Designing novel anti-plasmodial quinoline-furanone hybrids: computational insights, synthesis, and biological evaluation targeting Plasmodium falciparum lactate dehydrogenase.

To combat resistance against current antimalarials, modifying key pharmacophores and exploring novel parasite-specific drug targets remained one of the key drug design strategies. The resistance to quinoline-based antimalarials arises often due to the efflux of the drug. Hence, the development of newer agents containing bulkier pharmacophores will enable medicinal chemists to counteract drug resistance. In view of this, herein we designed bulkier quinoline-furanone hybrids. Initially, virtual drug-likeness and ADMET screening were conducted to optimize physicochemical properties followed by docking of the hybrids against the Plasmodium falciparum lactate dehydrogenase (PfLDH) enzyme. The most potent hybrids that emerged from the computational screening were synthesized and screened for their bioactivity against the resistant strain of Plasmodium through Schizont Maturation Inhibition assays. Among the compounds tested, 5g and 6e demonstrated the best activity, with IC50 values similar to chloroquine (CQ), and 5g exhibited superior LDH inhibition compared to CQ. Compounds 5f, 7a, and 7f showed IC50 values comparable to CQ and moderate LDH inhibition. Structure-activity relationship (SAR) analysis revealed that halogen substitutions, particularly Br and Cl, enhanced antimalarial activity, while strong electron-withdrawing (-NO2) or -donating (-OH) groups led to diminished activity. Additionally, bulkier aromatic substitutions were favoured for antimalarial activity and LDH inhibition. The investigation successfully found potent anti-plasmodial quinoline-furanone hybrids, demonstrating promising prospects for combating malaria.

Polymorphism Dependent Cytotoxicity, Cellular Uptake, and Live Cell Imaging Studies on Napthalimide-Vinyl-Phenothiazine Conjugate.

Polymorphism-dependent cytotoxicity and cellular uptake of drug molecules have been studied for the past two decades. However, the visualization of polymorph-dependent cellular uptake and cytotoxicity using microscopy imaging techniques has not yet been reported. The luminescent polymorph is an ideal candidate to validate the above hypothesis. Herein, we report the polymorph-dependent cellular uptake, cytotoxicity, and bio-imaging functions of polymorphs 1Y and 1R of a naphthalimide-phenothiazine dyad. These polymorphs show different luminescence colors in the solid state and exhibit aggregation-induced enhanced emission (AIEE) in the DMSO-Water mixture. Bioimaging, cytotoxicity assay, and fluorescence-activated cell sorting (FACS) studies revealed that these polymorphs show different levels of cytotoxicity, cellular uptake, localization, and imaging potential. Detailed photophysical, morphological, and biological studies revealed that the difference in molecular conformation in these polymorphs enables them to form aggregates of different sizes and morphology, which leads to the differential uptake of these into the cells and consequently shows different cytotoxicity and imaging potentials.

Psiguanol, a novel α-pyrone derivative from Psidium guajava leaves and vasorelaxant activity in rat aorta cells through intracellular cGMP-dependent opening of calcium-activated potassium channels.

The phytochemical investigation of Psidium guajava leaves led to the isolation of total nineteen compounds which belongs to meroterpenoids, flavonoid, phenolics, and triterpenoids. The compounds were isolated using extensive chromatography techniques and identified as psiguanol (4), as new compound along with guajadial (1), psidial A (2), ß-caryophyllene (3), quercetin (5), avicularin (6), guaijaverin (7), hyperin (8), rutin (9), ursolic acid (10), corosolic acid (11), asiatic acid (12), ß-sitosterol (13), ß-sitosterol-D-glucoside (14), ellagic acid (15), 3,3',4'-trimethylellagic acid 4-O-glucoside (16), protocatechuic acid (17), gallic acid (18), and tricosanoic acid (19) as known molecules. The compound 16 was isolated for the first time from this plant. The isolated compounds were evaluated for vasorelaxation activity in rat aorta cells and it was observed that compound 4 exhibited the most potent vasorelaxation response in the ex-vivo model in isolated rat aorta cells. Mechanistically, the vasorelaxation activity of 4 was mediated through cGMP-dependent BKCa channel opening.

Inherited thrombophilia: undetected comorbidity complicating COVID-19 infection.

