Motile cilia play a critical role in maintaining tissue homeostasis by driving fluid movement and clearing inhaled particles or pathogens. Dysfunction of these organelles underlies a range of ciliopathies, most notably affecting the respiratory system. Building on previous studies that identified molecules promoting motile cilia formation, we tried to discover novel small molecules that enhance motile ciliogenesis. To this end, we conducted a phenotype-based high-throughput screen using a Tg(foxj1a:eGFP) zebrafish reporter line, which led to the identification of a new chemotype hit. Subsequent structure–activity relationship (SAR) studies resulted in the development of compound 19b, which promoted motile cilia formation in zebrafish embryos. Its efficacy was further validated in ex vivo air–liquid interface (ALI) cultures of mouse tracheal epithelial cells, where treatment with 19b significantly increased the number of multiciliated cells. These findings suggest that compound 19b is a useful chemical probe for studying ciliogenesis and a potential lead for therapeutic development in motile ciliopathies.

Epilepsy is a neurological disorder associated with abnormal neuronal activity in the central nervous system, resulting in recurrent seizures. Various anti-seizure medications (ASMs) are effective against epilepsy. However, approximately one-third of patients still do not respond to currently available ASMs either alone or in combination because the etiology of their epilepsy remains unclear. To create a novel zebrafish epilepsy model, we analyzed the exomes of 400 Korean patients with epilepsy via whole-exome sequencing. We found 39 candidate genes and investigated these genes through in situ hybridization and loss-of-function studies, identifying SLC25A22, encoding a mitochondrial glutamate carrier, as a potential epilepsy gene. Subsequently, we generated zebrafish slc25a22a mutants and observed that they displayed spontaneous seizures, high-voltage deflections in local field potentials, and elevated Ca2+ levels propagating from the forebrain to the spinal cord. Of nine ASMs tested, valproic acid (VPA) was able to suppress spontaneous seizure activities in slc25a22a mutant larvae, highlighting the unique anti-seizure effect of VPA in this model. Our findings provide valuable insights into the pathogenesis of epilepsy and suggest slc25a22a as a potential target for novel ASM development.

Background: Aryl hydrocarbon receptor (AhR) is a transcription factor that is involved in the regulation of immunity. AhR inhibits T cell activation in tumors, which induces immune suppression in the blood and solid tumors. We identified effective small-molecule AhR antagonists for cancer immunotherapy. Methods: A new series of pyrazolopyrimidine derivatives was synthesized and evaluated for AhR antagonistic activity. Results: Compound 7k exhibited significant antagonistic activity against AhR in a transgenic zebrafish model. In addition, 7k exhibited good AhR antagonist activity, with a half-maximal inhibitory concentration (IC50) of 13.72 nM. Compound 7k showed a good pharmacokinetic profile with an oral bioavailability of 71.0% and a reasonable half-life of 3.77 h. Compound 7k selectively exerted anti-proliferative effects on colorectal cancer cells without affecting normal cells, concurrently suppressing the expression of AhR-related genes and the PD-1/PD-L1 signaling pathway. Compound 7k exhibited potent antitumor activity in syngeneic colorectal cancer models. Importantly, the combination of anti-PD1 and compound 7k enhanced antitumor immunity by augmenting cytotoxic T lymphocyte (CTL)-mediated activity. Conclusions: Collectively, a new pyrazolopyrimidine derivative, 7k, shows promise as a potential therapeutic agent for treating colorectal cancer.

Ferrite materials, possessing a suitable electronic band structure, are consistently superior candidates for photocatalytic environmental detoxification utilizing visible light and solar energy. This study presents the synthesis of silver-doped cerium ferrites CeFe1-xAgxO3 (where x = 0.0, 0.05, 0.1 and 0.15 designated as C1, C2, C3, C4) employing the sol-gel approach. The characterisation of prepared samples for phase identification via X-ray diffraction (XRD) indicates the formation of an orthorhombic structure with space group Pbnm (62). The uniform distribution of grains is demonstrated using FESEM analysis. The optical band gap for the synthesized silver doped cerium ferrites ranges from 1.499 to 2.113 eV. The photocatalyst CeFe0.9Ag0.05O3 demonstrated a 97.83 % degradation of Crystal violet dye (CV) during 90 min of exposure to visible light. The impact of factors such as pH, catalyst dose, CV concentration, and water matrix was examined comprehensively. The electrochemical analysis validates the pseudocapacitive behaviour of Ag-doped CeFeO3 nanoparticles, exhibits good capacitance and energy density. The dispersed Cerium ferrite nanoparticles showed potent antibacterial activity against Gram-ve bacteria ( Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi) and Gram +ve bacterium Bacillus subtilis. Among all the nanoparticles, CeFe0.95Ag0.05O3 showed the highest susceptibility against all the strains whereas demonstrated effectiveness Salmonella

This work investigates the structural, photocatalytic, and biological properties of Juglans regia leaves extract mediated chitosan-modified TiO2 nanoparticles (NPs) and Juglans regia mediated TiO2 NPs. The structural and morphological analysis conducted using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and FTIR revealed that synthesizing the TiO2 NPs using both chitosan and Juglans regia leaves extract results in lower particle size and less agglomeration in comparison to TiO2 NPs synthesized using only Juglans regia leaves extract. The photocatalytic activity for the degradation of Rhodamine B using phytomediated chitosan-modified TiO2 NPs has a remarkable degradation efficacy of 95.07% when subjected to UV-visible light. Further, phytomediated chitosan-modified TiO2 NPs have ability to reduce the E2 estrogen levels and which inhibits the growth of breast cancer cells (MCF-7) which was confirmed by yeast based XenoScreen XL YES assay, [3H] thymidine incorporation, and apoptosis gene expression (Casp 3 and Casp 9) analysis.

