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Background: Advances in kidney transplantation and dialysis have helped millions of people with ESRD. However, cost involved in terms of initial investment, maintenance, training, skilled personnel, subsidies on consumables and drugs add to the long-term cost involved with treatment. Objectives: 1. To study the treatment expenditure, out of pocket expenditure and catastrophic expenditure during Haemodialysis. 2) To study sociodemographic characteristics of ESRD patients on Haemodialysis Methodology: It is a cross sectional study conducted in 2 government and 2 private hospitals among patients with chronic kidney disease who were undergoing haemodialysis for a minimum period of 1 month. Data was collected using preformed questionnaire containing data on socio-demographic variables, illness details, dialysis details, medications and other expenditures. Results: 65.7% of participant gave history of having insurance coverage or any assistance for dialysis. But majority of patients used their savings (69.7%), or gifts (60.2%), sold assets (51.2%), made unsecured loans (23.9%), mortgaged their lands (11.9%). In addition, 97.5% had catastrophic expenditure on dialysis. Out of pocket expenditure for dialysis per month was Rs.8,310 in government institutes and Rs.29,655 in private institute. Among private, it was Rs.11,297 rupees in ECHS patients and Rs.18,642 in other social insurance scheme Conclusion: There is a high out of pocket expenditure among dialysis patients for their session with public private disparity

The paper presents the first detailed study on systematics, otolith structure and biology of Diaphus coeruleus , from the south-eastern Arabian Sea. The closely related and co-inhabiting species D. coeruleus and D. watasei are distinguished on the basis of morphometric, meristic and otolith characters. Analysis of gut content revealed that these fishes mainly feed on deep sea squids and shrimps. Six maturation stages of gonads are identified in males (immature, quiescent, mature, ripe, spawning and spent) and five stages (immature, quiescent, mature, ripening and spawning stages) in females. Overall sex ratio deviated in favour of males (1 male: 0.2 female) and the mean fecundity was 2150 ± 353 eggs. The length-weight relationship shows an overall isometric growth in males with N = 76 and b = 3.13 and for females with N = 17 and suggests negative allometric growth (b = 1.719). Otolith length (L O) and otolith weight (W O) are positively correlated to standard body length (L S) and body weight (B W). [ABSTRACT FROM AUTHOR]

Concepts, approaches and frameworks for assessing the impacts of climate change are evolving quickly. Due to their particular geographic location, proximity to oceans, concentration of populated regions, and infrastructure, coastal communities are particularly sensitive to the effects of climate change. The present study aims to develop a thematic map based on the CID (climatic impact-drivers) framework proposed in the assessment report-6 of the Intergovernmental Panel on Climate Change (IPCC) to evaluate the climate change’s physical hazards in the coastal districts of India. The study points out that West Bengal and Odisha are the two states with the highest cyclone hazard index values making them most vulnerable to cyclones. At the same time, Kerala, Andhra Pradesh and West Bengal respectively fall in the extremely severe category of flood, heatwave and shoreline change hazards. The maritime state of Gujarat along with Diu and Daman experiences maximum severity for the sea level rise hazard. The multi-hazards index developed in the study by considering 14 threshold-based CID indices showed that the coastal state of Andhra Pradesh has the highest proneness to the physical hazards due to climate change [ABSTRACT FROM AUTHOR]

Purpose: This study describes the epidemiology, clinical extent at diagnosis, and treatment modalities for prostate cancer in India., Methodology: This study is a secondary analysis of primary prostate cancer data sourced from the National Cancer Registry Programme. Data from population-based cancer registry for the period 2012-2016 were used to estimate the incidence rates, including crude incidence rate (CR), age-adjusted incidence rate (AAR), age-specific rate, and cumulative risk. Trends in the AAR were assessed using join-point regression. Hospital-Based Cancer Registry data from 2012 to 2019 were used to describe the clinical extent of the cancer at diagnosis and the treatment modalities., Results: The incidence of prostate cancers was higher in urban registries such as Delhi, Kamrup Urban, and Mumbai (AAR of 11.8 per 100,000, 10.9 per 100,000, and 9.7 per 100,000, respectively). Prostate cancer incidence showed a rise after the age of 50, with a notable acceleration after age 64. The overall annual percentage change for prostate cancer incidence from 1982 to 2016 was 2.6. Around 43.0% of all prostate cancers were diagnosed at the distant metastatic stage. Surgery and radiotherapy, either as standalone treatments or in combination with other modalities, contributed to the treatment of 78.5% of localized cancer, 74.2% of locoregional cancer, and 57.2% of distant metastatic stage of prostate cancer., Conclusion: There is heterogeneity in the incidence of prostate cancer, as evidenced by urban registries. Additionally, there is a need for downstaging the disease, without risking overdiagnosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Urology.)