The relation between the severity of COVID-19 and coexisting undiagnosed underlying thrombophilic conditions is not yet established. It may be possible that undiagnosed thrombophilia exaggerates an already pro-thrombotic state in COVID-19 patients and may be responsible for severe disease in absence of any known co-morbidity. The aim was to analyze the association of underlying thrombophilia with the severity of COVID-19 infection in post-COVID patients after a minimum of 6 weeks of recovery and to compare thrombophilia profile in severe versus non-severe COVID-19 patients. Forty severe and 40 non-severe COVID patients at least 6 weeks post recovery were selected for thrombophilia profile and complete blood count evaluation. The data were analyzed using Stata software, USA; version 13. The Chi-square test and Student's t-test were used to compare proportions and mean respectively. A total of 14/80 (17.5%) were positive for the thrombophilia screen. Protein C deficiency was noted in 6/40 (15%) severe COVID patients but not in the non-severe group. The Protein S deficiency was seen in 7/40 (17.5%) severe patients and only 1 patient was deficient in the non-severe group (2.5%). The mean Protein C and Protein S levels of severe and non-severe COVID patients were statistically significant (P-0.002) and (P-0.007) respectively. The difference in mean anti-COVID IgG antibody titer of severe and non-severe COVID patients was also statistically significant (P-0.0001). To Conclude, Protein C & S deficiencies were the commonest abnormalities detected in severe COVID patients. Positive thrombophilia profile and higher titers of anti-IgG COVID-19 antibodies were seen in a significant number of patients who had suffered from Severe COVID-19 than in non-severe infection, even after 6 weeks of recovery. Thereby, suggesting that underlying thrombophilia might have affected the severity of the disease.

The influence of non-thermal technologies on color pigments of food materials: An updated review.

The color of any food is influenced by several factors, such as food attributes (presence of pigments, maturity, and variety), processing methods, packaging, and storage conditions. Thus, measuring the color profile of food can be used to control the quality of food and examine the changes in chemical composition. With the advent of non-thermal processing techniques and their growing significance in the industry, there is a demand to understand the effects of these technologies on various quality attributes, including color. This paper reviews the effects of novel, non-thermal processing technologies on the color attributes of processed food and the implications on consumer acceptability. The recent developments in this context and a discussion on color systems and various color measurement techniques are also included. The novel non-thermal techniques, including high-pressure processing, pulsed electric field, ultrasonication, and irradiation which employ low processing temperatures for a short period, have been found effective. Since food products are processed at ambient temperature by subjecting them to non-thermal treatment for a very short time, there is no possibility of damage to heat-sensitive nutrient components in the food, any deterioration in the texture of the food, and any toxic compounds in the food due to heat. These techniques not only yield higher nutritional quality but are also observed to maintain better color attributes. However, suppose foods are exposed to prolonged exposure or processed at a higher intensity. In that case, these non-thermal technologies can cause undesirable changes in food, such as oxidation of lipids and loss of color and flavor. Developing equipment for batch food processing using non-thermal technology, understanding the appropriate mechanisms, developing processing standards using non-thermal processes, and clarifying consumer myths and misconceptions about these technologies will help promote non-thermal technologies in the food industry.

Vasorelaxant property of 2-phenyl ethyl alcohol isolated from the spent floral distillate of damask rose (Rosa damascena Mill.) and its possible mechanism.

ETHNOBOTANICAL RELEVANCE: Rosa damascena Mill. (Rosaceae), commonly known as damask rose, is an ancient medicinal and perfumery plant used in Traditional Unani Medicine due to various therapeutic effects, including cardiovascular benefits. AIM OF THE STUDY: This study aimed to evaluate the vasorelaxant effect of the 2-phenyl ethyl alcohol (PEA) isolated from the spent flowers of R. damascena which remain after the extraction of essential oil. MATERIALS AND METHODS: The freshly collected flowers of R. damascena were hydro-distilled in a Clevenger's type apparatus to extract the rose essential oil (REO). After removing the REO, the spent-flower hydro-distillate was collected and extracted with organic solvents to yield a spent-flower hydro-distillate extract (SFHE), which was further purified by column chromatography. The SFHE and its isolate were characterized by gas chromatography (GC-FID), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) techniques. The PEA, isolated from SFHE, was evaluated for vasorelaxation response in conduit blood vessels like rat aorta and resistant vessels like mesenteric artery. The preliminary screening of PEA was done in aortic preparation pre-constricted with phenylephrine/U46619. Further, a concentration-dependent relaxation response to PEA has been elicited in both endothelium-intact and endothelium-denuded arterial rings, and the mode of action was explored. RESULTS: The SFHE revealed the presence of PEA as the main constituent (89.36%), which was further purified by column chromatography to a purity of 95.0%. The PEA exhibited potent vasorelaxation response both in conduit vessels like the rat aorta and resistance vessels like the mesenteric artery. The relaxation response is mediated without any involvement of vascular endothelium. Further, TEA sensitive BKCa channel was found to be the major target for PEA-induced relaxation response in these blood vessels. CONCLUSIONS: The spent flowers of R. damascena, which remain after the extraction of REO, could be used to extract PEA. The PEA possessed marked vasorelaxation properties in both aorta and mesenteric artery and showed promise for development into an herbal product against hypertension.

