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This paper investigates the performance of combined and separate log type class of estimators of population mean under stratified ranked set sampling. The expressions of bias and mean square error of the proposed estimators are deduced. The theoretical comparison of the proposed estimators with the existing estimators is carried out and the efficiency conditions are reported. The credibility of theoretical results is extended by a simulation study conducted over various artificially generated symmetric and asymmetric populations. The results of the simulation study show that the proposed class of estimators dominate the well-known existing estimators. [ABSTRACT FROM AUTHOR]

In real life, situations may arise when the available data are insufficient to provide accurate estimates for the domain, the small area estimation (SAE) technique has been used to get accurate estimates for the variable under study. The problem of missing data is a serious problem that has an impact on sample surveys, but small area estimates are especially prone to it. This paper is a basic effort that suggests design based synthetic imputation methods for the domain mean estimation using simple random sampling in order to address the issue of missing data under SAE. The expression of the mean square error for the proposed imputation methods are obtained up to first order approximation. The efficiency conditions are determined and a thorough simulation study is carried out using artificially generated data sets. An application is included with real data that further supports this study. [ABSTRACT FROM AUTHOR]

Identifying the breeding grounds of fishes is crucial for the sustainable management of fisheries resources. The present study is aimed at identifying the potential breeding ground of Mugil cephalus along the estuary of the North Mumbai coast. A total of 1197 specimens of M. cephalus, including 546 eggs, 271 larvae, 235 juveniles, and 235 adults, were collected from four sampling stations in the Karanja estuary between January to October 2022. Water quality parameters, plankton dynamics in the estuary, and the reproductive and feeding biology of M. cephalus were also examined. The eggs, larvae, juveniles, and adults were identified using traditional morpho-meristic and DNA barcoding techniques. The results revealed a potential spawning ground of M. cephalus in the Karanja estuary. The results of reproductive biology also confirmed the occurrence of matured fishes during May–July. The abundance of eggs and larvae at the estuary's mouth and the presence of juveniles and mature individuals of M. cephalus dominantly in the Karanja estuary from May to July infer the presence of a spawning site. It is also recorded that M. cephalus spawn in higher salinity (35 ppt) and seawater temperature (33 °C) where the hatching of offspring takes place successfully. This study emphasizes the significance of DNA barcoding in guiding routine monitoring surveys and demonstrates its usefulness when combined with these techniques in identifying fish spawning grounds. The study findings will serve as baseline information to develop effective conservation and management strategies and protect the ideal spawning stock. [ABSTRACT FROM AUTHOR]

Wireless Sensor Networks (WSNs) play a crucial role in developing the Internet of Things (IoT) by collecting data from hostile environments like military and civil domains with limited resources. IoT devices need edge devices to perform real-time processing without compromising the security with the help of key management and authentication schemes. The above applications are prone to eavesdropper due to cryptographic algorithms' weaknesses for providing security in WSNs. The security protocols for WSNs are different from the traditional networks because of the limited resource of sensor nodes. Existing key management schemes require large key sizes to provide high-security levels, increasing the computational and communication cost for key establishment. This paper proposes a Hybrid Key Management Scheme for WSNs linking edge devices which use Elliptic Curve Cryptography (ECC) and a hash function to generate key pre-distribution keys. The Key establishment is carried out by merely broadcasting the node identity. The main reason for incorporating a hybrid approach in the key pre-distribution method is to achieve mutual authentication between the sensor nodes during the establishment phase. The proposed method reduces computational complexity with greater security and the proposed scheme can be competently applied into resource constraint sensor nodes. [ABSTRACT FROM AUTHOR]

Indiscriminate collection of Arnebia benthamii roots from wild for extraction of red pigments by traders prompted to put this Himalayan plant species under critically endangered category. Concerning the development of sustainable phytoconstituents sources, the present study is aimed at understanding the factors crucial for the scalability of A. benthamii cell suspension cultures. Here, the effect of orbital shaking speed (60–80 rpm) and inoculum density (5–15%) on leaf-induced cell suspension cultures during sequential scale up in shake flask (0.25–5 L) was assessed. The suspension cultures were established on Murashige and Skoog medium supplemented with 10 μM 6-benzylaminopurine and 5 μM indole-3-butyric acid having a 20-days cultivation cycle. The data revealed a significantly (p ≤ 0.05) high biomass productivity (523.80 ± 5.95 g/L, fresh weight) in 0.25 L vessel with 10% inoculum at 70 rpm as compared to large (5.0 L) volume flask (310.80 ± 32.85 g/L). Interestingly, the optimum inoculum density was found to vary with the size of culture vessels. Furthermore, noticeable effects of sequential scaleup with shaking speed and inoculum density were also observed on hydrogen peroxide (stress indicator) production as well as enzymatic (catalase and phenylalanine ammonia-lyase activity) and non-enzymatic (phenolic compounds) antioxidant potential. A. benthamii cells cultivated with optimized conditions had a significant amount of red pigment, with 669.17 ± 26.71 mg dry weight/L yield of total shikonin derivatives. In conclusion, the results clearly demonstrated the likelihood of scalability using optimized process variables for the production of natural red pigments using A. benthamii cell suspension cultures. [ABSTRACT FROM AUTHOR]

