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Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities.

Quantitative PCR (qPCR) is a technique commonly employed in laboratories and core facilities. In our previous study, we had shown the possibility to automate steps in a panel-specific gene expression workflow by pairing Mosquito HV with BioMark HD. Here we aimed to automate the full workflow and explore miniaturization capabilities. Each step of the gene expression workflow was scripted on Mosquito HV genomics software. We performed three different automated runs: i. Replicates of a Reference RNA sample (obtained by pooling RNA isolated from 10 healthy individuals) were run on an immunology gene expression panel. We tested the full reaction (FR) and three miniaturization conditions, namely: 1.5x, 2.5x and 5x; the data obtained from the automated FR replicates was compared to the data obtained from the manual processing; ii. Biological RNA samples (isolated from n=45 individuals) were run as FR and 1.5x on the immunology gene expression panel; iii. Biological RNA samples (isolated from n=45 individuals) were run as FR and 1.5x on a pregnancy gene expression panel. The expression of each gene was calculated using the 2 (-delta delta Ct) method. Successful amplification was observed for the reference samples when using FR and 1.5x conditions. The 2.5x condition exhibited suboptimal amplification with a lower success rate while the 5x condition retrieved no amplification. The 2.5x and 5x miniaturization conditions were excluded from further runs. A strong significant positive correlation was observed between the manual and automated workflows for the reference RNA sample, underscoring the robustness of the gene expression assay. The automation of the immunology and pregnancy gene expression panels on the 45 individual samples retrieved a success rate >70% for both the FR and the 1.5x miniaturization conditions. A significant positive correlation was also observed between the FR and 1.5x miniaturization conditions for both panels. Our results show that the adoption and the 1.5x miniaturization capabilities of Mosquito HV system for automating the gene expression workflow did not interfere with data quality and reproducibility., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests or relevant relationship related to the content of this paper., (Copyright © 2024. Published by Elsevier Inc.)

This emerging infectious disease poses one of the most severe threats to public health in these locations, but there are not many reliable therapies yet. In this work, we developed the Ebola virus dynamics and control factors epidemic model with a piecewise hybrid fractional Operator in time scale measure insight of Mittag-Leffler kernel. Patterns and structures that repeat at various scales are the focus of fractal analysis, which has applications in complex systems such as biological ones. Both qualitatively and statistically, a proposed model with the Lipschitz criteria and linear growth is examined, considering positive solutions, boundedness, and uniqueness at equilibrium points with Leray-Schauder results under time scale ideas. The regulation for linear responses approach will be used by Chaos Control to stabilize the system after its equilibrium points. A fractional-order framework with a controlled design will be considered, where solutions are bounded in the feasible domain of relations of different compartments. Ulam-Hyers stability results in the solution are treated when function (constant or rising) for the component of qualitative inquiry in generalized form. The dynamical behaviors of the suggested model are discussed with the Newton polynomial approach used to implement on model in the sense of classical piecewise and Mittag-Leffler kernel at different fractional order values. The model shows that solutions are stable and confined within a feasible range, ensuring reliability. Through detailed simulations, it effectively captures how different interventions and infection rates influence Ebola spread. This fractional-order model enhances understanding of Ebola transmission, providing a strong basis for predicting outbreaks and planning effective control measures, with practical applications for analyzing real-world data., (© 2024. The Author(s).)

Nitroaromatics impose severe health problems and threats to the environment. Therefore, the detection of such hazardous substances is essential to save the whole ecosystem. Herein, the C 5 N 2 sheet is used as an electrochemical sensor for the detection of 1,3-dinitrobenzene (1,3-DNB), trinitrotoluene (TNT), and picric acid (PA) using the PBE0/def2SVP level of theory as implemented in Gaussian 16. The highest interaction energy was observed for the picric acid@C 5 N 2 complex. The trend in interaction energies for the studied system is PA@C 5 N 2 >TNT@C 5 N 2 >1,3-DNB@C 5 N 2 . The studied systems were further analysed by qualitative and quantitative analyses to determine the interactions between the nitroaromatic analytes and the C 5 N 2 sheet. Electronic properties of all analytes@C 5 N 2 complexes have been examined by NBO, EDD, FMO and DOS analysis. QTAIM analysis depicts the stronger non-covalent interactions for the PA@C 5 N 2, which shows consistency with interaction energy and NCI analysis. Furthermore, NBO and FMO analyses show that the C 5 N 2 substrate exhibits high sensitivity and selectivity towards the picric acid compared to TNT and 1,3-DNB nitroaromatics. EDD and DOS analyses are in agreement with NBO and FMO analyses. Furthermore, the recovery time of the studied system has been computed to determine the efficiency of C 5 N 2 material as an electrochemical sensor. Overall, the results show that carbon nitride can be a good sensor for the detection of nitroaromatics., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In the present study, we investigated the interaction of alpha-2-macroglobulin (α2M) with naringenin using multi-spectroscopic, molecular docking, and molecular simulation approaches to identify the functional changes and structural variations in the α2M structure. Our study suggests that naringenin compromised α2M anti-proteinase activity. The results of absorption spectroscopy and fluorescence measurement showed that naringenin-α2M formed a complex with a binding constant of (k b )∼10 4 , indicative of moderate binding. The value of ΔG° in the binding indicates the process to be spontaneous and the major force responsible to be hydrophobic interaction. The findings of FRET reveal the binding distance between naringenin and the amino acids of α2M was 2.82 nm. The secondary structural analysis of α2M with naringenin using multi-spectroscopic methods like synchronous fluorescence, red-edge excitation shift (REES), FTIR, and CD spectra further confirmed the significant conformational alterations in the protein. Molecular docking approach reveals the interactions between naringenin and α2M to be hydrogen bonds, van der Waals forces, and pi interactions, which considerably favour and stabilise the binding. Molecular dynamics modelling simulations also supported the steady binding with the least RMSD deviations. Our study suggests that naringenin interacts with α2M to alter its confirmation and compromise its activity.Communicated by Ramaswamy H. Sarma.

