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This study presents a computational investigation of a stochastic Zika virus along with optimal control model using the Legendre spectral collocation method (LSCM). By accumulation of stochasticity into the model through the proposed stochastic differential equations, we appropriating the random fluctuations essential in the progression and disease transmission. The stability, convergence and accuracy properties of the LSCM are conscientiously analyzed and also demonstrating its strength for solving the complex epidemiological models. Moreover, the study evaluates the various control strategies, such as treatment, prevention and treatment pesticide control, and identifies optimal combinations that the intervention costs and also minimize the proposed infection rates. The basic properties of the given model, such as the reproduction number, were determined with and without the presence of the control strategies. For R 0 < 0 , the model satisfies the disease-free equilibrium, in this case the disease die out after some time, while for R 0 > 1 , then endemic equilibrium is satisfied, in this case the disease spread in the population at higher scale. The fundamental findings acknowledge the significant impact of stochastic phonemes on the robustness and effectiveness of control strategies that accelerating the need for cost-effective and multi-faceted approaches. In last the results provide the valuable insights for public health department to enabling more impressive mitigation of Zika virus outbreaks and management in real-world scenarios. [ABSTRACT FROM AUTHOR]

In this work, we study the cosmological dynamics of the early universe by employing a small field potential in the context of multifield inflation. By investigating analytically the cosmological observables, such as the number of e-folds N , potential slow-roll parameters ϵ V , η V , and spectral index n s which carry significant information, we show that they impact the inflationary universe considerably. The tensor-to-scalar ratio concerning the curvature perturbation is worked out for the potential under consideration which is another significant observable and comes out to be nonnegative. In multifield models of inflation, both types of curvature and isocurvature perturbations exist, while, in the present work, during the slow-roll, isocurvature perturbations are suppressed and therefore can be neglected. The surviving perturbations which are due to the curvature only can be tackled suitably by a mechanism developed by Sasaki and Stewart known as Sasaki–Stewart formalism. The effect of augmenting the number of e-folds on the power spectrum through the spectral index and its impact on the observable parameters of the slow-roll inflationary phase is observed by carrying out the analysis. It is observed analytically that the spectrum of multifield inflation is effectively different than its corresponding single-field inflation. The field values and their masses affect the results profoundly at the time of horizon-crossing. [ABSTRACT FROM AUTHOR]

This study investigated teachers’ perceptions regarding classroom practices in the induction program at primary level in Khyber Pakhtunkhwa (KP). The integral aim of this research was ‘to investigate teachers’ perceptions regarding classroom practices in the induction program at primary level’. The data was collected from 220 randomly sampled male primary schools teachers located in four tehsils of District Mardan of KP. To collect the data from the sample a questionnaire was used by the researcher. The findings of the study indicated that induction program enabled (in-service) trainees to implement the classroom management strategies, maintain discipline in classroom and teach the students confidently, to teach the students according to lesson plan, engage students in activity-based learning, provide opportunity to students for asking questions and engage students in co-curricular activities and encouraged trainees to evaluate students’ performance effectively. On the basis of findings, it is recommended that such types of productive trainings shall be implemented by the Government in order to build the capacity of teachers for effective teaching and learning. [ABSTRACT FROM AUTHOR]

Energy security has become an important topic, especially after the recent Russian-Ukraine conflict. Amongst the European Union (EU) nations, Italy in particular has been the most affected by such energy crises. To address such a concern, this study aims to determine a sustainable energy mix for Italy to ensure affordable, clean, and reliable energy in the country. The existing energy mix consisting of seven energy alternatives are evaluated based on the metrics of technological, socio-political, economic, and environmental aspects. A fuzzy quantitative strategic decision-making approach known as the Fuzzy Strength, Weakness, Opportunity, and Threat (F-SWOT) tool is employed to materialize this goal. In the SWOT matrix, hydro and biopower have been placed in the first quadrant showcasing strengths and opportunities for its development in Italy. Moreover, solar and wind power have been placed in the second quadrant both showcasing considerable opportunities for its development, however face a few weaknesses as well. Moreover, geothermal and coal power have been placed in the third quadrant, both showcasing weaknesses and threats to the energy security of the country. Lastly, natural gas in the fourth quadrant showcases strengths but poses a substantial threat to the energy security of the country. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the frequency of first-line antiretroviral therapy (ART) resistance among HIV patients and to identify the factors affecting the drug resistance. Methods: A cross-sectional study was conducted over a sample of 162 HIV-positive patients attending the Medicine Department of Lady Reading Hospital, Peshawar-Pakistan, from July 2020 to January 2021. Blood samples were collected for phylogenic profiles to determine first-line antiretroviral therapy resistance. Results: The frequency of ART resistance was detected in 64.8% of the enrolled HIV patients. Factors such as patient age, gender, comorbidities, and smoking status had no significant impact on drug resistance. While only body mass index (BMI) significantly affected ART resistance among HIV patients. The drug resistance mutations M184V and K103N were detected in the nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), respectively, whereas the mutations G73SC and I47VA were detected in the protease inhibitors (PIs). Conclusion: There is a high frequency of resistance to first-line antiretroviral therapy among HIV patients presenting to the selected healthcare facility in Peshawar. Furthermore, we found no significant factors impacting ART resistance among HIV patients other than BMI. [ABSTRACT FROM AUTHOR]

This article aims to investigate the pathwise convergence of the higher order scheme, introduced by Jentzen (2011) [9] , for the stochastic Burgers' equation (SBE) driven by space-time white noise. In particular, first and second order derivatives of the non-linear drift term of the SBE are assumed to be defined and bounded in Sobolev spaces using the definition of distribution derivative i.e. Lemma 4.7 in Blömker and Jentzen (2013) [2] is extended. Based on this extension, temporal convergence analysis of the higher order scheme is carried out for the SBE with additive noise. As a result, minimum temporal convergence order is improved from θ (Theorem 4.1 in Blömker et al. (2013) [3]) to 2 θ , where every θ ∈ (0 , 1 2)). Numerical experiments are performed to validate the theoretical findings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To Assess the Role of Antioxidant, Lipid Peroxidation Status and Lipid Profile in various stages of Psoriasis Patients. METHODOLOGY: The present study was a Case Control. It was carried out in the Department of Biochemistry, at Basic Medical Sciences Institute (BMSI) Jinnah Post Graduate Medical Centre from April - December 2015. One hundred and twenty cases of psoriasis patients grouped as Mild, Moderate, Severe and Forty healthy control for comparison was included in the study. Lipid Profile including serum total cholesterol, Triglyceride (TG), - high density lipoproteins (HDL) and low- density lipoproteins (LDL), were estimated by enzymatic colorimetric Method on Micro lab 300 (Merck & Germany) and Antioxidant status like Superoxide Dismutase (SOD) and Lipid Peroxidation status like Malondialdehyde (MDA) were measured by ELISA. The statistical analysis was performed by SPSS software Version 16. P value less than 0.005 was considered significant. RESULTS: Our result showed significantly increase in the mean serum level of triglycerides (TG), Total Cholesterol and low density lipoproteins in psoriatic patients when compared to control where as high density Lipoproteins was significantly decline in psoriatic groups when compared to control while SOD level was reduced in psoriasis patients as compared to control. The MDA level was raised in psoriasis patients as compared to control. CONCLUSION: The finding of our study support the hypothesis that imbalance in oxidant-antioxidant system play role in the etiology of psoriasis. Also dyslipidemia was observed risk factor for development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Abstract This paper aims to extend the scheme proposed in Jentzen et al. (2011) for stochastic partial differential equations (SPDEs) with global Lipschitz coefficients to non-global Lipschitz coefficients. We investigate the pathwise convergence of the scheme for a class of semilinear parabolic SPDEs with non-globally Lipschitz nonlinearity. We show first that the scheme is convergent uniformly in time and space under Lipschitz assumption on the nonlinearity of the SPDE, then we obtain the convergence in the case of non-globally Lipschitz nonlinearity via a localization technique. Compared to the scheme introduced in Jentzen (2009) for SPDEs under non-global Lipschitz coefficients, the scheme considered in this paper is simpler in the sense that the former uses two linear functionals of the noise while the latter uses one. [ABSTRACT FROM AUTHOR]

