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KEY POINTS Chronic stress (CS) is predicted to modify the electrical excitability of anterior pituitary corticotrophs. Electrophysiological recordings from isolated corticotrophs from CS male mice display spontaneous electrical bursting behaviour compared to the tonic spiking behaviour of unstressed corticotrophs. The increased spontaneous bursting from CS corticotrophs is BK-dependent and mathematical modelling reveals that the time constant of activation, properties and proportion of BK channels functionally coupled to L-type calcium channels determines the promotion of bursting activity. CS (but not unstressed) corticotrophs display CRH-induced bursting even when the majority of BK channels are pharmacologically inhibited, which can be explained by the stochastic behaviour of a small number of BK channels with distinct properties. Corticotroph excitability can be finely tuned by the stochastic behaviour of a small number of BK channels dependent on their properties and functional co-localisation with L-type calcium channels to control corticotroph excitability over diverse time domains and physiological challenges. ABSTRACT Coordination of an appropriate stress response is dependent upon anterior pituitary corticotroph excitability in response to hypothalamic secretagogues and glucocorticoid negative feedback. A key determinant of corticotroph excitability is large conductance calcium- and voltage- activated (BK) potassium channels that are critical for promoting CRH-induced bursting that enhances ACTH secretion. Previous studies revealed HPA axis hyperexcitability following chronic stress (CS) is partly a function of increased corticotroph output. Thus, we hypothesise that chronic stress promotes corticotroph excitability through a BK-dependent mechanism. Corticotrophs from CS mice displayed significant increases in spontaneous bursting, that was suppressed by the BK blocker paxilline. Mathematical modelling reveals that the time constant of BK channel activation, plus properties and proportion of BK channels functionally coupled to L-type calcium (Ca2+ ) channels determines bursting activity. Surprisingly, CS corticotrophs (but not unstressed) display CRH-induced bursting even when the majority of BK channels are inhibited by paxilline; that modelling suggests is a consequence of the stochastic behaviour of a small number of BK channels coupled to L-type Ca2+ channels. Our data reveal that changes in the stochastic behaviour of a small number of BK channels can finely tune corticotroph excitability through stress-induced changes in BK channel properties. Importantly, regulation of BK channel function is highly context dependent allowing dynamic control of corticotroph excitability over a large range of time domains and physiological challenges in health and disease. This is likely to occur in other BK-expressing endocrine cells, with important implications for the physiological processes they regulate and the potential for therapy. This article is protected by copyright. All rights reserved.

In this paper, a facility location model with fuzzy values parameters based on the hybrid meta-heuristic method is investigated. The proposed model uses fuzzy values to solve the installation problem. Problem hypotheses are considered fuzzy random variables, and the capacity of each facility is unlimited. This paper combines a modern nature-inspired procedure called the Whale Algorithm (WA) with genetic methods. WA and Genetic Algorithm (GA) have been tested with scientific optimization problems and modeling problems. To evaluate the performance of the proposed methods, we apply the methods to our spatial models in which fuzzy coefficients are used. The results of numerical optimization show that the proposed combined method performs better than conventional methods.

The influence of the pre-treatment process (freezing, drying) on the tensile properties of chitin paper obtained from nanofibers of three commercial species of fungi: oyster mushrooms (P. ostreatus), enoki (F. velutipes) and shiitake (L. edodes) was investigated. The chitin nanofibers were extracted by a mild alkaline process. The highest tensile strength was observed for paper obtained from fresh mushrooms fibers, which may result from the lack of the chitin fiber modification. Freezing and drying processes have been found to reduce the strength of the paper, possibly due to ice crystal formation and the keratinization effect of the nanofibers, respectively. The paper obtained from enoki fungus nanofibers was characterized by the highest tensile strength, which may be due to the very long fiber. However, in terms of elongation at break, the best results were obtained with oyster mushrooms nanofibers, probably due to the relatively shorter chitin fiber. The long enoki nanofibers can therefore be used as a good reinforcement of the paper.

This study aimed to evaluate the effects of intravenous injection of cysteamine (CS) on body weight (BW), growth hormone (GH), thyroid hormones (TH) secretion, and antioxidant status of growing lambs grazing on mountain pastures. Fifteen lambs (3–4 months of age) were randomly allocated into three experimental groups which received different dosages of CS: 0, 20, and 50 mg/kg BW−1. The CS was injected on the 1st, 10th, and 20th days of the experiment to the lambs through the jugular vein. Assessment of plasma concentration of GH and TH hormones was carried out at days 0 (a day before the start of CS injections), 15, and 30 of the experiment. The antioxidant enzymes were measured at the end of the experiment. Lambs were weighed at days 0, 10, 20, and 30 of the experiment. The results showed that treatment and time affected the BW, GH, triiodothyronine (T3), and tetraiodothyronine (T4) secretion. The intravenous injection of CS increased the BW of growing lambs (p, In this study, we studied the effect of cysteamine on body weight and secretions of GH and thyroid hormones and the antioxidant capacity of growing lambs in the extensive production system in growing lambs. Generally, we observed the positive effect of cysteamine on growth parameters and antioxidant capacity in growing lambs.

Cancers adapt to increasingly potent targeted therapies by reprogramming their phenotype. Here we investigated such a phenomenon in prostate cancer, in which tumours can escape epithelial lineage confinement and transition to a high-plasticity state as an adaptive response to potent androgen receptor (AR) antagonism. We found that AR activity can be maintained as tumours adopt alternative lineage identities, with changes in chromatin architecture guiding AR transcriptional rerouting. The epigenetic regulator enhancer of zeste homologue 2 (EZH2) co-occupies the reprogrammed AR cistrome to transcriptionally modulate stem cell and neuronal gene networks-granting privileges associated with both fates. This function of EZH2 was associated with T350 phosphorylation and establishment of a non-canonical polycomb subcomplex. Our study provides mechanistic insights into the plasticity of the lineage-infidelity state governed by AR reprogramming that enabled us to redirect cell fate by modulating EZH2 and AR, highlighting the clinical potential of reversing resistance phenotypes.

Abiotic stress is an important ecological problem limiting crop growth and productivity of other important substances like Carbohydrates, protein, and Chlorophyll ‘a’ and ‘b’ contents in plants. The objective of the present study was to investigate the effects of various concentrations of NaCl, 20ppm, 40ppm, 60ppm, 80ppm, 100ppm and non-saline concentration on two varieties, Ata Habib and Pirsabak of Triticum aestivum. Effects of NaCl were observed on Biochemicals contents (Carbohydrates, protein, Chlorophyll a and b) and germination percentage, seedling shoot length, seedling root length, seedling fresh and dry biomass, root numbering and leaf numbering. The result showed that germination and seedling growth reduced with the increasing concentration of NaCl while total carbohydrates and chl ‘a’ and ‘b’ increased with increasing salt application on both varieties but protein contents decrease significantly on a high level of sodium chloride. The overall comparison of both varieties in morphologically and biochemically parameters under sodium chloride showed that Pirsabak was more affected by NaCl compared to Ata Habib indicating that the species can tolerate NaCl laden soils. We recommend that the experiment be repeated with more varieties of Triticum aestivum under field conditions to compare results and to obtain more NaCl tolerant varieties.