Enterohemorrhagic Escherichia coli (EHEC) outbreaks have been frequently linked to the consumption of produce. Furthermore, produce grown on organic farms possess a higher risk, as the farmers avoid antibiotics and chemicals. This study sets out to evaluate the effectiveness of advanced postharvest disinfection processes using berry pomace extracts (BPEs) in reducing EHEC load in two common leafy greens, spinach and lettuce. Spinach and lettuce were inoculated with ~5 log CFU/leaf EHEC EDL-933 and then treated with three different concentrations of BPE (1, 1.5, and 2 gallic acid equivalent, GAE mg/mL) for increasing periods of time. After the wash, the bacteria were quantified. Changes in the relative expression of virulence genes and the genes involved in cell division and replication and response against stress/antibiotics were studied. We observed a significant reduction in EHEC EDL933, ranging from 0.5 to 1.6 log CFU/spinach leaf ( p < 0.05) washed with BPE water. A similar trend of reduction, ranging from 0.3 to 1.3 log CFU/mL, was observed in pre-inoculated lettuce washed with BPE water. We also quantified the remaining bacterial population in the residual treatment solutions and found the survived bacterial cells (~3 log CFU/mL) were low despite repeated washing with the same solution. In addition, we evaluated the phenolic concentration in leftover BPE, which did not change significantly, even after multiple uses. Alterations in gene expression levels were observed, with downregulation ranging from 1 to 3 log folds in the genes responsible for the adhesion and virulence of EHEC EDL933 and significant upregulation of genes responsible for survival against stress. All other genes were upregulated, ranging from 2 to 7 log folds, with a dose-dependent decrease in expression. This finding shows the potential of BPE to be used for sanitation of fresh produce as a natural and sustainable approach.

Senescent cells are characterized by multiple features such as increased expression of senescence-associated β-galactosidase activity (SA β-gal) and cell cycle inhibitors such as p21 or p16. They accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as Doxorubicin (Doxo) cause buildup of senescent cells, leading to the inhibition of tissue regeneration. Senescent cells influence the neighboring cells via numerous secreted factors which form the senescence-associated secreted phenotype (SASP). Lipids are emerging as a key component of SASP that can control tissue homeostasis. Arachidonic acid-derived lipids have been shown to accumulate within senescent cells, specifically 15d-PGJ 2 , which is an electrophilic lipid produced by the non-enzymatic dehydration of the prostaglandin PGD 2 . This study shows that 15d-PGJ 2 is also released by Doxo-induced senescent cells as an SASP factor. Treatment of skeletal muscle myoblasts with the conditioned medium from these senescent cells inhibits myoblast fusion during differentiation. Inhibition of L-PTGDS, the enzyme that synthesizes PGD 2 , diminishes the release of 15d-PGJ 2 by senescent cells and restores muscle differentiation. We further show that this lipid post-translationally modifies Cys184 of HRas in C2C12 mouse skeletal myoblasts, causing a reduction in the localization of HRas to the Golgi, increased HRas binding to Ras Binding Domain (RBD) of RAF Kinase (RAF-RBD), and activation of cellular Mitogen Activated Protein (MAP) kinase-Extracellular Signal Regulated Kinase (Erk) signaling (but not the Akt signaling). Mutating C184 of HRas prevents the ability of 15d-PGJ 2 to inhibit the differentiation of muscle cells and control the activity of HRas. This work shows that 15d-PGJ 2 released from senescent cells could be targeted to restore muscle homeostasis after chemotherapy., Competing Interests: SP, AB, AV, SS, MJ, RM, HL, MH, AR No competing interests declared, (© 2024, Pundlik et al.)

Background: This study examined inpatient mortality factors in geriatric patients with acute myeloid leukemia (AML) using data from the 2016 to 2020 National Inpatient Sample., Methods: Identifying patients through ICD-10 codes, a total of 127,985 individuals with AML were classified into age categories as follows: 50.58% were 65 to 74 years, 37.74% were 75 to 84 years, and 11.68% were 85 years or older. Statistical analysis, conducted with STATA, involved Fisher's exact and Student's t tests for variable comparisons. Mortality predictors were identified through multivariate logistic regression., Results: Various hospital and patient-level factors, including an increase in age, race, a higher Charlson Comorbidity Index score, insurance status, and specific comorbidities such as atrial fibrillation and protein-calorie malnutrition, independently elevated the risk of inpatient mortality. Asthma, hyperlipidemia, and inpatient chemotherapy were linked to lower mortality. Although there was no statistically significant mortality rate change from 2016 to 2020, a decline in chemotherapy use in the eldest age group was noted., Conclusion: This study highlights the complexity of factors influencing inpatient mortality among geriatric patients with AML, emphasizing the need for personalized clinical approaches in this vulnerable population., Competing Interests: The authors report no funding or conflicts of interests., (Copyright © 2024 Baylor University Medical Center.)

Microgrids (MGs) and energy communities have been widely implemented, leading to the participation of multiple stakeholders in distribution networks. Insufficient information infrastructure, particularly in rural distribution networks, is leading to a growing number of operational blind areas in distribution networks. An optimization challenge is addressed in multi-feeder microgrid systems to handle load sharing and voltage management by implementing a backward neural network (BNN) as a robust control approach. The control technique consists of a neural network that optimizes the control strategy to calculate the operating directions for each distributed generating point. Neural networks improve control during communication connectivity issues to ensure the computation of operational directions. Traditional control of DC microgrids is susceptible to communication link delays. The proposed BNN technique can be expanded to encompass the entire multi-feeder network for precise load distribution and voltage management. The BNN results are achieved through mathematical analysis of different load conditions and uncertain line characteristics in a radial network of a multi-feeder microgrid, demonstrating the effectiveness of the proposed approach. The proposed BNN technique is more effective than conventional control in accurately distributing the load and regulating the feeder voltage, especially during communication failure., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Adaptation to hypothermia is important for skeletal muscle cells under physiological stress and is used for therapeutic hypothermia (mild hypothermia at 32  °C). We show that hypothermic preconditioning at 32  °C for 72 hours improves the differentiation of skeletal muscle myoblasts using both C2C12 and primary myoblasts isolated from 3 month and 18-month-old mice. We analyzed the cold-shock proteome of myoblasts exposed to hypothermia (32  °C for 6 and 48 h) and identified significant changes in pathways related to RNA processing and central carbon, fatty acid, and redox metabolism. The analysis revealed that levels of the cold-shock protein RBM3, an RNA-binding protein, increases with both acute and chronic exposure to hypothermic stress, and is necessary for the enhanced differentiation and maintenance of mitochondrial metabolism. We also show that overexpression of RBM3 at 37  °C is sufficient to promote mitochondrial metabolism, cellular proliferation, and differentiation of C2C12 and primary myoblasts. Proteomic analysis of C2C12 myoblasts overexpressing RBM3 show significant enrichment of pathways involved in fatty acid metabolism, RNA metabolism and the electron transport chain. Overall, we show that the cold-shock protein RBM3 is a critical factor that can be used for controlling the metabolic network of myoblasts., (© 2024. The Author(s).)