Holy basil (Ocimum sanctum L.) and sweet basil (Ocimum basilicum L.) are the most commonly grown basil species in India for essential oil production and biosynthesis of potentially volatile and non-volatile phytomolecules with commercial significance. The aroma, flavor and pharmaceutical value of Ocimum species is a significance of its essential oil, which contains most of the monoterpenes and sesquiterpenes. A large number of plants have been studied for characterization and identification of terpene synthase genes, involved in terpenoids biosynthesis. The goal of this study is to discover and identify the putative functional terpene synthase genes in O. sanctum. HMMER search was performed by using a set of 13 well sequenced and annotated plant genomes including the newly sequenced genome of O. sanctum with Pfam-A database locally, using HMMER 3.0 hmmsearch for the two Pfam domains (PF01397 and PF03936). Using this search method 81 putative terpene synthases genes (OsaTPS) were identified in O. sanctum; the study further reveals 47 OsaTPS were putatively functional genes, 19 partial OsaTPS, and 15 OsaTPS as probably pseudogenes. All these identified OsaTPS genes were compared with other plant species, and phylogenetic analysis reveals the subfamily classification of OsaTPS in TPS-a, -b, -c, -e, -f and TPS-g subfamilies clusters. This genome-wide identification of OsaTPS genes, their phylogenetic analysis and secondary metabolite pathway mapping predictions together provide a comprehensive understanding of the TPS gene family in Ocimum sanctum and offer opportunities for the characterization and functional validation of numbers of terpene synthase genes. [ABSTRACT FROM AUTHOR]

Identification of hit compounds against specific target form the starting point for a drug discovery program. A consistent decline of new chemical entities (NCEs) in recent years prompted a challenge to explore newer approaches to discover potential hit compounds that in turn can be converted into leads, and ultimately drug with desired therapeutic efficacy. The vast amount of omics and activity data available in public databases offers an opportunity to identify novel targets and their potential inhibitors. State of the art in silico methods viz ., clustering of compounds, virtual screening, molecular docking, MD simulations and MMPBSA calculations were employed in a pipeline to identify potential ‘hits’ against those targets as well whose structures, as of now, could only predict through threading approaches. In the present work, we have started from scratch, amino acid sequence of target and compounds retrieved from PubChem compound database, modeled it in such a way that led to the identification of possible inhibitors of Dam1 complex subunit Ask1 of Candida albicans . We also propose a ligand based binding site determination approach. We have identified potential inhibitors of Ask1 subunit of a Dam1 complex of C. albicans , which is required to prevent precocious spindle elongation in pre-mitotic phases. The proposed scheme may aid to find virtually potential inhibitors of other unique targets against candida. [ABSTRACT FROM AUTHOR]

Pancreatic lipase (PL) plays a vital role in lipid metabolism-associated disorders, especially obesity. The present study demonstrates the targeted isolation of biologically active compounds from Andrographis paniculata root with dietary fat absorption capacity for obesity management. The HPLC-based micro-fractionation and off-line in-vitro pancreatic lipase inhibition assay have resulted in potential phytochemicals with IC 50 value 4.46–21.76 µg/mL. 7-O-methyl-dihydro wogonin (MDHW) was the most potent with IC 50 = 14.86 ± 0.19 μM than reported flavanones. The MDHW has also exhibited a synergistic effect with orlistat at a concentration lower than 14.86 μM. MDHW acts as a competitive inhibitor via energy transfer from PL. The binding interaction of MDHW with PL was hydrophobic (Ka=1.40 ×103 L/mol). FT-IR studies showed the stable and compact MDHW -PL complex as the percentage of β -turn, β-antiparallel and random coil increased, while the portion of the α-helix, β-sheet decreased. Additionally, in-silico studies have also confirmed the non-polar interaction of MDHW with the protein's active site (PBD:1ETH) by spontaneous H-bonds. Results suggested that MDHW isolated from A. paniculata root showed high PL inhibitory activity and binding affinity (Ki =7.4 µM), promising a potential anti-obesity agent for pharmaceutical and food industry applications. [Display omitted] • First report on pancreatic lipase (PL) inhibitory activity of 7-O-methyl-dihydro wogonin (MDHW). • MDHW showed high PL inhibitory activity than reported flavnone and iridoid glycoside. • Fluorescence, spectroscopic and thermodynamic studies supported the formation of PL-MDHW complex. • MDHW inhibits lipase spontaneously in a competitive manner. • MDHW showed potential for functional food for obesity management. [ABSTRACT FROM AUTHOR]

To achieve higher standards of sustainability, Pakistan has to shift towards the adoption of the Circular Bio-Economy (CBE) approach in its agriculture sector. However, to aid this transition, the determination of a sustainable waste management technology and supporting strategies is very essential. For this purpose, a hybrid methodology based on fuzzy Strength, Weakness, Opportunities, and Threats (SWOT) and fuzzy Technique for Order Preference by Similarity to the Ideal Solution (TOPSIS) is developed. The fuzzy approach used in both the cases is to address any sort of ambiguity during the decision-making process. From the fuzzy SWOT analysis, the decision-makers allocated the most importance to the "ease of adoption" criteria, among the list of internal factors. Whereas, from the list of external factors, the most importance was allocated to the "price competitiveness with respect to fossil feedstock" criteria. Also, composting and anaerobic digestion are considered to be the most sustainable technologies for valorizing the agricultural waste of Pakistan. However, composting showcases more opportunities for its adoption as compared to anaerobic digestion. Whereas, results from fuzzy TOPSIS suggest the provision of financial support to both the local farmers and investors to be the top-ranked strategy for the successful implementation of the CBE approach. [ABSTRACT FROM AUTHOR]

