A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor.
Sports video tracking is a research topic that has attained increasing attention due to its high commercial potential. A number of sports, including tennis, soccer, gymnastics, running, golf, badminton and cricket have been utilised to display the novel ideas in sports motion tracking. The main challenge associated with this research concerns the extraction of a highly complex articulated motion from a video scene. Our research focuses on the development of a markerless human motion tracking system that tracks the major body parts of an athlete straight from a sports broadcast video. We proposed a hybrid tracking method, which consists of a combination of three algorithms (pyramidal Lucas-Kanade optical flow (LK), normalised correlation-based template matching and background subtraction), to track the golfer's head, body, hands, shoulders, knees and feet during a full swing. We then match, track and map the results onto a 2D articulated human stick model to represent the pose of the golfer over time. Our work was tested using two video broadcasts of a golfer, and we obtained satisfactory results. The current outcomes of this research can play an important role in enhancing the performance of a golfer, provide vital information to sports medicine practitioners by providing technically sound guidance on movements and should assist to diminish the risk of golfing injuries.
Two series of novel acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors containing benzimidazole core structure were synthesized by a four-step reaction pathway starting from 4-fluoro-3-nitrobenzoic acid as the basic compound. The structure of the novel benzimidazoles was characterized and confirmed by the elemental and mass spectral analyses as well as (1)H NMR spectroscopic data. Of the 34 novel synthesized compounds, three benzimidazoles revealed AChE inhibition with IC50<10 μM. The highest inhibitory activity (IC50=5.12 μM for AChE and IC50=8.63 μM for BChE) corresponds to the compound 5IIc (ethyl 1-(3-(1H-imidazol-1-yl)propyl)-2-(4-nitrophenyl)-1H-benzo[d]imidazole-5-carboxylate). The relationship between lipophilicity and the chemical structures as well as their limited structure-activity relationship was discussed.
A series of novel 3-(substituted phenyl)-6,7-dimethoxy-3a,4-dihydro-3H-indeno[1,2-c]isoxazole analogues were synthesized by the reaction of 5,6-dimethoxy-2-[(E)-1-phenylmethylidene]-1-indanone with hydroxylamine hydrochloride. The title compounds were tested for their in vitro anti-HIV activity. Among the compounds, (4g) showed a promising anti-HIV activity in the in vitro testing against IIIB and ROD strains. The IC50 of both IIIB and ROD were found to be 9.05 microM and > 125 microM, respectively.
A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis H37Rv with a minimum inhibitory concentration of 10 μg/mL.
Series of pyrolidine analogues were synthesized and examined as acetylcholinesterase (AChE) inhibitors. Among the compounds, compounds 4k and 6k were the most potent inhibitors of the series. Compound 4k, showed potent inhibitory activity against acetyl cholinesterase enzyme with IC(50) 0.10 μmol/L. Pyrolidine analogues might be potential acetyl cholinesterase agents for AD.
A series of twelve dispiropyrrolidines were synthesized using [3+2]-cycloaddition reactions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H(37)Rv and INH resistant M. tuberculosis strains using agar dilution method, four of them showed good activity with MIC of less than 1 μM. Compound 4'-[5-(4-fluorophenyl)pyridin-3-yl]-1'-methyldispiro[indan-2,2' pyrrolidine-3',2″-indan]-1,3,1″-trione (4b) was found to be the most active with MIC of 0.1215 and 5.121 μM, respectively.
Medicinal plants are the main natural pools for the discovery and development of new drugs. In the modern era of computer-aided drug designing (CADD), there is need of prompt efforts to design and construct useful database management system that allows proper data storage, retrieval and management with user-friendly interface. An inclusive database having information about classification, activity and ready-to-dock library of medicinal plant's phytochemicals is therefore required to assist the researchers in the field of CADD. The present work was designed to merge activities of phytochemicals from medicinal plants, their targets and literature references into a single comprehensive database named as Medicinal Plants Database for Drug Designing (MPD3). The newly designed online and downloadable MPD3 contains information about more than 5000 phytochemicals from around 1000 medicinal plants with 80 different activities, more than 900 literature references and 200 plus targets. The designed database is deemed to be very useful for the researchers who are engaged in medicinal plants research, CADD and drug discovery/development with ease of operation and increased efficiency. The designed MPD3 is a comprehensive database which provides most of the information related to the medicinal plants at a single platform. MPD3 is freely available at: http://bioinform.info .
Cell contact formation, which is the process by which cells are brought into close proximity is an important biotechnological process in cell and molecular biology. Such manipulation is achieved by various means, among which dielectrophoresis (DEP) is widely used due to its simplicity. Here, we show the advantages in the judicious choice of the DEP microelectrode configuration in terms of limiting undesirable effects of dielectric heating on the cells, which could lead to their inactivation or death, as well as the possibility for cell clustering, which is particularly advantageous over the linear cell chain arrangement typically achieved to date with DEP. This study comprises of experimental work as well as mathematical modeling using COMSOL. In particular, we establish the parameters in a capillary-based microfluidic system giving rise to these optimum cell-cell contact configurations, together with the possibility for facilitating other cell manipulations such as spinning and rotation, thus providing useful protocols for application into microfluidic bioparticle manipulation systems for diagnostics, therapeutics or for furthering research in cellular bioelectricity and intercellular interactions.
