microRNA Isolation, Expression Profiling, and Target Identification for Neuroprotection in Alzheimer's Disease.

Millions of people throughout the world are affected by neurodegenerative disorders like Alzheimer's disease (AD), making them a major public health concern. To create successful medicines, early diagnosis and illness monitoring are required. Emerging as possible diagnostic and treatment tools for neurodegenerative illnesses are biomarkers such as microRNAs (miRNAs). In the realm of neuroscience, miRNAs have been discovered to function as essential regulators of gene expression, with roles spanning development, differentiation, and illness. Several neurodegenerative diseases, including AD, have been linked to miRNA dysregulation. As high-throughput methods have been developed for monitoring miRNA expression and identifying miRNA targets, miRNAs have become a prime candidate for use in diagnostics and therapy. The techniques for isolating miRNAs and the most up-to-date computational methods for finding miRNA target transcripts are both described in this chapter. This chapter will be a helpful reference for anyone investigating the role of miRNAs in AD and related neurodegenerative illnesses.

Deep Drug Discovery of Mac Domain of SARS-CoV-2 (WT) Spike Inhibitors: Using Experimental ACE2 Inhibition TR-FRET Assay, Screening, Molecular Dynamic Simulations and Free Energy Calculations.

SARS-CoV-2 exploits the homotrimer transmembrane Spike glycoproteins (S protein) during host cell invasion. The Omicron XBB subvariant, delta, and prototype SARS-CoV-2 receptor-binding domain show similar binding strength to hACE2 (human Angiotensin-Converting Enzyme 2). Here we utilized multiligand virtual screening to identify small molecule inhibitors for their efficacy against SARS-CoV-2 virus using QPLD, pseudovirus ACE2 Inhibition -Time Resolved Forster/Fluorescence energy transfer (TR-FRET) Assay Screening, and Molecular Dynamics simulations (MDS). Three hundred and fifty thousand compounds were screened against the macrodomain of the nonstructural protein 3 of SARS-CoV-2. Using TR-FRET Assay, we filtered out two of 10 compounds that had no reported activity in in vitro screen against Spike S1: ACE2 binding assay. The percentage inhibition at 30 µM was found to be 79% for "Compound F1877-0839" and 69% for "Compound F0470-0003". This first of its kind study identified "FILLY" pocket in macrodomains. Our 200 ns MDS revealed stable binding poses of both leads. They can be used for further development of preclinical candidates.

Designing of phenothiazine-based hole-transport materials with excellent photovoltaic properties for high-efficiency perovskite solar cells (PSCs).

In this study, a series of highly efficient organic hole-transporting materials (HTMs) were designed using Schiff base chemistry by modifying a phenothiazine-based core with triphenylamine through end-capped acceptor engineering via thiophene linkers. The designed HTMs (AZO1-AZO5) exhibited superior planarity and greater attractive forces, making them ideal for accelerated hole mobility. They also showed deeper HOMO energy levels (-5.41 eV to -5.28 eV) and smaller energy band gaps (2.22 eV to 2.72 eV), which improved charge transport behavior, open-circuit current, fill factor, and power conversion efficiency of perovskite solar cells (PSCs). The dipole moments and solvation energies of the HTMs revealed their high solubility, making them suitable for the fabrication of multilayered films. The designed HTMs showed tremendous enhancements in power conversion efficiency (26.19 % to 28.76 %) and open-circuit voltage (1.43 V to 1.56 V), with higher absorption wavelength than the reference molecule (14.43 %). Overall, the Schiff base chemistry-driven design of thiophene-bridged end-capped acceptor HTMs is highly effective in enhancing the optical and electronic properties of perovskite solar cells.

Strongly Coupled Plasmon Polaritons in Gold and Epsilon-Near-Zero Bifilms.

