Improving Access to Eye Care in Rural Communities: PocDoc's Web-Based Visual Acuity Screening Tool.

Objective: Visual acuity (VA) testing is crucial for early intervention in cases of visual impairment, especially in rural health care. This study aimed to determine the potential of a web-based VA test (PocDoc) in addressing the unique health care needs of rural areas through the comparison in its effectiveness against the conventional VA test in identifying visual impairment among an Indian rural population. Methods: Prospective comparative study conducted in December 2022 at a tertiary referral eye care center in central India. We evaluated all patients with the PocDoc VA tests using three device types, and the conventional VA test. Bland-Altman plot (BAP) compared PocDoc and conventional VA tests. Fisher's exact tests evaluated associations between categorical parameters. Kruskal-Wallis tests followed by post hoc Dunn's tests identified association between categorical parameters and numerical parameters. Results: We evaluated 428 patients (792 measurements of VA) with mean age 36.7 (±23.3) years. PocDoc resulted in slightly worse VA scores (mean logMAR: 0.345) than conventional (mean logMAR: 0.315). Correlation coefficient between the conventional and PocDoc logMAR VA values was rho = 0.845 and rho2 = 0.7133 (p = 6.617 × 10-215; adjusted p = 2.205 × 10-214). Most data points fell within the interchangeable range of ±0.32 on BAP. Difference between the two methods increased with higher logMAR values, indicating poorer agreement for worse VA scores. Conclusions: Identifying and addressing the unique health care needs of rural populations is critical, including access to appropriate and effective VA testing methods. Validating and improving VA testing methods can ensure early intervention and improve the quality of life for individuals with visual impairment.

Variants in exon 2 of MED12 gene causes uterine leiomyoma's through over-expression of MMP-9 of ECM pathway.

AIMS: To study the impact of Mediator complex subunit 12 (MED12) gene variants on the encoded protein's function and pathogenic relevance for genesis of uterine leiomyoma's (ULs). METHODS: Mutational analysis in exon-2 of MED12 gene was performed by PCR amplification and DNA sequencing in 89 clinically diagnosed ULs tissues. Pathogenicity prediction of variation was performed by computational analysis. The functional effects of missense variation were done by quantity RT-PCR and western blot analysis. RESULT(S): Out of 89 samples, 40 (44.94%) had missense variation in 14 different CDS position of exon-2 of MED12 gene. Out of 40 missense variation, codon 44 had 25 (62.5%) looking as a hotspot region for mutation for ULs, because CDS position c130 and c131present at codon 44 that have necleotide change G>A, T, C at c130 and c131 have necleotide change G>A and C. We also find somenovel somatic mutations oncodon 36 (T > C), 38 (G>T) of exon-2 and 88 (G>C) of intron-2. No mutations were detected in uterine myometrium samples. Our computational analysis suggests that change in Med12c .131 G>A leads to single substitution of amino acid [Glycine (G) to Aspartate (D)] which has a pathogenic and lethal impact and may cause instability of MED12 protein. Further, analysis of extracellular matrix (ECM) component (MMP-2 & 9, COL4A2 and α-SMA) mRNA and protein expression levels in the set of ULs having MED12 mutation showed significantly higher expression of MMP-9 and α-SMA. CONCLUSION(S): The findings of present study suggest that missense variation in codon 44 of MED12 gene lead to the genesis of leiomyoma's through over-expression of MMP-9 of ECM pathway which could be therapeutically targeted for non-surgical management of ULs.

Dissection of QTLs conferring drought tolerance in B. carinata derived B. juncea introgression lines.