Objective: To analyze the efficacy of a modified approach to thyroplasty type one using prolene mesh implant., Study Design: Interventional study., Place and Duration of Study: Combined Military Hospital Kharian, Pakistan, in Ent department, from July 2020 to Jan 2021., Methodology: Medialization thyroplasty with prolene mesh was performed on the patients satisfying the inclusion criteria. They were analyzed objectively as well as subjectively in terms of Mean Maximum phonation time, maximum word count, and visual analog score about the quality of voice. Data analysis was done with SPSS version 20. Pre-operative and post-operative records were compared using paired sample t-test., Results: A total of 39 patients underwent vocal cord medialization with prolene mesh implant. The Mean age for medialization was 41.09 + 13.37. 23 patients were females and 15 were males. 26 patients had unilateral and 13 patients had bilateral vocal dysfunction. 18 of them had vocal dysfunction due to thyroidectomy, eight had idiopathic causes and 13 had miscellaneous. The improvement in mean visual analog score was 2.87 postoperatively. Median maximum phonation time increased about five seconds postoperatively, seven seconds in males, and 4.5 seconds for females. The maximum word count increased from 11.33 preoperatively to 18.28 postoperatively. There were no major complications observed in our study., Conclusion: These results were comparable to many other studies for vocal cord medialization with different implant materials. But prolene mesh implant offers an easily available yet cost-effective alternative with similar benefits., Level of Evidence: III (Treatment benefits: Non-randomized controlled cohort/follow-up study)., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

It was an observational, cross-sectional study conducted at Ziauddin University, Karachi, from 10th March to 31st August 2021, to investigate the frequency of elevated resting heart rate in healthy young adults with normal BMI. A total of 420 participants were recruited for the study with age ranging from 18-30 years. Subsequently, candidates with normal BMI ranging between 18-24 kg/m2 were selected for the evaluation of elevated resting heart rate (RHR). The participants underwent an assessment of their heart rate at rest with a pulse oximeter whereas, stadiometer was used for height and weight measurements. The frequency of the elevated RHR (HR= 90-100 bpm) was found to be 49.6% with a mean RHR of 90.85 ± 12.45 bpm. The correlation between RHR and body weight was found to be weak (r = 0.141, p = 0.027) showing little or no association. Whereas, RHR and height depicted a moderate negative correlation (r = 0.160, p = 0.012). This study demonstrated high frequency of RHR in a young population. Efforts are needed to control the increased RHR. Key Words: Resting heart rate (RHR), Young adults, Cardiovascular disease (CVD), BMI, Tachycardia.

Novel spiropyrazoline-indolinones ( 4a-t ) have been synthesized successfully in neutral deep eutectic solvents by reacting 5-Cl/Br-isatin ( 1a-b ) with aromatic ketones ( 2a-b ) and a variety of substituted hydrazines ( 3a-e ) in good to excellent yields. This eco-friendly straightforward synthetic protocol discloses good functional group compatibility. The conventional synthetic approach was compared with the greener route of microwave-assisted synthesis of spiropyrazolines using ethanol. This approach utilized mild reaction conditions which furnished high yields in short reaction time employing one pot two-step multicomponent. All new compounds were structurally confirmed by detailed spectroscopic analysis and density functional theory calculations. This method provides efficient access to spiropyrazole derivatives using biodegradable and green solvent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The versatile coordinating nature of N,S bidentate ligands is of great importance in medicinal chemistry imparting stability and enhancing biological properties of the metal complexes. Phenylthiocarbamide-based N,S donor Schiff bases converted into Ru II /Os II (cymene) complexes and characterized by spectroscopic techniques and elemental analysis. The hydrolytic stability of metal complexes to undergo metal-halide ligand exchange reaction was confirmed both by the DFT and NMR experimentation. The ONIOM (QM/MM) study confirmed the histone protein targeting nature of aqua/hydroxido complex 2 aH with an excellent binding energy of -103.19 kcal/mol. The antiproliferative activity against a panel of cancer cells A549, MCF-7, PC-3, and HepG2 revealed that ruthenium complexes 1 a-3 a were more cytotoxic than osmium complexes and their respective ligands 1-3 as well. Among these ruthenium cymene complex bearing sulfonamide moiety 2 a proved a strong cytotoxic agent and showed excellent correlation of cellular accumulation, lipophilicity, and drug-likeness to the anticancer activity. Moreover, the favorable physiochemical properties such as bioavailability and gastrointestinal absorption of ligand 2 also supported the development of Ru complex 2 a as an orally active anticancer metallodrug., (© 2023 Wiley-VCH GmbH.)

Arsenic contamination is highly prevalent in food chain, soil and groundwater. Continuous exposure to elevated levels of this environmental toxin is a global concern. Studies have reported enriched accumulation of arsenic in the eyes compared to other body organs leading to various eye diseases. Here, the impact of arsenic exposure on the enzymatic eye ζ-crystallin has been investigated. Arsenic inhibited the activity of the enzyme with an IC 50 value of 35 µM. It decreased the free thiol group content of ζ-crystallin due to protein oxidation. The binding of arsenic with ζ-crystallin was explored using biophysical and computational tools. The enzyme undergoes some conformational changes upon arsenic binding. The binding constant ( K b ) was determined to be 1.2 × 10 2 M -1 . Thermodynamic parameters were determined by isothermal titration calorimetry (ITC) and the binding energy (Δ G ) was calculated to be -3.52 kcal/mol. Molecular docking studies helped in visualizing the amino acid residues (especially Cys165) of the enzyme involved in binding with arsenic. Continuous arsenic exposure is expected to increase the eye crystallin-related abnormalities, elevating the risk of cataractogenesis. Therefore, proper measures need to be taken by authorities to control the contamination of arsenic in the environment and groundwater.Communicated by Ramaswamy H. Sarma.

