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Aim: To evaluate the association of GDM and pre-eclampsia in women with obstetric cholestasis., Materials and Methods: Pregnant women with > 28 weeks gestation attending ANC, OPD and labor room of J.N.M.C.H, AMU, Aligarh UP (India) from 2020 to 2022 were included in the study after taking informed consent and ethical approval from the Institute. Women were divided into 2 groups, i.e. group 1 having 200 women with IHCP and group 2 having 200 healthy pregnant women; both the groups were followed up for the development of GDM and pre-eclampsia., Results: A statistically significant association was observed between IHCP and development of GDM [26.5% and odds ratio (OR) 1.64] and pre-eclampsia (17% and OR: 1.95) (p < 0.05), an also GDM and pre-eclampsia were found to be significantly associated with the severity of cholestasis (p < 0.05). Thus, on calculating OR, we found higher odds of developing GDM and pre-eclampsia in IHCP group with raised serum bile acid levels, maximum at 60 μmol/L level as compared to 10-40 μmol/L (GDM: OR: 8.647 and pre-eclampsia: OR: 6.303). Induction and cesarean rates were significantly higher in IHCP group (p < 0.05)., Conclusion: Our study concludes significant association of IHCP with GDM and pre-eclampsia as all three shares common pathogenetic pathways and greater risk of development at higher serum bile acid levels., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Senescence is a multifaceted and dynamic developmental phase pivotal in the plant's lifecycle, exerting significant influence and involving intricate regulatory mechanisms marked by a variety of structural, biochemical and molecular alterations. Biochemical changes, including reactive oxygen species (ROS) generation, membrane deterioration, nucleic acid degradation and protein degradation, characterize flower senescence. The progression of senescence entails a meticulously orchestrated network of interconnected molecular mechanisms and signalling pathways, ensuring its synchronized and efficient execution. Within flowering plants, petal senescence emerges as a crucial aspect significantly impacting flower longevity and postharvest quality, emphasizing the pressing necessity of unravelling the underlying signalling cascades orchestrating this process. Understanding the complex signalling pathways regulating petal senescence holds paramount importance, not only shedding light on the broader phenomenon of plant senescence but also paving the way for the development of targeted strategies to enhance the postharvest longevity of cut flowers. Various signalling pathways participate in petal senescence, encompassing hormone signalling, calcium signalling, protein kinase signalling and ROS signalling. Among these, the ethylene signalling pathway is extensively studied, and the manipulation of genes associated with ethylene biosynthesis or signal transduction has demonstrated the potential to enhance flower longevity. A thorough understanding of these complex pathways is critical for effectively delaying flower senescence, thereby enhancing postharvest quality and ornamental value. Therefore, this review adopts a viewpoint that combines fundamental research into the molecular intricacies of senescence with a practical orientation towards developing strategies for improving the postharvest quality of cut flowers. The innovation of this review is to shed light on the pivotal signalling cascades underpinning flower senescence and offer insights into potential approaches for modulating these pathways to postpone petal senescence in ornamental plants., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The fine-tuning of the intricate network of plant growth hormones empowers the balanced responses of plants to environmental and developmental signals. Salicylic acid and jasmonates are emerging as advanced hormones that provide plants with resistance to environmental stresses. Senescence is characterized by coordinated and systematic crosstalk between phytohormones that remodels the biochemical and physiological mechanisms in plants, resulting in cell death. The present investigation examines the role of jasmonates (methyl jasmonate and jasmonic acid) and salicylic acid (SA) in regulating the petal senescence of detached stalks of Cosmos sulphureus . Based on our results, it was revealed that SA and jasmonic acid (JA) at 40 μM and methyl jasmonate (MJ) at 0.75 μM concentration delayed the senescence of detached flowers of C. sulphureus considerably. These growth regulators improved the membrane stability, reinforced the antioxidant enzyme activities and averted the upsurge of hydrogen peroxide (H 2 O 2 ) content in the petals. Additionally, SA and jasmonates preserved higher content of total phenols, reducing sugars and soluble proteins in the petals, besides impeding the bacterial growth in testing solutions which corroborated with the maximum solution uptake. The elevated soluble protein content was found to be associated with low specific protease activity (SPA) and α-amino acid content in the petal tissues. Our study concluded that SA and jasmonates delayed flower senescence by averting oxidative stress and maintaining the nutritional status of the petals., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Prof. H.S. Srivastava Foundation for Science and Society 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Flower senescence is a fundamental aspect of the developmental trajectory in flowers, occurring after the differentiation of tissues and maturation of petals, and preceding the growth and development of seeds. It is accompanied by various alterations at the cytological, physiological, and molecular levels, similar to other forms of programmed cell death (PCD). It involves an intricate interplay of various plant growth regulators, with ethylene being the key orchestrator in ethylene-dependent petal senescence. Petal senescence mediated by ethylene is marked by various changes such as petal wilting, amplified oxidative stress, degradation of proteins and nucleic acids, and autophagy. Ethylene crosstalks with other growth regulators and triggers genetic and/or epigenetic reprogramming of genes during senescence in flowers. While our understanding of the mechanism and regulation of petal senescence in ethylene-sensitive species has advanced, significant knowledge gaps still exist, which demand critical reappraisal of the available literature on the topic. A deeper understanding of the various mechanisms and regulatory pathways involved in ethylene-dependent senescence has the capacity to facilitate a more precise regulation of the timing and site of senescence, thus leading to optimized crop yields, enhanced product quality, and extended longevity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nitric oxide releasing compound sodium nitroprusside (SNP) is regarded as novel chemical to beat the daunting challenges of postharvest losses in cut flowers. In the recent years, it has yielded propitious results as postharvest vase preservative for cut flowers. Our study explicates the efficacy of SNP in mitigating postharvest senescence in Consolida ajacis (L.) Schur cut spikes. The freshly excised C. ajacis spikes were subjected to different SNP treatments viz , 20μM, 40μM, 60μM and 80μM. The control spikes were held in distilled water. The spikes held in test solutions showed a marked improvement in vase life and flower quality. Our results indicate a profound surge in sugars, phenols and soluble proteins in SNP-treated spikes over control. Moreover, the SNP treatments improved membrane stability as signposted by decreased lipoxygenase activity (LOX). The SNP treatments also upregulated different antioxidant enzymes viz , ascorbate peroxidase (APX), catalase (CAT) and superoxide dismutase (SOD). The current study recommends 40μM SNP as optimum concentration for preserving floral quality and extending display period of C. ajacis spikes. Together, these findings reveal that SNP at proper dosage can efficiently alleviate deteriorative postharvest changes by modulating physiological and biochemical mechanisms underlying senescence.