Epsilon-near-zero (ENZ) polaritons in a thin transparent conducting-oxide film exhibit a significant electric field enhancement and localization within the film at frequencies close to their plasma frequency, but do not propagate. Meanwhile, plasmon polariton modes in thin metallic films can propagate for several microns, but are more loosely confined in the metal. Here, we propose a strongly coupled bilayered structure of a thin gold film on a thin indium tin oxide (ITO) film that supports hybrid polariton modes. We experimentally characterize the dispersion of these modes and show that they have propagation lengths of 4-8 µm while retaining mode confinement greater than that of the polariton in gold films by nearly an order of magnitude. We study the tunability of this coupling strength by varying the thickness of the ITO film and show that ultrastrong coupling is possible at certain thicknesses. The unusual linear and nonlinear optical properties of ITO at ENZ frequencies make these bifilms useful for the active tuning of strong coupling, ultrafast switching, and enhanced nonlinear interactions at near-infrared frequencies.

Burnout in health care workers during the fourth wave of COVID-19: A cross sectional study from Pakistan.

Objective: To assess the burnout among the healthcare workers during the fourth wave of COVID-19. Methods: In this cross-sectional study, burn out was measured in health care professionals using the MBI scale inventory during the fourth wave of COVID-19. Age, gender, marital status, having children, hospital, job type, experience, and workload, as well as the severity of burnout in each subscale, were all measured. We used the chi-square test to detect the difference between the level of burnout and other demographic variables, and a multiple logistic regression test was used to define the predicted correlation between the high level of burnout and the risk factors. Odds ratios and corresponding 95% confidence intervals (CI) were reported. A p-value of less than 0.05 indicated a statistically significant outcome. Results: Out of 776 healthcare workers who participated in our study, 468 (63.2%), 161 (21.7%) and 112 (15.1%) participants experienced low, moderate and high levels of emotional exhaustion, respectively. For the depersonalization subscale, 358 (48.3%), 188 (25.4%) and 195 (26.3%) people suffered from low, moderate, and high levels of depersonalization, respectively while 649 (87.6%), 40 (5.4%) and 52 (7.0%) respondents had low, moderate and high levels in the personal accomplishment subscale, respectively. Conclusion: During the fourth wave of COVID-19, the healthcare workers reported increased level of burnout overall possibly due to the long term physical and mental impacts that the pandemic has had over the time. Moreover, healthcare workers in Pakistan were more prone to burnout as compared to other countries.

Coverage Area Decision Model by Using Unmanned Aerial Vehicles Base Stations for Ad Hoc Networks.

Unmanned Aerial Vehicle (UAV) deployment and placement are largely dependent upon the available energy, feasible scenario, and secure network. The feasible placement of UAV nodes to cover the cellular networks need optimal altitude. The under or over-estimation of nodes' air timing leads to of resource waste or inefficiency of the mission. Multiple factors influence the estimation of air timing, but the majority of the literature concentrates only on flying time. Some other factors also degrade network performance, such as unauthorized access to UAV nodes. In this paper, the UAV coverage issue is considered, and a Coverage Area Decision Model for UAV-BS is proposed. The proposed solution is designed for cellular network coverage by using UAV nodes that are controlled and managed for reallocation, which will be able to change position per requirements. The proposed solution is evaluated and tested in simulation in terms of its performance. The proposed solution achieved better results in terms of placement in the network. The simulation results indicated high performance in terms of high packet delivery, less delay, less overhead, and better malicious node detection.

Impact of various heterocyclic π-linkers and their substitution position on the opto-electronic attributes of the A-π-D-π-A type IECIO-4F molecule: a comparative analysis.

To investigate the consequence of different substitution positions of various π-linkers on the photovoltaic properties of an organic solar cell molecule, we have introduced two series of six three-donor molecules, by the substitution of some effective π-linkers on the A-π-D-π-A type reference molecule IECIO-4F (taken as IOR). In series "a" the thienyl or furyl bridge is directly linked between the donor and acceptor moieties, while in series "b" the phenyl ring of the same bridge is working as the direct point of attachment. The frontier molecular orbitals, density of states, transition density matrix, molecular electrostatic potential surfaces, exciton binding energy, excitation energy, wavelength of maximum absorption, open-circuit voltage, fill factor, and some other photovoltaic attributes of the proposed molecules were analyzed through density functional theory (DFT) and its time-dependent (TD) approach; the TD-DFT method. Though both series of newly derived molecules were a step up from the reference molecule in almost all of the studied characteristics, the "a" series (IO1a to IO3a) seemed to be better due to their desirable properties such as the highest maximum absorption wavelength (λ max), open-circuit voltage, and fill factor, along with the lowest excitation and exciton dissociation energy, etc. of its molecules. Also, the studied morphology, optical characteristics, and electronic attributes of this series of proposed molecules signified the fact that the molecules with thienyl or furyl ring working as the direct link between the acceptor and donor molecules showed enhanced charge transfer abilities, and could provide a maximum quantum yield of the solar energy supplied.