Groundwater is a significant source of plant water use since groundwater consumption of plants reduces the volume of surface irrigation water. In this study, groundwater table effect on hard red spring wheat (Triticum aestivum L.) growth and yield parameters were investigated using a lysimeter technique in a controlled environment. Three different groundwater table depths including 30, 60, and 90 cm and a control treatment with surface irrigation were tested. The results showed that water consumption in the 90 cm water table depth was 11% and 31% lower than the water consumption in the 60 and 30 cm water table depths, respectively. Consequently, the groundwater table depth increased, and crop water consumption decreased. Similarly, with the increasing water table depth from 30 to 90 cm in the lysimeter, the crop water use efficiency and crop yield increased by 79% and 71%, respectively. The 90 cm water table produced the highest crop yield, above-ground biomass, and kernel quality compared to 30 and 60 cm water table depths. Quality analysis of the wheat kernels indicated that the kernels from the 90 cm depth had relatively higher starch content, pasting properties, and gluten proteins compared to the kernels from other water table depths. [ABSTRACT FROM AUTHOR]

East Kolkata Wetlands (EKW) is an important site for fish culture in sewage-fed areas, which are major receivers of pollutants and wastages from Kolkata. EKW is internationally important as the Ramsar site was declared on Aug 2002 with an area of 125 km2. EKW is a natural water body where wastewater-fed natural aquaculture has been practiced for more than 70 years. It is ecologically vulnerable due to the discharge of toxic waste through sewage canals from cities. Assessing the EKW to understand the inflow and load of the toxic metal (s) in fish, water, and sediments samples is essential. The field (samples collection from 13 sites) and lab (determination of toxic level of metals) based research were carried out to assess metal toxicity and health risk assessment in EKW. The levels of eighteen metals (18), namely Chromium, Vanadium, Cobalt, Manganese, Copper, Nickel, Zinc, Silver, Molybdenum, Arsenic, Selenium, Tin, Gallium, Germanium, Strontium, Cadmium, Mercury, and Lead, were determined using Inductively coupled plasma mass spectrometry (ICP-MS) in five fish tissues viz. muscle, liver, kidney, gill and brain, along with the water samples and soil sediments in 13 sampling sites. The bioaccumulation and concentration of metals in fish tissues, soil sediments, and water samples were well within the safe level concerning the recommendation of different national and international agencies except for a few metals in a few sampling sites like Cd, As, and Pb. The geoaccumulation index (Igeo) was also determined in the soil sediments, indicating moderate arsenic, selenium, and mercury contamination in a few sites. The contamination index in water was also determined in 13 sampling sites. The estimated daily intake (EDI), reference dose (RfD), target hazard quotient (THQ), slope factor and cancer risk of Cr, Mn, Co, Ni, Cu, Zn, As, Se, Cd, Pb and Hg from fish muscle were determined. Based on the results of the present investigation, it is concluded that fish consumption in the East Kolkata Wetland (EKW) is safe. The effects of bioaccumulation of metals in muscle tissue were well within the safe level for consumption as recommended by WHO/FAO. [ABSTRACT FROM AUTHOR]

The present study assessed the toxic effect of super-paramagnetic iron oxide nanoparticles (SPIONs) on haemato-immunological responses, antioxidant capacity, oxidative stress, and metabolic enzyme activities in Labeo rohita fingerlings, as well as the possible ameliorative effect of dietary vitamin E. The experiment was conducted for 30 days (15-day exposure and recovery each) under static bioassay. The LC50 concentration of SPIONs was estimated by 96-h exposure which was 3253.20 mg/L. The fishes were distributed in two groups and exposed to three levels 1/50th, 1/25th, and 1/10th of SPION-LC50 concentration. Group 1: fed with control diet and referred to as CS0, CS/50, CS/25, and CS/10, while group 2: fed vitamin E supplemented diet and referred to as ES0, ES/50, ES/25, and ES/10. Significant alterations were observed in haemato-immunological responses, malondialdehyde (MDA), and oxidative and metabolic enzymes activity even after supplementation of vitamin E. The exposure to SPIONs altered haemato-immunological parameters, MDA accumulation, and tissue enzyme activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione s-transferases (GST), xanthine oxidase (XO), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) in a dose-dependent manner. However, they relapsed to the level of control in S/50 exposed group at the end of the recovery period. The dietary vitamin E shows significant toxicity mitigating effect during the recovery period. Thus, SPIONs can be used up to a concentration of 65.06 mg/L in the culture water of Labeo rohita and its toxicity at higher doses can be partially ameliorated by feeding of vitamin E (at 250 mg/kg feed) for 15 days during post exposure period. Highlights: • The toxicity of SPIONs increased with increasing concentration of nanoparticle. • The lethal concentration (LC50) of SPIONs was 3253.20 mg/L. • At the end of the recovery period, dietary supplementation of vitamin E ameliorate toxic effect of SPIONs. • The physiological change caused due to the toxic effect of 65.04 mg/L SPIONs can be completely recovered in 15 days by dietary supplementation of vitamin E at 250 mg/kg in L. rohita. [ABSTRACT FROM AUTHOR]