Abstract: Background: Enamel synthesis is a highly dynamic process characterized by simultaneity of matrix secretion, assembly and processing during apatite mineralization. MMP-20 is the first protease to hydrolyze amelogenin, resulting in specific cleavage products that self-assemble into nanostructures at specific mineral compositions and pH. In this investigation, enzyme kinetics of MMP-20 proteolysis of recombinant full-length human amelogenin (rH174) under different mineral compositions is elucidated. Methods: Recombinant amelogenin was cleaved by MMP-20 under various physicochemical conditions and the products were analyzed by SDS-PAGE and MALDI-TOF MS. Results: It was observed that mineral ions largely affect cleavage pattern, and enzyme kinetics of rH174 hydrolysis. Out of the five selected mineral ion compositions, MMP-20 was most efficient at high calcium concentration, whereas it was slowest at high phosphate, and at high calcium and phosphate concentrations. In most of the compositions, N- and C-termini were cleaved rapidly at several places but the central region of amelogenin was protected up to some extent in solutions with high calcium and phosphate contents. Conclusion: These in vitro studies showed that the chemistry of the protein solutions can significantly alter the processing of amelogenin by MMP-20, which may have significant effects in vivo matrix assembly and subsequent calcium phosphate mineralization. General significance: This study elaborates the possibilities of the processing of the organic matrix into mineralized tissue during enamel development. [Copyright &y& Elsevier]

In the present work, quantitative structure-activity relationship (QSAR) models of camptothecin derivatives against DNA Topoisomerase-I (DNA Topo-I) were developed by multiple linear regression method using leave-one-out validation approach. The r2 and rCV2 of the model were 0.89 and 0.86, respectively. The QSAR study indicates that chemical descriptors, namely Connectivity Index (order 1, standard), Electron Affinity (eV), Molecular Weight, Group Count (ether) are correlated well with activity. Further, screening for drug likeness, ADME and toxicity showed that compound CPT9, CPT14, CPT20, CPT21 and CPT22 exhibits marked anticancer activity and possesses two times more potent than standard drug camptothecin. The docking study showed a high binding affinity of predicted active derivatives and showed H-bond formation with GLY363, ARG364, LYS374, GLN421, ARG488, and ASP-533 residues, therefore considered as more stable and potent anticancer compounds. The obtained results can be used for the design of novel potent and selective inhibitors of DNA Topo-I. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Two triterpenoids ursolic acid (1) and lupeol (2) isolated and characterized from Eucalyptus tereticornis and Gentiana kurroo were subjected to in silico QSAR modeling and docking studies and later the predicted results were confirmed through in vivo experiments. QSAR modeling results showed that both the triterpenoids possess immunomodulatory and anti-inflammatory activity comparable to boswellic and cichoric acids, but were less active than levamisol. Docking results suggested that both the triterpenoids (1 and 2) showed immune modulatory and anti-inflammatory activity due to high binding affinity to human receptors viz., NF-kappaB p52 (−50.549kcal/mol), tumor necrosis factor (TNF-alpha) (−47.632kcal/mol), nuclear factor NF-Kappa-B P50 (−16.798kcal/mol) and cyclooxygenase-2 (−55.244kcal/mol). Further both the triterpenoids (1 and 2) were subjected to in vivo immunomodulatory activity in female Swiss albino mice. The experimental mice were divided into nine groups, each comprised of six mice. These received oral treatment for a period of 28days. The triterpenoids (1 and 2) showed significant increased in humoral immune function, but no significant changes were observed in cell mediated immune response and hematological parameters. The in silico and in vivo experimental data suggested that both the triterpenoids 1 and 2 may be considered as potential immunomodulatory drug-like molecules. [Copyright &y& Elsevier]

Plasmodium falciparum, a causitive agent of malaria, is the third most prevalent factor for mortility in the world. Falciparum malaria is an example of evolutionary and balancing selection. Because of mutation and natural selection, the parasite has developed resistance to most of the existing drugs. Under such circumstances, there is a growing need to develop new molecular targets in P. falciparum. A four membrane bound organelles called apicoplast, very much similar to that of chloroplast of plants, have been found in parasite. Therefore, the proteins involved in metabolic pathways of apicoplasts are important drug targets. Among the pathways in apicoplast, fatty acid biosynthetic pathway is the most important metabolic pathway in P. falciparum. Several studies have explored the role of different proteins involved in this pathway and antimalarial compounds against this target. In this review, we have studied the role of different proteins in fatty acid metabolism and designing, synthesis and evaluation of compounds against the targets identified in fatty acid metabolic pathway. [ABSTRACT FROM AUTHOR]

Immunomodulation refers to an alteration in the immune response due to the intrusion of foreign molecules into the body. In the present communication, QSAR and docking studies of gallic acid derivatives were performed in relation to their immunomodulatory activities. Screening through the use of a QSAR model suggested that the compounds G-4, G-7, G-9, G-10, G-12, and G-13 possess immunomodulatory activity. Activity was predicted using a statistical model developed by the forward stepwise multiple linear regression method. The correlation coefficient ( r) and the prediction accuracy ( rCV) of the QSAR model were 0.99 and 0.96, respectively. The QSAR study indicated that chemical descriptors-dipole moment, steric energy, amide group count, λ (UV-visible) and molar refractivity-are well correlated with activity, while decreases in the dipole moment, steric energy, and molar refractivity were negatively correlated. A molecular docking study showed that the compounds had high binding affinities for the INFα-2, IL-6, and IL-4 receptors. Binding site residues formed H-bonds with the designed gallic acid derivatives G-3, G-4, G-5, G-6, G-7, and G-10. Moreover, based on screening for oral bioavailability, in silico ADME, and toxicity risk assessment, we concluded that compound G-7 exhibits marked immunomodulatory activity, comparable to levamisole. [ABSTRACT FROM AUTHOR]

Khan F, Li W, Habelitz S. Biophysical characterization of synthetic amelogenin C-terminal peptides. Eur J Oral Sci 2012; 120: 113-122. © 2012 Eur J Oral Sci Amelogenin plays a key role in the formation of the highly mineralized structure of tooth enamel. During the secretory stage, amelogenin is cleaved gradually by a protease, matrix metalloproteinase-20 (MMP-20), releasing hydrophilic C-terminal peptides. In this study, the biophysical properties of synthetic C-terminal peptides (of 28, 17, and 11 residues), mimicking native peptides, were explored in vitro. A sudden decrease was observed in the zeta (ζ)-potential upon the addition of calcium or phosphates, which was also accompanied by an increased aggregation propensity of the peptides. Under most of the experimental conditions, the particle size increased at a pH 2-3 units higher than the isoelectric point (pI) of the peptides, while the peptides existed as smaller particles (<2 nm) near their pI values and in the acidic range. They showed poor affinity for calcium and phosphates, comparable to full-length amelogenin and variants. The secondary structure determination showed that the 11-amino-acid peptide contained defined secondary structure comprising beta-sheets and turns. Atomic force microscopy analysis revealed the presence of thin, disk-like nanostructures of 54.4 nm diameter for the 28-amino-acid peptide and 54.9 nm diameter for the 11-amino acid peptide, whereas no definite structures were observed for the 17-amino-acid peptide. It is concluded that the amelogenin C-terminal peptides are capable of interacting with calcium and phosphate ions, of self-assembly into nanostructures, and may have some secondary structure, and hence may have some role in enamel synthesis. [ABSTRACT FROM AUTHOR]

