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The purpose of this work was to prepare new isatin- and monothiomalondiamide-based indole derivatives, as well as to study the properties of the new compounds. The four-component reaction of 5-R-isatins (R = H, CH3), malononitrile, monothiomalonamide (3-amino-3-thioxo- propanamide) and triethylamine in hot EtOH yields a mixture of isomeric triethylammonium 6′-amino-3′-(aminocarbonyl)-5′-cyano-2-oxo-1,2-dihydro-1′H- and 6′-amino-3′-(aminocarbonyl)- 5′-cyano-2-oxo-1,2-dihydro-3′H-spiro[indole-3,4′-pyridine]-2′-thiolates. The reactivity and structure of the products was studied. We found that oxidation of spiro[indole-3,4′-pyridine]-2′-thiolates with DMSO-HCl system produced only acidification products, diastereomeric 6′-amino-5′-cyano-5-methyl-2-oxo-2′-thioxo-1,2,2′,3′-tetrahydro-1′H-spiro-[indole-3,4′-pyridine]- 3′-carboxamides, instead of the expected isothiazolopyridines. The alkylation of the prepared spiro[indole-3,4′-pyridine]-2′-thiolates upon treatment with N-aryl α-chloroacetamides and α-bromoacetophenones proceeds in a regioselective way at the sulfur atom. In the case of α-bromoacetophenones, ring-chain tautomerism was observed for the S-alkylation products. According to NMR data, the compounds consist of a mixture of stereoisomers of 2′-amino-6′-[(2-aryl-2-oxoethyl)thio]-3′-cyano-2-oxo-1′H-spiro[indoline-3,4′-pyridine]-5′-carboxamides and 5′-amino-3′-aryl-6′-cyano-3′-hydroxy-2-oxo-2′,3′-dihydrospiro[indoline-3,7′-thiazolo[3,2-a]pyridine]-8′-carboxamides in various ratios. The structure of the synthesized compounds was confirmed by IR spectroscopy, HRMS, 1H and 13C DEPTQ NMR studies and the results of 2D NMR experiments (1H-13C HSQC, 1H-13C HMBC). Molecular docking studies were performed to investigate suitable binding modes of some new compounds with respect to the transcriptional regulator protein PqsR of Pseudomonas aeruginosa. The docking studies revealed that the compounds have affinity for the bacterial regulator protein PqsR of Pseudomonas aeruginosa with a binding energy in the range of −5.8 to −8.2 kcal/mol. In addition, one of the new compounds, 2′-amino-3′-cyano-5-methyl-2-oxo-6′-{[2-oxo-2-(p-tolylamino)ethyl]thio}-1′H-spiro-[indoline-3,4′-pyridine]-5′-carboxamide, showed in vitro moderate antibacterial effect against Pseudomonas aeruginosa and good antioxidant properties in a test with 1,1-diphenyl-2-picrylhydrazyl radical. Finally, three of the new compounds were recognized as moderately active herbicide safeners with respect to herbicide 2,4-D in the laboratory experiments on sunflower seedlings.

The integration of blockchain technology in educational institutions is gaining momentum due to its promise to improve the graduation system and the process of verifying educational qualifications. However, little research exists on the social aspects of incorporating blockchain technology in an educational environment. This study aims to evaluate the social impact of blockchain technology on internal and external stakeholders of a higher education institution, including educational leaders, management, graduates, and external organisations. Using the Social Impact Assessment methodology, this study reveals that the integration of blockchain technology can have an overall positive impact on industrial and alumni relations and resource optimization. This study also contributes to the literature on Social Impact Assessment by presenting a methodological model for the integration of blockchain technology in the context of a higher education environment.

This article contains results of the existence of fuzzy fixed points of fuzzy mappings that satisfy certain contraction conditions using the platform of partial b-metric spaces. Some non-trivial examples are provided to authenticate the main results. The constructed results in this work will likely stimulate new research directions in fuzzy fixed-point theory and related hybrid models. Eventually, some fixed-point results on multivalued mappings are established. These theorems provide an excellent application of main theorems on fuzzy mappings. The results of this article are extensions of many already existing results in the literature.