Relationship Between Physical Inactivity and Obesity in the Urban Slums of Lahore.

Introduction There are several factors such as physical inactivity, sedentary lifestyle, and diet that can be responsible for weight gain or obesity. Regular physical activity is important for better physical and emotional well-being. The objective of the study is to observe the prevalence of obesity or over-weight and how lack of physical activity contributes to weight gain and other health issues. Methods This cross-sectional study was conducted in Shalamar Town, Lahore on 646 participants. Data was collected using the WHO STEPS instrument. The inclusion criteria were a minimum age of 30 years and residents of Shalimar Town, Lahore for more than five years. The exclusion criteria were participants with comorbid conditions like HIV, TB, and terminal stage of cancer. Test of association and binary logistic regression analysis was performed to observe a significant association between demographic variables and non-communicable diseases among the participants involved in performing physical exercise. Results About 22.1% of the participants had normal BMI, 5.3% were underweight whereas 34.2% of the participants were overweight and 32.4% obese. Male participants were found to be more physically active compared to females. Hypertension and diabetes were statistically significantly associated with physical activity. BMI and waist-hip ratio were found to be associated with moderate physical exercise. Conclusion Most of the participants were not involved in moderate physical activity. Overall, an alarming 66.6% of the participants were either overweight or obese. In general, males were found to participate more in intense physical activity.

Design, crystal structure determination, molecular dynamic simulation and MMGBSA calculations of novel p38-alpha MAPK inhibitors for combating Alzheimer's disease.

The hallmark of the Alzheimer's disease (AD) is the accumulation of aggregated, misfolded proteins. The cause for this accumulation is increased production of misfolded proteins and impaired clearance of them. Amyloid aggregation and tau hyperphosphorylation are the two proteinopathies which accomplish deprivation of cell and tissue hemostasis during neuropathological process of the AD, as a result of which progressive neuronal degeneration and the loss of cognitive functions. p38 mitogen-activated protein kinase (p38 MAPK) has been implicated in both the events associated with AD: tau protein phosphorylation and inflammation. p38α MAPK pathway is activated by a dual phosphorylation at Thr180 and Tyr182 residues. Clinical and preclinical evidence implicates the stress related kinase p38α MAPK as a potential neurotherapeutic target. Drug design of p38α MAPK inhibitors is mainly focused on small molecules that compete for Adenosine triphosphate in the catalytic site. Here we have carried out the synthesis of phenyl sulfonamide derivatives Sulfo (I) and Sulfo (II). Crystal structures of Sulfo (I) and Sulfo (II) were solved by direct methods using SHELXS-97. Sulfo (I) and Sulfo (II) have Rint values of 0.0283 and 0.0660, respectively, indicating good quality of crystals and investigated their ability against p38α MAPK. Docking studies revealed that the Sulfo (I) had better binding affinity (-62.24 kcal/mol) as compared to Sulfo (II) and cocrystal having binding affinity of -54.61 kcal/mol and -59.84 kcal/mol, respectively. Molecular dynamics simulation studies of Sulfo (I) and cocrystal of p38α MAPK suggest that during the course of 30 ns simulation run, compound Sulfo (I) attained stability, substantiating the consistency of its binding to p38α MAPK compared to cocrystal. Binding free energy analysis suggests that the compound Sulfo (I) is better than the cocrystal. Thus, this study corroborates the therapeutic potential of synthesized Sulfo (I) in combatting AD.Communicated by Ramaswamy H. Sarma.

Insights in the structural understanding of amyloidogenicity and mutation-led conformational dynamics of amyloid beta (Aß) through molecular dynamics simulations and principal component analysis.

