Products In Presence Research Articles

Increasing rice productivity in presence of climate change using Internet of Things (IoT)

Increasing rice productivity in presence of climate change using Internet of Things (IoT)

Measurements of fluoride production in Resistive Plate Chambers

Resistive Plate Chambers (RPCs) are operated with a gas mixture made of C2H2F4, SF6 and iC4H10. It is well known that under the effect of a high electric field and radiation, the C2H2F4 molecule breaks into several compounds and free fluoride ions, which can accumulate under gas recirculation and could be harmful for the long-term detector operation. Furthermore, if High Pressure Laminate (HPL) electrodes are employed, the gas mixture is humidified and, in presence of water, the free fluoride ions become hydrofluoric acid (HF), a very reactive compound. The F− production depends on several factors such as radiation rate, gas flow, detector current and gas mixture. In this study we developed and tested two different set-ups for the F− concentration measurements by using an Ion Selective Electrode (ISE) station. The measurement on the F− production were performed on 2 mm gas gap bakelite RPC detector irradiated at the CERN Gamma Irradiation Facility (GIF++) with different absorption factors. Several gas mixtures were tested to understand how the formation of HF is affected. The F− production of the standard gas mixture was compared with the one of the standard gas mixture with the addition of 30% CO2 at several gamma rates. Different concentrations of SF6 were also investigated to understand if and how the SF6 could affect the F− production. Finally, two gas mixtures containing HFO1234ze, C2H2F4 and He or CO2 were used to study the RPC F− production in presence of the HFO1234ze, which is less stable in atmosphere with respect to the C2H2F4.

Thermodynamics analysis and response surface methodology to investigate decomposition behaviors for lepidolite sulfation products in presence of coal

The process consisting of sulfation and decomposition has been proved to utilize lepidolite efficiently, while the conditions of sulfation products are relatively harsh. In this paper, the decomposition behaviors for lepidolite sulfation products in presence of coal were studied to optimize the conditions required. The feasibility was first verified theoretically by calculating the thermodynamic equilibrium composition with different amounts of carbon addition. The priority of each component reacted with carbon was concluded as Al2(SO4)3, KAl(SO4)2, RbAl(SO4)2, and FeSO4. Based on the batch experimental results, response surface methodology was purposed to simulate and predict the effect of various parameters. The verification experimental results showed the extraction of Al and Fe were only 0.05 % and 0.01 % under the optimal conditions of 750 °C, 20 min, and 20 % coal dosage. The separation of alkali metals and impurities was realized. The decomposition behaviors for lepidolite sulfation products in presence of coal was clarified by discussing the contradiction between theoretical thermodynamic calculation and actual experimental results. It indicated that carbon monoxide was more active than carbon in promoting decomposition. The addition of coal decreased the temperature and time required, which not only cut the energy consumption, but also reduced the operation difficulty. This study provided more theoretical and technical support for the application of sulfation and decomposition process.

Evaluation of relative efficiency of PDT photosensitizers in producing hydroxyl radicals and singlet oxygen in aqueous media using a UV-visible spectroscopy pNDA dosage.

In order to improve the performance of PDT, it is important to develop new photosensitizers that induce the formation of both hydroxyl radicals and singlet oxygen. In this work, we developed and validated the experimental conditions and reproducibility for the evaluation of relative efficiency of hydroxyl radicals and singlet oxygen production by studying the bleaching of p-nitrosoaniline (pNDA) using a continuous flow UV-visible spectroscopy method in presence of photosensitizers in PBS media. Rapid data sampling made possible to analyze the kinetics of the bleaching by using a mathematical modeling. The pNDA dosage is specific of hydroxyl radicals' production without l-histidine and of singlet oxygen production in presence of l-histidine. A statistical approach is used to precisely evaluate the reliability of the results and to be able to compare different photosensitizers between them such as Methylene Blue and Brillant Blue G.

