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Seaweeds are regarded as one of the greatest sources of biologically active substances with potent biological activities among the innumerable marine organisms. It finds numerous industrial applications in areas such as food and dairy, pharmaceuticals, medicine, cosmeceuticals, and nutraceuticals because it is a significant source of bioactive ingredients. It has been reported that the brown seaweed Padina boergesenii, also known as the leafy rolled-blade alga, has anti-venom activity against the Naja nigricollis. However, it is still unclear how these actions are prompted by it. Using in vitro and in vivo animal models, the current work seeks to evaluate the mechanistic anti-venom activity of Padina boergesenii methanolic extract (PBME) against Naja naja (N. naja) venom. The total antioxidant activity, deoxyribose radical scavenging activity, DPPH (2, 2-diphenyl-1-picrylhydrazylhydrate), and ferric reducing antioxidant power (FRAP) assay were used to measure the in vitro antioxidant activity. In vivo (venom neutralization, suppression of hemorrhagic, necrotic, myotoxic, and paw edema) and in vitro (inhibiting phospholipase A2 and procoagulant effects) anti-venom properties of PBME were studied against N. naja venoms. In every anti-oxidant test, the extracts demonstrated potency. Naja naja venom's median lethal dose was 0.5943 mg/kg of body weight. The N. naja venom–induced phospholipase A2, hemorrhagic, necrotic, myotoxic, and paw edema in mice were all considerably reduced by PBME. Animals exposed to PBME substantially and dose-dependently neutralized the N. naja venom by various mechanisms. Therefore, additional research into PBME's anti-venom characteristics as a neutralizing agent for snake venoms is a possibility. [ABSTRACT FROM AUTHOR]

The desert teak defoliator, Patialus tecomella Pajni, Kumar and Rose, 1991 is redescribed for the first time with habitus images, morphometric details and images of diagnostic characters. Tecomella undulata, an endangered desert forest plant, is frequently and severely attacked by a notorious curculionid pest, P. tecomella, throughout its range in arid and semi-arid areas of India. A DNA barcode was obtained and reported for molecular identification using cytochrome oxidase I (COI). Observations were made on the biology of the species: egg period 4–6 days, larval development period 10–12 days, pupal period 3–6 days and adult longevity 11–13 days. The total lifespan was 28–37 days. [ABSTRACT FROM AUTHOR]

Spherical tanks have been predominantly used in process industries due to their large storage capability. The fundamental challenges in process industries require a very efficient controller to control the various process parameters owing to their nonlinear behavior. The current research work in this paper aims to propose the Approximate Generalized Time Moments (AGTM) optimization technique for designing Fractional-Order PI (FOPI) and Fractional-Order PID (FOPID) controllers for the nonlinear Single Spherical Tank Liquid Level System (SSTLLS). This system features a large dead time, and its real-time modeling generally represents a Single Input Single Output (SISO) model. However, in practice, the derived SISO model is often a First Order Plus Dead Time (FOPDT) model, necessitating an effective controller to maintain the tank's steady-state level. In this research, the proposed AGTM method, based on the conventional Proportional Integral (PI) and Proportional Integral Derivative (PID) controllers, is compared with the FOPI and FOPID controllers for the nonlinear SSTLLS. The performance of these controllers is contrasted using metrics such as Integral Squared Error (ISE) and Integral Absolute Error (IAE), as well as time-domain characteristics containing Rise time, Peak time, Settling time, Peak overshoot, and Steady-state error. The implementation of the aforementioned controllers is done in simulation and real-time employing the MATLAB software environment and the Data Acquisition (DAQ) device National Instrument NI-DAQmx 6211. The simulation and experimental results demonstrate the exceptional performance of the designed Fractional-Order controllers based on the proposed method which offers an increased degree of freedom despite the more complex design process. [ABSTRACT FROM AUTHOR]

This study aims to reduce engine emissions while maintaining engine performance and providing a sustainable fuel source for long-term use. It introduces a novel approach by combining pine oil (PO) and lemon grass oil (LGO) with diesel fuel in a specific ratio (10% PO + 10% LGO + 80% Diesel). This work is innovative in that it employs these two distinct low-viscosity biofuel blends in conjunction with diesel fuel in an agricultural engine, resulting in reduced carbon footprints in the tailpipe. The blend tested in a single-cylinder diesel engine showed that using PO and LGO together reduced UHC emissions by 42.96%, CO emissions by 20.79%, and smoke emissions by 26.26%, while keeping the BTE the same. However, there was a 7.16% rise in NOx emissions. To decrease NOx emissions, antioxidants—250 mg of p-phenylene diamine (10% PO + 10% LGO + 80% + 250 mg PPDA) and 100 mg of butylated hydroxy toluene (10% PO + 10% LGO + 80% + 100 mg BHT) were added. The blends were injected at different injection pressures of 300 bar, 450 bar, and 600 bar, which can result in a reduction in NOx emissions of up to 11.78% and 10.99% for B2 + 300 bar and B3 + 300 bar, respectively. We used the SWOT study to evaluate the advantages and disadvantages of the mixed fuel, and employed the PUGH Matrix decision tool to carry out the sustainability assessment. The results showed that the blend (10% PO + 10% LGO + 80% Diesel + Antioxidant + 600 bar) is a sustainable fuel, considering environmental, social, and economic factors to be more feasible than pure diesel. [ABSTRACT FROM AUTHOR]

Background: Green synthesis techniques have drawn a lot of interest lately since they are beneficial to the environment and have potential uses in a variety of industries, including biomedicine. Because of their special physicochemical characteristics, copper nanoparticles (CuNPs) have become one of the most interesting options for use in biological applications among nanomaterials. An overview of green synthesis methods for CuNPs is given in this review, along with a discussion of their applications in cancer therapeutics. The benefits and drawbacks of certain green synthesis techniques, such as plant-mediated, microorganism-mediated, and other environmentally friendly processes, are discussed. Moreover, a thorough discussion is given of CuNPs' biological uses, including their antibacterial activity, anticancer potential, drug transport, and bioimaging capabilities. Furthermore, difficulties and prospects for the application of green-synthesised CuNPs in biomedicine are discussed. [ABSTRACT FROM AUTHOR]

Slow cooling was allowed for the successful growth of metal–organic single crystal of lithium bis (oxalato) borate (LBOB). The single crystal XRD was used to analysis the lattice cell parameters of grown LBOB crystal. The LBOB single crystal belongs to orthorhombic system with space group Pbca and calculated parameters are found to be a = 6.43 Å, b = 7.58 Å, and c = 13.22 Å. The crystalline perfection of the grown crystal was analyzed by high-resolution X-ray diffraction (HRXRD) rocking curve measurement. UV–Vis spectral analysis was used to determine the grown LBOB crystal’s band gap and transmittance (%) value. From the observed UV–Vis spectrum, the lower cut-off wavelength and band gap values of LBOB crystal are 231 nm and 5.1 eV, respectively. Thermal stability of LBOB compound was studied using TG–DTA analysis. The laser-induced damage threshold study revealed that the grown LBOB crystal possesses excellent resistance to laser radiation with a high laser damage threshold value up to 9.74 GW/cm2. Vickers hardness tester was used to examine the LBOB crystal’s hardness value. Z-scan technique was employed to clarify that the third-order nonlinear susceptibility was found to be (χ3) = 3.0371 X 10–11 esu. [ABSTRACT FROM AUTHOR]

