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Abstract This study explored the recovery of oil from lemon peel biomass and then tested it in a spark ignition as a substitute for gasoline. The study adopted the micro-arc oxidation coating technique, intending to improve the engine performance of the lemon peel oil-gasoline blends. The oil was recovered from discarded lemon peel biomass using steam distillation and then tested in the engine as a fuel by blending it with gasoline at volume ratios of 10, 20, and 30%. An endoscopic visualization approach was employed in this research work to assess the combustion initiation and flame characteristics of gasoline and lemon peel oil blends under different test conditions. Compared to gasoline and blends comprising 20 and 30% lemon peel oil, the 10% lemon peel oil mix produced higher thermal efficiency and lower emissions. The optical analysis demonstrated that premixed combustion with the 10% blend was found to be the highest, resulting in improved combustion and subsequently increased cylinder pressure. To improve the engine performance of the lemon peel oil blends with higher substitution (20 and 30%), the piston was coated with a ceramic coating. A novel technique, namely the micro-arc oxidation technique, was utilized for the coating. The coated piston engine fueled with a 20% lemon peel oil blend showed a 3% and 4.69% increase in thermal efficiency compared to the uncoated piston fueled with a 20% blend and sole gasoline, respectively. The hydrocarbon and carbon monoxide emissions of the engine with a coated piston fueled by the 20% lemon peel oil blend were reduced by 12.7% and 12%, respectively, as compared to gasoline operation in the engine with an uncoated piston.

The use and manufacture of nanomaterials are expanding, which is concerning for human health. Graphene oxide (GO), magnesium oxide (MgO), and quercetin (QU) have typically had significant growth because of their diverse range of applications in nanomedicine. They are utilised in the treatment of cancer, medication delivery, tissue engineering, healing of wounds, and biosensor. In this work, MgO-QU/GO nanocomposite was synthesized and its antioxidant was tested in a zebrafish model. Further obtained MgO-QU/GO nanocomposite was characterized through UV, XRD, FTIR, and SEM with EDAX analysis. Zebrafish adult seven test groups were used in the experiment with each group containing 10 fish follows fish fed the control, and exposed to MgO-QU/GO nanocomposite concentration 0+0.0+20.0+40.0+80.0+20+0.0+40+0.0+80+0 mg/L. The outcome shows that the toxicity of the utilised nanocomposite was comparatively low after zebrafish were exposed to MgO-QU/GO and recovered. Exploratory MgO-QU/GO treatment to zebra fish significant by decreased the Lipid Peroxidation (LPO) and elevated the antioxidant. These findings imply that nanocomposite at the concentration considered here might be a workable substitute for water recovery as they have no negative effects on the long-term life and welfare of humans and animals.

Current study establishes synthesis of AgNPs from Solanum trilobatum by a simple microwave protocol. Major phytoconstituents such as solasodine, solanine, solanidine were present in the leaves extract of Solanum trilobatum were examined and explored by GC-MS analysis. In vitro anti-oxidant analysis of green synthesized AgNPs from Solanum trilobatum leaf extract using DPPH and ABTS assays reveals that IC50 values (14.10 µg/ml and 12.90 µg/ml) equipotent anti-oxidant activity with reference standard trolox IC50 values (9.10 µg/ml and 9.80 µg/ml) respectively. UV–Visible spectroscopy analysis of green synthesized AgNPs shown its maximal absorbance of at 420 nm, which affirms that green mediated synthesis of silver nanoparticles from Solanum trilobatum. The results of FT-IR spectral analysis showed that flavonoids, sterols, saponin alkaloids, terpenoids, and polysaccharides were existed in Solanum trilobatum aqueous plant leaf extract, which were responsible for the reduction and subsequent capping of AgNPs. X-ray diffraction method confirmed that silver nanoparticles have spherical crystals with face-centered cubic structure. Zeta potential spectroscopy revealed the stability of green synthesized silver nanoparticles. The results of the particle size analyzer confirm that the average size of the green-synthesised AgNPs is 50 nm. Scanning electron microscope images of green synthesized silver nanoparticles show the formation of spheres and stones. HR-TEM results further affirm that sphere size of AgNPs. Further green synthesized AgNPs screened for its anti-microbial potential against bacterial cultures of E.coli (MTCC 452), P. aeruginosa (MTCC 1688), S. typhi (MTCC 733) and K. pneumonia (MTCC 39) and their result revealed that zone of inhibition 19 ± 0.11, 17 ± 0.08, 13 ± 0.07 and 16 ± 0.11 mm respectively. Finally, the explored phytocompounds from Solanum trilobatum and standard drugs tetracyclin was screened against four clinical pathogen membrane target proteins reveals that excellent binding affinity with maximal docking score -9.4 kcal/mol by solasodine against target protein Klebsiella pneumonia AcrB with the BDM91288 efflux pump (PDB ID 8P1I). Significance of silver nanoparticles (AgNPs) synthesis from Solanum trilobatum offers significant antimicrobial and antioxidant benefits. Silver nanoparticles from S. trilobatum act as promising candidates for therapeutic applications, particularly in combating infections and oxidative damage in biomedical applications.