Photocatalytic hydrogen production using bimetallic and trimetallic hydrotalcite as photocatalysts

• Bimetallic and trimetallic hydrotalcites were synthesized by coprecipitation method. • The formation of 2D structure characteristic of this type of material was observed. • The chemical composition was determined by XPS and FTIR analysis. • A difference in the positions of VB and CB was observed between both hydrotalcites. • Both hydrotalcites presented a higher production of H 2 than TiO 2. Bimetallic ZnAl and trimetallic ZnCuAl hydrotalcites were synthesized using the coprecipitation method. The presence of the characteristic peaks of layered double hydroxide phases was observed by XRD analysis, as well as the typical like flower morphology of these materials by FESEM and HRTEM analysis. Changes in the valence and conduction bands position, as well as in the band gap calculated by UV-vis spectroscopy and XPS techniques was noted by the presence of Cu in the material. In the photocatalytic behavior for H 2 production in presence of UV irradiation, ZnCuAl hydrotalcite showed the highest yield of H 2 in comparison to ZnAl material, being both photocatalysts more actives that the reference photocatalyst, consisting in commercial TiO 2 (Degussa P-25).

One Thrombin Generation Method Can Monitor Both Standard and Extended Half Life FVIII Products in Haemophilia a Patients with or without Emicizumab

Introduction Severe haemophilia A (SHA) is a bleeding disorder characterized by absent Factor VIII (FVIII). Traditionally, these patients are treated with intravenous prophylactic FVIII replacement concentrates to prevent spontaneous bleeding episodes. As an alternative, various extended half-life (EHL) FVIII products were introduced, since conventional standard factor FVIII (SHL) concentrates have a short half life time. Recently, a non-factor product, emicizumab, was introduced that mimics FVIII activity. Subcutaneous administration of this drug may clinically resemble a mild haemophilia. Conventional laboratory tests are unreliable for these new agents. However, techniques are needed for monitoring in emergency situations and in case of surgery. Global coagulation assays, like thrombin generation (TG), may be promising as an universal laboratory test to measure the full coagulation product spectrum in order to monitor the effectiveness of various FVIII and non-FVIII replacement products. Aim The aim of this pilot study was to assess FVIII and/or emicizumab activity levels by a commercially available thrombin generation assay (TGA), using plasma samples of patients treated with conventional or EHL FVIII products in presence or absence of emicizumab were tested. Methods Blood was collected in standard citrated tubes (0,109 M BD) used for routine coagulation testing, without adding a contact activator inhibitor. Platelet poor plasma was prepared by double centrifugation. In total, plasma samples were obtained from 10 healthy volunteers and 18 patients. Four samples were taken from 4 patients with trough levels FVIII, 10 samples from 6 patients on prophylactic replacement therapy using SHL or EHL FVIII products, 22 samples from 12 patients on emicizumab and 10 samples of 3 patients on emicuzimab plus EHL FVIII. FVIII One Stage Clotting Assay (OSA), emicizumab levels and bovine FVIII chromogenic substrate assay (CSA) were determined using Siemens reagents on CS2500. TG was measured using PPP Reagent LOW by Calibrated Automated Thrombogram (CAT) method (Stago). TG is represented by both normalized Endogenous Thrombin Potential (ETP%) and Peakheight (Peak%) as a percentage of a normal pooled plasma composed of more than 120 healthy volunteers. Results FVIII levels by OSA showed the best correlation with TG ETP% and Peak% with Spearman correlation coefficients (r) of both 0,8. Emicuzimab had a moderate correlation with ETP% (r=0,42) and Peak % (r=0,58). In patients with emicuzimab and SHL the correlation between FVIII by bovine CSA was also moderate, 0,47 (ETP%) and 0,50 (Peak%). Lowest ETP% and Peak% were suggested in de patients in their through levels (Figure 1, red bars). Patients on emicizumab have higher ETP% and Peak%, although the median levels are not within the normal range (Figure 1, green bars). Patients on SHL or EHL replacement therapy with or without emicizumab give the impression that their ETP% and Peak% are approaching normal values (Figure 1, blue bars and yellow bars, respectively). Conclusion The commercial available TG assay (PPP Reagent LOW) may be used to test different Haemophilia A replacement therapies in double centrifuged, plasma samples collected without a contact activator inhibitor. Since one reliable uniform test is clinically needed, future applicability for this assay in monitoring SHA patients has to be studied in larger cohorts. Furthermore, the relevance of ETP% and Peak% has to be related to clinical outcomes such as severity of bleeding. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lepton pair production from a hot and dense QCD medium in the presence of an arbitrary magnetic field