Abnormal protein aggregation in the nervous tissue leads to several neurodegenerative disorders like Alzheimer's disease (AD). In AD, accumulation of the amyloid beta (Aß) peptide is proposed to be an early important event in pathogenesis. Significant research efforts are devoted so as to understand the Aß misfolding and aggregation. Molecular dynamics (MD) simulations complement experiments and provide structural information at the atomic level with dynamics without facing the same experimental limitations. Artificial missense mutations are employed experimentally and computationally for providing insights into the structure-function relationships of amyloid-ß in relation to the pathologies of AD. Present work describes the MD simulations for 100 ns so as to probe the structural and conformational dynamics of Aß1-42 assemblies and its mutants. Essential dynamics analysis with respect to conformational deviation of Cα was evaluated to identify the largest residual fluctuation of Cα. Conformational stability of all Aß mutants was analyzed by computing RMSD, deciphering the convergence is reached in the last 20 ns in all replicas. To highlight the low frequency mode of motion corresponding to the highest amplitude, atomic displacements seen in trajectory, distance pair principal component analysis (dpPCA) was performed, which adumbrated mutations strongly affect the conformational dynamics of investigated model when compared with wild type. Dynamic cross correlation matrix (DCCM) also suggests the conserved interactions of wild Aß and imply mutations in ß3-ß4 loop region induce deformity and residual fluctuations as observed from simulation. Present study indicate the mutational energy landscape which induces deformation leading to fibrillation.Communicated by Ramaswamy H. Sarma.

Network-based identification of miRNAs and transcription factors and in silico drug screening targeting δ-secretase involved in Alzheimer's disease.

BACKGROUND: System medicine approaches have played a pivotal role in identifying novel disease networks especially in miRNA research. It is no wonder that miRNAs are implicated in multiple clinical conditions, allowing us to establish the hubs and nodes for network models of Alzheimer's Disease (AD). AD is an age-related, progressive, irreversible, and multifactorial neurodegenerative disorder characterized by cognitive and memory impairment and is the most common cause of dementia in older adults. Worldwide, around 50 million people have dementia, and there are nearly 10 million new cases every year. δ-secretase, also known as asparagine endopeptidase (AEP) or legumain (LGMN), is a lysosomal cysteine protease that cleaves peptide bonds C-terminally to asparagine residues in both amyloid precursor protein (APP) and tau, mediating the amyloid-ß and tau pathology in AD. The patient's miRNA expression was found to be deregulated in the brain, extracellular fluid, blood plasma, and serum. METHODS: Protein-Protein Interaction (PPI) networks of LGMN or δ-secretase were constructed using the Genemania database. Network Analyzer, a Cytoscape plugin, analyzed the network topological properties of LGMN. miRNAs related to Alzheimer's were extracted from the HMDD (Human microRNA Disease Database) and experimentally verified miRNA-gene interaction was obtained by searching miRWalk. Starbase v2.0 and miRanda were used for screening miRNA of LGMN genes. Moreover, to understand the regulatory mechanism in AD, we have screened major transcription factors of LGMN targeted genes using the Network Analyst 3.0, TRRUST (v2.0) server, and ENCODE. The Genotype-Tissue Expression (GTEx) and BEST tool were used to investigate the expression pattern of the LGMN gene. In parallel, we performed in-silico drug designing of the novel inhibitor scaffold of δ-secretase as powerful therapeutic targets by using the concept of scaffolds and frameworks. In this context, this study also aimed at identifying effective small molecule inhibitors targeting δ-secretase. RESULTS: Among the 16 experimentally verified miRNAs, Network analysis of the LGMN and its associated miRNA identify novel hsa-miRNA-106a-5p and hsa-miRNA-34a-5p being more expressed in the brain. Our in silico high throughput screening, followed by XP docking revealed Oprea1 as the lead. Molecular dynamic simulations of the δ-secretase-docked complex have been carried out for a time period of 200 ns and revealed that Root Mean Square Deviation (RMSD) of the protein Cα-backbone with respect to its starting position increased to 1.20 Å for the first 25 ns of the trajectory and then became stable around 0.6 Å in the last 170 ns course of the simulation. The radius of gyration (RGYR) reveals that compactness was maintained till the end of simulations. CONCLUSION: Network analysis of LGMN associated miRNAs lead to the identification of two novel miRNAs, being highly expressed in the brain. This study also lead to the identification and expression of 10 Transcription factors associated with LGMN. Expression Heatmap results show high and continuous expression of LGMN in most of the regions of the brain, especially in the frontal cortex. Further, in silico drug analysis led us to the identification of Oprea1 which could be taken for further investigation to explore its potential for AD therapy.