Plant leaves provide a unique insight into the changes that occur in organs, tissues and cells as they approach senescence. As part of the parental outlay, plants instigate leaf senescence to reallocate resources from older tissues to new organs towards the termination of the growing season. The aim of crop breeding initiatives is to optimize senescence for specific species. Considering hormonal regulation and their crosstalk during leaf senescence through integration of developmental signals, this work examines the efficacy of polyamines (PAs) in modulating several biochemical and physiological aspects with an ultimate aim to delay leaf senescence in leaf discs of Berginia ciliata (Haw.) sternb. Leaf discs were treated with putrescine (Put), spermidine (Spd) and spermine (Spm) at 20μM, 20μM and 15μM concentration, respectively. A set of leaf discs kept in distilled water served as the control. Leaf discs treated with PAs were green and fresh by about 4 days compared to the control, thus exhibited delayed senescence. This delayed leaf senescence corroborated with the maintenance of high activity of reactive oxygen species (ROS) scavenging antioxidant enzymes viz , superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and higher content of chlorophylls. A marked increase was also observed in membrane stability and soluble proteins in leaf discs treated with PAs. Exogenous PAs reduced oxidative stress in the leaf discs, as revealed by lower malondialdehyde (MDA) level, which is manifested as reduced lipid peroxidation (LPO). Improved membrane stability was proportional to lower LPO, as measured by the membrane stability index (MSI).

The Newborn Behavioral Observations (NBO) system is a relationship-based tool that helps parents recognize their infant's competencies and learn their behavioral cues, with the goals of enhancing parental responsiveness and satisfaction in the infant-parent relationship. In our study, a pediatrician integrated the NBO into 44 pediatric health care visits of infants in rural Pakistan villages, under the remote guidance of two U.S.-based child psychiatrists. A clinician then gave the mothers a survey about their experience of the NBO and found that the mothers were highly satisfied, reporting greater appreciation of their infant's strengths, greater understanding of their infant's behavioral cues, stronger attachment to their infant, and greater self-confidence as a mother. In their consideration of these results, the authors explore cultural reasons for the mothers' responses and generate hypotheses to inform an outcome study of a similar intervention. This was a feasibility and acceptability study and was not randomized, had no control group, and did not use objective measures of outcome., (© 2022 Michigan Association for Infant Mental Health.)