Synthesis of 6-alkoxy and 6-hydroxy-alkyl amine derivatives of braylin as vasorelaxing agents.

Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b, 15-19), and twelve 6-hydroxy-alkyl amine (20a-20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA). The compounds showed l-type VDCC channel blockade depended and endothelium-independent vasorelaxation within the range of Emax < 50.00-96.70 % at 30 µM. Amongst all, 6-alkoxy derivatives were more active than 6-hydroxy-alkyl amine derivatives. The structural refinements about braylin showed that deletion of its methoxy group or homologation beyond ethoxy group presented deleterious effect on vasorelaxation response of braylin. Interestingly, substituting the ethoxy group in 10b presented the best activity and selectivity towards l-type VDCC channel blockade, a specific target cardiovascular function.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Data on antibiotic resistance among indoor microbiome at Meerut, India.

Microbial dynamics of the domestic environment and their antibiotic-resistant properties have been poorly characterized. We surveyed the microbial community and their antibiotic profiling located in the rural and urban areas of Meerut city, Uttar Pradesh, India. Results show that bacterial community load across all samples had more than 100-fold higher than fungal community (all p<0.05.). Based on population load, the kitchen of both rural (Fungal: 4.16±1.81 vs Bacteria: 160.5±27.13) and urban areas (Fungal: 6.2±1.02 vs Bacteria: 205.46±30.9) were more contaminated than living rooms (rural area-Fungal: 2.13±0.74 vs Bacteria: 62.17±20.68 and urban area- Fungal: 4.75±1.68 vs Bacteria: 74.88±7.53). Six bacteria, namely Pseudomonas sps; Citrobacter sps; Bacillus Subtilis; Brevundimonas diminuta; Bacillus megaterium; and Klebsiella pneumonia, showed dominance on all other bacterial and fungal sp hence, only these six bacteria were subjected to antibiotic sensitivity test (AST). In AST, Klebsiella pneumoniae, Bacillus Subtilis, Bacillus megaterium, were resistant to more than three antibiotics. The most sensitive strain for Ciprofloxacin, Streptomycin was Citrobacter sp. However, Pseudomonas sp was found sensitive only to Amoxillin. Brevundimonas diminuta is found most sensitive to all antibiotics. Plasmid profiling of selected bacteria suggests that antibiotic resistance properties arose from plasmids, not genomic ones. These findings give new insights into the local-scale distribution of MDR bacteria in a household environment.

A substrate-dependent reaction of 1-aryl-2-alkyl-1,2-diketones with 2-aroyl-1-chlorocyclopropanecarboxylates: selective access to 2',5'-dicyclopropoxy-1,1':4',1''-teraryls and pentafulvenes.

An interesting substrate-controlled one-pot approach to highly substituted 2',5'-dicyclopropoxy-1,1':4',1''-teraryls and 6-hydroxypentafulvenes involving various 1,2-diketones and 2-aroyl-1-chlorocyclopropanecarboxylates as 3C Michael acceptors triggered by Cs2CO3 has been developed. We noticed that 1,2-diketones play a decisive role in this reaction to determine the product's selectivity. For example, aryl rings having electron-poor functionalities at the para and meta-positions of 1,2-diketones led to 2,5-diarylhydroquinones selectively via a cyclodimerization/double oxa-Michael process with highly strained cyclopropenes. However, when 1-naphthyl/electron-donating aryl/ortho-aryl-substituted 1,2-diketones were chosen, the Michael-initiated ring expansion reaction (C-C and CC bonds) took place under the same conditions that gave the corresponding pentafulvenes predominately. Moreover, this reaction has several imperative features such as good to high diastereoselectivities, wide substrate scope, good functional group tolerance, transition metal-free process, etc.

Probing the topological surface states in superconducting Sn4Au single crystal: a magneto transport study.

