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A Genome-wide association (GWAS) study was conducted for phosphorous (P)-use responsive physiological traits in bread wheat at the seedling stage under contrasting P regimes. A panel of 158 diverse advanced breeding lines and released varieties, and a set of 10,800 filtered single nucleotide polymorphism (SNP) markers were used to study marker-trait associations over the eight shoot traits. Principle component analysis separated the two environments (P regimes) because of the differential response of the traits indicating the essentiality of the separate breeding programmes for each environment. Significant variations for genotypic, environmental, and genotype × environment (GEI) effects were observed for all the traits in the combined analysis of variance with moderately high broad sense heritability traits (0.50-0.73). With the different algorithms of association mapping viz., BLINK, FarmCPU, and MLM, 38 unique QTLs under non-limiting P (NLP) and 45 QTLs for limiting P (LP) conditions for various shoot traits were identified. Some of these QTLs were captured by all three algorithms. Interestingly, a Q. iari.dt.sdw.1 on chromosome 1D was found to explain the significant variations in three important physiological traits under non-limiting phosphorus (NLP) conditions. We identified the putative candidate genes for QTLs namely Q.iari.dt.chl.1, Q.iari.dt.sdw.16, Q.iari.dt.sdw.9 and Q.iari.dt.tpc.1 which are potentially involved in the mechanism regulating phosphorus use efficiency through improved P absorption due to improved root architectural traits and better mobilization such as sulfotransferase involved in postembryonic root development, WALLS ARE THIN1 (WAT1), a plant-specific protein that facilitates auxin export; lectin receptor-like kinase essentially involved in plant development, stress response during germination and lateral root development and F-box component of the SKP-Cullin-F box E3 ubiquitin ligase complex and strigolactone signal perception. Expression profiling of putative genes located in identified genomic regions against the wheat expression atlas revealed their significance based on the expression of these genes for stress response and growth development processes in wheat. Our results thus provide an important insight into understanding the genetic basis for improving PUE under phosphorus stress conditions and can shape the future breeding programme by developing and integrating molecular markers for these difficult-to-score important traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dharmateja, Yadav, Kumar, Babu, Jain, Mandal, Pandey, Shrivastava, Gaikwad, Bainsla, Tomar, Sugumar, Saifi and Ranjan.)

Breast cancer is the most prevalent form of cancer that can strike at any age; the higher the age, the greater the risk. The presence of malignant tissue has become more frequent in women. Although medical therapy has improved breast cancer diagnostic and treatment methods, still the death rate remains high due to failure of diagnosing breast cancer in its early stages. A classification approach for mammography images based on nonsubsampled contourlet transform (NSCT) is proposed in order to investigate it. The proposed method uses multiresolution NSCT decomposition to the region of interest (ROI) of mammography images and then uses Z-moments for extracting features from the NSCT-decomposed images. The matrix is formed by the components that are extracted from the region of interest and are then subjected to singular value decomposition (SVD) in order to remove the essential features that can generalize globally. The method employs a support vector machine (SVM) classification algorithm to categorize mammography pictures into normal, benign, and malignant and to identify and classify the breast lesions. The accuracy of the proposed model is 96.76 percent, and the training time is greatly decreased, as evident from the experiments performed. The paper also focuses on conducting the feature extraction experiments using morphological spectroscopy. The experiment combines 16 different algorithms with 4 classification methods for achieving exceptional accuracy and time efficiency outcomes as compared to other existing state-of-the-art approaches., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Suman Mann et al.)

Cancer research currently is heavily skewed toward high-income countries (HICs), with little research conducted in, and relevant to, the problems of low- and middle-income countries (LMICs). This regional discordance in cancer knowledge generation and application needs to be rebalanced. Several gaps in the research enterprise of LMICs need to be addressed to promote regionally relevant research, and radical rethinking is needed to address the burning issues in cancer care in these regions. We identified five top priorities in cancer research in LMICs based on current and projected needs: reducing the burden of patients with advanced disease; improving access and affordability, and outcomes of cancer treatment; value-based care and health economics; quality improvement and implementation research; and leveraging technology to improve cancer control. LMICs have an excellent opportunity to address important questions in cancer research that could impact cancer control globally. Success will require collaboration and commitment from governments, policy makers, funding agencies, health care organizations and leaders, researchers and the public., (© 2022. Springer Nature America, Inc.)

Quantitative information regarding the local behavior of interfaces in an inhomogeneous material during shock loading is limited due to challenges associated with time and spatial resolution. This paper reports the development of a novel method for in-situ measurement of the thermo-mechanical response of polymer bonded sugar composite where measurements are performed during propagagtion of shock wave in sucrose crystal through polydimethylsiloxane binder. The time-resolved measurements were performed with 5 ns resolution providing an estimation on local pressure, temperature, strain rate, and local shock viscosity. The experiments were performed at two different impact velocities to induce shock pressure of 4.26 GPa and 2.22 GPa and strain rate greater than 10 6 /s. The results show the solid to the liquid phase transition of sucrose under shock compression. The results are discussed with the help of fractography analyses of sucrose crystal in order to obtain insights into the underlying heat generation mechanism., (© 2022. The Author(s).)

Repeat dosing poses a major hurdle for the development of an adeno-associated virus (AAV)-based gene therapy for cystic fibrosis, in part because of the potential for development of an immune reaction to the AAV1 capsid proteins. Here, to dampen the immune response to AAV1, we treated Rhesus monkeys with methylprednisolone before and after the instillation of two doses of AAV1Δ27-264-CFTR into their airways at 0 and 30 days, followed by a single dose of AAV1-GFP on day 60. Animals were euthanized on day 90, except for one monkey that was sacrificed at 1 year. No adverse events occurred, indicating that the two AAV1 vectors are safe. rAAV1-CFTR and AAV1-GFP vector genomes and mRNA transcripts were detectable in all lung sections and in the liver and pancreas at day 90 and after 1 year at levels comparable with animals necropsied at 90 days. The numbers of vector genomes for cystic fibrosis transmembrane regulator (CFTR) and green fluorescent protein (GFP) detected here were higher than those found in the monkeys infected without methylprednisolone treatment that we tested previously. 1 Also, lung surface and keratin 5-positive basal cells showed higher CFTR and GFP staining than did the cells from the uninfected monkey control. Positive immunostaining, also detected in the liver and pancreas, remained stable for at least a year. All animals seroconverted for anticapsid antibodies by 90 days post-treatment. The neutralizing antibody titer declined in the animal necropsied at 1 year. Conclusion: AAV1 safely and effectively transduces monkey airway and basal cells. Both the presence of vector genomes and transduction from AAV1-CFTR and AAV1-GFP virus seen in the monkeys 4 months to 1 year after the first instillation suggest that repeat dosing with AAV1-based vectors is achievable, particularly after methylprednisolone treatment.

