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Purpose: Response to neoadjuvant chemotherapy in form of tumor necrosis predicts outcome in osteosarcoma; although response-adapted treatment escalation failed to improve outcome among patients treated with high-dose methotrexate-based (HDMTx) chemotherapy. This study aimed to identify factors predicting tumor necrosis and its impact on survival among patients with non-metastatic osteosarcoma treated with a response-adapted non-HDMTx regimen. Methods: A retrospective single-institutional study was conducted among non-metastatic osteosarcoma patients treated with neoadjuvant therapy between 2004–2019. Patients were treated uniformly with three cycles of neoadjuvant cisplatin/doxorubicin. Post-operatively, patients with favourable necrosis (≥90 %) received 3 cycles of cisplatin/doxorubicin, while patients with poor necrosis (

Background: The proximal humerus is a common site for primary malignant and benign aggressive bone tumors, necessitating wide resection and subsequent skeletal defect reconstruction. Various reconstruction options include osteoarticular allografts, autografts, endoprosthesis, nail-cement spacer, reverse shoulder arthroplasty, and allograft-prosthesis composites. However, there is no consensus on the optimal reconstruction method. This study aims to compare functional outcomes and complications between these two methods. Methods: A total of 40 patients with proximal humerus tumors who underwent endoprosthesis or nail-cement spacer reconstruction between March 2012 and December 2020 were included. The mean follow-up in the study was 31.37 +/− 12 months. Demographic and clinical data were collected, and functional outcomes were assessed using the Musculoskeletal Tumor Society 93 scoring system and the Disabilities of the Arm, Shoulder, and Hand questionnaire. Complications and oncological outcomes were recorded. Results: Both groups were similar in terms of demographic and clinical variables. Endoprosthesis reconstruction demonstrated significantly better active shoulder forward flexion compared to nail-cement spacer (45.8 vs. 25.2 degrees) (P = .015). Endoprosthesis group also exhibited greater active shoulder internal rotation (68.25 vs. 63.25 degrees) (P = .004). No statistically significant differences were observed in overall functional outcomes. Complications, including radial nerve palsy and infection, were comparable between groups, with one case of spacer loosening. Conclusion: Both endoprosthesis and nail-cement spacer reconstruction provide comparable functional outcomes and complication rates following proximal humerus tumor resection. Nail-cement spacer offers a cost-effective alternative for patients in resource-constrained settings.

In this study, the resistance of selected canola genotypes to the mustard aphid Lipaphis erysimi (Kaltenbach) was investigated. Molecular characterization of plant resistance was conducted, and genetic variability was observed between the resistant (KS-75) and susceptible (Abaseen) genotypes of brassica. Three RAPD markers were identified that were associated with the resistance. This study was conducted to compare the genetic data between two genotypes (KS-75 resistant and Abaseen susceptible), with an average of 4.3 bands per primer. The amplification bands per primer ranged from 9 to polymorphic fragments of 8, with fragment sizes ranging from 450 to 1700 base pairs to 9 kilo base pairs (kbps). Amplification of the largest fragment in 9 kbps using four primers (A 1–12, B 1–12, K 1–12 and L 1–12) resulted in a mean 92 percent identity index between the first two resistant and susceptible genotypes. KS-75 resistant had the highest mean genetic diversity of 92 percent, while Abaseen susceptible had the lowest mean genetic diversity of 8 percent. Out of the three markers tested, two were found to be positively associated with aphid resistance, while one was negatively correlated. These markers can be used to help develop a pre-emptive strategy for aphid resistance in brassica species, without having to simultaneously select for yield and quality related traits.