Abstract: In the following respects, tooth enamel is a unique tissue in the mammalian body: (a) it is the most mineralized and hardest tissue in it comprising up to 95wt% of apatite; (b) its microstructure is dominated by parallel rods composed of bundles of 40–60nm wide apatite crystals with aspect ratios reaching up to 1:10,000 and (c) not only does the protein matrix that gives rise to enamel guides the crystal growth, but it also conducts its own degradation and removal in parallel. Hence, when mimicking the process of amelogenesis in vitro, crystal growth has to be coupled to proteolytic digestion of the amelogenin assemblies that are known to play a pivotal role in conducting the proper crystal growth. Experimental settings based on controlled and programmable titration of amelogenin sols digested by means of MMP-20 with buffered calcium and phosphate solutions were employed to imitate the formation of elongated, plate-shaped crystals. Whilst amelogenin can act as a promoter of nucleation and crystal growth alone, in this study we show that proteolysis exerts an additional nucleation- and growth-promoting effect. Hydrolysis of full-length amelogenin by MMP-20 decreases the critical time needed for the protein and peptides to adhere and to cover the substrate. The formation and immobilization of a protein layer subsequently reduces the time for calcium phosphate crystallization. Coupling the proteolytic reaction to titration in the presence of 0.4mg/ml rH174 has been shown to have the same effect on the crystal growth promotion as quadrupling the concentration of rH174 to 1.6mg/ml. Controlling the rate and the extent of the proteolytic cleavage can thus be used to control the nucleation and growth rates in a protein-guided crystallization system. [Copyright &y& Elsevier]

The article examines past arms control agreements and confidence-building measures undertaken between India and Pakistan, and how they could be made more effective in the future. Major agreements and treaties between the two countries since partition in 1947 are reviewed, including the 1949 Karachi Agreement following the Kashmir War, the 1966 Tashkent Agreement following the 1965 Indo-Pakistani conflict, the 1999 Lahore Agreement over nuclear weapons, and others. The strategic concerns and military doctrine of each nation are discussed as well.

Abstract: Advancement in the field of proteomics and bioinformatics offers tremendous opportunities for the development of novel epitope-based effective vaccine against human malaria. In this study, we have characterized 25 antigens as a vaccine candidate and screened the potential T-lymphocyte epitopes presented by human leukocyte antigen (HLA)-A, -B, and -DR molecules based on the proteomic data of Plasmodium falciparum. Of the 25 proteins, 22 were predicted as probable antigens and two were predicted as adhesions. In addition, seven proteins were predicted to contain signal peptide for secretary pathway and six proteins were found similar to the human and mouse reference proteins, whereas none of the proteins were predicted as allergen. A total of 14,841 peptides were predicted as epitope, presented by HLA class I and II supertypes that covered a broad human population (∼95%). Our results suggest that HLA-based multistage and multiepitope malaria vaccine would likely be needed to induce broader CD8+ as well as CD4+ T-cell responses. The predicted epitopes may be served as a useful diagnostic reagent for evaluating T-cell responses in the context of natural infection and/or vaccine trials. [Copyright &y& Elsevier]

The solute quenching studies of a lectin from endophytic fungus Fusarium solani were carried out using different quenchers such as acrylamide, succinimide, potassium iodide and cesium chloride. The lectin showed emission maximum at 348 nm indicating relative exposure of tryptophan. The quenchable fraction of the fluorophore was 100% with acrylamide, whereas it was only 50% with succinimide. The ionic quenchers iodide and cesium showed opposite effects at different pH. In the case of cesium, raising the pH resulted in increased quenching and accessibility of typtophan residue, while the iodide showed just opposite effect. These studies showed that the single tryptophan residue of the lectin (per monomer) is relatively exposed, and might be in the vicinity of positively charged amino acid residues. Various amino acids of the F. solani lectin were modified using different reagents to obtain information about the hemagglutinating site. The chemical modification studies suggested tyrosine residues can be modified using Nacetylimidazole, which results in complete loss of hemagglutination activity of the lectin. Kinetics of chemical modification suggested involvement of only 2 tyrosine residues. Modification of arginine, cysteine, histidine, lysine, aspartate, glutamate and tryptophan did not result in loss of hemagglutinating activity of the lectin. [ABSTRACT FROM AUTHOR]

The intrinsic fluorescence intensity of Fusarium solani lectin was quenched upon binding to mono- and oligosaccharides without any change in the emission maximum and it was used to determine association constants for several sugars and glycans. The lectin interacted very poorly with monosaccharides but well with disaccharides (T-antigen and LacNAc) with a distinction between β1→4 and β1→3 linkages. Among the monosaccharides, the interaction was observed only with Gal/GalNAc derivatives and not with Glc/Man derivatives. Thermodynamic studies revealed that the binding of the lectin with all the saccharides is enthalpically driven and exothermic in nature. Asialo-triantennary N-glycan and asialo-biantennary N-glycan showed higher affinity than monovalent LacNAc with significant increase in binding enthalpy, pointing towards the importance of multivalency in the lectin–ligand interactions. Time-resolved fluorescence measurement indicated the lectin has two lifetimes for tryptophan and the shorter lifetime is affected on ligand binding. [ABSTRACT FROM AUTHOR]

Abstract: A lectin from the mycelial extract of an endophytic strain of Fusarium solani was purified. Its hemagglutinating activity was inhibited by glycoproteins possessing N-linked as well as O-linked glycans. The thermodynamics and kinetics of binding of glycans and glycoproteins to F. solani lectin was studied using surface plasmon resonance. The lectin showed high affinity for asialofetuin, asialomucin, asialofibrinogen, and thyroglobulin; and comparatively low affinity for mucin, fetuin, fibrinogen, and holotransferrin. Glycoproteins showed several fold higher affinity than their corresponding glycans with significant contribution from enthalpy and positive entropy, suggesting the involvement of non-polar protein–protein interaction. Moreover, the higher affinity of the glycoproteins was due to their faster association rates and low activation energy. [Copyright &y& Elsevier]

The effect of urea, guanidine thiocyanate, temperature and pH was studied on the conformational stability of Fusarium solani lectin. Equilibrium unfolding with chemical denaturants showed that the lectin was least stable at pH 12 and maximally stable at pH 8.0 near its pI (8.7). Guanidine thiocyanate (the concentration of denaturant at which the protein is half folded, D1/2 = 0.49 M at pH 12) was found to be an eight times stronger denaturant than urea (D1/2 = 3.88 M at pH 12). The unfolding curves obtained with fluorescence and CD measurements showed good agreement indicating a monophasic nature of unfolding and excluded the possibility of formation of any stable intermediate. The effect of pH on the lectin was found to be unusual as at acidic pH, the lectin showed a flexible tertiary structure with pronounced secondary structure, and retained its hemagglutinating activity. On the other hand, the lectin did not show any loss of conformation or activity upto 70°C for 15 min. Moreover, thermal denaturation did not result in the aggregation or precipitation of the protein even at high temperatures. Thermal denaturation was also carried out in the presence of a low concentration of guanidine thiocyanate. Change in the enthalpy of transition (ΔHm) varied linearly with transition temperature (Tm), which indicated that the heat capacity (ΔCp = 3.95 kJ · mol-1 · K-1) of the lectin remained constant during the unfolding. IUBMB Life, 59: 34–43, 2007 [ABSTRACT FROM AUTHOR]