The concepts of environmental and business sustainability are well-established in the business lexicon of progressive firms. However, firms are yet to examine the effects of environmental management practices (EMPs) on environmental performance (EP) and financial performance (FP) by connecting the missing linkage of environment, social, and governance disclosure (ESGD). This study analyses the impact of EMPs on EP and FP and offers empirical evidence of whether ESGD mediates the relationship between EP and FP of firms in Malaysia. The data from 141 listed firms on Bursa Malaysia was extracted between 2009-2020. The data was analyzed using data envelopment analysis (DEA) and the generalized method of moments (GMM) technique. The findings reflect that EMPs have a significant positive effect on EP and all five proxies of EP have a significant positive effect on ESGD (except 'S') and FP. Also, ESGD together with its three proxies mediates the relationship between EP and FP. The findings of this research offer an empirical rationale for regulators and policymakers of industrial firms to accelerate their EMPs and improve ESGD mechanisms for better environmental and financial outcomes., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin ( 10 ) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC 50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC 50 values of 6.65 and 5.55 μM, respectively, while compounds 18b , 18c , 18f , and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC 50 values ranging between 2.9 and 10.5 μM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC 50 value of 2.91 μM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The integration of Industry 4.0 (I4.0) has emerged as an innovative paradigm for industrial firms contemplating environmental and economic issues. This study explicates the role of I4.0 technologies (I4.0TEC) in reinforcing the management of environmental assets (ENVASS) as well as optimizing financial performance (FP). The data in this research was collected from 738 industrial firms in Malaysia between 2009 and 2018. The analyses of ordinary least square statistics (OLS) and structural equation modeling (SEM) delineated three major findings. The individual effect of ENVASS, robotization, and flexibility in production technologies has a marginal impact on sales, exports, and labor productivity indicators. The complementarities of these variables represent a similar effect on the performance indicators. The findings related to gross operating margin elucidate that ENVASS and I4.0TEC have neither individual nor complementarity effects. This was explained by developing a robust model by integrating ENVASS, I4.0TEC, spending and investing in R&D, flexibility in production, and human capital management. Our findings have confirmed that the proposed model offers a functional toolkit for the firms considering optimizing their profitability by leveraging ENVASS and I4.0TEC. This research also contributes to developing an ethical business model for the circular economy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Molecular cosensitization is favorable for manipulating solar radiation through the judicious choice of cosensitizers having complementary absorption spectra. For greenhouse-integrated dye-sensitized solar cells (DSCs), the manipulation of solar radiation is crucial in order to maximize the flow of photosynthetically active radiation (PAR) for the effectual photosynthetic activity of plants; meanwhile, non-PAR is utilized in agrivoltaics for generating electricity. In this study, we report the synthesis of novel four UV-selective absorbers, based on the diimide scaffold, functionalized with carboxylate and pyridyl anchoring groups, for adequate adsorption onto the TiO 2 electrode in DSC. The UV/Vis absorption spectra of the DMF solution-based free dyes were measured experimentally. Basic photophysical and energetics requirements for operating greenhouse-integrated DSCs were examined at the molecular level via (time-dependent) density functional theory-based calculations. The computational results revealed the outperformance of the biphenyldiimide-structured DI-CA1 dye, especially for maximum charge transferred to its anchor, lower thermodynamic barrier for dissociating the photogenerated exciton, largest Stokes' shift, strong electronic coupling with TiO 2 nanoparticles, and higher degree of charge separation at the DI-CA1/TiO 2 interface. PDOS showed deeper existence for the LUMO level in the CB of TiO 2 , which expedites the electron injection process. The chemical and optical compatibility of DI-CA1 were then investigated as a potential cosensitizer of a reference BTD-DTP1, a green light-absorbing dye. Considerable overlap between the fluorescence spectrum of DI-CA1 and absorption spectrum of the reference BTD-DTP1 advocated the opportunity of excitation energy transfer via the radiative trivial reabsorption mechanism, which confirms the cosensitization functionality. Energy decomposition analysis and reduced density gradient maps estimated the chemical compatibility owing to weak dispersion interactions as the dominant stabilizing attractive force. This noncovalent functionalization retains the chemical compatibility without distorting the π-π conjugation and the associated physicochemical properties of the individual dye molecules. Along with the expanded consumption of non-photosynthetically active solar radiation, an improved power conversion efficiency of greenhouse-integrated DSC is accordingly expected., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Postharvest losses of cut flowers is one of the considerable challenges restricting their efficient marketability. Consequently, such challenges have triggered a constant hunt for developing compatible postharvest treatments to mitigate postharvest losses. Interestingly, recent studies entrench extensive role of salicylic acid (SA) in mitigating postharvest losses in various flower systems. The current investigation focusses on role of SA in augmenting physiological and biochemical responses to mitigate postharvest senescence in cut spikes of Consolida ajacis . The cut spikes of C. ajacis were supplemented with various SA treatments viz, 2 mM, 4 mM, 6 mM. The effects of these treatments were evaluated against control set of spikes placed in distilled water. Our study indicates considerable increment in postharvest longevity of cut spikes, besides an increase in solution uptake, sugar and protein content of tepal tissues.SA augmented antioxidant system via upsurge in phenolic content and antioxidant enzymes viz, superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) to forfend reactive oxygen species (ROS) related oxidative damage. SA profoundly reduced lipoxygenase (LOX) activity to preserve the membrane integrity and thus prevented seepage of solutes from tepal tissues. These results authenticate SA particularly 4 mM concentration as effective postharvest treatment to preserve the postharvest quality of C. ajacis cut spikes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The fabrication of colorless and see-through dye-sensitized solar cells (DSCs) requires the photosensitizers to have little or no absorption in the visible light region of the solar spectrum. However, a trade-off between transparency and power conversion efficiency (PCE) has to be tackled, since most transparent DSCs are showing low PCE when compared to colorful and opaque DSCs. One strategy to increase PCE is applying two cosensitizers with selective conversion of the UV and NIR radiation, therefore, the non-visible part only is absorbed. In this study, we report synthesis of novel five UV-selective absorbers, based on diimide and Schiff bases incorporating carboxyl and pyridyl anchoring groups. A systematic computational investigation using density functional theory (DFT) and time-dependent DFT approaches was employed to evaluate their prospect of application in transparent DSCs. Experimental UV/Vis absorption spectra showed that all dyes exhibit an absorption band covering the mid/near-UV region of solar spectrum, with a bathochromic shift and a hyperchromic shifts for Py-1 dye. Computational results showed that the studied dyes satisfied the basic photophysical and energetics requirements of operating DSC as well as the stability and thermodynamical spontaneity of adsorption onto surface of TiO 2 . However, results revealed outperformance of the thienothiophene core-containing Py-1 UV-dye, owing to its advantageous structural attributes, improved conjugation, intense emission, large Stokes shift and maximum charge transferred to the anchor. Chemical compatibility of Py-1 dye was then theoretically investigated as a potential cosensitizer of a reference VG20-C2 NIR-dye. By the judicious selection of pyridyl anchor-based UV-absorber (Py-1) and carboxyl anchor-based NIR-absorber (VG20), the advantage of the optical complementarity and selectivity of different TiO 2 -adsorption-site (Lewis- and Bronsted-acidic) can be achieved. An improved overall PCE is estimated accordingly.

