuticals on different gut bacterial species when grown alone or as part of a community shows that complex microbial communities can protect, and less frequently sensitize, community members to the treatment. Both drug biotransformation and bioaccumulation are key to community protection, which can be overwhelmed at high drug concentrations. [ABSTRACT FROM AUTHOR]

Aims: Due to the perpetual increase in antifungal resistance, the significance of unconventional approaches, such as electric and magnetic fields to inhibit fungal growth has been accentuated. The present study focuses on the potential fungicidal effects of fluconazole electronically-activated physiological saline against Candida guilliermondii BDU-217. Methodology and results: In vitro transfer of information from fluconazole to the physiological saline solution using a bioresonance therapy (BRT) was carried out. Three different forms of fluconazole, i.e., capsule, powder and solution were used. Fluconazole at a 150 µg/mL concentration inhibited fungal growth by 84%. Electronically activated physiological saline by fluconazole capsule, powder and solution inhibited the growth of test culture by 40%, 52% and 60%, respectively, compared with negative control (6%). Conclusion, significance and impact of study: The research findings suggest that the fluconazole solution was the most effective antifungal agent. It showed the maximum suppression of the growth of C. guilliermondii BDU-217 compared to the powder and capsule form. Thus, fluconazole electronically activated physiological saline has a potential antifungal spectrum. [ABSTRACT FROM AUTHOR]

The application of synthetic fungicides has resulted in environmental pollution and adverse effects on non-target species. To reduce the use of agrochemicals, crop disease management requires microbial biological control agents. Bacillus-related genera produce secondary metabolites to control fungal pathogens. Bacillus velezensis GYUN-1190, isolated from soil, showed antagonistic activity against Colletotrichum fructicola, the apple anthracnose pathogen. Volatile organic compounds and culture filtrate (CF) from GYUN-1190 inhibited C. fructicola growth in vitro, by 80.9% and 30.25%, respectively. The CF of GYUN-1190 inhibited pathogen spore germination more than cell suspensions at 108 cfu/ml. Furthermore, GYUN-1190 CF is effective in inhibiting C. fructicola mycelial growth in vitro, and it suppresses apple fruit bitter rot more effectively than GYUN-1190 cell suspensions and pyraclostrobin in planta. The mycelial growth of C. fructicola was completely inhibited 48 h after immersion into the CF, in compared with positive controls and GYUN-1190 cell suspensions. The genetic mechanism underlying the biocontrol features of GYUN-1190 was defined using its whole-genome sequence, which was closely compared to similar strains. It consisted of 4,240,653 bp with 45.9% GC content, with 4,142 coding sequences, 87 tRNA, and 28 rRNA genes. The genomic investigation found 14 putative secondary metabolite biosynthetic gene clusters. The investigation suggests that B. velezensis GYUN-1190 might be more effective than chemical fungicides and could address its potential as a biological control agent.

Abstract Endophytic fungal-based biopesticides are sustainable and ecologically-friendly biocontrol agents of several pests and diseases. However, their potential in managing tomato fusarium wilt disease (FWD) remains unexploited. This study therefore evaluated effectiveness of nine fungal isolates against tomato fusarium wilt pathogen, Fusarium oxysporum f. sp. lycopersici (FOL) in vitro using dual culture and co-culture assays. The efficacy of three potent endophytes that inhibited the pathogen in vitro was assessed against FWD incidence, severity, and ability to enhance growth and yield of tomatoes in planta. The ability of endophytically-colonized tomato (Solanum lycopersicum L.) plants to systemically defend themselves upon exposure to FOL were also assessed through defence genes expression using qPCR. In vitro assays showed that endophytes inhibited and suppressed FOL mycelial growth better than entomopathogenic fungi (EPF). Endophytes Trichoderma asperellum M2RT4, Hypocrea lixii F3ST1, Trichoderma harzianum KF2R41, and Trichoderma atroviride ICIPE 710 had the highest (68.84–99.61%) suppression and FOL radial growth inhibition rates compared to EPF which exhibited lowest (27.05–40.63%) inhibition rates. Endophytes T. asperellum M2RT4, H. lixii F3ST1 and T. harzianum KF2R41 colonized all tomato plant parts. During the in planta experiment, endophytically-colonized and FOL-infected tomato plants showed significant reduction of FWD incidence and severity compared to non-inoculated plants. In addition, these endophytes contributed to improved growth promotion parameters and yield. Moreover, there was significantly higher expression of tomato defence genes in T. asperellum M2RT4 colonized than in un-inoculated tomato plants. These findings demonstrated that H. lixii F3ST1 and T. asperellum M2RT4 are effective biocontrol agents against FWD and could sustainably mitigate tomato yield losses associated with fusarium wilt.

Triclosan (TCS), an emerging pollutant, is a notable contributor to adverse impacts on aquatic organisms due to its widespread use during COVID-19 and hydrophobic properties. There is extensive documented literature on TCS toxicity in commercially important fish species; however, studies on aquatic plants remain limited. In this prelude, the present study aims to evaluate the effect of TCS on Lemna minor, a commercially important aquatic plant species for 7 days. The results showed dose-dependent significant alterations in growth, pigments and stress enzymes of L. minor at varied concentrations of TCS (1 to 8 mg L−1). Median inhibitory concentration (IC50) was found to be 4.813 mg L−1. Total chlorophyll and carotenoid levels decreased 73.11 and 81.83%, respectively after 7 days of TCS exposure. A significant increase in catalase and superoxide dismutase activity was observed in TCS exposed groups as compared to the control. Bioconcentration factor was found to be in the range of 5.855 to 37.129 signifying TCS ability to accumulate and transfer through the food chain. Scanning electron microscopy (SEM) analysis showed deformation in the cell surface and alteration of stroma morphology of TCS exposed groups. Furthermore, the Fourier transform infrared spectroscopy (FTIR) study also revealed that higher concentrations of TCS could cause alteration in the functional groups in the plant. This study demonstrates that TCS negatively impacts the growth and metabolism of primary producers, offering crucial insights into its interactions with aquatic plants and establishing baseline information essential for crafting effective mitigation strategies for TCS contamination in aquatic environments. [ABSTRACT FROM AUTHOR]