This study was conducted for the comparative analysis of antioxidant activity and untargeted metabolomics of dark- and light-colored sour cherry cultivars grown in Canada. Based on our previous study, we selected four cultivars-'Heimann R', 'Gorsemska', V70142, and 'Montmorency'-to determine the untargeted metabolites and their role in antioxidant activities. A total of 473 metabolites were identified from four sour cherry genotypes using UPLC-ToF-MS. Untargeted metabolomics revealed the dominant chemical groups present in sour cherries. PCA showed that the diversity in sour cherry metabolites was due to the genotype differences indicating iditol, malic acid, chlorobenzene, 2-mercaptobenzothiazole, and pyroglutamic acid as the predominant contributors. The variable importance in the projection (VIP > 1.0) in partial least-squares-discriminant analysis described 20 biomarker metabolites representing the cherry metabolome profiles. A heatmap of Pearson's correlation analysis between the 20 biomarker metabolites and antioxidant activities identified seven antioxidant determinants that displayed the highest correlations with different types of antioxidant activities. TPC and TAC were evaluated using the Folin-Ciocalteu method. The total antioxidant activity was performed using three different assays (ABTS, FRAP, and DPPH). This study of correlating metabolomics and antioxidant activities elucidated that the higher nutritional value and biological functions of sour cherry genotypes can be useful for the development of nutraceutical and functional foods.

Background: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India., Methods: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively., Results: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively., Conclusions: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Black knot (BK) is a deadly disease of European ( Prunus domestica ) and Japanese ( Prunus salicina ) plums caused by the hemibiotrophic fungus Apiosporina morbosa. Generally, phytopathogens hamper the balance of primary defense phytohormones, such as salicylic acid (SA)-jasmonic acid (JA) balance, for disease progression. Thus, we quantified the important phytohormone titers in tissues of susceptible and resistant genotypes belonging to European and Japanese plums at five different time points. Our previous results suggested that auxin-cytokinins interplay driven by A. morbosa appeared to be vital in disease progression by hampering the plant defense system. Here, we further show that such hampering of disease progression is likely mediated by perturbance in SA, JA, and, to some extent, gibberellic acid. The results further indicate that SA and JA in plant defense are not always necessarily antagonistic as most of the studies suggest but can be different, especially in woody perennials. Together, our results suggest that the changes in phytohormone levels, especially in terms of SA and JA content due to BK infection and progression in plums, could be used as phytohormonal markers in the identification of BK-resistant cultivars.

Fruits and vegetables are an integral part of our diet attributed to their appealing taste, flavor, and health-promoting characteristics. However, due to their high-water activity, they are susceptible to microbial spoilage and diseases at any step in the food supply chain, from pre-harvest treatment to post-harvest storage and transportation. As a result, food researchers and engineers are developing innovative technologies that can be used to reduce the loss of fruits and vegetables on-farm and during postharvest processing. The purpose of this study was to gather and discuss the scientific data on the disease-suppressive activity of nanoparticles against plant pathogens. The progress and limitations of innovative approaches for improving nanoparticles' efficiency and dependability have been studied to develop effective substitutes for synthetic chemical fungicides and pesticides, in managing disease in fruits and vegetables. The findings of this study strongly suggests that nanotechnology has the required ability for disease suppression in fruits and vegetables. Applications of specific nanoparticles under specified conditions can enhance nutrition delivery to plants, provide better antibacterial and disease suppression activity. Nanoparticles can also lessen the quantity of agrichemicals/metals released into the environment as compared to standard formulations, which is one of the most impressive advances.

Semiconductor metal oxide with TiO 2 nanoparticles removes hazardous compounds from environmental samples. TiO 2 nanoparticles have shown potential as an efficient photocatalyst by being employed as a nano-catalyst for the breakdown of organic contaminants in wastewater samples. To separate substances from contaminated samples, combined UV and visible light irradiation has been used. Sol-gel synthesis was used to produce a copper chromite-titanium nanocomposite, which was then evaluated using analytical methods, such as XRD, BET, DRS-UV, and FT-IR. Using visible light, the photocatalytic activity of a nanocomposite made of CuCr 2 O 4 and TiO 2 was investigated for its role in the breakdown of malachite green. The effects of several parameters, including pH change, anions presence, contact time, catalyst amount, concentration variation, and the kinetics of photocatalytic degradation were investigated. The magnitude of transition energy calculated using UV-DRS spectra was found to be 3.1 eV for CuCr 2 O 4 - TiO 2 nanocomposite. Maximum degradation was observed at pH 7.0. The surface area and pore volume of the co-doped samples of Cr 2 O 4 - TiO 2 obtained from BET were found to be 6.1213 m 2 /g and 0.045063 cm 3 /g respectively. The average particle size of the catalyst of the nano-catalysts calculated from XRD was found to be 8 nm for TiO 2 and 66 nm for TiO 2 -CuCrO 4 . The peaks obtained in FTIR between the range of 900-500 cm -1 were due to the presence of an aromatic compound. The binding mechanism of a dye molecule to the surface of CuCr 2 O 4 -TiO 2 nanocomposite was analysed using quantum chemical calculations with the self-consistent reaction field technique employing integral equation formalism for the polarized continuum method and the UFF atomic radii set., Competing Interests: Declaration of competing interest 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Black Knot (BK) is a deadly disease of European ( Prunus domestics ) and Japanese ( Prunus salicina ) plums caused by the hemibiotrophic fungus Apiosporina morbosa . After infection, the appearance of warty black knots indicates a phytohormonal imbalance in infected tissues. Based on this hypothesis, we quantified phytohormones such as indole-3-acetic acid, tryptophan, indoleamines (N-acetylserotonin, serotonin, and melatonin), and cytokinins (zeatin, 6-benzyladenine, and 2-isopentenyladenine) in temporally collected tissues of susceptible and resistant genotypes belonging to European and Japanese plums during of BK progression. The results suggested auxin-cytokinins interplay driven by A. morbosa appears to be vital in disease progression by hampering the plant defense system. Taken together, our results indicate the possibility of using the phytohormone profile as a biomarker for BK resistance in plums.