This paper suggests some novel class of log type estimators for the estimation of population mean of study variable under ranked set sampling by utilizing information on population mean of auxiliary variable. The mean square error of the proposed class of estimators is obtained to the first order of approximation. We have compared the proposed class of estimators with some existing competitors under some specific conditions. The theoretical results are validated by a computational study using real and simulated data sets. On the lines of McIntyre (Aust. J. Agr. Res.3, 385–390 1952), Dell (1969) and Dell and Clutter (Biometrics28, 545–555 1972), the effect of skewness and kurtosis over the efficiency of the proposed class of estimators have also studied and reported. [ABSTRACT FROM AUTHOR]

The main goal of Denial of Service (DoS) attack is to restrict authorized users from gaining access to available services and resources or to prevent from processing the benign events. When a DoS attack is launched by multiple connected devices distributed over a network, the attack becomes a Distributed DoS attack (DDoS). The research community addressed various types of DDoS attacks in literature. DDoS attacks are very hazardous and difficult to resolve in real time. Each of these types of attacks has some key features that are identified to improve network security in real time. In this paper, an approach using Random Forest method is presented to extract the basic features from KDDCUP'99 dataset. With these features as the input, the proposed approach is smoothly extended for detection of new and unseen DDoS attacks with the assistance of nine support vector machine kernel functions namely Hyperbolic tangent kernel, Linear kernel, ANOVA RBF kernel, Spline kernel, Radial Basis kernel, Polynomial kernel, Laplacian kernel, Bessel kernel, and String kernel. The experimental study clearly shows that Laplace Dot support vector machine kernel (Laplacian kernel) function gives the paramount performance in terms of detecting seen and unseen DDoS attacks. [ABSTRACT FROM AUTHOR]

In vitro adventitious roots were induced from leaves of Valerianajatamansi to assess their potential as a sustainable alternative to extract pharmaceutically important phytoconstituents. Among the different media used, a significantly (p ≤ 0.05) high root induction (90%) was achieved on Schenk and Hildebrandt (SH) medium fortified with 9.84 µM indole-3-butyric acid (IBA). In addition, various process parameters i.e. IBA concentration, sucrose and medium strength were also optimized under submerged cultivation. The maximum fresh root biomass (144.09 ± 11.36 g/L) with a high relative growth rate (2.01 ± 0.04) and growth index (13.41) was achieved in half-strength SH medium having 2% sucrose and 4.92 µM IBA. Further, a significantly high yield of total valerenic acid derivatives [1525.14 µg/g dry weight (DW)] was recorded in adventitious roots as compared to donor plant parts. Individually, valerenic acid (506.27 µg/g DW) was accumulated higher in plant rhizomes, while acetoxyvalerenic (534.91 µg/g DW) and hydroxyl valerenic acid (919.57 µg/g DW) in adventitious roots. Interestingly, hydroxy valerenic acid was unmeasurable in donor plant parts. The phenolic compounds were also found maximum in adventitious roots (451.85 µg/g DW) with the dominance of pharmaceutically important kaempferol and rutin. A substantial increase in phytochemicals was evident at subsequent culture stages with shortened in vitro cultivation cycle (2 months) than field-grown plants (24 months). Moreover, adventitious roots also accumulated 0.059% essential oil with patchouli alcohol (24%) as a key constituent. Conclusively, an enriched metabolic profile and substantially shorter growth cycle under submerged cultivation undoubtedly demonstrated the potential of induced V. jatamansi adventitious roots as a feasible source of phytoconstituents. Key message: In vitro adventitious roots induced leaf of Valerianajatamansi showed improved metabolic profile and shorter cultivation cycle, thereby exhibiting potential as a sustainable alternative for extraction of industrially important phytoconstituents. [ABSTRACT FROM AUTHOR]

Wireless sensor network (WSN) is used to sense the environment, collect the data, and further transmit it to the base station (BS) for analysis. A synchronized tree-based approach is an efficient approach to aggregate data from various sensor nodes in a WSN environment. However, achieving energy efficiency in such a tree formation is challenging. In this research work, an algorithm named fuzzy attribute-based joint integrated scheduling and tree formation (FAJIT) technique for tree formation and parent node selection using fuzzy logic in a heterogeneous network is proposed. FAJIT mainly focuses on addressing the parent node selection problem in the heterogeneous network for aggregating different types of data packets to improve energy efficiency. The selection of parent nodes is performed based on the candidate nodes with the minimum number of dynamic neighbors. Fuzzy logic is applied in the case of an equal number of dynamic neighbors. In the proposed technique, fuzzy logic is first applied to WSN, and then min–max normalization is used to retrieve normalized weights (membership values) for the given edges of the graph. This membership value is used to denote the degree to which an element belongs to a set. Therefore, the node with the minimum sum of all weights is considered as the parent node. The result of FAJIT is compared with the distributed algorithm for Integrated tree Construction and data Aggregation (DICA) on various parameters: average schedule length, energy consumption data interval, the total number of transmission slots, control overhead, and energy consumption in the control phase. The results demonstrate that the proposed algorithm is better in terms of energy efficiency. [ABSTRACT FROM AUTHOR]