Mutations in either of the polycystic kidney disease genes, PKD1 or PKD2, engender the growth of cysts, altering renal function. Cystic growth is supported by major changes in cellular metabolism, some of which involve the mitochondrion, a major storage site for Ca 2+ and a key organelle in cellular Ca 2+ signaling. The goal here was to understand the role of components of the mitochondrial Ca 2+ uptake complex in PC1-mutant cells in autosomal dominant polycystic kidney disease (ADPKD). We found that the mitochondrial Ca 2+ uniporter (MCU) and voltage-dependent anion channels 1& 3 (VDAC) were down-regulated in different mouse and cell models of ADPKD along with the Ca 2+ -dependent enzyme, pyruvate dehydrogenase phosphatase (PDHX). The release of Ca 2+ from the endoplasmic reticulum, and Ca 2+ uptake by the mitochondria were upregulated in PC1(polycystin)-null cells. We also observed an enhanced staining with MitoTracker Red CMXRos in PC1-null cultured cells than in PC1-containing cells and a substantially higher increase in response to ER Ca 2+ release. Increased colocalization of the Ca 2+ sensitive dye, rhodamine2, with MitoTracker Green suggested an increase Ca 2+ entry into the mitochondria in PC1 null cells subsequent to Ca 2+ release from the ER or from Ca 2+ entry from the extracellular solution. These data clearly demonstrate abnormal release of Ca 2+ by the ER and corresponding alterations in Ca 2+ uptake by the mitochondria in PC1 - null cells. Importantly, inhibiting mitochondrial Ca 2+ uptake with the specific inhibitor Ru360 inhibited cyst growth and altered both apoptosis and cell proliferation. We further show that the decrease in mitochondrial proteins and abnormally high Ca 2+ signaling can be reversed by application of the cystic fibrosis (CFTR) corrector, VX-809. We conclude that enhanced Ca 2+ signaling and alterations in proteins association with the mitochondrial Ca 2+ uptake complex are associated with malfunction of PC1. Finally, our results identify novel therapeutic targets for treating ADPKD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In this paper, the determined economic impact of the Sugar industry of the Coronavirus pandemic for aggravating items with a ramp-type demand with inflation effects in two-Distribution center storage devices and waste-material treatment cost using Taboo Search is developed. The owned Distribution center has a permanent ability of W units; rented Distribution center has unlimited capacity. Here, we hypothesized that the Block chain Economic Impact of the Coronavirus Pandemic Sugar Industry in Inventory Cost of Inventory in RW is greater than that in owned Distribution center using Taboo Search. The shortcomings of the economic impact of the Coronavirus pandemic Sugar industry are allowed and partially lagged behind, and it is assumed that Block chain's economic impact of the Coronavirus Sugar pandemic industry decreases over time with a variable deterioration rate and waste-material treatment cost using Taboo Search. The effect of inflation was also considered due to the different costs associated with Taboo Search applying the Economic Impact of the Coronavirus Sugar Industry Inventory System and waste-material treatment cost using Taboo Search. The mathematical sample is as well used to study the performance of the model using particle size optimization. The cost minimization technique is second-hand to get hold of expressions for total costs and erstwhile parameters., 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 Elsevier Ltd. All rights reserved. Selection and peer-review under responsibility of the scientific committee of the 1st International Conference on Computations in Materials and Applied Engineering – 2021.)

Genomic selection (GS) has the potential to improve the selection gain for complex traits in crop breeding programs from resource-poor countries. The GS model performance in multi-environment (ME) trials was assessed for 141 advanced breeding lines under four field environments via cross-predictions. We compared prediction accuracy (PA) of two GS models with or without accounting for the environmental variation on four quantitative traits of significant importance, i.e., grain yield (GRYLD), thousand-grain weight, days to heading, and days to maturity, under North and Central Indian conditions. For each trait, we generated PA using the following two different ME cross-validation (CV) schemes representing actual breeding scenarios: (1) predicting untested lines in tested environments through the ME model (ME_CV1) and (2) predicting tested lines in untested environments through the ME model (ME_CV2). The ME predictions were compared with the baseline single-environment (SE) GS model (SE_CV1) representing a breeding scenario, where relationships and interactions are not leveraged across environments. Our results suggested that the ME models provide a clear advantage over SE models in terms of robust trait predictions. Both ME models provided 2-3 times higher prediction accuracies for all four traits across the four tested environments, highlighting the importance of accounting environmental variance in GS models. While the improvement in PA from SE to ME models was significant, the CV1 and CV2 schemes did not show any clear differences within ME, indicating the ME model was able to predict the untested environments and lines equally well. Overall, our results provide an important insight into the impact of environmental variation on GS in smaller breeding programs where these programs can potentially increase the rate of genetic gain by leveraging the ME wheat breeding trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tomar, Singh, Dhillon, Chung, Poland, Singh, Joshi, Gautam, Tiwari and Kumar.)

The root system architectures (RSAs) largely decide the phosphorus use efficiency (PUE) of plants by influencing the phosphorus uptake. Very limited information is available on wheat's RSAs and their deciding factors affecting phosphorus uptake efficiency (PupE) due to difficulties in adopting scoring values used for evaluating root traits. Based on our earlier research experience on nitrogen uptake efficiency screening under, hydroponics and soil-filled pot conditions, a comprehensive study on 182 Indian bread wheat genotypes was carried out under hydroponics with limited P (LP) and non-limiting P (NLP) conditions. The findings revealed a significant genetic variation, root traits correlation, and moderate to high heritability for RSAs traits namely primary root length (PRL), total root length (TRL), total root surface area (TSA), root average diameter (RAD), total root volume (TRV), total root tips (TRT) and total root forks (TRF). In LP, the expressions of TRL, TRV, TSA, TRT and TRF were enhanced while PRL and RAD were diminished. An almost similar pattern of correlations among the RSAs was also observed in both conditions except for RAD. RAD exhibited significant negative correlations with PRL, TRL, TSA, TRT and TRF under LP (r = -0.45, r = -0.35, r = -0.16, r = -0.30, and r = -0.28 respectively). The subclass of TRL, TSA, TRV and TRT representing the 0-0.5 mm diameter had a higher root distribution percentage in LP than NLP. Comparatively wide range of H' value i.e. 0.43 to 0.97 in LP than NLP indicates that expression pattern of these traits are highly influenced by the level of P. In which, RAD (0.43) expression was reduced in LP, and expressions of TRF (0.91) and TSA (0.97) were significantly enhanced. The principal component analysis for grouping of traits and genotypes over LP and NLP revealed a high PC1 score indicating the presence of non-crossover interactions. Based on the comprehensive P response index value (CPRI value), the top five highly P efficient wheat genotypes namely BW 181, BW 103, BW 104, BW 143 and BW 66, were identified. Considering the future need for developing resource-efficient wheat varieties, these genotypes would serve as valuable genetic sources for improving P efficiency in wheat cultivars. This set of genotypes would also help in understanding the genetic architecture of a complex trait like P use efficiency., Competing Interests: No conflict of interest.

Stripe rust is one of the most destructive diseases of wheat ( Triticum aestivum L.), caused by Puccinia striiformis f. sp. tritici ( Pst ), and responsible for significant yield losses worldwide. Single-nucleotide polymorphism (SNP) diagnostic markers were used to identify new sources of resistance at adult plant stage to wheat stripe rust (YR) in 141 CIMMYT advanced bread wheat lines over 3 years in replicated trials at Borlaug Institute for South Asia (BISA), Ludhiana. We performed a genome-wide association study and genomic prediction to aid the genetic gain by accumulating disease resistance alleles. The responses to YR in 141 advanced wheat breeding lines at adult plant stage were used to generate G × E (genotype × environment)-dependent rust scores for prediction and genome-wide association study (GWAS), eliminating variation due to climate and disease pressure changes. The lowest mean prediction accuracies were 0.59 for genomic best linear unbiased prediction (GBLUP) and ridge-regression BLUP (RRBLUP), while the highest mean was 0.63 for extended GBLUP (EGBLUP) and random forest (RF), using 14,563 SNPs and the G × E rust score results. RF and EGBLUP predicted higher accuracies (∼3%) than did GBLUP and RRBLUP. Promising genomic prediction demonstrates the viability and efficacy of improving quantitative rust tolerance. The resistance to YR in these lines was attributed to eight quantitative trait loci (QTLs) using the FarmCPU algorithm. Four ( Q.Yr.bisa-2A.1 , Q.Yr.bisa-2D , Q.Yr.bisa-5B.2 , and Q.Yr.bisa-7A ) of eight QTLs linked to the diagnostic markers were mapped at unique loci (previously unidentified for Pst resistance) and possibly new loci. The statistical evidence of effectiveness and distribution of the new diagnostic markers for the resistance loci would help to develop new stripe rust resistance sources. These diagnostic markers along with previously established markers would be used to create novel DNA biosensor-based microarrays for rapid detection of the resistance loci on large panels upon functional validation of the candidate genes identified in the present study to aid in rapid genetic gain in the future breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tomar, Dhillon, Singh, Singh, Poland, Chaudhary, Bhati, Joshi and Kumar.)