In this article, we have explored the very important quantity of lepton pair production from a hot and dense QCD medium in presence of an arbitrary external magnetic field for simultaneous nonzero values of both the parallel (along the direction of the external field) and perpendicular (lying on the transverse plane to the external field) components of the dilepton momentum. As opposed to the zero magnetic field case (the so-called Born rate) or the lowest Landau level approximated rate, where only the annihilation process contributes, here we observe contributions also arising out of the quark and antiquark decay processes. We found the encouraging result of considerable enhancement of lepton pair production in presence of an arbitrary magnetic field. We decompose the total rate into different physical processes and discuss their behaviors for both zero and nonzero baryon density. The whole analysis is then subjected to an effective model treatment, where we have incorporated the magnetic field induced novel effects of magnetic catalysis (MC) and inverse MC (IMC) through a medium dependent scalar coupling, which leads to some further interesting observations.

Biogenic synthesis of nano-photocatalysts doped TiO2 nanoparticles and their application in photocatalytic degradation

The significant effect of TiO2 predominantly used as photocatalytic degradation catalyst and could also be used against viruses in future. The modified TiO2 nano-photocatalyst with F and I-doping was prepared using expired egg-white as template through sol-gel method at different concentrations. In this study, aqueous solution of methylene-blue used as target degradation product in presence of prepared TiO2-nanoparticles under simulated-sunlight and LED visible-light. Therefore, particle size of F and I-doped nanoparticles was observed at 12 and 11.8nm (low-concentration) and, 13.2 and 16.2nm (high-concentration) respectively, where removal efficiency exhibited 6.2 and 43.0% at higher and lower-concentration simultaneously of F-doped TiO2 nanoparticles.

Vilazodone-phospholipid mixed micelles for enhancing oral bioavailability and reducing pharmacokinetic variability between fed and fasted states

Despite the effectiveness and high tolerability of vilazodone (VLZ) as an antidepressant, its use is still limited due to its poor solubility and food dependent absorption. This study aims to load VLZ-phospholipid complex into self-assembled micelles forming VLZ-PL mixed micelles (VLZ-PL-MM), that can enhance VLZ solubility, improve its bioavailability and reduce the pharmacokinetic variability between the fed and fasting conditions. The effect of surfactant type and concentration was assessed using four different non-ionic surfactants (Brij 58, Tween 80, Labrasol and Pluronic F127) in four different weight ratios between the drug-complex and surfactant (1:0.5, 1:1, 1:2 and 1:3 w/w). Two VLZ-PL-MM formulae prepared using Brij 58 and Labrasol in 1:3 w/w ratio were selected as optimised ones since they have the highest encapsulation efficiency (100.83 and 93.87%, respectively), a particle size below 250 nm (206.73 and 221.33 nm, respectively) and negative zeta potential values (−29.63, −17.20 mV, respectively). Lyophilisation of these formulations using 3% sucrose was successful with no statistical changes in particle size and zeta potential upon rehydration. Both formulations elicited faster and higher in-vitro drug release profiles compared to the pure drug and the marketed tablet. In addition, both selected formulae improved ex-vivo permeation across rabbit intestinal membrane compared to the pure drug and the marketed tablet, with marked superiority of the one prepared using Brij 58. The results of the in-vivo study in male albino rabbits revealed similar AUC0-24 values after the oral administration of the best achieved VLZ-PL-MM system under fed and fasted conditions (769.89 and 741.55 ng.h mL−1, respectively). On the other hand, the marketed product showed significantly lower values of the AUC0-24 relative to the VLZ-PL-MM system and there was a marked enhancement of absorption of drug from the marketed product in presence of food (244.24 and 174.96 ng.h mL−1 under fed and fasted conditions, respectively). In addition, VLZ concentrations in the brain after 24 h obtained from the selected VLZ-PL-MM were significantly higher than those obtained from marketed tablet under fed and fasted conditions. Thus, the phospholipid mixed micelles formulation enhances the oral bioavailability of the poorly soluble drug and reduces the pharmacokinetic variability between fasting and fed conditions.