The current treatment of glioma is facing drug resistance, which limits the efficacy of traditional chemotherapy drugs. This study aims to explore the potential mechanisms of the trifluoromethylquinazoline compound (KZL204) against glioma. Through the Cell Counting Kit-8 (CCK- 8) assay, we found that KZL204 significantly inhibits the growth of drug-resistant cancer cells, with a 48-hour half-maximal inhibitory concentration (IC50) of 3.63±0.38 µmol/L, which is significantly better than the positive control drug temozolomide (TMZ) (IC50 value of 81.67±5. 49 µmol/L). Additionally, flow cytometry analysis showed that KZL204 treatment significantly increased the apoptosis rate of drug-resistant tumor cells and arrested the cell cycle at the G2/M phase. At the same time, the Transwell assay confirmed the inhibitory effect of KZL204 on the migration and invasion of drug-resistant cancer cells. Transcriptome analysis revealed 2 435 differentially expressed genes in drug-resistant cancer cells treated with KZL204, of which 1 320 were upregulated, and 1 115 were downregulated. KEGG and GO enrichment analysis showed that these differential genes were significantly enriched in apoptosis-related signaling pathways. Further bioinformatics prediction and Venn diagram analysis identified 35 potential core targets, with the PI3K-AKT signaling pathway being the most significant among the differentially expressed genes. Quantitative real-time PCR (RT-qPCR) experiments confirmed the downregulating effects of KZL204 on genes such as CREB3L1, CSF1, CXCL5, BCL3, and the upregulating effects on genes like FOS, LTA, PTGS2, MAP2K3. Immunoblotting experiments at the protein level also confirmed the impact of KZL204 on the expression of apoptotic proteins, including the upregulation of Bax, cleaved Caspase-3 protein, and the downregulation ofAKT, Bcl-2, Caspase-3, and Caspase-8 protein expression. In summary, KZL204 significantly inhibits the growth and metastasis of drug-resistant glioblastoma and induces apoptosis and cell cycle arrest by regulating the PI3K-AKT and apoptosis-related signaling pathways, demonstrating its potential as a candidate drug against drug-resistant glioma. [ABSTRACT FROM AUTHOR]

Shigella flexneri is a gram-negative bacterium responsible for shigellosis and bacterial dysentery. Despite using various synthetic antimicrobial agents and antibiotics, their efficacy is limited, prompting concerns over antibiotic resistance and associated health risks. This study investigated eugenol, a polyphenol with inherent antioxidant and antibacterial properties, as a potential alternative treatment. We aimed to evaluate eugenol’s antibacterial effects and mechanisms of action against S. flexneri and its impact on biofilm formation. We observed significant growth suppression of S. flexneri with eugenol concentrations of 8–10 mM (98.29%). Quantitative analysis using the Crystal Violet assay demonstrated a marked reduction in biofilm formation at 10 mM (97.01 %). Assessment of Cell Viability and morphology via Fluorescence-Activated Cell Sorting and Scanning Electron Microscopy confirmed these findings. Additionally, qPCR analysis revealed the downregulation of key genes responsible for adhesion (yebL), quorum sensing (rcsC, sdiA), and EPS production (s0482) associated with bacterial growth and biofilm formation. The present study suggests eugenol could offer a promising alternative to conventional antibiotics for treating shigellosis caused by S. flexneri. [ABSTRACT FROM AUTHOR]

The increasing intrusion of weed species into alpine regions is an alarming threat to native floras because their strong and deep root systems cause a scarcity of nutrients to native alpine plant species. Considering the sensitive nature of alpine ecosystems, integrated weed management may be a means of preventing invasive species from going out of control. The present study investigated the allelopathic effect of Elsholtzia strobilifera on the germination and growth characteristics of Himalayan knotweed (Koenigia polystachya, syn. Polygonum polystachyum) under both field and laboratory conditions. The germination of seeds under laboratory conditions was studied by using different dilutions of hydrosol and aqueous extracts derived from E. strobilifera. In our field study, seedlings of K. polystachya were planted together with E. strobilifera in their natural habitat at a nursery. The study indicates that the seed germination and morphological parameters of seedlings were significantly inhibited by different dilutions of hydrosol and extract (reduction by 83–96% and 62–73%, respectively). In field conditions, significant inhibition in the morphological characteristics of K. polystachya was observed when grown in association with E. strobilifera. The results reveal that E. strobilifera has a significant allelopathic effect on K. polystachya. Based on the results of the present study, it can be concluded that growing plants of E. strobilifera around K. polystachya may be a novel approach to curbing the spread of the latter and suppressing the population of this species in ecologically sensitive alpine or other endangered areas. [ABSTRACT FROM AUTHOR]

Using a pathogenic fungus and selected endophytic fungi of the ash tree, we propose a modified model of fungal dual cultures that allows us to obtain two new parameters particularly useful in the search for fungal pathogen control agents. The first of these, called the vitality parameter, is applicable to the study of both biotic and abiotic factors affecting fungal growth. It is measured as the ratio of fungal growth radius in the direction of a studied factor to the growth radius in the opposite direction. The second parameter, called the inhibition parameter, relates to biofactors and is the ratio of the vitality parameters of the two tested fungi in dual cultures. This parameter combines the information on the growth of both dual culture components, for the first time, as a one value. In order to correctly determine the values of both parameters, a required inoculation configuration in dual cultures and a method for calibrating the duration of such cultures have been developed. All this together creates a new tool for a more sophisticated look at the use of dual cultures in the search for means to control fungal pathogens, including those that threaten the stability of forest ecosystems. [ABSTRACT FROM AUTHOR]

This study investigates the inhibitory and hormetic effects of Myriophyllum spicatum extract on Microcystis aeruginosa in a controlled, continuous culture environment. To address the global challenge posed by harmful algal blooms, we used a range of extract concentrations to delineate the growth response patterns. At very low concentrations (6.25 and 12.5 mg/L), the addition of M. spicatum extract shows no discernible reduction in M. aeruginosa cell density or growth rate; instead, a slight increase is observed during exposure, suggesting a hormetic effect. However, at higher concentrations (75 and 100 mg/L), there is a drastic reduction of more than 50% in cell density and growth rate at 75 mg/L, with complete inhibition at 100 mg/L, leading to pronounced oxidative stress, damage to antioxidant defense systems, and increased cell mortality. Increased levels of malondialdehyde, catalase, and superoxide dismutase activities indicate the involvement of these enzymes in combating oxidative stress. Furthermore, intracellular and extracellular microcystins were significantly decreased at higher extract concentrations (50, 75, and 100 mg/L) in a dose-dependent manner. Our results indicate a dose-dependent response and provide insight into the potential application of natural water treatment solutions. Implications for ecological management and future research directions are discussed. [ABSTRACT FROM AUTHOR]

The emergence of superhydrophobic antibacterial materials represents a promising approach to maintaining surface cleanliness and hygiene by effectively preventing bacterial adhesion. This research outlines the synthesis of a superhydrophobic coating with anti-adhesion and bacteriostatic properties, utilizing silica nanoparticles (SiO2 NPs) modified with 1H,1H,2H,2H-Perfluorodecyltriethoxysilane (PFDTES). Transmission electron microscopy (TEM), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy were conducted to analyze the coating's morphology and surface characteristics. The coating was applied to glass substrates using the spray coating method, and the number of layers was varied to evaluate its antibacterial and bacteriostatic properties. These properties were measured using turbidimetry and inhibition halo techniques. Additionally, the durability of the coatings was assessed by exposing them to outdoor conditions for 35 days. This study aimed to evaluate the antibacterial and bacteriostatic capacities of the superhydrophobic coating, along with its resistance to outdoor weathering. The results indicate that a superhydrophobic coating with a contact angle ≥ 150° and a sliding angle ≤ 10° was successfully synthesized using SiO2 NPs smaller than 10 nm, modified with PFDTES. The coating demonstrated an ability to inhibit bacterial growth by preventing the adhesion of bacteria such as Escherichia coli and Staphylococcus aureus. Furthermore, the number of coating layers significantly influenced its bacteriostatic efficacy. The coating also exhibited strong durability under outdoor conditions. These findings highlight the potential application of superhydrophobic coatings for the prevention of bacterial adhesion and growth in environments where such contamination poses risks. [ABSTRACT FROM AUTHOR]