Despite a profound evidence of the human unsustainable behaviours' impact on the environment, stark disparities prevail on this narrative especially in the context of the current epidemiological situation ushered by the COVID-19. The ongoing pandemic is a global public health concern due to its sagacious impacts on environmental sustainability, social responsibility and people's quality of life. This study primarily focuses on analysing the impact of COVID-19 (COV) on the environmental awareness (EA), sustainable consumption (SC) and social responsibility (SR). Additionally, we aspire to investigate the impact of demographics of generations and religion on the proposed nexus in this study. The data was collected from 700 participants of different age groups and religious backgrounds in Malaysia, and structural equation modelling (SEM) was used to analyse this data and test the hypotheses. The findings indicate that COVID-19 has a significantly positive impact on EA, SC and SR, and the generations and religiosity moderate the relationship between COVID-19 and its impact on sustainable behaviours. This study contributes to analyse the difference in the perception of EA, SC and SR among the people that eventually will stimulate the scientific reasoning among the governments, policymakers and scientists to develop a holistic framework to combat unprecedented event such as COVID-19 and ensure the authentication of sustainable environment and exceptional quality of life. The policymakers in Malaysia may use the findings of this study to inspect the social and environmental aspects of the people during the transformation events., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The COVID-19 outbreak has not only affected the physical health of the public but also resulted in severe psychological outcomes. This study aims to investigate the psychological effects of the COVID-19 outbreak on Pakistan's general public. In order to identify the main psychological factors that have emerged due to the current pandemic, extensive literature and opinion pieces of psychologists were reviewed. After a thorough study of the existing scholarship, four main psychological factors were investigated: stress and anxiety, obsessive compulsive disorder (OCD), delusions of getting infected from the disease, and religiosity. A research survey was circulated among the sample population online. A total 356 valid responses were received in the period of two to three weeks. Findings showed that the respondents reported a moderate level of anxiety, occasional symptoms of OCD, and delusions. However, respondents showed a high inclination toward religion during the current pandemic situation. Furthermore, respondents highlighted a few other psychological factors, such as financial strain and loneliness, in the survey. The primary sources of COVID-19-related information were social media and television among the general public of Pakistan. Finally, guidelines and tips from the reviewed psychologists and psychiatrists on overcoming the highlighted psychological problems that have arisen due to the COVID-19 outbreak were summarised., (© 2021 John Wiley & Sons Ltd.)

The present investigation primarily focussed on evaluating the efficacy of exogenous proline on the flower longevity of Dianthus chinensis L. Floral buds were harvested at the paint brush stage (i.e., a day prior to anthesis) and divided into 6 sets, with one set of buds (i.e., control) held in distilled water and rest of the 5 sets were supplemented with various concentrations of proline, viz., 10 mM, 20 mM, 30 mM, 40 mM and 50 mM. The application of proline at 40 mM concentration proved out to be most effective in improving the longevity of the flowers by about 4 days as compared to the control. The ameliorated longevity coincided with enhanced floral diameter, fresh mass, dry mass and water content. The flowers with delayed senescence also maintained higher soluble proteins, sugars and phenols. The results suggest that exogenous proline effectively alleviates oxidative stress in the petal tissue, as evident by a relatively lower maloendialdehyde content, which is manifested in the form of reduced lipid peroxidation (LPO). Reduced LPO was commensurate with increased membrane stability, quantified by membrane stability index. Moreover, the flowers with improved longevity exhibited a decline in lipoxygenase activity and significant augmentation of antioxidant enzymes superoxide dismutase, catalase and ascorbate peroxidase., (© Prof. H.S. Srivastava Foundation for Science and Society 2021.)