Advanced glycation end products (AGEs) are formed through non-enzymatic glycation, that have been linked to various diseases, including polycystic ovarian syndrome (PCOS) playing a critical role leading to secondary comorbidities such as diabetes-related problems, cardiovascular complications, infertility, etc. As a result, there has been a lot of research into AGE-inhibiting phytochemicals for the remediation and obstruct progression of glycation-related illnesses. The current study is based on in-vitro protein model, in which human serum albumin have been used to investigate the cumulative effect of chlorogenic acid (CGA) and cholecalciferol (vitamin D) on glycation and evaluate their inhibitory impact on AGEs production in the presence of methylglyoxal. Through the application of several biochemical and biophysical techniques, we were able to examine the synergistic impact of both the compounds on albumin structure and its biochemical properties during different stages of glycation. According to Nitro-blue tetrazolium assay results indicate that CGA and vitamin D inhibited fructosamine (early glycation product) production. Moreover, free thiol and lysine residues were significantly increased whereas protein carbonyl levels were significantly decreased. Additive effect of CGA and vitamin D were associated with reduced AGEs fluorescence and increased tryptophan and tyrosine fluorescence. Amadori-albumin after treatment showed some evidence of regaining its alpha-helicity as measured by far-UV CD spectrum. Furthermore, secondary structural alterations were confirmed by Fourier transform infrared spectroscopy (FTIR). ANS (1-anilinonaphthalene-8-sulfonic acid) fluorescence spectra also displayed less revelation of hydrophobic patches. Bilirubin binding capacity was also restored which showed functional recovery of HSA. The electrophoretic mobility was also restored which is portrayed by SDS-PAGE. Additionally, to predict the anti-aggregation potential of CGA and vitamin D, congo red assay and ThT fluorescence was performed which reveal low aggregate formation after treatment. These results corroborated with scanning electron microscopy and confocal microscopy. Docking and simulation results also reveal spontaneous binding of CGA and vitamin D on subdomain IIA of HSA favoring their binding thermodynamically. All the findings suggest that chlorogenic acid and cholecalciferol given in combination might help in prevention of PCOS progression and its related complications., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bioallethrin is an insecticide that is widely used in households resulting in human exposure. Bioallethrin is cytotoxic to human erythrocytes. Here we have studied the interaction of bioallethrin with human hemoglobin (Hb) using in silico and biophysical approaches. Incubation of Hb (5 μM) with bioallethrin (1-50 µM) led to increase in absorbance at 280 nm while the Soret band at 406 nm was slightly reduced. The intrinsic fluorescence of Hb was enhanced with the appearance of a new peak around 305 nm. Synchronous fluorescence showed that the binding of bioallethrin to Hb mainly affects the tyrosine microenvironment. The structural changes in Hb were confirmed with a significant shift in CD spectra and about 25% loss of α-helix. Molecular docking and visualisation through Discovery studio confirmed the formation of Hb-bioallethrin complex with a binding energy of -7.3 kcal/mol. Molecular simulation showed the stability and energy dynamics of the binding reaction between bioallethrin and Hb. The structural changes induced by bioallethrin led to inhibition of the esterase activity of Hb. In conclusion, this study shows that bioallethrin forms a stable complex with human Hb which may lead to loss of Hb function in the body.Communicated by Ramaswamy H. Sarma.

Fructosylation of proteins results in the formation of advanced glycation end-products (AGEs). A diet rich in fructose along with hyperglycemia can cause fructose mediated glycation (fructosylation) of proteins, which results in AGEs formation. Insulin is a peptide hormone that is glycated when exposed to carbohydrates such as glucose. In this study, we have analysed the interaction of insulin with fructose and biophysically characterized fructose modified insulin. In silico studies performed through molecular docking and molecular dynamics simulation revealed that fructose binds to insulin with strong affinity resulting in the formation of insulin-fructose complex. Fructosylation of insulin caused hyperchromicity, loss of intrinsic fluorescence, gain in AGEs specific fluorescence and elevated the carbonyl and fructosamine content. Enhanced thioflavin T fluorescence suggested the presence of fibrillar structures at higher concentrations of fructose. Electron microscopy revealed the formation of characteristic amorphous and amyloid like aggregates at lower and higher concentrations of fructose, respectively. These findings show that fructosylation of insulin causes AGEs production, aggregation and alters its gross structural integrity. These changes may reduce the biological activity of insulin that can aggravate conditions like type II diabetes mellitus.Communicated by Ramaswamy H. Sarma.

Alzheimer's disease (AD) is a progressive neurological illness that is distinguished clinically by cognitive and memory decline and adversely affects the people of old age. The treatments for this disease gained much attention and have prompted increased interest among researchers in this field. As a springboard to explore new anti-Alzheimer's chemical prototypes, the present study was carried out for the synthesis of benzoxazole-oxadiazole analogues as effective Alzheimer's inhibitors. In this research work, we have focused our efforts to synthesize a series of benzoxazole-oxadiazole ( 1 - 19 ) and evaluating their anti-Alzheimer properties. In addition, the precise structures of synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1 H-NMR, 13 C-NMR and HREI-MS. To find the anti-Alzheimer potentials of the synthesized compounds ( 1 - 19 ), in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), inhibitory activities were performed using Donepezil as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were due to different substitution patterns of substituent(s) at the variable position of both acetophenone aryl and oxadiazole aryl rings. The results of the anti-Alzheimer assay were very encouraging and showed moderate to good inhibitory potentials with IC 50 values ranging from 5.80 ± 2.18 to 40.80 ± 5.90 µM (against AChE) and 7.20 ± 2.30 to 42.60 ± 6.10 µM (against BuChE) as compared to standard Donepezil drug (IC 50 = 33.65 ± 3.50 µM (for AChE) and 35.80 ± 4.60 µM (for BuChE), respectively. Specifically, analogues 2 , 15 and 16 were identified to be significantly active, even found to be more potent than standard inhibitors with IC 50 values of 6.40 ± 1.10, 5.80 ± 2.18 and 6.90 ± 1.20 (against AChE) and 7.50 ± 1.20, 7.20 ± 2.30 and 7.60 ± 2.10 (against BuChE). The results obtained were compared to standard drugs. These findings reveal that benzoxazole-oxadiazole analogues act as AChE and BuChE inhibitors to develop novel therapeutics for treating Alzheimer's disease and can act as lead molecules in drug discovery as potential anti-Alzheimer agents.