BACKGROUND: Drought is one of the important abiotic stresses that can significantly reduce crop yields. In India, about 24% of Brassica juncea (Indian mustard) cultivation is taken up under rainfed conditions, leading to low yields due to moisture deficit stress. Hence, there is an urgent need to improve the productivity of mustard under drought conditions. In the present study, a set of 87 B. carinata-derived B. juncea introgression lines (ILs) was developed with the goal of creating drought-tolerant genotypes. METHOD: The experiment followed the augmented randomized complete block design with four blocks and three checks. ILs were evaluated for seed yield and its contributing traits under both rainfed and irrigated conditions in three different environments created by manipulating locations and years. To identify novel genes and alleles imparting drought tolerance, Quantitative Trait Loci (QTL) analysis was carried out. Genotyping-by-Sequencing (GBS) approach was used to construct the linkage map. RESULTS: The linkage map consisted of 5,165 SNP markers distributed across 18 chromosomes and spanning a distance of 1,671.87 cM. On average, there was a 3.09 cM gap between adjoining markers. A total of 29 additive QTLs were identified for drought tolerance; among these, 17 (58.6% of total QTLs detected) were contributed by B. carinata (BC 4), suggesting a greater contribution of B. carinata towards improving drought tolerance in the ILs. Out of 17 QTLs, 11 (64.7%) were located on the B genome, indicating more introgression segments on the B genome of B. juncea. Eight QTL hotspots, containing two or more QTLs, governing seed yield contributing traits, water use efficiency, and drought tolerance under moisture deficit stress conditions were identified. Seventeen candidate genes related to biotic and abiotic stresses, viz., SOS2, SOS2 like, NPR1, FAE1-KCS, HOT5, DNAJA1, NIA1, BRI1, RF21, ycf2, WRKY33, PAL, SAMS2, orf147, MAPK3, WRR1 and SUS, were reported in the genomic regions of identified QTLs. CONCLUSIONS: The significance of B. carinata in improving drought tolerance and WUE by introducing genomic segments in Indian mustard is well demonstrated. The findings also provide valuable insights into the genetic basis of drought tolerance in mustard and pave the way for the development of drought-tolerant varieties.

Recent Breakthroughs in Understanding the Cerebellum's Role in Fetal Alcohol Spectrum Disorder: A Systematic Review.

Exposure to alcohol during fetal development can lead to structural and functional abnormalities in the cerebellum, a brain region responsible for motor coordination, balance, and specific cognitive functions. In this systematic review, we comprehensively analyze a vast body of research conducted on vertebrate animals and humans over the past 13 years. We identified studies through PubMed and screened them following PRISMA guidelines. Data extraction and quality analysis were conducted using Covidence systematic review software. A total of 108 studies met our inclusion criteria, with the majority (79 studies) involving vertebrate animal models and 29 studies focusing on human subjects. Animal models included zebrafish, mice, rats, sheep, and non-human primates, investigating the impact of ethanol on cerebellar structure, gene/protein expression, physiology, and cerebellar-dependent behaviors. Additionally, some animal studies explored potential therapeutic interventions against ethanol-induced cerebellar damage. The human studies predominantly adopted cohort designs, exploring the effects of prenatal alcohol exposure on cerebellar structure and function. Certain human studies delved into innovative cerebellar-based diagnostic approaches for fetal alcohol spectrum disorder (FASD). The collective findings from these studies clearly indicate that the cerebellum is involved in various neurophysiological deficits associated with FASD, emphasizing the importance of evaluating both cerebellar structure and function in the diagnostic process for this condition. Moreover, this review sheds light into potential therapeutic strategies that can mitigate prenatal alcohol exposure-induced cerebellar damage.

Gender parity in high impact neurology journals.

Background: Although female representation has been growing among physicians, women continue to be underrepresented in neurology, particularly regarding academic research in authorship and leadership. Analyzing recent trends in high-impact neurology journals highlights the underrepresentation of women and helps explore barriers to female representation in academic neurology. Methods and results: Journal Citation Reports (JCR) for 2021 was used to screen neurology journals for selection. The first 15 journals with the highest impact factors (JIF) were included. 15,404 total articles in neurology were examined for gender distribution of editorial staff and authorship with the highest total citations from January 1st, 2018 to October 31st, 2021. Gender was classified using biographical information from public and personal media sources. Genderize.io was used in cases of ambiguity, predicting gender at probability of ≥95%. Our data demonstrated that these journals only had 13% female editor-in-chiefs and 35% female editorial staff. The data further demonstrated that females accounted for 39% of first authors and 26% for last authors. During the four years examined males continued to account for the vast majority of both first and last authors for publications accepted and journal editorial staff members. Conclusion: Women are significantly under-represented in the field of neurological research in leadership positions as editor-in-chiefs, editorial board members as well as first or senior authors in top neurology medical journals. With continued underrepresentation of women occupying leading publishing roles, parity with men is still a work in progress. Additional work is needed to identify and address barriers to academic advancement for women physicians in academic neurology.