Herein, we report the synthesis and single crystal X-ray structure of Cu(II)-picolinic acid complex, 1 as a potent topoisomerase I inhibitor. The complex 1 crystallized in the triclinic crystal system with space group P -1. Comparative in vitro binding studies of complex 1 with CT DNA and tRNA were carried out revealing an electrostatic binding mode with higher binding propensity towards tRNA. The intrinsic bonding constant value, K b was calculated to be 4.36 × 10 4 and 8.78 × 10 4 M -1 with CT DNA and tRNA respectively. DNA cleavage activity was carried out with a pBR322 plasmid DNA substrate to ascertain the cleaving ability. Furthermore, Topo-I inhibition assay of complex 1 , performed via gel electrophoresis revealed a significant inhibitory effect on the enzyme catalytic activity at a minimum concentration of 15 µM. The DFT studies were carried out to provide better insight in the electronic transitions observed in the absorption spectrum of the complex 1 . Molecular docking studies were carried out with DNA, RNA and Topo-I to determine the specific binding preferences at the target site and complement the spectroscopic studies. The antimicrobial potential of complex 1 was screened against E. coli , S. aureus , P. aeruginosa , B. subtilis and C. albicans ; and compared with doxycycline, exhibiting an excellent maximum zone of inhibition of 28 mm against E. coli. Communicated by Ramaswamy H. Sarma.

Biocompatible tryptophan-derived copper ( 1 ) and zinc ( 2 ) complexes with norharmane (β-carboline) were designed, synthesized, characterized, and evaluated for the potential anticancer activity in vitro and in vivo. The in vitro cytotoxicity of both complexes 1 and 2 were assessed against two cancerous cells: (human breast cancer) MCF7 and (liver hepatocellular cancer) HepG2 cells with a non-tumorigenic: (human embryonic kidney) HEK293 cells. The results exhibited a potentially decent selectivity of 1 against MCF7 cells with an IC 50 value of 7.8 ± 0.4 μM compared to 2 (less active, IC 50 ~ 20 μM). Furthermore, we analyzed the level of glutathione, lipid peroxidation, and visualized ROS generation to get an insight into the mechanistic pathway and witnessed oxidative stress. These in vitro results were ascertained by in vivo experiments, which also supported the free radical-mediated oxidative stress. The comet assay confirmed the oxidative stress that leads to DNA damage. The histopathology of the liver also ascertained the low toxicity of 1 .

A new chiral BODIPY-based fluorescent compound, 5-bromo-4,4-difluoro-3(S)-1-phenylethyl)amino) BODIPY, 4 was synthesized for biomedical applications. Optical, antimicrobial, antioxidant properties of the compound 4 are investigated. The partition coefficient suggested that the compound 4 has the potential to be developed as an active antibacterial and antioxidant candidate. In this context, antibacterial assay was carried out for compound 4 against various bacterial strains, revealing maximum inhibition zone (24 ± 2.19 mm) in Escherichia coli. Moreover, results of antioxidant activity of compound 4 revealed IC 50 values to be greater than ascorbic acid. Molecular docking has given brief insight about the binding of the compound 4 , suggesting that it has a strong potential to inhibit bacterial target enzymes viz., DNA gyrase, enzymes in the type II fatty acid synthesis and Ddl (d-alanine: d-alanine ligase) in peptidoglycan synthesis. The molecular geometry and electrostatic potential of compound 4 , was established by DFT (Density Functional Theory) calculations.AbbreviationsBBBblood‒brain barrierBDEbond dissociation energyBODIPYboron-dipyrromethaneDdlD-alanine:D-alanine ligaseDDQ2,3-dichloro-5,6-dicyano-1,4-benzoquinoneDFTdensity functional theoryDNAdeoxyribonucleic acidDPPH1,1‒diphenyl‒2‒picrylhydrazylNBS N -bromo succinimideROSreactive oxygen speciesUV-visultraviolet-visibleFMOfrontier molecular orbitalsHOMOhighest occupied molecular orbitalLUMOlowest unoccupied molecular orbitalCommunicated by Ramaswamy H. Sarma.