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding ability of fluorinated drug target proteins has also been reported in some cases. An emerging line of research on F substitution has been addressed by using 18F as a radiolabel tracer atom in the extremely sensitive methodology of positron emission tomography (PET) imaging. This review aims to report on the fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2016 to 2022. It cites selected examples from a variety of therapeutic and diagnostic drugs. FDA-approved drugs in this period have a variety of heterocyclic cores, including pyrrole, pyrazole, imidazole, triazole, pyridine, pyridone, pyridazine, pyrazine, pyrimidine, triazine, purine, indole, benzimidazole, isoquinoline, and quinoline appended with either F-18 or F-19. Some fluorinated oligonucleotides were also authorized by the FDA between 2019 and 2022.

Background: Lung cancer is one of the most fatal cancers worldwide, and malignant tumors are characterized by the growth of abnormal cells in the tissues of lungs. Usually, symptoms of lung cancer do not appear until it is already at an advanced stage. The proper segmentation of cancerous lesions in CT images is the primary method of detection towards achieving a completely automated diagnostic system. Method: In this work, we developed an improved hybrid neural network via the fusion of two architectures, MobileNetV2 and UNET, for the semantic segmentation of malignant lung tumors from CT images. The transfer learning technique was employed and the pre-trained MobileNetV2 was utilized as an encoder of a conventional UNET model for feature extraction. The proposed network is an efficient segmentation approach that performs lightweight filtering to reduce computation and pointwise convolution for building more features. Skip connections were established with the Relu activation function for improving model convergence to connect the encoder layers of MobileNetv2 to decoder layers in UNET that allow the concatenation of feature maps with different resolutions from the encoder to decoder. Furthermore, the model was trained and fine-tuned on the training dataset acquired from the Medical Segmentation Decathlon (MSD) 2018 Challenge. Results: The proposed network was tested and evaluated on 25% of the dataset obtained from the MSD, and it achieved a dice score of 0.8793, recall of 0.8602 and precision of 0.93. It is pertinent to mention that our technique outperforms the current available networks, which have several phases of training and testing.

Cotton leaf curl virus (CLCuV) causes devastating losses to fiber production in Central Asia. Viral spread across Asia in the last decade is causing concern that the virus will spread further before resistant varieties can be bred. Current development depends on screening each generation under disease pressure in a country where the disease is endemic. We utilized quantitative trait loci (QTL) mapping in four crosses with different sources of resistance to identify single nucleotide polymorphism (SNP) markers associated with the resistance trait to allow development of varieties without the need for field screening every generation. To assist in the analysis of multiple populations, a new publicly available R/Shiny App was developed to streamline genetic mapping using SNP arrays and to also provide an easy method to convert and deposit genetic data into the CottonGen database. Results identified several QTL from each cross, indicating possible multiple modes of resistance. Multiple sources of resistance would provide several genetic routes to combat the virus as it evolves over time. Kompetitive allele specific PCR (KASP) markers were developed and validated for a subset of QTL, which can be used in further development of CLCuV-resistant cotton lines.

Carbapenem resistance has become major concern in healthcare settings globally; therefore, its monitoring is crucial for intervention efforts to halt resistance spread. During May 2019–April 2022, 2170 clinical strains were characterized for antimicrobial susceptibility, resistance genes, replicon and sequence types. Overall, 42.1% isolates were carbapenem-resistant, and significantly associated with Klebsiella pneumoniae (K. pneumoniae) (p = 0.008) and Proteus species (p = 0.043). Carbapenemases were detected in 82.2% of isolates, with blaNDM-1 (41.1%) associated with the ICU (p < 0.001), cardiology (p = 0.042), pediatric medicine (p = 0.013) and wound samples (p = 0.041); blaOXA-48 (32.6%) was associated with the ICU (p < 0.001), cardiology (p = 0.008), pediatric medicine (p < 0.001), general surgery (p = 0.001), general medicine (p = 0.005) and nephrology (p = 0.020); blaKPC-2 (5.5%) was associated with general surgery (p = 0.029); blaNDM-1/blaOXA-48 (11.4%) was associated with general surgery (p < 0.001), and wound (p = 0.002), urine (p = 0.003) and blood (p = 0.012) samples; blaOXA-48/blaVIM (3.1%) was associated with nephrology (p < 0.001) and urine samples (p < 0.001). Other detected carbapenemases were blaVIM (3.0%), blaIMP (2.7%), blaOXA-48/blaIMP (0.1%) and blaVIM/blaIMP (0.3%). Sequence type (ST)147 (39.7%) represented the most common sequence type identified among K. pneumoniae, along with ST11 (23.0%), ST14 (15.4%), ST258 (10.9%) and ST340 (9.6%) while ST405 comprised 34.5% of Escherichia coli (E. coli) isolates followed by ST131 (21.2%), ST101 (19.7%), ST10 (16.0%) and ST69 (7.4%). Plasmid replicon types IncFII, IncA/C, IncN, IncL/M, IncFIIA and IncFIIK were observed. This is first report describing the carbapenem-resistance burden and emergence of blaKPC-2-ST147, blaNDM-1-ST340 and blaNDM-1-ST14 in K. pneumoniae isolates and blaNDM-1-ST69 and blaNDM-1/blaOXA-48-ST69 in E. coli isolates coharboring extended-spectrum beta-lactamases (ESBLs) from Pakistan.