In the pursuit of sustainable and environmentally friendly engineering materials, this study investigates the potential of Ipomoea carnea fibers (ICF) as a reinforcement agent in bran particulates epoxy matrix used to fabricate the composite laminates by a traditional process with varying filler weight fraction. The composite material’s characteristics were comprehensively analyzed using various techniques, including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Mechanical Testing, Scanning Electron Microscopy (SEM), and Thermogravimetric Analysis (TGA). The results of this study reveal the promising potential of Ipomoea carnea fibers reinforced bran particulates epoxy composite as a novel engineering material. The analysis indicates improved mechanical properties such as tensile, flexural, and impact strength, enhanced thermal stability, and desirable morphological characteristics. Subsequently, the structural and chemical properties of the Ipomoea carnea fiber composite were explored using XRD and FTIR, shedding light on the crystalline nature (CI = 68.29%) and chemical bonding within the material. Bacterial inhibition was identified from the antibacterial activity; this viable material is for applications in various engineering sectors, including construction, automotive, and aerospace industries.

Small molecule-driven JNK activation has been found to induce apoptosis and paraptosis in cancer cells. Herein pharmacological effects of synthetic oxazine (4aS, 7aS)-3-((4-(4‑chloro-2-fluorophenyl)piperazin-1-yl)methyl)-4-phenyl-4, 4a, 5, 6, 7, 7a-hexahydrocyclopenta[e] [1,2]oxazine (FPPO; BSO-07) on JNK-driven apoptosis and paraptosis has been demonstrated in human breast cancer (BC) MDA-MB231 and MCF-7 cells respectively. BSO-07 imparted significant cytotoxicity in BC cells, induced activation of JNK, and increased intracellular reactive oxygen species (ROS) levels. It also enhanced the expression of apoptosis-associated proteins like PARP, Bax, and phosphorylated p53, while decreasing the levels of Bcl-2, Bcl-xL, and Survivin. Furthermore, the drug altered the expression of proteins linked to paraptosis, such as ATF4 and CHOP. Treatment with N-acetyl-cysteine (antioxidant) or SP600125 (JNK inhibitor) partly reversed the effects of BSO-07 on apoptosis and paraptosis. Advanced in silico bioinformatics, cheminformatics, density Fourier transform and molecular electrostatic potential analysis further demonstrated that BSO-07 induced apoptosis and paraptosis via the ROS/JNK pathway in human BC cells.