• Janus kinase 1 (JAK1) is highly expressed in colorectal cancer (CRC). • Several natural compounds possess significant anticancer properties. • Methyl betulate, EGCG & Eriocalyxin B were found as potential JAK1 inhibitors. • Compounds are also cytotoxic and have the potential to induce apoptosis in CRC. Colorectal cancer (CRC) has become a global threat worldwide with constantly increasing incidence and mortality rates every year, especially in the US and China. Janus kinase (JAK) is an intracellular non-receptor tyrosine that mediates the signal transducer and activator of transcription (STAT) which orchestrates cytokine signalling, oncogene expression, and modulation of transcription factors. Targeting JAK holds promise as a therapeutic strategy for CRC. This present study focused on natural products, due to their renowned for their diverse pharmacological properties including anticancer, antimicrobial, anti-proliferative, and antioxidant effects. Employing a range of bioinformatics analyses such as molecular docking, drug-likeness evaluation, ADME profiling, toxicity assessment, in silico cytotoxicity prediction, and molecular target identification, and in vitro assays such as cytotoxicity assay & ROS induction assay were performed to investigate the potency of the natural compounds. Among the screened compounds, Methyl betulate (L1), Epigallocatechin-3-gallate (EGCG) (L2), and Eriocalyxin B (L3) exhibited stronger binding affinities than the standard Golidocitinib (AZD4205). These compounds not only met Lipinski's criteria for drug-likeness and displayed favourable ADME properties but also demonstrated reduced toxicity profiles and exhibited promising activity against various kinases. Furthermore, molecular dynamics simulations revealed the stability of these compounds with JAK1. Notably, they also exhibited potent cytotoxicity and induced apoptosis in SW480 and HT29 colon adenocarcinoma cells. Consequently, the findings suggest that these three compounds hold potential as potent JAK1 inhibitors, warranting further investigation in future in vivo studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethanol has been reported as a supplementary substrate for microalgae cultivation, however, information about its effect on the morphology, growth and desired metabolites accumulation of Chlorella sorokiniana is limited. To bridge this gap, the effects of exogenous ethanol on C. sorokiniana was screened by providing 0.00, 0.0025, 0.025, 0.1 and 1% (v/v) ethanol. Results showed ethanol caused multifaceted effects. 0.0025% and 0.025% ethanol caused a small increase in cell volume, growth and photosystem II (PSII) function. In contrast, cell volume conspicuously increased and was up to 2.5-fold (63.5 µm3) and 3.6-fold (91.3 µm3) higher in the 0.1% and 1% ethanol treatment groups, respectively, compared with the control (25.1 µm3). 1% ethanol conspicuously reduced chlorophyll concentration, inhibited growth, damaged the photosynthetic apparatus and decreased PSII electron transport. Carbohydrate and lipid accumulation increased in the 0.1% (112.6±7.8 µg mL-1) and 1% (217.87±31.6 µg mL-1) ethanol by 1.6 and 50-fold, compared to the control (70.5±2.2 µg mL-1and 7.2±2.6 µg mL-1). The cell permeability also increased coinciding with the pronounced increse of reactive oxygen species, particularly in the 0.1 and 1% ethanol treatment groups. There were giant palmloid-like cells containing unequal and numerous daughter cells in the higher ethanol treatments, indicating the cell cycle has been altered through suppression of mother cell cytokinesis, which could serve as a protective function to overcome ethanol stress. The results suggest that ethanol has the potential to be used as an impotent substrate to induce lipid and carbohydrate accumulation in C. sorokiniana cultivation. [ABSTRACT FROM AUTHOR]

The growing challenge of antibiotic resistance necessitates novel approaches for combating bacterial infections. This study explores the distinctive synergy between chlorhexidine, an antiseptic and disinfectant agent, and azithromycin, a macrolide antibiotic, in their impact on bacterial growth and virulence factors using Escherichia coli strain Crooks (ATCC 8739) as a model. Our findings reveal that the chlorhexidine and azithromycin combination demonstrates enhanced anti-bacterial effects compared to individual treatments. Intriguingly, the combination induced oxidative stress, decreased flagellin expression, impaired bacterial motility, and enhanced bacterial autoaggregation. Notably, the combined treatment also demonstrated a substantial reduction in bacterial adherence to colon epithelial cells and downregulated NF-κB in the epithelial cells. In conclusion, these results shed light on the potential of the chlorhexidine and azithromycin synergy as a compelling strategy to address the rising challenge of antibiotic resistance and may pave the way for innovative therapeutic interventions in tackling bacterial infections. [ABSTRACT FROM AUTHOR]

Pathogenic bacteria employ virulence factors (VF) to establish infection and cause disease in their host. Yeasts, Saccharomyces cerevisiae and Saccharomyces pombe, are useful model organisms to study the functions of bacterial VFs and their interaction with targeted cellular processes because yeast processes and organelle structures are highly conserved and similar to higher eukaryotes. In this review, we describe the principles and applications of the yeast model for the identification and functional characterisation of bacterial VFs to investigate bacterial pathogenesis. The growth inhibition phenotype caused by the heterologous expression of bacterial VFs in yeast is commonly used to identify candidate VFs. Then, subcellular localisation patterns of bacterial VFs can provide further clues about their target molecules and functions during infection. Yeast knockout and overexpression libraries are also used to investigate VF interactions with conserved eukaryotic cell structures (e.g., cytoskeleton and plasma membrane), and cellular processes (e.g., vesicle trafficking, signalling pathways, and programmed cell death). In addition, the yeast growth inhibition phenotype is also useful for screening new drug leads that target and inhibit bacterial VFs. This review provides an updated overview of new tools, principles and applications to study bacterial VFs in yeast. [ABSTRACT FROM AUTHOR]