Genetic diversity and population structure information are crucial for enhancing traits of interest and the development of superlative varieties for commercialization. The present study elucidated the population structure and genetic diversity of 141 advanced wheat breeding lines using single nucleotide polymorphism markers. A total of 14,563 high-quality identified genotyping-by-sequencing (GBS) markers were distributed covering 13.9 GB wheat genome, with a minimum of 1,026 SNPs on the homoeologous group four and a maximum of 2,838 SNPs on group seven. The average minor allele frequency was found 0.233, although the average polymorphism information content (PIC) and heterozygosity were 0.201 and 0.015, respectively. Principal component analyses (PCA) and population structure identified two major groups (sub-populations) based on SNPs information. The results indicated a substantial gene flow/exchange with many migrants (Nm = 86.428) and a considerable genetic diversity (number of different alleles, Na = 1.977; the number of effective alleles, Ne = 1.519; and Shannon's information index, I = 0.477) within the population, illustrating a good source for wheat improvement. The average PIC of 0.201 demonstrates moderate genetic diversity of the present evaluated advanced breeding panel. Analysis of molecular variance (AMOVA) detected 1% and 99% variance between and within subgroups. It is indicative of excessive gene traffic (less genetic differentiation) among the populations. These conclusions deliver important information with the potential to contribute new beneficial alleles using genome-wide association studies (GWAS) and marker-assisted selection to enhance genetic gain in South Asian wheat breeding programs., Competing Interests: Daljit Singh was a postdoc in the Department of Plant Pathology, Kansas State University, Manhattan, KS, USA, at the start of this project. He then joined The Climate Corporation, Bayer Crop Science, Creve Coeur, MO, USA. The Climate Corporation has no role in the project., (©2021 Tomar et al.)

Wheat grain yield (GY) improvement using genomic tools is important for achieving yield breakthroughs. To dissect the genetic architecture of wheat GY potential and stress-resilience, we have designed this large-scale genome-wide association study using 100 datasets, comprising 105,000 GY observations from 55,568 wheat lines evaluated between 2003 and 2019 by the International Maize and Wheat Improvement Center and national partners. We report 801 GY-associated genotyping-by-sequencing markers significant in more than one dataset and the highest number of them were on chromosomes 2A, 6B, 6A, 5B, 1B and 7B. We then used the linkage disequilibrium (LD) between the consistently significant markers to designate 214 GY-associated LD-blocks and observed that 84.5% of the 58 GY-associated LD-blocks in severe-drought, 100% of the 48 GY-associated LD-blocks in early-heat and 85.9% of the 71 GY-associated LD-blocks in late-heat, overlapped with the GY-associated LD-blocks in the irrigated-bed planting environment, substantiating that simultaneous improvement for GY potential and stress-resilience is feasible. Furthermore, we generated the GY-associated marker profiles and analyzed the GY favorable allele frequencies for a large panel of 73,142 wheat lines, resulting in 44.5 million datapoints. Overall, the extensive resources presented in this study provide great opportunities to accelerate breeding for high-yielding and stress-resilient wheat varieties.

Spot blotch disease caused by Bipolaris sorokiniana is a major constraint for wheat production in tropics and subtropics. The introgression of spot blotch resistance alleles to the disease susceptible lines is critical to securing the wheat production in these regions. Although genome-wide association studies (GWASs) for spot blotch were attempted earlier, the present study focused on identifying new quantitative trait loci (QTLs) for spot blotch under natural disease pressure in diverse field conditions. A total of 139 advanced spring wheat lines were evaluated in three environments (three years and two locations) in India and Bangladesh. The GWAS using 14,063 polymorphic genotyping-by-sequencing (GBS) markers identified eight QTLs associated with spot blotch disease resistance belonging to eight chromosomes across the wheat genome. Here, we report the identified marker-trait associations (MTAs), along with the allele effects associated with the disease. The functional annotation of the significant markers identified NBS-LRR, MADS-box transcription factor, and 34 other plant-related protein families across multiple chromosomal regions. The results indicate four promising new QTLs on chromosomes 1A (497.2 Mb), 1D (89.84 Mb), 2B (421.92 Mb), and 6D (6.84 Mb) associated with several disease resistance protein families. These results provide insights into new genomic regions associated with spot blotch disease, and with additional validation, could be utilized in disease resistance breeding efforts in wheat development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tomar, Singh, Dhillon, Singh, Poland, Joshi, Singh, Bhati, Kumar, Rahman, Tiwari and Kumar.)

Background & Aims: Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in PKHD1, encoding fibrocystin/polyductin (FPC). Severe disease occurs in perinates. Those who survive the neonatal period face a myriad of comorbidities, including systemic and portal hypertension, liver fibrosis, and hepatosplenomegaly. The goal here was to uncover therapeutic strategies for ARPKD., Methods: We used wild-type and an FPC-mutant cholangiocyte cell line in 3-dimenional cysts and in confluent monolayers to evaluate protein expression using western blotting and protein trafficking using confocal microscopy., Results: We found that the protein level of the cystic fibrosis transmembrane conductance regulator (CFTR) was downregulated. The levels of heat shock proteins (HSPs) were altered in the FPC-mutant cholangiocytes, with HSP27 being downregulated and HSP90 and HSP70 upregulated. FPC-mutant cholangiocytes formed cysts, but normal cells did not. Cyst growth could be reduced by increasing HSP27 protein levels, by HSP90 and HSP70 inhibitor treatments, by silencing HSP90 through messenger RNA inhibition, or by the novel approach of treating the cysts with the CFTR corrector VX-809. In wild-type cholangiocytes, CFTR is present in both apical and basolateral membranes. FPC malfunction resulted in altered colocalization of CFTR with both apical and basolateral membranes. Whereas, treatment with VX-809, increasing HSP27 or inhibiting HSP70 or HSP90 restored CFTR localization toward normal values., Conclusions: FPC malfunction induces the formation of cysts, which are fueled by alterations in HSPs and in CFTR protein levels and miss-localization. We suggest that CFTR correctors, already in clinical use to treat cystic fibrosis, could also be used as a treatment for ARPKD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

RuBisCO (Ribulose 1,5 bisphosphate carboxylase/oxygenase) by virtue of its dual specificity towards oxygen and carbon dioxide is an important rate-limiting step in photosynthesis and is believed to be the key factor for limited productivity of higher plants and algae. The photoautotrophic growth rate of cyanobacteria is a culmination of several factors including, rates of photosynthetic reactions, stress combating mechanisms and basic biomass generation metabolism in combination with optimal nutrient availability, irradiance, gaseous environment, etc. In case of cyanobacteria, the effect of RuBisCO in affecting the multiplication rate has been observed to show varied response. The current paper presents the RuBisCO activity of an early diverging cyanobacterium, Gloeobacter violaceus PCC 7421 and also compares the growth rates and RuBisCO activity of various cyanobacteria. A spectrophotometric estimation in a coupled enzyme assay system of the heterologous expressed G. violaceus PCC 7421 RuBisCO in E. coli, upon purification, revealed a carboxylation activity of LSu to be 5 nMol of phosphoglycerate min -1 mg -1 of protein, which is in coherence with the organism's slow growth rate. Further, the in vitro complementation of RbcL with RbcS in presence of RbcX of G. violaceus facilitated partial reconstitution of the protein and was hence found to cause a four-fold enhancement in its specific activity. The unique characteristics of the primitive cyanobacteria, such as, absence of thylakoids, lack of several photosystem constituting genes, slow carboxylation rate, pose limitation for its rapid multiplication. The RuBisCO carboxylation rate is observed as not the sole but an important parameter for obtaining optimal cell multiplication rates in photo-autotrophically multiplying cyanobacteria.