This article deals with some new imputation methods by extending the work of Bhushan and Pandey using multi-auxiliary information. The popularly used imputation like mean imputation, ratio method of imputation, regression method of imputation and power transformation method are special cases of the proposed methods apart from being less efficient than the proposed methods. The proposed imputation methods can be considered as an efficient extension to the work of Singh and Deo (Stat Pap 44:555–579, 2003), Singh (Stat A J Theor Appl Stat 43(5):499–511, 2009), Ahmed et al. (Stat Transit 7(6):1247–1264, 2006), Diana and Perri (Commun Stat Theory Methods 39:3245–3251, 2010) and Bhushan and Pandey (J Stat Manag Syst 19(6):755–769, 2016, Commun Stat Theory Methods 47(11):2576–2589, 2018). The theoretical results are derived and comparative study is conducted using real and simulated data and the results are found to be quite encouraging providing the improvement over the all discuss work. [ABSTRACT FROM AUTHOR]

Apple fruit processing is not variety specific in India, which affect the overall quality of the final processed product. The present study was aimed at elucidation of the nutritive value, phenolic content, antioxidant activity and bioactive phenolic constituents of five widely used apple varieties (Royal Delicious, Red Delicious, Golden Delicious, Red Chief and Red Gold) of western Himalayas. The pomace obtained from different varieties was evaluated to assess the fruit quality. Royal Delicious pomace had significantly high (p < 0.05) total dietary fibre content (42.63 ± 1.26%) together with soluble (8.25 ± 0.95%) and insoluble fibre (32.90 ± 0.89%), as compared to other apple varieties. The pomace samples were extracted with 70% aqueous methanol to obtain polyphenol enriched extracts. The results of Folin–Ciocalteau assay showed that hydroalcoholic extract of Royal Delicious pomace exhibit higher phenolic content as compared to other varieties and ranged between 2.19 ± 0.09 and 4.59 ± 0.47 mg GAE/g. Royal Delicious pomace also possess higher antioxidant capacity i.e. 3.35 ± 0.10 mg/g, 2.71 ± 0.10 mg/g and 4.67 ± 0.03 mg/g as measured by DPPH, ABTS free radical scavenging assay and FRAP reducing assay, respectively. The higher phenolic content in Royal Delicious pomace was also confirmed by RP-HPLC-DAD analysis. Results of HPLC analysis revealed the presence of phloridzin (487.07 ± 0.04 µg/g), quercetin (241.18 ± 0.03 µg/g), quercitrin (178.34 ± 0.02 µg/g) and quercetin-3-glucoside (195.21 ± 0.05 µg/g) as major constituents. Present results indicate that Royal Delicious variety is rich in dietary fibre and phenolic compounds that might be used by the food sector as a source of bioactive health promoting constituents/dietary supplements. [ABSTRACT FROM AUTHOR]

Security and safety are fundamental issues in any wireless network. The problem becomes serious when the specified network is Vehicular Adhoc Network (VANET). VANET faces Distributed Denial of Service (DDoS) attacks, when several vehicles carry out various types of Denial of Service (DoS) attacks to disrupt the normal functioning of network, thereby endangering human lives. A highly efficient and reliable algorithm is required to be developed to detect and prevent DDoS attacks in VANET. This paper presents a hybrid detection algorithm based on the SVM kernel methods of AnovaDot and RBFDot for detecting DDoS attacks in VANETs. In this hybrid algorithm, features like collisions, packet drop, jitter etc. have been used to simulate real time network communication scenario where the network is operating under normal conditions, as well as under DDoS attacks. These features are used both for training and for testing the model based on the proposed hybrid algorithm. The performance of the model based on the proposed hybrid algorithm is compared with the models based on single SVM kernel algorithms AnovaDot and RBFDot based on Accuracy, Gini, KS, MER and H. The experimental results show that the model based on the proposed hybrid algorithm is superior to detect DDoS attacks as compared to the models based on single SVM kernel algorithms AnovaDot and RBFDot. The results also prove that by combining the the SVM kernel algorithms, an efficient and effective hybrid algorithm can be developed. [ABSTRACT FROM AUTHOR]

Pyrazinamide is a sterilizing first-line tuberculosis drug. Genetic, metabolomic and biophysical analyses previously demonstrated that pyrazinoic acid, the bioactive form of the prodrug pyrazinamide (PZA), interrupts biosynthesis of coenzyme A in Mycobacterium tuberculosis by binding to aspartate decarboxylase PanD. While most drugs act by inhibiting protein function upon target binding, we find here that pyrazinoic acid is only a weak enzyme inhibitor. We show that binding of pyrazinoic acid to PanD triggers degradation of the protein by the caseinolytic protease ClpC1-ClpP. Thus, the old tuberculosis drug pyrazinamide exerts antibacterial activity by acting as a target degrader, a mechanism of action that has recently emerged as a successful strategy in drug discovery across disease indications. Our findings provide the basis for the rational discovery of next generation PZA. It has been shown that the bioactive component of pyrazinamide, pyrazinoic acid (POA), blocks coenzyme A biosynthesis in M. tuberculosis by binding to the aspartate decarboxylase PanD. Here the authors show that pyrazinamide triggers degradation of PanD by stimulating its degradation by the caseinolytic protease Clp. [ABSTRACT FROM AUTHOR]