In the present study, we identified and characterized two defensin‐like peptides in an antifungal fraction obtained from Capsicum chinense pepper fruits and inhibited the growth of Colletotrichum scovillei, which causes anthracnose. AMPs were extracted from the pericarp of C. chinense peppers and subjected to ion exchange, molecular exclusion, and reversed‐phase in a high‐performance liquid chromatography system. We investigated the endogenous increase in reactive oxygen species (ROS), the loss of mitochondrial functioning, and the ultrastructure of hyphae. The peptides obtained from the G3 fraction through molecular exclusion chromatography were subsequently fractionated using reverse‐phase chromatography, resulting in the isolation of fractions F1, F2, F3, F4, and F5. The F1‐Fraction suppressed C. scovillei growth by 90, 70.4, and 44% at 100, 50, and 25 μg mL−1, respectively. At 24 h, the IC50 and minimum inhibitory concentration were 21.5 μg mL−1 and 200 μg mL−1, respectively. We found an increase in ROS, which may have resulted in an oxidative burst, loss of mitochondrial functioning, and cytoplasm retraction, as well as an increase in autophagic vacuoles. MS/MS analysis of the F1‐Fraction indicated the presence of two defensin‐like proteins, and we were able to identify the expression of three defensin sequences in our C. chinense fruit extract. The F1‐Fraction was also found to inhibit the activity of insect α‐amylases. In summary, the F1‐Fraction of C. chinense exhibits antifungal activity against a major pepper pathogen that causes anthracnose. These defensin‐like compounds are promising prospects for further research into antifungal and insecticide biotechnology applications. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The widespread presence of polycyclic aromatic hydrocarbons (PAHs) and toxic heavy metals in soils is having harmful effects on food crops and the environment. However, the defense mechanisms and capacity of plants to counteract these substances have not been comprehensively explored, necessitating a systematic categorization of their inhibitory effects. Accordingly, an experimental investigation was conducted to examine the growth and physiological response of maize (Zea mays L.) to different concentrations and combinations of pyrene, copper (Cu), and cadmium (Cd), with an indicator developed to assess the joint stress. The results showed that 57-day culture with contaminations significantly inhibited the plant biomass via causing root cell necrosis, inducing lipid peroxidation, and damaging photosynthesis. Cd (50-100 mg/kg) induced stronger inhibition than Cu (800-1000 mg/kg) under both single and joint stress, and their co-existence further aggravated the adverse effects and generated synergetic inhibition. Although the presence of pyrene at a low concentration (5-50 mg/kg) can somewhat diminish the metal stress, the elevated pollutant concentrations (400-750 mg/kg pyrene, 50-100 mg/kg Cd, and 800-1000 mg/kg Cu) switched the antagonistic effect to additive inhibition on maize growth. A satisfactory tolerance of a low-level pyrene and/or metal stress was determined, associated with a relative stability of chlorophyll-a (Chl-a) content and antioxidant enzymes activity. Nevertheless, the photosynthesis and antioxidant system were significantly damaged with increasing contaminant concentrations, resulting in chlorosis and biomass reduction. These findings could provide valuable knowledge for ensuring crop yield and food quality as well as implementing soil phytoremediation.

Fungal diseases pose a major threat to global agriculture, leading to reduced crop yields, health issues and significant economic impact. Application of nanoparticles are being explored in agriculture because of its ecofriendly as well as enhanced antimicrobial properties. In this study, using an aqueous extract of air-dried tea leaves, zinc oxide nanoparticles (ZnO NPs) are synthesized and it was characterized using various techniques such as X-ray diffraction, UV–Vis, FTIR spectroscopy and microscopic analysis. The growth inhibition activity of the ZnO-NPs was investigated against a phytopathogenic fungus, which was isolated and identified as Fusarium equiseti from tomato plant leaves. Our result showed that application of ZnO NPs at 750 ppm–1200 ppm concentration range inhibited the growth of F. equiseti by 77.6 %–85.1 % at 7 days of seeding the fungi in PDA media. Microscopic observation of the fungal strain treated with ZnO NPs showed that the presence of the nanoparticles agglomerates the normal hyphae of F. equiseti and formed curve tips and breakage of mycelia. Hence, our study shows that application ZnO NPs is promising approach for fungal growth inhibition and can be deployed to inhibit other plant diseases causing microbes in agriculture.

The essential oil extracted from Tenebrio molitor larvae (EOTM) is a natural product containing trace elements with potential therapeutic properties. This study aimed to assess the anticancer effects of EOTM and its synergistic interactions with zoledronic acid, a bisphosphonate drug, on prostate cancer cell lines. The chemical composition of EOTM was analyzed using GC-MS revealing a high concentration of fatty acids. The cytotoxicity of EOTM, both as a standalone treatment and in combination with zoledronic acid, was evaluated on prostate cancer cell lines (LNCaP, PC3) and normal hSKM using MTT assays. Results demonstrated that EOTM exhibited selective toxicity, inhibiting the growth of cancer cells in a dose-dependent manner while sparing normal cells. Morphological assessments and gene expression analyses of BCL2 and BAX were conducted through microscopy, Western blotting, and real-time RT-qPCR. These analyses indicated that EOTM induced apoptosis in cancer cells, as evidenced by cellular shrinkage, membrane blebbing, and nuclear fragmentation. Western blot results showed that EOTM downregulated the anti-apoptotic protein BCL2 and upregulated the proapoptotic protein BAX, suggesting activation of apoptosis pathways. Additionally, the combination of EOTM with zoledronic acid amplified these effects. Hoechst 33258 staining further confirmed the purity of cells following treatment. In conclusion, EOTM exhibits strong anticancer properties by inducing apoptosis in prostate cancer cells and demonstrates synergistic potential when combined with zoledronic acid. These findings warrant further investigation of EOTM as a natural and effective cancer treatment option.

This study was performed to evaluate the role of TSC2 (tuberous sclerosis complex 2) in the regulation of growth inhibition of fish exposed to chronic ammonia nitrogen. Firstly, the full-length cDNA of TSC2 in juvenile blunt snout bream, Megalobrama amblycephala was cloned using RACE technology (5’ and 3’ rapid amplification of cDNA ends). Then, TSC2 was analyzed by bioinformatics methods containing Seqman, BLAST, DNAMAN 8.0, EXPASY, and MEGA 6.0 program. Finally, the growth and gene expression level of AMKP-mTOR signaling pathway of blunt snout bream under ammonia nitrogen were investigated. The results showed that the full length of TSC2 was 6145 bp containing 5’- untranslated region of 179 bp, 3’-UTR of 992 bp and an open reading frame of 4974 bp encoding a peptide of 1657 amino acids. The estimated theoretical PI and MW (molecular weight) of TSC2 protein were 7.13 and 183016 Da, respectively. Meanwhile, TSC2 protein had three structural domains: DUF3384 domain (residues 5–303), Tuberin domain (residues 386–735) and Rap-GAP domain (residues 1409–1597). TSC2 from Megalobrama amblycephala gathered Pimephales promelas and Danio rerio clade belonging to Cyprinidae, and showed further distance to Ictalurus punctatus and Tachysurus fulvidraco. Final body weight and weight gain of fish under ammonia nitrogen stress significantly decreased (p < 0.05). Meanwhile, ammonia nitrogen stress significantly decreased Rheb, mTOR and S6K1 mRNA expression levels of blunt snout bream (p < 0.05). However, ammonia nitrogen stress significantly up-regulated the AMPKα1, AMPKα2, TSC2, 4E-BP2 mRNA expression levels (p < 0.05). Taken together, ammonia nitrogen stress inhibited protein synthesis of muscle via activating the AMKP-mTOR signaling pathway mediated by TSC2, which led to decreased body weight of blunt snout bream. The results obtained here will provide the theoretical foundation for completing the research of TSC2 functions involving protein synthesis in fish exposed to chronic ammonia nitrogen.