Lemongrass (Poaceae) is one of the aromatic plants with strong odors. Traditionally, lemon grass oil has been used for the treatment of many diseases such as gastrointestinal cramps, high blood pressure, high body temperatures, and fatigue, and is also considered an antibacterial and anti-diarrheal agent. Therefore, this study aims to investigate volatile active constituents and a few important biological activities of the volatile oil of lemongrass (Cymbopogon citratus) grown in Oman. To support the results of experimental studies, and to find out the main active constituents responsible for exhibiting biological activities molecular docking studies have also been performed. A sufficient amount of essential oil was obtained using steam distillation from fresh leaves of lemongrass. Volatile constituents were identified with the GC-MS analysis. Lemon grass oil exhibited a very good in vitro antioxidant activity (65.08–90.48 % inhibition of DPPH) with increasing concentration (31.25–1000 µg/mL) of oil. Isolated oil also exhibited good cytotoxic activity against the brine shrimps (100 % mortality at 1000 mcg/mL). Furthermore, molecular docking studies confirmed that beta citral is the monoterpene compound responsible for antioxidant and cytotoxic activity.

Decaprenyl-phosphoryl-ribose 2′-epimerase (DprE1) inhibitors are an innovative and futuristic orally active group of antituberculosis agents. A few DprE1 inhibitors are in the clinical trial for tuberculosis (TB), including macozinone. This review highlights the discovery, developmental status, clinical studies, patents, and prospects of macozinone (MCZ). The patent and non-patent literature search was done by entering keywords such as macozinone; MCZ; PBTZ169; PBTZ-169 in Pubmed, Espacenet, Patentscope, and the USPTO databases. However, data on Sci-Finder was searched using CAS registry number: 1377239–83–2. MCZ clinical trial studies were retrieved from the clinicaltrials.gov database using the exact keywords. The chemical structure of MCZ was disclosed in 2009. Accordingly, patents/patent applications published from 2009 to June 12, 2022, have been discussed herein. MCZ and MCZ hydrochloride salt patents were granted in 2014 and 2019, respectively, in the USA. The patent literature and the clinical trial studies suggest capsule, tablet, and suspension formulations of crystalline MCZ and its hydrochloride salt as the possible and prospective dosage forms to treat TB. Some combinations of MCZ with other drugs (chloroquine, telacebec, tafenoquine, TBI-166, and sanfetrinem) with improved anti-TB efficacy have been documented. Based on the literature covered in this review article on the clinical studies and patents applied/granted to MCZ, it can be inferred that MCZ seems to be a promising DprE1 inhibitor and could help to tackle the emerging dilemma of drug-resistant either as a monotherapy or in combination with additional anti-TB agents. Furthermore, the authors anticipate the development of new combinations, salts, and polymorphs of MCZ as anti-TB agents shortly. This review article might prove beneficial to the scientific community as it summarizes chemistry, pharmacology and provides an update on the clinical studies and patents/patent applications of one of the emerging anti-TB drugs in one place.

Purchase intention has become a critical issue to the marketers of smartphones as the market has become very competitive, volatile, uncertain and dynamic during Covid-19 than ever before. For sustaining in the competitive market, every marketer is trying to upgrade its product appearance, product quality, service quality, attractive features, and latest version of software as a whole. This study has investigated the effects of product features, brand image, product price, and social influences on young customers' purchase intention of smartphone during this Covid-19 pandemic time. Survey was conducted using structured questionnaire by collecting data from 305 respondents by using convenience sampling technique. Statistical Package for the Social Sciences (SPSS) integrated with AMOS was employed for data analysis. Cronbach's alpha, composite reliability and average variance extracted (AVE) were used to test the reliability and validity of the collected data while hypotheses were tested by using Structural equation modeling (SEM). The findings of the study shows that, there is a significant effect of product features, brand image, and product price on purchase intention of a smartphone but social influences has no significant impact on young customers' purchase intention. The study results will help the smartphone marketers to redesign their pandemic and post pandemic segmenting, targeting, differentiation and positioning strategies. Practical and managerial implications along with the future research directions have been discussed at the end of this paper also.