NodD transcription factor is a regulatory protein of nitrogen fixing bacteria, which activates expression of nod genes participating in nodulation during interaction with its symbiont legumes. It's DNA binding motifs have been characterized and reported in Sinorhizobium meliloti and this pattern information has been used in our theoretical analyses to detect its novel regulated genes in genomes of S. meliloti and Mesorhizobium loti. M. loti, a symbiont to model legume plant Lotus japonicus, showed presence of these regulatory motifs in upstream sequences of nod and other functionally related genes. The methodology involved comparative potential weight matrix construction through GIBBS SAMPLER (RSAT) and MEME tools, using information of conserved upstream sequences of nine genes including nod and neighboring genes of both genomes possessing nod-box like motif. The resultant DNA consensus sequence had highly conserved nod-box like 17 bp long motif consensus sequence pattern for binding of detected NodD transcription factors as analyzed by homologous clustering method and therefore the genome wide predictions were considered highly accurate since confirmed by operon delineation method and the described methodology can be used in other nitrogen fixing bacteria to pursue the study in detail. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) caused by the Mycobacterium tuberculosis (MTB) pathogen is a serious contagious illness that endangers the public's health. However, TB is treatable but due to the result of ineffective and protracted medication, MDR‐MTB and XDR‐MTB were able to develop, making their eradication highly challenging and necessitating potential treatments to be cured. This study aimed to identify the novel inhibitor for the InhA enzyme, a potential target of MTB. Initially, 2721 phytochemicals libraries were screened for ADME/Tox profiling and 49 phytochemicals were filtered out. Moreover, these phytochemicals with reference inhibitor triclosan were docked against InhA (PDB ID: 1BVR)., were showing binding energies ranging from −9.16–−6.3 kcal/mol, whereas triclosan showed −6.90 kcal/mol of binding energy. The docking results reveal that irilone (−9.16 kcal/mol) and aurantio‐obtusin (−8.84 kcal/mol) exhibit promising binding energy and perfectly occupy the binding site of InhA. Furthermore, molecular dynamics simulation (MDS) and MMGBSA studies showed better affinities of selected compounds in terms of stability, compactness, flexibility, and total BFE in complexes with InhA. This study concluded that irilone and aurantio‐obtusin could be promising InhA inhibitors based on their impressive pharmacokinetic profiling, toxicity, binding affinity, and stability. However experimental validation is a subject of further research. [ABSTRACT FROM AUTHOR]

Key message: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand. [ABSTRACT FROM AUTHOR]

Mesoaxial synostotic syndactyly (MSSD) with phalangeal reduction is an uncommon congenital limb abnormality characterized by central osseous synostosis at a metacarpal level, mesoaxial reduction of the fingers, and preaxial cutaneous syndactyly in toes. In rare cases, the disease is also associated with fifth finger clinodactyly and postaxial polydactyly. It has autosomal recessive inheritance pattern caused by homozygous variants in the gene BHLHA9 mapped at chromosome 17p13.3. In the present study, a consanguineous family of Pakistani origin segregating MSSD in autosomal recessive form was characterized at clinical and genetic levels. Clinically, the diseased individuals have MSSD associated with clinodactyly and polydactyly. Homozygosity mapping followed by Sanger sequencing of BHLHA9 revealed a novel frameshift variant NM_001164405.1: c.409-409delC; p.(His137Thrfs*61) segregating with the disease phenotypes in the family. This is the second report providing evidence of association of polydactyly with MSSD caused by frameshift variant in the gene BHLHA9. The present molecular investigation will support genetic counselling of the local population carrying diseased variants. [ABSTRACT FROM AUTHOR]

Flavones are known as an inhibitor of tankyrase, a potential drug target of cancer. We here expedited the use of different computational approaches and presented a fast, easy, cost-effective and high throughput screening method to identify flavones analogs as potential tankyrase inhibitors. For this, we developed a field point based (3D-QSAR) quantitative structure-activity relationship model. The developed model showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 (0.89) and q2 (0.67). This model may help to explain SAR data and illustrated the key descriptors which were firmly related with the anticancer activity. Using the QSAR model a dataset of 8000 flavonoids were evaluated to classify the bioactivity, which resulted in the identification of 1480 compounds with the IC50 value of less than 5 µM. Further, these compounds were scrutinized through molecular docking and ADMET risk assessment. Total of 25 compounds identified which further analyzed for drug-likeness, oral bioavailability, synthetic accessibility, lead-likeness, and alerts for PAINS & Brenk. Besides, metabolites of screened compounds were also analyzed for pharmacokinetics compliance. Finally, compounds F2, F3, F8, F11, F13, F20, F21 and F25 with predicted activity (IC50) of 1.59, 1, 0.62, 0.79, 3.98, 0.79, 0.63 and 0.64, respectively were find as top hit leads. This study is offering the first example of a computationally-driven tool for prioritization and discovery of novel flavone scaffold for tankyrase receptor affinity with high therapeutic windows. [ABSTRACT FROM AUTHOR]

Artemisia annua is well-known for producing the antimalarial phytomolecule, artemisinin. The role of peroxidases has been hypothesized in artemisinin metabolism owing to the presence of an -O-O- linkage in this sesquiterpene lactone. Earlier, using a microarray, we identified differentially expressed genes, including peroxidases, in plant growth stages having contrasting artemisinin content. Here, three peroxidases—Aa547, having higher expression in low-artemisinin stage, and Aa540 and Aa528, having higher expression in high artemisinin stage, which could be associated with trichomes on the basis of their approximate gene expression pattern inferred from EST counts in UniGene—were selected for full-length cloning, tissue-specific expression profiling, and in silico analyses. The upstream genomic region of Aa547 was cloned and various cis-regulatory elements were identified. All the three candidates were predicted to be class III plant peroxidases. Further, this study aimed to check the responsiveness of the logically selected peroxidase genes to various abiotic stress factors. Taking cues from previous reports and the regulatory elements observed in the Aa547 promoter, hydration, salinity, temperature, salicylic acid, hydrogen peroxide, and methyl jasmonate, were selected to study their effect on the expression of the peroxidase genes through qRT-PCR. The peroxidases were found to be highly sensitive to the various factors but differed in their responses. Broadly, except for responses to high temperature and salicylic acid, the response of Aa547 to various factors was distinct from that of Aa540 and Aa528, which was in line with its distinctness from the other two peroxidases, considering the in planta artemisinin content and predicted structural features. [ABSTRACT FROM AUTHOR]