The functional tea CFT-1 has been introduced into China as a nutraceutical beverage according to the "Healthy China" national project. The effects on human hepatocellular carcinoma (HCC) cells remain unclear and were investigated with the functional tea extract (purity > 98%). The morphological changes in the cells were observed with microscopes. Cell proliferation, migration, cycle distribution, and apoptotic effects were assessed by MTT, Transwell assays, and flow cytometry, respectively, while telomerase inhibition was evaluated with telomerase PCR ELISA assay kits. The CFT-1 treatment resulted in cell shrinkage, nuclear pyknosis, and chromatin condensation. CFT-1 suppressed the growth of Hep3B cells with IC50 of 143 μg/mL by inducing apoptosis and G0/G1 arrest in Hep3B cells. As for the molecular mechanism, CFT-1 treatment can effectively reduce the telomerase activity. The functional tea extract inhibits cell growth in human HCC by inducing apoptosis and G0/G1 arrest, possibly through a reduction in telomerase activity. These results indicate that CFT-1 extract exhibited in vitro anticancer activities and provided insights into the future development and utilization of CFT-1 as functional foods to inhibit the proliferation of HCC cells. [ABSTRACT FROM AUTHOR]

Response surface methodology (RSM) was employed to optimize the process parameters of the supercritical carbon dioxide extraction of hop cones in terms of their antifungal properties against Fusarium culmorum and Aspergillus niger. The effects of temperature (40–50 °C), pressure (200–300 bar), and CO2 consumption (25–75 kgCO2/kg) on the extraction yield, content of α- and β-acids, as well as pathogens' growth inhibition were investigated. Both pressure and CO2 consumption had a significant effect on antifungal properties. It was observed that the best results for antifungal properties were obtained when hop cones were extracted with pure carbon dioxide at the temperature of 50 °C, under the pressure of 300 bar with CO2 consumption at the level of 75 kgCO2/kg of feed for extraction. The highest antifungal properties of hop cone supercritical carbon dioxide extracts were analyzed as 100% for Fusarium culmorum and 68% for Aspergillus niger, calculated as the growth inhibition of tested pathogens. The aim of the study was to determine the optimum values of extraction parameters to achieve the maximum response and enable us to investigate the interaction of these parameters on the antifungal properties of hop cone extracts. [ABSTRACT FROM AUTHOR]

This research aims to assess the influence of varying concentrations of caffeine (CA), one of the pharmaceutically active compounds, and its metabolites (i.e., paraxanthine (PX), theophylline (TP), and theobromine (TB)) on the growth of common marine phytoplankton (Isochrysis galbana and Thalassiosira pseudonana) under controlled laboratory conditions. Additionally, the study estimates the daily discharge of CA into marine ecosystems utilizing a developed model. The most effective metabolite inhibiting the proliferation of I. galbana was determined as TP (68.5%) at a concentration of 500 mg/L, while it was CA (65.8%) at the same concentration for T. pseudonana. After exposure to CA, the IC50 values for I. galbana and T. pseudonana were calculated as 107.3 mg/L and 136.8 mg/L, respectively after 96 hours. Furthermore, the lowest IC50 concentration was 7.4 mg/L in TP treatment in I. galbana. Based on a computational model developed in the paper, in a province with about 2 million inhabitants, where all wastewater is treated in wastewater treatment plants (WWTP), the quantity of CA discharged into the sea was computed as 8.11 kg/day. The CA amounts reaching the sea were potentially increased in regions devoid of wastewater treatment infrastructure. Consequently, WWTPs should undergo expansion and enhancement of their capacity, including advanced treatment for chemical removal for sustainable marine life. Additionally, further studies are needed to elucidate the mechanisms underlying the inhibition effects of CA on phytoplankton. [ABSTRACT FROM AUTHOR]

Effective microorganism (EM) – a mixture of beneficial microbial formulation are extensively utilized worldwide in agriculture as plant growth promotor and biocontrol agent. Because of their wide spectrum usage, it is necessary to study the non‐target effect against the beneficial organisms used in crop production. Though, the wider applications of EM in agriculture and the environment have revealed, the environmental quality management of EM mainly metabolites‐ biochemical compounds derived from EM have yet to be studied. With this objective, the present study is undertaken to evaluate the compatibility of EM derived metabolites on the selected microbial biofertilizers, biocontrol agents including biopesticidal agents. Metabolites were extracted from the culture‐free broth of EM culture using various solvents and the extracted metabolites were characterized by the gas chromatography‐ mass spectroscopy (GC‐MS). The food poisoning technique was adapted for the screening of toxic effects. Toxic effect of the metabolites derived from the respective solvent was confirmed by measuring the growth of the respective microbial strain's vegetative growth and sporulation efficacy by dual plate assay, dual liquid assay, and spore germination microscopic slide assay. Active principles of the metabolites were readily extracted in all the solvents and the possible presence of bioactive metabolites were characterized by GC‐MS. There was no significant difference between the control and extract recorded. In the case of Rhizobium leguminosarum, the colony diameters of ethyl acetate and acetone extract were 1.6 and 1.8 cm, respectively, as in control (1.8 cm). Similar findings were also recorded for Azospirillum lipoferum, Phosphobacterium sp., and Pseudomonas flurescens. However, growth inhibition including spore germination was recorded in petroleum ether and acetone extract. Further study will be useful to exploit the principles of EM and EM derived metabolites in agriculture and environment without affecting non target beneficial organism. [ABSTRACT FROM AUTHOR]

Aim The main objective of the study was to develop and validate a model for the growth of Aspergillus brasiliensis on surfaces, specifically on agar culture medium. An additional aim was to determine conditions for complete growth inhibition of this micromycete using two different nonthermal plasma (NTP) sources. Methods and results The developed model uses two key parameters, namely the growth rate and growth delay, which depend on the cultivation temperature and the amount of inoculum. These parameters well describe the growth of A. brasiliensis and the effect of NTP on it. For complete fungus inactivation, a single 10-minute exposure to a diffuse coplanar surface barrier discharge was sufficient, while a point-to-ring corona discharge required several repeated 10-minute exposures at 24-h intervals. Conclusions The article presents a model for simulating the surface growth of A. brasiliensis and evaluates the effectiveness of two NTP sources in deactivating fungi on agar media. [ABSTRACT FROM AUTHOR]

Background: Animal manure-based compost is a valuable organic fertilizer and biological soil amendment. To ensure the microbiological safety of compost products, the effectiveness of competitive exclusion microorganisms (CE) in reducing Escherichia coli O157:H7 in dairy manure-based compost was evaluated. Methods: A cocktail of E. coli O157:H7 strains were inoculated into dairy compost along with CE strains isolated from compost, and the reduction in E. coli O157:H7 by CE was determined in compost with 20%, 30%, and 40% moisture levels at 22 °C and 30 °C under laboratory conditions, as well as in fall, winter, and summer seasons under greenhouse settings. Results: Under lab conditions, CE addition resulted in 1.1–3.36 log reductions in E. coli O157:H7 in compost, with enhanced pathogen reduction by higher moisture and lower temperature. In the greenhouse, >99% of the E. coli O157:H7 population in compost with ≥30% moisture due to cross-contamination can be effectively inactivated by CE within 2 days during colder seasons. However, it took ≥8 days to achieve the same level of reduction for heat-adapted E. coli O157:H7 cells. Conclusions: Our results demonstrated that the competitive exclusion of microorganisms can be an effective tool for controlling foodborne pathogens in compost and reducing the potential for soil and crop contamination. [ABSTRACT FROM AUTHOR]