Comparative assessment of surface irregularities of enamel after bonding with different techniques followed by three composite removal methods: An atomic force microscopic study.

Background: To compare and assess the enamel surface roughness by Atomic Force Microscopy between ceramic and metal brackets after adhesive removal with 3 different methods. Methods: 90 extracted premolars were collected and divided equally into 3 groups G, Y, and R. With group G bonded with metallic brackets (using primer and Transbond XT), group Y with ceramic brackets (primer and Transbond XT), and group R with ceramic brackets (silane and Transbond XT). Each group was subdivided into 3 sub-groups (10 premolars each) based on the resin removal method as A: 12- flute tungsten carbide (TC) bur (high speed), B: 12- flute TC bur (low speed), and C: 30 flute TC bur (low speed). Surface roughness values were calculated and compared before bonding and also after adhesive removal by atomic force microscope (AFM). Measured data were analyzed using paired student t-test, ANOVA, and Tukey's tests. Results: Among the groups, group G showed increased surface roughness after debonding compared to group Y and group R, with Rq value showing a statistically significant difference (P<0.047). Whereas, within the subgroups, subgroup A (12-flute TC, high speed) with Rq showed increased surface roughness which was found to be statistically significant (P<0.042). Conclusion: None of the adhesive removal methods was capable to restore the enamel to its earlier morphology; a statistically significant increase in surface roughness parameters was reported with a high-speed 12 flute TC bur for Rq and Rt.

Machine learning for cognitive behavioral analysis: datasets, methods, paradigms, and research directions.

Human behaviour reflects cognitive abilities. Human cognition is fundamentally linked to the different experiences or characteristics of consciousness/emotions, such as joy, grief, anger, etc., which assists in effective communication with others. Detection and differentiation between thoughts, feelings, and behaviours are paramount in learning to control our emotions and respond more effectively in stressful circumstances. The ability to perceive, analyse, process, interpret, remember, and retrieve information while making judgments to respond correctly is referred to as Cognitive Behavior. After making a significant mark in emotion analysis, deception detection is one of the key areas to connect human behaviour, mainly in the forensic domain. Detection of lies, deception, malicious intent, abnormal behaviour, emotions, stress, etc., have significant roles in advanced stages of behavioral science. Artificial Intelligence and Machine learning (AI/ML) has helped a great deal in pattern recognition, data extraction and analysis, and interpretations. The goal of using AI and ML in behavioral sciences is to infer human behaviour, mainly for mental health or forensic investigations. The presented work provides an extensive review of the research on cognitive behaviour analysis. A parametric study is presented based on different physical characteristics, emotional behaviours, data collection sensing mechanisms, unimodal and multimodal datasets, modelling AI/ML methods, challenges, and future research directions.

Discovery of andrographolide hit analog as a potent cyclooxygenase-2 inhibitor through consensus MD-simulation, electrostatic potential energy simulation and ligand efficiency metrics.

Cyclooxygenase-2 (COX-2) is the key enzyme responsible for the conversion of arachidonic acid to prostaglandins that display pro-inflammatory properties and thus, it is a potential target protein to develop anti-inflammatory drugs. In this study, chemical and bio-informatics approaches have been employed to find a novel potent andrographolide (AGP) analog as a COX-2 inhibitor having better pharmacological properties than aspirin and rofecoxib (controls). The full amino acid sequenced human Alpha fold (AF) COX-2 protein (604AA) was selected and validated for its accuracy against the reported COX-2 protein structures (PDB ID: 5F19, 5KIR, 5F1A, 5IKQ and 1V0X) followed by multiple sequence alignment analysis to establish the sequence conservation. The systematic virtual screening of 237 AGP analogs against AF-COX-2 protein yielded 22 lead compounds based on the binding energy score (< - 8.0 kcal/mol). These were further screened out to 7 analogs by molecular docking analysis and investigated further for ADMET prediction, ligand efficiency metrics calculations, quantum mechanical analysis, MD simulation, electrostatic potential energy (EPE) docking simulation, and MM/GBSA. In-depth analysis revealed that AGP analog A3 (3-[2-[(1R,4aR,5R,6R,8aR)-6-hydroxy-5,6,8a-trimethyl-2-methylidene-3,4,4a,5,7,8-hexahydro-1H-naphthalen-1-yl]ethylidene]-4-hydroxyoxolan-2-one) forms the most stable complex with the AF-COX-2 showing the least RMSD value (0.37 ± 0.03 nm), a good number of hydrogen bonds (protein-ligand H-bond = 11, and protein H-bond = 525), minimum EPE score (- 53.81 kcal/mol), and lowest MM-GBSA before and after simulation (- 55.37 and - 56.25 kcal/mol, respectively) value compared to other analogs and controls. Thus, we suggest that the identified A3 AGP analog could be developed as a promising plant-based anti-inflammatory drug by inhibiting COX-2.