Background: Cancer survival data from Population Based Cancer Registries (PBCR) reflect the average outcome of patients in the population, which is critical for cancer control efforts. Despite decreasing incidence rates, cervical cancer is the second most common female cancer in India, accounting for 10% of all female cancers. The objective of the study is to estimate the five-year survival of patients with cervical cancer diagnosed between 2012 and 2015 from the PBCRs in India., Methods: A single primary incidence of cervical cancer cases of 11 PBCRs (2012-2015) was followed till June 30, 2021 (n = 5591). Active follow-ups were conducted through hospital visits, telephone calls, home or field visits, and public databases. Five-year Observed Survival (OS) and Age Standardised Relative Survival (ASRS) was calculated. OS was measured by age and clinical extent of disease for cervical cancers., Findings: The five-year ASRS (95% CI) of cervical cancer was 51.7% (50.2%-53.3%). Ahmedabad urban (61.5%; 57.4%-65.4%) had a higher survival followed by Thiruvananthapuram (58.8%; 53.1%-64.3%) and Kollam (56.1%; 50.7%-61.3%). Tripura had the lowest overall survival rate (31.6%; 27.2%-36.1%). The five-year OS% for pooled PBCRs was 65.9%, 53.5%, and 18.0% for localised, regional, and distant metastasis, respectively., Interpretation: We observed a wide variation in cervical cancer survival within India. The findings of this study would help the policymakers to identify and address inequities in the health system. We re-emphasise the importance of awareness, early detection, and increase the improvement of the health care system., Funding: The National Cancer Registry Programme is funded through intra-mural funding by Indian Council of Medical Research, Department of Health Research, India, Ministry of Health & Family Welfare., Competing Interests: None. The National Cancer Registry Programme is funded through intra-mural funding by Indian Council of Medical Research, Department of Health Research, Ministry of Health & Family Welfare., (© 2023 The Author(s).)

The dynamics of physico-chemical, nutrient, and chlorophyll-a variables were studied in the bloom and non-bloom locations along the off-Gujarat coastal waters to understand the variability in biogeochemistry using multivariate analytical tests. The dissolved oxygen was significantly lower in the bloom stations (3.89 ± 0.44 mgL -1 ) than in the non-bloom stations (5.50 ± 0.70 mg L -1 ), due to the biological degradation of organic matter in addition to anaerobic microbial respiration. Nutrients (PO 4 and NO 3 ) and Chl-a concentrations were recorded higher in the bloom locations at 0.83 ± 0.21 µmol L -1 , 4.47 ± 0.69 µmol L -1 , 4.14 ± 1.49 mg m -3 , respectively. PO 4 and NO 3 have shown a significantly higher positive correlation of r = 0.73 and r = 0.69 with Chl-a for bloom data than the non-bloom data. The percentage variance contributed by PC1 and PC2 for both bloom and non-bloom locations were estimated at 52.33%. The variable PO 4 explains the highest 24.19% variability in PC1, followed by Chl-a (19.89%). The PO 4 triggers the bloom formation and also correlates to the higher concentrations of Chl-a in the bloom locations. The bloom concentration ranges from 9553 to 12,235 trichomes L -1 . The bloom intensity has shown a significant positive correlation with Chl-a (r = 0.77), NO 3 (r = 0.56), and PO 4 (r = 0.30), but a negative correlation was noticed with DO (r =  - 0.63) and pH (r =  - 0.49). The study also initiates a way forward research investigation on ocean-color technologies to identify and monitor blooms and climate change-driven factors for bloom formation. The occurrence of bloom and its influence on fishery resources and other marine biotas will open many research windows in marine fisheries, oceanography, remote sensing, marine biology, and trophodynamics., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aims: Retinal ischemia/reperfusion (I/R) injury is a common pathological basis for various ophthalmic diseases. This study aimed to investigate the potential of sulforaphane (SFN) and Homer1a in regulating cell apoptosis induced by retinal I/R injury and to explore the underlying regulatory mechanism between them., Materials and Methods: In in vivo experiments, C57BL/6J mice and Homer1 flox/- /Homer1a +/- /Nestin-Cre +/- mice were used to construct retinal I/R injury models. In vitro experiments utilized the oxygen-glucose deprivation-reperfusion (OGD/R) injury model with primary retinal ganglion cells (RGCs). The effects of Homer1a and SFN on cell apoptosis were observed through pathological analyses, flow cytometry, and visual electrophysiological assessments., Key Findings: We discovered that after OGD/R injury, apoptosis of RGCs and intracellular Ca 2+ activity significantly increased. However, these changes were reversed upon the addition of SFN, and similar observations were reproduced in in vivo studies. Furthermore, both in vivo and in vitro studies confirmed the upregulation of Homer1a after I/R, which could be further enhanced by the administration of SFN. Moreover, upregulation of Homer1a resulted in a reduction in cell apoptosis and pro-apoptotic proteins, while downregulation of Homer1a had the opposite effect. Flash visual evoked potential, oscillatory potentials, and escape latency measurements in mice supported these findings. Furthermore, the addition of SFN strengthened the neuroprotective effects in the OGD/R + H + group but weakened them in Homer1 flox/- /Homer1a +/- /Nestin-Cre +/- mice., Significance: These results indicate that Homer1a plays a significant role in the therapeutic potential of sulforaphane for retinal I/R injury, thereby providing a theoretical basis for clinical treatment., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier Inc.)