The objective of this study is to achieve a fundamental understanding of polymorphic interconversion during the tableting process, including during compaction, dwell, decompression/unloading, and ejection using an in situ mechanical Raman spectroscopy. The fit-for-purpose in situ mechanical Raman spectroscopy developed herein can provide simultaneous measurement of Raman spectra and densification for the powder compacts. Chlorpropamide (CPA), an antidiabetic drug, was selected as a model pharmaceutical compound because of its mechanical shear-induced polymorphic conversions. The results confirm that CPA polymorph A (CPA-A) was transformed to CPA polymorph C (CPA-C) under different compaction stresses. We also observed that the converted polymorph CPA-C could be reverted to the CPA-A due to the elastic recovery of powder compacts as detected during dwelling and unloading. This study is the first depiction of the dynamics of CPA polymorphic interconversion during compression, dwell, unloading, and ejection. Mechanistically, this study illustrates a correlation between the change in the powder compact's relative density and polymorphic interconversion of the drug substance in different solid-state forms. The present research suggests that the process-induced polymorph conversion is a complicated dynamic process, which could be affected by the compaction pressure, the elasticity/plasticity of the material, the level of elastic recovery, and the dissipation of residual stress. In summary, this study demonstrates that the in situ mechanical Raman spectroscopy approach enables the simultaneous detection of mechanical and chemical information of the powder compact throughout the tableting process.

Amyloidosis is a well-known but poorly understood phenomenon caused by the aggregation of proteins, often leading to pathological conditions. For example, the aggregation of insulin poses significant challenges during the preparation of pharmaceutical insulin formulations commonly used to treat diabetic patients. Therefore, it is essential to develop inhibitors of insulin aggregation for potential biomedical applications and for important mechanistic insights into amyloidogenic pathways. Here, we have identified a small molecule M1, which causes a dose-dependent reduction in insulin fibril formation. Biophysical analyses and docking results suggest that M1 likely binds to partially unfolded insulin intermediates. Further, M1-treated insulin had lower cytotoxicity and remained functionally active in regulating cell proliferation in cultured Drosophila wing epithelium. Thus, M1 is of great interest as a novel agent for inhibiting insulin aggregation during biopharmaceutical manufacturing.

Chalcone, a privileged structure, is considered as an effective template in the field of medicinal chemistry for potent drug discovery. In the present study, a privileged template chalcone was designed, synthesized, and characterized by various spectroscopic techniques (NMR, high-resolution mass spectrometry, Fourier transform infrared (FT-IR) spectroscopy, UV spectroscopy, and single-crystal X-ray diffraction). The mechanism of binding of chalcone with bovine serum albumin (BSA) was determined by multispectroscopic techniques and computational methods. Steady-state fluorescence spectroscopy suggests that the intrinsic fluorescence of BSA was quenched upon the addition of chalcone by the combined dynamic and static quenching mechanism. Time-resolved spectroscopy confirms complex formation. FT-IR and circular dichroism spectroscopy suggested the presence of chalcone in the BSA molecule microenvironment and also the possibility of rearrangement of the native structure of BSA. Moreover, molecular docking studies confirm the moderate binding of chalcone with BSA and the molecular dynamics simulation analysis shows the stability of the BSA-drug complex system with minimal deformability fluctuations and potential interaction by the covariance matrix. Moreover, pharmacodynamics and pharmacological analysis show good results through Lipinski rules, with no toxicity profile and high gastrointestinal absorptions by boiled egg permeation assays. This study elucidates the mechanistic profile of the privileged chalcone scaffold to be used in therapeutic applications., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

In present investigation, an attempt was undertaken to modify the C-9 position of noscapine (Nos), an opium alkaloid to yield 9 -hydroxy methyl and 9 -carbaldehyde oxime analogues for augmenting anticancer potential. The synthesis of 9-hydroxy methyl analogue of Nos was carried out by Blanc reaction and 9-carbaldehyde oxime was engineered by oxime formation method and characterized using FT-IR, 1 H NMR, 13 C NMR, mass spectroscopy, and so on techniques. In silico docking techniques informed that 9-hydroxy methyl and 9-carbaldehyde oxime analogues of Nos had higher binding energy score as compared to Nos. The IC50 of Nos was estimated to be 46.8 µM signficantly (P < 0.05) higher than 8.2 µM of 9-carbaldehyde oxime and 4.6 µM of 9-hydroxy methyl analogue of Nos in U87, human glioblastoma cells. Moreover, there was significant (P < 0.05) difference between the IC50 of 9-carbaldehyde oxime and 9-hydroxy methyl analogue of Nos. Consistent to in vitro cytotoxicity data, 9-hydroxy methyl analogue of Nos induced significantly (P < 0.05) higher degree of apoptosis of 84.6% in U87 cells as compared to 78.5% and 64.3% demonstrated by 9-carbaldehyde oxime and Nos, respectively. Thus the higher therapeutic efficacy of 9-hydroxy methyl analogue of Nos may be credited to higher solubility and inhibitory constant (K).

The prevalence of obesity is increasing at an alarming rate worldwide with about 30% of the world population classified as obese. Obese body structure results when energy intake exceeds energy expenditure in an individual. Increase in the consumption of high-energy eatables, in the context of portion and energy provided, has resulted in obese populations which is becoming the leading cause of metabolic disorders related to morbidity. The obesity-related comorbidity is an enormous liability on health services and will affect measures taken in tackling the increasing obesity rate. Prevention of an obese phenotype is the most suitable long-term strategy. Another approach towards the treatment of obesity is weight management through phytotherapeutics. In this study, we explored the anti-obesity effects of Cinnamon ( Cinnamomum zeylanicum ) in adult male zebrafish. Through BMI measurements, blood glucose level analyses, serum triglyceride analyses, Oil Red O staining as well as quantitative Real Time-PCR, the ability of cinnamon to reduce metabolic disorders associated with obesity is investigated for the first time in a zebrafish model. Our studies indicate that cinnamon ameliorates the genotypic and phonotypic characteristics associated with obesity through lowering of BMI, blood glucose, triglyceride levels, lipid levels in the liver and through gene modulation.

Duplex kidney with an ectopic upper moiety ureter usually presents with urinary incontinence in young females. If the ectopic ureter belongs to a non-functioning moiety, it is treated with surgical resection of the moiety. Renal artery embolization has been used in patients with a poorly functioning kidney for various indications. In the present report, a 30-year old lady presented with continuous urinary incontinence with normal voids in between. On evaluation, she was found to have duplex left kidney with poorly functioning upper moiety associated with an ectopic ureter opening into the vagina. She underwent successful upper segmental renal artery embolization with no postoperative complications and uneventful recovery. Hence, renal artery embolization is a minimally invasive and well tolerated alternative to surgical partial or heminephrectomy for a non-functioning duplex renal moiety.