Raman Evidence of Multiple Adsorption Sites and Structural Transformation in ZIF-4.

The zeolitic imidazolate framework, ZIF-4, exhibits soft porosity and is known to show pore volume changes with temperatures, pressures, and guest adsorption. However, the mechanism and adsorption behavior of ZIF-4 are not completely understood. In this work, we report an open to narrow pore transition in ZIF-4 around T ∼ 253 K upon lowering the temperature under vacuum (10-6 Torr) conditions, facilitated by C-H···π interactions. In the gaseous environment of N2 and CO2 around the framework, characteristic Raman peaks of adsorbed gases were observed under ambient conditions of 293 K and 1 atm. A guest-induced transition at ∼153 K resulting in the opening of new adsorption sites was inferred from the Raman spectral changes in the C-H stretching modes and low-frequency modes (<200 cm-1). In contrast to a single vibrational mode generally reported for entrapped N2, we show three Raman modes of adsorbed N2 in ZIF-4. The adsorption is facilitated by dispersive and quadrupolar interactions. From our temperature-dependent Raman results and theoretical analysis based on the density functional tight-binding approach, we conclude that the C-Hs are the preferred adsorption sites on ZIF-4 in the following order: C4-H, C5-H > C2-H > center of the Im ring (interacting with C-H centers) > center of the cavity. We also show that with an increasing concentration of N2 adsorbed at low temperatures, the ZIF-4 structure undergoes shear distortion of the window formed by 4-imidazole rings and consequent volumetric expansion. Our results have immediate implications in the field of porous materials and could be vital in identifying subtle structural transformations that may favor or hinder guest adsorption.

Comparing Clinical Outcomes of COVID-19 and Influenza-Induced Acute Respiratory Distress Syndrome: A Propensity-Matched Analysis.

Acute respiratory distress syndrome (ARDS) is one the leading causes of mortality and morbidity in patients with COVID-19 and Influenza, with only small number of studies comparing these two viral illnesses in the setting of ARDS. Given the pathogenic differences in the two viruses, this study shows trends in national hospitalization and outcomes associated with COVID-19- and Influenza-related ARDS. To evaluate and compare the risk factors and rates of the adverse clinical outcomes in patients with COVID-19 associated ARDS (C-ARDS) relative to Influenza-related ARDS (I-ARDS), we utilized the National Inpatient Sample (NIS) database 2020. Our sample includes 106,720 patients hospitalized with either C-ARDS or I-ARDS between January and December 2020, of which 103,845 (97.3%) had C-ARDS and 2875 (2.7%) had I-ARDS. Propensity-matched analysis demonstrated a significantly higher in-hospital mortality (aOR 3.2, 95% CI 2.5-4.2, p < 0.001), longer mean length of stay (18.7 days vs. 14.5 days, p < 0.001), higher likelihood of requiring vasopressors (aOR 1.7, 95% CI 2.5-4.2) and invasive mechanical ventilation (IMV) (aOR 1.6, 95% CI 1.3-2.1) in C-ARDS patients. Our study shows that COVID-19-related ARDS patients had a higher rate of complications, including higher in-hospital mortality and a higher need for vasopressors and invasive mechanical ventilation relative to Influenza-related ARDS; however, it also showed an increased utilization of mechanical circulatory support and non-invasive ventilation in Influenza-related ARDS. It emphasizes the need for early detection and management of COVID-19.

Introgression of Heterotic Genomic Segments from Brassica carinata into Brassica juncea for Enhancing Productivity.