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix's structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM. Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions. Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway. Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression., 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 © 2023 Reivan Ortiz, Ciongradi, Chaitanya, Narayanan, Mohany, Al-Rejaie, Arias-Gonzáles, Sârbu, Assefi, Akram, Döğüş, Bahrami and Akhavan-Sigari.)

Demyelinating disorders of the central nervous system (CNS) occur when myelin and oligodendrocytes are damaged or lost. Remyelination and regeneration of oligodendrocytes can be achieved from endogenous oligodendrocyte precursor cells (OPCs) that reside in the adult CNS tissue. Using a cuprizone mouse model of demyelination, we show that infusion of fractalkine (CX3CL1) into the demyelinated murine brain increases de novo oligodendrocyte formation and enhances remyelination in the corpus callosum and cortical gray matter. This is achieved by increased OPC proliferation in the cortical gray matter as well as OPC differentiation and attenuation of microglia/macrophage activation both in corpus callosum and cortical gray matter. Finally, we show that activated OPCs and microglia/macrophages express fractalkine receptor CX3CR1 in vivo, and that in OPC-microglia co-cultures fractalkine increases in vitro oligodendrocyte differentiation by modulating both OPC and microglia biology. Our results demonstrate a novel pro-regenerative role of fractalkine in a demyelinating mouse model., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Camelina sativa is a self-pollinating and facultative outcrossing oilseed crop. Genetic engineering has been used to improve camelina yield potential for altered fatty acid composition, modified protein profiles, improved seed and oil yield, and enhanced drought resistance. The deployment of transgenic camelina in the field posits high risks related to the introgression of transgenes into non-transgenic camelina and wild relatives. Thus, effective bioconfinement strategies need to be developed to prevent pollen-mediated gene flow (PMGF) from transgenic camelina. In the present study, we overexpressed the cleistogamy (i.e. floral petal non-openness)-inducing PpJAZ1 gene from peach in transgenic camelina. Transgenic camelina overexpressing PpJAZ1 showed three levels of cleistogamy, affected pollen germination rates after anthesis but not during anthesis, and caused a minor silicle abortion only on the main branches. We also conducted field trials to examine the effects of the overexpressed PpJAZ1 on PMGF in the field, and found that the overexpressed PpJAZ1 dramatically inhibited PMGF from transgenic camelina to non-transgenic camelina under the field conditions. Thus, the engineered cleistogamy using the overexpressed PpJAZ1 is a highly effective bioconfinement strategy to limit PMGF from transgenic camelina, and could be used for bioconfinement in other dicot species., (© The Author(s) 2023. Published by OxfordUniversity Press on behalf of Nanjing AgriculturalUniversity.)

Carrot processing industries produce 25-30% of waste in the form of carrot rejects, peels, and pomace which contain a large amount of high-value bioactive components. Green extraction of the bioactive components from carrot rejects with green solvents using closed-vessel energy-intensive microwave-assisted extraction was the objective of this work. In this work, three experimental studies were implemented. One uses 8 different green solvents for maximum yield of bioactive using green technology, and the other for the optimization of Microwave-assisted Extraction (MAE) parameters to enhance the bioactive components yield. Response Surface Methodology was employed to optimize the processing parameters including temperature, time, solid to solvent ratio, and solvent type. The optimized extraction conditions: treatment temperature of 50 °C for 5 min gave a significantly higher yield of total carotenoids (192.81 ± 0.32 mg carotenoids/100 g DW), total phenolic (78.12 ± 0.35 g GAE/100 g DW), and antioxidants by FRAP (5889.63 ± 0.47 mM TE/100 g DW), ABTS (1143.65 ± 0.81 mM TE/100 g DW), and DPPH (823.14 ± 0.54 mM TE/100 g DW) using a solvent combination of hexane and ethanol (1:3) with solid to solvent ratio of 1:40 (w/v). This green technology in combination with GRAS solvents promoted the best recovery of bioactive from carrot rejects. Moreover, the solid residue remained after the extraction of bioactive components exhibited higher carbon content (46.5%) and calorific value (16.32 MJ/kg), showcasing its potential to be used as an energy source., (© 2022. The Author(s).)