Mapping the role of pH-adjusted potassium in diabetic ketoacidosis: Hypokalemia and the patient outcomes.

BACKGROUND: Incidence of hypokalemia during the management of diabetic ketoacidosis (DKA) is high despite detailed potassium replacement guidelines in its treatment. AIM: We aimed to find the role of pH-adjusted potassium (pHK ) in the development of hypokalemia, and their mutual impact on patient outcomes during DKA management. METHODOLOGY: Adult DKA patient's admission data of preceding 3 years (2015-2017) were retrospectively clerked. Outcomes of interest were time to develop hypokalemia and to terminate emergency department (ED) care (hours), severity of hypokalemia and hospitalisation length (days). Linear regression was used to determine significant associations/predictors. RESULTS: The study was concluded on 85 patients. Hypokalemia was observed in nearly 3/4th of all admissions and occurred by the time of ED care termination. Each 1 mmol/L increase in pHK significantly (a) reduced the degree of hypokalemia by 0.07 mmol/L, (b) delayed time to develop hypokalemia by 4.58 hours, (c) and reduced the ED care time by 1.28 hours. Arterial pH was the other factor significantly delaying time to develop hypokalemia (36.25 hours) and facilitating early discharge from ED (13.86 hours). Moreover, each 1 mmol/L reduction in the degree of hypokalemia increased hospitalisation length by 1.86 days. Though significant, acute kidney injury negligibly increased hospitalisation length by 0.01 days. CONCLUSION: pH-adjusted potassium shall be used as a marker for hypokalemia and to initiate potassium replacement instead of measured serum potassium in DKA. Utilising pHK will help to avoid hypokalemia, reduce its severity and shorten ED care which will subsequently reduce hospitalisation length. We expect pHK to improve pharmacoeconomics in the future.

DFT study of superhalogen-doped borophene with enhanced nonlinear optical properties.

The concern of the present study is to investigate the nonlinear optical properties of superhalogen-doped borophene owing to its broad applications. The first principle study of the material for its nonlinear optical properties elaborated its use for electrical and optical applications. The superhalogen-based borophene in lithium ion-based batteries and medical appliances have made it one of the most potential materials for optoelectronics. First, hyperpolarizability (ßo) of pure and doped B36 is computed, and the difference between their values was examined. The vertical ionization energy (VIE) was calculated for pure and doped systems. The interaction energy (Ei) for all combinations was computed. It would be expected to be one of the best materials to have high capacity and resistance. For all the calculations and to calculate the highest occupied molecular orbital and lowest unoccupied molecular orbital energy gap, the density functional theory (DFT) method was used. It is predicted that these combinations are more beneficial and can display better nonlinear optical (NLO) properties in electronic devices. Superhalogen-doped BF4 borophene-36 ground state optimized geometry, frontier molecular orbitals HOMO and LUMO, maximum absorption (λmax), density of states (DOS) analysis, and electrostatic potential diagram (MEP) are displayed here.

DFT study of superhalogen and superalkali doped graphitic carbon nitride and its non-linear optical properties.

DFT calculations are carried out to investigate nonlinear optical (NLO) properties of superhalogen (BCl4) and superalkali (NLi4) doped graphitic carbon nitride (GCN). It is noted that the geometries of doped GCN are sufficiently stable. The energy gap for GCN is 3.89 and it reduces to 0.53 eV in our designed molecule G4. Change in the dipole and transition dipole moment is observed along with small transition energies which are responsible for higher hyperpolarizabilities. Doped GCN has larger first and second hyperpolarizabilities which are basic requirements for NLO response. The second hyperpolarizability of GCN enhances from 1.59 × 104 to 2.53 × 108 au when doping with BCl4 and NLi4. TD-DFT calculations show the absorption maxima of doped GCN range from 700 nm to 1350 nm. EDDM analysis provides information on electronic distribution from excited to ground state. All these consequences show doped GCN can be a promising NLO material.