Background: Pyrethrins are monoterpenoids and consist of either a chrysanthemic acid or pyrethric acid with a rethrolone moiety. Natural pyrethrins are safe and eco-friendly while possessing strong insecticidal properties. Despite such advantages of commercial value coming with the eco-friendly tag, most enzymes/genes involved in the pyrethrin biosynthesis pathway remain unidentified and uncharacterized. Since the flowers of Tanacetum cinerariifolium are rich in major pyrethrins, next generation transcriptome sequencing was undertaken to compare the flowers and the leaves of the plant de novo to identify differentially expressed transcripts and ascertain which among them might be involved in and responsible for the differential accumulation of pyrethrins in T. cinerariifolium flowers. Results: In this first tissue specific transcriptome analysis of the non-model plant T. cinerariifolium, a total of 23,200,000 and 28,500,110 high quality Illumina next generation sequence reads, with a length of 101 bp, were generated for the flower and leaf tissue respectively. After functional enrichment analysis and GO based annotation using public protein databases such as UniRef, PFAM, SMART, KEGG and NR, 4443 and 8901 unigenes were identified in the flower and leaf tissue respectively. These could be assigned to 13344 KEGG pathways and the pyrethrin biosynthesis contextualized. The 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway was involved in the biosynthesis of acid moiety of pyrethrin and this pathway predominated in the flowers as compared to the leaves. However, enzymes related to oxylipin biosynthesis were found predominantly in the leaf tissue, which suggested that major steps of pyrethrin biosynthesis occurred in the flowers. Conclusions: Transcriptome comparison between the flower and leaf tissue of T. cinerariifolium provided an elaborate list of tissue specific transcripts that was useful in elucidating the differences in the expression of the biosynthetic pathways leading to differential presence of pyrethrin in the flowers. The information generated on genes, pathways and markers related to pyrethrin biosynthesis in this study will be helpful in enhancing the production of these useful compounds for value added breeding programs. Related proteome comparison to overlay our transcriptome comparison can generate more relevant information to better understand flower specific accumulation of secondary metabolites in general and pyrethrin accumulation in particular. [ABSTRACT FROM AUTHOR]

Remarkably the c-Jun-NH2-terminal kinase (JNK) pathway is all evolutionarily conserved across species. In view of the hypothesis that increased stress resistance subdue aging, we investigated the role of ursolic acid (3β-Hydroxy-urs-12-en-28-oic acid; UA) in the pioneering aging model Caenorhabditis elegans with an increase in mean and maximum lifespan by up to 30%. Our genetic study unravelled the underlying pathway where JNK-1 is acting independently of insulin-IGF-1 signalling (IIS) pathway to modulate longevity. In support of in vivo results in silico docking study of UA with C. elegans JNK-1 ATP-binding site suggested promising binding affinity exhibiting binding energy of −8.11 kcalmol −1 . UA induced JNK-1 activation in wild-type animals underlie the importance of pharmacological interventions in the delineation of molecular targets for aging and associated pathologies. [ABSTRACT FROM AUTHOR]

The emergence of multi-drug-resistant Mycobacterium tuberculosis (Mtb) strains has rendered many of the currently available anti-TB drugs ineffective. Hence, there is a pressing need to discover new potential drug targets/candidates. In this study, attempts have been made to identify novel inhibitors of the ribonuclease VapC2 of Mtb H37Rv using various computational techniques. Ribonuclease VapC2 Mtb H37Rv's protein structure was retrieved from the PDB databank, 22 currently used anti-TB drugs were retrieved from the PubChem database, and protein–ligand interactions were analyzed by docking studies. Out of the 22 drugs, rifampicin (RIF), being a first-line drug, showed the best binding energy (−8.8 Kcal/mol) with Mtb H37Rv VapC2; hence, it was selected as a parent molecule for the design of its derivatives. Based on shape score and radial plot criteria, out of 500 derivatives designed through SPARK (Cresset®, Royston, UK) program, the 10 best RIF derivatives were selected for further studies. All the selected derivatives followed the ADME criteria concerning drug-likeness. The docking of ribonuclease VapC2 with RIF derivatives revealed the best binding energy of −8.1 Kcal/mol with derivative 1 (i.e., RIF-155841). A quantitative structure–activity relationship study revealed that derivative 1's activity assists in the inhibition of ribonuclease VapC2. The stability of the VapC2–RIF155841 complex was evaluated using molecular dynamics simulations for 50 ns and the complex was found to be stable after 10 nsec. Further, a chemical synthesis scheme was designed for the newly identified RIF derivative (RIF-155841), which verified that its chemical synthesis is possible for future in vitro/in vivo experimental validation. Overall, this study evaluated the potential of the newly designed RIF derivatives with respect to the Mtb VapC2 protein, which is predicted to be involved in some indispensable processes of the related pathogen. Future experimental studies regarding RIF-155841, including the exploration of the remaining RIF derivatives, are warranted to verify our current findings. [ABSTRACT FROM AUTHOR]

Objective: To assess the author and journal self-citation amongst journals of Khyber Pakhtunkhwa. Methods: This is a cross-sectional study conducted from January 2021 to July 2021. In total, manuscript published in 10 journals of Khyber Pakhtunkhwa, either recognized by the Higher Education Commission or Pakistan Medical Commission, in the years 2018 and 2019 were included in the present research. All types of manuscripts were analyzed using a pre-designed data extraction table. Results were extracted, analyzed and appropriate statistics were applied. Results: About 1235 manuscripts published in 68 issues over a period of two years’ time were analyzed. The majority of manuscripts were 1039 (84.1%) original articles followed by case reports 90 (7.3%). Author selfcitation came out to be 11.26% and journal self-citation was 6.5%. The same institute’s author affiliation came out to be 40.6%. Conclusion: The trend of author self-citation was found to be high while that of journal self-citation was low when compared with already prevalent literature. [ABSTRACT FROM AUTHOR]

Multiferroics are multifunctional materials possessing particularly two significant ferroic orders i.e. ferroelectricity and ferromagnetism. Owing to the technological importance of the multiferroics in a variety of electromagnetic appliances, intensive research has been focused on exploring co-existence and coupling of ferroelectricity and magnetism at room temperature and above. PbTiO 3 is a ferroelectric material with the highest spontaneous polarization P s among all the ferroelectric perovskites. Due to scarcity of multiferroic materials, PbTiO 3 is being extensively studied for induction of magnetism. This review deals with the synthesis and study of induced multiferroic behavior in ferroelectric PbTiO 3 . A variety of synthesis techniques have been discussed for PbTiO 3 powders and films which can be modified to tune the electric and magnetic properties in the material. A detailed discussion is presented on the induction and enhancement of multiferroicity in PbTiO 3 by substitution of suitable transition-metal dopants and tailoring the size and morphologies. Device applications of the material have been briefly discussed to illustrate its technological importance. Finally the review has been concluded with future perspectives. [ABSTRACT FROM AUTHOR]