While spatial proteomics by fluorescence imaging has quickly become an essential discovery tool for researchers, fast and scalable methods to classify and embed single-cell protein distributions in such images are lacking. Here, we present the design and analysis of the results from the competition Human Protein Atlas - Single-Cell Classification hosted on the Kaggle platform. This represents a crowd-sourced competition to develop machine learning models trained on limited annotations to label single-cell protein patterns in fluorescent images. The particular challenges of this competition include class imbalance, weak labels and multi-label classification, prompting competitors to apply a wide range of approaches in their solutions. The winning models serve as the first subcellular omics tools that can annotate single-cell locations, extract single-cell features and capture cellular dynamics., (© 2022. The Author(s).)

Anthocyanins, a major class of flavonoids, are important pigments of grape berries. Despite the recent discovery of the genetic cause underlying the loss of color, the metabolomic and molecular responses are unknown. Anthocyanin quantification among diverse berry color muscadines suggests that all genotypes could produce adequate anthocyanin quantities, irrespective of berry color. Transcriptome profiling of contrasting color muscadine genotypes proposes a potential deficiency that occurs within the anthocyanin transport and/or degradation mechanisms and might cause unpigmented berries. Genome-wide association studies highlighted a region on chromosome-4, comprising several genes encoding glutathione S-transferases involved in anthocyanin transport. Sequence comparison among genotypes reveals the presence of two GST4b alleles that differ by substituting the conserved amino acid residue Pro 171 -to-Leu. Molecular dynamics simulations demonstrate that GST4b2-Leu 171 encodes an inactive protein due to modifications within the H-binding site. Population genotyping suggests the recessive inheritance of the unpigmented trait with a GST4b2/2 homozygous. A model defining colorless muscadines' response to the mutation stimulus, avoiding the impact of trapped anthocyanins within the cytoplasm is established., (© 2022. The Author(s).)

Residual Maximum Likelihood (REML) analysis is the most widely used method to estimate variance components and heritability. This method is based on large sample theory under the assumption that the parameter estimates are asymptotically multivariate normally distributed with covariance matrix given by the inverse of the information matrix. Hence, these sampling variances could be biased if the assumption of asymptotic approximation is incorrect, especially when the sample size is small. Though it is difficult to assess the impact of sample size, an alternative option is to generate a full distribution of the parameters to determine the uncertainty of estimates. In this study, we compared the REML estimates of variance components, heritability and sampling variances of body-weight (BW), body-depth (BD), and condition-factor (K) with those obtained from four sampling-based methods viz., parametric and nonparametric bootstrap, asymptotic sampling and Bayesian estimation. The aim was to understand if a sample size of order 1413 was sufficient to contain adequate information for a reliable asymptotic approximation. The REML solution was close to values obtained from different sampling-based methods indicating that the present sample size was sufficient to estimate reliable genetic variation in different traits with varying heritability. The variance and heritability estimated by a nonparametric bootstrap estimate based on randomization of family effects gave comparable results as evaluated by REML for different traits. Hence, the nonparametric bootstrap estimate can be effectively used to understand whether the sample size is large enough to contain sufficient information under likelihood estimation assumptions., (© 2022. The Author(s), under exclusive licence to The Genetics Society.)

Acute myeloid leukemia (AML) is an aggressive blood cancer with limited chemotherapy options and negative patient outcomes. Investigations with bioactive compounds from dietary sources against cancer have increased in the recent years, which highlight the need for novel therapeutic approaches and new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. Bioactive compounds demonstrated the ability to induce cell cycle blockage and apoptosis or autophagy in cancer cells, as well as inhibition of proliferation/migration and tumor progression, etc. Bioactive compounds isolated from dietary sources such as mango ginger show promise for AML treatment. Curcuma amada roots have been used in traditional medicine and showed antioxidant, antimicrobial and anticancer properties. Bioactive molecules isolated from C. amada showed effects on the mitochondrial metabolism and reduced the viability of multiple leukemic cell lines.