Multi-target directed ligands (MTDLs) have recently attracted significant interest due to their exceptional effectiveness against multi-factorial Alzheimer's disease. The present work described the development of pyrazine-based MTDLs using multicomponent Petasis reaction for the dual inhibition of tau-aggregation and human acetylcholinesterase (hAChE). The molecular structure of synthesized ligands was validated by 1 H & 13 C NMR and mass spectrometry. The screened compounds were shown to have a strong inhibitory effect at 10 μM concentration against tau-oligomerization and hAChE, but only moderate inhibitory activity against Aβ 42 . Among all the compounds, the half-maximal inhibitory concentration (IC 50 ) for 21 and 24 against hAChE were 0.71 μM and 1.09 μM, respectively, while they displayed half-maximal effective concentrations (EC 50 ) values of 2.21 μM and 2.71 μM for cellular tau-oligomerization, respectively. Additionally, an MTT experiment using tau-expressing SH-SY5Y neuroblastoma cells revealed that 21 was more neuroprotective than the FDA-approved medication donepezil. Furthermore, an MD simulation study was performed to investigate the dynamics and stability of AChE-21 and AChE-24 complexes in an aqueous environment. The MM-PBSA calculations were performed to evaluate the binding of 21 and 24 with AChE, and the relative binding energy was calculated as -870.578 and -875.697 kJ mol -1 , respectively. As a result, the study offered insight into the design of new MTDLs and highlighted 21 as a potential roadblock to the development of anti-AD medications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Glycation of human low-density protein (LDL) has an essential contribution to cardiovascular diseases. Natural compounds like rutin have been extensively studied in preventing glycation-induced oxidative stress. This study examined rutin's anti-glycation potential with glycated LDL utilizing spectroscopic and in silico methods. Glycated LDL treated with rutin, showed around 80 % inhibition in advanced glycation end-product production. Carbonyl content and lipid peroxidation like assays were used to establish the development of oxidative stress. Rutin was seen to lower the generation of oxidative stress in a dose-dependent manner. Using thioflavin-T assay and electron microscopy, rutin was suggested to restore the structural disturbances in glycated LDL. Moreover, CD spectroscopy suggested reinstation of secondary structure of glycated LDL treated with rutin. Mechanistic insights between rutin and LDL were observed through spectroscopic measures. Molecular docking study confirmed the LDL-rutin binding with a binding energy of -10.0 kcal/mol. The rutin-LDL complex was revealed to be highly stable by molecular dynamics simulation, with RMSD, RMSF, Rg, SASA, and the secondary structure of LDL remaining essentially unchanged during the simulation period. Our study suggests that rutin possesses strong anti-glycating properties, which can be useful in therapeutics, as glycated LDL has an important role in atherosclerotic cardiovascular diseases., Competing Interests: Declaration of competing interest The authors of this paper declare no social or financial conflict of interest in this research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Enantiomers have the same physical properties but different chemical properties due to the difference in the orientation of groups in space and thus Chiral discrimination is quite necessary, as an enantiomer of drug can have lethal effects. In this study, we used the CC2 cage for chiral discrimination of amino acids using density functional theory. The results indicated the physisorption of amino acids in the central cavity of the cage. Among the four selected amino acids, proline showed maximum interactions with the cage and maximum chiral discrimination energy is also observed in the case of proline that is 2.78 kcal/mol. Quantum theory of atoms in molecules and noncovalent interaction index analyses showed that the S enantiomer in each case has maximum interactions. The charge transfer between the analyte and surface is further studied through natural bond orbital analysis. It showed sensitivity of cage for both enantiomers, but a more pronounced effect is seen for S enantiomers. In frontier molecular orbital analysis, the least E H-L gap is observed in the case of R proline with a maximum charge transfer of -0.24 e - . Electron density difference analysis is carried out to analyze the pattern of the charge distribution. The partial density of state analysis is computed to understand the contribution of each enantiomer in overall density of the complexes. Our results show that S-CC2 porous organic cages have a good ability to differentiate between two enantiomers. S-CC2 porous organic cages efficiently differentiated the S enantiomer from the R enantiomers of selected amino acids.

The Arabian Camelus dromedarius contains significant concentration of eye lens ζ-crystallin. This enzyme is also present in other life forms including humans, however in lower catalytic amounts. The recombinant camel ζ-crystallin was expressed in the E. coli BL21 (DE3) pLysS strain and purified using HisTrap column. The K m of the enzyme for 9,10-phenanthrenequinone (9,10-PQ) substrate and NADPH cofactor was determined to be 11.66 and 50.93 µM, respectively. The V max for 9,10-PQ and NADPH was obtained as 23.19 and 19.98 μM min -1 , respectively. The optimum activity of the purified enzyme was found to be at pH 6.0 and at 55 °C. Different physico-chemical parameters were analysed including instability index (II), aliphatic index (AI) and the GRAVY index to establish proper characterization. The sequence of the recombinant ζ-crystallin was subjected to homology modelling using SWISS-MODEL webserver followed by validation of the modelled target structure. The evaluation of the modelled ζ-crystallin was performed by several parameters including Ramachandran plot, Z-score values followed by molecular dynamics (MD) simulation. The cumulative analysis of the physico-chemical, quantitative, qualitative and the essential dynamics of simulation of ζ-crystallin and its complexes with 9,10-PQ and NADPH helped in verifying the acceptable quality and stability of the ζ-crystallin structure.Communicated by Ramaswamy H. Sarma.

We report the determination of the absolute configuration of a diterpenoid, namely, ballonigrin lactone A (BLA), by comparison of the computed optical rotations, [α] D , of its two diastereomers using density functional theory (DFT) calculations to the experimental [α] D value of +22.4. One of the diastereomers having configurations 4S, 5R, 6S, 10S, 15S was named "α-BLA," and the other one with configuration 4S, 5R, 6S, 10S, 15R was called "β-BLA". Six conformers for each diastereomer (α-BLA and β-BLA) of BLA were identified through their conformational analysis. [α] D values of these six conformations for each diastereomer were calculated using DFT at the mPW1PW91/6-311G(d,p)/SMD Chloroform level of theory, leading to the conformationally averaged [α] D values of -96.8 for α-BLA and +65.1 for β-BLA. Thus, it was found that the experimental [α] D value of +22.4 was of 4S, 5R, 6S, 10S, 15R, i.e., β-BLA. Experimental and computed nuclear magnetic resonance (NMR) data were also compared, and this comparison was in accordance with the conclusion drawn from the comparison of [α] D values. Finally, the results were augmented with the calculation of the DP4 analysis, and the probability obtained also endorsed our earlier calculations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The implications of surfactant-enzyme/protein interactions in a variety of fields, including biotechnology, cosmetics, paints and pharmaceuticals, have attracted a lot of attention in contemporary studies. Herein, we have employed several in vitro and in silico techniques such as excitation and absorption spectroscopies, circular dichroism and FT-IR spectroscopies, density functional and molecular dynamics simulations to understand the interaction behavior of oxy-diester-based green cationic Gemini surfactants, N 1 ,N 1 ,N 14 ,N 14 -tetramethyl-2,13-dioxo-N 1 ,N 14 -dialkyl-3,6,12-tetraoxateradecane-1,14-diaminiumdichloride (abbreviated as C m -E2O2-C m , where 'm' stands for alkyl chain length, m  = 12 and 14) with one of the main digestive proteins, pepsin. The spectroscopic techniques confirm the static quenching effect of surfactants on pepsin. The calculated physical parameters ( K sv , K b and ΔG ) and their order reveal the distinguished implications for the surfactants' chain lengths. The spontaneity of interaction was also confirmed by negative Gibbs free energy change values. The extrinsic spectroscopic study with pyrene as fluorescence probe, FT-IR and CD techniques indicated a potential conformational change in pepsin induced by the Gemini surfactants. DFT, docking and MD simulations provided the theoretical understanding regarding the quantum mechanical environment, location of binding and stability of the protein-surfactant complexation in energy terms. We believe this study will be a humble addition to our existing knowledge in the field of protein-surfactant interactions.Communicated by Ramaswamy H. Sarma.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is considered a global public health concern since it causes high morbidity and mortality. Recently, it has been reported that repurposed anti-COVID-19 drugs might interact with multidrug resistance ABC transporter, particularly ABCB1. In the current study, a series of thiourea derivatives were screened as potential inhibitors against SARS-CoV-2 by targeting the attachment of receptor binding domain (RBD) of spike protein with ACE2 and their interaction with human ABCB1 has also been explored. The results indicated strong impairment of RBD-ACE2 attachment by BB IV-46 with a percentage inhibition of 95.73 ± 1.79% relative to the positive control, while BB V-19 was proven inactive with a percentage inhibition of 50.90 ± 0.84%. The same compound (BB IV-46) interacted with ABCB1 and potentially inhibited cell proliferation of P-gp overexpressing cell line with an IC 50 value of 4.651 ± 0.06 μM. BB V-19, which was inactive against SARS-CoV-2, was inactive against ABCB1 with a higher IC 50 value of 35.72 ± 0.09 μM. Furthermore, molecular dynamics simulations followed by binding free-energy analysis explored the binding interaction of BB IV-46 and BB V-19 to RBD region of spike protein of SARS-CoV-2. The results confirmed that compound BB IV-46 interacted strongly with RBD with a significant binding energy (-127.0 kJ/mol), while BB V-19 interacted weakly (-29.30 kJ/mol). The key interacting residues of the RBD involved in binding included Leu441, Lys444, and Tyr449. This study highlights the importance of BB IV-46 against SARS-CoV-2; however, further pharmacokinetic and pharmacodynamics studies are needed to be done., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Globally, cancer is the second leading cause of mortality and morbidity. The growth and development of cancer are extremely complex. It is caused by a variety of pathways and involves various types of enzymes. Pyruvate kinase M2 (PKM2) is an isoform of pyruvate kinase, that catalyses the last steps of glycolysis to produce energy. PKM2 is relatively more expressed in tumour cells where it tends to exist in a dimer form. Various medicinal plants are available that contain a variety of micronutrients to combat against different cancers. The phytocompounds of the olive tree ( Olea europaea) leaves play an important role in inhibiting the proliferation of several cancers. In this study, the phytocompounds of olive leaf extract (OLE) were studied using various in silico tools, such as pkCSM software to predict ADMET properties and PASS Online software to predict anticancer activity. However, the molecular docking study provided the binding energies and inhibition constant and confirmed the interaction between PKM2 and the ligands. The dynamic behaviour, conformational changes, and stability between PKM2 and the top three hit compounds (Verbascoside (Ver), Rutin (Rut), and Luteolin&#95;7&#95; O &#95;glucoside (Lut)) are studied by MD simulations.