It would be of great significance to introduce a new biocompatible Layered Double Hydroxide (LDH) for the efficient remediation of wastewater. Herein, we designed a facile, biocompatible and environmental friendly layered double hydroxide (LDH) of NiFeTi for the very first time by the hydrothermal route. The materialization of NiFeTi LDH was confirmed by FTIR, XRD and Raman studies. BET results revealed the high surface area (106 m 2 /g) and the morphological studies (FESEM and TEM) portrayed the sheets-like structure of NiFeTi nanoparticles. The material so obtained was employed as an efficient adsorbent for the removal of organic dyes from synthetic waste water. The dye removal study showed >96% efficiency for the removal of methyl orange, congo red, methyl blue and orange G, which revealed the superiority of material for decontamination of waste water. The maximum removal (90%) of dyes was attained within 2 min of initiation of the adsorption process which supported the ultrafast removal efficiency. This ultrafast removal efficiency was attributed to high surface area and large concentration of -OH and CO 3 2- groups present in NiFeTi LDH. In addition, the reusability was also performed up to three cycles with 96, 90 and 88% efficiency for methyl orange. Furthermore, the biocompatibility test on MHS cell lines were also carried which revealed the non-toxic nature of NiFeTi LDH at lower concentration (100% cell viability at 15.6 μg/ml). Overall, we offer a facile surfactant free method for the synthesis of NiFeTi LDH which is efficient for decontamination of anionic dyes from water and also non-toxic.

Introduction: laparoscopic pyeloplasty is an important tool in urology armamentarium. The most important & also the difficult part of this surgery is intracorporial suturing and knotting. There are only a few reports of knotless Barbed sutures for upper tract reconstruction. We report the comparative outcomes of Laparoscopic Pyeloplasty with barbed suture vs non barbed sutures used for uretero-pelvic anastomosis., Materials and Methods: We retrospectively reviewed patients' records that underwent Laparoscopic pyeloplasty at our Institution from January 2013 to May 2014. Total 37 patients were underwent LP in this period. Whole of the procedure was same as conventional LP except suture material. 3-0 barbed suture was used in 21 patients and 3-0 vicryl used in 16 patients for uretero-pelvic anastomosis and continuous suturing technique was employed. Patients' demographics, total operative time, intracorporial suturing time, post operative complications, symptoms & renal isotope scan were recorded., Results: Average total operative time was significantly less in barbed suture group vs vicryl group (162 vs 208 minutes) (p=0.0811). Average time taken for intracorporial suturing was 31.2 minutes vs 70 minutes (p=0.0576). 1 patient developed post operative urine leak which persisted for 5 days in barbed group (4.76 %) vs no leak in vicryl group. Most common complication was UTI presented in 2 patients (9.5 %) vs 2 in vicryl (12.5%). JJ stent was removed at 4 weeks. Median follow up was 3 months with 7 patients lost to follow up. None of the patients found to have obstructive drainage or deterioration of split function on follow up isotope renogram at 3 months., Conclusions: In this study, Laparoscopic pyeloplasty with barbed suture has acceptable outcome when compared to conventional non barbed suture on short term basis. Laparoscopic Pyeloplasty with barbed suture can potentially become the standard approach in near future., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Urology Annals.)

Lysozyme is a well-characterized protein in terms of its structure, dynamics, and functions. It has thus emerged as a potential target to understand protein-drug interactions. The aim of our study is to gain a biophysical outlook on the interaction of lysozyme (Lyz), a well-known model protein, with Noscapine, a potent tubulin-binding anticancer drug. Noscapine (Nos) is effective against a wide range of cancer and shows low toxicity and few side effects. We report the underlying mechanism of complex formation between Nos and Lyz using spectroscopic and advanced computational avenues. The spectroscopic techniques, that is, absorption and steady-state and time-resolved fluorescence, proved that Lyz-Nos forms a complex, and the quenching mechanism was of the static type. The binding constant was in the order of 10 3 indicative of moderate binding, while the stoichiometry of the protein-drug complex was 1:1 at 298 K. The secondary structural analysis using CD and UV thermal denaturation further confirmed the conformational changes in the protein upon binding with Nos. Molecular dynamics simulation studies confirmed the stable binding with minimum deviations in RMSD. The above conclusions are significant to the development of the pharmacokinetics and pharmacodynamic properties of Nos, and its successful interaction with a versatile protein like Lyz will help in overcoming its previous limitations., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Temperature rise in Lithium-ion batteries (LIBs) due to solid electrolyte interfaces breakdown, uncontrollable exothermic reactions in electrodes and Joule heating can result in the catastrophic failures such as thermal runaway, which is calling for reliable real-time electrode temperature monitoring. Here, we present a customized LIB setup developed for early detection of electrode temperature rise during simulated thermal runaway tests incorporating a modern additive manufacturing-supported resistance temperature detector (RTD). An advanced RTD is embedded in a 3D printed polymeric substrate and placed behind the electrode current collector of CR2032 coin cells that can sustain harsh electrochemical operational environments (acidic electrolyte without Redox, short-circuiting, leakage etc.) without participating in electrochemical reactions. The internal RTD measured an average 5.8 °C higher temperature inside the cells than the external RTD with almost 10 times faster detection ability, prohibiting thermal runaway events without interfering in the LIBs' operation. A temperature prediction model is developed to forecast battery surface temperature rise stemming from measured internal and external RTD temperature signatures.

A simple, rapid and selective high-performance thin-layer chromatographic (HPTLC) method has been developed and validated for simultaneous determination of three withanolides (withaferin A, withanone and withanolide A) and three phenolic acids (caffeic acid, ferulic acid and benzoic acid) from different parts (root, stem and leaf) of Withania somnifera and its two commercially available polyherbal formulations. The extraction efficiency of withanolides and phenolic acids were tested using two solvents, chloroform and methanol, respectively. HPTLC separation was performed on silica coated aluminium plates Si 60F 254 ; using toluene, ethyl acetate and acetic acid (60:40:4). The samples were quantitated at 231 nm. The purity and identity of peaks of all the six analytes were confirmed by matching Rf values and UV-spectrum with authentic standards. The identity of three withanolides was further confirmed by positive ion electrospray ionization mass spectrometry (ESI-MS/MS) analyses. The developed method was validated for sensitivity, linearity, reproducibility, accuracy, the limit of detection (LOD) and limit of quantification (LOQ) following the guidelines of the International Conference on Harmonization (ICH). The method was found to be linear (r > 0.99) in the range of 50-2000 ng/band for benzoic acid and 50-1000 ng/band for the other five studied metabolites. This simple and accurate HPTLC method provided enhanced resolution of studied analytes as compared to other phytoconstituents present in W. somnifera extracts. It has also been successfully applied in the analysis and quantification of two polyherbal formulations containing W. somnifera plant parts., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: The objective of this study is to compare postoperative morbidity of closure versus nonclosure of the lingual mucosa graft (LMG) harvest site in augmentation urethroplasty., Materials and Methods: From January 2015 to November 2016, a total of 42 patients who underwent LMG urethroplasty randomized in 2 groups. In Group 1, donor-harvesting site was left open while in Group 2, donor site was closed. Self-made questionnaires were to assess postoperative pain, difficulty in tongue protrusion, swelling and numbness in graft harvest site, speech impairment, and difficulty in tolerating liquid and regular diet., Results: Mean visual analog scales score was 7.1 in Group 1, and 7.9 in Group 2 on day 0, which was statistically significant. Nearly 90.47% of patients in closure group and 95.23% in nonclosure group were able to swallow liquid diet on day 0 ( P = 0.5604). On day 3, 95.71% of patients in Group 1 and 80% in Group 2 were able to swallow soft diet ( P = 0.1604). Numbness was present in 80.95% Group 1 and 71.42% in Group 2 on day 0, which improved to 28.57% pts in Group 1 and 33.33% in Group 2 on day 3. On day 3, slurring of speech was more frequent in closure group (80%). However, at the end of a week, there was no difference in both groups. Saliva production was significantly increased in Group 1 in the 1 st week., Conclusion: Long-term morbidities of closing or nonclosing the LMG donor site are similar, but in short term, there is less pain, less edema, early recovery of tongue movements in nonclosure groups., Competing Interests: There are no conflicts of interest.

