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Abstract Background Equisetum diffusum D. Don commonly known as ‘Himalayan horsetail’, has been traditionally used in the treatment of back pain, bone fracture and dislocation, and arthritis by various tribal communities of India. Our previous study confirmed the anti-inflammatory efficacy of the plant through in silico, in vitro, and in vivo model studies. Therefore, the current research is focused on safety dose evaluation for the first-time of the whole-plant methanol extract (EDME) of E. diffusum through appropriate in silico, in vitro, and in vivo approaches. Method The whole plant, along with its rhizomes, was collected, and the methanol extract was prepared. The in silico ADMET study was performed to predict the pharmacokinetics profile and toxicity of all the identified phyto-compounds of EDME previously screened by GC–MS study. In vitro cytotoxicity study of EDME was performed using two cell lines: kidney (HEK293) and liver (Huh7) cell lines. The in vivo toxicity study of EDME was validated by the acute toxicity (OECD 423, 2002) and sub-acute toxicity assays (OECD 407, 2008) in the Wistar Albino rat model. Results The in silico ADMET study of all 47 bioactives predicted good pharmacokinetic and low toxicity profiles. In vitro cytotoxicity showed higher IC50 values of EDME viz., 672 ± 15.7 μg/mL and 1698 ± 6.54 μg/mL for both kidney (HEK293) and liver (Huh7) cell lines, respectively, which were considered as low-toxic. Based on acute oral toxicity, the LD50 value of the extract was considered “non-toxic” up to a feeding range of 2000 mg/kg of body weight. The regular consumption of the extract for an extended period (28 days) was also qualified as safe based on the body and organ weight, hematological, biochemical, and histoarchitecture results in the sub-acute toxicity assay. Conclusion The detailed in silico, in vitro, in vivo (acute and sub-acute oral toxicity) studies gave us a new insight to the safety dose evaluation of Equisetum diffusum, which may serve as a reliable documentation for undertaking the experimental validation of the ethnobotanical uses of the plant which would help in the field of drug development for the treatment of inflammation related complications.

Abstract In this paper we revisit a generalised crossing equation that follows from harmonic analysis on the conformal group, and is of particular interest for the cosmological bootstrap programme. We present an exact solution to this equation, for dimensions two or higher, in terms of 6j symbols of the Euclidean conformal group, and discuss its relevance. In the process we provide a detailed derivation of the analogue of the Biedenharn-Elliot identity for said 6j symbols.

Fruits are crucial components of a balanced diet and a good source of natural antioxidants, that have proven efficacy in various chronic illnesses. Various kinds of waste generated from fruit industries are considered a global concern. By utilizing this fruit waste, the international goal of “zero waste” can be achieved by sustainable utilization of these waste materials as a rich source of secondary metabolites. Moreover, to overcome this waste burden, research have focused on recovering the bioactive compounds from fruit industries and obtaining a new strategy to combat certain chronic diseases. The separation of high-value substances from fruit waste, including phytochemicals, dietary fibers, and polysaccharides which can then be used as functional ingredients for long-term health benefits. Several novel extraction technologies like ultrasound-assisted extraction (UAE), pressurized liquid extraction (PLE), and supercritical fluid extraction (SFE) could provide an alternative approach for successful extraction of the valuable bioactives from the fruit waste for their utilization as nutraceuticals, therapeutics, and value-added products. Most of these waste-derived secondary metabolites comprise polyphenols, which have been reported to have anti-inflammatory, insulin resistance-treating, cardiovascular disease-maintaining, probiotics-enhancing, or even anti-microbial and anti-viral capabilities. This review summarizes the current knowledge of fruit waste by-products in pharmacological, biological, and probiotic applications and highlights several methods for identifying efficacious bioactive compounds from fruit wastes.