During the processing of the fishery resources, the significant portion is either discarded or used to produce low-value fish meal and oil. However, the discarded portion is the rich source of valuable proteins such as collagen, vitamins, minerals, and other bioactive compounds. Collagen is a vital protein in the living body as a component of a fibrous structural protein in the extracellular matrix, connective tissue and building block of bones, tendons, skin, hair, nails, cartilage and joints. In recent years, the use of fish collagen as an increasingly valuable biomaterial has drawn considerable attention from biomedical researchers, owing to its enhanced physicochemical properties, stability and mechanical strength, biocompatibility and biodegradability. This review focuses on summarizing the growing role of fish collagen for biomedical applications. Similarly, the recent advances in various biomedical applications of fish collagen, including wound healing, tissue engineering and regeneration, drug delivery, cell culture and other therapeutic applications, are discussed in detail. These applications signify the commercial importance of fish collagen for the fishing industry, food processors and biomedical sector.

Human leukocyte antigen (HLA) system is the most polymorphic and gene dense region of human DNA that has shown many disease associations. It has been further divided into HLA classes I, II, and III. Polymorphism in HLA class II genes has been reported to play an important role in the pathogenesis of type 1 diabetes (T1D). It also showed association with T2D in different ethnic populations. However, a little is known about the relationship of HLA class I gene polymorphism and T2D. This study has evaluated the association of HLA-B (class I gene) variants with T2D in Pashtun ethnic population of Khyber Pakhtunkhwa. In the first phase of the study, whole exome sequencing (WES) of 2 pooled DNA samples was carried out, and DNA pools used were constructed from 100 diabetic cases and 100 control subjects. WES results identified a total of n = 17 SNPs in HLA-B gene. In the next phase, first 5 out of n = 17 reported SNPs were genotyped using MassARRAY® system in order to validate WES results and to confirm association of selected SNPs with T2D. Minor allele frequencies (MAFs) and selected SNPs×T2D association were determined using chi-square test and logistic regression analysis. The frequency of minor C allele was significantly higher in the T2D group as compared to control group (45.0% vs. 13.0%) ( p = 0.006 ) for rs2308655 in HLA-B gene. No significant difference in MAF distribution between cases and controls was observed for rs1051488, rs1131500, rs1050341, and rs1131285 ( p > 0.05 ). Binary logistic regression analyses showed significant results for SNP rs2308655 ( OR = 2.233 , CI 95 % = 1.223 ‐ 4.077 , and p = 0.009 ), while no considerable association was observed for the other 4 SNPs. However, when adjusted for these variants, the association of rs2308655 further strengthened significantly ( adjusted OR = 7.485 , CI 95 % = 2.353 ‐ 23.812 , and p = 0.001 ), except for rs1131500, which has no additive effect. In conclusion, the finding of this study suggests rs2308655 variant in HLA-B gene as risk variant for T2D susceptibility in Pashtun population.

Ca2+ is a universal intracellular signal that regulates many cellular functions. In Toxoplasma gondii, the controlled influx of extracellular and intracellular Ca2+ into the cytosol initiates a signaling cascade that promotes pathogenic processes like tissue destruction and dissemination. In this work, we studied the role of proton transport in cytosolic Ca2+ homeostasis and the initiation of Ca2+ signaling. We used a T. gondii mutant of the V-H+ -ATPase, a pump previously shown to transport protons to the extracellular medium, and to control intracellular pH and membrane potential and we show that proton gradients are important for maintaining resting cytosolic Ca2+ at physiological levels and for Ca2+ influx. Proton transport was also important for Ca2+ storage by acidic stores and, unexpectedly, the endoplasmic reticulum. Proton transport impacted the amount of polyphosphate (polyP), a phosphate polymer that binds Ca2+ and concentrates in acidocalcisomes. This was supported by the co-localization of the vacuolar transporter chaperone 4 (VTC4), the catalytic subunit of the VTC complex that synthesizes polyP, with the V-ATPase in acidocalcisomes. Our work shows that proton transport regulates plasma membrane Ca2+ transport and control acidocalcisome polyP and Ca2+ content, impacting Ca2+ signaling and downstream stimulation of motility and egress in T. gondii.

In current study, α-amylase of fungal origin was immobilized using cross-linking strategy. The influence of precipitant (ammonium sulphate) and cross-linker (glutaraldehyde) concentration revealed that 60% (w/v) precipitant and 1.5% (v/v) cross-linker saturation was required to attain optimum activity. Cross-linked amylase aggregates (CLAAs) were characterized and 10-degree shift in optimum temperature (soluble enzyme: 50 °C; cross-linked: 60 °C) and 1-unit shift in pH (soluble enzyme: pH -6; cross-linked: pH -7) was observed after immobilization. The Vmax for soluble α-amylase and its cross-linked form was 1225 U ml−1 and 3629 U ml−1, respectively. The CLAAs was more thermostable than its soluble form and retained its 30% activity even after 60 min of incubation at 70 °C. Moreover, cross-linked amylase retained its activity after two months while its soluble counterpart lost its complete activity after 10 and 20 days at 30 °C and 4 °C storage, respectively. Reusability test showed that cross-linked amylase could retain 13% of its residual activity after 10 repeated cycles. Therefore, 10 times more glucose was produced after cross-linking than soluble amylase when it was utilized multiple times. This study indicates that amylase aggregates are highly effective for continuous liquefaction of starch, hence have strong potential to be used for different industrial processes.

Sustainable development is development that meets the needs of the present without compromising the ability of future generations to meet their own needs. During a study near an ecotourism site, we recorded a melanistic Leopard Panthera pardus delacouri on top of Bukit Kudung in Jeli District. This finding is considered important because the Indochinese Leopard P.p. delacouri is classified as Critically Endangered in the Red List of Threatened Species by the International Union for Conservation of Nature (IUCN). We hope that this record will foster conservation efforts in the area.

Background & Aims of the Study: The prevalence of food insecurity in many countries and the challenges emerging to feed more than 9 billion people by 2050 have led the researchers to look for alternative sources of protein in human and animal diets. In this regard, today, the use of insects has attracted a lot of attention since they contain high nutritional value and help to preserve environmental resources. Among the various species of insects, particular attention has been paid to the black soldier fly (BSF) since it can consume from a variety of substrates, including organic waste. Various factors, such as temperature, humidity, density, light, and diet, are involved in the breeding of this insect. It seems that temperature is more effective in the breeding stages of this species than the other factors. Due to the insufficient information on finding the optimal temperature in breeding this species, this study was conducted to determine the mentioned factor in the maximum production and reproduction of black soldier flies to eliminate organic waste and turn it into valuable material in animal food. Materials and Methods: Organic waste, including kitchen fruit and food, was used to feed the larvae. Adult flies were then reared in cotton net cages (40´40´40 cm) and under the temperature range of 25-35°C. Afterward, the eggs were collected by fine needles and transferred to a temperature-controlled incubator during the hatching stage to undergo experiments in the specified temperature range (i.e., 25-35°C). The larvae fed freely from the formulated diet (i.e., chicken feed) until the pre-pupal stage. The produced pupae were monitored for growth and survival in the temperature range of 25-35°C. The emergence of adult BSFs at different temperatures was examined after the completion of the pupal stage under controlled temperature. In this descriptive study after the completion of each insectchr('39')s development stage, the percentage of insect survival in each stage of measured temperature condition was determined by estimating the proportion of the attribute present in the population. Results: According to the results of this study, the highest hatching percentage (80%) was recorded at 30°C for 4 days, while the slowest growth period was obtained at 30°C for 13 days with a survival rate of 92%. It was also revealed that the highest pre-pupal and pupal survival rates were 82% at 30°C for 10 days and 77% at 30°C for 7 days, respectively. The lifespan of adult flies at 30°C was reported to be 9 days. The statistical population of this consisted of 300 pupae at each temperature. The survival percentage was reported after the survived pupae were counted. Conclusion: The results of this study showed that the growth and reproduction of BSFs were significantly affected by temperature. In this study, the optimum temperature in the breeding of BSFs was obtained as 30°C. Temperature can also affect the insectchr('39')s biological life cycle, such as immaturity survival and adult lifespan, growth, fertility, gender ratio, and population growth parameters.