Highly susceptible fish cell lines are required to isolate and propagate fish nodavirus and the main purpose of the present study is to develop highly susceptible cell lines from Lates calcarifer which is highly vulnerable to viral nervous necrosis. Three permanent cell lines, brain (SBB), eye (SBE) and optic nerve (SBON) were developed from L. calcarifer by explant culture technique and sub-cultured for 97, 128 and 75 respectively, at 28 °C in Leibovitz's L-15 media supplemented with 10% fetal bovine serum (FBS). The plating efficiency of SBB, SBE and SBON cells was determined as 69.09, 63.19 and 48.22%, respectively, and the doubling time was 27, 29 and 38 h, respectively. All these cell lines were stored by cryopreservation at various passage levels, and a recovery rate of 75–95% was observed. Immunostaining of the SBB and SBON cell lines showed that they are of neuronal origin, whereas the SBE cell line is of retinal pigment epithelial origin. Amplification of mitochondrial 16S rRNA gene confirmed that the SBB, SBE and SBON cell lines were of L. calcarifer origin. Three established cell lines showed 15–18% of transfection efficiency. These cell lines were highly susceptible to striped jack nervous necrosis virus (SJNNV) and infection in these cells was confirmed by RT-PCR, immunocytochemistry, Western blot, ELISA and qRT-PCR. The cell lines established from L. calcarifer were continuous, stable and potentially valuable for virological and biomedical studies. [ABSTRACT FROM AUTHOR]

Objective: Green and medicinal chemistry share the common objective of creating easy-to-use, cost-effective catalytic systems using commonly available materials. To synthesize 4H-pyrans derivatives by one-pot chemical reaction of cycloalkanones, substituted aldehyde with malononitrile at conventional, and ultrasonic method using uranyl nitrate hexahydrate acting as a catalyst were produced pyrans derivatives (IVa–IVj) in good to high yields. Methods: The main benefits of this eco-friendly approach are its high efficiency, solvent-free or low solvent reaction conditions, ease of operation, and utilization of readily available catalysts. After conducting additional research on the binding manner of the contacts between the most active frameworks and the α-glucosidase active sites, docking analysis was carried out to investigate the α-glucosidase enzyme's active cavity. Results and Discussion: Upon interpreting the data, it became evident that scaffolds (IVa) and (IVc) were the most effective inhibitors of α-glucosidase, exhibiting excellent binding contacts with the enzyme's active region. Conclusions: We propose a simple and green synthetic methodology for the synthesis of pyran derivatives and the molecular docking experiments showed that these compounds are strongly bound to the protein-binding sites of glycogen synthase kinase-3 beta receptor. [ABSTRACT FROM AUTHOR]

The species Bacillus velezensis is known for its biosynthetic potential and metabolic versatility in producing several secondary metabolites and promoting plant growth. In this study, we isolated two B. velezensis strains, WGTg-8 and WGTm-299, from the termite gut and termitarium, which exhibited antimicrobial activity against multiple clinical and phytopathogens. The whole genomes of these strains were sequenced using the Illumina platform and annotated. The genome mining of the draft genome sequences revealed 48 biological gene clusters (BGCs) responsible for synthesizing various secondary metabolites. The construction of the similarity network of the BGCs and the comparative analysis with the genetically related organisms are aided in the identification of metabolites produced by these strains. We identified biosynthetic gene clusters (BGCs) coding for macrolactin H, bacilysin, bacillibactin, amylocyclin, comX4, and LCI, found in both strains with 100% similarity. The difficidin, bacillaene, thusin_alpha, and cericidin BGCs are exclusively found in strain WGTg-8, while the colicin BGC is exclusively present in the WGTm-299 strain. The fengycin and surfactin gene clusters are present in both strains with 80% similarity. Furthermore, 28 putative NRPS BGCs, NRPS-T1PKS hybrid clusters, a T1PKS, and a bacteriocin BGC were identified with very low similarity (≤ 25%) or no similarity with known antibiotics. In addition, we found several genes coding for plant growth-promoting properties, including nitrogen metabolism, hormone synthesis, sulfur metabolism, phosphate metabolism, and a few other properties. [ABSTRACT FROM AUTHOR]

During the space travel mission, astronauts' physiological and psychological behavior will alter, and they will start consuming terrestrial drug products. However, factors such as microgravity, radiation exposure, temperature, humidity, strong vibrations, space debris, and other issues encountered, the drug product undergo instability This instability combined with physiological changes will affect the shelf life and diminish the pharmacokinetic and pharmacodynamic profile of the drug product. Consequently, the physicochemical changes will produce a toxic degradation product and a lesser potency dosage form which may result in reduced or no therapeutic action, so the astronaut consumes an additional dose to remain healthy. On long-duration missions like Mars, the drug product cannot be replaced, and the astronaut may relay on the available medications. Sometimes, radiation-induced impurities in the drug product will cause severe problems for the astronaut. So, this review article highlights the current state of various space-related factors affecting the drug product and provides a comprehensive summary of the physiological changes which primarly focus on absorption, distribution, metabolism, and excretion (ADME). Along with that, we insist some of the strategies like novel formulations, space medicine manufacturing from plants, and 3D printed medicine for astronauts in longer-duration missions. Such developments are anticipated to significantly contribute to new developments with applications in both human space exploration and on terrestrial healthcare. [ABSTRACT FROM AUTHOR]

Arabian Sea is a highly productive Ocean owing to deep upwelling with reports on phosphorus cycling in ocean sediments. In this study, microbes from sea mounts of the Arabian Sea at varying depths (400 m, 900 m) were screened to isolate and characterize phosphate-solubilizing bacteria (PSB) with plant growth-promoting properties. Out of the seven morphologically different PSBs, two bacterial strains with maximum phosphate solubilization index were identified as Priestia megaterium (H1) and Bacillus velezensis (H2) based on biochemical and molecular characteristics. Different factors influencing phosphatase production were optimized, which showed maximum solubilization at temperature of 30 °C (97.5 μg/mL), glucose as best carbon source (70 µg/mL), 1-M NaCl (114.1 µg/mL), and pH 8 (134.3 µg/mL) indicating their halophilic and alkaliphilic characteristics. Alkaline phosphatase enzyme was extracted and partially purified from both PSBs wherein H2 strains showed greater specific activity (24.83 U/mg). Metabolomics studies through HPLC revealed maximum production of gluconic acid (483.75 mg/L) in addition to lactic, oxalic, acetic, and succinic acid during solubilization. Biopriming effect of PSBs on tomato seed germination showed high germination index (80%) in consortia of both isolates which was also validated through root colonization by SEM analysis. Further studies using pot assay experiments also showed comparable results in marine PSB consortia with positive control (Phosphobacteria) for plant growth attributes including root height and weight. These findings suggest that the halophilic PSB strains from marine sediments could be used as potential bio-inoculants to enhance plant growth and combat saline stress for sustainable Agriculture. [ABSTRACT FROM AUTHOR]