Tryptamine, a neuromodulator derived from tryptophan, has been shown to significantly impact the host gut homeostasis through its production by the gut microbiota. However, the characterization of tryptamine-producing gut bacteria remains limited, the factors regulating tryptamine production largely unexplored, and its effects on the rest of the gut microbial community unknown. In this study, we screened 13 intestinal strains closely related to known tryptamine producers, characterized their production kinetics, and evaluated whether tryptophan decarboxylation to tryptamine contributes to acid stress tolerance, as shown in other amino acid-dependent acid tolerance systems. We also examined the impact of tryptamine on the composition and function of four healthy human gutmicrobiota by conducting 48-h ex vivo fecal batch fermentations. To complement the ex vivo experiments, we tested the effect of tryptamine exposure (range: 0.5-mM) on the growth of 18 intestinal strains. We identified tryptamine production in five taxa, i.e., Enterocloster asparagiformis, Blautia hansenii, Clostridium nexile, Clostridium sporogenes, and Ruminococcus gnavus,with R. gnavus DSM 108212 accumulating up to 3.4 mM tryptamine after 48 h. An increased tryptophan concentration led to higher tryptamine production. However, tryptamine production was not promoted at low pH andmay not protect cells fromacid-induced cellular damage. Exposing gut microbial communities to 2.4 mM tryptamine caused mild changes in gut microbiota function and composition. All donors showed reduced carbohydrate consumption after 5 h, leading to donor-specific alterations of short-chain fatty acids (SCFAs) (i.e., propionate, acetate, butyrate) and branched-chain fatty acids (BCFAs) (i.e., isobutyrate and isovalerate) after 48 h. Tryptamine also induced a mild change of community structure, with a consistent reduction in the phylum Bacteroidota as well as amplicon sequence variants (ASVs) related to the genera Bacteroides, Blautia, and Faecalibacterium. We confirmed the sensitivity of Bacteroides and Faecalibacterium strains in vitro at concentrations of 2 mM and above. Multiple gut commensals remained unaffected when exposed to 8 mM tryptamine. Taken together, our findings demonstrated that intestinal bacteria-derived tryptamine is a bioactive molecule that not only alters host homeostasis locally but alsomodulates the physiology of gut microbial communities. The specific mechanism through which tryptamine exerts its inhibitory effects on specific gut microbes while leaving others unaffected remains to be elucidated. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to investigate the anti-staphylococcal activity of liposomal daptomycin against four biofilm-producing S. aureus and S. epidermidis clinical strains, three of which are methicillin-resistant. Neutral and negatively charged daptomycin-loaded liposomes were prepared using three methods, namely, thin-film hydration (TFH), a dehydration–rehydration vesicle (DRV) method, and microfluidic mixing (MM); moreover, they were characterized for drug encapsulation (EE%), size distribution, zeta-potential, vesicle stability, drug release, and drug integrity. Interestingly, whilst drug loading in THF and DRV nanosized (by extrusion) vesicles was around 30–35, very low loading (~4%) was possible in MM vesicles, requiring further explanatory investigations. Liposomal encapsulation protected daptomycin from degradation and preserved its bioactivity. Biofilm mass (crystal violet, CV), biofilm viability (MTT), and growth curve (GC) assays evaluated the antimicrobial activity of neutral and negatively charged daptomycin-liposomes towards planktonic bacteria and biofilms. Neutral liposomes exhibited dramatically enhanced inhibition of bacterial growth (compared to the free drug) for all species studied, while negatively charged liposomes were totally inactive. Biofilm prevention and treatment studies revealed high antibiofilm activity of liposomal daptomycin. Neutral liposomes were more active for prevention and negative charge ones for treating established biofilms. Planktonic bacteria as well as the matured biofilms of low daptomycin-susceptible, methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE) strains were almost completely eradicated by liposomal-daptomycin, indicating the need for their further exploration as antimicrobial therapeutics. [ABSTRACT FROM AUTHOR]

The phenology has gained considerably more attention in recent times of climate change. The transition from vegetative to reproductive phases is a critical process in the life history of plants, closely tied to phenology. In an era of climate change, understanding how environmental factors affect this transition is of paramount importance. This study consisted of field surveys and a greenhouse experiment on the reproductive biology of Northern pipevine (Aristolochia contorta Bunge). During field surveys, we investigated the environmental factors and growth characteristics of mature A. contorta, with a focus on both its vegetative and reproductive phases. In its successful flowering during the reproductive phase, A. contorta grew under the conditions of 40% relative light intensity and 24% soil moisture content, and had a vertical rhizome. In the greenhouse experiments, we examined the impact of increased CO2 concentration on the growth and development of 10-year-old A. contorta, considering the effect of rhizome direction. Planted with a vertical rhizome direction, A. contorta exhibited sufficient growth for flowering under ambient CO2 concentrations. In contrast, when planted with a horizontal rhizome direction, it was noted to significantly impede successful growth and flowering under elevated CO2 concentrations. This hindered the process of flowering, highlighting the pivotal role of substantial vegetative growth in achieving successful flowering. Furthermore, we observed a higher number of underground buds and shoots under the conditions of elevated CO2 concentration and a horizontal rhizome direction instead of flowering. Elevated CO2 concentrations also exhibited diverse effects on mature A. contorta's flower traits, resulting in smaller flower size, shorter longevity, and reduced stigma receptivity, and pollen viability. The study shed light on elevated CO2 concentrations can hinder growth, potentially obstructing sexual reproduction and diminishing genetic diversity. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer. [ABSTRACT FROM AUTHOR]

The occurrence of the market-leading glyphosate active ingredient in surface waters is a globally observed phenomenon. Although co-formulants in pesticide formulations were considered inactive components from the aspects of the required main biological effect of the pesticide, several studies have proven the high individual toxicity of formulating agents, as well as the enhanced combined toxicity of the active ingredients and other components. Since the majority of active ingredients are present in the form of chemical mixtures in our environment, the possible combined toxicity between active ingredients and co-formulants is particularly important. To assess the individual and combined phytotoxicity of the components, glyphosate was tested in the form of pure active ingredient (glyphosate isopropylammonium salt) and herbicide formulations (Roundup Classic and Medallon Premium) formulated with a mixture of polyethoxylated tallow amines (POEA) or alkyl polyglucosides (APG), respectively. The order of acute toxicity was as follows for Roundup Classic: glyphosate < herbicide formulation < POEA. However, the following order was demonstrated for Medallon Premium: herbicide formulation < glyphosate < APG. Increased photosynthetic activity was detected after the exposure to the formulation (1.5–5.8 mg glyphosate/L and 0.5–2.2 mg POEA/L) and its components individually (glyphosate: 13–27.2 mg/L, POEA: 0.6–4.8 mg/L), which indicates hormetic effects. However, decreased photosynthetic activity was detected at higher concentrations of POEA (19.2 mg/L) and Roundup Classic (11.6–50.6 mg glyphosate/L). Differences were demonstrated in the sensitivity of the selected algae species and, in addition to the individual and combined toxicity of the components presented in the glyphosate-based herbicides. Both of the observed inhibitory and stimulating effects can adversely affect the aquatic ecosystems and water quality of surface waters. [ABSTRACT FROM AUTHOR]