Interspecific hybridization resulted in the creation of B. juncea introgression lines (ILs) generated from B. carinata with increased productivity and adaptability. Forty ILs were crossed with their respective B. juncea recipient parents to generate introgression line hybrids (ILHs) and the common tester (SEJ 8) was used to generate test hybrids (THs). Mid-parent heterosis in ILHs and standard heterosis in THs were calculated for eight yield and yield-related traits. Heterotic genomic regions were dissected using ten ILs with significant mid-parent heterosis in ILHs and standard heterosis in THs for seed yield. A high level of heterosis for seed yield was contributed by 1000 seed weight (13.48%) in D31_ILHs and by total siliquae/plant (14.01%) and siliqua length (10.56%) in PM30_ILHs. The heterotic ILs of DRMRIJ 31 and Pusa Mustard 30 were examined using polymorphic SNPs between the parents, and a total of 254 and 335 introgressed heterotic segments were identified, respectively. This investigation discovered potential genes, viz., PUB10, glutathione S transferase, TT4, SGT, FLA3, AP2/ERF, SANT4, MYB, and UDP-glucosyl transferase 73B3 that were previously reported to regulate yield-related traits. The heterozygosity of the FLA3 gene significantly improved siliqua length and seeds per siliqua in ILHs of Pusa Mustard 30. This research proved that interspecific hybridization is an effective means of increasing the diversity of cultivated species by introducing new genetic variants and improving the level of heterosis.

Comparative transcriptomic and metabolite profiling reveals genotype-specific responses to Fe starvation in chickpea.

Iron deficiency is a major nutritional stress that severely impacts crop productivity worldwide. However, molecular intricacies and subsequent physiological and metabolic changes in response to Fe starvation, especially in leguminous crops like chickpea, remain elusive. In the present study, we investigated physiological, transcriptional, and metabolic reprogramming in two chickpea genotypes (H6013 and L4958) with contrasting seed iron concentrations upon Fe deficiency. Our findings revealed that iron starvation affected growth and physiological parameters of both chickpea genotypes. Comparative transcriptome analysis led to the identification of differentially expressed genes between the genotypes related to strategy I uptake, metal ions transporters, reactive oxygen species-associated genes, transcription factors, and protein kinases that could mitigate Fe deficiency. Our gene correlation network discovered several putative candidate genes like CIPK25, CKX3, WRKY50, NAC29, MYB4, and PAP18, which could facilitate the investigation of the molecular rationale underlying Fe tolerance in chickpea. Furthermore, the metabolite analysis also illustrated the differential accumulation of organic acids, amino acids and other metabolites associated with Fe mobilization in chickpea genotypes. Overall, our study demonstrated the comparative transcriptional dynamics upon Fe starvation. The outcomes of the current endeavor will enable the development of Fe deficiency tolerant chickpea cultivars.

Identification of potential andrographolide-based drug candidate against Keap1-Nrf2 pathway through rigorous cheminformatics screening.

The Keap1-Nrf2 [Kelch-like ECH-associated protein-1-Nuclear factor erythroid-2-related factor-2] regulatory pathway plays a vital role in the protection of cells by regulating transcription of antioxidant and detoxification genes. Andrographolide (AGP) regulates the Keap1-Nrf2 pathway by inhibiting the Keap1 protein. To identify a more potent AGP analog as a therapeutic agent against Keap1 protein, in this work, cheminformatics analysis of 237 AGP analogs was carried out. Amongst these, five AGP analogs were screened through virtual screening followed by their molecular docking analysis against Keap1 protein, which revealed greater binding affinities (binding energy = - 4.15 to - 5.59 kcal/mol) for the shortlisted AGP analogs compared to AGP (binding energy = - 4.02 kcal/mol). Pharmacophore mapping indicated 14 spatial features, including 3 hydrogen bond acceptors and 11 hydrophobic, while ADME analysis established the potential of all five analogs as orally-active drug-like candidates based on Lipinski's rule of five. We also examined the chemical reactivity of AGP and the shortlisted AGP analogs using DFT analysis, which revealed that except for one analog (AGP_A2) all are more chemically reactive than AGP. Further, molecular dynamics simulation analysis and MM/GBSA evidenced that AGP_A1 (PubchemID-123361152), AGP_A3 (PubchemID-58209855) and AGP_A4 (PubchemID-101362374) are the best drug like candidates compared to AGP and have greater potential to activate the Keap1-Nrf2 pathway by inhibiting the Keap1 protein.