IntroductionNuclear factor kappa (NF-κB) plays a key role in cancer cell proliferation; thus, small molecule inhibitors of NF-κB activity can effectively inhibit breast cancer (BC) progression. We have previously reported oxazine and piperazine-linked pyrimidines as novel anti-cancer agents that can suppress NF-κB activation in BC cells. Moreover, the TRX-01 compound, an oxazine-linked pyrimidine, inhibited MCF-7 cells at a concentration of 9.17 µM in the Alamar Blue assay.MethodsThis work involved the analysis of frontier molecular orbitals, HOMO-LUMO interactions, and molecular electrostatic potential for the TRX-01 structure. Additionally, the TRX-01 compound was studied for cytotoxicity, and migration as well as invasion assays were performed on BC cells.ResultsFinally, TRX-01 blocked the translocation of NF-κB from the cytoplasm to the nucleus in MCF-7 cells and reduced NF-κB and IκBα levels in a dose-dependent manner. It also suppressed migratory and invasive properties of BC cells.ConclusionOverall, the data indicates that TRX-01 can function as a novel blocker of BC growth and metastasis by targeting NF-κB activation.

Environmental consciousness motivates scientists to devise an alternative method for producing natural fiber composite materials in order to decrease the demand for synthetic fibers. This study explores the potential of a novel composite material derived from madar fiber-reinforced epoxy with porcelain filler particulates, designed specifically for biomedical instrumentation applications. The primary focus is to assess the material's structural, mechanical, and antibacterial properties. X-ray Diffraction analysis was employed to discern the crystalline nature of the composite, revealing enhanced crystallinity due to the inclusion of porcelain particulates. Fourier-Transform Infrared Spectroscopy confirmed the chemical interactions and bonding mechanisms between madar fiber, epoxy matrix, and porcelain filler. Mechanically, the composite exhibited superior properties when addition of porcelain fillers, maximum results obtain in tensile strength of 51.28 MPa, flexural strength of 54.21 MPa, and impact strength of 0.0155 kJ/m2, making it ideal for robust biomedical applications. Scanning Electron Microscopy provided detailed insights into the morphology and distribution of the reinforcing agents within the epoxy matrix, emphasizing the fibrillated structure of madar fiber and the uniform dispersion of porcelain particulates. Importantly, antibacterial assays demonstrated the composite's potential resistance against common pathogenic bacteria, which is crucial for biomedical instrumentation. Collectively, this research underscores the promising attributes of the madar fiber reinforced epoxy composite with porcelain particulates, suggesting its suitability for advanced biomedical applications.

Actinomycetes provide a potentially limitless source of novel bioactive compound, possessing a wide range of potential therapeutic uses. Around 25,000 microbial secondary metabolites have been recognized; actinomycetes produce some 75%, of them, with fungi yielding 15%, Bacillus spp. 6%, and other bacteria producing around 1–3%. Species of Streptomyces provide 50–60 percent of the known antibiotics. Over the last seventy or so years, a vast array of microorganisms has been isolated from soils and other readily accessible environments and the screened for antibiotics. Such screening programs have significantly reduced the likelihood that novel antimicrobial compounds, particularly active against drug resistant species, will now be found. Fortunately, unusual marine environments may act as a future source of actinomycetes and other microorganisms capable of producing new secondary metabolite possessing antifungal, antibacterial, anticancer, insecticidal, enzyme inhibitory and other therapeutic properties. The aim of this review is to highlight marine actinomycetes as a novel source of such potentially critical novel antibiotic and bioactive compounds.

ZnO and ZnO-Y2O3 nanocomposites (NCs) were investigated for their photocatalytic degradation of Methylene blue (MB) dye. X-ray diffraction study demonstrates that the hexagonal structure of ZnO has crystallite size compared to ZnO-Y2O3 NCs and confirms the cubic configuration of Y2O3. Scanning electron microscopy shows that the ZnO nanoparticles are spherical and ZnO-Y2O3 NCs have smaller particles with less agglomeration. The decreased recombining of excited e−/h+ of ZnO-Y2O3 NCs is confirmed over fluorescence study. ZnO-Y2O3 exhibits a more significant degradation efficiency (96%) than ZnO nanoparticles (86%) in 120 min. ZnO-Y2O3 NCs have antibacterial as well as antioxidant activity.