The most promising eco-friendly green synthesized iron nanoparticles (FeNPs) using jujube leaf extract to decolorize methylene blue (MB) dye was established. Synthesized nanoparticles were characterized through different techniques like TEM, SEM, and FTIR. Various parameters such as dye concentration (5 to 20 mg L−1), nanoparticles load (0.5 to 2.5 mg), temperature, pH, and contact time (30 to 150 min) were optimized. A maximum MB dye removal efficiency of 93.5% is achieved at a time interval of 150 min, temperature 30 °C and pH 9 with 2.5 mg FeNPs for a concentration of 20-mgL−1 methylene blue. The adsorption behavior was monitored using a wide range of isotherm models which includes Freundlich, Dubinin–Radushkevich, Langmuir, and Temkin. The Elovich and intraparticle diffusion models, as well as the dynamical models of pseudo-first- and pseudo-second order has been analyzed for the data obtained from dynamic adsorption. Experimental results were consistent along the paradigm of pseudo-second order. Langmuir adsorption isotherm well suited for adsorption data across exclusive concentration range in comparison to other models. The green synthesized FeNPs has high sorption capacity (1000 mg/g) and environmentally friendly in nature, makes it a potential candidate for wastewater treatment applications. [ABSTRACT FROM AUTHOR]

The rapid spread of the drug-resistance among microbes has made the treatment of infections a problematic task. Microbial biofilms are complex aggregations of microbial cells encapsulated in a polymeric matrix that further worsens the treatment of microbial infections. In this study, ZnONPs were synthesized via green route using the aqueous tuber extract of Drynaria quercifolia. Biophysical property of ZnONPs was characterized by UV-vis spectroscopy, XRD, FTIR, SEM with EDS, and HR-TEM analyses and was found to have a size of 10 nm. Synthesized ZnNOPs demonstrated good antimicrobial activity against bacterial (B. cereus, S. typhi, and E. coli) and fungal (A. flavus and C. albicans) strains. Subsequently, the ZnONPs also exhibited excellent antioxidant property DPPH (78.52%), ABTS assay (70.18%), and hydroxyl scavenging assay (77.34%) at 100 μg/ml concentration. The biofilm inhibitory activity against E. coli, B. cereus, and S. typhi was recorded. Additionally, we also evaluated the larvicidal activity of ZnONPs against Cx. quinquefasciatus and recorded LC50 value of 130.725 μg/ml. Histopathology studies revealed that the region of hind and mid intestine, epithelial cells, and cortex were affected severely upon the treatment with ZnONPs. Photocatalytic activity was tested on crystal violet for dye degradation. Nearly complete degradation of the tested dye occurred within 72 min. The study suggests that green-synthesized ZnONPs could be a preferred alternative for various biomedical applications and contribute to the eventual elimination of environmental pollutants in the near future. [ABSTRACT FROM AUTHOR]

Microbial afflictions represent a significant global public health concern. The overuse of antibiotics and the ineffectiveness of conventional antibiotic therapies present substantial challenges in the biomedical field. Consequently, research scientific efforts are focused on developing nanoparticle-based microbial agents to address the escalating issue of antimicrobial resistance. In the present study, we synthesized fucoidan combined with molybdenum disulfide (MoS2) nanosheets using the liquid exfoliation technique, followed by thorough characterization. The UV-visible spectrum analysis revealed prominent absorption peaks at 610 and 672 nm, indicative of the successful formation of F-MoS2 nanosheets. Subsequent antimicrobial assays demonstrated the exceptional antibacterial efficacy of the developed F-MoS2 nanosheets against Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans). Moreover, in vivo toxicity assessment using the Caenorhabditis elegans (C. elegans) model disclosed that concentrations exceeding 125 µg/mL led to a reduction in the number of fertilized eggs laid by the worms. Furthermore, concentrations of 250 µg/mL resulted in delays in the reproductive cycle and impaired developmental fitness. Thus, the developed F-MoS2 nanosheets exhibit promising prospects for application within the realm of biomedicine. [ABSTRACT FROM AUTHOR]

Overactivation of mineralocorticoid receptors occurs in cardiorenal diseases. Many patients with type 2 diabetes often progress to chronic kidney disease (CKD) and require dialysis. Finerenone is the first oral non-steroidal mineralocorticoid receptor (MR) antagonist used in patients with diabetic kidney disease and heart failure. Finerenone (also known as Kerendia) is more potent than spironolactone in reducing the progression of CKD and exerts its effect equally on the heart and kidneys, improving cardiovascular outcomes. Research demonstrates that finerenone improves proteinuria and glomerular filtration rate (GFR) if taken alone or in combination with sodium-glucose transporter 2 inhibitors (SGLT2i). Finerenone has been found to decrease mortality in patients with diabetic renal disease and improve quality of life. Its side effects, unlike those of spironolactone, do not include gynecomastia. However, it can result in hyperkalemia, which needs to be monitored. In this narrative review, we aim to investigate the mechanisms of action of finerenone and its implications in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Cycas L. is an economically important threatened genus at risk of extinction due to natural population degradation. The present study observed unexplored populations in the Kannur district, Kerala, India, including the Kannavam Forest Reserve (KF) during 2021–2023. The normality of the datasets was checked using the Anderson-Darling test in R using the "nortest" package, and the variability in distribution was found using integrated R scripts in QGIS 3.0. and SPSS 25. "corr" and "ggcorrplot" packages of RStudio plotted the Pearson's correlation matrix from normalised datasets. Hierarchical clustering on principal components utilised Euclidean distance matrix and Ward linkage method from "FactoMineR" and "factoextra" packages in RStudio. Normality tests and histograms showed the variability and skewness in the data. Pearson's correlation matrix revealed a high positive correlation of petiole length with spines to the total length of the petiole (0.74) and the spine percentage on the petiole (0.71). Moreover, megasporophyll characters exhibited a high positive correlation between apical spine length and the length of the infertile lamina of the megasporophyll (0.84) and fertile region length with the number of ovules (0.70). Hierarchical clustering analysis suggested two clusters in the area by retaining eight principal components concerning eigenvalues, scree plots and cumulative variance. Cluster one was Cycas circinalis L., and cluster two was Cycas nathorstii J. Schust. based on the recorded morphological features. The study reported the existence of Cycas nathorstii for the first time in the Kannur district and the Kannavam Forest Reserve. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the most common movement disorder worldwide. PD is primarily associated with the mutation, overexpression, and phosphorylation of α-synuclein. At the molecular level, the upstream protein c-Abl, a tyrosine kinase, has been shown to regulate α-synuclein activation and expression patterns. This study aimed to identify potential c-Abl inhibitors through in silico approaches. Molecular docking was performed using PyRx software, followed by Prime MM-GBSA studies. BBB permeability and toxicity were predicted using CBligand and ProTox-II, respectively. ADME was assessed using QikProp. Molecular dynamics were carried out using Desmond (Academic version). DFT calculations were performed using the Gaussian 16 suite program. The binding scores of the top hits, norimatinib, DB07326, and entinostat were − 11.8 kcal/mol, − 11.8 kcal/mol, and − 10.8 kcal/mol, respectively. These hits displayed drug-likeness with acceptable ADME properties, except for the standard, nilotinib, which violated Lipinski's rule of five. Similarly, the molecular dynamics showed that the top hits remained stable during the 100 ns simulation. DFT results indicate DB04739 as a potent reactive hit. While based on toxicity prediction, entinostat may be a potential candidate for preclinical and clinical testing in PD. Further studies are warranted to confirm the activity and efficacy of these ligands for PD. [ABSTRACT FROM AUTHOR]