A synergistic effect of the activated limestone-based catalyst (LBC) and microwave irradiation on the transesterification of waste cooking oil (WCO) was screened using a two-level factorial design and response surface methodology. The catalyst was prepared using a wet-impregnation method and was characterised for its surface element, surface morphology, surface area and porosity. The reaction was performed in a purpose-built continuous microwave assisted reactor (CMAR), while the conversion and yield of biodiesel were measured using a gas chromatography. The results showed that the catalyst loading, methanol to oil molar ratio and the reaction time significantly affect the WCO conversion. The optimum conversion of oil to biodiesel up to 96.65% was achieved at catalyst loading of 5.47 wt%, methanol to oil molar ratio of 12.21:1 and the reaction time of 55.26 min. The application of CMAR in this work reduced the transesterification time by about 77% compared to the reaction time needed for a conventional reactor. The biodiesel produced in this work met the specification of American Society for Testing and Materials (ASTM D6751). Engine test results shows the biodiesel has a lower NOx and particulate matters emissions compared to petrodiesel.
Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5-4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.
Rice blast, an extremely destructive disease caused by the filamentous fungal pathogen Magnaporthe oryzae, poses a global threat to the production of rice (Oryza sativa L.). The emerging trend of reducing dependence on chemical fungicides for crop protection has increased interest in exploring bioformulated nanomaterials as a sustainable alternative antimicrobial strategy for effectively managing plant diseases. Herein, we used physiomorphological, transcriptomic, and metabolomic methods to investigate the toxicity and molecular action mechanisms of moringa-chitosan nanoparticles (M-CNPs) against M. oryzae. Our results demonstrate that M-CNPs exhibit direct antifungal properties by impeding the growth and conidia formation of M. oryzae in a concentration-dependent manner. Propidium iodide staining indicated concentration-dependent significant apoptosis (91.33%) in the fungus. Ultrastructural observations revealed complete structural damage in fungal cells treated with 200 mg/L M-CNPs, including disruption of the cell wall and destruction of internal organelles. Transcriptomic and metabolomic analyses revealed the intricate mechanism underlying the toxicity of M-CNPs against M. oryzae. The transcriptomics data indicated that exposure to M-CNPs disrupted various processes integral to cell membrane biosynthesis, aflatoxin biosynthesis, transcriptional regulation, and nuclear integrity in M. oryzae., emphasizing the interaction between M-CNPs and fungal cells. Similarly, metabolomic profiling demonstrated that exposure to M-CNPs significantly altered the levels of several key metabolites involved in the integral components of metabolic pathways, microbial metabolism, histidine metabolism, citrate cycle, and lipid and protein metabolism in M. oryzae. Overall, these findings demonstrated the potent antifungal action of M-CNPs, with a remarkable impact at the physiological and molecular level, culminating in substantial apoptotic-like fungal cell death. This research provides a novel perspective on investigating bioformulated nanomaterials as antifungal agents for plant disease control.
A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 μM) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-α-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds in three classes, 6a, 6b, and 6m, were found to be the most potent derivatives showing 64%, 87%, and 74% antiproliferative activity in MDA-MB-231, SK-OV-3, and CCRF-CEM cells, respectively. Compound 6b showed an IC50 value of 3.6 mM in CCRF-CEM cells. These data suggest the potential antiproliferative activity of spiro-pyrrolidines/pyrrolizines.
We employed dielectrophoresis to a yeast cell suspension containing amyloid-beta proteins (Aβ) in a microfluidic environment. The Aβ was separated from the cells and characterized using the gradual dissolution of Aβ as a function of the applied dielectrophoretic parameters. We established the gradual dissolution of Aβ under specific dielectrophoretic parameters. Further, Aβ in the fibril form at the tip of the electrode dissolved at high frequency. This was perhaps due to the conductivity of the suspending medium changing according to the frequency, which resulted in a higher temperature at the tips of the electrodes, and consequently in the breakdown of the hydrogen bonds. However, those shaped as spheroidal monomers experienced a delay in the Aβ fibril transformation process. Yeast cells exposed to relatively low temperatures at the base of the electrode did not experience a positive or negative change in viability. The DEP microfluidic platform incorporating the integrated microtip electrode array was able to selectively manipulate the yeast cells and dissolve the Aβ to a controlled extent. We demonstrate suitable dielectrophoretic parameters to induce such manipulation, which is highly relevant for Aβ-related colloidal microfluidic research and could be applied to Alzheimer's research in the future.