Poor soil fertility due to continuous depletion of micronutrients is a major problem for the production of Prunus domestica L. Low level of soil organic matter and calcareous parent material decrease the bioavailability of these micronutrients to plum plants. Thus, less micronutrients uptake resulted in deterioration of plum fruit quality and decreased yield. On the other hand, balance and correct combination of micronutrients used as a foliar has potential to overcome this problem. Foliar application method provides plants a chance for rapid and easy uptake of micronutrients. Therefore, the present research was carried out to select the best combination of micronu-trients using foliar method. Aim of the study was to select a balanced combination of micronutrients for better production and improved quality of plum (Prunus domestica L., variety Fazal manai) fruit. Seven treatments in three replications were applied. Our results showed that the quality of fruit was significantly improved through the application of T6 micronutrients consortia. A significant increase in total soluble solids (16%), fruit yield per tree (92%) and fruit size (12%) validated the effectiveness of treatment T6 (Zn + Cu + Fe + Mn + B = 0.5% + 0.2% + 0.5% + 0.5% + 0.1%) over control. Application of treatment T6 also enhanced quality attributes, that is, juice acid-ity (22%), juice sugar (22%) and juice contents (16%), as compared to control. It is concluded that use of treatment T6 as a foliar application is a better approach for significant improvement in quality and yield attributes of plum in micronutrients deficient conditions.

Paternally expressed gene 10 (PEG10) has been associated with neuroendocrine muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in The Cancer Genome Atlas database of 412 patients with MIBC, and found that, compared with other subtypes, PEG10 mRNA level was enhanced in neuroendocrine-like MIBC and highly correlated with other neuroendocrine markers. PEG10 protein level also associated with neuroendocrine markers in a tissue microarray of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared with parental cells, and knocking down of PEG10 resensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell-cycle regulators p21 and p27 and delayed G1–S-phase transition, while overexpression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation, and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers.

AIMS NOX-derived reactive oxygen species (ROS) are mediators of signaling pathways implicated in vascular smooth muscle cell (VSMC) dysfunction in hypertension. Among the numerous redox-sensitive kinases important in VSMC regulation is c-Src. However, mechanisms linking NOX/ROS to c-Src are unclear, especially in the context of oxidative stress in hypertension. Here we investigated the role of NOX-induced oxidative stress in VSMCs in human hypertension focusing on NOX5, and explored c-Src, as a putative intermediate connecting NOX5-ROS to downstream effector targets underlying VSMC dysfunction. METHODS AND RESULTS VSMC from arteries from normotensive (NT) and hypertensive (HT) subjects were studied. NOX1,2,4,5 expression, ROS generation, oxidation/phosphorylation of signaling molecules, actin polymerization and migration were assessed in the absence and presence of NOX5 (melittin) and Src (PP2) inhibitors. NOX5 and p22phox-dependent NOXs (NOX1-4) were downregulated using NOX5 siRNA and p22phox-siRNA approaches. As proof of concept in intact vessels, vascular function was assessed by myography in transgenic mice expressing human NOX5 in a VSMC-specific manner. In HT VSMCs NOX5 was upregulated, with associated oxidative stress, hyperoxidation (c-Src, peroxiredoxin, DJ-1) and hyperphosphorylation (PKC, ERK1/2, MLC20) of signaling molecules. NOX5 siRNA reduced ROS generation in NT and HT subjects. NOX5 siRNA, but not p22phox-siRNA, blunted c-Src phosphorylation in HT VSMCs. NOX5 siRNA reduced phosphorylation of MLC20 and FAK in NT and HT. In p22phox- silenced HT VSMCs, Ang II-induced phosphorylation of MLC20 was increased, effects blocked by melittin and PP2. NOX5 and c-Src inhibition attenuated actin polymerization and migration in HT VSMCs. In NOX5 transgenic mice, vascular hypercontractilty was decreased by melittin and PP2. CONCLUSIONS We define NOX5/ROS/c-Src as a novel feedforward signaling network in human VSMCs. Amplification of this system in hypertension contributes to VSMC dysfunction. Dampening the NOX5/ROS/c-Src pathway may ameliorate hypertension-associated vascular injury. TRANSLATIONAL PERSPECTIVE Oxidative stress is a major factor contributing to vascular damage in hypertension. We corroborate experimental evidence that NOX-derived ROS generation is increased in human vascular smooth muscle cells (VSMC) and demonstrate that in human hypertension NOX5 upregulation is a major trigger of VSMC dysfunction. We uncover new regulatory molecular mechanisms of NOX5 and define NOX5/ROS/c-Src as a novel signaling pathway in human VSMCs. This system is augmented in hypertension contributing to abnormal VSMC redox signaling, cytoskeletal disorganization and vascular dysfunction. Modulating the NOX5/ROS/c-Src pathway may have therapeutic potential by targeting redox signaling pathways involved in vascular dysfunction associated with hypertension.

An experiment was conducted to estimate the genetic variability and regression analysis for yield and quality traits in a set of eight brassica genotypes in a randomized complete block design with three replications at The University of Agriculture Peshawar, during 2011-12 cropping season. Significant genetic variability was recorded among genotypes for plant height, pods main receme-1, pod length, seed yield plant-1, 1000-seed weight, seeds pod-1, oil content, protein content, glucosinolate content, erucic acid content, oleic acid content and linolenic acid content except for primary branch plant-1 and pods plant-1 which showed non-significant differences. Genotypes, AUP-401, AUP-402, AUP-404 and AUP-407 showed potential performance for glucosinolate content (55.1 µmol g-1), seed yield plant-1 (23.93 g), pods plant-1 (268.83), protein contents (21.1 %), erucic acid contents (42.7 %) and oil contents (53.3 %). Seed yield plant-1 was taken as a dependent variable to study the effects of many morphological yield traits on it. Branches plant-1, pods main raceme-1, pods plant-1, and seed pod-1 showed a positive effect on seed yield plant-1, while 1000-seed weight, pod length, and plant height showed a negative effect on seed yield plant-1. Seed yield plant-1 as an independent variable showed a negative effect on oil content. Protein content as an independent variable showed a positive effect on erucic acid content, while oil contents as independent variables show a negative effect on protein contents, respectively. The developed germplasm could be used in the upcoming brassica breeding programs to release high yielding, disease resistance, stress tolerance, and insect resistance varieties, which will eventually upsurge the productivity and decrease the gap between demand and domestic production of the brassica crop.