Orf or contagious ecthyma is a highly contagious, zoonotic, and economically important global viral disease of small ruminants and is endemic in India. Vaccination of susceptible goats/sheep along with suitable recombinant protein-based serological assay will be useful in the control of the infection. In this study, the full-length and truncated versions of F1L encoding gene (ORF 059) of orf virus were cloned into pFasBac HT A vector, transformed in DH10Bac cells, and expressed in insect cells. The full-length and truncated recombinant F1L proteins were expressed as a 6 × histidine-tagged fusion protein for ease of purification by Ni–NTA affinity chromatography under denaturing conditions. A protein with ~ 40 kDa and ~ 35 kDa for full-length and truncated F1L protein, respectively, were expressed and confirmed by SDS-PAGE and western blot. The protein reactivity evaluated by western blot analysis and indirect ELISA using ORFV hyperimmune serum was also found to be reactive. The results of the present study showed that the purified recombinant F1L protein can be used as a diagnostic antigen in sero-surveillance of ORFV infection in small ruminants. To the best of authors' knowledge, this is the first report on the expression of ORFV F1L in insect cells using a baculovirus vector and its successful purification to use as the potential diagnostic antigen in ELISA. [ABSTRACT FROM AUTHOR]

We report an uncommon odontogenic actinomycotic cervicothoracic Nectrotizing Fasciitis (NF), treated with tracheostomy, immediate surgical debridement and antibiotics. Red flags for early identification, LRINEC scoring for prognostication, surgical debridement with aerobic & anaerobic culture specific antibiotics to improve survival in this life-threatening cervicothoracic NF in a young diabetic is discussed. [ABSTRACT FROM AUTHOR]

A reflective dual-band linear-to-circular polarizer for C and X-band application is presented. The proposed elliptical Frequency Selective Surface (FSS) is capable of enhancing the polarization control and minimizes the cross-polarization compared to traditional circular or square geometries. The linear-to-circular polarization is achieved through two elliptical apertures, where each shape generates orthogonal modes with a 90° phase shift. The inner element targets higher frequencies while the outer element handles lower frequencies, enabling efficient polarization conversion across both bands. The proposed unit cell comprises 14 mm × 14 mm and is fabricated on Rogers RT5880 substrate. It exhibits a reflective polarizer at a center frequency of 7.70 GHz with a bandwidth of (7.64–7.76 GHz) and other at 9.42 GHz with a bandwidth of (9.27–9.57 GHz), respectively. In the proposed FSS, the 7.70 GHz exhibits LH-CP, and RH-CP conversion is provided at 9.42 GHz. In addition, an axial ratio of the FSS of (< 3 dB) demonstrated a circular polarization with a polarization conversion ratio (PCR) of 99.9%. In addition, an equivalent circuit model (ECM) of a reflective polarizer has been verified. Furthermore, angular stability of the FSS can be achieved at various incident angles at 0°, 30°, 60°, and 90°. The polarization conversion operates in frequency bands of C-/X, suitable for wireless systems, radar systems, electromagnetic shielding, and satellite communications. [ABSTRACT FROM AUTHOR]

Background: The global landscape of public health faces significant challenges attributed to the prevalence of cancer and the emergence of treatment resistance. This study addresses these challenges by focusing on Cyclin-dependent Kinase 2 (CDK2) and employing a systematic computational approach for the discovery of novel cancer therapeutics. Results: Initial ligand-based pharmacophore modelling, utilizing a training set of five reported CDK2 inhibitors, yielded a robust model characterized by Aro|Hyd| and |Acc|Don| features. Screening this validated model against the ZINC database identified 1881 hits, which were further subjected to molecular docking studies. The top 10 compounds (Z1–Z10) selected from the docking studies underwent Pharmacokinetic parameters Absorption, Distribution, Metabolism, Excretion and Toxicity profiling, Density Functional Theory (DFT) studies and the top two went for 100ns molecular dynamics (MD) simulations by comparing them with the standard Roscovitine. Compounds Z1 and Z2 emerged as the most promising, with docking scores of − 8.05 kcal/mol and − 8.02 kcal/mol, respectively. DFT analysis of the top 10 compounds revealed minimal variations in highest occupied molecular orbital–lowest unoccupied molecular orbital energy gaps, indicating consistent electronic stability and reactivity across the candidates. MD simulations of Z1 and Z2 confirmed their stable interactions with CDK2, with root mean square deviation (RMSD) values ranging from 1.4 to 2.5 Å for Z1 and 1.5 to 2.4 Å for Z2. Conclusion: The current research identified compounds Z1 and Z2, which demonstrated significant potential as potent CDK2 inhibitors for cancer therapy, providing valuable insights into the development of more effective CDK2 inhibitors and addressing the critical need for innovative therapeutic strategies in cancer treatment. [ABSTRACT FROM AUTHOR]

The development of eco-friendly materials is a challenging one in the research field. Natural fibers are more accessible, biodegradable, inexpensive, and less dense. They offer fewer health risks and are eco-friendly compared to synthetic fibers. Natural fiber-reinforced polymer composites are new, eco-friendly materials with excellent mechanical and practical applications. Adding biofillers to composites improves strength and will replace synthetic materials. Utilizing cellulose as a filler for a natural starch matrix is an effective way to reduce the environmental impact of non-biodegradable materials. This study covers the influence of natural Borassus flabellifer flower microcrystalline cellulose (BFF MCC) fillers on banana fiber-reinforced polymer matrix composites. Fourier-transform infrared spectroscopic peaks at 2357, 1730, and 1245 cm-1 were absent. This indicates that the amorphous proportion of banana fiber mat/BFF MCC-reinforced hybrid composites decreased. At 1% BFF MCC, thermogravimetric examination revealed an increase in the peak temperature of maximum degradation (389.6 °C). The hybrid banana composite's tensile strength (31.36 ± 4.39 to 39.83 ± 3.07 MPa) and flexural strength (71.05 ± 2.66 to 82.4 ± 1.66 MPa) were also improved after adding 3% BFF MCC as filler material. The primary objective is to evaluate the suitability of fiber-reinforced hybrid polymers with natural fillers for future engineering applications such as automotive parts, construction materials, 3D printing, etc. In addition, this study investigated how the reinforcement of microcrystalline cellulose can result in a material with enhanced performance as well as its mechanical characteristics (XRD, FTIR, TGA, and SEM characterization). [ABSTRACT FROM AUTHOR]

Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction1,2. However, the molecular mechanisms driving immune–fibroblast cell communication in human cardiac disease remain unexplored and there are at present no approved treatments that directly target cardiac fibrosis3,4. Here we performed multiomic single-cell gene expression, epitope mapping and chromatin accessibility profiling in 45 healthy donor, acutely infarcted and chronically failing human hearts. We identified a disease-associated fibroblast trajectory that diverged into distinct populations reminiscent of myofibroblasts and matrifibrocytes, the latter expressing fibroblast activator protein (FAP) and periostin (POSTN). Genetic lineage tracing of FAP+ fibroblasts in vivo showed that they contribute to the POSTN lineage but not the myofibroblast lineage. We assessed the applicability of experimental systems to model cardiac fibroblasts and demonstrated that three different in vivo mouse models of cardiac injury were superior compared with cultured human heart and dermal fibroblasts in recapitulating the human disease phenotype. Ligand–receptor analysis and spatial transcriptomics predicted that interactions between C-C chemokine receptor type 2 (Cbibr2) macrophages and fibroblasts mediated by interleukin-1β (IL-1β) signalling drove the emergence of FAP/POSTN fibroblasts within spatially defined niches. In vivo, we deleted the IL-1 receptor on fibroblasts and the IL-1β ligand in Cbibr2+ monocytes and macrophages, and inhibited IL-1β signalling using a monoclonal antibody, and showed reduced FAP/POSTN fibroblasts, diminished myocardial fibrosis and improved cardiac function. These findings highlight the broader therapeutic potential of targeting inflammation to treat tissue fibrosis and preserve organ function. A fibroblast lineage marked by FAP gives rise to POSTN-expressing fibroblasts resembling matrifibrocytes and IL-1β regulates FAP/POSTN fibroblast specification by directly signalling to cardiac fibroblasts, highlighting a role for immunomodulators in targeting cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Multidrug resistance in clinical pathogens is a significant challenge in healthcare, requiring the development of novel approaches to combat infections. In this study, we report the identification of novel antimicrobial biosynthetic gene clusters from Brevibacillus parabrevis WGTm-23, the bacterial strain isolated from a termitarium. This strain showed an antagonistic effect against drug-resistant clinical pathogens, such as Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella paratyphi, Streptococcus gordonii, and enteropathogenic Escherichia coli. The whole genome of this strain was sequenced using the Illumina platform. The genome mining revealed a total of 17 biosynthetic gene clusters (BGCs) responsible for the synthesis of secondary metabolites. The metabolites produced by this strain were predicted by constructing an identity network of the BGCs and performing a comparative analysis with genetically related strains. The genome contains multiple BGCs coding for ribosomally synthesized and post-translationally modified peptides (RiPPs). In the genome of Br. parabrevis WGTm-23, we identified BGCs that code for ulbactin F, ulbactin G, gramicidin, and bacillopaline with the highest identity. We also identified a few BGCs with less than 50% sequence identity to MC-LR/MC-LHty/MC-HphHty/MC-LHph/MC-HphHph, xenocoumacin 1/xenocoumacin II, and tyrocidine. In addition, we found fourteen BGCs that do not resemble or show identity to any entries within the antiSMASH database. Therefore, Br. parabrevis WGTm-23 has the potential to synthesize new classes of antimicrobial compounds. [ABSTRACT FROM AUTHOR]

Over the last decade, India has witnessed unintentional entry of five species of invasive species of mealybugs, perhaps due to globalization and global trade, leading to negative economic and ecological consequences. Through this paper, the first occurrence of the destructive mealybug Hypogeococcus pungens Granara de Willink is reported in India infesting two nursery plant species of Alternanthera and a wild Portulaca sp. As early detection, identification, and rapid reporting are essential for the successful management of destructive species, the field and diagnostic characters of slide mounted H. pungens were described in details with help of field and microphotographic images. The identity of the mealybug was also confirmed through molecular studies by sequencing mitochondrial cytochrome c oxidase I (COX I) and 28 S ribosomal gene regions. Information on host range, natural enemies, and distribution of the mealybug is provided. Management options in the event of an outbreak are discussed briefly. This new arrival warrants special attention in India as it is a potentially damaging plant pest in landscapes, and vertical gardening practiced in offices, commercial complexes, and luxury apartments. [ABSTRACT FROM AUTHOR]

Titanium oxide pigment industries produce a large amount of undissolved particles called sludge during the sulfate process of ilmenite. The sludge mainly constituted 48% TiO2, 15% SiO2, 11% Fe2O3, 4.5% SO3, and 2% Al2O3. Zirconium, vanadium, magnesium, and calcium oxides are also in small amounts. The presence of sulfur induces an acidic nature to the sludge and reduces its further utilization. Using a simultaneous process to reduce sulfur content and extract important metals is crucial. The paper describes use of acidic sludge to extract titanium to prepare titanium rich alloy. The method involves initial neutralization and reduction roasting followed by magnetic separation. The separated magnetic part was then utilized for aluminothermic reduction by smelting, resulting in titanium-rich alloy. Analytical techniques such as XRD, SEM–EDS and Thermal analysis were conducted during the studies. Titanium-rich alloys having a composition of ~ 51.8% Ti, 22.4% Al, 9.5% Si, and 16.3% Fe were achieved. [ABSTRACT FROM AUTHOR]

The rapid growth of cellular network users poses a significant challenge for providers to maintain Quality of Service and reduce network power consumption. The proposed work presents two power saving strategies, namely BS sleeping and Cell zooming, which are executed based on predictive evaluation of network traffic. The proposed work integrates two distinct cell zooming methodologies i.e. centralized and distributed cell zooming, tailored for various traffic load scenarios. The cell zooming technique is implemented using Reinforcement learning that helps network to learn from the environment and take decisions based on traffic conditions. In the proposed distributed cell zooming the traffic load is balanced using Spider Monkey Optimization algorithm. The proposed system provides the 37% power saving when compared with the always on condition of network. When compared with existing techniques BS utilization is reduced by 3%, spectral efficiency is increased by 1% and Energy Efficiency is increased by 4% with proposed system. [ABSTRACT FROM AUTHOR]

Having antioxidant properties of nanomaterials plays an important role in developing cosmeceuticals and pharmaceuticals to treat various diseases that occur through reactive oxygen species (ROS). Nanomaterials with enzyme-like properties can suppress ROS, which can be useful for the development of medicinal substances. Recently, transition metal nanoparticles have gained much attention in the development of nanozyme properties, owing to their simple experimental procedure and low-cost production. In this study, we developed gallic acid-mediated iridium nanoparticles (Ir-GA NPs) using the sodium borohydride reduction method and subsequently characterized them using different analytical techniques. The sizes of the Ir-GA NPs were in the nano range. The physicochemical properties of Ir-GA NPs were confirmed by dynamic light scattering analysis (DLS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), elemental analysis, and high-resolution transmission electron microscopy (TEM). Additionally, the antioxidant activity of the developed Ir-GA NP was evaluated using reactive oxygen species (ROS), and the results supported the significantly compromised intracellular redox conditions. Additionally, CCK-8 and DCFH-DA assays were used to evaluate the biocompatibility and toxicological profile of the produced Ir-GA NPs using the A549 lung cancer cell line. The Ir-GA NPs significantly scavenged ROS. Hence, the developed Ir-GA NPs could act as antioxidants for biological and biomedical applications. [ABSTRACT FROM AUTHOR]