Navigating the Space Between Hermeneutics and Aesthetics: Dhvani and Comparative Poetics

ABSTRACT In Production of Presence: What Meaning Can’t Convey (2003), Hans Ulrich Gumbrecht suggests that through their unremitting emphasis on hermeneutics, modern critics have ignored the ineffable, bodily aspect of aesthetic experience that he calls “presence.” In the realm of poetics, such a theory implies a dissociation between the hermeneutic activity of a poem and a reader’s emotional response to it. Two aestheticians from medieval Kashmir, Ānandavardhana, c. ninth century CE, and his tenth-century commentator Abhinavagupta, propose a cause of poetic beauty and aesthetic effect that is still grounded in meaning: dhvani. They delineate how, in certain poetic conditions, dhvani leads to rasa, roughly “aesthetic enjoyment,” an experience at once mental and visceral. Whereas the poetic forms the Indian aestheticians discuss go beyond the lyric per se, this paper brings some of the most critical aspects of their poetics in conversation with current critical overtures as well as resonant poetry we might be more familiar with today in order to inspire further work on comparative literary aesthetics and “world criticism.”

PORTRAITS OF CLOSE ONES. PHOTOS IN MODERN BELARUSIAN INTERIORS

Photos are an integral part of most modern Belarusian rural interiors, but until now they have not become the object of a separate study. Appearing in rural interiors only in the twentieth century, most often in the second half of it, they find themselves on the periphery of research optics, focused on the description and study of objects of folk culture. The purpose of the article is to lay the foundations for our understanding of the meaning of photography in rural interiors and to develop interpretive schemes for further research. In the course of the research, the genealogy of the appearance of photographs in interiors was reconstructed in the context of the tradition of the existence of other images there, first of all, icons. A typology of the main ways of placing photographs in the space of the house has been developed. Models of the interpretation of this cultural phenomenon through its meaning as a method of symbolic gathering of a family, production of presence and use as a spatial mediator of memory are proposed. The article demonstrates photography as a complex and multidimensional object that can be fully studied only in the context of its existence – in a rural interior, in the meanings of folk culture. It also outlines opportunities for further development of the study.

Sterile neutrino dark matter production in presence of nonstandard neutrino self-interactions: An EFT approach

Sterile neutrinos with keV-scale masses are popular candidates for warm dark matter. In the most straightforward case they are produced via oscillations with active neutrinos. We introduce effective self-interactions of active neutrinos and investigate the effect on the parameter space of sterile neutrino mass and mixing. Our focus is on mixing with electron neutrinos, which is subject to constraints from several upcoming or running experiments like TRISTAN, ECHo, BeEST and HUNTER. Depending on the size of the self-interaction, the parameter space moves closer to, or further away from, the one testable by those future experiments. In particular, we show that phase 3 of the HUNTER experiment would test a larger amount of parameter space in the presence of self-interactions than without them. We also investigate the effect of the self-interactions on the free-streaming length of the sterile neutrino dark matter, which is important for structure formation observables.

Biodiesel production from Chlorella Vulgaris microalgal-derived oil via electrochemical and thermal processes

Chlorella Vulgaris microalgal as a renewable and economically feasible oil feedstock is used in this study for producing biodiesel through electrochemical and thermal processes. The effect of operating parameters on non-catalytic and catalytic biodiesel production from the derived-oil is investigated and compared in a wide range of condition. According to the revealed data, during non-catalytic processes, electrochemical process proposed higher biodiesel production yield in comparison to thermal process with relative biodiesel production yield of 25% and 18%, respectively. According to the experimental results, although biodiesel production is restricted in presence of water in thermal process, electrochemical method enables biodiesel production in presence of water. Addition of H2SO4 in the range of 1–15 wt% through electrochemical process at the obtained optimum condition results in gradual increase in the biodiesel production yield to 95%. The optimum operating condition in electrochemical process are as follows: methanol to oil molar ratio of 20:1, tetrahydrofuran (THF) to methanol molar ratio of 0.25:1, reaction time of 2 h, voltage of 20 V/cm, water content of 2 wt% and H2SO4 loading of 15 wt%.