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aβ 1-40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ -8.05 kcal mol -1 ) targeting Aβ 1-40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zia, Rehman, Hashmi, Siddiqui, Bin Dukhyil, Ahmed, Jamal, Banawas, Almalki, Owais, Aldhafeeri, Ibrahim, Alturaiki, AlAjmi, Alsieni and Alqurashi.)

We are facing a high risk of exposure to emerging contaminants and increasing environmental pollution with the concomitant growth of industries. Persistence of these pollutants is a major concern to the ecosystem. Laccases, also known as "green catalysts" are multi-copper oxidases which offers an eco-friendly solution for the degradation of these hazardous pollutants to less or non-toxic compounds. Although various other biological methods exist for the treatment of pollutants, the fact that laccases catalyze the oxidation of broad range of substrates in the presence of molecular oxygen without any additional cofactor and releases water as the by-product makes them exceptional. They have a good possibility of utilization in various industries, especially for the purpose of bioremediation. Besides this, they have also been used in medical/health care, food industry, bio-bleaching, wine stabilization, organic synthesis and biosensors. This review covers the catalytic behaviour of laccases, their immobilization strategies, potential applications in bioremediation of recalcitrant environmental pollutants and their engineering. It provides a comprehensive summary of most factors to consider while working with laccases in an industrial setting. It compares the benefits and drawbacks of the current techniques. Immobilization and mediators, two of the most significant aspects in working with laccases, have been meticulously discussed., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Carbonic anhydrases (CAs and EC 4.2.1.1) are the Zn 2+ containing enzymes which catalyze the reversible hydration of CO 2 to carbonate and proton. If they are not functioning properly, it would lead towards many diseases including tumor. Synthesis of hydrazide-sulfonamide hybrids (19-36) was carried out by the reaction of aryl (10-11) and acyl (12-13) hydrazides with substituted sulfonyl chloride (14-18) . Final product formation was confirmed by FT-IR, NMR, and EI-MS. Density functional theory (DFT) calculations were performed on all the synthesized compounds to get the ground-state geometries and compute NMR properties. NMR computations were in excellent agreement with the experimental NMR data. All the synthesized hydrazide-sulfonamide hybrids were in vitro evaluated against CA II, CA IX, and CA XII isozymes for their carbonic anhydrase inhibition activities. Among the entire series, only compounds 22 , 32 , and 36 were highly selective inhibitors of h CA IX and did not inhibit h CA XII. To investigate the binding affinity of these compounds, molecular docking studies of compounds 32 and 36 were carried out against both h CA IX and h CA XII. By using BioSolveIT's SeeSAR software, further studies to provide visual clues to binding affinity indicate that the structural elements that are responsible for this were also studied. The binding of these compounds with h CA IX was highly favorable (as expected) and in agreement with the experimental data., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Adil Khushal et al.)