Objectives: The study aimed to synthesize and evaluate the potential anti-inflammatory and analgesic activities of rationally designed hybrid molecules of imidazolone and indole nuclei linked through a methylene bridge. Methods: Indolyl-imidazolone hybrids were synthesized in three simple steps starting from 2-phenyl-1H-indole (1). In the first step, compound 1 was converted to 2-phenyl-1H-indole-3-carbaldehyde (2) using standard conditions of the Vilsmeier Haack reaction. Benzoyl glycine was reacted with 2 (step 2) followed by treatment with aromatic/aliphatic amines (step 3) to furnish the indolyl-imidazolone hybrids. In vivo anti-inflammatory and analgesic activity along with ulcerogenicity of the prepared hybrids were evaluated in experimental animals. Molecular properties and pharmacokinetic profile were also predicted using online computational software. Cyclooxygenase-2 (COX-2) enzyme (PDB: 3pgh) was used for molecular docking studies. Indomethacin and aspirin were used as reference compounds for the comparison purpose. Results: The percentage inhibition in edema in rats and reduction in frequency of acetic acid induced writhes in mice indicated that two compounds namely 3-(3-Hydroxpropyl)-2-phenyl-5-[(2-phenyl-1H-indol-3-yl)methylene]-4H-imidazol-4-one (4g) and 3-(2,4-Dinitrophenyl)-2-phenyl-5-[(2-phenyl-1H-indol-3-yl) methylene]- 4H-imidazol-4-one (4b) could be useful in treating pain and inflammatory conditions. Both the hybrid molecules exhibited better biological spectrum than the standard drug indomethacin. Additionally, both the potent compounds were noted to be less ulcerogenic than indomethacin. Pharmacokinetic profile predicted using ADMETsar and SwissADME cheminformatic software indicated compound 4g to be orally bioavailable with high blood brain barrier permeability. However, molecular docking studies revealed that compound 4b binds to COX-2 enzyme more strongly than 4g as indicated by a lower binding energy and formation of hydrogen bond interactions with amino acid residues in the binding pocket. Conclusions: It could be concluded that hybrid compounds 4b and 4g are promising lead candidates and should be further studied to develop compounds for the treatment of inflammatory conditions.

Introduction: Alzheimer’s disease (AD) is one of the most common and prevalent forms of neurodegenerative diseases. Coumarin is a versatile scaffold that exhibits a wide range of biological properties including cholinesterase inhibitory activity and therefore is an important heterocyclic moiety to develop anti-AD drugs. Objectives: This study aimed to design and synthesize coumarin linked 1,3,4-oxadiazole hybrid derivatives as multi-target directed ligands (MTDLs) and to investigate their in vitro anticholinesterase, antioxidant and anti-inflammatory activities. Methods: Two series (4a-n and 7a-m) of low molecular weight ligands (27 compounds) containing coumarin linked 1,3,4-oxadiazole hybrids were synthesized and their chemical structures were characterized using analytical data. In vitro acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) inhibitory activity, antioxidant activity and cyclooxygenase (COX) inhibitory activity were investigated following standard spectrophotometric methods. Molecular docking studies to predict the binding mode with AChE and BuChE in addition to the pharmacokinetic profile of the synthesized compounds were studied with the help of online cheminformatics software. Results: Amongst the tested compounds for anticholinesterase activity, 4e and 4g hybrid derivatives were found to be the most potent AChE inhibitors (IC50 values = 29.56 and 28.68 μM), respectively. Compound 4m exhibited the maximum inhibitory activity against BuChE (IC50 value = 23.97 μM). Compounds 4g and 4e also showed higher selectivity index (SI) of 1.652 and 1.552 as compared to standard galantamine (SI = 1.132). Molecular docking studies revealed that 4g and 4e, two most potent AChE inhibitors identified through in vitro assay, binds well to AChE (binding energy scores of −9.7 and −10.1 Kcal/Mol). Synthesized hybrid molecules also exhibited good to excellent in vitro antioxidant and anti-inflammatory activities. Conclusion: Based on the results of in vitro and in-silico studies, it could be concluded that coumarin-oxadiazole hybrids acts as MTDLs and are promising source of anti-AD drugs. Further detailed investigations and modification of these compounds can lead to the development of highly potent therapeutics for the treatment of AD.