Rapid, high throughput protein estimation method for saponin and alhydrogel adjuvanted R21 VLP Malaria vaccine based on intrinsic fluorescence

Protein content estimation of recombinant vaccines at drug product (DP) stage is a crucial lot release and stability indicating assay in biopharmaceutical industries. Regulatory bodies such as US-FDA and WHO necessitates the quantitation of protein content to assess process parameters as well as formulation losses. Estimation of protein content at DP stage in presence of adjuvants (e.g AlOOH, AlPO4, saponin and squalene) is quite challenging, and the challenge intensifies when the target protein is in Virus like particles (VLP) form, owing to its size and structural complexity. Methods available for protein estimation of adjuvanted vaccines mostly suffer from inaccuracy at lower protein concentrations and in most cases require antigen desorption before analysis. Present research work is based on the development of a rapid plate-based method for protein estimation through intrinsic fluorescence by using Malaria vaccine R21 VLP as a model protein. Present method exhibited linearity for protein estimation of R21, in the range of 5–30 µg/mL in Alhydrogel and 4–20 µg/mL for Matrix M adjuvant. The method was validated as per ICH guidelines. The limit of quantification was found to be 0.94 µg/mL for both Alhydrogel and Matrix M adjuvanted R21. The method was found specific, precise and repeatable. This method is superior in terms of less sample quantity requirement, multiple sample analysis, short turnaround time and is non-invasive. This method was found to be stability indicating, works for other proteins containing tryptophan residues and operates well even in presence of host cell proteins. Based on the study, present method can be used in vaccine industries for routine in-process sample analysis (both inline and offline), lot release of VLP based drug products in presence of Alhydrogel and saponin based adjuvant systems.

Mediation of Candida species growth and virulence by the proinflammatory cytokine IL-6

Abstract Interleukin-6 (IL-6) is a cytokine with pleiotropic effects that might also influence the virulence traits of some microorganisms, but its direct influence over Candida spp. is currently unknown. The objective of the study is to determine the influence of IL-6 (250 pg/ml) on the growth rate and biofilm formation of C. albicans, C. parapsilosis, C. krusei, C. auris, and C. guilliermondii, as well as to analyze the influence of this citokine on the expression of three virulence genes (ALS3, HSP70, SAP2), respectively on the germ tube formation ability of C. albicans. The influence of IL-6 on growth rate was assessed by incubating the fungal cells in presence of IL-6 for 48 hours and assessing the optical density of the samples at five timepoints. The biofilm production in presence of IL-6 was studied in microtiter plates, using crystal-violet assay, the intensity of biofilms being evaluated by spectrophotometry. The expression of ALS3, HSP70, and SAP2 in C. albicans was studied by RT-PCR, reported to ACT1 housekeeping gene. The germ-tube test was performed to assess the influence of IL-6 on the filamentation rate of C. albicans. All test results were normalized against control, without added IL-6. The results showed that IL-6 influences the growth rate of C. albicans, C. parapsilosis, C. krusei, C. auris, and C. guilliermondii in a time-dependent way. Also, IL-6 inhibited the formation of biofilms for C. albicans and C. guilliermondii. In C. albicans cells, IL-6 induced upregulation of ALS3 and HSP70, while it down-regulated the SAP2 gene. IL-6 did not influence the germ-tube formation in C. albicans. In conclusion, IL-6 might exert, in vitro, direct effects on the virulence traits of Candida spp., and its influence is dependent on the exposure time. Non-albicans Candida species presented particular responses to IL-6.