Alzheimer’s disease (AD) is a neurodegenerative disorder, in which amyloid precursor protein (APP) misprocessing and tau protein hyperphosphorylation are well-established pathogenic cascades. Despite extensive considerations, the central mediator of neuronal cell death upon AD remains under debate. Therefore, we examined the direct interplay between tauopathy and amyloidopathy processes. We employed primary culture neurons and examined pathogenic P-tau and Aβ oligomers upon hypoxia treatment by immunofluorescence and immunoblotting. We observed both tauopathy and amyloidopathy processes upon the hypoxia condition. We also applied Aβ1–42 or P-tau onto primary cultured neurons. We overexpressed P-tau in SH-SY5Y cells and found Aβ accumulation. Furthermore, adult male rats received Aβ1–42 or pathogenic P-tau in the dorsal hippocampus and were examined for 8 weeks. Learning and memory performance, as well as anxiety behaviors, were assessed by Morris water maze and elevated plus-maze tests. Both Aβ1–42 and pathogenic P-tau significantly induced learning and memory deficits and enhanced anxiety behavior after treatment 2 weeks. Aβ administration induced robust tauopathy distribution in the cortex, striatum, and corpus callosum as well as CA1. On the other hand, P-tau treatment developed Aβ oligomers in the cortex and CA1 only. Our findings indicate that Aβ1–42 and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner, while tauopathy seems to be more distributable than amyloidopathy.

The current study was carried out to assess the effect of the crude methanolic extract of Aerva javanica for hepatoprotective and nephroprotective assessment along with their antioxidant potential against 2,2-azinobis(3-ethylenbenzthiazolin)-6sulfonic acid (ABTS) and 2,2diphenyle-1-picrylhyzyl (DPPH) using a standard protocol. Result of the crude methanolic extract of Aerva javanica showed 65.55, 59.37, 53.86, 47.49 and 34.76% inhibition against DPPH while against ABTS it showed 60.12, 48.45, 41.36, 37.99 and 31.89% inhibition at the concentrations 1000, 500, 250, 125 and 62.5 μg/mL. Ascorbic acid was used as a positive control and displayed a dose-dependent response. Results of Total phenolic content (TPC) and total flavonoid content (TFC) have shown 52% and 67%.The crude methanolic extract of Aerva javanicawas tested at two different doses for hepatoprotective and nephroprotective effect (150 and 300 mg/kg) in rabbits model. In comparison with the standard drug and normal saline, the test sample showed a significant hepatoprotective and nephroprotective effect. The effects of all the analyzed biomarkers of the liver (AST, ALT, ALP, serum triglyceride, serum cholesterol, and serum bilirubin) and Urea (Blood serum, Blood sugar, and Serum creatinine) showed significant effects both at 150 and 300 mg/kg. Both doses were found hepatoprotective (150 mg/kg and 300 mg/kg). Whereas, some liver biomarkers (ALT, ALP, serum triglyceride) of the methanolic extract at a dose of 300mg/kg showed significant hepatoprotective while some biomarkers (AST, serum cholesterol and serum bilirubin) was found effective at a dose of 150 mg/kg rather than the higher dose. The nephroprotective effect of the plant also increases in a dose-dependent manner i.e it is more effective at a dose of 300 mg/kg as compared to 150 mg/kg body weight. On the bases of these biomarkers, the plant extract was found an effective hepatoprotective at both the test doses.

This paper focuses on the characterized of the mechanical properties and hyper elastic behavior of lab made skin. Bovine Serum Albumin (BSA) combined with gelatin as a base. BSA is a plasma lead concentrations or heparin plasma which is separated from blood sample and it is not associated with significant changes in iron or hemoglobin concentrations. In general, the gelatin is widely used as the best material for skin substitution since it exhibits the characteristic of human skin. However, the lab made skin layer was made of non-halal type gelatin (Type B). The methodology process started by adding the BSA and using the type A gelatin to carry out the mechanical properties and hy-per elastic behavior of halal lab made skin layer. A uniaxial tensile test standard that being used in this study is ASTM D412. The raw data (Load-Extension) from computational was plotted on graph stress-strain. The numerical approach such as Mooney-Rivlin model and Yeoh’s model were selected to analyze a stress-stretch of composition gelatin and BSA. From the results Mooney-Rivlin model, the con-stant, C1 is in the range of (0.0187-0.0658) MPa and C2 is in the range of (0.0628-0.0737) MPa. Meanwhile the constant, CP for Yeoh model is in the range of (0.0748-0.0861) MPa. As a conclusion, the composition of gelatin and Bovine Serum Albumin is a best combina-tion as it increases the strength of the lab made skin layer. Therefore, the most suitable composition is 10 wt.% of gelatin and Bovine Serum Albumin.

Persian sturgeon, Acipenser persicus Borodin, has been the most significant proportion of Iranian commercial sturgeon catches in the Caspian Sea over in the last three decades. This endemic species has suffered continuous population declines from the impact of anthropogenic factors. The present study filled in information gaps on underlying population biology parameters, evaluated the population status, and determined the vulnerability risk of the stock extinction of Persian sturgeon in the south Caspian basin of Iran. Growth parameters were L ∞ = 224.7 cm, K = 0.058 years−1, t 0 = -3.4 years. Sexual maturity of 50% for males and females was FL = 127.2 cm and 137.5 cm, respectively. The long-term age composition data showed 35 age groups, and the ages of 14–18 years comprised 80% of the total catch. Natural mortality was 0.123 years−1, and fishing mortality ranged between 0.104 and 0.331 years −1. The total biomass trend decreased and collapsed from 6,071.3 tons in 1990–91 to 144.1 tons in 2014–15. Although >93% of the catch included maturing specimens, the Persian sturgeon stock is now critically endangered because of several anthropogenic factors.

Different seeds are dispersed from infested to uninfested areas possibly due to several biotic and abiotic mechanisms, and this spread of seed aids the invasion process across the landscape. Currently, in District Charsadda KP, Pakistan, there are about thousands of motorized vehicles, each capable of carrying infested seeds and therefore spreading crop seeds and plant seeds. Studies were conducted in 2019 to investigate the role of the utility vehicles in the dispersal of seeds in District Charsadda. A large number of seeds were found on vehicles. In the current study undertaken in KP, the maximum number of species from the family Apiaceae (3.00), Poaceae (3.00) and Solanaceae (3.00) were found dominant on the vehicles. Whereas, the minimum species number from the family Asteraceae (1.00), Fabaceae (1.00), Ebenaceae (1.00), Umbelliferae (1.00) and Cucurbitaceae (1.00) were associated with the vehicle. These seeds were found on several parts of the vehicles and were contained within mud or dust that had presumably transferred to the vehicle as it undertook its routine activities. The early implications from this present study is that utility vehicles are capable of collecting, carrying, and presumably distributing large numbers of seeds that seed is carried on many parts of the vehicle. Thus, any washing or cleaning procedure used to remove seeds from vehicles will need to concentrate on all parts of the vehicle. Cleaning vehicles at appropriate places should be seen as a possible way to reduce seed spread by utility vehicles.