'Honeycrisp' ( Malus domestica Borkh.), a premium applecultivar, is highly susceptible to bitter pit and decline in quality during long-term storage. In order to enhance the quality, an aqueous composition containing hexanal was applied as a preharvest spray. The effects of hexanal were assessed on the treated fruit and compared with Harvista TM (a sprayable 1-Methylcyclopropene based commercial formulation) applied and control fruit under both cold (2.5 °C; four months) and cold after room temperature storage (20 °C; 14 days) conditions. Color, firmness, and total soluble solids (TSS) did not show a significant change in response to any treatment at harvest, while abscisic acid (ABA) significantly reduced and tryptophan increased in response to hexanal, compared to Harvista TM and control. The treatment effects on quality traits were observed during storage. Both hexanal and Harvista TM sprayed apples had higher TSS under both cold and room temperature storage. In addition, both sprays enhanced firmness at room temperature storage. However, the effects of sprays on other quality traits showed a different pattern. Apples sprayed with hexanal had lower phospholipase D enzyme (PLD) activity, lower incidence of bitter pit, and decreased expression of MdPLDα1 compared to Harvista TM and control. On the other hand, Harvista TM treated fruit produced lower ethylene. Both sprays decreased the expression of MdPLDα4, MdCaM2, MdCaM4 and MdCML18 genes. Generally, PLD alpha has a direct role in promoting fruit senescence, whereas the calcium senor proteins (CaM/CMLs) may involve in fruit ripening process via calcium and ethylene interactions. Therefore, improved postharvest qualities, including the lower incidence of bitter pit in hexanal treated 'Honeycrisp', may be associated with lower membrane damage due to lower PLD enzyme activity and decreased expression of MdPLDα1 and MdPLDα4 genes throughout the storage period.

Plums are affected by a cancerous disease called "black knot disease" caused by the fungus Apiosporina morbosa . It affects both Japanese ( Prunus salicina ) and European ( Prunus domestica ) plums equally. To understand the spread of the disease, histological analysis was performed in two different European plum cultivars (susceptible and tolerant). Light and scanning electron microscope (SEM) analyses confirmed the presence of the growing hyphae in the internal tissues of the susceptible trees. By using stereoscopic analysis with a fluorescence filter, we were able to detect the hyphae in the visible lesion area. At about 2 inches from above and below the knots, no spore or hypha were visible with the light microscope. However, SEM images showed strong evidence that the fungus is capable of migrating to adjacent vessels in the susceptible plum genotype. In fact, at that distance below and above the knots, conidia were detected inside xylem vessels suggesting a systemic movement of the fungus that has not been shown so far. No symptoms were observed in the resistant genotype. Starch granules, vessel occlusions, and lipid droplets were the main distinguishable characteristics between susceptible and tolerant varieties.

Apples ( Malus   domestica Borkh) are prone to preharvest fruit drop, which is more pronounced in 'Honeycrisp'. Hexanal is known to improve fruit retention in several economically important crops. The effects of hexanal on the fruit retention of 'Honeycrisp' apples were assessed using physiological, biochemical, and transcriptomic approaches. Fruit retention and fruit firmness were significantly improved by hexanal, while sugars and fresh weight did not show a significant change in response to hexanal treatment. At commercial maturity, abscisic acid and melatonin levels were significantly lower in the treated fruit abscission zone (FAZ) compared to control. At this stage, a total of 726 differentially expressed genes (DEGs) were identified between treated and control FAZ. Functional classification of the DEGs showed that hexanal downregulated ethylene biosynthesis genes, such as S-adenosylmethionine synthase ( SAM2 ) and 1-aminocyclopropane-1-carboxylic acid oxidases ( ACO3 , ACO4 , and ACO4-like ), while it upregulated the receptor genes ETR2 and ERS1 . Genes related to ABA biosynthesis ( FDPS and CLE25 ) were also downregulated. On the contrary, key genes involved in gibberellic acid biosynthesis ( GA20OX-like and KO) were upregulated. Further, hexanal downregulated the expression of genes related to cell wall degrading enzymes, such as polygalacturonase ( PG1 ), glucanases (endo-β-1,4-glucanase), and expansins ( EXPA1-like , EXPA6 , EXPA8 , EXPA10-like , EXPA16-like ). Our findings reveal that hexanal reduced the sensitivity of FAZ cells to ethylene and ABA. Simultaneously, hexanal maintained the cell wall integrity of FAZ cells by regulating genes involved in cell wall modifications. Thus, delayed fruit abscission by hexanal is most likely achieved by minimizing ABA through an ethylene-dependent mechanism.