One of the most well-known vegetables used by the majority of the population worldwide, known as tomato (Solanum lycopersicum), is affected by wilt disease caused by Fusarium oxysporum f. sp. lycopersici (FOL), mainly in the tropics. In the current scenario, a residue-free management approach using a biological control agent is being explored to address the invasion of phytopathogens. This investigation assessed the ability of Trichoderma asperellum (Tv1) to reduce pathogen growth and promote plant growth. A dual culture assay demonstrated that Trichoderma asperellum Tv1 inhibited the growth of the pathogen mycelia by up to 79.63

This book provides information about the major diseases of horticultural crops in India. It discusses the pest, disease, and nematode issues affecting essential vegetable crops in the country. The management of pests in vegetable crops has been addressed through many methods, including regulatory, physical, cultural, chemical, and biological approaches, host resistance, and integrated pest management strategies. The subject matter of the book is helpful for farmers who cultivate vegetable crops and is a valuable reference point for policymakers, researchers, extension workers, and students. Print edition not for sale in South Asia (India, Sri Lanka, Nepal, Bangladesh, Pakistan and Bhutan)

This book provides information about the major diseases of horticultural crops in India and discusses the significant pest, disease, and nematode issues affecting essential fruit crops in the country. It also addresses the management of pests in vegetable crops through several methods such as regulatory, physical, cultural, chemical, and biological approaches, host resistance, and integrated pest management strategies. Print edition not for sale in South Asia (India, Sri Lanka, Nepal, Bangladesh, Pakistan and Bhutan)

Bacterial wilt caused by Ralstonia solanacearum, is one of the most notorious plant diseases of potato and causes severe yield losses globally. R. solanacearum produces fluidal white coloured colonies with a light pink centre on casamino acid-peptone-glucose medium. Bacterial wilt pathogen is soil as well as tuber borne, so early detection of bacterial wilt pathogen is necessary to take up timely management practices. Traditional methods used for detection of R. solanacearum are labour-intensive, expensive, time-consuming and can be carried out only in well-equipped laboratories. Hence, the present study was aimed to develop a loop-mediated isothermal amplification (LAMP) assay for R. solanacearum, as an alternative approach for quick and efficient detection of the bacterial wilt. LAMP reaction mix was optimized by adjusting the concentrations of MgSO4, dNTPs, betaine, and time, temperature etc. The optimum temperature and time for the detection of R. solanacearum were 65 °C and 50 min, respectively. The positive samples showed colour change from violet and were reconfirmed in 2

Using first principles methodology, we investigate the microsolvation of protonated benzene (BzH+), protonated coronene (CorH+) and protonated dodecabenzocoronene (DbcH+). Gas phase complexes of these small protonated polyaromatic hydrocarbons (H+PAHs) with mono-, di-, and tri-hydrated water molecules are considered. Their most stable forms are presented, where we discuss their structural, energetic aromaticity and IR and UV spectral features. In particular, we focus on the analysis of the bonding and various non-bonded interactions between these protonated aromatics and water clusters. The strength of non-bonded interactions is quantified and correlated with their electron density profiles. Furthermore, insights into the interfacial interactions and stability of these complexes were obtained through non-covalent index and symmetry-adapted perturbation theory (SAPT0) analyses. We also discuss the effects of the extension of the pi aromatic cloud on the water solvation of these protonated aromatics. In particular, we extended our predictions for the S0 -> S1 and S0 -> T1 wavelength transitions of micro hydrated H+PAHs to deduce those of these species solvated in aqueous solution. The present findings should be useful for understanding, at the microscopic level, the effects of water interacting with H+PAHs, which are relevant for organic chemistry, astrochemistry, atmospheric chemistry, combustion and materials science. Using first principles methodology, we investigate the microsolvation of protonated benzene (BzH+), protonated coronene (CorH+) and protonated dodecabenzocoronene (DbcH+).

Motile cilia are crucial for maintaining healthy bodily functions by facilitating fluid transport and removing foreign substances or debris from the body. The dysfunction of motile cilia leads to ciliopathy. In particular, damage to the motile cilia of the airways can cause or worsen respiratory disease, making it an attractive target for therapeutic interventions. However, there are no treatments to induce motile ciliogenesis. Forkhead box transcription factor J1 (FOXJ1), the master regulator, has been implicated in motile cilia formation. Mice lacking the Foxj1 gene show loss of axoneme, a key component of cilia, that further highlights the importance of FOXJ1 in motile cilia formation. This prompted us to identify new small molecules that could induce motile ciliogenesis. A phenotype-based high-throughput screening (HTS) in a Tg(foxj1a:eGFP) zebrafish model was performed and a novel hit compound was identified. Among the synthesized compounds, compound 16c effectively enhanced motile ciliogenesis in a transgenic zebrafish model. To further test the efficacy of compound 16c on a mammalian airway system consisting of multiciliated cells (MCCs), ex vivo mice tracheal epithelial cell culture was adopted under an air-liquid interface system (ALI). Compound 16c significantly increased the number of MCCs by enhancing motile ciliogenesis. In addition, compound 16c exhibited good liver microsomal stability, in vivo PK profiles with AUC, and oral bioavailability. There was no significant inhibition of CYP and hERG, and no cell cytotoxicity was shown. In an elastase-induced COPD (chronic obstructive pulmonary disease) mouse model, compound 16c effectively prevented the development and onset of COPD. Taken together, compound 16c has great promise as a therapeutic agent for treating and alleviating motile ciliopathies.