Abstract Introduction: Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). Methods: A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers; higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. Results: 737 subjects were evaluated; 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity [6.0 (5.0–8.0) vs. 7.0 (5.0–9.0), p = 0.002], convenience [4.0 (3.0–6.0) vs. 5.0 (4.0–6.0), p

Abstract Thin-film saturable absorbers (SAs) are extensively used in mode-locked fiber laser due to the robust and simple application methods that arise because SAs are alignment-free and self-standing. Single-walled carbon nanotubes (SWCNTs) are the most suitable low dimensional material uesd for SAs because of their high nonlinearity and the wavelength control of absorption based on tube diameters. The most challenging problem with the use of CNT-based thin film SAs is thermal damage caused during high power laser operation, which mainly occurs due to aggregation of CNTs. We have demonstrated improved thermal damage resistance and enhanced durability of a film-type SA based on functionalization of SWCNTs, which were subjected to a mechanical functionalization procedure to induce covalent structural modifications on the SWCNT surface. Increased intertube distance was shown by X-ray diffraction, and partial functionalization was shown by Raman spectroscopy. This physical change had a profound effect on integration with the host polymer and resolved aggregation problems. A free-standing SA was fabricated by the drop casting method, and improved uniformity was shown by scanning electron microscopy. The SA was analyzed using various structural and thermal evaluation techniques (Raman spectroscopy, thermogravimetric analysis, etc.). Damage tests at different optical powers were also performed. To the best of our knowledge, a comprehensive analysis of a film-type SA is reported here for the first time. The partially functionalized SWCNT (fSWCNT) SA shows significant structural integrity after intense damage tests and a modulation depth of 25.3%. In passively mode-locked laser operation, a pulse width of 152 fs is obtained with a repetition rate of 77.8 MHz and a signal-to-noise ratio of 75 dB. Stable operation of the femtosecond fiber laser over 200 h verifies the enhanced durability of the fSWCNT SA.

Abstract The aim of this article is to present the slope stability charts for two layered soil slopes by using the strength reduction method (SRM). The primary focus is to provide a quantitative estimation of the improvement of slope stability when a stronger layer is placed over the weaker layer. The SRM carried in this work comprises a series of finite element lower bound (LB) and upper bound (UB) limit analysis in conjunction with nonlinear optimization. Unlike the limit equilibrium method (LEM), there is no need to consider any prior assumptions regarding the failure surface in SRM. The study is carried out for different combinations of (i) slope angles (β), (ii) strength properties of the top and the bottom layer (c, ϕ) and (iii) different thickness of the top layer. The failure patterns are shown for a few cases.

In this study, the two lactic acid bacterial strains Enterococcus durans and Enterococcus lactis previously isolated from soft chhurpi, a traditionally fermented milk product prepared by the indigenous community of Sikkim Himalayas and healthy human gut were used. In this study, we attempted to investigate the probiotic attributes, safety, and health beneficial role, and hypercholesterolemia of Enterococcus durans and Enterococcus lactis. Both probiotic potential strains showed good hypocholesterolemic activity in vitro along with tolerance to acid pH (2 and 2.5), tolerance to three bile salts, oxbile, cholic acid, and taurocholic acid (0.5 and 1%), presence of BSH enzyme and its activity, and cell surface adherence. On assessing for safety, both LAB strains were sensitive to antibiotics and exhibited no hemolytic activity. The probiotic strains were tested in vivo in the Sprague–Dawley rats which were divided into five experimental groups: Normal Control (ND), probiotic strain Enterococcus durans HS03 (BSH-negative) and high-cholesterol diet (HCD1), probiotic strain Enterococcus lactis YY1 (BSH-positive) and high-cholesterol diet (HCD2), and a combination of both strains and high-cholesterol diet (HCD3) and Negative Control (HCD). The probiotic-treated groups HCD1, HCD2, and HCD3 showed a decrease in serum cholesterol levels up to 22.55, 6.67, and 31.06%; the TG and VLDL concentrations were 25.39, 26.3, and 33.21%; reduction in LDL-cholesterol was 33.66, 28.50, and 35.87%; and increase of HDL was 38.32, 47.9, and 41.92%. Similarly, the effects of total cholesterol and TG in the liver, kidney and liver histopathology, liver and body lipid index, and oxidative stress in rat liver were also studied. The fecal lactobacilli were more in the samples of the probiotic-treated groups and their fecal coliform and E. coli counts decreased relatively as compared to the control groups in 0, 7, 14, and 21 days. This is the first report on the probiotic potential of Enterococcus durans HS03 and Enterococcus lactis YY1 strains that gives a new insight into the cholesterol-lowering and probiotic product development with wide health attributes.