Influence of prefoldin subunit 4 on the tolerance of Kluyveromyces marxianus to lignocellulosic biomass-derived inhibitors

BackgroundKluyveromyces marxianus is a potentially excellent host for microbial cell factories using lignocellulosic biomass, due to its thermotolerance, high growth rate, and wide substrate spectrum. However, its tolerance to inhibitors derived from lignocellulosic biomass pretreatment needs to be improved. The prefoldin complex assists the folding of cytoskeleton which relates to the stress tolerance, moreover, several subunits of prefoldin have been verified to be involved in gene expression regulation. With the presence of inhibitors, the expression of a gene coding the subunit 4 of prefoldin (KmPFD4), a possible transcription factor, was significantly changed. Therefore, KmPFD4 was selected to evaluate its functions in inhibitors tolerance.ResultsIn this study, the disruption of the prefoldin subunit 4 gene (KmPFD4) led to increased concentration of intracellular reactive oxygen species (ROS) and disturbed the assembly of actin and tubulin in the presence of inhibitors, resulting in reduced inhibitor tolerance. Nuclear localization of KmPFD4 indicated that it could regulate gene expression. Transcriptomic analysis showed that upregulated gene expression related to ROS elimination, ATP production, and NAD+ synthesis, which is a response to the presence of inhibitors, disappeared in KmPFD4-disrupted cells. Thus, KmPFD4 impacts inhibitor tolerance by maintaining integration of the cytoskeleton and directly or indirectly affecting the expression of genes in response to inhibitors. Finally, overexpression of KmPFD4 enhanced ethanol fermentation with a 46.27% improvement in productivity in presence of the inhibitors.ConclusionThis study demonstrated that KmPFD4 plays a positive role in the inhibitor tolerance and can be applied for the development of inhibitor-tolerant platform strains.

Improving sustainable hydrogen production from green waste: [FeFe]-hydrogenases quantitative gene expression RT-qPCR analysis in presence of autochthonous consortia

BackgroundBio-hydrogen production via dark fermentation of low-value waste is a potent and simple mean of recovering energy, maximising the harvesting of reducing equivalents to produce the cleanest fuel amongst renewables. Following several position papers from companies and public bodies, the hydrogen economy is regaining interest, especially in combination with circular economy and the environmental benefits of short local supply chains, aiming at zero net emission of greenhouse gases (GHG). The biomasses attracting the largest interest are agricultural and urban green wastes (pruning of trees, collected leaves, grass clippings from public parks and boulevards), which are usually employed in compost production, with some concerns over the GHG emission during the process. Here, an alternative application of green wastes, low-value compost and intermediate products (partially composted but unsuitable for completing the process) is studied, pointing at the autochthonous microbial consortium as an already selected source of implementation for biomass degradation and hydrogen production. The biocatalysts investigated as mainly relevant for hydrogen production were the [FeFe]-hydrogenases expressed in Clostridia, given their very high turnover rates.ResultsBio-hydrogen accumulation was related to the modulation of gene expression of multiple [FeFe]-hydrogenases from two strains (Clostridium beijerinckii AM2 and Clostridium tyrobutyricum AM6) isolated from the same waste. Reverse Transcriptase quantitative PCR (RT-qPCR) was applied over a period of 288 h and the RT-qPCR results showed that C. beijerinckii AM2 prevailed over C. tyrobutyricum AM6 and a high expression modulation of the 6 different [FeFe]-hydrogenase genes of C. beijerinckii in the first 23 h was observed, sustaining cumulative hydrogen production of 0.6 to 1.2 ml H2/g VS (volatile solids). These results are promising in terms of hydrogen yields, given that no pre-treatment was applied, and suggested a complex cellular regulation, linking the performance of dark fermentation with key functional genes involved in bio-H2 production in presence of the autochthonous consortium, with different roles, time, and mode of expression of the involved hydrogenases.ConclusionsAn applicative outcome of the hydrogenases genes quantitative expression analysis can be foreseen in optimising (on the basis of the acquired functional data) hydrogen production from a nutrient-poor green waste and/or low added value compost, in a perspective of circular bioeconomy.