The discovery of three new natural products ( 1, 4, and 5), one semi-synthetic derivative ( 3) along with two known compounds ( 2 and 6) were isolated from an endophytic fungus Cryptosporiopsis sp. The structural elucidations of 1- 6 were authenticated by one-dimensional and two-dimensional nuclear magnetic resonance, mass spectroscopy, and X-ray diffraction analysis. Herein, we intervention of diazomethane as tool that help in the crystallization and isolation of inseparable mixtures of compounds 1 and 2. Compounds ( 1- 6) were screened for cytotoxic activity against six cancer cell lines in which the 4-epi-ethisolide ( 2) exhibited moderate activity with IC values 11 µM in HL-60, whereas the compound 3 lost its cytotoxic potentiality, but it displayed moderate antimicrobial activity. The result illustrates that the methylene moiety in 2 plays significant role in cytotoxic potential. [ABSTRACT FROM AUTHOR]

Polygonum multiflorum Thunb. is an important medicinal plant that synthesizes an array of phenolic compounds. Its roots are used in a variety of pharmacological and cosmetic formulations, notably as hair dye. In the present study, the inoculum density (3-15 g/L) and culture period (1-7 weeks) were optimized in a 3 L bioreactor. High root biomass (14.18 g/L dry weight (DW)) was recorded with an inoculum of 7 g/L ( p ≤ 0.05), which is consistent with the results for 5 and 10 g/L. However, significantly higher yield of bioactive compounds (53.87 mg/g DW total phenolics and 27.96 mg/g DW total flavonoids) with high free radical scavenging activity was obtained in root samples from 5 g/L inoculum density. A 4 week culture period was sufficient for optimum root growth and metabolite production. The optimized conditions were used for large-scale (5 and 20 L) and pilot-scale (500 L) studies. Considering that the continuous aeration of root cultures may lead to oxidative stress, antioxidant enzyme activity and lipid peroxidation also were studied. The results revealed high catalase (CAT) and guaiacol peroxidase (G-POD) activities, and low malondialdehyde (MDA) production, with increasing culture scale (20 and 500 L), which may indicate low-level oxidative damage to the cultures. An optimal yield of 4.01 kg dry root biomass with 287.12 mg/L of total phenolic productivity was achieved in a 500 L pilot-scale bioreactor. This work can pave the way for commercial production of biomass and secondary metabolites at the industrial level, and meet the rising demand for natural ingredients, especially in the pharmaceutical and cosmetic industries. [ABSTRACT FROM AUTHOR]

Chitosan is a widely employed polysaccharide with positive zeta-potential and better tissue/cell adhesion. Its hydrophilicity, high viscosity, and insolubility at physiological pH are major hurdles in proper utilization of this macromolecule. Therefore, it was conjugated with biocompatible stearic acid and the conjugate was employed to develop polymeric micelles for delivery of tamoxifen to breast cancer cells. The conjugate was characterized by FT-IR and NMR, and the nanocarrier was characterized for micromeritics, surface charge, drug loading, and morphological attributes. The efficacy was evaluated by in vitro MTT studies, safety by erythrocyte compatibility, and biodistribution by in vivo pharmacokinetic studies. Despite better drug loading and sustained drug release, cytotoxicity on MCF-7 breast cancer cells was substantially enhanced and the pharmacokinetic profile was significantly modified. The AUC was enhanced manifolds along with reduced clearance. The findings are unique and provide an alternative to the conventional lipid-based nanocarriers for better dose delivery, tissue adhesion, and desired pharmacokinetic modulation. [ABSTRACT FROM AUTHOR]

Humankind is presently engulfed by convenience quench, modern life style and urbanized diet system leading to progression in array of health disorders. The past decade confronted cardiometabolic disorder (21.8 %), lower respiratory and chronic obstructive lung disease (12.5 %) as the major causes of death world over. In anticipation, scientific communities' have demonstrated the role of healthy diets, especially those rich in fruits and vegetables, for management of such health related issues. These horticultural crops are considered as a good source of polyphenols such as dihydrochalcones, flavanols, flavonols, anthocyanins and phenolic acids. The present article reviews the efforts made to assess the potential of apple phenolic compounds present in fresh fruits, leaves, bark and pomace as dietary polyphenols. Considering the positive impact of such phytochemicals on human health, various nutraceuticals, dietary supplements and phenolic-rich food products are presently available on market shelves. On analytical front, improved instrumentation based on liquid chromatography (HPLC, UPLC, LC/MS/MS) have made the assessment of phenolics more rapid and reliable. Thus, owing to the emergent interest in natural compounds, it is pertinent to discuss the latest significant research findings on therapeutic aspects along with probable metabolic mechanisms of dietary polyphenols found in apples and their implications on human health. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s13571-021-00270-1 [ABSTRACT FROM AUTHOR]