The DNA damage response (DDR) pathway is a promising target for anticancer therapies. The androgen receptor and myeloblastosis transcription factors have been reported to regulate expression of an overlapping set of DDR genes in prostate cancer cells. Here, we found that histone demethylase JMJD1A regulates expression of a different set of DDR genes largely through c-Myc. Inhibition of JMJD1A delayed the resolution of γ-H2AX foci, reduced the formation of foci containing ubiquitin, 53BP1, BRCA1 or Rad51, and inhibited the reporter activity of double-strand break (DSB) repair. Mechanistically, JMJD1A regulated expression of DDR genes by increasing not only the level but also the chromatin recruitment of c-Myc through H3K9 demethylation. Further, we found that ubiquitin ligase HUWE1 induced the K27-/K29-linked noncanonical ubiquitination of JMJD1A at lysine-918. Ablation of the JMJD1A noncanonical ubiquitination lowered DDR gene expression, impaired DSB repair, and sensitized response of prostate cells to irradiation, topoisomerase inhibitors or PARP inhibitors. Thus, development of agents that target JMJD1A or its noncanonical ubiquitination may sensitize the response of prostate cancer to radiotherapy and possibly also genotoxic therapy.

There is a significant lack of data for the biological parameters of beluga or great sturgeon, the largest fish in the Caspian Sea. The age, growth and fisheries indices for the stock status of beluga was investigated in the south Caspian Basin of Iran between 1990 and 2011. Fork lengths ranged between 113-420 cm and weights from 8.0 to 725.0 kg. The growth parameters were L ∞ = 440 cm, K = 0.027 year−1, t 0 = − 5.8 years. The age at first capture (t c ) was 13.1 years. The long-term age composition data showed age up to 63 years, and the ages 12-19 years comprised 76.7% of the total catch. The generation length was 33 years. The values of “KF” were close to 1 or >1, indicating that beluga sturgeon is in a favorable condition in the southern Caspian Sea. The length distribution showed that 24.2% of the catch is comprised of juveniles. Based on the age structure and age at first maturity, recruitment and growth overfishing occurred in beluga stocks. Therefore, increased length or age at first capture in future fishery policies should be implemented. The mega-spawners represented 4.4% of the fish captured and revealed an unhealthy population structure.

Objective: This study was aimed to investigate the in vitro antioxidant, antimicrobial, cytotoxicity, and enzyme inhibition activities of Tragopogon porrifolius and Polygonum cognatum which are naturally grown and consumed intensively by people in Sivas, Turkey. Methods: Plant materials were extracted with aqueous ethanol by maceration method. The components of the extracts were determined using the Gas Chromatography Mass Spectrometry. Antimicrobial, cytotoxic and enzyme inhibition activities of the extracts were investigated by micro dilution, XTT assay and 96-micro-well plate methods, respectively. The antioxidant activity evaluated using the DPPH radical scavenging, thiobarbituric acid and reducing power methods. The total phenol and total flavonoid content was also examined. Results: GC–MS analysis revealed the presence of 31 compounds inP. cognatum extract and 29 compounds in T. porrifolius extract. According to the results, T. porrifolius extract showed high level of antioxidant activity in comparison to P. Cognatum extract. T. porrifolius exhibited higher ?-glucosidase inhibitory activity, and both extract showed strong ?-amylase inhibition activity compared to reference drug acarbose. T. porrifolius and P. cognatum ethanolic extracts exhibited antimicrobial activity in the concentration range of 0.039–2.5 mg/ml. Both extracts also exhibited significant anticancer effect on MDA-MB-231 breast cancer cells. The IC50 values of T. porrifolius and P. cognatum extracts in MDA-MB-231 cells were determined as 0.0625 mg/mL and 0.053 mg/mL, respectively. Conclusion: Our findings demonstrated that T. porrifolius and P. cognatum ethanolic extracts have promising effect on antioxidant, antimicrobial and cytotoxic activity as well as enzyme inhibition activity, and hence further studies required to identify specific compounds responsible for these activities. © 2019, Sivas Cumhuriyet Ãœniversitesi, The authors would like to acknowledge the C?BAP project (NO: ECZ20 and ECZ26) for financial support to the realization of these studies. The authors also would like to thank the Sivas Cumhuriyet University Advanced Technology Applications and Research Center for providing laboratory facilities to conducting these studies.

Kallikrein‐related peptidase 14 (KLK14) is one of the several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumor microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analyzed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic, and in vitro assays with the goal to identify substrates, related‐signaling pathways, and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neoadjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression reoccurred in patients who developed castrate‐resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14 substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14‐regulated genes (Interleukin 32, midkine, SRY‐Box 9), particularly an involvement of the mitogen‐activated protein kinase 1 and interleukin 1 receptor pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumors. Additional work is necessary to determine the benefits and implications of targeting/cotargeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment., Kallikrein‐related peptidase 14 (KLK14) is a secreted serine protease belonging to the kallikrein‐related‐peptidase family. We identified that KLK14 is overexpressed in advanced prostate cancer and acts on various substrates involved in adhesion, migration, and invasion of cancer cells, thus modulating genes and signaling pathways essential for prostate cancer progression. These results suggest that KLK14 is a potential target to control aggressiveness of prostate tumors.

Animal derived milk which is an important part of human diet due to its high nutritional value not only supports humans but also presents a growth environment for pathogenic bacteria. Milk may become contaminated with bacteria through udder infections or through contact within the dairy farm environment. Infections are treated with antibiotics, with β-lactams most commonly used in veterinary medicine. However, their frequent use leads to the emergence of β-lactam resistant bacterial strains, which causes difficulties in the treatment of infections in both humans and animals. Detection of pathogens as well as their antibiotic sensitivity is a pre-requisite for successful treatment and this is generally achieved with laboratory-based techniques such as growth inhibition assays, enzyme-linked immunosorbent assays (ELISA) or polymerase chain reactions (PCRs), which are unavailable in resource-limited settings. Here, we investigated paper-based analytical devices (μPADs) for the presumptive detection of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) and their antibiotic resistant bacterial strains in milk samples. The μPADs were fabricated on filter paper using wax printing, and then impregnated with chromogenic substrates, which reacted with bacterial enzymes to form coloured products. Limits of detection of S. aureus and E. coli and their antibiotic resistant strains in milk samples were found to be 106 cfu mL-1. Enrichment of milk samples in a selective medium for 12 h enabled detection as low as 10 cfu mL-1. The paper devices tested on a set of 640 milk samples collected from dairy animals in Pakistan demonstrated more than 90% sensitivity and 100% selectivity compared to PCR, showing promise to provide inexpensive and portable diagnostic solutions for the detection of pathogenic bacteria in resource-limited settings.