The effect of crump rubber on the dry sliding wear behavior of epoxy composites is investigated in the present study. Wear tests are carried out for three levels of crump rubber (10, 20, and 30 vol.%), normal applied load (30, 40, and 50 N), and sliding distance (1, 3, and 5 km). The wear behavior of crump rubber-epoxy composites is investigated against EN31 steel discs. The hybrid mathematical approach of Taguchi-coupled Grey Relational Analysis (GRA)-Principal Component Analysis (PCA) is used to examine the influence of crump rubber on the tribological response of composites. Mathematical and experimental results reveal that increasing crump rubber content reduces the wear rate of composites. Composites also show a significant decrease in specific wear values at higher applied loads. Furthermore, the coefficient of friction also shows a decreasing trend with an increase in crump rubber content, indicating the effectiveness of reinforcing crump rubber in a widely used epoxy matrix. Analysis of Variance (ANOVA) results also reveal that the crump rubber content in the composite is a significant parameter to influence the wear characteristic. The post-test temperature of discs increases with an increase in the applied load, while decreasing with an increase in filler loading. Worn surfaces are analyzed using scanning electron microscopy to understand structure-property correlations. Finally, existing studies available in the literature are compared with the wear data of the present study in the form of a property map.
This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.
Nitrogen dioxide (NO2) and sulfur dioxide (SO2) are two major atmospheric pollutants that significantly threaten human health, the environment, and ecosystems worldwide. Despite this, only some studies have investigated the spatiotemporal hotspots of NO2 and SO2, their trends, production, and sources in Asia. Our study presents a literature review covering the production, trends, and sources of NO2 and SO2 across Asian countries (e.g., Bangladesh, China, India, Iran, Japan, Pakistan, Malaysia, Kuwait, and Nepal). Based on the findings of the review, NO2 and SO2 pollution are increasing due to industrial activity, fossil fuel burning, biomass burning, heavy traffic movement, electricity generation, and power plants. There is significant concern about health risks associated with NO2 and SO2 emissions in Bangladesh, China, India, Malaysia, and Iran, as they pay less attention to managing and controlling pollution. Even though the lack of quality datasets and adequate research in most Asian countries further complicates the management and control of NO2 and SO2 pollution. This study has NO2 and SO2 pollution scenarios, including hotspots, trends, sources, and their influences on Asian countries. This study highlights the existing research gaps and recommends new research on identifying integrated sources, their variations, spatiotemporal trends, emission characteristics, and pollution level. Finally, the present study suggests a framework for controlling and monitoring these two pollutants' emissions.
The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.
Cadmium (Cd) is an extremely toxic heavy metal that can originate from industrial activities and accumulate in agricultural soils. This study investigates the potential of biologically synthesized silicon oxide nanoparticles (Bio-SiNPs) in alleviating Cd toxicity in bayberry plants. Bio-SiNPs were synthesized using the bacterial strain Chryseobacterium sp. RTN3 and thoroughly characterized using advanced techniques. A pot experiment results demonstrated that Cd stress substantially reduced leaves biomass, photosynthesis efficiency, antioxidant enzyme activity, and induced oxidative damage in bayberry (Myrica rubra) plants. However, Bio-SiNPs application at 200 mg kg-1 significantly enhanced plant biomass, chlorophyll content (26.4 %), net photosynthetic rate (8.6 %), antioxidant enzyme levels, and mitigated reactive oxygen species production under Cd stress. Bio-SiNPs modulated key stress-related phytohormones by increasing salicylic acid (13.2 %) and abscisic acid (13.7 %) contents in plants. Bio-SiNPs augmented Si deposition on root surfaces, preserving normal ultrastructure in leaf cells. Additionally, 16S rRNA gene sequencing demonstrated that Bio-SiNPs treatment favorably reshaped structure and abundance of specific bacterial groups (Proteobacteria, Actinobacteriota, and Acidobacteriota) in the rhizosphere. Notably, Bio-SiNPs application significantly modulated the key metabolites (phenylacetaldehyde, glycitein, maslinic acid and methylmalonic acid) under both normal and Cd stress conditions. Overall, this study highlights that bio-nanoremediation using Bio-SiNPs enhances tolerance to Cd stress in bayberry plants by beneficially modulating biochemical, microbial, and metabolic attributes.
A search for new long-lived particles decaying to leptons is presented using proton-proton collisions produced by the LHC at √[s]=8 TeV. Data used for the analysis were collected by the CMS detector and correspond to an integrated luminosity of 19.7 fb(-1). Events are selected with an electron and muon with opposite charges that both have transverse impact parameter values between 0.02 and 2 cm. The search has been designed to be sensitive to a wide range of models with nonprompt e-μ final states. Limits are set on the "displaced supersymmetry" model, with pair production of top squarks decaying into an e-μ final state via R-parity-violating interactions. The results are the most restrictive to date on this model, with the most stringent limit being obtained for a top squark lifetime corresponding to cτ=2 cm, excluding masses below 790 GeV at 95% confidence level.