[Display omitted] Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC 50 value 8.5–25.0 µM. Amongst all, four potential molecules viz 19b , 19e , 22a , and 22c , were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -β. [ABSTRACT FROM AUTHOR]

A new COVID-19 variant, Omicron, has emerged from South Africa, indicating that the pandemic will not be over anytime soon. An unimaginable amount of economic damage has resulted from the pandemic. Omicron and its economic implications are discussed in detail in this review article. It also includes statistics on occurrence, mortality, and recuperation in Pakistan and data on the country's immunization coverage. Developing countries with unstable economies, such as Pakistan, have experienced increased economic difficulties. As a result, all developed and underdeveloped countries should strictly adhere to preventive measures and improvements in diagnostic tests and vaccine development to bring the pandemic under control. [ABSTRACT FROM AUTHOR]

BACKGROUND: Developing safe drugs for tuberculosis (TB), is a major challenge due to upsurge in drug resistance, hepatotoxicity, and the presence of Mycobacterium tuberculosis (Mtb) targets orthologs in human and its non-pathogenic host E. coli. Prostaglandin G/H synthase-2 and 30S ribosomal-S12 protein of Mtb show 100 and 48% similarity with human proteins respectively. Thus, targeting these Mtb proteins by p-aminosalicylic acid and streptomycin for the treatment of TB adversely affect human metabolism, and warrants to identify novel and unique drug targets of Mtb. METHODS: In the present study, in-silico study has been performed to find novel and unique drug targets of Mtb H37Rv. RESULTS : We report ten unique target proteins of Mtb, which do not possess any similarity with human/ non-pathogenic E. coli proteins. Out of 3,993 retrieved proteins of Mtb H37Rv, a total of 1596 and 913 proteins unique to Mtb were identified by comparing with human and E. coli proteome, respectively. Further comparison of 1596 and 913 proteins led to the identification of 515 (out of which, 230 are functionally known) unique proteins of Mtb that are absent in both humans and E. coli. CONCLUSIONS: Gene ontology (GO) analysis of these 230 proteins finally led to the recognition of 10 proteins participated in the various biological processes of Mtb that may serve as potential novel antitubercular drug targets. [ABSTRACT FROM AUTHOR]

• Triple-negative breast cancer (TNBC), is the most aggressive breast cancer subtype, resistant to HER2-targeted and hormonal therapies. • Developed a highly accurate 2D-QSAR model with a regression coefficient (r²) of 0.86 and a cross-validated r² (q²) of 0.8448 to predict IC 50 of triterpene derivatives against TNBC cell line MDA-MB231. • Key molecular descriptors contributing to cytotoxicity against the TNBC MDA-MB231 cell line include electronegativity (Epsilon-3), five-bond carbon separation (T_C_C_5), –CH2 group electrotopological indices (SssCH2count), z-coordinate dipole moment (Zcomp Dipole), and distance between highest positive and negative electrostatic potential on van-der Waals surface area (Most +ve & -ve potential Distance). • Developed an R-package and software tool for virtual screening, available for download on GitHub, aiding in the optimization and development of potent anti-cancer inhibitors against TNBC. Triple-negative breast cancer (TNBC) is the most aggressive cancer type that tests negative for progesterone, estrogen, and HER2 protein receptors. Therefore, TNBC is unlikely to respond either to drugs that target HER2 receptors or to hormonal therapy drugs. In the present study, 2D-QSAR model was developed to predict the inhibitory concentration (IC 50) of terpene derivatives against human breast cancer metastatic cell line MDA-MB231, using V-Life MDS v4.5, module. The model was developed using the forward stepwise multiple linear regression method, with a regression coefficient (r 2) of 0.86, and a cross-validated r 2 (q 2) of 0.8448. Molecular descriptors namely electronegativity (Epsilon-3), carbon atoms separated through five bond distances (T_C_C_5), Sum of Electrotopological state indices of –CH2 group (SssCH2count), Dipole moment of coordinate-z (Zcomp Dipole), and Distance between highest positive and negative electrostatic potential on van-der Waals surface area (Most +ve & -ve Potential Distance) were found to be the most potent contributing chemical descriptors for cytotoxicity against TNBC MDA-MB231 cell line. Additionally, binding affinities and interaction patterns revealed that the proposed compounds exhibit good binding affinities and substantial stability with c-Met-and β-tubulin receptors, as assessed by docking studies. Molecular dynamics simulations (100 ns) and binding free energy calculations were also performed using the MMGBSA method. The pharmacokinetic and eADME/T analysis of predicted compounds were assessed through Discovery Studio software. These findings may be of immense importance in the optimization and development of dual inhibitory potent anti-cancer inhibitors against the MDA-MB231 TNBC cell line. Moreover, this novel QSAR based prediction model/method is implemented in R-package and software tool developed for virtual screening purposes and available online for download through the public repository GitHub. [Display omitted] [ABSTRACT FROM AUTHOR]

The severity and perseverance of inflammation have been demonstrated in many health conditions. The limitations of existing medications suggest the need for new alternative anti-inflammatory medications. In our earlier studies, we demonstrated the topical anti-inflammatory potential of the crude ethanolic extract of Tetrastigma sulcatum leaves and its fractions. In the present study, we further explored the anti-inflammatory activity of T. sulcatum extract, fractions, pure compound and its derivatives using in vitro and in vivo bioassay techniques. We attempted to isolate a pure compound from the leaf extract and identified it as a Friedelan-3β-ol (CI). Furthermore, Friedelinol acetate (C II) and friedelinol methyl ether (C III), derivatives of Friedelan-3β-ol (CI) were synthesised. LPS-induced inflammatory RAW 264.7 macrophages were used as in vitro model to study anti-inflammatory and anti-oxidative effects. Inflammation-induced oxidative damage was found to be restricted significantly (P < 0.001), with scavenging activity and increased SOD activity of crude extract and fractions. Treatment with crude extract (TSETOH) and fractions (TSHEX, TSTOL) significantly reduced (P < 0.001) the mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and nitric oxide (NO) production in LPS-stimulated inflammation in RAW 264.7 cells in a dose-dependent manner. Likewise, compounds CI and CIII showed a similar pattern of significant inhibition (P < 0.001) of pro-inflammatory cytokines and NO production in a dose-dependent manner. An in vivo study in a carrageenan-induced mouse paw oedema model demonstrated reduced paw oedema and pro-inflammatory cytokines in a dose-dependent manner upon treatment with the extract, its fractions, pure compound (CI), and their derivatives (CII, and CIII). The present study confirmed the anti-inflammatory activity of T. sulcatum, suggesting that Friedelan-3β-ol is an active component of the crude extract. [ABSTRACT FROM AUTHOR]