Nigericin is a potent antibiotic derived from Streptomyces hygroscopicus which acts as a polyether ionophore. The anticancer property of nigericin was extensively studied, and it has been proven to inhibit cancer cell proliferation, progression, and invasion in prostate, colorectal, nasopharyngeal, and lung cancer. It also stimulates bacterial clearance in macrophages. The protective role of nigericin in sepsis, which is the foremost risk factor for acute lung injury and acute respiratory distress syndrome. Since bacteremia is frequently associated with lung injury, in this study we evaluated the potency of nigericin against an lipopolysaccharide (LPS)-induced sepsis mice model. BALB/c mice were challenged with intratracheal administration of LPS and simultaneously treated with 10 mg/kg and 20 mg/kg nigericin for 3 consecutive days. The mice were euthanized, and the lung tissue was excised to determine the lung wet/dry ratio. Bronchoalveolar lavage fluid was collected and assessed for protein content, LDH, and immune cell count. The antioxidant activity of nigericin was evaluated by measuring the MPO, MDA, SOD, and GSH activities in the lung tissues. The proinflammatory cytokines TNF-α and IL-6 were quantified to assess the anti-inflammatory potency against LPS-induced inflammation. iNOS, COX-2 and PGE-2 levels in lung tissue of nigericin-treated LPS-challenged mice were estimated to assess the immunomodulatory activity of nigericin. Finally, the antiapoptotic potency and cytoprotective effect of nigericin were analyzed by estimating apoptotic protein levels in lung tissue and assessing lung tissue histopathology with hematoxylin & eosin staining. Nigericin treatment significantly reduced immune cell infiltration, synthesis of proinflammatory cytokines, immunomodulatory proteins, and proapoptotic proteins in LPS-challenged mice. It also increased antioxidants and antiapoptotic protein Bcl2, thereby ameliorating lung tissue from LPS-induced inflammation. Our results indicate nigericin suppressed the LPS induced sepsis in an in vivo model and has the therapeutic potency to cure sepsis induced acute lung injury.

Regulation of intracellular concentration of calcium levels is crucial for cell signaling, homeostasis, and in the pathology of diseases including cancer. Agonist-induced entry of calcium ions into the non-excitable cells is mediated by store-operated calcium channels (SOCs). This pathway is activated by the release of calcium ions from the endoplasmic reticulum and further regulated by the calcium uptake through mitochondria leading to calcium-dependent inactivation of calcium-release activated calcium channels (CARC). SOCs including stromal interaction molecules (STIM) and ORAI proteins have been implicated in tumor growth, progression, and metastasis. In the present study, we analyzed the mRNA and protein expression of genes mediating SOCs—STIM1, STIM2, ORAI1, ORAI2, ORAI3, TRPC1, TRPC3, TRPC4, TRPC5, TRPC6, TRPC7, TRPV1, TRPV2, TRPM1, and TRPM7 in head and neck squamous cell cancer (HNSC) patients using TCGA and CPTAC analysis. Further, our in silico analysis showed a significant correlation between the expression of SOCs and genes involved in the mitochondrial dynamics (MDGs) both at mRNA and protein levels. Protein-protein docking results showed lower binding energy for SOCs with MDGs. Subsequently, we validated these results using gene expression and single-cell RNA sequencing datasets retrieved from Gene Expression Omnibus (GEO). Single-cell gene expression analysis of HNSC tumor tissues revealed that SOCs expression is remarkably associated with the MDGs expression in both cancer and fibroblast cells.