Key message: Induction of parthenogenesis (embryo formation from unfertilized egg cells) by embryogenic transcription factors is associated with twin formation at high frequencies, and involves two distinct mechanisms. Synthetic apomixis has been achieved through the induction of parthenogenesis by ectopic expression of the Baby Boom family of transcription factors. An associated phenomenon from this process is the formation of polyembryony including twin progeny at high frequencies, but the underlying mechanisms have not been explored. Here, we provide a brief description of the phenomenon, discuss potential mechanisms for twin formation in flowering plants, propose two possible models for their occurrence, and evaluate the available evidence from both dizygotic and monozygotic twins in relation to these models. The two proposed models are independent, but they can operate in combination. We conclude that both models are required to explain the types of twins and triplets that we and others have observed. These models provide future directions for basic research, as well as suggest possible approaches towards reducing polyembryony when incorporating synthetic apomixis into crop plants such as maize where twinning is not desirable. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) has the potential to bring unprecedented accessibility and efficiency to a wide range of critical applications and access control services. With the advent of IoT technology, there is a surge in potential threats and challenges that engender the risk of IoT devices interconnected over the Internet infrastructure. The mitigation of potential threats and risks needs a comprehensive analysis of security threats and relevant attack vectors in IoT networks, especially in IoT devices. Auditing is crucial to ensure that all IoT devices in the ecosystem are operating accurately and securely. This research has examined several physical and remote IoT security auditing tools to identify their drawbacks. This paper has also explored possible security threats, audited these threats to prevent them proactively by using the proposed novel seven-layer architecture, and presented expanded security requirements for IoT devices. Even more, we have examined the existing audit tools using an IoT device (IP camera). The analysis has shown that audit features concerning security requirements are missing from the existing audit tools. Our proposed seven-layer IoT device architecture with expanded security requirements has the potential to be a security audit benchmark for all IoT devices at the manufacturing and end-user levels. [ABSTRACT FROM AUTHOR]

The Intertropical Convergence Zone (ITCZ) is a narrow tropical belt of deep convective clouds, intense precipitation, and monsoon circulations encircling the Earth. Complex interactions between the ITCZ and local geophysical dynamics result in high climate variability, making weather forecasting and prediction of extreme rainfall or drought events challenging. We unravel the complex spatio-temporal dynamics of the ITCZ and the resulting teleconnection patterns via a novel tropical climate classification achieved using complex network analysis and community detection. We reduce the high-dimensional complex ITCZ dynamics into a simple yet insightful community structure that classifies the tropics into seven regions representing distinct ITCZ dynamics. The two largest communities, encompassing landmasses over the Northern and Southern hemispheres, are associated with coherent seasonal ITCZ dynamics and have significant long-range connections. Temporal analysis of the community structure highlights that the tropical Pacific and Atlantic Oceans communities exhibit substantial variation on multidecadal scales. Further, these communities exhibit incoherent dynamics due to atmosphere-ocean interactions driven by equatorial and coastal oceanic upwelling. [ABSTRACT FROM AUTHOR]

In this study, we report the successful growth of polycrystalline SnSe/SnSe2 heterophase thin films using single precursor compounds consisting of SnCl2.2H2O and 1,1-dimethyl l-2-selenourea via chemical spray pyrolysis. The films were deposited on soda-lime glass substrates within a narrow temperature range of 270–300 °C followed by annealing in vacuum at temperature in the range of 250–450 °C for 1 h. The structural and morphological properties of the films were investigated using X-ray diffraction (XRD), Raman mapping, high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The presence of both SnSe2 (hexagonal) and SnSe (orthorhombic) phases was confirmed and their ratios were determined using the Reference Intensity Ratio (RIR) method from XRD data. This narrow deposition temperature induces intrinsic atomic defects (VSn, VSe, SnSe) with lower formation energies during nucleation, enabling the formation and growth of SnSe/SnSe2 heterophase. These defects act as electron donors, and in addition the energy band bending at the SnSe/SnSe2 interface favors the formation of electron-rich regions showing n-type conductivity. The excess electrons contribute to a higher electron concentration leading to a higher Seebeck coefficient resulting in an improved power factor. Interestingly, the as-deposited films with a higher ratio of SnSe2 phase exhibited an increased power factor compared to their annealed counterparts, indicating the importance of the preferential growth of SnSe2 in enhancing carrier concentration and carrier mobility at the interfaces of the SnSe2/SnSe heterophase. [ABSTRACT FROM AUTHOR]

Hydroxyapatite (HA) is an extensively used biomaterial for dental and orthopaedic applications because of its biocompatibility and biomimetic nature. HA is extensively used as a bone-graft substitute. HA bone graft substitutes of bovine or synthetic origins have been extensively studied. However, caprine-based HA has not been explored. In this study, we aimed to determine the utilization of goat bone-derived HA for commercial applications. HA from caprine bone and teeth was isolated using thermal calcination. The developed HA can be used as a bone graft substitute. Chemical characterization of the isolated HA was carried out using Fourier transform infrared spectroscopy, X-Ray Diffraction, Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy. The biocompatibility and apatite formation of isolated HA were assessed using MG-63 cells, MC3T3-E1, L929 cells, MSCs, adipose derived stem cells, human dermal tissue derived fibroblast cells and osteoblast-like cell line, The studies demonstrate that HA support cell adhesion and osteogenic properties. To improve sheep, lamp, or caprine bone-derived HA, several other composites have been developed with MgO2, ZrO2, ZnO2, and other polymeric substances. 3D printed technology was used to develop a bioink using sheep-derived HA and printed the composite scaffold as a bone graft substitute. Furthermore, the biomedical applications of sheep-derived HA been studied in terms of their antimicrobial activity, bone-forming ability, and wound healing applications. Sheep-, goat-, and caprine-derived HA are still underutilized and require further research to develop commercial possibilities and sustainable raw materials for HA-based bone graft substitutes. [ABSTRACT FROM AUTHOR]

