Search

With the interest and knowing the importance of ferrocenyl conjugates, a direct amidation of ferrocenyl aldehyde has been developed under feasible conditions. Varieties of amines has been oxidatively coupled with ferrocene aldehyde in the presence of highly economical and robustly stable iron chalcogenide ironcarbonyl clusters [Fe3E2(CO)9, E= S, Se, and Te] and TBHP. The reaction worked in greener solvent water at a moderate temperature of 70 °C and synthesized the ferrocenyl-amides in just 30 minutes. All the varieties of amines were found to be well tolerated for the present method, and due to the high medicinal importance of ferrocenyl-amides, sole focus of this report was concentrate on the synthesis of various new ferrocenyl-amides in good to excellent amounts., (© 2024 Wiley‐VCH GmbH.)

Background: A pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn's disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T., Methods: Here, we used the Pediatric Risk Stratification Study (RISK) cohort to perform a secondary analysis of 16S ribosomal RNA gene sequencing data obtained from ileal and rectal mucosa to study associations between ZIP8 A391T carrier status and microbiota composition., Results: We found sequence variants mapping to Veillonella were decreased in the ileal mucosa of ZIP8 A391T carriers. Prior human studies have demonstrated the sensitivity of Veillonella to bile acid abundance. We therefore hypothesized that bile acid homeostasis is differentially regulated in carriers of ZIP8 A391T. Using a mouse model of ZIP8 A391T, we demonstrate an increase in total bile acids in the liver and stool and decreased fibroblast growth factor 15 (Fgf15) signaling, consistent with our hypothesis. We confirmed dysregulation of FGF19 in the 1000IBD cohort, finding that plasma FGF19 levels are lower in ZIP8 A391T carriers with ileocolonic Crohn's disease., Conclusions: In the search for genotype-specific therapeutic paradigms for patients with Crohn's disease, these data suggest targeting the FGF19 pathway in ZIP8 A391T carriers. Aberrant bile acid metabolism may precede development of Crohn's disease and prioritize study of the interactions between manganese homeostasis, bile acid metabolism and signaling, and complicated ileal Crohn's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The treatment of defective glycosylation in clinical practice has been limited to patients with rare and severe phenotypes associated with congenital disorders of glycosylation (CDG). Carried by approximately 5% of the human population, the discovery of the highly pleiotropic, missense mutation in a manganese transporter ZIP8 has exposed under-appreciated roles for Mn homeostasis and aberrant Mn-dependent glycosyltransferases activity leading to defective N-glycosylation in complex human diseases. Here, we test the hypothesis that aberrant N-glycosylation contributes to disease pathogenesis of ZIP8 A391T-associated Crohn's disease. Analysis of N-glycan branching in intestinal biopsies demonstrates perturbation in active Crohn's disease and a genotype-dependent effect characterized by increased truncated N-glycans. A mouse model of ZIP8 391-Thr recapitulates the intestinal glycophenotype of patients carrying mutations in ZIP8. Borrowing from therapeutic strategies employed in the treatment of patients with CDGs, oral monosaccharide therapy with N-acetylglucosamine ameliorates the epithelial N-glycan defect, bile acid dyshomeostasis, intestinal permeability, and susceptibility to chemical-induced colitis in a mouse model of ZIP8 391-Thr. Together, these data support ZIP8 391-Thr alters N-glycosylation to contribute to disease pathogenesis, challenging the clinical paradigm that CDGs are limited to patients with rare diseases. Critically, the defect in glycosylation can be targeted with monosaccharide supplementation, providing an opportunity for genotype-driven, personalized medicine.

Abstract: Medical Thoracoscopy (MT) is commonly performed by respiratory physicians for diagnostic as well as therapeutic purposes. The aim of the study was to provide evidence-based information regarding all aspects of MT, both as a diagnostic tool and therapeutic aid for pulmonologists across India. The consensus-based guidelines were formulated based on a multistep process using a set of 31 questions. A systematic search of published randomized controlled clinical trials, open labelled studies, case reports and guidelines from electronic databases, like PubMed, EmBase and Cochrane, was performed. The modified grade system was used (1, 2, 3 or usual practice point) to classify the quality of available evidence. Then, a multitude of factors were taken into account, such as volume of evidence, applicability and practicality for implementation to the target population and then strength of recommendation was finalized. MT helps to improve diagnosis and patient management, with reduced risk of post procedure complications. Trainees should perform at least 20 medical thoracoscopy procedures. The diagnostic yield of both rigid and semirigid techniques is comparable. Sterile-graded talc is the ideal agent for chemical pleurodesis. The consensus statement will help pulmonologists to adopt best evidence-based practices during MT for diagnostic and therapeutic purposes., (Copyright © 2024 Copyright: © 2024 Indian Chest Society.)