Huge amount of organic wastes including agricultural field wastes, food wastes, municipal solid waste and manures can be converted into a safe and usable product that can be used as a possible substitute for chemical fertilizers. In this regard, the proposed study was designed with the aim to prepare macro and micronutrients rich vermicompost from different bio-wastes that can be used as a possible substitute to chemical fertilizers for improving plant growth. A 90 days vermicomposting experiment was conducted in wooden boxes (1×1 m) containing animal manure and waste material (grasses, brewed black tea leaf and dry leaf) mixed in 3:1 ratio with a 2.5 cm thin layer of soil. The material was at the bottom of the bed and around 10.000 earthworms of Eisenia fetida were settled in the box. The boxes were irrigated by sprinkled water daily and tilled from the top once every week for maintaining aeration and proper decomposition. The vermicompost production was continued for about 90 days in each box under 21-23°C room temperature. The results showed that by using animal manure and waste materials, the physical parameters like moisture content was increased upto50 % on day 90. Likewise, the percent increase recorded for total N, organic N, total P and soluble K content on day 90 was maximum in the vermicompost prepared from animal manure and waste material. It can be concluded from this experiment that with the help of earthworm‘s, different field and garden residues, wastes and manures can be converted into a nutrient rich and environment friendly vermicompost that can be used as a possible substitute to chemical fertilizers for improving plant growth.

Iron oxide nanoparticles (Fe2O3 NPs) were fabricated through green route using pomegranate (Punica granatum) seeds extract. The Fe2O3 NPs were characterized by UV–vis, XRD, EDX, SEM and AFM techniques. The adopted green rout furnished semi spherical Fe2O3 NPs, uniformly distributed and particle size in the range of 25–55 nm. The LCMS/MS was performed for the identification of biomolecule present in the extract of pomegranate seeds and p-hydroxy benzoic acid, gallic acid, methyl gallate, catechin, kaempferol-3-O-sophoroside, 3-deoxyflavonoids, magnolol, ferulic acid, vanillic acid and pinocembrin along with other minor constituents were detected in the extracts using for Fe2O3 NPs. The synthesized Fe2O3 NPs showed excellent photocatalytic activity against reactive blue under UV light irradiation and maximum degradation of 95.08% was achieved with 56 min of reaction time. In view of promising activity, the Fe2O3 NPs could be used photocatalyst for the degradation of dyes in wastewater and pomegranate seeds extract can be applied as eco-benign and cost effective approach for Fe2O3 NPs synthesis. Keywords: Punica granatum, Green synthesis, Iron oxide nanoparticles, Photocatalysis, Dye degradation

Contexts: Sauromatum guttatum (Wall.) Schott (Araceae) has been traditionally used for the treatment of wounds. Objectives: This study evaluates the healing and tissue regeneration potential of S. guttatum extract in burn wounds. Materials and methods: S. guttatum extract was analysed using various chemical tests, thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Moreover, the extract was tested against burn associated bacteria and minimum inhibitory concentration (MIC) was also calculated. Wound healing and tissue regeneration potential was assessed using a thermally induced burn BALBc mouse model. S. guttatum extract (2% w/w) prepared in petroleum jelly, vehicle and positive control [silver sulfadiazine (SD)] groups was applied three times a day. The treatment was continued for 15 d and wound closure was measured and photographed on day 5, 10 and 15. The burnt tissues excised from wounds were subjected to histological and comparative gene expression analysis. Results: The results of the chemical tests indicated the presence of alkaloids, saponins, phenols, phytosterols, tannins, and flavonoids, while TLC and HPLC analysis indicated the presence of various compounds. The extract showed excellent activity against the tested pathogens. The lowest MIC (125 µg/mL) was observed against Staphylococcus aureus. A considerable decrease in wound area (72%) was observed in extract-treated group. Histological examination of extract-treated group showed good signs of wound healing with complete re-epithelialization and better tissue regeneration. Comparative gene expression analysis revealed the up-regulation of wound healing related PDGF, EGF and FGF genes. Conclusions: S. guttatum extract may be used to isolate bioactive constituents for the treatment of burn wounds.

In the current study, APOB (rs1052031) genotype-guided proteomic analysis was performed in a cohort of Pakistani population. A total of 700 study subjects, including Coronary Artery Disease (CAD) patients (n = 480) and healthy individuals (n = 220) as a control group were included in the study. Genotyping was carried out by using tetra primer-amplification refractory mutation system-based polymerase chain reaction (T-ARMS-PCR) whereas mass spectrometry (Orbitrap MS) was used for label free quantification of serum samples. Genotypic frequency of GG genotype was found to be 90.1%, while 6.4% was for GA genotype and 3.5% was for AA genotypes in CAD patients. In the control group, 87.2% healthy subjects were found to have GG genotype, 11.8% had GA genotype, and 0.9% were with AA genotypes. Significant (p = 0.007) difference was observed between genotypic frequencies in the patients and the control group. The rare allele AA was found to be strongly associated with the CAD [OR: 4 (1.9–16.7)], as compared to the control group in recessive genetic model (p = 0.04). Using label free proteomics, altered expression of 60 significant proteins was observed. Enrichment analysis of these protein showed higher number of up-regulated pathways, including phosphatidylcholine-sterol O-acyltransferase activator activity, cholesterol transfer activity, and sterol transfer activity in AA genotype of rs562338 (G>A) as compared to the wild type GG genotype. This study provides a deeper insight into CAD pathobiology with reference to proteogenomics, and proving this approach as a good platform for identifying the novel proteins and signaling pathways in relation to cardiovascular diseases.

Purpose: The current study aimed to determine the phytochemicals and anti-breast cancer potential of Sphaeranthus indicus.Methods: S. indicus flowers were extracted with methanol followed by fractionation using n-hexane. For the chemical composition of n-hexane fraction, qualitative phytochemical and GC-MS analysis were performed. The anti-proliferative activity was measured by MTT assay, whereas, cytotoxic and proapoptotic effects in MCF-7 (breast cancer) cells were determined using propidium iodide, 4′,6-diamidino- 2-phenylindole, dichlorofluorescin diacetate, and JC-1 staining through fluorescent microscopy.Results: The phytochemical analysis indicated presence of phytosterols, oils and resins in the nhexane fraction. GC-MS analysis showed that n-hexane fraction comprises of 11 compounds including methyl esters of caprylic acid, myristic acid, pentadecanoic acid, palmitic acid, margaric acid, stearic acid, oleic acid, elaidic acid, linoleic acid, linolenic acid and behanic acid. The tested fraction showed remarkable cytotoxic activity against breast cancer (MCF-7) cells while it was found less toxic towards non-cancerous (BHK-21) cells. Furthermore, morphological assessment through fluorescent microscopy revealed cytotoxic and apoptotic effects by improved cell membrane permeability, increased reactive oxygen species level, compromised mitochondrial activity and condensation of chromatin network.Conclusion: The n-hexane fraction of S. indicus contains phytosterols, oils and fatty acid methyl esters and produced apoptotic effect against breast cancer cells.