Binding effect and interaction of N , N '-dialkyl cystine based gemini surfactant (GS); 2(C 12 Cys) with human serum albumin (HSA) were systematically investigated by the techniques such as surface tension measurement, UV-visible spectroscopy, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and molecular docking studies. The surface tension measurement exhibited that HSA shifted the critical micelle concentration of the 2(C 12 Cys) GS to the higher side that confirms the complex formation among 2(C 12 Cys) GS and HSA which was also verified by UV-visible, fluorescence, and CD spectroscopy. Increase in the concentration of 2(C 12 Cys) GS increases the absorption of the HSA protein but has a reverse effect on the fluorescence intensity. The analysis of UV-visible study with the help of a static quenching method showed that the value acquired for the bimolecular quenching constant ( k q ) quenches the intrinsic fluorescence of the HSA protein. Synchronous fluorescence spectrometry declared that the induced-binding conformational changes in HSA and CD results explained the variations in the secondary arrangement of the protein in presence of 2(C 12 Cys) GS. The present study revealed that the interaction between 2(C 12 Cys) GS and HSA is important for the preparation and properties of medicines. Molecular docking study provides insight into the specific binding site of 2(C 12 Cys) GS into the sites of HSA., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Ras proteins are highly conserved small GTPases in eukaryotes. GTP-bound Ras binds to effectors to trigger signaling cascades. In order to understand how extensive is the functional homology between the highly homologous proteins, S. cerevisiae Ras2 and C. albicans Ras1, we examined whether ScRas2 could functionally complement CaRas1 in activating hyphal morphogenesis as well as GPI anchor biosynthesis. We show that ScRas2 functionally complements CaRas1 in rescuing growth as well as activating hyphal growth, a process that involves plasma membrane localized Ras activating cAMP/PKA signaling via Cyr1. However, ScRas2 is unable to activate the GPI-N-acetylglucosaminyl transferase (GPI-GnT) which catalyzes the first step of GPI biosynthesis. That CaRas1 alone activates GPI-GnT and not ScRas2 suggests that this process is cAMP independent. Interestingly, CaRas1 transcriptionally activates CaGPI2, encoding a GPI-GnT subunit that has been shown to interact with CaRas1 physically. In turn, CaGPI2 downregulates CaGPI19, encoding another GPI-GnT subunit. This has direct consequences for expression of CaERG11, encoding the target of azole antifungals. This effect too is specific to CaRas1 and ScRas2 is unable to replicate it., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Polymer therapeutics encompasses polymer-drug conjugates that are nano-sized, multicomponent constructs already in the clinic as antitumor compounds, either as single agents or in combination with other organic drug scaffolds. Nanoparticle-based polymer-conjugated therapeutics are poised to become a leading delivery strategy for cancer treatments as they exhibit prolonged half-life, higher stability and selectivity, water solubility, longer clearance time, lower immunogenicity and antigenicity and often also specific targeting to tissues or cells. Compared to free drugs, polymer-tethered drugs preferentially accumulate in the tumor sites unlike conventional chemotherapy which does not discriminate between the cancer cells and healthy cells, thereby causing severe side-effects. It is also desirable that the drug reaches its site of action at a particular concentration and the therapeutic dose remains constant over a sufficiently long period of time. This can be achieved by opting for new formulations possessing polymeric systems of drug carriers. However, many challenges still remain unanswered in polymeric drug conjugates which need to be readdressed and therefore, can broaden the scope of this field. This review highlights some of the antitumor polymer therapeutics including polymer-drug conjugates, polymeric micelles, polymeric liposomes and other polymeric nanoparticles that are currently under investigation., Competing Interests: The authors declare that they have no conflicts of interest to disclose., (This journal is © The Royal Society of Chemistry.)

Microwave assisted approach was adopted for obtaining copper (II) oxide and Iron (III) oxide nanoparticles using leaves extract of Euphorbia helioscopia. Tanins component extracted from Euphorbia helioscopia were responsible for the formation of stable nanoscopic particles. Nanoparticles of iron and copper oxide was characterized using powder X-ray Diffractometer (PXRD), Scanning electron microscopy (SEM), Energy Dispersive X-ray Analysis (EDAX) and Transmission Electron Microscopy (TEM). PXRD result confirmed the formation of α-phase and monoclinic iron and copper oxide nanoparticles respectively. Nanoparticles of iron and copper oxide were of spherical shape with average diameter in range of 7-10 nm. Antifungal potential of fabricated oxide nanoparticles was tested using Cladosporium herbarum as role model fungus. Iron oxide nanoparticles exhibit greater antifungal activities against the Cladosporium herbarum as compared to copper oxide nanoparticles., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles with particle size 10-30 nm were prepared by a green approach using tannic acid as reducing and capping agent. These nanoparticles were characterized by X-ray diffractometry (XRD), high resolution field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). The prepared iron oxide nanoparticles were also evaluated for their antifungal activity against Trichothecium roseum, Cladosporium herbarum, Penicillium chrysogenum, Alternaria alternata and Aspergillus niger. The antifungal activity was observed as inhibition in spore germination and by determining the zone of inhibition of fungal pathogens caused by different concentrations of iron oxide nanoparticles on culture media. It was observed from the present study that Fe 2 O 3 nanoparticles showed significant antimycotic activity against all the tested fungal pathogens. Highest inhibition in spore germination was caused against T. roseum (87.74%) followed by C. herbarum (84.89%). The highest zone of inhibition by iron oxide nanoparticles was reported against P. chrysogenum (28.67 mm) followed by A. niger (26.33 mm), T. roseum (22.67 mm), A. alternata (21.33 mm) and least against C. herbarum (18.00 mm). Activity index was recorded highest against P. chrysogenum (0.81). The MIC value of Fe 2 O 3 NP varies between 0.063 and 0.016 mg/ml for different fungal pathogens that is comparable with the MIC value shown by the standard, revealing the efficacy of iron oxide NP's against different fungal pathogens., (Copyright © 2017. Published by Elsevier Ltd.)