Palmer Amaranth (Amaranthus palmeri) Growth and Seed Production When in Competition with Peanut and Other Crops in North Carolina

Palmer amaranth (Amaranthus palmeri S. Wats.) is a highly competitive weed that can be difficult to manage in many cropping systems. Research to date has not quantified the growth and development of A. palmeri in a manner that allows direct comparisons across cropping systems. Research was conducted to compare the growth, development, and seed production of A. palmeri when competing with corn (Zea mays L.), cotton (Gossypium hirsutum L.), peanut (Arachis hypogaea L.), and soybean [Glycine max (L.) Merr.] when emerging with crops or emerging three weeks after crops emerge. Regardless of when A. palmeri emerged, seed production was greatest and similar in cotton and peanut and exceeded that of corn and soybean; seed production in soybean exceeded that of corn. However, seed production was approximately 10-fold greater when A. palmeri emerged with crops compared with emergence three weeks later. These results illustrate the importance of controlling weeds during the first three weeks of the season relative to contributions of A. palmeri to the weed seed bank and is the first report comparing seed production in presence of these crops in a manner allowing a statistical comparison of seed production and highlighting the importance of crop sequence for seed bank management.

Mechanistic insights into the antimycobacterial action of unani formulation, Qurs Sartan Kafoori

Background and aimTuberculosis (TBC) is a deadly disease and major health issue in the world. Emergence of drug resistant strains further worsens the efficiency of available anti-TBC drugs. Natural compounds and particularly traditional medicines such as Unani drugs are one of the promising alternatives that have been widely used nowadays. This study aims to evaluate the efficacy of unani drug Qurs-e-Sartan Kafoori (QSK) on Mycobacterium tuberculosis (MTB). Experimental proceduresDrug susceptibilities were estimated by broth microdilution assay. Cell surface integrity was assessed by ZN staining, colony morphology and nitrocefin hydrolysis. Biofilms were visualized by crystal violet staining and measurement of metabolic activity and biomass. Lipidomics analysis was performed using mass spectrometry. Host pathogen interaction studies were accomplished using THP-1 cell lines to estimate cytokines by ELISA kit, apoptosis and ROS by flow cytometry. ResultsQSK enhanced the susceptibilities of isoniazid and rifampicin and impaired membrane homeostasis as depicted by altered cell surface properties and enhanced membrane permeability. In addition, virulence factor, biofilm formation was considerably reduced in presence of QSK. Lipidomic analysis revealed extensive lipid remodeling. Furthermore, we used a THP-1 cell line model, and investigated the immunomodulatory effect by estimating cytokine profile and found change in expressions of TNF-α, IL-6 and IL-10. Additionally, we uncover reduced THP-1 apoptosis and enhanced ROS production in presence of QSK. ConclusionTogether, this study validates the potential of unani formulation (QSK) with its mechanism of action and attempts to highlight its significance in MDR reversal.

IRE1α Is a Therapeutic Target for Cystic Fibrosis Airway Inflammation.

New anti-inflammatory treatments are needed for CF airway disease. Studies have implicated the endoplasmic reticulum stress transducer inositol requiring enzyme 1α (IRE1α) in CF airway inflammation. The activation of IRE1α promotes activation of its cytoplasmic kinase and RNase, resulting in mRNA splicing of X-box binding protein-1 (XBP-1s), a transcription factor required for cytokine production. We tested whether IRE1α kinase and RNase inhibition decreases cytokine production induced by the exposure of primary cultures of homozygous F508del CF human bronchial epithelia (HBE) to supernatant of mucopurulent material (SMM) from CF airways. We evaluated whether IRE1α expression is increased in freshly isolated and native CF HBE, and couples with increased XBP-1s levels. A FRET assay confirmed binding of the IRE1α kinase and RNase inhibitor, KIRA6, to the IRE1α kinase. F508del HBE cultures were exposed to SMM with or without KIRA6, and we evaluated the mRNA levels of XBP-1s, IL-6, and IL-8, and the secretion of IL-6 and IL-8. IRE1α mRNA levels were up-regulated in freshly isolated CF vs. normal HBE and coupled to increased XBP-1s mRNA levels. SMM increased XBP-1s, IL-6, and IL-8 mRNA levels and up-regulated IL-6 and IL-8 secretion, and KIRA6 blunted these responses in a dose-dependent manner. Moreover, a triple combination of CFTR modulators currently used in the clinic had no effect on SMM-increased XBP-1s levels coupled with increased cytokine production in presence or absence of KIRA6. These findings indicate that IRE1α mediates cytokine production in CF airways. Small molecule IRE1α kinase inhibitors that allosterically reduce RNase-dependent XBP-1s may represent a new therapeutic strategy for CF airway inflammation.