The natural fiber nanocomposite materials employed in this study, which included sappanwood (SW), polyvinyl alcohol (PVA), polyethylene (PE), aluminum nitride (AlN), and epoxy resin (EP), were made by hand lay-up processes. Acryl Silane Coupling Agent (ASCA) was employed in the deep-dip coating method to enhance the tribology and microstructure of the natural fiber nano composite materials. For composite materials made of sappanwood and polyethylene, the resin microstructure was largely responsible for the observed homogeneous phase and hexagonal structure. The solid outer and secondary phases of the outer and inner surface layers of the EP-PE-SW-AlN composite materials were created using the silane coating process. Tensile properties of EP-PVA-SW-PE-AlN samples were reached at 42.8 MPa, and three-point bending tests were reached at 47.6 MPa. Furthermore, 597 °C was obtained for EP-PVA-SW-PE-AlN composite materials on TGA results. The average hardness value of (60) EP combined (10%) PVA, (10%) SW, (10%) PE, and (10%) AlN nano particle was highly present 98 (shore-D) throughout the silane coating process. Wear resistance and friction tests were performed on EP-PVA-SW-AlN, EP-PE-SW-AlN, and EP-PVA-SW-PE-AlN composite materials in order to improve the outer surface layers and interior composite structure. Dimples, micro voids, microscopic holes, and basket voids were seen on the fracture surfaces of each composite sample. [ABSTRACT FROM AUTHOR]

Atrazine (ATZ, C8H14ClN5) is a widely used synthetic herbicide that contaminates drinking water. It is a known endocrine disruptor that disrupts various molecular pathways involved in hormone signaling, and DNA damage, and can cause reproductive disorders, including decreased fertility, and abnormal development of reproductive organs, as revealed in animal model studies. However, the effect of ATZ on steroidogenesis in the male reproductive system, especially reduction of ketosteroids to hydroxysteroids, remains unclear. This study investigated the toxicity of ATZ on the male reproductive system in the Wistar rat model, with an emphasis on its adverse effect on aldo-ketoreductase family 1 member C2 (AKR1C2). Male Wistar rats were administered ATZ for 56 days (duration of one spermatogenic cycle) through oral route, at 20, 40 and 60 mg/kg body weight (bw) doses. The results indicate that ATZ exposure affects the body weight, impairs sperm production, and decrease FSH, LH, and testosterone levels. Additionally, the down-regulation of key steroidogenic enzymes by ATZ disrupted the synthesis of testosterone, leading to decreased levels of this essential male hormone. On the other hand, the expression of AKR1C2 (mRNA and protein) in the testis was upregulated. The findings suggest that AKR1C2 plays a role in androgen metabolism. Furthermore, its overexpression may lead to alteration in the expression of genes in the connected pathway, causing an increase in the breakdown or inactivation of androgens, which would result in lower androgen levels and, thereby, lead to hypoandrogenism, as the combined effects of down-regulation of steroidogenic genes and up-regulation of AKR1C2. These findings reveal direct implication of disrupted AKR1C2 in male reproductive health and highlight the need for further research on the impact of environmental toxins on human fertility, ultimately providing for better patient care. [ABSTRACT FROM AUTHOR]

Nowadays, nanosized drugs continue to lead the pharmacological field because of their small molecular size, solubility and penetrability, which are suitable for passive membrane transmission. In the current research, we produced zinc oxide nanoparticles (ZnO NPs) from Lablab purpureus leaf aqueous extract and assessed their antioxidant, antidiabetic and antimicrobial efficacy. In the biosynthesis process, we characterized biosynthesized ZnO NPs by UV-Vis spectroscopy, X-ray diffractometer, Fourier transform infrared spectroscopy, high resolution-scanning electron microscopy with energy-dispersive X-ray spectroscopy and high resolution-transmission electron microscopy (HR-TEM) analyses. The HR-TEM images reveal flocculated particles, which were mostly rods with a few hexagonal and sphere-shaped, with a typical particle size of 28±3.00 nm. ZnO NPs showed potential α-amylase and α-glucosidase activity inhibition, with IC50 values of 103.20±1.03 and 94.14±0.37 μg/mL, respectively. Furthermore, ZnO NPs exhibited excellent free radical scavenging potential on DPPH, ABTS, nitric oxide and superoxide with IC50 values of 114.95±2.11, 147.37±1.55, 90.94±0.57 and 152.52±0.56 μg/mL, respectively. Bacteria of gram-positive and gram-negative strains were inhibited growth with MIC ranging from 118.75 to 950 μg/mL. ZnO NPs have shown promise in reducing oxidative stress, which is associated with the development of chronic diseases. They also act as a hypoglycemic agent, which helps to maintain healthy glucose levels. Future phytochemical research will be necessary to standardize L. purpureus components with significant antidiabetic action and create a better substitute nano-herbal combination to replace the synthetic drugs. [ABSTRACT FROM AUTHOR]

Wireless sensor networks (WSNs) enable seamless data gathering and communication, facilitating efficient and real-time decision-making in IoT monitoring applications. However, the energy required to maintain communication in WSN-based IoT networks poses significant challenges, such as packet loss, packet drop, and rapid energy depletion. These issues reduce network life and performance, increasing the risk of delayed packet delivery. To address these challenges, this work presents a novel energy-efficient distributed neuro-fuzzy routing model executed in two stages to enhance communication efficiency and energy management in WSN-based IoT applications. In the first stage, nodes with high energy levels are predicted using a fusion of distributed learning with neural networks and fuzzy logic. In the second stage, clustering and routing are performed based on the predicted eligible nodes, incorporating thresholds for energy and distance with two combined metrics. The cluster head (CH) combined metric optimizes cluster head selection, while the next-hop combined metric facilitates efficient multi-hop communication. Extensive simulation results demonstrate that the proposed model significantly enhances network lifetime compared to EANFR, RBFNN T2F, and TTDFP by 9.48%, 25%, and 31.5%, respectively. [ABSTRACT FROM AUTHOR]

Phytohormones promote growth in the vegetative phase, flowering and fruit development. A novel class of PGR comprises brassinosteroids (BRs) and polyamines (PAs). In fruit crops, fruit drop at the maturity stage is controlled by the external application of BRs and PAs. BRs such as brassinolide, 24-epibrassinolide and 28-homobrassinolide and PAs such as putrescine, spermidine and spermine play significant roles in plant growth and development. Brassinolide provides tolerance against biotic and abiotic stresses. 24-Epibrassinolide promotes blossoming, fruit retention, fruit set and fruit growth. 28-homobrassinolide promotes cell division and cell elongation. Putrescine enhances seed germination and adventitious root formation in seedlings. Moreover, spermidine provides tolerance against drought and salinity. Furthermore, spermine promotes flowering and fruiting and competes with ethylene precursors. It would be beneficial to apply plant growth regulators such as BRs and PAs to increase fruit yield and quality. This review discusses how phytohormone (BR and PA) application can improve the productivity, quality, physiological, biochemical and postharvest aspects of some tropical, subtropical and temperate fruits and focuses on research areas such as the mode of action and stage of application of BRs and PAs which enhance the yield and quality of these perishable fruit crops. Article highlights: The newly emerged plant growth hormones brassinosteroids and polyamines are vital PGRs for the cultivation of horticulture commodities. BRs and PAs are environmentally safe phytohormones that improve the yield and quality of fruits. These materials are effectively utilized in both fruit production and postharvest management. [ABSTRACT FROM AUTHOR]