Processing of apple fruits for juice/cider production generates large volume of pomace at industrial scale. This biomass (cell wall material and pulp tissues) is rich in array of nutrients, especially dietary fiber and polyphenols. Apple fruits confront various processing conditions at industrial level, influencing the biochemical composition of generated pomace, including its phenolic profile. In present study, a simple, fast and reproducible reversed-phase high-performance liquid chromatography method using diode array detector was developed and validated for separation of different phenolics present in industrial apple pomace. The present method showed reliable and reproducible intraday (0.2-4.0 % RSD) and interday (3.7-8.1 % RSD) precision with limits of detection and quantification values in range of 0.14-0.58 and 0.48-1.95 μg ml, respectively, for all the phenolics. Different solvent-mediated extraction of dried pomace powder was also performed to evaluate its total antioxidant potential using standard spectrophotometric assays. The major phenolics found in industrial apple pomace extracts were quercetin (1.4-10.3 μg mg), phloretin (1.1-9.3 μg mg) and phloridzin (0.62-2.0 μg mg). [ABSTRACT FROM AUTHOR]

Cell suspension cultures of Arnebia euchroma were established from the friable callus on liquid Murashige and Skoog medium supplemented with 6-benzylaminopurine (10.0 μM) and indole-3-butyric acid (5.0 μM). Salicylic acid was used to study its effect on the enzymes which participate in shikonin biosynthesis with respect to metabolite (shikonin) content in the cell suspension culture of A. euchroma. In our study, phenylalanine ammonia lyase and PHB geranyltransferase were selected from the entire biosynthetic pathway. Results showed that phenylalanine ammonia lyase is responsible for growth and PHB geranyltransferase for metabolite production. Salicylic acid exhibited an inverse relationship with the metabolite content (shikonin); salicylic acid (100 μM) completely inhibited shikonin biosynthesis. The results presented in the current study can be successfully employed for the metabolic engineering of its biosynthetic pathway for the enhancement of shikonin, which will not only help in meeting its industrial demand but also lead to the conservation of species in its natural habitat. [ABSTRACT FROM AUTHOR]

PI3K/Akt and ERK pathways are important for growth and proliferation of many types of cancers. Therefore, PI3K inhibitor LY294002 (LY) and MEK1/2 inhibitor PD98059 (PD) are used to sensitize many types of cancer cell lines to chemotherapeutic agents, where AKT and ERK pathways are over activated. However, in this study, we show for the first time that PD could protect the leukemia cells independent of ERK pathway inhibition, besides, we also report a detailed mechanism for antiapoptotic effect of LY in HL-60 cells against the cytotoxicity induced by a boswellic acid analog BA145. Apoptosis induced by BA145 is accompanied by downregulation of PI3K/Akt and ERK pathways in human myelogenous leukemia HL-60 cells, having activating N-Ras mutation. Both LY and PD protected the cells against mitochondrial stress caused by BA145, and reduced the release of cytochrome c and consequent activation of caspase-9. LY and PD also diminished the activation of caspase-8 without affecting the death receptors. Besides, LY and PD also reversed the caspase dependent DNA damage induced by BA145. Further studies revealed that LY and PD significantly reversed the inhibitory effect of BA145 on cell cycle regulatory proteins by upregulating hyperphosphorylated retinoblastoma, pRB (S795) and downregulating p21 and cyclin E. More importantly, all these events were reversed by caspase inhibition by Z-VAD-fmk, suggesting that both LY and PD act at the level of caspases to diminish the apoptosis induced by BA145. These results indicate that inhibitors of PI3K/Akt and ERK pathways can play dual role and act against chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Chemical investigation of industrial apple pomace waste has led to the isolation of two water-soluble polysaccharides (AS-3 and AS-5). Both polysaccharides were identified as arabinans on the basis of GC-MS, IR, 1D, 2D NMR, and MALDI-TOF-MS studies. GC-MS analysis of alditol acetate derivatives of AS-3 suggested the presence of arabinose and glucose sugars in the ratio of 4:1, whereas AS-5 was composed of only arabinose. The structure of AS-3 was identified as circular with three arabinose and one glucose in the circle and one arabinose unit branched at the C-4 position of the arabinose. AS-5 consists of four arabinose units, out of which three were linked linearly through 1 → 5 and 1 → 3 linkage and one in the side chain linked through 1 → 2 linkage. [ABSTRACT FROM AUTHOR]

This study was undertaken to isolate and characterize saponins from seeds of Camellia sinensis. Four triterpene saponins S, S, S, and S were isolated by chromatography on silica (60-120 mesh), followed by purification on Sep-Pak C-18 columns. The chemical structures ( S- S) were elucidated on the basis of 1-D and 2-D NMR. All the saponins show broad-spectrum antifungal activity against Candida albicans, Issatchenkia orientalis, Aspergillus flavus, A. niger, A. ochraceous, A. parasiticus, A. sydowii, and Trichophyton rubrum. The most susceptible test fungus was T. rubrum inhibited at a minimum inhibitory concentration of 31.25 μg/ml by all the four saponins. Cytotoxicity of these saponins was evaluated by methyl thiazole tetrazolium and sulfo-rhodamine B assays. The saponins when tested against five human cancer cells lines, viz., OVCAR-5 (ovarian carcinoma cells), MCF-7 (human breast adenocarcinoma cells), PC-3 (human prostate cancer cells), Colo-205 (colorectal adenocarcinoma cells), and HL-60 (human promyelocytic leukemia cells) showed high cytotoxicity activity (99 %) by S and S on PC-3 cells at concentration of 100 μg/ml. Similarly, when these saponins were tested against human PBMCs by lymphocytes proliferation assay, none showed significant activity. S (IC = 1.72 mg/ml) showed high metal-chelating activity at a concentration of 20 mg/ml. [ABSTRACT FROM AUTHOR]