Yolk sac tumors (endodermal sinus tumors) are an important subgroup of germ cell tumors of the ovary. They are seen in young females and are highly aggressive, but respond well to treatment. Although different morphological patterns can be seen on light microscopy, granulomatous reaction and giant cells are a very rare occurrence. We report the case of a young female with ovarian yolk-sac tumor in which a widespread granulomatous reaction was seen, causing a diagnostic dilemma.

Objectives. To compare the efficacy and safety of intravaginal misoprostol with transcervical Foley catheter for labour induction. Material and Methods. One hundred and four women with term gestation, with Bishop score < 4, and with various indications for labour induction were randomly divided into two groups. In Group I, 25 μg of misoprostol tablet was placed intravaginally, 4 hourly up to maximum 6 doses. In Group II, Foley catheter 16F was placed through the internal os of the cervix under aseptic condition and then inflated with 50 cc of sterile saline. Statistical analysis was done using SPSS software. Results. The induction to delivery interval was 14.03 ± 7.61 hours versus 18.40 ± 8.02 hours (p < 0.01). The rate of vaginal delivery was 76.7% versus 56.8% in misoprostol and transcervical Foley catheter group, respectively. Uterine hyperstimulation was more common with misoprostol. Neonatal outcome was similar in both the groups. Conclusion. Intravaginal misoprostol is associated with a shorter induction to delivery interval as compared to Foley's catheter and it increases the rate of vaginal delivery in cases of unripe cervix at term. Transcervical Foley catheter is associated with a lower incidence of uterine hyperstimulation during labour.

Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis, molar conductance and spectroscopic data (IR, NMR, EPR, UV-vis). In vitro DNA binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV-vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity measurements were carried out for Cu(II) complexes 1(a and b). Both the enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were found to be 5.6×10(4), 9.8×10(3), 8.2×10(3) and 6.7×10(3)M(-1), respectively suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA cleavage activity of complexes 1(a and b), investigated by agarose gel electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the molecular docking studies of complexes 1(a and b) were carried out with B-DNA revealing that the complexes bind to the adenine-thymine residues in the minor groove of the DNA. The resulting binding energies of docked metal complexes 1(a and b) were found to be -265.1 and -218.9KJmol(-1), respectively. Furthermore, enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial activity., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Dipeptide (Pro-Gly and Pro-Leu) Zinc(II) complexes 1 and 2 were designed and synthesized for potential use as cancer chemotherapeutic agents. In order to augment the DNA recognition of metallonuclease activity, zinc metal ion was tethered to peptide motif to carry out DNA site specific hydrolytic cleavage. The structural formulation of the complexes 1 and 2 was done by elemental analysis, spectroscopic methods (IR, NMR, electronic) and molar conductance measurements. Their in vitro DNA binding profile was investigated by UV-vis titrations, fluorescence titrations and circular dichroism which revealed that these complexes bind to CT DNA by electrostatic interactions via groove binding mode. Zn(II) Pro-Gly complex 1 showed greater binding affinity to CT DNA as compared to the Zn(II) Pro-Leu complex 2 due to steric constraints in the latter. The supercoiled pBR322 DNA cleavage activity of complex 1, ascertained by gel electrophoresis demonstrated efficient DNA cleaving ability via hydrolytic mechanistic pathway. Further, the molecular docking studies confirmed that complex 1 bind to the minor groove of DNA having AT-rich sequences with relative binding energy of -196.72kJmol(-1)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: To examine the outcomes of surgical repair of atrial septal defects in paediatric and adult patients., Methods: The retrospective study comprised data of 84 patients who had undergone surgical correction of atrial septal defect at the Aga Khan University Hospital, Karachi, between June 2006 and December 2011. All patients with isolated atrial septal defect (ostium secundum, ostium primum and sinus venosus with or without partial anomalous pulmonary venous connection) were included. Clinical and transthoracic echocardiographic data was reviewed. SPSS 17 was used for statistical analysis., Results: There were no deaths in the study population. The mean time for follow-up was 6.5 +/- 9.9 months. Most of the patients (n = 80; 95.2%) were in NewYork Heart Association class I at follow-up, while the remaining 4 (4.8%) were in New York Heart Association class II. Post-operatively, 8 (9.5%) patients developed brief episodes of arrhythmias. There were 3 (3.57%) patients who were re-admitted within 30 days; 2 (66.7%) had superficial wound infection, while 1 (33.3%) had to be re-opened because of cardiac tamponade., Conclusion: Surgical repair of atrial septal defects is a safe procedure which is associated with excellent results and low morbidity.