Ethylene oxide (EtO), although banned for use, is still being detected in foodstuffs that have been fumigated to eradicate pests during storage and transport. Residual levels over the European Union's (EU) maximum residue limit (MRL) pose severe health concerns. Recent detection of EtO and its by-product 2-chloroethanol (2-CE) at alarming levels have led to product recalls throughout the EU. Here, a simple, automated headspace (HS)-trap method for the simultaneous determination of EtO and its derivative 2-CE by gas chromatography-mass spectrometry (GC-MS) at the required MRL of ≤ 0.05 mg/kg has been implemented. Syringe-based HS combined with backflushed trapping technology provided enrichment of multiple extractions from the same sample vial (known as multi-step enrichment or MSE®) to increase sensitivity for EtO and 2-CE analysis by GC-MS using single-ion-monitoring (SIM) mode. Method detection limits (MDLs) of 0.00059 mg/kg and 0.00219 mg/kg for EtO and 2-CE, respectively, were obtained without the need for manual handling, solvent extraction or derivatization methods. Recoveries were shown to average ( n  = 5) at 98% and 107% for EtO and 2-CE, respectively, and the reproducibility was <10% for both compounds.

The YopJ group of acetylating effectors from phytopathogens of the genera Pseudomonas and Ralstonia have been widely studied to understand how they modify and suppress their host defence targets. In contrast, studies on a related group of effectors, the Eop1 group, lag far behind. Members of the Eop1 group are widely present in the Erwinia-Pantoea clade of Gram-negative bacteria, which contains phytopathogens, non-pathogens and potential biocontrol agents, implying that they may play an important role in agroecological or pathological adaptations. The lack of research in this group of YopJ effectors has left a significant knowledge gap in their functioning and role. For the first time, we perform a comparative analysis combining AlphaFold modelling, in planta transient expressions and targeted mutational analyses of the Eop1 group effectors from the Erwinia-Pantoea clade, to help elucidate their likely activity and mechanism(s). This integrated study revealed several new findings, including putative binding sites for inositol hexakisphosphate and acetyl coenzyme A and newly postulated target-binding domains, and raises questions about whether these effectors function through a catalytic triad mechanism. The results imply that some Eop1s may use a catalytic dyad acetylation mechanism that we found could be promoted by the electronegative environment around the active site.

Direct access to internal temperature readings in lithium-ion batteries provides the opportunity to infer physical information to study the effects of increased heating, degradation, and thermal runaway. In this context, a method to insert temperature sensors into commercial 18650 cells to determine the short- and long-term effects through characterization testing is developed. Results show that sensor insertion only causes a decrease in capacity of 0.5-2.3%, and an increase in DC resistance of approximately 15 mΩ. The temperatures of the modified cells are approximately 0.5 °C higher than the control cells, the difference between the internal and external temperature readings of the modified cells is approximately 0.4 °C, and the modified cells exhibit the same temperature behavior and trend during cycling as the control cells. The cells are able to operate and collect data for 100-150 cycles before their capacities fade and resistances increase beyond what is observed in the control cells. The results of the testing show that cells modified with internal temperature sensors provide useful internal temperature data for cells that have experienced little or no cyclic aging., (© 2023. Springer Nature Limited.)

Manganese is a diet-derived micronutrient that is essential for critical cellular processes like redox homeostasis, protein glycosylation, and lipid and carbohydrate metabolism. Control of Mn availability, especially at the local site of infection, is a key component of the innate immune response. Less has been elucidated about Mn homeostasis at the systemic level. In this work, we demonstrate that systemic Mn homeostasis is dynamic in response to inflammation and infection in mice. This phenomenon is evidenced in male and female mice, mice of two genetic backgrounds (C57BL/6 and BALB/c), in multiple models of acute (dextran sodium sulfate-induced) and chronic (enterotoxigenic Bacteroides fragilis) colitis, and systemic infection with Candida albicans. When mice were fed a standard corn-based chow with excess Mn (100 ppm), liver Mn decreased and biliary Mn increased threefold in response to infection or colitis. Liver iron, copper, and zinc were unchanged. When dietary Mn was restricted to minimally adequate amounts (10 ppm), baseline hepatic Mn levels decreased by approximately 60% in the liver, and upon induction of colitis, liver Mn did not decrease further, however, biliary Mn still increased 20-fold. In response to acute colitis, hepatic Slc39a8 mRNA (gene encoding the Mn importer, Zip8) and Slc30a10 mRNA (gene encoding the Mn exporter, Znt10) are decreased. Zip8 protein is decreased. Inflammation/infection-associated dynamic Mn homeostasis may represent a novel host immune/inflammatory response that reorganizes systemic Mn availability through differential expression of key Mn transporters with down-regulation of Zip8., (© 2023 Federation of American Societies for Experimental Biology.)