Background: Essential oils have been known to possess useful biological activities and are widely used in aromatherapy owing to their peculiar aroma. The present study compared the essential oil composition isolated from the Chinese and Saudi ginger cultivars and determined their antimicrobial activity. Methods: The volatile compounds were extracted by a hydrodistillation method and the composition was analysed by gas chromatography coupled with mass spectrometry (GC–MS). The antibacterial activity of oils was tested against the pathogenic Gram positive and Gram negative bacterial strains. Potential bioactivities were predicted with the help of Prediction of activity spectra for substances (PASS) software and the molecular docking studies on the mycobacterial protein were carried out using Pyrex with Vina wizard tool. Results: A total of 43 and 30 volatile components were identified in the Chinese and Saudi varieties respectively. α–zingiberene in the Chinese and ar-curcumene in Saudi ginger oil were found to be the major volatile constituents. Ginger oil showed better antibacterial activity against Gram positive than Gram negative bacteria. Molecular docking studies showed ar-curcumene to have high binding affinity for the inhibition of bacterial protein. Conclusion: The presence of the biological active compounds such as α–zingiberene, ar-curcumene and β-sesquiphellandrene makes ginger essential oil a potential source of antimicrobial agents and as an additive/preservative in the food industry.

Thyme is an evergreen shrub that has been utilized in traditional medicine and culinary packages for centuries because of its aroma and medicinal properties. The medicinal properties of thyme leaves are attributed to its volatile constituents. The study aimed to identify the volatile constituents in the oil extracted from the Thyme sp grown in Oman and to evaluate its in vitro antibacterial and antioxidant activity. Fresh Thyme leaves were collected from Muscat, Sultanate of Oman in the month of September 2018. Thyme oil was isolated from leaves by hydro-distillation. The volatile chemical constituents present in the thyme oil were analyzed by Gas Chromatograph coupled with Mass Spectrometer. The ability of isolated oil to scavenge free radicals was evaluated by an in vitro DPPH assay method while antimicrobial activity was tested against S. aureus and E. coli bacterial strains by disc diffusion method. The bioactivity of the major constituent of the oil was predicted with the help of PASS and CLC-pred software. Molecular docking studies were performed by docking server. GC–MS analysis of thyme oil revealed the presence of 11 components. Carvacrol and γ-terpinene were identified as the major volatile constituents in thyme oil. Thyme oil inhibited 71.57% of DPPH radicals at 40 µg/mL concentration. Thyme oil displayed the better antimicrobial activity than the standard drug ampicillin against both the bacteria. Antiseptic, antiinfective, reductant and antimutagenic bioactivities of carvacrol as predicted by PASS support the in vitro experimental results. CLC-pred showed carvacrol to be active against Metastatic melanoma, Oligodendroglioma and Non small cell lung cancer cell lines. The antioxidant and antimicrobial activity of Omani thyme oil could be due to its high content of carvacrol. Omani thyme oil seems to be a viable alternative source of natural antimicrobial agent(s) and warrants further studies to ascertain its therapeutic spectrum of biological studies. Keywords: Antimicrobial, Antioxidant, DPPH, Essential oil, Hydro-distillation, Thyme

Based on the heterocyclic core of bendamustine, four series (4a–g, 5a–f, 8a–b and 9a–b) of benzimidazole derivatives were designed and synthesized starting from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide. In the rational design of target molecules, the benzimidazole ring of bendamustine was retained and the bis-(chloroethyl) amine group (mechlorethamine) was substituted with several biologically active scaffolds such as oxadiazole, thiadiazole, and triazolo-thiadiazines, in the hope of obtaining novel cytotoxic agents with improved efficacy and safety. Cytotoxic activities of the designed analogues were carried out at the National Cancer Institute (NCI), USA, against full NCI 60 human cell lines. Among all the tested compounds, 4f (761982/1) exhibited significant antiproliferative activity and was further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI50 values ranging from 0.09 to 16.2 μM and found superior for CNS cancer cell line SNB-75 (GI50 0.09, TGI 1.39, LC50 >100 and log10GI50 −7.0, log10TGI-5.86, log10LC50 >−4.00). Docking study was also performed to provide an insight about the binding mode into binding sites of topoisomerase enzyme. Hopefully in future, compound 4f could be used as a lead compound for developing new anticancer agents. Keywords: Bendamustine, Benzimidazole, Chlorambucil, Sulforhodamine B, Human cell lines