This study describes the mechanism of trolox and tiron induced potentiation of cytotoxicity caused by Ery5, an analog of magnolol, in human myeloid leukemia HL-60 cells. Ery5 induced cytotoxicity in HL-60 cells by involving activation of bax and cleavage of caspase 3, which contributed towards activation of both apoptotic and autophagic pathways. Trolox and tiron, even at non-toxic concentrations, contributed to the cytotoxicity of Ery5 by activation of autophagic proteins like ATG7, ATG12 and LC3-II. Z-VAD-fmk mediated reduction in the cytotoxicity and expression of autophagic proteins, further suggested that autophagy induced by Ery5 is largely dependent upon caspases. Interestingly, Ery5 induced autophagy was accompanied by the downregulation of PI3K/AKT pathway whereas, trolox and tiron strongly enhanced this effect. In addition to that treatment of cells with Ery5, trolox and tiron individually, displayed a marked upregulation of Bax. The involvement of Bax in trolox and tiron induced enhancement of the cytotoxicity of Ery5 was confirmed, when siRNA induced silencing of Bax led to increased viability of the cells and exerted a strong inhibitory effect on LC3-II accumulation and p62 degradation in case of cells treated by the combination of Ery5 with trolox or tiron. Additionally, an important role of PARP in Ery5 mediated cell death has been suggested by PARP silencing experiments, however, potentiation of autophagic cytotoxicity by trolox and tiron did not seem to be dependent on PARP-1. Therefore, Bax seems to play a vital role in trolox and tiron mediated potentiation of autophagic cell death by Ery5 in HL-60 cells. [ABSTRACT FROM AUTHOR]

As translation proceeds, the nascent polypeptide chain passes through a tunnel in the large ribosomal subunit. Although this ribosomal exit tunnel was once thought only to be a passive conduit for the growing nascent chain, accumulating evidence suggests that it may in fact play a more active role in regulating translation and initial protein folding events. Here we have determined single-particle cryo–electron microscopy reconstructions of eukaryotic 80S ribosomes containing nascent chains with high α-helical propensity located within the exit tunnel. The maps enable direct visualization of density for helices as well as allowing the sites of interaction with the tunnel wall components to be elucidated. In particular regions of the tunnel, the nascent chain adopts distinct conformations and establishes specific contacts with tunnel components, both ribosomal RNA and proteins, that have been previously implicated in nascent chain–ribosome interaction. [ABSTRACT FROM AUTHOR]

Induction of apoptosis in cancer cells has become the major focus of anti-cancer therapeutics development. WithaferinA, a major chemical constituent of Withania somnifera, reportedly shows cytotoxicity in a variety of tumor cell lines while its molecular mechanisms of action are not fully understood. We observed that withaferinA primarily induces oxidative stress in human leukemia HL-60 cells and in several other cancer cell lines. The withanolide induced early ROS generation and mitochondrial membrane potential (Δψmt) loss, which preceded release of cytochrome c, translocation of Bax to mitochondria and apoptosis inducing factor to cell nuclei. These events paralleled activation of caspases −9, −3 and PARP cleavage. WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-à-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-κB and caused nuclear cleavage of p65/Rel by activated caspase-3. N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA. The results of our studies demonstrate that withaferinA induced early ROS generation and mitochondrial dysfunction in cancer cells trigger events responsible for mitochondrial -dependent and -independent apoptosis pathways. [ABSTRACT FROM AUTHOR]

A triterpenediol (TPD) comprising of isomeric mixture of 3α, 24-dihydroxyurs-12-ene and 3α, 24-dihydroxyolean-12-ene from Boswellia serrata induces apoptosis in cancer cells. An attempt was made in this study to investigate the mechanism of cell death by TPD in human leukemia HL-60 cells. It inhibited cell proliferation with IC50 ∼ 12 μg/ml and produced apoptosis as measured by various biological end points e.g. increased sub-G0 DNA fraction, DNA ladder formation, enhanced AnnexinV-FITC binding of the cells. Further, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation, which were significantly inhibited by their respective inhibitors. Persistent high levels of NO and ROS caused Bcl-2 cleavage and translocation of Bax to mitochondria, which lead to loss of mitochondrial membrane potential (Δψm) and release of cytochrome c, AIF, Smac/DIABLO to the cytosol. These events were associated with decreased expression of survivin and ICAD with attendant activation of caspases leading to PARP cleavage. Furthermore, TPD up regulated the expression of cell death receptors DR4 and TNF-R1 level, leading to caspase-8 activation. These studies thus demonstrate that TPD produces oxidative stress in cancer cells that triggers self-demise by ROS and NO regulated activation of both the intrinsic and extrinsic signaling cascades. [ABSTRACT FROM AUTHOR]