Materials exhibiting bulk superconductivity along with magnetoresistance (MR) in their normal state have emerged as suitable candidates for topological superconductivity. In this article, we report a flux free method to synthesize single crystal of topological superconductor candidate Sn4Au. The phase purity and single crystalline nature are confirmed through various characterizations viz. x-ray diffraction, field emission scanning electron microscopy, selected area electron diffraction, and transmission electron microscopy. Chemical states of the constituent element viz. Sn and Au are analysed through x-ray photoelectron spectroscopy. Superconductivity in synthesized Sn4Au single crystal is evident formρ-Tplot, for which the critical field (Hc) is determined throughρ-Hplot at 2 K i.e. just below critical temperatureTc. A positive MR is observed inρ-Hmeasurements at different temperatures aboveTc, viz. at 3 K, 5 K, 10 K and 20 K. Further, the magnetoconductivity (MC) is analysed by using Hikami-Larkin-Nagaoka formalism, which signifies the presence of weak antilocalization (WAL) effect in Sn4Au. Angle dependent magneto-transport measurement has been performed to detect the origin of observed WAL effect in Sn4Au single crystal. Normalized MC vsHcosθplot shows presence of topological surface states in the studied system. It is evident that Sn4Au is a 2.6 K topological superconductor.

Osmo-air drying of banana slices: multivariate analysis, process optimization and product quality characterization.

In the present work, osmotic dehydration (OD) was applied as a pretreatment to hot air drying of banana slices and the effect of OD parameters on mass transfer characteristics, color profile was analysed. Principal component analysis (PCA) of OD process revealed that solid gain, weight reduction, water loss and total soluble solids were positively correlated with each other but were found to be negatively correlated with moisture content (MC) of sample. Response surface methodology was used for optimizing the OD of banana slices and and the optimum conditions were 61.26°Brix sucrose concentration at 50 °C for 6 h, resulting in moisture reduction from 75 to 49.78%. PCA-biplot of osmo-air drying (OAD) process showed the association among response parameters, which further revealed a positive correlation of MC with bioactive components. Additionally, OAD samples were also studied for microstructure and Fourier Transform Infra-red analysis. Addition of calcium lactate to sucrose solution resulted in preserving the firmness and bioactive components during osmosis, in addition to fortifying the sample with calcium. The present study provides new possibilities for food industries in preserving the ripe banana and developing calcium fortified functional food products.

Blockchain-based rumor detection approach for COVID-19.

The ubiquity of handheld devices and easy access to the Internet help users get easy and quick updates from social media. Generally, people share information with their friends and groups without inspecting the posts' veracity, which causes false information propagation in the network. Moreover, detecting false news and rumors in such a massive load of unstructured information is a very tedious task. Results, many literature papers explored different machine learning and deep learning approaches to detect the presence of rumors on social media networks. Although detection of misleading news and rumors is not sufficient, therefore, we have proposed a model for the detection and prevention of transmitted rumors in this paper. In this paper, we use blockchain technology to verify the credibility of information and design a framework with four layers: network layer, blockchain layer, machine layer, and device layer, to prevent the propagation of rumors in the network. We also use deep learning techniques to identify the anomalies in the network. The Bi-directional Long Short Term Memory (Bi-LSTM) model is used to prevent the introduction of new rumors by continuously monitoring incoming messages in the network. The experimental results demonstrate that the proposed Bi-LSTM model outperforms state-of-the-art machine learning methods and recent baseline work. Performance is compared over different metrics such as accuracy, precision, recall, f1-score, and specificity. Experiment results show that our Bi-LSTM model outperforms all the other approaches and achieved 99.63 % accuracy. Additionally, the probability of incorrect detection is significantly low with only 0.13% false positive.

Static smartphone images supplemented by videoconferencing for breast telepathology.

BACKGROUND: Both static images and videoconferencing by smartphone have been tried for telepathology. Combining the two approaches for telepathology might offset some of the limitations of both techniques. METHODS: A total of 150 cases of breast pathology were retrieved and were photographed by a trained junior pathologist using a smartphone camera and binocular microscope and the images were sent as Google photos attachments with email to three pathologists. The pathologists opened the emailed attachments during separate prescheduled google meet videoconferencing sessions and rendered the diagnosis verbally to the junior pathologist. The pathologists were given the option of asking for live dynamic images of the cases during the meet which were transmitted using the rear camera of the smartphone with the video option of google meet. RESULTS: The overall concordance rates for the three pathologists were 96.6%, 99.3% and 98.0% (Mean 98.0%). The reporting pathologists asked for dynamic live images in 23, 20 and 18 cases respectively. Out of these 61 cases, a discrepant diagnosis was made in 7 cases (11.4%). The reporting pathologist was satisfied with the quality of static images (Mean Likert score 4.2/5). However, concerns were raised on the consistency of video quality (Mean Likert score 2.5/5). The screen share option of Google meet was found useful to discuss specific features of the case. (Mean Likert Score 4.6/5) CONCLUSION: The combined approach to telepathology has shown some promise and it is hoped that with adequate training the discordance can be reduced.