In the last few decades, metabolite identification and detection have become an integral component of drug discovery process. The detection and depiction of an identified metabolite is significant for the development of safe and effective therapeutic agents as these metabolites may be pharmacologically active or toxic in nature. A (UPLC-MS/MS) method was developed for the quantification of eslicarbazepine acetate metabolite (M3), cis-10,11-dihydro-5H-dibenz[b,f]azepine-10,11-diol, in rat plasma. Eslicarbazepine acetate was extracted from rat plasma by precipitation technique using acetonitrile as a precipitating solvent. Chromatographic separation was accomplished using acetonitrile-0.01 M potassium dihydrogen phosphate (60:40, v/v) as mobile phase at a flow rate of 0.2 ml/min on Waters Acquity BEH 150 × 2.1 mm, 1.7 µm, C18 column at 30˚ C. The linearity of the calibration curve was 5–100 ng/ml for metabolite M3. The overall intra- and inter-day precision did not exceed 3%. In silico, in vitro and in vivo approaches have been used to facilitate the detection and depiction of eslicarbazepine acetate metabolites. MetabolExpert was used to predict the probable metabolites of the compounds. Metabolite of eslicarbazepine acetate was identified using human liver microsomes.

This paper investigates ballistic performance of two different ceramic-based armor designs using finite element analysis. The first design is a bi-layer armor consists of a ceramic front layer and a Kevlar-29 composite backing layer. The second design consists of a ceramic filled honeycomb front layer and a Kevlar-29 composite backing layer. 3D finite element models are developed with the commercial software Abaqus/Explicit. The models are validated by comparing against experimental results from different sources. Both single-hit and double-hit impacts were carried out using an ogival-nosed hardened steel 4340 projectile of mass 5.5 g. The ballistic performances of the two designs are compared in terms of penetration mechanisms and ballistic resistance. It was found that the presence of honeycomb in the second armor design has a significant effect on its ballistic performance. The cell walls interrupted the stress wave propagation and confined the fracture in a local area. The ballistic limit of the second armor design in a single-hit impact decreased significantly but the resistance to a second hit did not decrease.

A detailed design optimization of a composite over wrapped pressure vessel (COPV) is performed through finite element analysis (FEA) and testing. The design optimization of a type IV polymer-lined composite overwrapped pressure vessel is performed by means of the finite element method using ABAQUS software. A plug-in named WCM in ABAQUS is used that automates the entire process of constructing a COPV FEA model. This work investigates the influence of winding angle, number of layers, and sequence of layers on the burst strength of COPV. Maximum stress, maximum strain, Tsai Hill, Tsai Wu and Hashin progressive failure criteria are used to find the burst strength of the COPV. Comparing all the results obtained using above the failure criteria, it is found that the maximum strain criterion is more conservative, and the Hashin criterion is the least conservative. Digital Image Correlation (DIC) was utilized during burst testing to quantify the failure strain in different directions. The numerical results were compared with the experimental burst testing results and a reasonably good comparison was found.

Based on the core structure of Felbinac drug, three series (4a–d, 5a–d and 6a–n) of five membered heterocyclic derivatives containing three heteroatoms were designed and synthesized starting from Felbinac. In the rational design of the target molecules, the biphenyl ring along with the methylene bridge of felbinac was retained while the carboxyl group was substituted with biologically active substituents like 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole, with an intent to obtain novel, better and safer anti-inflammatory agents with improved efficacy. The prepared molecules were then investigated for their anti-inflammatory, ulcerogenicity and analgesic activity in experimental animals. The tested compounds exhibited varying degrees of inflammatory activity (25.21–72.87%), analgesic activity (27.50–65.24%) and severity index on gastric mucosa in the range of 0.20–0.80 in comparison to positive control felbinac (62.44%, 68.70% and 1.5, respectively). Among all the prepared compounds, 2-(biphenyl-4-ylmethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole (6c) emerged as the most potent NSAID compound exhibiting the highest anti-inflammatory activity (72.87% inhibition) and analgesic activity (65.24%) along with the least severity index on gastric mucosa (0.20). Further, molecular docking on cyclooxygenase and in silico ADME-Toxicity prediction studies also supported the experimental biological results and indicated that 6c has a potential to serve as a drug candidate or lead compound for developing novel anti-inflammatory and analgesic therapeutic agent(s) with minimum toxicity on gastric mucosa. Keywords: Felbinac, Oxadiazole, Triazole, Thiadiazole, Anti-inflammatory, Molecular docking