Development of a Lung Cancer Model in Wistar Rat and In Silico Screening of its Biomarkers.

BACKGROUND: Cancer is usually caused by three factors: Nutrition, inflammation and cigarette smoke. This study on rat experimental models would enable us to understand the mechanism of lung cancer caused by NNK to which humans are continuously exposed, help us understand possible molecular targets, and assist in designing drugs for humans against lung cancer. AIM: A lung cancer model was developed by administering tobacco-specific carcinogen: NNK [4- methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats for 24 weeks. Furthermore, in silico approach was followed to screen the molecular targets. METHODS: A method was established in which subcutaneous and intraperitoneal injections of NNK were administered to male Wistar rats simultaneously. For authentication of lung cancer in vivo, we performed molecular docking simulations with protein biomarkers: Cox-2, p53, p38 MAPKs and EGFR using Hex-Discovery Studio, Schrödinger-maestro software. RESULTS: Lung morphology and histopathology indicated the initiation of bronchiolar epithelial hyperplasia and squamous dysplasia in the cancer 1 group after 16 weeks of NNK exposure. 66.66% incidence of squamous cell carcinoma (SCC) and 33.3% incidence of adenocarcinoma were observed in cancer 2 group after being exposed to NNK. Results indicated that the incidence of SCC and adenocarcinoma gradually increased from 66.66% to 85.71% in cancer 2 group and from 33.33% to 42.58% in cancer 3 group, respectively. Docking results indicate the total binding energy and glide energy of Cox-2, p53, p38 MAPKs, EGFR : 38.14, -211.58, -181.58, -213.05 Kcal/mol and -39.25, -32.16,-36.49, -40.19 Kcal/mol, respectively. CONCLUSION: Pulmonary adenocarcinoma model was developed by administering tobacco-specific carcinogen: NNK [4-methylnitrosamino)-1-(3-pyridyl)-1-butanone] to male Wistar rats in 24 weeks. In silico experiments confirmed EGFR to be the most potential target for NNK induced lung Cancer.

Relationship of sociodemographic and lifestyle factors and diet habits with metabolic syndrome (MetS) among three ethnic groups of the Malaysian population.

OBJECTIVES: Literature shows a high prevalence of MetS among Malaysians, varying across the major ethnicities. Since sociodemographic characteristics, lifestyle factors and diet habits of such communities have been reported to be diverse, the objective of this study was to investigate the association of various sociodemographic characteristics, lifestyle factors and diet habits with MetS overall, as well as with the three major ethnic communities in Malaysia, specifically. MATERIALS AND METHODS: We conducted a cross-sectional study among 481 Malaysians of ages 18 years and above living in the state of Johor, Malaysia. Information on demographics, lifestyle and diet habits were collected using a structured questionnaire. Harmonized criteria were used to assess the status of MetS. Multiple logistic regression was employed to determine any associations between sociodemographic and lifestyle factors and dietary behaviours with MetS. RESULTS: MetS was found among 32.2% of the respondents and was more prevalent among the Indians (51.9%), followed by the Malays (36.7%) and the Chinese (20.2%). Overall, increasing age (AOR = 2.44[95%CI = 1.27-4.70] at 40-49 years vs. AOR = 4.14[95%CI = 1.97-8.69] at 60 years and above) and Indian ethnicity (AOR = 1.95[95%CI = 1.12-3.38)] increased the odds of MetS, while higher education (AOR = 0.44[95%CI = 0.20-0.94] decreased the odds of MetS in this population. Quick finishing of meals (AOR = 2.17[95%CI = 1.02-4.60]) and low physical activity (AOR = 4.76[95%CI = 1.49-15.26]) were associated with increased odds of MetS among the Malays and the Chinese, respectively. CONCLUSION: The population of Johor depicts a diverse lifestyle and diet behaviour, and some of these factors are associated with MetS in certain ethnic groups. In the light of such differences, ethnic specific measures would be needed to reduce the prevalence of MetS among those in this population.