Fruit development is orchestrated by a complex network of interactions between hormone signaling pathways. The phytohormone gibberellin (GA) is known to regulate a diverse range of developmental processes; however, the mechanisms of GA action in perennial fruit species are yet to be elucidated. In the current study, a GA signaling gene PslSLY1, encoding a putative F-box protein that belongs to the SLY1 (SLEEPY1)/GID2 (gibberellin-insensitive dwarf2) gene family, was isolated from Japanese plum (Prunus salicina). PslSLY1 transcript abundance declined as fruit development progressed, along with potential negative feedback regulation of PslSLY1 by GA. Subcellular localization and protein-protein interaction assays suggested that PslSLY1 functions as an active GA signaling component that interacts with the ASK1 (Arabidopsis SKP1) subunit of an SCF-ubiquitin ligase complex and with PslDELLA repressors, in a GA-independent manner. By using a domain omission strategy, we illustrated that the F-box and C-terminal domains of PslSLY1 are essential for its interactions with the downstream GA signaling components. PslSLY1 overexpression in wild-type and Arabidopsissly1.10 mutant backgrounds resulted in a dramatic enhancement in overall plant growth, presumably due to triggered GA signaling. This includes germination characteristics, stem elongation, flower structure, and fertility. Overall, our findings shed new light on the GA strategy and signaling network in commercially important perennial crops., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu → Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In the deoxygenated state, polymerization of HbS leads to sickling of red blood cells (RBC). Several downstream consequences of polymerization and RBC sickling include vaso-occlusion, hemolytic anemia, and stroke. We report the design of a noncovalent modulator of HbS, clinical candidate PF-07059013 ( 23 ). The seminal hit molecule was discovered by virtual screening and confirmed through a series of biochemical and biophysical studies. After a significant optimization effort, we arrived at 23 , a compound that specifically binds to Hb with nanomolar affinity and displays strong partitioning into RBCs. In a 2-week multiple dose study using Townes SCD mice, 23 showed a 37.8% (±9.0%) reduction in sickling compared to vehicle treated mice. 23 (PF-07059013) has advanced to phase 1 clinical trials.

Individuals with demyelinating diseases often experience difficulties during social interactions that are not well studied in preclinical models. Here, we describe a novel juvenile focal corpus callosum demyelination murine model exhibiting a social interaction deficit. Using this preclinical murine demyelination model, we discover that application of metformin, an FDA-approved drug, in this model promotes oligodendrocyte regeneration and remyelination and improves the social interaction. This beneficial effect of metformin acts through stimulating Ser436 phosphorylation in CBP, a histone acetyltransferase. In addition, we found that metformin acts through two distinct molecular pathways to enhance oligodendrocyte precursor (OPC) proliferation and differentiation, respectively. Metformin enhances OPC proliferation through early-stage autophagy inhibition, while metformin promotes OPC differentiation into mature oligodendrocytes through activating CBP Ser436 phosphorylation. In summary, we identify that metformin is a promising remyelinating agent to improve juvenile demyelination-associated social interaction deficits by promoting oligodendrocyte regeneration and remyelination., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Increased fructose consumption and its subsequent metabolism have been implicated in metabolic disorders such as nonalcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) and insulin resistance. Ketohexokinase (KHK) converts fructose to fructose-1-phosphate (F1P) in the first step of the metabolic cascade. Herein we report the discovery of a first-in-class KHK inhibitor, PF-06835919 ( 8 ), currently in phase 2 clinical trials. The discovery of 8 was built upon our originally reported, fragment-derived lead 1 and the recognition of an alternative, rotated binding mode upon changing the ribose-pocket binding moiety from a pyrrolidinyl to an azetidinyl ring system. This new binding mode enabled efficient exploration of the vector directed at the Arg-108 residue, leading to the identification of highly potent 3-azabicyclo[3.1.0]hexane acetic acid-based KHK inhibitors by combined use of parallel medicinal chemistry and structure-based drug design.

Rationale: Monoacylglycerol lipase (Mgll), a hydrolase that breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG) to produce arachidonic acid (ARA), is a potential target for neurodegenerative diseases, such as Alzheimer's disease (AD). Increasing evidence shows that impairment of adult neurogenesis by perturbed lipid metabolism predisposes patients to AD. However, it remains unknown what causes aberrant expression of Mgll in AD and how Mgll-regulated lipid metabolism impacts adult neurogenesis, thus predisposing to AD during aging. Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce β-amyloid accumulation. Methods: Mgll expression was assessed in both human AD patient post-mortem hippocampal tissues and 3xTg-AD mouse model. In addition, we used both the 3xTg-AD animal model and the Cbp S436A genetic knock-in mouse model to identify that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway, involving atypical protein kinase C (aPKC)-stimulated Ser436 phosphorylation of histone acetyltransferase CBP through biochemical methods. Furthermore, we performed in vivo adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway. Finally, we performed in vitro adult neurosphere assays using both animal models to study the role of the aPKC-CBP mediated Mgll repression in determining adult neural stem/progenitor cell (NPC) fate. Results: Here, we demonstrate that aging-dependent induction of Mgll is observed in the 3xTg-AD model and human AD patient post-mortem hippocampal tissues. Importantly, we discover that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway. The accumulation of Mgll in the 3xTg-AD mice reduces the genesis of newborn neurons and perturbs spatial memory. However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD. In addition, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and Cbp S436A animal models are responsible for their NPC neuronal differentiation deficits. Conclusion: Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Hexanal, a C-6 aldehyde has been implicated to have antimicrobial properties. Hence, this study was conducted to determine the antifungal activities of hexanal vapor against major postharvest pathogens of banana viz ., Colletotrichum gloeosporioides and Lasiodiplodia theobromae . The pathogens were cultured in vitro and exposed to hexanal vapor at 600, 800, 1,000 and 1,200 ppm. Mycelial growth of both fungal pathogens were inhibited completely at 800 ppm and the incidence of anthracnose and stem-end rot diseases reduced by 75.2% and 80.2%, respectively. The activities of peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase and glucanase had transiently increased in hexanal vapor treated banana by 5 to 7 days and declined thereafter. Postharvest treatment of banana with hexanal vapor resulted in phospholipase D inhibition and also resulted in cell wall thickening of the treated fruit, which impeded the penetration of the pathogenic spores. This was further confirmed by scanning electron micrographs. The defense-related protein intermediaries had increased in hexanal vapor treated banana fruit, which suggests induced resistance against C. gloeosporioides and L. theobromae , via., the phenylpropanoid pathway which plays a significant role in hindering the pathogen quiescence. Delayed ripening due to inhibition of phospholipase D enzyme, inhibition of mycelial growth and induced systemic resistance by defense enzymes collectively contributed to the postharvest disease reduction and extended shelf life of fruit., (© The Korean Society of Plant Pathology.)