The research was carried out on newly planted bare-root plants at an early stage of their cultivation. The scope of the growth responses of woody plants was verified in relation to the recommended herbicide rate, namely for herbicide solution application rates of 0.825% and 1.025%. The new increment of the longest shoot and the mortality rate were evaluated. The selective efficacy on weeds was observed. Data collection took place at 2, 4, 8, 12 and 24 weeks after application. The experiment followed the manufacturer's recommendations for application. It was conducted on an experimental area of loamy sand soil in 2019 and it was not affected by extreme weather conditions. The application of the herbicide to privet (Ligustrum vulgare) showed a small inhibitory effect, reducing the average increment of the longest plant shoot by 4.7% and 8.3%, respectively, by the end of the study period compared to the control. By contrast, in the case of the European Bladdernut (Staphylea pinnata), the application was found to have an adverse effect. The role of the application rate was secondary. The average increment of the longest shoot was reduced by 45.68% and 50.13%, respectively, and the mortality rate of the treated woody plants reached 10% at the end of the study period. The highest inhibitory effect of the herbicide on the ornamental woody plants that had been treated was observed in the first 2 and 4 weeks after treatment, respectively. The application of the herbicide proved ineffective against horseweed (Conyza canadensis) and groundsel (Senecio vulgaris).

Background & objectives: Insect growth regulators (IGRs) are biological hormone analogue or mimics used as pesticides to inhibit the growth of larva during their molting and skin shedding. This study aimed to test the effect of IGRs on the eggs hatching and post-hatching inhibition of Aedes mosquitoes and understanding its effect in the mosquito breeding habitats for reduction in adult emergence. Methods: Experiments on the evaluation of three insect growth regulators (IGRs) for the control of different stages of Aedes aegypti was carried out during 2020-21. Each experiment consisted of four treatments viz., Pyriproxyfen, Novaluron, and Larvicol at 1.0 ppm and distilled water as a control. All experiments were carried out in completely randomized design (CRD) except eggs which were carried out in factorial design each with three replications. Results: All tested IGRs performed better in affecting eggs, larval and pupal stages of Ae. aegypti. Highest eggs hatching inhibition (80%) of fresh eggs occurred in Pyriproxyfen followed by Novaluron (66%) and lowest in Larvicol (62%). Eggs hatch inhibition of embryonated eggs was lower than fresh eggs. Pyriproxyfen caused 69%, Novaluron 59% and Larvicol 39% eggs hatch inhibition of embryonated eggs. Both Pyriproxyfen and Novaluron performed better in causing 98–100% larval mortality followed by Larvicol (39%). Larval development to pupal stage was completely prevented by both Pyriproxyfen and Novaluron. Although Larvicol resulted in lowest eggs hatch and larval inhibition but prevented pupae to emerge as adults. Results further showed 70–89% mortality of 3rd instar larvae of Ae. aegypti when exposed to Pyriproxyfen and Novaluron solutions after 30 days storage at lab. temperature (27±2°C), RH 70±5. Interpretation & conclusion: None of the IGRs was more effective at the pupal stage but showed carry-on activity of growth inhibition and mortality of the successive stages of development when used against eggs stages. Therefore, we recommend early application of IGRs at mosquito habitats during the beginning and onset of the season when very early stages of mosquitoes are available in the field.

Pseudomonas aeruginosa is a multidrug-resistant pathogen known for chronic infections, mainly due to biofilm formation. This study aimed to explore the potential repurposing of 5-fluorouracil (5-FU), an anticancer drug, to treat P. aeruginosa infections. Firstly, we investigated the inhibitory effects of 5-FU on bacterial growth using the microdilution method. Secondly, the impact of 5-FU on biofilm formation and disassembly was assessed via biofilm biomass measurements with the crystal violet staining method and confocal microscopy analyses. Lastly, the potential synergy between 5-FU and the antibiotics gentamicin and meropenem was evaluated using a checkerboard assay. Results revealed that 5-FU inhibited bacterial growth in a dose-dependent manner, with 100% inhibition observed at concentrations of 25 µg/mL and higher. Also, 70% and 100% reductions in biofilm biomass were demonstrated at concentrations of 12 and 100 µg/mL, respectively. Controversy, these higher concentrations unexpectedly increased biofilm biomass in pre-formed biofilms. Synergistic interactions were observed between 5-FU and gentamicin in both growth inhibition (FICI 0.31) and biofilm inhibition (ZIP 14.1), while no synergy was found with meropenem. These findings highlight the potential of 5-FU as an adjunctive therapy for P. aeruginosa infections, especially in combination with gentamicin. However, further research is required to address 5-FU limitations against mature biofilms.

Black root rot (BRR) and Verticillium wilt of cotton are caused by soilborne Berkeleyomyces rouxiae and Verticillium dahliae, respectively, and can individually cause yield loss of a 10–50% in New South Wales (NSW). Both diseases were first detected in a northern valley of NSW but are now present across the state. ‘Come Clean Go Clean’ is a widely practiced biosecurity measure used to minimize the risk of further introducing the pathogens from one field to another by restricting the movement of soil-contaminated farm equipment and machinery. We rely on cleaning agents to effectively wash down and decontaminate the equipment and machinery. In this study, we examined 12 locally available, commercial disinfectants for their efficacy against B. rouxiae and V. dahliae reproductive structures with and without soil contamination of 10% (w/v). We found a significant interaction between pathogens, disinfectants, and soil amendment (p < 0.01). The germination of B. rouxiae chlamydospores and endoconidia in both the presence and absence of soil contamination was completely suppressed even after a short 10 sec exposure to 70% ethanol and 25% bleach. Both 70% ethanol and bleach were highly lethal at 10 sec exposures in similar assays against V. dahliae microsclerotia and conidia. Some other commercial products were able to reduce the germination rate significantly but did not completely kill microsclerotia and conidia even after 30 min of exposure. The lethal effect against B. rouxiae and V. dahliae warrants further exploration of both 70% ethanol and bleach to improve their field applications. Additionally, the efficacy of most tested commercial disinfectants was time-dependent; however, this is not recommended on the labels for their effectiveness. This study provides an additional integrated disease management option aiming to limit the spread of the pathogens.