New dimethyltin derived antitumor drug candidates (S)- and (R)-[4-(2-hydroxy-1-phenylethylimino)pent-2-ol]dimethyltin(iv), 1 and (S)- and (R)-[2,2-dimethyl-4-phenyl-1,3,2-oxazastannolidine], 2 derived from (R)- and (S)-enantiomers of [4-(2-hydroxy-1-phenylethylimino)pent-2-ol] and 2-amino-2-phenylethanol, respectively, were synthesized and thoroughly characterized. Preliminary complex-DNA interaction studies employing various optical methods revealed that the (S)-enantiomer displayed a higher propensity towards the drug target DNA double helix. This was quantified by K(b) and K(sv) values of ligands L and L' and (S)-/(R)-1 and (S)-/(R)-2 complexes, which demonstrated a multifold increase in the case of the (S)-enantiomers in comparison to their (R)-enantiomeric forms. This clearly demonstrates the chiral preference of the (S)-enantiomer over the (R)-enantiomer, and its potency to act as a chemotherapeutic agent. Therefore, the in vitro antitumor activity of the (S)-enantiomer of 1 and 2 was evaluated by the sulforhodamine-B (SRB) assay to assess cellular proliferation against five different human cell lines viz., Hop62, DWD, K562, DU145 and MCF-7. The complex (S)-1 displayed a remarkably pronounced and specific activity for K562, while complex (S)-2 exhibited significant activity towards Hop62, DWD, DU145 and MCF-7. The in vivo antitumor activity of (S)-1 and (S)-2 was carried out, which revealed significant regression in human lung tumors.

To explore the therapeutic potential of copper-based benzimidazole complexes, tetranuclear Cu(II) complex 1 and dinuclear ternary amino acid complexes 2 and 3 {L-trp and L-val, respectively} were synthesized and thoroughly characterized. In vitro DNA binding studies of complexes 1-3 were carried out employing UV-vis titrations, fluorescence, circular dichroic and viscosity measurements which revealed that the complexes 1-3 bind to CT DNA preferably via groove binding. Complex 1 cleaved pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay), accessible to major groove while 2 followed oxidative mechanism, binding to minor groove of DNA double helix; binding events were further validated by molecular docking studies. Additionally, the complexes 1 and 2 exhibit high Topo-I inhibitory activity at different concentrations. The complexes 1-3 were evaluated for antibacterial activity against Escherichia coli and Staphylococcus aureus, and 2 was found to be most effective against Gram-positive bacteria., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A novel heterobimetallic Cu(II)-Sn(IV) complex 1 bearing bioactive 1,10-phenanthroline pharmacophore ligand scaffold was synthesized and characterized by elemental analysis, IR, UV-vis spectroscopy, Mass (ESI and FAB) and X-ray crystallography. The in vitro DNA binding studies of complex 1 with CT DNA was carried out by various biophysical and molecular docking techniques which revealed that complex 1 binds to DNA through intercalation in the minor groove having AT-rich sequences. Complex 1 exhibits high chemical nuclease activity cleaving supercoiled pBR322 DNA via hydrolytic pathway which was further evidenced by T4 DNA ligase assay. The complex 1 shows high inhibitory activity against Topo I at a very low concentration (15 μM), suggesting that complex 1 is an efficient catalytic inhibitor of human Topo I and further validated by molecular docking studies., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Novel ternary dizinc(II) complexes 1-3, derived from 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol and l-form of amino acids (viz., tryptophan, leucine and valine) were synthesized and characterized by spectroscopic (IR, (1)H NMR, UV-vis, ESI-MS) and other analytical methods. To evaluate the biological preference of chiral drugs for inherently chiral target DNA, interaction of 1-3 with calf thymus DNA in Tris-HCl buffer was studied by various biophysical techniques which reveal that all these complexes bind to CT DNA non-covalently via electrostatic interaction. The higher K(b) value of L-tryptophan complex 1 suggested greater DNA binding propensity. Further, to evaluate the mode of action at the molecular level, interaction studies of complexes 1 and 2 with nucleotides (5'-GMP and 5'-TMP) were carried out by UV-vis titrations, (1)H and (31)P NMR which implicates the preferential selectivity of these complexes to N3 of thymine rather than N7 of guanine. Furthermore, complex 1 exhibits efficient DNA cleavage with supercoiled pBR322. The complex 1 cleaves DNA efficiently involving hydrolytic cleavage pathway. Such chiral synthetic hydrolytic nucleases with asymmetric centers are gaining considerable attention owing to their importance in biotechnology and drug design, in particular to cleave DNA with sequence selectivity different from that of the natural enzymes., (Copyright © 2011 Elsevier B.V. All rights reserved.)