A non-invasive ultrasonic technique (UT) is developed to determine gas-liquid-solid composition inside digester of a biogas plant. The technique involves sweeping a contact type UT probe along the wall of pipes to determine the relative fraction of gas, liquid and solid phases under segregated conditions. The technique is validated at laboratory scale for two-phase (air-water) and three-phase (air-water-solid) systems. The average absolute error in prediction of segregated interfaces is ∼2.5%. Field trials are done on horizontal pipe sections (5 coils) of digester in the plant. More than 50% of the top most pipe run is occupied by gas. For second/third pipe runs solid fraction is around 20–25% while gas fraction is 10–15%. However, for the 4th and 5th pipe rows, the solid fraction is around 40–55%. A gradual increase of gas hold up towards the top regions and larger accumulation of solids at the bottom is expected because of waste feeding at the bottom. The described UT based system represents a novel way forward in use of ultrasound technology to detect segregated multiphase phases in digesters of biogas plants.

Abstract We derive an optical theorem for perturbative CFTs which computes the double discontinuity of conformal correlators from the single discontinuities of lower order correlators, in analogy with the optical theorem for flat space scattering amplitudes. The theorem takes a purely multiplicative form in the CFT impact parameter representation used to describe high-energy scattering in the dual AdS theory. We use this result to study four-point correlation functions that are dominated in the Regge limit by the exchange of the graviton Regge trajectory (Pomeron) in the dual theory. At one-loop the scattering is dominated by double Pomeron exchange and receives contributions from tidal excitations of the scattering states which are efficiently described by an AdS vertex function, in close analogy with the known Regge limit result for one-loop string scattering in flat space at finite string tension. We compare the flat space limit of the conformal correlator to the flat space results and thus derive constraints on the one-loop vertex function for type IIB strings in AdS and also on general spinning tree level type IIB amplitudes in AdS.

Abstract Background The fronds of Drynaria quercifolia have traditionally been used in rheumatic pain management. The goal of the present study was to validate the potent anti-inflammatory and anti-rheumatoid properties of the methanolic-extract of its rhizome using in vitro, in vivo and in silico strategies. Methods The plant was collected and the methanolic extract was prepared from its rhizome. Protein denaturation test, hypotonicity and heat-induced haemolysis assays were performed in vitro. The in vivo anti-rheumatoid potential was assessed in Freund’s complete adjuvant (FCA)-induced Wistar rat model through inflammatory paw-edema, haematological, biochemical, radiological and histopathological measurements. Moreover, metabolites of methanolic extract were screened by gas chromatography-mass spectrometry (GC-MS) and 3D molecular structures of active components were utilized for in silico docking study using AutoDock. Results In vitro results evinced a significant (p

In the present study 12 native Bt strains isolated from insect cadavers were screened for their bioefficacy against neonates of economically important polyphagous pests Spodoptera litura and Spodoptera exigua by feeding assays at single concentrations of 10 μg/g of diet. Toxicity of Bt strains against neonates of S. litura and S. exigua varies from 39.04% (VKK-EV and VKK-PX2) to 70.97% (VKK-AC1) and 20.0% (VKK-AC1 and VKK-MPS) to 88.00% (VKK-AC2) on 7th day after treatment respectively. The LC50 values for potential Bt strains against S. litura varied from 0.87 μg/gm (VKK-AC1) to 9.36 μg/gm (VKK-AG2) while, against S. exigua ranged from 1.00 μg/g (VKKAC2) to 13.95 μg/g (VKK-SO) of diet. Gene profiling of potential Bt strains revealed the presence of cry1A, cry1D, cry1I, and cry2 gene. Further studies on characterization of these novel cry genes from potential native Bt strains will be valuable for management of Spodoptera spp.

The quantitative analysis of a biological analyte directly through fluorescence imaging is essential in biomedical sciences but remains as a challenge owing to the environment-sensitive nature of fluorescence intensity. We show that a fluorescent hydrogen peroxide probe based on an in cellulo super-bright benzothiazolyl-benzocoumarin dye of which emission properties are insensitive to environmental changes offers a reliable and practical means for the quantitative analysis of hydrogen peroxide in cells and tissues directly through ratiometric imaging both under one-photon and two-photon excitation conditions. Different cellular hydrogen peroxide concentrations were determined for several cell lines and also for tumour and normal tissues.