Hsf1 is an ancient transcription factor that responds to protein folding stress by inducing the heat-shock response (HSR) that restore perturbed proteostasis. Hsp70 chaperones negatively regulate the activity of Hsf1 via stress-responsive mechanisms that are poorly understood. Here, we have reconstituted budding yeast Hsf1-Hsp70 activation complexes and find that surplus Hsp70 inhibits Hsf1 DNA-binding activity. Hsp70 binds Hsf1 via its canonical substrate binding domain and Hsp70 regulates Hsf1 DNA-binding activity. During heat shock, Hsp70 is out-titrated by misfolded proteins derived from ongoing translation in the cytosol. Pushing the boundaries of the regulatory system unveils a genetic hyperstress program that is triggered by proteostasis collapse and involves an enlarged Hsf1 regulon. The findings demonstrate how an apparently simple chaperone-titration mechanism produces diversified transcriptional output in response to distinct stress loads., Competing Interests: AM, WK, JR, JM, JQ, MF, CA No competing interests declared, (© 2019, Masser et al.)

Lead fluorosilicate (SKNPfLfDy) glasses doped with various Dy 3+ ion concentrations employed via melt-quenching method have been prepared and studied their thermal, optical and spectral properties for the spreading out of yellow laser applications. The emission spectra have prominent emission at 575 nm ( 4 F 9/2  →  6 H 13/2 ) transition. The stimulated emission cross-section (5.14 × 10 -21  cm 2 ) and branching ratio (62%) for the 4 F 9/2  →  6 H 13/2 transition were found to be relatively high. Lifetime is decreased from 1192 μs to 34 μs with increase in concentration due to concentration quenching as well cross-relaxation among the Dy 3+ ions. The quantum efficiency found to be 69%. The optical gain, figure of merit, yellow/blue (Y/B) intensity ratio and gain bandwidth for 1.0 mol% Dy 3+ :SKNPfLf glass is found to be 27.55 × 10 -25  cm 2  s, 19.01 × 10 -25  cm 2  s, 3.96 and 63.32 × 10 -28  cm 3 , respectively. The obtained results revealed that the SKNPfLfDy glasses possibly useful for yellow laser applications., (Copyright © 2019. Published by Elsevier B.V.)

Neuroinflammation has been observed in post-mortem Alzheimer's disease (AD) brains which could be due to Aβ interacting with microglia and astrocytes. SLOH, a carbazole-based fluorophore, was shown to bind to Aβ peptides. Herein, we investigated the anti-neuroinflammatory effects of SLOH using a BV-2 microglial cell model and a triple transgenic AD (3xTg-AD) mouse model. BV-2 cells were incubated with Aβ in the presence of SLOH for 24 h. The levels of pro-inflammatory and anti-inflammatory cytokines were determined. Moreover, 3xTg-AD mice were administrated with SLOH (2 mg kg -1 ) for one month. The mice were then sacrificed and the brains were used to assess the levels of pro-inflammatory, anti-inflammatory cytokines and the activation of ionized calcium-binding adapter molecule 1 (Iba1). BV-2 cell studies suggested that SLOH reduced the production and mRNA levels of pro-inflammatory cytokines TNF-α, IL-1β, COX-2, iNOS, and increased IL-10. Animal study confirmed that SLOH reduced the production of pro-inflammatory cytokines and increased the level of anti-inflammatory cytokine. Moreover, SLOH inhibited the activity of GSK-3β. In 3xTg-AD mouse model, SLOH treatment significantly decreased the number of Iba1-positive cells in mouse brains. Our results demonstrated that SLOH significantly attenuated the neuroinflammation through down-regulating the activity of GSK-3β., (Copyright © 2018 Elsevier B.V. All rights reserved.)