A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid (3) and 3-(biphenyl-4-yl)propionic acid (4), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes (2a–d) to obtain the corresponding furan-2(3H)-ones (5a–h). The purified and characterized furanones were then converted into their corresponding 2(3H)-pyrrolones (6a–h) and N-benzyl-pyrrol-2(3H)-ones (7a–h). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve (Staphylococcus aureus and Bacillus subtilis), Gram −ve bacteria (Escherichia coli and Pseudomonas aeruginosa) and against fungal strains of Aspergillus niger and Aspergillus flavus. In vivo anti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds (5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h) which exhibited >53% inhibition in edema, were also screened for their in vivo analgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds (5d, 5h and 7h) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated using in silico approach and maximum mol doc score was obtained for compounds 7a–h. On comparing the in vivo and in silico anti-inflammatory results of synthesized compounds, N-benzyl pyrrolones (7a–h) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as Cl or NO2 are more biologically active.

In the present study, two new series of pyrazolines (3a–h & 4a–h) were synthesized starting from p-acetamidophenol (paracetamol) and evaluated for their antibacterial, antifungal and antitubercular activities. Chalcones (2a–h) prepared by condensing 3-acetyl-4-hydroxyphenyl acetamide (1) with different aromatic aldehydes were reacted with phenyl hydrazine and isonicotinic acid hydrazide to obtain phenyl-pyrazolines (3a–h) and isoniazid-pyrazolines (4a–h), respectively. The structures of the synthesized compounds were confirmed by spectral and microanalysis studies. Newly prepared pyrazoline compounds exhibited significant antibacterial activity against the organisms Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa when compared with the standard antibiotic Ciprofloxacin. Compound 4g showed potent antibacterial activity against P. aeruginosa and S. aureus (MIC-3.12 μg/mL), however, against E. coli compound 3d, 4c, 4d, 4f & 4g were found to have an MIC of 6.25 μg/mL. Antifungal activity of compound 4d against Candida albicans and Aspergillus niger (MIC-3.12 μg/mL) was found to be better than the standard drug Ketoconazole. The results of antitubercular activity of the synthesized compounds against Mycobacterium tuberculosis H37Rv by the agar microdilution method are quite promising. The antitubercular activity of compounds 4c, 4d & 4g (MIC-3.12 μg/mL) was found to be superior than that of the reference drug Streptomycin which showed MIC equal to 6.25 μg/mL. It was observed that pyrazolines with chloro, nitro or methoxy substituent showed better activity. Also, the pyrazolines derived from isoniazid (4a–h) were found to be better in their antibacterial, antifungal and antitubercular action than those derived from phenyl-hydrazine (3a–h).

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a–k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a–k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. Keywords: Imidazolidine, Indomethacin, Anti-inflammatory, Analgesic

In continuation of our research on nitrogen containing heterocyclic compounds to develop potent antimicrobial and antimycobacterial agents, some novel 2(3H) pyrrolone derivatives were synthesized. We report here two new series of 3-Arylidene-5-(4-chloro/methyl phenyl)-2(3H) pyrrolones (14–19) and 3-Arylidene-5-(4-chloro/methyl phenyl)-1-benzyl-2(3H) pyrrolones (20–25) prepared by reacting intermediate furanone compounds (6–13) with ammonia gas and benzylamine respectively. The structures of the title compounds were established on the basis of IR, 1H NMR, mass spectral data and elemental analysis results. All the synthesized pyrrolone derivatives were evaluated for their possible antibacterial, antifungal and antitubercular activities. Among all the synthesized compounds, compound 17, 3-(4-Hydroxy-3-methoxybenzylidene)-5-(4-chlorophenyl)-2(3H)-pyrrolone, emerged as a lead compound exhibiting the highest antibacterial, antifungal and antitubercular activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Mycobacterium tuberculosis with 6.25 μg/mL MIC (minimum inhibitory concentration). Molecular properties of pyrrolones were also calculated by Molinspiration software for drug likeness. It was observed that all 2(3H) pyrrolones (14–19) obeyed Lippinski’s rule of five and expected to be orally active. They were also found to be more potent antimicrobial agents than 1-benzyl-2(3H) pyrrolones (20–25) and their activity was comparable with standard drugs such as Ciprofloxacin, Ketoconazole and Streptomycin.