Since its first detection in December 2019, more than 232 million cases of COVID-19, including 4.7 million deaths, have been reported by the WHO. The SARS-CoV-2 viral genomes have evolved rapidly worldwide, causing the emergence of new variants. This systematic review and meta-analysis was conducted to provide a global mutational profile of SARS-CoV-2 from December 2019 to October 2020. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), and a study protocol was lodged with PROSPERO. Data from 62 eligible studies involving 368,316 SARS-CoV-2 genomes were analyzed. The mutational data analyzed showed most studies detected mutations in the Spike protein (n = 50), Nucleocapsid phosphoprotein (n = 34), ORF1ab gene (n = 29), 5′-UTR (n = 28) and ORF3a (n = 25). Under the random-effects model, pooled prevalence of SARS-CoV-2 variants was estimated at 95.1% (95% CI; 93.3–96.4%; I2 = 98.952%; p = 0.000) while subgroup meta-analysis by country showed majority of the studies were conducted ‘Worldwide’ (n = 10), followed by ‘Multiple countries’ (n = 6) and the USA (n = 5). The estimated prevalence indicated a need to continuously monitor the prevalence of new mutations due to their potential influence on disease severity, transmissibility and vaccine effectiveness.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has attracted public attention. The gold standard for diagnosing COVID-19 is reverse transcription–quantitative polymerase chain reaction (RT-qPCR). However, RT-qPCR can only be performed in centralized laboratories due to the requirement for advanced laboratory equipment and qualified workers. In the last decade, clustered regularly interspaced short palindromic repeats (CRISPR) technology has shown considerable promise in the development of rapid, highly sensitive, and specific molecular diagnostic methods that do not require complicated instrumentation. During the current COVID-19 pandemic, there has been growing interest in using CRISPR-based diagnostic techniques to develop rapid and accurate assays for detecting SARS-CoV-2. In this work, we review and summarize reverse-transcription loop-mediated isothermal amplification (RT-LAMP) CRISPR-based diagnostic techniques for detecting SARS-CoV-2.

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5.

The unique properties and advantages of edible films over conventional food packaging have led the way to their extensive exploration in recent years. Moreover, the incorporation of bioactive components during their production has further enhanced the intrinsic features of packaging materials. This study was aimed to develop edible and bioactive food packaging films comprising yeast incorporated into bacterial cellulose (BC) in conjunction with carboxymethyl cellulose (CMC) and glycerol (Gly) to extend the shelf life of packaged food materials. First, yeast biomass and BC hydrogels were produced by Meyerozyma guilliermondii (MT502203.1) and Gluconacetobacter xylinus (ATCC53582), respectively, and then the films were developed ex situ by mixing 30 wt.% CMC, 30 wt.% Gly, 2 wt.% yeast dry biomass, and 2 wt.% BC slurry. FE-SEM observation showed the successful incorporation of Gly and yeast into the fibrous cellulose matrix. FTIR spectroscopy confirmed the development of composite films through chemical interaction between BC, CMC, Gly, and yeast. The developed BC/CMC/Gly/yeast composite films showed high water solubility (42.86%). The yeast-incorporated films showed antimicrobial activities against three microbial strains, including Escherichia coli, Pseudomonas aeruginosa, and Saccharomyces aureus, by producing clear inhibition zones of 16 mm, 10 mm, and 15 mm, respectively, after 24 h. Moreover, the films were non-toxic against NIH-3T3 fibroblast cells. Finally, the coating of oranges and tomatoes with BC/CMC/Gly/yeast composites enhanced the shelf life at different storage temperatures. The BC/CMC/Gly/yeast composite film-coated oranges and tomatoes demonstrated acceptable sensory features such as odor and color, not only at 6 °C but also at room temperature and further elevated temperatures at 30 °C and 40 °C for up to two weeks. The findings of this study indicate that the developed BC/CMC/Gly/yeast composite films could be used as edible packaging material with high nutritional value and distinctive properties related to the film component, which would provide protection to foods and extend their shelf life, and thus could find applications in the food industry.

Biofilms are a multicellular way of life, where bacterial cells are close together and embedded in a hydrated macromolecular matrix which offers a number of advantages to the cells. Extracellular polysaccharides play an important role in matrix setup and maintenance. A water-insoluble polysaccharide was isolated and purified from the biofilm produced by Burkholderia cenocepacia strain H111, a cystic fibrosis pathogen. Its composition and glycosidic linkages were determined using Gas&ndash, Liquid Chromatography&ndash, Mass Spectrometry (GLC&ndash, MS) on appropriate carbohydrate derivatives while its complete structure was unraveled by 1D and 2D NMR spectroscopy in deuterated sodium hydroxide (NaOD) aqueous solutions. All the collected data demonstrated the following repeating unit for the water-insoluble B. cenocepacia biofilm polysaccharide: [3)-&alpha, d-Galp-(1&rarr, 3)-&alpha, d-Glcp-(1&rarr, d-Manp-(1&rarr, ]n Molecular modelling was used, coupled with NMR Nuclear Overhauser Effect (NOE) data, to obtain information about local structural motifs which could give hints about the polysaccharide insolubility. Both modelling and NMR data pointed at restricted dynamics of local conformations which were ascribed to the presence of inter-residue hydrogen bonds and to steric restrictions. In addition, the good correlation between NOE data and calculated interatomic distances by molecular dynamics simulations validated potential energy functions used for calculations.

Cannabis abuse is a common public health issue and may lead to considerable adverse effects. Along with other effects, the dependence on cannabis consumption is a serious problem which has significant consequences on biochemical and clinical symptoms. This study intends to evaluate the harmful effects of the use of cannabis on thyroid hormonal levels, cardiovascular indicators, and psychotic symptoms in the included patients. This prospective multicenter study was conducted on cannabis-dependent patients with psychotic symptoms (n = 40) vs. healthy control subjects (n = 40). All participants were evaluated for psychiatric, biochemical, and cardiovascular physiological effects. Patients were selected through Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and urine samples, exclusively for the evaluation of cannabis presence. Serum thyroid stimulating hormone (TSH), T3, and T4 levels were measured using the immunoassay technique. Patients were assessed for severity of depressive, schizophrenic, and manic symptoms using international ranking scales. Various quantifiable factors were also measured for the development of tolerance by cannabis. Among the patients of cannabis abuse, 47.5% were found with schizophrenia, 20% with schizoaffective symptoms, 10% with manic symptoms, and 22.5% with both manic and psychotic symptoms. In the group–group and within-group statistical analysis, the results of thyroid hormones and cardiovascular parameters were non-significant. The psychiatric assessment has shown highly significant (p < 0.001) difference of positive, negative, general psychopathology, and total scores [through Positive and Negative Syndrome Scale (PANSS) rating scales] in patients vs. the healthy control subjects. The study revealed that cannabis abuse did not significantly alter thyroid hormones and cardiovascular parameters due to the development of tolerance. However, the cannabis abuse might have a significant contributing role in the positive, negative, and manic symptoms in different psychiatric disorders.