Impact of maternal body mass index on the accuracy of third trimester sonographic estimation of fetal weight.

OBJECTIVES: To Determine whether maternal body mass index (BMI) can affect the accuracy of sonographic estimation of fetal weight (EFW) in the third trimester when compared to neonatal birthweight (BW). METHODS: Secondary analysis from our original prospective cohort of pregnant women beyond 34 weeks, distributed in 4 groups according to their BMI: normal, overweight, obese and morbid obese. Fetal biometry and fluid measurements were obtained by two experienced sonographers, blinded for patient's clinical information and to each other's measurements. Average EFW and neonatal BW were converted into gestational-specific Z-scores. Interobserver correlation coefficient (ICC) and Cronbach's reliability coefficient (CRC) were calculated. Bland-Altman (BA) plots were constructed to assess the level of accuracy. RESULTS: 100 women were enrolled (800 measurements obtained by 17 sonographers): 17 had normal BMI (17%), 27 were overweight (27%), 29 were obese (29%) and 27 were morbidly obese (27%). There was no statistical difference for GA at delivery (p = 0.74), EFW (p = 0.05) or BW (p = 0.09) between groups (Table 1). Mean Z-score for EFW was - 0.17 (SD 0.81) and for neonatal BW was - 0.25 (SD 0.74). ICC was 0.69 (95% CI 0.57, 0.78) and CRC was 0.82. Mean Z-score difference was small (Table 2). When stratifying according to BMI categories, the ICC ranged from 0.49 to 0.76. Reliability indices ranged from 0.66 to 0.86. The Z-scores' differences were overall small with no statistical difference (Table 3). BA showed evenly distributed interobserver differences (Fig. 1). CONCLUSIONS: When performed by trained sonographers, fetal weight estimation in the third trimester is accurate when compared to neonatal birthweight at increasing BMI categories.

Selection of suitable internal control gene for assaying gene expression in rice through qRT-PCR during sheath blight infection.

qRT-PCR is a globally accepted technique for assaying gene expression in relative terms which compares the difference between critical threshold (CT) values of a gene calculated form two independently isolated RNA samples. Independent RNA isolations, however, include error due to batch effect which must be normalized for error-free calculation of relative gene expression. Hence, CT values of internal control (IC) genes are used for normalization during the calculation of expression fold-change in gene expression analysis. The expression of ICs genes expected to be stable in all the experimental conditions. However, it is almost impossible to find such a gene which do not depict expression fluctuation in response to the changes in experimental conditions. Hence, it is necessary to identify suitable IC gene(s) for any given experimental condition before conducting any particular gene expression study. Here, we examined the suitability of eight candidate IC genes, namely glyceraldehyde 3-phosphate dehydrogenase (GAPDH), eukaryotic elongation factor-1 (eEF-1α), 25 S rRNA (25 S), 18 S rRNA (18 S), ubiquitin C E2 ligase (UBC), Actin (Act), ubiquitin 5 (UBQ5) and ubiquitin 10 (UBQ10), for assaying gene expression in rice during sheath blight infection. Our analysis suggest that GAPDH might be the IC of choice when expression studies include contrasting genotypes differing in their tolerance to sheath blight pathogen as well as progressive infection time. While if expression analysis have to be performed only in one genotype but under progressive sheath blight infection, UBQ5 might be chosen as IC because of its high expression stability under the proposed experimental setup.

Andrographolide-based potential anti-inflammatory transcription inhibitors against nuclear factor NF-kappa-B p50 subunit (NF-κB p50): an integrated molecular and quantum mechanical approach.