This study was undertaken to assess the antifungal potential of the essential oil and various extracts of Mikania scandens (L.) Willd. The hydrodistilled leaf essential oil of M. scandens was analysed by GC–MS. Twenty-four compounds representing 97.45% of the total leaves oil were identified, of which β-caryophyllene (16.98%), δ-cadinene (12.22%), α-cubebene (11.33%), 1,2-benzenedicarboxylic acid (10.17%), caryophyllene oxide (7.74%), β-himachalene (4.68%), T-cadinol (3.98%), tetratetracontane (3.83%), 1H-cyclopropa[a]naphthalene (3.56%), β-farnesene (3.08%) etc. were the major compounds. The essential oil and extracts (chloroform, ethyl acetate and methanol) of M. scandens were tested for antifungal activity, which was determined by disc diffusion and minimum inhibitory concentration (MIC) determination methods. The essential oil and various extracts displayed a great potential of antifungal activity as a mycelial growth inhibition against the tested phytopathogenic fungi such as Rhizoctonia solani AG-1 (IB) KACC 40111, R. solani AG-2-2 (IV) KACC 40132, Pythium graminicola KACC 40155, Tricoderma harzianum KACC 40791 and Fusarium oxysporum KACC 40052, in the range of 40.0–75.4% and the minimum inhibitory concentration ranging from 125 to 500 μg/ml. The present results demonstrated that M. scandens mediated oil and extracts could be potential sources of natural fungicides to protect crops from fungal diseases.

Background: Phthalates, a large group of endocrine disruptors, are ubiquitous in the environment and detrimental to human health. This scoping review aimed to summarize the effects of phthalates on laboratory animals relevant to humans, assess toxicity, and analyze mechanisms of toxicity for public health concerns. Methods: Articles were retrieved from Google Scholar, PubMed, ScienceDirect, and Web of Science search engines. The search used the term “toxicity of phthalates in vivo, animals or birds or fish.” Original research articles published between 2010 and 2024 describing in vivo toxicity in rat, mouse, bird, and fish models, were included. Conversely, articles that did not meet the above criteria were excluded from this scoping review. Two authors independently extracted data using data extraction tools based on themes, while a third arbitrated if consensus was not met. A senior researcher developed the themes, which were further refined through discussions. Data analysis involved quantitative (percentage of studies) and qualitative (content analysis) methods. Results: Of the 8180 articles screened, 153 met the inclusion criteria. Most of them were published after 2015 (74.50 %). The scoping review showed that DEHP (56.20 %) and DBP (21.57 %) were the most studied phthalates followed by BBP, DiBP, DMP, DEP, BBOP, and DiNP. Scarce data were available on DnOP, DPHP, DPeP, DUDP, DTDP, DMiP, and DiOP. Interestingly, studies of combinations of two or more phthalates were also present. The main laboratory animals employed were rats (48.37 %) and mice (39.87 %), while the least studied were birds (5.22 %) and fish (6.53 %). Most studies related to testicular toxicity (37.60 %), hepatotoxicity (23.53 %), and ovarian toxicity (18.30 %) investigations, while the rest consisted of neurotoxicity (6.88 %), renal toxicity (6.53 %), and thyroid toxicity studies (4.57 %). Studies focused on oxidative stress (34.64 %), apoptosis (22.22 %), steroid hormone deprivation (20.26 %), lipid metabolism disorder (11.76 %), and immunotoxicity (5.88 %) as mechanisms of toxicity. The most commonly used techniques were H&E, RT-qPCR, ROS assay, WB, IHC, ELISA, RIA, TUNEL, TEM, IFM, FCM, and RNA-seq. Conclusions: DEHP and DBP are the most toxic and studied phthalates, while BBP, DiNP, DiBP, DiDP, BBOP, DMP, and DiOP and their combinations require more accurate studies to confirm their toxic effects on human health and mechanisms of action. These will assist policymakers in adopting strategies to minimize public exposure and adverse effects.