Extrusion of fermented rice-black gram flour for development of functional snacks: Characterization, optimization and sensory analysis.

Considering the health benefits of fermentation, extrusion of fermented rice black gram mix flour can lead to developing nutritionally rich expanded snack. Hence, present study details the effect of various extrusion process variables, barrel temperature (100, 110, 120 °C), screw speed (250, 300, 350 rpm) and die opening diameter (3, 3.5 mm) on physicochemical and bioactive properties of extrudates from fermented rice-black gram flour (Rice flour: black gram flour = 3:1). Results indicated that temperature rise led to the production of a more expanded product with higher water solubility index (WSI) and lower water absorption index (WAI). Higher puffing, WSI, and bioactive content were observed in 3 mm die opening extrudates. Interestingly, extrusion cooking of fermented flour has shown a remarkable increment in phenolic content and antioxidant activity from 63.47 up to 210.3 and 7.28 up to 13.889 mg GAE/100 g, respectively. However, rise in barrel temperature showed a negative impact on bioactive attributes. Further, the optimal conditions determined by numerical optimization method for development of fermented flour-based extrudates having superior functional and enhanced bioactive properties were found to be 100 °C temperature, 289 rpm of screw and 3 mm die diameter. Principal component analysis indicated that bulk density-moisture content and phenolic content-antioxidant activity were highly positively correlated, while expansion ratio-bulk density was negatively correlated. The microstructure of extrudates showed continuous and compact structure lacking starch granules. The fuzzy logic analysis revealed that fermented flour-based extruded product had superior overall acceptability over unfermented flour extrudates.

Modelling of moisture migration during convective drying of pineapple slice considering non-isotropic shrinkage and variable transport properties.

The present work aims to develop a 3-dimensional finite element (FE) model to analyze moisture migration during drying of pineapple ring considering moisture dependent diffusion coefficient (D) and mass transfer coefficient (hm) along with radial and longitudinal shrinkage. Pineapple rings were dried at 70 °C temperature and 0.6 m/s air velocity to study the moisture loss and shrinkage kinetics during drying. Thickness, outer radius and inner radius of hollow cylindrical pineapple slices were reduced by 79.3%, 32.2%, and 51.2%, respectively due to the occurrence of shrinkage during drying. Non-linear regression analysis showed the quadratic model to best fitted to the experimental moisture ratio data for explaining the shrinkage phenomenon in pineapple slice during drying. Shrinkage was accommodated into FE modelling using the arbitrary lagrange-eulerian method. Consideration of variable D showed better agreement with the experimental data than consideration of constant D, however constant and variable hm predicted similar results. Incorporation of shrinkage phenomena during modelling led to prediction of more accurate result showing 0.06% deviation from experimental curve, but neglecting the shrinkage resulted in a 17% deviation. Hence, model developed with consideration of shrinkage along with variable D and hm presented best fit with experimental drying curve. Developed model allowed the visualization of spatial moisture profile within the sample during drying, which would be useful for estimating the correct drying time, optimizing and designing of drying process.

Data-driven modelling and prediction of COVID-19 infection in India and correlation analysis of the virus transmission with socio-economic factors.

AIMS: The current study attempts to model the COVID-19 outbreak in India, USA, China, Japan, Italy, Iran, Canada and Germany. The interactions of coronavirus transmission with socio-economic factors in India using the multivariate approach were also investigated. METHODS: Actual cumulative infected population data from 15 February to May 15, 2020 was used for determination of parameters of a nested exponential statistical model, which were further employed for the prediction of infection. Correlation and Principal component analysis provided the relationships of coronavirus spread with socio-economic factors of different states of India using the Rstudio software. RESULTS: Cumulative infection and spreadability rate predicted by the model was in good agreement with the actual observed data for all countries (R2 = 0.985121 to 0.999635, and MD = 1.2-7.76%) except Iran (R2 = 0.996316, and MD = 18.38%). Currently, the infection rate in India follows an upward trajectory, while other countries show a downward trend. The model claims that India is likely to witness an increased spreading rate of COVID-19 in June and July. Moreover, the flattening of the cumulative infected population is expected to be obtained in October infecting more than 12 lakhs people. Indian states with higher population were more susceptible to virus infection. CONCLUSIONS: A long-term prediction of cumulative cases, spreadability rate, pandemic peak of COVID-19 was made for India. Prediction provided by the model considering most recent data is useful for making appropriate interventions to deal with the rapidly emerging pandemic.