Silver nanoparticles (Ag. NPs) have shown a biological activity range, synthesized under different environment-friendly approaches. Ag. NPs were synthesized using aqueous crude extract (ACE) isolated from Plantago lanceolata. The ACE and Ag. NPs were characterized and assessed their biological and antioxidant activities. The existence of nanoparticles (NPs) was confirmed by color shift, atomic force microscopy (AFM), and UV–Vis’s spectroscopy. The FT-IR analysis indicated the association of biomolecules (phenolic acid and flavonoids) to reduce silver (Ag+) ions. The SEM study demonstrated a sphere-shaped and mean size in the range of 30 ± 4 nm. The EDX spectrum revealed that the Ag. NPs were composed of 54.87% Ag with 20 nm size as identified by SEM and TEM. AFM has ended up being exceptionally useful in deciding morphological elements and the distance across of Ag. NPs in the scope of 23–30 nm. The TEM image showed aggregations of NPs and physical interaction. Ag. NPs formation also confirmed by XPS, DRS and BET studies. Ag. NPs showed efficient activity as compared to ACE, and finally, the bacterial growth was impaired by biogenic NPs. The lethal dose (LD50) of Ag. NPs against Agrobacterium tumefaciens, Proteus vulgaris, Staphylococcus aureus, and Escherichia coli were 45.66%, 139.71%, 332.87%, and 45.54%, with IC50 (08.02 ± 0.68), (55.78 ± 1.01), (12.34 ± 1.35) and (11.68 ± 1.42) respectively, suppressing the growth as compared to ACE. The antioxidant capacity, i.e., 2,2-diphenyl-1-picrylhydrazyl (DPPH) of Ag. NPs were assayed. ACE and Ag. NPs achieved a peak antioxidant capacity of 62.43 ± 2.4 and 16.85 ± 0.4 μg mL−1, compared to standard (69.60 ± 1.1 at 100 μg mL−1) with IC50 (369.5 ± 13.42 and 159.5 ± 10.52 respectively). Finally, the Ag. NPs synthesized by P. lanceolata extract have an excellent source of bioactive natural products (NP). Outstanding antioxidant, antibacterial activities have been shown by NPs and can be used in various biological techniques in future research.

Treatment‐induced adaptive pathways converge to support androgen receptor (AR) reactivation and emergence of castration‐resistant prostate cancer (PCa) after AR pathway inhibition (ARPI). We set out to explore poorly defined acute adaptive responses that orchestrate shifts in energy metabolism after ARPI and identified rapid changes in succinate dehydrogenase (SDH), a TCA cycle enzyme with well‐known tumor suppressor activity. We show that AR directly regulates transcription of its catalytic subunits (SDHA, SDHB) via androgen response elements (AREs). ARPI acutely suppresses SDH activity, leading to accumulation of the oncometabolite, succinate. Succinate triggers calcium ions release from intracellular stores, which in turn phospho‐activates the AR‐cochaperone, Hsp27 via p‐CaMKK2/p‐AMPK/p‐p38 axis to enhance AR protein stabilization and activity. Activation of this pathway was seen in tissue microarray analysis on prostatectomy tissues and patient‐derived xenografts. This adaptive response is blocked by co‐targeting AR with Hsp27 under both in vitro and in vivo studies, sensitizing PCa cells to ARPI treatments., Prostate cancer becomes resistant to treatments targeting oncogenic androgen receptor (AR) via coordinated activity of multiple adaptive responses. This study defines metabolic reprogramming in response to AR pathway inhibition (ARPI) that supports AR reactivation.

Biochar prepared from various feedstock materials has been utilized in recent years as a potential stabilizing agent for heavy metals in smelter-contaminated soils. However, the effectiveness of animal bone-derived biochar and its potential for the stabilization of contaminants remains unclear. In the present study, sheep bone-derived biochar (SB) was prepared at low (500 °C; SBL) and high temperatures (800 °C; SBH) and amended a smelter-contaminated soil at 2, 5, and 10% (w/w). The effects of SB on soil properties, bioavailable Zn and Cd and their geochemical fractions, bacterial community composition and activity, and the response of plant attributes (pigments and antioxidant activity) were assessed. Results showed that the SBH added at 10% (SBH10) increased soil organic carbon, total nitrogen, and phosphorus, and also increased the oxidizable and residual Zn and Cd fractions at the expense of the bioavailable fractions. The SBH10 lowered the Zn and Cd contents in maize roots (by 57 and 60%) and shoot (by 42 and 61%), respectively, compared to unamended control. Additionally, SBH10 enhanced urease (98%) and phosphates (107%) activities, but reduced dehydrogenase (58%) and β-glucosidase (30%) activities. Regarding the effect of the pyrolysis temperature, SBH enhanced the activity of Acidobacteria, Bacteroidetes, Firmicutes, Nitrospirae, Verrucomicrobia, Chlorobi, and Microgenomates, but reduced Actinobacteria and Parcubacteria in comparison to SBL. However, only the SBL10 reduced the Proteobacteria community (by 9%). In conclusion, SB immobilized Zn and Cd in smelter-affected soils, enhanced the bacterial abundance and microbial function (urease, phosphates), and improved plant growth. However, validation of the results, obtained from the pot experiment, under field conditions is suggested.

Climate change is occurring and is influencing biological systems through augmented temperatures, more inconstant precipitation, and rising CO2 in the atmosphere. For sustainable landscaping, it was essential to assess the diversity of native/wild grasses and their suitability for turf and to combat the salinity problem in the region. For this purpose, a native halophytic grass, Aeluropus lagopoides, was investigated by conducting mowing tests on its ecotypes during the year 2014–2016 under desert climatic conditions. The research was carried out in two phases, i.e. Phase-I was for collection and establishment of ecotypes from various parts of UAE, while in Phase-II, mowing tests were conducted. During mowing tests, 50 ecotypes of A. lagopoides were given various mowing treatments (i.e. they were cut back at 1-, 2-, 3-, 4- and 5-cm heights) in field conditions. Significant differences were found among various ecotypes for different agronomic parameters such as ground cover, canopy stiffness, leaf number, clippings fresh and dry weights and internode length. Overall, the grass exhibited better performance at mowing heights of 3 and 4 cm, which are the standard mowing heights for turfgrasses. Ecotypes FA5, RA3, RUDA2, RUDA7 and RUADA1 of A. lagopoides showed the best performance against mowing shock and became the candidates for the turfgrass varieties from the native Arabian flora.

Deregulated expression of circular RNAs (circRNAs) is associated with various human diseases, including many types of cancer. Despite their growing links to cancer, there has been limited characterization of circRNAs in metastatic castration-resistant prostate cancer, the major cause of prostate cancer mortality. Here, through the analysis of an exome-capture RNA-seq dataset from 47 metastatic castration-resistant prostate cancer samples and ribodepletion and RNase R RNA-sequencing of patient-derived xenografts (PDXs) and cell models, we identified 13 circRNAs generated from the key prostate cancer driver gene-androgen receptor (AR). We validated and characterized the top four most abundant, clinically relevant AR circRNAs. Expression of these AR circRNAs was upregulated during castration-resistant progression of PDXs. The upregulation was not due to global increase of circRNA formation in these tumors. Instead, the levels of AR circRNAs correlated strongly with that of the linear AR transcripts (both AR and AR-variants) in clinical samples and PDXs, indicating a transcriptional mechanism of regulation. In cultured cells, androgen suppressed the expression of these AR circRNAs and the linear AR transcripts, and the suppression was attenuated by an antiandrogen. Using nuclear/cytoplasmic fractionation and RNA in-situ hybridization assays, we demonstrated predominant cytoplasmic localization of these AR circRNAs, indicating likely cytoplasmic functions. Overall, this is the first comprehensive characterization of circRNAs arising from the AR gene. With greater resistance to exoribonuclease compared to the linear AR transcripts and detectability of AR circRNAs in patient plasma, these AR circRNAs may serve as surrogate circulating markers for AR/AR-variant expression and castration-resistant prostate cancer progression.