The correlation between sports participation and psychological well-being is well-documented, revealing a complex interplay influenced by competition level and cultural context. This is particularly relevant in Korea, where the university sports culture significantly impacts student life. This study evaluates how competitive versus non-competitive sports affect Korean university students' psychological well-being using a quantitative approach with SmartPLS 4 for multi-group analysis. Findings reveal that competitive sports significantly enhance mental toughness and stress management through structured coping mechanisms and robust social support, improving coping strategy effectiveness by 34 % compared to non-competitive sports. Conversely, participants in non-competitive sports experience greater general well-being with a 40 % higher use of informal support. These insights suggest that university sports programs could benefit from targeted interventions incorporating specific coping strategies and social support frameworks tailored to the competitive context. This research underscores the need for precise stress management techniques and resilience-building exercises in sports curricula to optimize psychological well-being across different sports environments in Korean universities.

Expansive soil dual behavior (swell/shrink) exhibits high compressibility and volumetric instability against the frequent moisture imbalance, rendering premature failure of lightweight structures. The present research highlighted the geotechnical behavior of expansive soil treated with industrial waste pozzolanic fly ash (FA) materials. Fly ash, a leftover from coal burning in power plants is considered a problematic solid waste globally. The typical disposal technique for fly ash can lead to the degradation of flora and fauna and contamination of fertile land. However, numerous research studies reveal that fly ash can be used to effectively strengthen the geoengineering properties, including physical, chemical, and biological. This paper critically reviews past research on the efficiency of fly ash as a soil stabilizer in enhancing the mechanical behavior of expansive soils. The effect of varying dosages and types of fly ash in soil mixture on the Atterberg limits, unconfined compressive strength (UCS), California Bearing Ratio (CBR), and swell potential is critically reviewed through a series of geotechnical and microstructural characterization tests. The addition of varying percentages of fly ash (25–40%) to expansive soil shows an improvement in plastic behavior (up to 30–33%), compressive shear strength (40–48%), penetration resistance (52–55%) with least swelling (42–48%), and compressibility (36–40%) of fly ash-soil. Furthermore, the volumetric stability (swell/shrink) of clayey soil is attributed to mineral alteration and chemical compositions due to active pozzolanic reactions. This study may prove to be very effective in devising an alternative stabilizer to address the dual nature problems associated with expansive soil.

Escherichia coli is one of the major pathogens causing mastitis in lactating mammals. We hypothesized that E. coli from the gut and mammary glands may have similar genomic characteristics in the causation of mastitis. To test this hypothesis, we used whole genome sequencing to analyze two multidrug resistant E. coli strains isolated from mammary tissue (G2M6U) and fecal sample (G6M1F) of experimentally induced mastitis mice. Both strains showed resistance to multiple (>7) antibiotics such as oxacillin, aztreonam, nalidixic acid, streptomycin, gentamicin, cefoxitin, ampicillin, tetracycline, azithromycin and nitrofurantoin. The genome of E. coli G2M6U had 59 antimicrobial resistance genes (ARGs) and 159 virulence factor genes (VFGs), while the E. coli G6M1F genome possessed 77 ARGs and 178 VFGs. Both strains were found to be genetically related to many E. coli strains causing mastitis and enteric diseases originating from different hosts and regions. The G6M1F had several unique ARGs (e.g., QnrS1, sul2, tetA, tetR, emrK, blaTEM-1/105, and aph(6)-Id, aph(3″)-Ib) conferring resistance to certain antibiotics, whereas G2M6U had a unique heat-stable enterotoxin gene (astA) and 7192 single nucleotide polymorphisms. Furthermore, there were 43 and 111 unique genes identified in G2M6U and G6M1F genomes, respectively. These results indicate distinct differences in the genomic characteristics of E. coli strain G2M6U and G6M1F that might have important implications in the pathophysiology of mammalian mastitis, and treatment strategies for mastitis in dairy animals.