Staphylococcus aureus (S. aureus) is a major causative agent of mastitis and is resistant to many antibiotics. Thus, there is a need to characterize the genetic determinants of S. aureus erythromycin resistance, such as ermA, ermB and ermC. The current study aimed to determine the phenotypic and genotypic erythromycin resistance profile and relatedness of S. aureus recovered from bovine mastitis and humans in close contact. A total of 14 mastitis-infected buffalo milk samples and 16 samples from their respective milkers were collected from different farms of Lahore, Pakistan. The antibiotic resistance profile was determined through the disk diffusion test. The overall prevalence of S. aureus in mastitis-affected buffaloes was found to be 75%, of which 52.1% were resistant to erythromycin and 42.8% to clindamycin. S. aureus isolates recovered from milker nasal samples showed 56.25% resistance to erythromycin and 44% resistance to clindamycin. Genotypic antibiotic resistance profiles were determined from 14 milk samples through PCR. Overall, eight (52.1%), three (21.4%) and five (35.7%) S. aureus isolates were positive for the ermA, ermB and ermC genes, respectively. Moreover, 16 milker nasal S. aureus isolates were also tested for the presence of ermA, ermB and ermC genes. The ermA, ermB and ermC genes were observed in nine(56.7%), five (31.3%) and seven (43.7%) isolates, respectively. A significant association was shown between phenotypic and genotypic erythromycin resistance. The results indicate both that there are sufficient genetic similarities, and the actual transmission of erythromycin resistance genes between these two hosts of S. aureus.

The emergence of carbapenem-resistant Escherichia coli (E. coli) is considered an important threat to public health resulting in resistance accumulation due to antibiotics misuse and selection pressure. This warrants periodic efforts to investigate and develop strategies for infection control. A total of 184 carbapenem-resistant clinical strains of E. coli were characterized for resistance pattern, resistance genes, plasmids, sequence types and in vitro efficacy of silver nanoparticles (AgNPs). Carbapenem resistance was prevalent in E. coli isolated from female patients (64.7%), urine samples (40.8%) and surgical wards (32.1%). Polymyxin-B showed higher susceptibility. ESBLs and carbapenemases were produced in 179 and 119 isolates, respectively. Carbapenemase-encoding genes were observed among 104 strains with blaNDM-1 (45.1%), blaOXA-48 (27%), blaNDM-7 (3.8%), blaNDM-1/blaOXA-48 (15.4%), blaNDM-7/blaOXA-48 (2.9%), blaOXA-48/blaVIM (3.8%) and blaNDM-1/blaVIM (2%). ESBL resistance genes were detected in 147 isolates, namely blaSHV (24.9%), blaCTX-M (17.7%), blaTEM (4.8%), blaSHV/blaCTX-M (29.2%), blaSHV/blaTEM (15%) and blaCTX-M/blaTEM (8.8%). ST405 (44.4%) and ST131 (29.2%) were more frequent sequence types with ST101 (9.7%), ST10 (9.7%) and ST648 (7%). The replicon types IncFII, IncFIIK, IncA/C, IncN and IncL/M were detected. The combination of MEM/AgNPs remained effective against carbapenemase-positive E. coli. We reported genetically diverse E. coli strains coharboring carbapenemases/ESBLs from Pakistan. Moreover, this study highlights the enhanced antibacterial activity of MEM/AgNPs and may be used to manage bacterial infections.