Abstract We study the spectrum of local operators living on a defect in a generic conformal field theory, and their coupling to the local bulk operators. We establish the existence of universal accumulation points in the spectrum at large s, s being the charge of the operators under rotations in the space transverse to the defect. Our tools include a formula that inverts the bulk to defect OPE, analogous to the Caron-Huot formula for the four-point function [1]. Analyticity of the formula in s implies that the scaling dimensions of the defect operators are aligned in Regge trajectories Δ^s $$ \widehat{\Delta}(s) $$. These results require the correlator of two local operators and the defect to be bounded in a certain region, a condition that we do not prove in general. We check our conclusions against examples in perturbation theory and holography, and we make specific predictions concerning the spectrum of defect operators on Wilson lines. We also give an interpretation of the large s spectrum in the spirit of the work of Alday and Maldacena [2].

Abstract We define Mellin amplitudes for the fermion-scalar four point function and the fermion four point function. The Mellin amplitude thus defined has multiple components each associated with a tensor structure. In the case of three spacetime dimensions, we explicitly show that each component factorizes on dynamical poles onto components of the Mellin amplitudes for the corresponding three point functions. The novelty here is that for a given exchanged primary, each component of the Mellin amplitude may in general have more than one series of poles. We present a few examples of Mellin amplitudes for tree-level Witten diagrams and tree-level conformal Feynman integrals with fermionic legs, which illustrate the general properties.

The two component Monte-Carlo Glauber model predicts a knee-like structure in the centrality dependence of elliptic flow v2 in Uranium + Uranium collisions at sNN=193 GeV. It also produces a strong anti-correlation between v2 and dNch/dy in the case of top ZDC events. However, none of these features have been observed in data. We address these discrepancies by including the effect of nucleon shadowing to the two component Monte-Carlo Glauber model. Apart from addressing successfully the above issues, we find that the nucleon shadow suppresses the event by event fluctuation of various quantities, e.g. ε2 which is in accordance with expectation from the dynamical models of initial condition based on gluon saturation physics.

Introduction: Citelli’s abscess is an extratemporal complication of otitis media. It occurs when pus from the mastoid tip trickles down along the posterior belly of the digastric muscle to the occipital and cervical region. It is a very unusual presenting complication of chronic otitis media with no available data in the until now. Case Report: A 10-year-old female was presented to our outpatient department with a 1 month history of hi-grade fever and headache and pain around the left half of the face. During physical examination a huge swelling present in the left temporal and occipital region was observed. The swelling crossed the midline, was tender to touch, and was fluctuant. During otological examination left sided chronic suppurative otitis media, of the attico-antral type with cholesteatoma, and a profuse foul smelling purulent discharge was observed. After complete investigation, drainage of the patient’s abscess was performed under general anesthesia. A postaural incision was administered and around 500 ml of pus drained out. Immediately after the operation, the patient showed signs of recovery. After 3 weeks of parenteral antibiotic therapy, the primary focus was debrided by performing left modified radical mastoidectomy. Conclusion: Citelli's abscess is a rare complication of otitis media. Urgent radiology, followed by drainage of pus is performed to reduce pain and further progression of the infective process. The primary ear pathology is managed surgically after adequate treatment with intra venous antibiotics.

Fibroblast growth factor receptor 3–transforming acidic coiled-coil containing protein 3 (FGFR3–TACC3; FT3) is a gene fusion resulting from rearrangement of chromosome 4 that has been identified in many cancers including those of the urinary bladder. Altered FGFR3 signalling in FT3-positive cells is thought to contribute to cancer progression. However, potential changes in TACC3 function in these cells have not been explored. TACC3 is a mitotic spindle protein required for accurate chromosome segregation. Errors in segregation lead to aneuploidy, which can contribute to cancer progression. Here we show that FT3-positive bladder cancer cells have lower levels of endogenous TACC3 on the mitotic spindle, and that this is sufficient to cause mitotic defects. FT3 is not localized to the mitotic spindle, and by virtue of its TACC domain, recruits endogenous TACC3 away from the spindle. Knockdown of the fusion gene or low-level overexpression of TACC3 partially rescues the chromosome segregation defects in FT3-positive bladder cancer cells. This function of FT3 is specific to TACC3 as inhibition of FGFR3 signalling does not rescue the TACC3 level on the spindle in these cancer cells. Models of FT3-mediated carcinogenesis should, therefore, include altered mitotic functions of TACC3 as well as altered FGFR3 signalling.