Crystal structures and Hirshfeld surface analyses of 4,4'-{[1,3-phenyl-enebis(methyl-ene)]bis-(-oxy)}bis-(3-meth-oxy-benzaldehyde) and 4,4'-{[(1,4-phenyl-ene-bis(methyl-ene)]bis-(-oxy)}bis-(3-meth-oxy-benzalde-hyde).

The title compounds, C24H22O6 (I) and C24H22O6 (II), each crystallize with half a mol-ecule in the asymmetric unit. The whole mol-ecule of compound (I) is generated by twofold rotation symmetry, the twofold axis bis-ecting the central benzene ring. The whole mol-ecule of compound (II) is generated by inversion symmetry, the central benzene ring being located on an inversion center. In (I), the outer benzene rings are inclined to each other by 59.96 (10)° and by 36.74 (9)° to the central benzene ring. The corresponding dihedral angles in (II) are 0.0 and 89.87 (12)°. In the crystal of (I), mol-ecules are linked by C-H⋯O hydrogen bonds and C-H⋯π inter-actions, forming ribbons propagating along the [10] direction. In the crystal of (II), mol-ecules are linked by C-H⋯O hydrogen bonds, forming a supra-molecular framework. The Hirshfeld surface analyses indicate that for both compounds the H⋯H contacts are the most significant, followed by O⋯H/H⋯O and C⋯H/H⋯C contacts.

Divergent Synthesis and Evaluation of the in†vitro Cytotoxicity Profiles of 3,4-Ethylenedioxythiophenyl-2-propen-1-one Analogues.

A new series of 3,4-ethylenedioxythiophene (EDOT)-appended propenones were prepared by condensation reaction and their in vitro cytotoxicity effects were evaluated against five human cancer cell lines. Preliminary structure-activity relationships of EDOT-incorporated 2-propenone derivatives were also established. The EDOT-appended enones demonstrated significant cytotoxicity against human cancer cell lines. The most active analogue, (E)-3-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (3 p, GI50 =110 nm), severely inhibited the clonogenic potential of cancer cells, and induced cell-cycle arrest in the G2/M phase and caused an accumulation of HCT116 colon cancer cells with >4 N DNA content. Also, 3 p exhibited weak inhibition of the enzymatic activity of human topoisomerase I. Molecular docking studies indicated preferential binding of the compounds to the ATP-binding pocket of the human checkpoint 2 kinase (Chk2) catalytic domain, thus, identifying a novel diaryl 2-propenone chemotype for the development of potent inhibitors of Chk2.

A Single Step Fast Track Methodology for In-Situ Detection of Hazardous Melamine by Using Highly Sensitive Polyphenolics Modified Nanogold Probe.

A single step fast track method is proposed to determine melamine based on strong hydrogen bonding between exocyclic amine group in melamine moiety and hydroxyl group of tannic acid (TA); acting as reducing and functionalizing agent for synthesis of gold nanoparticles (Au NPs). The proposed strategy is facile and highly time saving; as the detection of melamine with labelfree gold nanoparticles was accomplished within five minutes. The colorimetric probe exhibits high detection limit of 8 nM for melamine determination in raw milk, which is very low as compared to other capping ligands employed for Au NPs such as borohydride, citrate and 3,5-dihydroxybenzoic acid. The results show a highly sensitive linear range (0.03-2.5 µM) between absorption ratio and concentration of melamine with a correlation coefficient of 0.991. Proposed methodology is proven effective for on-site screening without using costly instrumentation.

Relationship of sociodemographic factors with serum levels of vitamin D in a healthy population of Pakistan.

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and monthly household income emerged as predictors of hypovitaminosis D. Mean serum 25(OH)D levels in the groups with monthly household income less than Pakistani Rupees (PKR) 20,000, between PKR 20,000-50,000 and above PKR 50,000 were found to be 11.0±7.5, 13.9±9.6 and16.9±11.7 ng/ml, respectively. Using logistic regression the odds of having vitamin D deficiency was 3.22 (95% CI, 1.65-6.28) in the group with household income less than PKR 50,000 per month compared to the group with household income more than PKR 50,000 per month when the model was adjusted for gender and exposure to sunlight. There is an association between household income and hypovitaminosis D in a healthy Pakistani population.