In the current study, a covalent triazine framework (CTF-0) was evaluated as an electrochemical sensor against industrial pollutants i.e. , O 3 , NO, SO 2 , SO 3 , and CO 2 . The deep understanding of analytes@CTF-0 complexation was acquired by interaction energy, NCI, QTAIM, SAPT0, EDD, NBO and FMO analyses. The outcome of interaction energy analyses clearly indicates that all the analytes are physiosorbed onto the CTF-0 surface. NCI and QTAIM analysis were employed to understand the nature of the non-covalent interactions. Furthermore, SAPT0 analysis revealed that dispersion has the highest contribution towards total SAPT0 energy. In NBO analysis, the highest charge transfer is obtained in the case of SO 3 @CTF-0 (-0.167 e - ) whereas the lowest charge transfer is observed in CO 2 @CTF-0. The results of NBO charge transfer are also verified through EDD analysis. FMO analysis revealed that the highest reduction in the HOMO-LUMO energy gap is observed in the case of O 3 (5.03 eV) adsorption onto the CTF-0 surface, which indicates the sensitivity of CTF-0 for O 3 analytes. We strongly believe that these results might be productive for experimentalists to tailor a highly sensitive electrochemical sensor using covalent triazine-based frameworks (CTFs)., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Two-dimensional (2D) monolayer nanomaterials are the thinnest possible membranes with interesting selective permeation characteristics. Among two-dimensional materials, graphenes and hexagonal boron nitride (h-BN) are the most promising membrane materials, which can even allow the separation of proton isotopes. The current work aims at understanding the higher reported permeability of h-BN by sequential doping of B and N atoms in graphene nanoflakes. The kinetic barriers were calculated with two different models of graphenes; coronene and dodecabenzocoronene via zero-point energy calculations at the transition state for proton permeability. The lower barriers for h-BN are mainly due to boron atoms. The trends of kinetic barriers are B < BN < N-doped graphenes. The permeation selectivity of graphene models increases with doping. Our studies suggest that boron-doped graphene models show an energy barrier of 0.04 eV for the permeation of proton, much lower than that of the model graphene and h-BN sheet, while nitrogen-doped graphenes have a very high energy barrier up to 7.44 eV for permeation. Therefore, boron-doped graphene models are suitable candidates for proton permeation. Moreover, the presence of carbon atoms in the periphery of BN sheets has significant negative effects on the permeation of proton isotopes, an unexplored dimension of the remote neighboring effect in 2-D materials. This study illustrates the need for permeation study through other hetero-2D surfaces, where interesting hidden chemistry is still unexplored., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In the present study, pyrazole-thiophene-based amide derivatives were synthesized by different methodologies. Here, 5-Bromothiophene carboxylic acid ( 2 ) was reacted with substituted, unsubstituted, and protected pyrazole to synthesize the amide. It was observed that unsubstituted amide (5-bromo- N -(5-methyl-1 H -pyrazol-3-yl)thiophene-2-carboxamide ( 7 ) was obtained at a good yield of about 68 percent. The unsubstituted amide ( 7) was arylated through Pd (0)-catalyzed Suzuki-Miyaura cross-coupling, in the presence of tripotassium phosphate (K 3 PO 4 ) as a base, and with 1,4-dioxane as a solvent. Moderate to good yields (66-81%) of newly synthesized derivatives were obtained. The geometry of the synthesized compounds ( 9a - 9h ) and other physical properties, like non-linear optical (NLO) properties, nuclear magnetic resonance (NMR), and other chemical reactivity descriptors, including the chemical hardness, electronic chemical potential, ionization potential, electron affinity, and electrophilicity index have also been calculated for the synthesized compounds. In this study, DFT calculations have been used to investigate the electronic structure of the synthesized compounds and to compute their NMR data. It was also observed that the computed NMR data manifested significant agreement with the experimental NMR results. Furthermore, compound ( 9f ) exhibits a better non-linear optical response compared to all other compounds in the series. Based on frontier molecular orbital (FMO) analysis and the reactivity descriptors, compounds ( 9c ) and ( 9h ) were predicted to be the most chemically reactive, while ( 9d ) was estimated to be the most stable among the examined series of compounds.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality and morbidity across the Globe. A meta-analysis was conducted to determine the effectiveness of different modes of resistance training on FEV1 and functional exercise capacity among COPD patients. Data bases of Cochrane, PEDro, Embase, CINAHL, PubMed and Google Scholar were searched seeking research articles of interest. All those studies were included in which effect of resistance training was determined on FEV1 and functional exercise capacity of COPD patients and published in English language. All those studies that predated to 2011 were excluded from the review. A sample of 180 COPD patients was included in 5 RCTs. Results of the study demonstrated that resistance training has a mild pool effect in increasing FEV1 with an effect size of (SMD) of 0.160 (95% CI of -0.840 to 0.521) calculated at random effect model, I2 = 62.99% (95% CI of 0.00 to 89.42); whereas, functional exercise capacity demonstrated large pool effect size 0.886 (95% CI of 0.401 to 1.371) with I2 = 0.0 (95% CI of 0.00 to 0.00). The study concludes that there is a small to large impact of resistance exercises in improving functional exercise capacity and forced expiratory volume. Key Words: Resistance training, 6-minute walk test 6MWT, Chronic obstructive pulmonary disease, Functional exercise capacity, Forced expiratory volume.

Synthesis of 5-aryl- N -(pyrazin-2-yl)thiophene-2-carboxamides ( 4a - 4n ) by a Suzuki cross-coupling reaction of 5-bromo- N -(pyrazin-2-yl)thiophene-2-carboxamide ( 3 ) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine ( 1 ) with 5-bromothiophene-2-carboxylic acid ( 2 ) mediated by TiCl 4 . The target pyrazine analogs ( 4a - 4n ) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (E HOMO , E LUMO ), HOMO-LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO-LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of 1 H NMR of all the synthesized compounds 4a - 4n were calculated and compared with the experimental values.

Benzanthrone dyes are organic luminophores with excellent optoelectronic properties. This computational investigation is based on density functional theory and aims to explore the photophysical behavior of some of the reported aminobenzanthrones in addition to many unreported dyes containing different electron-donating substituents. Significant changes in the dipole moment and the overall structure of the dyes upon solvation in ethanol have been observed. We find that intramolecular charge transfer is more pronounced in the solvent medium, which facilitates the emission to shift bathochromically. Intersystem crossing is predicted to be absent, which makes relaxation of the molecule to ground state more efficient by emitting in the visible region., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

A series of ( E )-4-bromo- N -((3-bromothiophen-2-yl)methylene)-2-methylaniline analogs synthesized in considerable yields through Suzuki cross-coupling reactions. Various electron donating and withdrawing functional moieties were successfully incorporated under the employed reaction conditions. Reaction of 4-bromo-2-methylaniline ( 1 ) with 3-bromothiophene-2-carbaldehyde ( 2b ) in the existence of glacial acetic acid, provided ( E )-4-bromo- N -((3-bromothiophen-2-yl)methylene)-2-methylaniline ( 3b ) in excellent yield (94%). Suzuki coupling of 3b with different boronic acids in the presence of Pd(PPh 3 ) 4 /K 3 PO 4 at 90 °C led to the synthesis of the monosubstituted and bisubstituted products 5a - 5d and 6a - 6d in moderate yields (33-40% and 31-46%, respectively). Density functional theory (DFT) investigations were performed on different synthesized analogues 5a - 5d , 6a - 6d to determine their structural characteristics. The calculations provide insight into the frontier molecular orbitals (FMOs) of the imine-based analogues and their molecular electrostatic potential (MESP). Reactivity descriptors like ionization energy (I), electron affinity (A), chemical hardness ( ƞ ) and index of nucleophilicity have been calculated for the first time for the synthesized molecules.