Background Arteriovenous fistulas (AVFs) are considered the first and best access for patients with end-stage renal disease who need permanent vascular access for hemodialysis over arteriovenous grafts and central venous catheters for reasons that have been well-established. Poor early patency rates pose the biggest challenge in creating vascular access as they cause increased morbidity and economic/psychological concerns among patients. To minimize such effects, it is critical to use a patient-centered approach and carefully choose patients for AVF access creation. This study aimed to compare the primary patency of distal vascular access provided by continuous suturing versus that provided by interrupted suturing. Methodology This prospective study was conducted in the urology department of a superspecialty, tertiary care center from November 2021 to November 2022. Patency was assessed immediately after surgery (on the table), one month later, and six months later by palpating thrill and auscultating bruit. A total of 50 patients between the ages of 18 and 70 years who met the inclusion criteria were randomly assigned to two groups of 25 each. Results The baseline characteristics of both groups were comparable. At six months (p = 0.09), the continuous suturing group was observed to be somewhat better than the interrupted suturing group, with no significant difference in immediate and one-month patency rates. When compared to the continuous suturing group, the primary patency failure rate was significantly higher in the interrupted suturing group. Conclusions Thus, under appropriate circumstances, continuous sutures can be performed with greater ease, resulting in anastomosis that is as patent as that performed with interrupted sutures., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Roy et al.)

In India, approximately 1.4 million new cases of cancer are recorded annually, with 26.7 million people living with cancer in 2021. Providing care for family members with cancer impacts caregivers' health and financial resources. Effects on caregivers' health and financial resources, understood as family and caregiver "financial toxicity" of cancer, are important to explore in the Indian context, where family members often serve as caregivers, in light of cultural attitudes towards family. This is reinforced by other structural issues such as grave disparities in socioeconomic status, barriers in access to care, and limited access to supportive care services for many patients. Effects on family caregivers' financial resources are particularly prevalent in India given the increased dependency on out-of-pocket financing for healthcare, disparate access to insurance coverage, and limitations in public expenditure on healthcare. In this paper, we explore family and caregiver financial toxicity of cancer in the Indian context, highlighting the multiple psychosocial aspects through which these factors may play out. We suggest steps forward, including future directions in (1) health services research, (2) community-level interventions, and (3) policy changes. We underscore that multidisciplinary and multi-sectoral efforts are needed to study and address family and caregiver financial toxicity in India., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and objective Since early 2020, the novel coronavirus disease 2019 (COVID-19) has turned into a global healthcare concern. The usual clinical presentation of COVID-19 infection includes myalgia, headache associated with pyrexia, and sore throat. Our study aimed to assess the severity of lower urinary tract symptoms (LUTS) in COVID-19 patients and determine its correlation with the prognosis of the disease. Methods We conducted an observational study in the COVID-19 care unit at a tertiary care teaching center in Rajasthan on patients diagnosed as COVID-19-positive. The overactive bladder (OAB) symptom scoring system for LUTS and the CT scoring system for lung involvement in COVID-19 patients were used to evaluate the sample population. Results While our findings showed a non-significant association between OAB and CT score (p>0.05), correlation analysis revealed that the length of hospital stay was significantly longer and oxygen needs were significantly more frequent with severe LUTS. Conclusions Based on our findings, de novo LUTS, particularly storage symptoms, may be present in COVID-19-positive cases, and the severity of these symptoms may have an impact on the patient's length of stay in the hospital. Hence, doctors and other medical professionals should consider COVID-19-related bladder dysfunctions such as de novo LUTS as part of COVID-19 symptomatology., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Jain et al.)

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&#95;CV1) and (2) predicting tested lines in untested environments through the ME model (ME&#95;CV2). The ME predictions were compared with the baseline single-environment (SE) GS model (SE&#95;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.