As a prevalent progressive neurodegenerative disorder, Parkinson’s disease (PD) is characterized by the neuropathological hallmark of the loss of nigrostriatal dopaminergic (DAergic) innervation and the appearance of Lewy bodies with aggregated α-synuclein. Although several familial forms of PD have been reported to be associated with several gene variants, most cases in nature are sporadic, triggered by a complex interplay of genetic and environmental risk factors. Numerous epidemiological studies during the past two decades have shown positive associations between PD and several environmental factors, including exposure to neurotoxic pesticides/herbicides and heavy metals as well as traumatic brain injury. Other environmental factors that have been implicated as potential risk factors for PD include industrial chemicals, wood pulp mills, farming, well-water consumption, and rural residence. In this review, we summarize the environmental toxicology of PD with the focus on the elaboration of chemical toxicity and the underlying pathogenic mechanisms associated with exposure to several neurotoxic chemicals, specifically 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat (PQ), dichloro-diphenyl-trichloroethane (DDT), dieldrin, manganese (Mn), and vanadium (V). Our overview of the current findings from cellular, animal, and human studies of PD provides information for possible intervention strategies aimed at halting the initiation and exacerbation of environmentally linked PD.

One of the most important renewable energy technologies used nowadays are wind power turbines. In this paper, we are interested in identifying the operating status of wind turbines, especially rotor blades, by means of multiphysical models. It is a state-of-the-art technology to test mechanical structures with ultrasonic-based methods. However, due to the density and the required high resolution, the testing is performed with high-frequency waves, which cannot penetrate the structure in depth. Therefore, there is a need to adopt techniques in the fields of multiphysical model-based inversion schemes or data-driven structural health monitoring. Before investing effort in the development of such approaches, further insights and approaches are necessary to make the techniques applicable to structures such as wind power plants (blades). Among the expected developments, further accelerations of the so-called “forward codes” for a more efficient implementation of the wave equation could be envisaged. Here, we employ electromagnetic waves for the early detection of cracks. Because in many practical situations, it is not possible to apply techniques from tomography (characterized by multiple sources and sensor pairs), we focus here on the question of whether the existence of cracks can be determined by using only one source for the sent waves.

Polygonum hydropiper L. is a traditionally used medicinal plant. The present study was designed to explore the α-amylase inhibitory, antioxidant, and antimicrobial activities of Polygonum hydropiper L. Polarity-based solvent extracts (n-hexane, acetone, chloroform, methanol, ethanol, and water) of Polygonum hydropiper leaves and stem were used. Antioxidant activity was assessed by free radical scavenging assay (FRAP) and 2,2-diphenylpicrylhydrazyl (DPPH) free radical scavenging activity methods. Quantitative phytochemical analyses suggested that the stem of Polygonum hydropiper L. contains higher levels of bioactive compounds than its leaves (p < 0.05). The results suggested that stem-derived extracts of Polygonum hydropiper L. are more active against bacterial species, including two Gram-positive and three Gram-negative strains. Moreover, our results showed that the bioactive compounds of Polygonum hydropiper L. significantly inhibit α-amylase activity. Finally, we reported the polarity-based solvent extracts of Polygonum hydropiper L. and revealed that the stem, rather than leaves, has a high antioxidant potential as measured by FRAP and DPPH assay with IC50 values of 1.38 and 1.59 mg/mL, respectively. It may also be deducted from the data that the Polygonum hydropiper L. could be a significant candidate, which should be subjected to further isolation and characterization, to be used as an antidiabetic, antimicrobial and antioxidant resource in many industries, like food, pharmaceuticals and cosmetics.

This work highlights how the treatment of ZSM-5 (parent Zeolite Socony Mobil–5, Si/Al = 23) with different surfactant templates and alkaline solution, improved the catalytic performance in the Friedel-Crafts acylation of anisole with a propionic anhydride to obtain p-methoxypropiophenone. The modified microporous to mesoporous zeolite catalysts were characterized using different analytical techniques, including X-ray diffraction (XRD), nitrogen porosimetry, Fourier-transform infrared spectroscopy (FT-IR), temperature-programmed desorption (ammonia-TPD) and field emission scanning electron microscopy (FE-SEM) to analyze the crystallographic structure, surface acidity, surface area, porosity, morphology, and particle size. The results showed that the formed mesoporous zeolite by NaOH solution had smaller mesopores (ca. 3.7 nm) as compared to the mesoporous zeolites obtained by surfactant templates, such as, CTAB (ca. 14.9 nm), TPAOH (ca. 11.1 nm) and mixture of CTAB/TPAOH (ca. 15.2 nm). The catalytic acylation reaction was conducted in a batch glass reactor at various temperatures and the products were analyzed using off-line gas chromatography–mass spectrometry (GC-MS). It was found that the activity of treated ZSM-5 with mixed surfactant templates (CTAB/TPAOH) exhibited enhanced selectivity towards the main product (p-methoxypropiophenone) by a factor 1.7 or higher than unmodified ZSM-5 due to its increased surface area by 1.5 times and enhanced acid sites.