Introduction: In the year 2003, Joshi et al . developed a validated outcome assessment tool to measure the ureteral stent-related symptoms. The original English language Ureteral Stent Symptom Questionnaire (USSQ) has been validated in various languages worldwide. Our objective was to develop the USSQ in Hindi, a commonlyused language in India, by validating it in patients undergoing ureteroscopic lithotripsy., Materials and Methods: A final Hindi version of the USSQ was derived from the original English version to apply to the study population by translation, back translation, and face-to-face interviews. The Hindi and English versions were completed by 70 patients undergoing ureteroscopic lithotripsy with stent in situ , on postoperative days 7 and 8, and 4 weeks after stent removal. Similarly, discriminant validity was checked among 50 healthy individuals. A detailed statistical analysis was used to correlate results (Cronbach's α coefficient, Spearman's correlation, and Mann-Whitney U-test)., Results: A total of 70 patients were enrolled in the study and 61 completed the final assessment. The median age was 35 years (range: 18-60 years). The USSQ domain scores with the stent in situ were higher than poststent status. The test-retest reliability checked by Cronbach's α coefficient (>0.44) and Spearman's correlation coefficient (>0.44) were acceptable to good. We found high discriminant validity of the questionnaire between patients with stent and the healthy controls ( P < 0.05)., Conclusion: Our results demonstrate satisfactory validity for the Hindi version of the USSQ for the assessment of quality of life in patients with stent. This is ready for application in the clinical studies and the future stent-related research in Hindi language., Competing Interests: Conflict of Interest: There are no conflicts of interest.

MicroRNA 155 (miR-155) is an oncomir, generated as a noncoding RNA from the BIC gene whose promoter activity is mainly controlled via activation protein 1 (AP-1) and NF-κB transcription factors. We found that the expression levels of miR-155 and programmed cell death 4 (Pdcd4) exhibit inverse relationships in tongue cancer cells (SAS and AWL) and tumor tissues compared to their relationships in normal FBM cells and normal tongue tissues, respectively. In silico and in vitro studies with the 3' untranslated region (UTR) of Pdcd4 via luciferase reporter assays, quantitative PCR (qPCR), and Western blotting showed that miR-155 directly targets Pdcd4 mRNA and blocks its expression. Ectopic expression of Pdcd4 or knockdown of miR-155 in tongue cancer cells predominantly reduces AP-1-dependent transcriptional activity of the BIC promoter and decreases miR-155 expression. In this study, we demonstrate that miR-155 expression is modulated by a feedback loop between Pdcd4, AP-1, and miR-155 which results in enhanced expression of miR-155 with a consequent progression of tongue tumorigenesis. Further, miR-155 knockdown increases apoptosis, arrests the cell cycle, regresses tumor size in xenograft nude mice, and reduces cell viability and colony formation in soft-agar and clonogenic assays. Thus, the restoration of Pdcd4 levels by the use of molecular manipulation such as using a miR-155 sponge has an essential role in the therapeutic intervention of cancers, including tongue cancer., (Copyright © 2019 American Society for Microbiology.)

Objective: Histopathological changes in oral (buccal or lingual) mucosa after exposure to urine are still not completely understood. We evaluated these changes in free oral mucosal graft integrated in human urethra., Material and Methods: Total 19 patients with recurrent urethral stricture after oral mucosa urethroplasty (buccal 12 and lingual 7) were prospectively evaluated. Intraoperatively integrated buccal or lingual mucosal graft sample that was previously engrafted to urethra was completely excised along with healthy oral mucosa, and it was sample processed for histopathological evaluation by dedicated pathologist. Preoperative clinical data were properly collected from all the study participants., Results: The mean age of the patients was 30 years, and the mean preoperative peak flow rate was 4.2 mL/s. Etiology of initial stricture was idiopathic in 13 (68.42%) patients and traumatic urethral catheterization in 6 (31.58%) patients. Mean interval from previous buccal mucosal urethroplasty to current urethroplasty was 21.9 months (range 12-46 months). On repeat urethroplasty, the mean stricture segment length was 59.2 (38-77) mm [60.08 (38-74.6) mm buccal, and 58.32 (39.6-77) mm lingual]. These integrated oral mucosal grafts maintained their histopathological characteristics in all patients except some kind of changes like submucosal fibrosis in seven (58.33%) cases of buccal and vacuolar degeneration in five (71.42%) cases of lingual mucosal urethroplasty., Conclusion: Histopathological characteristics of integrated oral (buccal and lingual) mucosal grafts were maintained even on exposure to urine except some changes like submucosal fibrosis and vacuolar degeneration. Impact of these changes require further research.

Surgical clipping and endovascular coiling are well recognized as conventional treatments of Penetrating Brain Injury aneurysms. These clinical approaches show partial success, but often result in thrombus formation and the rupture of aneurysm near arterial walls. The authors address these challenging brain traumas with a unique combination of a highly biocompatible biopolymer hydrogel rendered magnetic in a flexible and resilient membrane coating integrated to a scaffold stent platform at the aneurysm neck orifice, which enhances the revascularization modality. This work focuses on the in situ diagnosis of nano-mechanical behavior of bacterial nanocellulose (BNC) membranes in an aqueous environment used as tissue reconstruction substrates for cerebral aneurysmal neck defects. Nano-mechanical evaluation, performed using instrumented nano-indentation, shows with very low normal loads between 0.01 to 0.5 mN, in the presence of deionized water. Mechanical testing and characterization reveals that the nano-scale response of BNC behaves similar to blood vessel walls with a very low Young´s modulus, E (0.0025 to 0.04 GPa), and an evident creep effect (26.01 ± 3.85 nm s -1 ). These results confirm a novel multi-functional membrane using BNC and rendered magnetic with local adhesion of iron-oxide magnetic nanoparticles., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ankyloblephron filiform adnatum (AFA) is a rare benign congenital anomaly that can arise either in isolation or associated with a syndrome. It should be treated as early as possible due to its ambylogenic potential. We report a case of a successfully managed newborn that had sporadic AFA detected at birth. Our case is unique in the sense that sporadic AFA with Atrial septal defect has not been reported in the literature., (© NEPjOPH.)

Antibiotic resistance is not only a global public health threat but also a huge economic burden to our society that urgently needs to be addressed by improved antibiotics and continuing development of novel molecules to treat resistant bacterial infections. Nowadays combination therapies offer a competent approach to counteract antibiotic resistance in bacteria. Better knowledge of mechanisms of antibiotic resistance has lead to the finding of new alternatives to antibiotic therapy. Hence, in this article, we report a novel series of indoline derivatives and their computational study as potent antimicrobials. The present study investigates the indoline based derived library interaction with DNA gyrase B enzyme to be used as a potential antimicrobial drug. Computational approaches were employed to carry out the molecular interactions and pharmacological studies. In this study, we have compared indoline with its derivatives and have found that compound 13 (1m) resulted in the strong binding with the highest score (-9.02 kcal/mol) in the designed library where indoline showed (-6.43 kcal/mol). Furthermore, molecular dynamics simulation run also confirmed the strongest interaction of a compound and target protein with less RMSD and RMSF deviation of the complex. Notably, the compound was also found to possess the good pharmacological properties and pharmacokinetic properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Bromo-Noscapine (BrNs) is a tubulin-binding cytotoxic agent with significant activity against breast and lung cancer. The mechanistic interaction insight into the binding of bovine serum albumin (BSA) with BrNs can provide critical information about the pharmacodynamics and pharmacokinetics properties. Here, various spectroscopic techniques and computational methods were employed to understand the dynamics of BrNs and BSA interaction. The intrinsic fluorescence of BSA was quenched by BrNs through a static quenching procedure. The stoichiometry of BrNs-BSA complex was 1:1 and binding constant of the complex was in the order of 10 3  M -1 at 298 K. Based on thermodynamic analysis, it was deduced that binding process of the BrNs with BSA was spontaneous and exothermic, and the major forces between BrNs and BSA were van der waals forces and hydrogen bonding. Moreover, results of FT-IR, CD, UV spectra concluded significant conformational change in BSA on binding with BrNs. The in vitro findings were further confirmed by in silico assays. Molecular docking showed strong interactions with score of -8.08 kcal/mol. Molecular dynamics simulation analysis also suggested the stable binding with lower deviation in RMSD and RMSF values through persistent long simulation run. This study suggests optimal efficiency of diffusion of the BrNs into the bloodstream for the treatment of cancer.