In the present work, the effect of α-Fe2O3-nanoparticles (IONPs) supplementation at varying doses (0, 10, 20 and, 30 mg L−1) at the intermittent stage (after 12th day of growth period) was studied on the growth and biogas production potential of Chlorella pyrenoidosa. Significant enhancements in microalgae growth were observed with all the tested IONPs doses, the highest (2.94 ± 0.01 g L−1) being at 20 mg L−1. Consequently, the composition of the biomass was also improved. Based on the precedent determinations, theoretical chemical oxygen demand (CODth) as well as theoretical and stoichiometric methane potential (TMP, and SMP) were also estimated. The CODth, TMP, SMP values indicated IONPs efficacy for improving biogas productivity. Further, the biochemical methane potential (BMP) test was done for IONPs supplemented biomass. The BMP test revealed up to a 25.14% rise in biogas yield (605 mL g–1 VSfed) with 22.4% enhanced methane content for 30 mg L−1 IONPs supplemented biomass over control. Overall, at 30 mg L−1 IONPs supplementation, the cumulative enhancements in biomass, biogas, and methane content proffered a net rise of 98.63% in biomethane potential (≈ 2.86 × 104 m3 ha−1 year−1) compared to control. These findings reveal the potential of IONPs in improving microalgal biogas production. [ABSTRACT FROM AUTHOR]

Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing proteins 1/2 (NOD1 and NOD2). Dysregulation of this signaling pathway leads to defects in bacterial detection and in some cases autoimmune diseases. Here, we show that the Caspase-activation-and-recruitment-domain (CARD) of RIP2 (RIP2-CARD) forms oligomeric structures upon stimulation by either NOD1-CARD or NOD2-2CARD. We reconstitute this complex, termed the RIPosome in vitro and solve the cryo-EM filament structure of the active RIP2-CARD complex at 4.1 Å resolution. The structure suggests potential mechanisms by which CARD domains from NOD1 and NOD2 initiate the oligomerization process of RIP2-CARD. Together with structure guided mutagenesis experiments at the CARD-CARD interfaces, we demonstrate molecular mechanisms how RIP2 is activated and self-propagating such signal. The pathogen recognition receptors NOD1/2 recognize bacterial cell wall components and signal through their downstream adapter kinase RIP2 via a CARD (Caspase activation and recruitment domain) mediated oligomerization process. Here the authors present the cryo-EM structure of the active RIP2-CARD filament and discuss implications for NOD1/2-RIP2 signalling. [ABSTRACT FROM AUTHOR]

Introduction: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19.In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18–75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints.A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference − 0.01 (95% CI − 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8–11) in the AQCH group versus 11 days (IQR 8–11) in the control group [HR 1.27 (95% CI 0.95–1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted.Clinical Trials Registry – India (CTRI/2020/05/025397).Methods: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19.In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18–75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints.A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference − 0.01 (95% CI − 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8–11) in the AQCH group versus 11 days (IQR 8–11) in the control group [HR 1.27 (95% CI 0.95–1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted.Clinical Trials Registry – India (CTRI/2020/05/025397).Results: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19.In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18–75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints.A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference − 0.01 (95% CI − 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8–11) in the AQCH group versus 11 days (IQR 8–11) in the control group [HR 1.27 (95% CI 0.95–1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted.Clinical Trials Registry – India (CTRI/2020/05/025397).Conclusions: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19.In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18–75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints.A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference − 0.01 (95% CI − 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8–11) in the AQCH group versus 11 days (IQR 8–11) in the control group [HR 1.27 (95% CI 0.95–1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted.Clinical Trials Registry – India (CTRI/2020/05/025397).Trial Registration: There is an urgent need for an effective, oral therapy for COVID-19. Purified aqueous extract of Cocculus hirsutus (AQCH) has shown robust antiviral activity in in vitro studies. We aimed to evaluate the efficacy and safety of AQCH plus standard of care in hospitalized patients with moderate COVID-19.In an open-label, multicenter, randomized controlled trial conducted in India, eligible patients (aged 18–75 years) were randomized (1:1) to receive AQCH 400 mg orally three times a day plus standard of care (AQCH group) or standard of care alone (control group) for 10 days. Primary endpoint was the proportion of patients showing clinical improvement by day 14. Time to clinical improvement, time to viral clearance, and duration of hospitalization were secondary endpoints.A total of 210 patients were randomized. By day 14 most patients in both groups showed clinical improvement [difference − 0.01 (95% CI − 0.07 to 0.05); p = 1.0]. Median time to clinical improvement was 8 days (IQR 8–11) in the AQCH group versus 11 days (IQR 8–11) in the control group [HR 1.27 (95% CI 0.95–1.71); p = 0.032]. Time to viral clearance and duration of hospitalization were also significantly shorter in the AQCH group (p = 0.0002 and p = 0.016, respectively). AQCH was well tolerated, with no safety concerns identified.AQCH significantly reduced time to clinical improvement, time to viral clearance, and duration of hospitalization. In a pandemic, this has significant potential to decrease healthcare resource utilization and increase hospital bed availability. Further investigation of the therapeutic potential of AQCH in patients with COVID-19 is warranted.Clinical Trials Registry – India (CTRI/2020/05/025397). [ABSTRACT FROM AUTHOR]