Most bacteria exist in nature in the form of biofilms. One of the key survival strategies by bacteria to withstand chemical and physical stresses is by forming biofilms on biotic and abiotic surfaces. A different set of genes are expressed in biofilms compared to the planktonic mode of bacterial growth. According to data from the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC), nearly 80 percent of all human infections are encouraged by biofilms and roughly 65 percent of all hospital-acquired infections are associated with biofilms. Hence, considering the role of biofilms in clinical settings, there is an urgent need for the discovery/development of novel antibiofilm agents. In this study, we have tested the effect of freshly prepared titanium dioxide nanoparticles (TiO 2 -NPs) synthesized using Carum copticum extract on biofilms, both against Gram +ve and Gram -ve bacteria. Being environment friendly in nature, the green route of nanoparticle synthesis is believed to be advantageous over chemical synthesis of metal nanoparticles. The synthesized nanoparticles were found to be predominantly spherical or spheroidal in shape with an average size of 12.01 ± 5.58 nm. As evident from data, more than 70% inhibition of biofilms of test bacteria was achieved in the presence of TiO 2 -NPs. Electron microscopic analysis revealed that the adherence and colonization of bacteria on the glass surface were remarkably reduced by the treatment of TiO 2 -NPs. The EPS secretion of E. coli ATCC 25922 and P. aeruginosa PAO1 were inhibited by 62.08 and 74.94%, respectively. The EPS secretion of S. aureus MTCC 3160 was least inhibited (<55%) compared to other test bacteria. Moreover, TiO 2 -NPs successfully eradicated the preformed biofilms of E. coli ATCC 25922, P. aeruginosa PAO1, and S. aureus MTCC 3160 by 60.09, 64.14, and 48.30%, respectively. The findings demonstrate the efficacy of green synthesized titanium dioxide nanoparticles in inhibiting and eradicating the biofilms of bacterial pathogens and they may be further exploited for the development of a new alternative antibiofilm agent., Competing Interests: The authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The low concentration of graphene (<5%) in graphene/polypyrrole composites makes it quite challenging to devise a theoretical model for these composites. Thus, herein, we present theoretical calculations to determine the geometric electronic and optical properties of graphene/polypyrrole composites. Ribbon and sheet models of various sizes were considered for graphene. Oligopyrrole of various lengths was deposited in the graphene model in different orientations including π-stacking, tilted and vertical orientations. Theoretical calculations at the M062X/def2-SVP level revealed that π-stacking is the preferred orientation. To model a lower concentration of graphene, sandwich complexes of oligopyrrole were considered with graphene nanoribbons. Interaction energies revealed that sandwich complexes possessed superior additivity. The NCI analysis established that weak van der Waals interactions existed in all composites. Moreover, the HOMO-LUMO gap decreases as the concentration of graphene increases. Thus, the computed optical band gap of the C 58 H 24 -based composite is about 1.7 eV, which is consistent with the reported experimental value (2.1-1.81 eV). The computed band gap further decreases to ∼1.6 eV when the proportion of graphene increases to C 64 H 26 . Thus, our results for the graphene nanoribbon-based polypyrrole composites are in good agreement with experimental results. The UV/visible spectra revealed that as the concentration of graphene increases, a red shift is observed for all the configurations, which is consistent with experimental results.

High levels of stress in the parenting domain can lead to parental burnout , a condition that has severe consequences for both parents and children . It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; M age = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress., Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-020-00028-4., Competing Interests: Conflict of InterestThe authors declare no competing financial interests or funding source that could have influenced the data collection, analysis, or conclusions. M.M. and I.R. have now founded a training institute (name currently masked for blind review) which delivers training on parental burnout to professionals. The institute did not participate in the funding of this study nor did it influence the process, the results, or their interpretation in any manner., (© The Society for Affective Science 2021.)

Both exohedral and endohedral complexes of second row elements doped X 12 Y 12 (X = B, Al and Y = P) nano-cages are evaluated for thermodynamic stabilities, electronic properties and kinetic barriers. Interaction energies are calculated to deeply perceive the stability of these complexes. Further, interconversion of exohedral and endohedral complexes is explored through an unprecedented approach, where 2nd row elements translate into nano-cages through boundary crossing. Subsequently, the kinetic barriers for encapsulation and decapsulation are also investigated through PES scanning of all elements by passing through hexagon of nano-cages. Systematic investigations revealed that due to larger diameter, AlP nanocage exhibits low encapsulation barriers in comparison to BP nano-cage. Such as; the encapsulation barrier of F@AlP (7.57 kcal mol -1 ) is lower than that of F@BP (129.78 kcal mol -1 ). Moreover, distortion of nano-cages due to translation of elements is also estimated by distortion energies. Large distortion energies of 113.81/118.39 kcal mol -1 are noticed for exo-B@AlP/exo-C@BP complexes. In addition, the electronic properties for all the complexes are probed and depicted that the endohedral doping have remarkable influence on the electronic properties of the nanocage in comparison to exohedral doping. NBO charge analysis shows that Be metal delivers charges of 0.08 |e|/0.03 |e| to the AlP/BP nanocage, causing the later more electron rich. Contrary to Be, all other doped atoms show negative charges., Competing Interests: Declaration of competing interest All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To determine the frequency and antimicrobial sensitivity pattern of microbial agents causing neonatal sepsis., Study Design: Descriptive study., Place and Duration of Study: Neonatal ICU, Fauji Foundation Hospital, Rawalpindi; Foundation University, Islabambad, from May 2017 to April 2019., Methodology: Data of all neonates admitted with sepsis during study period was retrieved from computer database. Age at admission, gender, duration of hospital stay and culture reports were recorded. Culture positive patients were further analysed regarding their antibiotic sensitivity., Results: A total of 1,070 neonates, male:female = 1.36:1, mostly newborn, were included in the study. Total mortality was 182 (17%). Blood culture was positive in 79 (7.4%). Gram positive organisms were identified in 37 (46.8%) Staphylococci in 29 (36.7%), Enterococci 7 (8.9%), Corynebacterium species in 1 (1.3%). Gram negative were isolated in 42 (53.2%) Acinetobacter Baumanni in 14 (17.7%), Klebsiella in 12 (15.2%), Enterobacter spp. In 7 (8.8%), E.coli in 5 (6.3%), Pseudomonas in 2 (2.5%) and Proteus in 1 (1.3%) and Serratia in 1 (1.3%) each. Sensitivity pattern of Gram positive organisms was: vancomycin 30/37 (81.1%), ciprofloxacin 13/37 (35.1%) and Gentimicin 12/37 (32.4%). Gram negative organisms sensitivity pattern was: meropenem 12/42 (28.6%), chloramphenical 10/42 (23.8%), gentimicin 6/42 (14.3%), ciprofloxacin 5/42 (11.9%). Highly resistant strains of Klebsiella (13/14) and Acinitobacter (5/12) were sensitive to colomycin only., Conclusion: Common organisms responsible for neonatal sepsis were Styphylococci, Acinitobacter, Klebsiella and E.Coli. Gram positive organisms showed sensitivity to vancomycin and gentamicin. Gram negative organisms were highly sensitive to colomycin. Key Words: Neonatolgy, Neonatal sepsis, Antimicrobial sensitivity, Neonatal mortality.