Bacteria can either exist in the planktonic (free floating) state or in the biofilm (encased within an organic framework) state. Bacteria biofilms cause industrial concerns and medical complications and there has been a great deal of interest in the discovery of small molecule agents that can inhibit the formation of biofilms or disperse existing structures. Herein we show that, contrary to previously published reports, d-amino acids do not inhibit biofilm formation of Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), and Staphylococcus epidermis (S. epidermis) at millimolar concentrations. We evaluated a diverse set of natural and unnatural d-amino acids and observed no activity from these compounds in inhibiting biofilm formation.

Quiescence and gametogenesis represent two distinct survival strategies in response to nutrient starvation in budding yeast. Precisely how environmental signals are sensed by yeast cells to trigger quiescence and gametogenesis is not fully understood. A conserved signalling module consisting of Greatwall kinase, Endosulfine and Protein Phosphatase PP2ACdc55 proteins regulates entry into mitosis in Xenopus egg extracts and meiotic maturation in flies. We report here that an analogous signalling module consisting of the serine-threonine kinase Rim15, the Endosulfines Igo1 and Igo2 and the Protein Phosphatase PP2ACdc55, regulates entry into both quiescence and gametogenesis in budding yeast. PP2ACdc55 inhibits entry into gametogenesis and quiescence. Rim15 promotes entry into gametogenesis and quiescence by converting Igo1 into an inhibitor of PP2ACdc55 by phosphorylating at a conserved serine residue. Moreover, we show that the Rim15-Endosulfine-PP2ACdc55 pathway regulates entry into quiescence and gametogenesis by distinct mechanisms. In addition, we show that Igo1 and Igo2 are required for pre-meiotic autophagy but the lack of pre-meiotic autophagy is insufficient to explain the sporulation defect of igo1Δ igo2Δ cells. We propose that the Rim15-Endosulfine-PP2ACdc55 signalling module triggers entry into quiescence and gametogenesis by regulating dephosphorylation of distinct substrates.

Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, a single round of DNA replication is followed by two rounds of nuclear divisions (referred to as meiosis I and II). While sister kinetochores bind to microtubules emanating from opposite spindle poles during mitosis, they bind to microtubules originating from the same spindle pole during meiosis I. This phenomenon is referred to as mono-orientation and is essential for setting up the reductional mode of chromosome segregation during meiosis I. In budding yeast, mono-orientation depends on a four component protein complex referred to as monopolin which consists of two nucleolar proteins Csm1 and Lrs4, meiosis-specific protein Mam1 of unknown function and casein kinase Hrr25. Monopolin complex binds to kinetochores during meiosis I and prevents bipolar attachments. Although monopolin associates with kinetochores during meiosis I, its binding site(s) on the kinetochore is not known and its mechanism of action has not been established. By carrying out an imaging-based screen we have found that the MIND complex, a component of the central kinetochore, is required for monopolin association with kinetochores during meiosis. Furthermore, we demonstrate that interaction of monopolin subunit Csm1 with the N-terminal domain of MIND complex subunit Dsn1, is essential for both the association of monopolin with kinetochores and for monopolar attachment of sister kinetochores during meiosis I. As such this provides the first functional evidence for a monopolin-binding site at the kinetochore.

Cyclin-dependent kinases (CDK) are master regulators of the cell cycle in eukaryotes. CDK activity is regulated by the presence, post-translational modification and spatial localization of its regulatory subunit cyclin. In budding yeast, the B-cyclin Clb1 is phosphorylated and localizes to the nucleus during meiosis I. However the functional significance of Clb1's phosphorylation and nuclear localization and their mutual dependency is unknown. In this paper, we demonstrate that meiosis-specific phosphorylation of Clb1 requires its import to the nucleus but not vice versa. While Clb1 phosphorylation is dependent on activity of both CDK and polo-like kinase Cdc5, its nuclear localization requires CDK but not Cdc5 activity. Furthermore we show that increased nuclear localization of Clb1 during meiosis enhances activation of FEAR (Cdc Fourteen Early Anaphase Release) pathway. We discuss the significance of our results in relation to regulation of exit from meiosis I.

The steps essentially involved in the evaluation of transport coefficients in linear response theory using Kubo formulas are to relate the defining retarded correlation function to the corresponding time-ordered one and to evaluate the latter in the conventional perturbation expansion. Here we evaluate the viscosities of a pion gas carrying out both the steps in the real-time formulation. We also obtain the viscous coefficients by solving the relativistic transport equation in the Chapman-Enskog approximation to leading order. An in-medium π π cross-section is used in which spectral modifications are introduced in the propagator of the exchanged ρ .