We report a case of 20-year-old young male with hematuria caused by bulbar artery pseudoaneurysm. There was neither history of trauma nor prior bladder catheterization. Nontraumatic, non-iatrogenic bulbar artery pseudoaneurysm is a very rare cause of hematuria. Endovascular management by gel foam embolization after selective catheterization of bulbar branch of internal pudendal artery was done. The reason behind gel foam embolization was that gel foam provides temporary arterial occlusion to allow time for mucosal healing and so erectile function will not be affected.

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (‒38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 μg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

Even after huge strides in medicine, cancer continues to be a formidable disease, which is slated to become the leading cause of death worldwide. The present study investigates the 1,3-benzodioxole and its propargyl ether derivatives as a novel histone deacetylase enzyme inhibitor in order to cure cancer, as aberrant expression of histone deacetylases (HDACs) is associated with carcinogenesis. Bioinformatics approaches were employed to carry out preclinical and pharmacological evaluations of designed benzodioxole derivatives. Furthermore, their interaction with HDAC-1 enzyme was studied through computational methods for their specific inhibitory effects and evaluated for their LD50 (oral rat acute toxicity) value. In addition to this work, three-dimensional (3D) structure of HDAC-1 enzyme was extracted and evaluated using various parameters including Ramachandran plot and molecular docking stimulation. In our study, we found that compound 7 and compound 9 have higher binding score than approved drugs (SAHA, TSA and VPA). Importantly, these compounds were found to possess good pharmacological and pharmacokinetic properties and can be considered as potent novel compound to combat the HDAC-1 enzyme to cure cancer. Compounds were also analyzed and validated with parameters like absorption, metabolism, excretion, toxicity and synthetic accessibility during the preclinical evaluation. This study paves way to search for novel and potent small chemical compounds for inhibiting HDAC-1 enzyme and in particular to combat the cancer progression by interrupting the cell cycle.

A piezoelectric material KNbO3 has been co-substituted with the magnetic ions Sm3+ and Fe3+ in order to explore the relation between piezoelectricity and magnetism. The samples K1-xSmxNb1-xFexO3 [x = 0.0-0.1] were synthesized using a solid state reaction route, after estimating the structural stability with the substitution. Structural studies were employed using XRD with Rietveld refinement and Raman analysis suggesting Amm2 symmetry. Also, the transition temperature was observed to change with the increase in Sm and Fe content. This transition temperature was also confirmed through high temperature XRD and high temperature Raman results. The dielectric and piezoelectric properties were found to be in correlation with the intensity of Raman modes for substituted samples, indicating better ferroelectricity at x = 0.05. A correlation between piezoelectric and magnetic properties was established in terms of the coercive field and exchange energy.

Introduction: The study aimed to evaluate the factors which affect the spontaneous passage of lower ureteric calculus on the basis of noncontrast computed tomography kidneys, ureters, and bladder (NCCT KUB) stone diameter, stone density, and plasma C-reactive protein (CRP) level., Materials and Methods: We conducted a prospective study of 200 patients with lower ureteric calculus 5-10 mm in size, from October 2015 to December 2016. All patients underwent NCCT KUB region with a 5 mm axial and reformatted coronal section. Edema just above the calculus and rim sign at the level of calculus and density of calculus is evaluated. Only scan with isolated, unilateral, solitary ureteric calculus was included in the final analysis and monitored up to 4 weeks, and plasma CRP is estimated in all patients to determine the clinical outcome., Results: A total of 200 patients (145 males, 55 females; mean age ± standard deviation, 34.73 ± 10.29) were included in the study. Lower ureteric calculus between 5-7 mm passed in 70% and 7-10 mm passed in 40%. There was 18% underestimation of maximum stone diameter in axial plane as compared to coronal plane. For spontaneous passage of calculus, craniocaudal (CC) diameter is more reliable then axial in NCCT. Rim sign and edema is absent in 64% of those passed spontaneous calculus. CRP level more than 2.45 mg/dl has low spontaneous expulsion rate. The stone with different HU passes through the ureter with same rate., Conclusion: Plasma CRP level and CC diameter and absence of rim sign on NCCT KUB are more reliable factors then density for spontaneous passage of ureteric calculus., Competing Interests: There are no conflicts of interest.

Autoimmunity arises when highly active immune responses are developed against the tissues or substances of one's own body. It is one of the most prevalent disorders among the old-age population with prospects increasing with age. The major cause of autoimmunity and associated diseases is the dysregulation of host immune surveillance. Impaired repairment of immune system and apoptosis regulation can be seen as major landmarks in autoimmune disorders such as the mutation of p53 gene which results in rheumatoid arthritis, bowel disease which consequently lead to tissue destruction, inflammation and dysfunctioning of body organs. Cytokines mediated apoptosis and proliferation of cells plays a regulatory role in cell cycle and further in cancer development. Anti-TNF therapy, Treg therapy and stem cell therapy have been used for autoimmune diseases, however, with the increase in the use of immunomodulatory therapies and their development for autoimmune diseases and cancer, the understanding of human immune system tends to become an increasing requirement. Hence, the findings associated with the relationship between autoimmune diseases and cancer may prove to be beneficial for the improvement in the health of suffering patients. Here in, we are eliciting the underlying mechanisms which result in autoimmune disorders causing the onset of cancer, exploration of interactome to find the pathways which are mutual to both, and recognition of hotspots which might play important role in autoimmunity mediated therapeutics with different therapies such as anti-TNF therapy, Treg therapy and stem cell therapy.

Serotonin is one of the important neurotransmitters of our body. It's abnormal concentration is associated with multiple disorders and diseases. Sensitive and precise electrochemical determination of serotonin is not possible with bare working electrodes due to various reasons viz. electro-chemical fouling, presence of other biological molecules having similar oxidation potential, and lower concentration of serotonin in biological samples. Surface modification of working electrode is required for fast, precise, selective, and sensitive detection of serotonin. We have extensively reviewed the research approaches where serotonin has been sensitively detected using surface modified electrodes in the presence of other interfering agents. This review aims at presenting the electrochemical detection of serotonin using various surface modified electrodes such as glassy carbon, graphite, carbon fiber, diamond, screen printed, ITO, and metal electrodes modified with conducting polymers and polyelectrolytes, carbon nanomaterials, metal or metal oxide nanoparticles, biological compounds, and other conducting materials. The analytical figures of merits of various research approaches for detection of serotonin have been compared in the article. The properties of material used for surface modification, chemical interactions at the interfaces, and electrocatalytic effects of modified surfaces on sensing of serotonin have been thoroughly discussed in this review., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Renal LGFMS is an extremely rare tumor. So far, only four cases have been reported in literature. LGFMS are indolent tumor with distinctive histopathological features with potential for late recurrences and metastasis. The diagnosis is made on histopathological examination and supported by immunohistochemical analysis. A 35-year-old young male was presented with flank pain and lump and diagnosed as low-grade fibromyxoid sarcoma after surgery on immunohistochemical analysis. This is the fifth case of renal LGFMS and we presented the review of literature. Radical surgery remains the primary treatment modality. Long follow-up is mandatory., Competing Interests: Compliance with Ethical StandardsThe authors declare that they have no conflict of interest.