Background: Osteoarthritis is a severe degenerative joint disease characterized by swelling, joint pain, degradation of cartilage extracellular matrix, synovitis, callus formation, and loss of normal joint movements, which leads to functional limitations and seriously affect the patient’s life quality. Objective: The current research work was focussed to synthesize and characterize the chitosan-sodium alginate-polyethylene glycol-d-pinitol nanocomposites (CSP-dP-NCs) and evaluate its antiarthritic activity against the freund’s complete adjuvant (FCA)-triggered arthritis in animals. Methodology: The CSP-dP-NCs were synthesized by standard method. The development and properties of formulated CSP-dP-NCs were confirmed by several characterization techniques like UV–visible, photoluminescence, X-ray diffractometer (XRD), Fourier Transform-Infrared (FT-IR), scanning electron microscopic (SEM), energy dispersive X-ray (EDX), and dynamic light scattering (DLS) analyses. The arthritis was induced in experimental rats via administering 0.1 ml of FCA subcutaneously and then treated with 10 and 25 mg/kg of synthesized CSP-dP-NCs for 25 days. The bodyweight of animals were tabulated and then haematological parameters, organ index, and paw volume was examined. The levels of liver marker enzymes were assessed by standard techniques. The contents and pro-inflammatory cytokines and antioxidant parameters were quantified using assay kits. Results: The findings of characterization studies confirmed the development of CSP-dP-NCs with size ranging from 180 nm, tetragonal appearance, and narrowed distribution. The CSP-dP-NCs treated arthritic animals demonstrated the improved bodyweight and haematological parameters. The levels of thymus and spleen index and hind paw volume was decreased by the CSP-dP-NCs. The administration of CSP-dP-NCs to the arthritic rats also exhibited the decreased contents of IL-6, IL-10, IL-1β, TNF-α, MDA levels and increased the GSH level, CAT and SOD activities. The activities of ALP, ALT, and ASP also decreased in arthritic rats by the CSP-dP-NCs treatment. Conclusion: Altogether, the findings of this study demonstrated the antiarthritic activity of formulated CSP-dP-NCs against FCA-induced arthritic rats via modulating oxidative stress and inflammatory parameters. Hence, it could be the effective drug for the arthritis treatment in the future.

In breast cancer (BC), STAT3 is hyperactivated. This study explored the design of imidazopyridine-tethered pyrazolines as a de novo drug strategy for inhibiting STAT3 phosphorylation in human BC cells. This involved the synthesis and characterization of two series of compounds namely, 1-(3-(2,6-dimethylimidazo [1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-(substituted)piperazin-1-yl)ethanone and N-substituted-3-(2,6-dimethylimidazo[1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides. Compound 3f with 2,3-dichlorophenyl substitution was recognized among the tested series as a lead structure that inhibited the viability of MCF-7 cells with an IC50 value of 9.2 μM. A dose- and time-dependent inhibition of STAT3 phosphorylation at Tyr705 and Ser727 was observed in MCF-7 and T47D cells when compound 3f was added in vitro. Calculations using density functional theory showed that the title compounds HOMOs and LUMOs are situated on imidazopyridine-pyrazoline and nitrophenyl rings, respectively. Hence, compound 3f effectively inhibited STAT3 phosphorylation in MCF-7 and T47D cells, indicating that these structures may be an alternative synthon to target STAT3 signaling in BC.

Small molecules are being used to inhibit cyclin dependent kinase (CDK) enzymes in cancer treatment. There is evidence that CDK is a drug-target for cancer therapy across many tumor types because it catalyzes the transfer of the terminal phosphate of ATP to a protein that acts as a substrate. Herein, the identification of pyranopyrazoles that were CDK inhibitors was attempted, whose synthesis was catalyzed by nano-zirconium dioxide via multicomponent reaction. Additionally, we performed an in-situ analysis of the intermediates of multicomponent reactions, for the first-time, which revealed that nano-zirconium dioxide stimulated the reaction, as estimated by Gibbs free energy calculations of spontaneity. Functionally, the novel pyranopyrazoles were tested for a loss of cell viability using human breast cancer cells (MCF-7). It was observed that compounds 5b and 5f effectively produced loss of viability of MCF-7 cells with IC50 values of 17.83 and 23.79 µM, respectively. In vitro and in silico mode-of-action studies showed that pyranopyrazoles target CDK1 in human breast cancer cells, with lead compounds 5b and 5f having potent IC50 values of 960 nM and 7.16 μM, respectively. Hence, the newly synthesized bioactive pyranopyrazoles could serve as better structures to develop CDK1 inhibitors against human breast cancer cells.

EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3βS9 with a parallel increase in β-TrCP and phosphorylation of GSK-3βY216. Lithium chloride treatment increased the phosphorylation of GSK-3βS9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells.

A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound 5e IC50 value was found to be 18 μM. Thouracil amide compounds 5a and 5e inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound 5e interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.