Recently, piezoelectric materials have achieved remarkable attention for charging wireless sensor nodes. Among piezoelectric materials, non-ferroelectric materials are more cost effective because they can be prepared without a polarization process. In this study, a non-ferroelectric nanogenerator was manufactured from 0.7PbZn0.3Ti0.7O3-0.3Na2TiO3 (PZnT-NT). It was demonstrated that the increment of conductivity via adding the Na2TiO3 plays an essential role in increasing the permittivity of the non-ferroelectric nanogenerator and hence improved the generated power density. The dielectric measurements of this material demonstrated high conductivity that quenched the polarization phase. The performance of the device was studied experimentally over a cantilever test rig; the vibrating cantilever (0.4 ms−2) was excited by a motor operated at 30 Hz. The generated power successfully illuminated a light emitting diode (LED). The PZnT-NT nanogenerator produced a volume power density of 0.10 μw/mm3 and a surface power density of 10 μw/cm2. The performance of the proposed device with a size of (20 × 15 × 1 mm3) was higher in terms of power output than that of the commercial microfiber composite (MFC) (80 × 57 × 0.335 mm3) and piezoelectric bimorph device (70 × 50 × 0.7 mm3). Compared to other existing ferroelectric and non-ferroelectric nanogenerators, the proposed device demonstrated great performance in harvesting the energy at low acceleration and in a low frequency environment

The present study explored Euphorbia larica essential oil (ELEO) constituents for the first time, obtained via hydro-distillation by means of Gas Chromatography-Mass Spectrometry (GC-MS) profiling. The essential oil was screened in vitro against breast cancer cells, normal cell lines, α-glucosidase, carbonic anhydrase-II (CA-II), free radical scavenging and in vivo analgesic and anti-inflammatory capabilities. The GC-MS screening revealed that the ELEO comprises sixty compounds (95.25%) with the dominant constituents being camphene (16.41%), thunbergol (15.33%), limonene (4.29%), eremophilene (3.77%), and β-eudesmol (3.51%). A promising antidiabetic capacity was noticed with an IC 50 of 9.63 ± 0.22 μg/mL by the ELEO as equated to acarbose with an IC 50 = 377.71 ± 1.34 μg/mL, while a 162.82 ± 1.24 μg/mL inhibition was observed against CA-II. Regarding breast cancer, the ELEO offered considerable cytotoxic capabilities against the triple-negative breast cancer (MDA-MB-231) cell lines, having an IC 50 = 183.8 ± 1.6 μg/mL. Furthermore, the ELEO was also tested with the human breast epithelial (MCF-10A) cell line, and the findings also presumed that the ELEO did not produce any damage to the tested normal cell lines. The ELEO was effective against the Gram-positive bacteria and offered a 19.8 ± 0.02 mm zone of inhibition (ZOI) against B. atrophaeus . At the same time, the maximum resistance with 18.03 ± 0.01 mm ZOI against the fungal strain Aspergillus parasiticus was observed among the tested fungal strains. An appreciable free radical significance was observed via the DPPH assay with an IC 50 = 133.53 ± 0.19 µg/mL as equated to the ABTS assay having an IC 50 = 154.93 ± 0.17 µg/mL. The ELEO also offered a substantial analgesic capacity and produced 58.33% inhibition in comparison with aspirin, a 68.47% decrease in writhes, and an anti-inflammatory capability of 65.54% inhibition, as equated to the standard diclofenac sodium having 73.64% inhibition. Hence, it was concluded that the ELEO might be a natural source for the treatment of diabetes mellitus, breast cancer, analgesic, inflammatory, and antimicrobial-related diseases. Moreover, additional phytochemical and pharmacological studies are needed to isolate responsible chemical ingredients to formulate new drugs for the examined activities.