Purpose: To report our initial experience with urethral reconstruction using a combined dorsal lingual mucosal graft (LMG) and ventral onlay preputial flap for long obliterative or near-obliterative strictures in circumcised patients., Materials and Methods: This was a retrospective study of 10 patients from January 2015 to June 2017 with long obliterative or near-obliterative anterior urethral strictures and circumcised prepuces. All patients underwent a combined approach using a dorsally LMG and a narrow preputial onlay flap ventrally to create a 26-30 Fr. neourethra over a 14-Fr Foley catheter. Success was defined as no requirement for additional urethral instrumentation. The follow-up period ranged from 6 to 32 months., Results: The patients ranged in age from 17 to 44 years (mean, 32.3±9.59 years) and stricture length ranged from 9 to 12.5 cm (mean, 10.77±1.15 cm). Four strictures were obliterative and six were near-obliterative. Two patients had a history of prior urethroplasty. The length of the LMGs harvested ranged from 11 to 14 cm (mean, 12.8±1.03 cm). The preputial flaps available were from 1 to 1.5 cm in width (1.29±0.16 cm) and the desired length. Maximum urinary flow rate (Qmax) achieved ranged from 12 to 26 mL/s (mean, 20.46±3.71 mL/s) after 3 months. One patient needed a single direct visualized internal urethrotomy and another patient develop temporary superficial penile necrosis. The success rate was 90%., Conclusions: Long obliterative and near-obliterative penile and penobulbar urethral strictures can still be treated in circumcised patients using available preputial skin along with lingual mucosa with good outcomes., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Objective: To evaluate the efficacy and safety of silodosin, solifenacin, tadalafil and their combinations in reducing double J (DJ) stent-related symptoms (SRS)., Material and Methods: A total of 335 patients who underwent DJ stenting and develop SRS at 1 st week were randomized into eight groups. Ureteral stent symptom questionnaire (USSQ) and Quality of life (QOL) scores were noted in each group: Group A-Silodosin (8 mg OD)+ Solifenacin (10 mg OD)+ Tadalafil (5 mg OD), B - Silodosin 8 mg OD, C - Solifenacin 10 mg OD, D- Tadalafil 5 mg OD, E- Silodosin (8 mg OD) + Solifenacin (10 mg OD), F- Silodosin (8 mg 0D)+ Tadalafil (5 mg OD), G- Solifenacin (10 mg OD)+ Tadalafil (5 mg OD) and H-placebo. Analgesic (diclofenac 50 mg) was given as per requirement. All groups received the drugs for 14 days and again USSQ, QOL score with analgesic requirement were noted in each group., Results: USSQ score was similar in all groups at 1 st week but all groups (Groups A-G) led to significant decrease in USSQ score at 3 rd week as compared to Group H with less requirement of analgesic. However when we compared groups with each other we found that mean USSQ score and analgesic requirement was favoring Group E as compared to other groups. Quality of life score was also best in Group E (mean 1.5) (p<0.05)., Conclusion: Combination therapy with silodosin and solifenacin (group E) was effective for relieving SRS with improved quality of life and less requirement of analgesic than any other groups and should be considered in patients who develop SRS.

Objective: To compare differences of morbidity profile, oncological yield, and efficacy between video endoscopic inguinal lymphadenectomy and open inguinal lymphadenectomy cases., Materials and Methods: A total of 29 patients with proven squamous cell carcinoma of the penis were selected for inguinal lymphadenectomy from August 2013 to January 2017. Video endoscopic lymphadenectomy was performed on 1 limb and open inguinal lymphadenectomy was performed on the contralateral side. Relevant outcome data such as operative time, complication rate, number of lymph nodes removed, number of positive nodes, and recurrence during the follow-up period were collected, analyzed, and compared., Results: The mean operative time was significantly longer for the video endoscopic inguinal lymphadenectomy group (mean = 162.83 minutes) as compared with the open group (mean = 92.35 minutes). However, the mean numbers of lymph nodes removed were 7.6 in the endoscopic group and 8.3 in the open group. Postoperative complications occurred in 10 limbs (34.48%) in the open group and in 3 limbs (10.34%) in the endoscopic group. In the follow-up period ranging from 7 to 28 (mean 14) months, 2 patients died because of either distant or visceral metastasis., Conclusion: The present study clearly outlines the fact that video endoscopic inguinal lymphadenectomy can deliver an equivalent lymph node yield similar to open inguinal lymphadenectomy with significantly less morbidity and is not affected by either the palpability or the number of palpable nodes. Thus, we believe that this minimally invasive technique can provide a prudent alternative for the management of the inguinal region in carcinoma of the penis., (Copyright © 2017. Published by Elsevier Inc.)

Purpose: The aim of the current study was to compare Guy's score and STONE score in predicting the success and complication rate of percutaneous nephrolithotomy (PCNL)., Materials and Methods: A total of 445 patients were included in the study between July 2015 and December 2016. The patients were given STONE score and Guy's Stone Score (GSS) grades based on CT scan done preoperatively and intra- and post-operative complications were graded using the modified Clavien grading system. The PCNL were done by a standard technique in prone positions., Results: The success rate in our study was 86.29% and both the GSS and STONE score were significantly associated with a success rate of the procedure. Both the scoring systems correlated with operative time and postoperative hospital stay. Of the total cases, 102 patients (22.92%) experienced complications. A correlation between STONE score stratified into low, moderate, and high nephrolithometry score risk groups (low scores 4-5, moderate scores 6-8, high scores 9-13), and complication was also found ( P = 0.04) but not between the GSS and complication rate ( P = 0.054)., Conclusion: Both GSS and STONE scores are equally effective in predicting success rate of the procedure., Competing Interests: There are no conflicts of interest.

Objectives: To study the differential expression of oestrogen receptor (ER) subtypes in human urinary bladder tissue using immunohistochemistry (IHC) methods and to explore their correlation with various measures of lower urinary tract symptoms (LUTS)., Methods: In this prospective case-control study, the case group comprised 34 patients with bothersome LUTS who underwent transurethral resection of prostate (TURP), while the control group comprised 19 age-matched, otherwise healthy patients who underwent cystoscopy to investigate microscopic haematuria. Cystoscopy and bladder biopsy were performed in both groups. IHC evaluation of biopsy specimens was carried out for ER subtypes (ER-α and ER-β) and for Ki 67 in semi-quantitative fashion. Correlations of receptors with various measures of benign prostatic hyperplasia (BPH)/LUTS were also assessed., Results: Expression of ER-α (in both epithelial and stromas cells) was statistically significantly greater in the case group than in the control group, but ER-β expression was not significantly different between the groups. Ki 67 expression was also significantly greater in the case group. Comparison of clinical variables according to receptor status showed that International Prostate Symptom Score (IPSS), post-void residual urine volume (PVR) and prostate volume were significantly associated with epithelial and stromal ER-α; however, ER-β was associated only with PVR., Conclusion: We found significant correlation between bladder ER levels (specifically ER-α) and various clinical measures of BPH. We conclude that ER-α is the key mediator that could be responsible for various clinical measures of BPH/LUTS., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)