The current Indian stock market structure is fully centralized, with each party's government, financial institutions, and private sector relying on one another to authenticate transactions. Because of the prior party's reliance, the settlement in client Demat accounts takes T + 2. Most of the time, the T + 2 rule causes retail short-term investors or traders to lose money or fail to make a profit. The current settlement method is extremely difficult to comprehend, resulting in anomalies in customer Demat accounts. Blockchain is an immutable append-only data chain that is always developing. The SHA-256 cryptographic technique prevents data from being removed or changed after it has been inserted. There is no central database to maintain the chain; instead, each node stores a copy and processes data locally, updating it in milliseconds. In the form of fresh blocks, new information is added to the chain, ensuring that all parties have the same picture of the blockchain at all times. Everyone has access to the information, so they may verify and confirm transactions, in the end, resulting in complete transparency for all transactions. This work proposes a decentralized stock exchange architecture based on permissioned blockchain to address the T + 2 settlement cycle rule problem. Before designing this architecture it considers every aspect so, it excludes the traditional party name custodian member party because of its traditional functionality so that our architecture becomes cost-efficient at the time of implementation. [ABSTRACT FROM AUTHOR]

The global crisis of antimicrobial resistance (AMR) necessitates the development of broad-spectrum antibacterial drugs effective against multi-drug resistant (MDR) pathogens. BWC0977, a Novel Bacterial Topoisomerase Inhibitor (NBTI) selectively inhibits bacterial DNA replication via inhibition of DNA gyrase and topoisomerase IV. BWC0977 exhibited a minimum inhibitory concentration (MIC90) of 0.03–2 µg/mL against a global panel of MDR Gram-negative bacteria including Enterobacterales and non-fermenters, Gram-positive bacteria, anaerobes and biothreat pathogens. BWC0977 retains activity against isolates resistant to fluoroquinolones (FQs), carbapenems and colistin and demonstrates efficacy against multiple pathogens in two rodent species with significantly higher drug levels in the epithelial lining fluid of infected lungs. In healthy volunteers, single-ascending doses of BWC0977 administered intravenously (https://clinicaltrials.gov/study/NCT05088421) was found to be safe, well tolerated (primary endpoint) and achieved dose-proportional exposures (secondary endpoint) consistent with modelled data from preclinical studies. Here, we show that BWC0977 has the potential to treat a range of critical-care infections including MDR bacterial pneumonias. In this work, the authors probe the efficacy of BWC0977, a bacterial topoisomerase inhibitor, in pre-clinical animal models, also demonstrating that BWC0977 is safe and well tolerated in healthy human volunteers, in a phase 1 trial. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the cardiotoxicity effect of formulated agar (FA) from Turbinaria conoides in zebrafish embryos (ZFE). The agar was formulated by aqueous extract method. The physio-chemical and structural characterization was analyzed by texture analysis, Fourier transformed infrared spectroscopy (FTIR), scanning electron microscope (SEM), and thermogravimetric analysis. Spreadability and in vitro sample diffusion assays were determined. The agar isolated from T. conoides had a yield of 84.2% and moisture content of 38%. The FTIR analysis indicated the presence of alkanes and aliphatic amines while SEM analysis showed densely packed structure. The FA showed a water loss of 115.2, spreadability of 72.12%, and in vitro release of 98% in 3 h. At a concentration of 0.02 μg/mL in ZFE, FA's cardiotoxicity and teratogenic effects did not change significantly (P>0.05). [ABSTRACT FROM AUTHOR]

The synthesis of 3,4-dihydropyrimidin-2-(1H)-ones (DHPMs) was made by utilizing newly synthesized heterogeneous mixed ligand-based Ni-phen MCM-41 catalyst with variety of aryl aldehydes (viz. electron donating, electron withdrawing, fused, disubstituted and unsaturated substituents), ethylacetoacetate, urea and ethanol as a solvent by using two different energy sources: conventional and ultrasonication methods. The effectiveness of the two methods was compared and found that the formation of Biginelli products in ultrasonication method (65–92% yield at 60 °C, 45 min) is better than the conventional method (63–90% yield at 78 °C, 2 h) by yield, temperature and time of the reaction. The formation, heterogeneous nature and morphology of the catalyst have been characterized by Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma-optical emission spectrometry (ICP-OES), thermogravimetric analysis (TGA) and N2 adsorption–desorption isotherm (BET) techniques. Moreover, the catalyst was recoverable, reusable and very much efficient for three consecutive runs without any significant loss of its catalytic activity. The heterogeneity nature of the recovered catalyst was checked by hot filtration test. [ABSTRACT FROM AUTHOR]

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis. [ABSTRACT FROM AUTHOR]

The main goal of this study is to use the ψ -Caputo fractional derivative of order ϑ ∈ (0 , 1) to construct the criteria for controllability in non-instantaneous impulsive dynamical systems. To obtain the necessary and sufficient conditions for the controllability of linear fractional systems by incorporating the positiveness of the Grammian matrices. To obtain sufficient conditions for controllability criteria for nonlinear systems, we have used Schaefer’s fixed point theorem. To enhance comprehension of the theoretical findings, several numerical examples have been provided. [ABSTRACT FROM AUTHOR]

The focus of this study lies in developing and evaluating a Caputo–Fabrizio fractional derivative model that encapsulates the dynamics of the worldwide HIV/AIDS epidemic while integrating an antiretroviral therapy component. The methodology involves employing iterative techniques alongside the fixed-point theorem to establish the existence and uniqueness solutions of the model. In particular, the model identifies equilibrium points corresponding to disease outbreaks and disease-free scenarios. Additionally, it showcases the local asymptotic stability of the disease-free equilibrium point and outlines the criteria for the presence of the endemic equilibrium point. The findings verify that as the fractional order decreases, the disease-free equilibrium point becomes more stable. To demonstrate the impact of altering the fractional order and to bolster the theoretical finding, numerical simulations are conducted over the fractional order range. [ABSTRACT FROM AUTHOR]

In the current study, a novel experimental approach was used to fabricate a biobased packaging film made of poly(butylene adipate-co-terephthalate) (PBAT) blended with cellulose (CL) and gallic acid (GA). By adding 1 wt%, 2 wt%, 3 wt%, and 5 wt% of GA to PBAT and cellulose in a 70/30 (w/w) ratio, PBAT composites have been produced using the solution casting method, with GA working as a crosslinking agent. With the use of attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis/differential scanning calorimeter (TGA/DSC) analysis, the physicochemical properties of the PBAT film reinforced with CL and PBAT-CL/GA composite film were studied. Results depicted that increasing the level of GA enhanced the mechanical properties, resistance to oxygen and water vapor permeability, hydrophobicity, and antibacterial activity of the resulting films. The PBAT/CL film prepared with 5 wt% GA had higher tensile strength (33.1 MPa) in comparison to neat PBAT film (21.9 MPa). The addition of CL and GA significantly reduced the water contact angle values of the PBAT film. In addition, the PBAT composite films exhibited strong antibacterial activity, suggesting their potential application in food packaging. Food quality analysis revealed that PBAT-CL/GA film extends the shelf life of strawberries compared to the commercial low-density polyethylene film. Therefore, the use of these composite materials prolongs the freshness of perishable fruits. Current research has revealed that the PBAT-based composite film is an excellent material for food packaging. [ABSTRACT FROM AUTHOR]