The unregulated activation of nuclear factor-κB (NF-κB) is a critical event in the progression of various inflammatory diseases such as ulcerative colitis, asthma, rheumatoid arthritis, bacterial induced gastritis, etc. Hence, blocking the transcriptional activity of NF-κB is a promising strategy towards the development of an anti-inflammatory agent. In this study, an integrated molecular and quantum mechanical approach was carried out to find a new potent andrographolide (AGP)-based analog that can inhibit DNA binding to NF-κB p50 and manifest anti-inflammatory activity. Our approach includes multiple sequence alignment, virtual screening, molecular docking (protein-ligand and protein-DNA), in silico site-directed mutagenesis, ADMET prediction, DFT (HOMO, LUMO, HLG, and EPM energy) analysis, MD simulation, and MM/GBSA rescoring. The virtual screening analysis of 237 AGP analogs yielded the five lead compounds based on the binding affinity. Further, molecular interactive docking and ADMET prediction of hit analogs revealed that Ana2 ((3Z,4S)-3-[2-[(4aR,6aS,7R,10aS,10bR)-3,3,6a,10b-tetramethyl-8-methylidene-1,4a,5,6,7,9,10,10a-octahydronaphtho[2,1-d][1,3]dioxin-7-yl]ethylidene]-4-hydroxyoxolan-2-one) is the most potent moiety as it displays the strongest binding affinity and better molecular/pharmacokinetic features. Moreover, DFT, MD simulation, and MM/GBSA studies corroborated the docking results and demonstrated better chemical and dynamic stability with the least binding free energy (- 29.99 kcal/mol) for the Ana2. Site-directed mutagenesis investigation (Cys62Ala) establishes the importance of the Cys62 amino acid residue towards the binding interaction and stability of Ana2 with NF-κB p50. Overall, the identified NF-κB p50 inhibitor opens up a new research horizon towards the development of plant-based anti-inflammatory drugs to combat progressive inflammatory diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03431-9.

Bioconjugate-loaded solid lipid nanoparticles for enhanced anticancer drug delivery to brain cancer cells: An in vitro evaluation.

Background & objectives: The treatment of brain cancer is still challenging for an oncologist due to the presence of the blood-brain barrier (BBB) which inhibits the entry of more than 98 per cent of drugs used during the treatment of brain disease. The cytotoxic drugs used in chemotherapy for brain cancer treatment also affect the normal cells due to lack of targeting. Therefore, the objective of the study was to develop tween 80-coated solid lipid nanoparticles (SLNs) loaded with folic acid-doxorubicin (FAD) conjugate for site-specific drug delivery to brain cancer cells. Methods: The FAD conjugate was synthesized by the conjugation of folic acid with doxorubicin and characterized by Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy. SLNs loaded with FAD were prepared by the solvent injection method. The SLNs were characterized by the particle size, zeta potential, surface morphology, entrapment efficiency, etc. Results: The average particle size of FAD conjugate-loaded SLNs (SLN-C) was found to be 220.4±2.2 nm, with 36.2±0.6 per cent entrapment efficiency. The cytotoxicity and cellular uptake were determined on U87 MG cell lines. Half maximal inhibitory concentration value of the SLN-C was found to be 2.5 µg/ml, which confirmed the high antitumour activity against brain cancer cells. Interpretation & conclusions: The cell line studies confirmed the cytotoxicity and internalization of SLN-C in U87 MG brain cancer cells. The results confirmed that tween 80-coated SLNs have the potential to deliver the doxorubicin selectively in the brain cancer cells.

Escalate protein plates from legumes for sustainable human nutrition.

Protein is one of the most important, foremost, and versatile nutrients in food. The quantity and quality of protein are determinants of its nutritional values. Therefore, adequate consumption of high-quality protein is essential for optimal growth, development, and health of humans. Based on short-term nitrogen balance studies, the Recommended Dietary Allowance of protein for the healthy adult with minimal physical activity is 0.8 g protein/kg body weight (BW) per day. Proteins are present in good quantities in not only animals but also in plants, especially in legumes. With the growing demand for protein, interest in plant proteins is also rising due to their comparative low cost as well as the increase in consumers' demand originating from health and environmental concerns. Legumes are nutrient-dense foods, comprising components identified as "antinutritional factors" that can reduce the bioavailability of macro and micronutrients. Other than nutritive value, the physiochemical and behavioral properties of proteins during processing plays a significant role in determining the end quality of food. The term "complete protein" refers to when all nine essential amino acids are present in the correct proportion in our bodies. To have a balanced diet, the right percentage of protein is required for our body. The consumption of these high protein-containing foods will lead to protein sustainability and eradicate malnutrition. Here, we shed light on major opportunities to strengthen the contribution of diversity in legume crops products to sustainable diets. This review will boost awareness and knowledge on underutilized proteinous foods into national nutritional security programs.