Key message: ANN-based combinatorial model is proposed and its efficiency is assessed for the prediction of optimal culture conditions to achieve maximum productivity in a bioprocess in terms of high biomass. Abstract: A neural network approach is utilized in combination with Hidden Markov concept to assess the optimal values of different environmental factors that result in maximum biomass productivity of cultured tissues after definite culture duration. Five hidden Markov models (HMMs) were derived for five test culture conditions, i.e. pH of liquid growth medium, volume of medium per culture vessel, sucrose concentration (%w/v) in growth medium, nitrate concentration (g/l) in the medium and finally the density of initial inoculum (g fresh weight) per culture vessel and their corresponding fresh weight biomass. The artificial neural network (ANN) model was represented as the function of these five Markov models, and the overall simulation of fresh weight biomass was done with this combinatorial ANN-HMM. The empirical results of Rauwolfia serpentina hairy roots were taken as model and compared with simulated results obtained from pure ANN and ANN-HMMs. The stochastic testing and Cronbach's α-value of pure and combinatorial model revealed more internal consistency and skewed character (0.4635) in histogram of ANN-HMM compared to pure ANN (0.3804). The simulated results for optimal conditions of maximum fresh weight production obtained from ANN-HMM and ANN model closely resemble the experimentally optimized culture conditions based on which highest fresh weight was obtained. However, only 2.99 % deviation from the experimental values could be observed in the values obtained from combinatorial model when compared to the pure ANN model (5.44 %). This comparison showed 45 % better potential of combinatorial model for the prediction of optimal culture conditions for the best growth of hairy root cultures. [ABSTRACT FROM AUTHOR]

In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient ( r) and the cross-validation regression coefficient ( rCV) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation ( r = 0.99 and rCV = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their H and C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values. [ABSTRACT FROM AUTHOR]

Design, synthesis, and bioactivity evaluation of novel mannich bases (2a‐2j) and triazole‐chalcone derivatives (7a‐7k) of Eugenol 1 were reported. Among all the derivatives tested for antiproliferative activity, di‐amine manich derivative 2b (32.92 μM), and 4‐methoxy chalcone triazole derivative 7d (33.05 μM) significantly inhibited HepG2 cell lines when compared to the standard doxorubicin (37.29 μM). Whereas most of the compounds such as diethylamine 2a (17.75 μM), (aminomethyl) methane diamine 2b (17.02 μM), and bis (chloromethyl) amine 2c (20.12 μM) showed moderate to better inhibition towards MCF‐7 cell lines. The synthesized analogues were also tested for antidiabetic and antiobesity potentials. Compounds 2f (55.50%), 2c (54.34%), 7g (55.5%), and 2a (55.5%) have shown moderate inhibitory potentials toward intestinal α‐glucosidase enzyme when compared to the standard Acarbose (72.86%). Likewise, compounds 7d (82.95%), 7f (76.19%), 7g (74.81%), 7e (74.81%), and 2g (72.50%) have shown significant to moderate inhibitory potentials toward Pancreatic lipase enzyme when compared to the standard orlistat (91.10%). ROS induces life‐threatening diseases like diabetes, cancer, etc., and antioxidants play a major role in controlling their production. Compounds 2c (99.81%), 2i (99.80%), 2d (99.26%), 2g (98.79%), and 2f (98.42%) have shown significant antioxidant profiles in ABTS assay when compared to the standard Trolox (99.07%). Further, In silico Molecular docking and pharmacokinetic screening of the eugenol derivatives complemented the in vitro results indicating the drug likeness of the obtained active compounds. [ABSTRACT FROM AUTHOR]

Background: Bangladesh experienced a sudden, large influx of forcibly displaced persons from Myanmar in August 2017. A cholera outbreak occurred in the displaced population during September-December 2019. This study aims to describe the epidemiologic characteristics of cholera patients who were hospitalized in diarrhea treatment centers (DTCs) and sought care from settlements of Forcibly Displaced Myanmar Nationals (FDMN) as well as host country nationals during the cholera outbreak. Methods: Diarrhea Treatment Center (DTC) based surveillance was carried out among the FDMN and host population in Teknaf and Leda DTCs hospitalized for cholera during September-December 2019. Results: During the study period, 147 individuals with cholera were hospitalized. The majority, 72% of patients reported to Leda DTC. Nearly 65% sought care from FDMN settlements. About 47% of the cholera individuals were children less than 5 years old and 42% were aged 15 years and more. Half of the cholera patients were females. FDMN often reported from Camp # 26 (45%), followed by Camp # 24 (36%), and Camp # 27 (12%). Eighty-two percent of the cholera patients reported watery diarrhea. Some or severe dehydration was observed in 65% of cholera individuals. Eighty-one percent of people with cholera received pre-packaged ORS at home. About 88% of FDMN cholera patients reported consumption of public tap water. Pit latrine without water seal was often used by FDMN cholera individuals (78%). Conclusion: Vigilance for cholera patients by routine surveillance, preparedness, and response readiness for surges and oral cholera vaccination campaigns can alleviate the threats of cholera. Author summary: Bangladesh observed a large-scale arrival of forcibly displaced individuals from Myanmar in August 2017. The Bangladesh Government, UN agencies, and international and national non-governmental organizations responded immediately with extensive humanitarian response. However, threats of cholera outbreaks were prevailing. The Government of Bangladesh as lead, with technical support from icddr,b collaborating with international agencies undertook a massive oral cholera vaccination (OCV) campaign immediately as a pre-emptive measure to alleviate threats of the cholera outbreak. Despite that mass OCV campaign, threats of cholera outbreak were existing due to new arrivals of the displaced population with compromised host susceptibility, frequent visits to settlements by Bangladesh nationals without exposure to OCV, and the declining vaccine immunity among OCV recipients as well as an increasing number of cohort children without any exposure to OCV. The population faced a cholera outbreak during September-December 2019. This study aims to describe the characteristics of cholera patients, their care-seeking pattern, camp-wise distribution, source of drinking water, sanitation facility, OCV status, and share the experiences from effective interventions to prevent a cholera outbreak. Vigilance for cholera patients by routine surveillance, preparedness for both preventive and control measures, and response readiness for surges and OCV campaigns can alleviate the threats of cholera. [ABSTRACT FROM AUTHOR]

This paper presents a new implementation of the dual reciprocity method (DRM) in connection with the dual interpolation boundary face method (DiBFM) for the Poisson equation. In DiBFM, the nodes of an element are categorized into two groups: (i) source nodes (ii) virtual nodes. First layer interpolation is used to interpolate the physical variables, while boundary integrals are evaluated on the source nodes only. Moreover, moving least squares (MLS) interpolation is used and provides additional constraints equations to establish the relationship between source and virtual nodes. Additionally, augmented thin plate spline (ATPS) is used to better interpolate the non-homogeneous term. Finally, it is claimed that the proposed method is much superior to the DRM for Poisson type equation with different geometries, especially for complex geometry. Numerical examples are evaluated and compared with the DRM to ensure the superiority of the proposed method. • A novel implementation of DRM for Poisson equation with dual interpolation boundary face method. • The integrand quantities are calculated from curves rather than from elements, which eliminate the geometric error. • Augmented thin plate spline is used to better interpolate the non-homogeneous term. • The proposed method is more accurate and efficient than the DRM, especially for problems with complex geometries. [ABSTRACT FROM AUTHOR]