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae, transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae. [ABSTRACT FROM AUTHOR]

The rapid inclusion of zinc oxide nanoparticles (ZnO NPs) in nanotechnology-based products over the last decade has generated a new threat in the apprehension of the environment. The massive use of zinc nanosized products will certainly be disposed of and be released, eventually entering the aquatic ecosystem, posing severe environmental hazards. Moreover, nanosized ZnO particles owing the larger surface area per volume exhibit different chemical interactions within the aquatic ecosystem. They undergo diverse potential transformations because of their unique physiochemical properties and the feature of receiving medium. Therefore, assessment of their impact is critical not only for scavenging the present situation but also for preventing unintended environmental hazards. Algae being a primary producer of the aquatic ecosystem help assess the risk of massive NPs usage in environmental health. Because of their nutritional needs and position at the base of aquatic food webs, algal indicators exhibit relatively unique information concerning ecosystem conditions. Moreover, algae are presently the most vital part of the circular economy. Hence, it is imperative to understand the physiologic, metabolic, and morphologic changes brought by the ZnO NPs to the algal cells along with the development of the mechanism imparting toxicity mechanism. We also need to develop an appropriate scientific strategy in the innovation process to restrain the exposure of NPs at safer levels. This review provides the details of ZnO NP interaction with algae. Moreover, their impact, mechanism, and factors affecting toxicity to the algae are discussed. [ABSTRACT FROM AUTHOR]

Bioassays were conducted under controlled conditions to determine the response of Spodoptera frugiperda (J. E. Smith) larvae fed with corn materials expressing Bacillus thuringiensis (Bt) insecticidal endotoxins: (1) VT Double Pro® (VT2P) expressing Cry1A.105-Cry2Ab2 proteins and (2) VT Triple Pro® (VT3P) expressing Cry1A.105-Cry2Ab2-Cry3Bb1 proteins. The parameters assessed were: (i) mortality rate, and (ii) growth inhibition (GI) with respect to the control. To conduct this study, larvae were collected from commercial non-Bt corn fields, in four agricultural sub-regions in Colombia, between 2018 and 2020. Fifty-two populations were assessed from the field and neonate larvae from each of the populations were used for the bioassays. The study found that mortality rates in the regions for larvae fed with VT2P corn ranged from 95.1 to 100.0%, with a growth inhibition (%GI) higher than 76.0%. Similarly, mortality rate for larvae fed with VT3P corn were between 91.4 and 100.0%, with a %GI above 74.0%. The population collected in Agua Blanca (Espinal, Tolima; Colombia) in 2020, showed the lowest mortality rate of 53.2% and a %GI of 73.5%, with respect to the control. The population that exhibited the lowest %GI was collected in 2018 in Agua Blanca (Espinal, Tolima, Colombia) with a 30.2%, growth inhibition, with respect to the control. In recent years, the use of plant tissue to monitor susceptibility to fall armyworm has proven to be useful in the resistance management program for corn in Colombia determining that the FAW populations are still susceptible to Bt proteins contained in VT2P and VT3P. [ABSTRACT FROM AUTHOR]

This work discusses the synthesis of (Cu-Se) core-shell nanoparticles using a plasma jet, using aqueous solutions of copper and selenium salts as a precursor. The structural properties of the resultant (Cu-Se) core-shell nanostructures were examined using UV, XRD, and SEM. The diameter of the granules with a concentration of 3:7 is 17 nm. Thus, utilising the designated diameter. Next, a comparison was made between the MDA cell line—which had been treated to Cu-Se NPs as an anti-cancer (breast cancer) agent—and the normal cell line REF. For every set, the following parameter was evaluated: (i) the proportion of breast cancer cells whose proliferation was inhibited after exposure for (24, 48) hours; (ii) the cytotoxicity of normal cells after (24, 48) hours. We diluted the nanomaterial five times and found that the cytotoxicity in normal cells does not exceed 22%, indicating that its effect is not detrimental to normal cells. Meanwhile, the nanomaterial’s effects were observed on cancer cells after 24 hours, at roughly 63%, and after 48 hours, at roughly 93%, and the census was carried out with these cells. [ABSTRACT FROM AUTHOR]

The role of the epidermal growth factor receptor (EGFR) in tumor progression and survival is often underplayed. Its expression and/or dysregulation is associated with disease advancement and poor patient outcome as well as drug resistance in breast cancer. EGFR is often overexpressed in breast cancer and particularly triple-negative breast cancer (TNBC), which currently lacks molecular targets. We examined the synergistic potential of an EGFR inhibitor (EGFRi) in combination with doxorubicin (Dox) in estrogen-positive (ER+) MCF-7 and MDA-MB-231 TNBC cell lines. The exposure of MDA-MB-231 and MCF-7 to EGFRi produced an IC50s of 6.03 µM and 3.96 µM, respectively. Dox induced MDA-MB-231 (IC50 9.67 µM) and MCF-7 (IC50 1.4 µM) cytotoxicity. Combinations of EGFRi-Dox significantly reduced the IC50 in MCF-7 (0.46 µM) and MBA-MB 231 (0.01 µM). Synergistic drug interactions in both cell lines were confirmed using the Bliss independence model. Pro-apoptotic Caspase-3/7 activation occurred in MCF-7 at 0.1–10 µM of EGFRi and Dox single treatments, whilst 1 μM Dox yielded a more potent effect on MDA-MB-231. EGFRi and Dox individually and in combination downregulated the EGFR gene expression in MCF-7 and MDA-MB-231 (p < 0.001). This study demonstrates EGFRi's potential for eliciting synergistic interactions with Dox, causing enhanced growth inhibition, apoptosis induction, and downregulation of EGFR in both cell lines. [ABSTRACT FROM AUTHOR]

The era of ongoing research is clearly progressing in the direction of chemical profiling and the evaluation of pharmacological and toxicological potential of plant extracts. The trend of sourcing essential oils (EOs) from various aromatic plants continues to hold great promise, providing anti-inflammatory, antimicrobial, and anticancer compounds as leads. Given this enormous potential, the EO of Allardia tridactylites (Kar. & Kir.) Sch. Bip., a highly unexplored plant from Ladakh widely known for its therapeutic uses, was explored for its phytotoxic and pharmacological potential in the present study, with a special mention of its antigerminative, antibacterial, and cytotoxic activities. The oil was analysed for its chemical constitution using the GC–MS technique and found to contain an almost equal proportion of monoterpenes (44.74%) and sesquiterpenes (45.08%), with α-pinene (15.85%), α-thujone (15.78%), valeranone (17.44%), and α-bisabolol (9.47%) identified as the major compounds. EO was found to be phytotoxic against the weed Bidens pilosa L., as it reduced the germination and seedling length of the weed with increasing concentrations of EO (0.01–0.1 mg mL–1). The antibacterial effect of EO (at 25–400 µg mL–1) was evaluated against six bacterial strains: Bacillus cereus, Streptomyces scabiei, Bacillus pumilus, Rhodococcus fascians, Erwinia herbicola, and Pseudomonas syringae. Except for B. pumilus, a strong dose-dependent inhibition was observed in the growth of all the bacteria with EO treatments. R. fascians was found to be the most susceptible to EO (at 400 µg mL–1). The cytotoxic effect of EO was confirmed by a reduced mitotic index and an increased percentage of chromosomal aberrations (CAs), especially at treatments of ≥ 0.05 mg mL–1, in Allium cepa L. The type and frequency of CAs also increased at the highest EO concentration. The study concludes that the EO of A. tridactylites possesses strong phytotoxic, antibacterial, and cytotoxic activities and, thus, can be a potential candidate for weed management, alongside its use in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]