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The lightweight concrete (LWC) has been successfully employed, by the ancient Romans and its popularity has grown for its reduced density and higher thermal insulation capabilities. Compared to ordinary mix concrete (OMC), LWC can substantially lessen the dead load of high-rise structures. The density of LWC is comparatively low i.e. 300 to 1850 kg/m3, whereas conventional concrete has a unit weight of 2200kg/m3 to 2600kg/m3. Many pieces of research on adding disposable industrial wastes LWC focus on "semi-lightweight" or concrete built of lightweight materials which have provided both structural, financial, and environmental achievements. Synthetic lightweight aggregate derived from industries/environmental waste is not possible for reuse openly dumped and makes it environmental abuse. The lowering self-load of a structure made of lightweight concrete makes it easy the handling heavier pre-cast pieces. Present research involves of amalgamation of low specific weight “cinder” as coarse and fine aggregate replacements at various percentages and comparing the physical and mechanical characteristics of concrete made from it with orthodox concrete. The replacement was 10%, which will boost the flexural, tensile, and compressive strength if replaced as a fine Aggregate. The compressive strength, flexural splitting, and tensile strength of SF were raised by 20%. Will be cut back. Cinder added as coarse and fine aggregate in concrete, makes the LWC that enhances workability, foaminess, and up to 20% replacement as CA behaves as the ordinary normal concrete.

Engineering design often requires engaging with users, clients, and stakeholders of products and systems. It is therefore important for designers to reflect on the societal and environmental implications of their design work so that they can design equitably, ethically, and justly. We conduct a review of three leading scholarly engineering design publications to investigate how, when, and why these terms—“ethics,” “equity,” and “justice,” and variations—appear in the engineering design literature and what scholars mean when they use them. We find that these terms are minimally present within the field's scholarship and posit that design researchers may be using other terms to refer to their work that is aligned with principles of ethics, equity, and justice. We find that the prevalence of these terms has increased over time and that the terms come up throughout various stages of the design process. There appear to be a variety of motivations for including these terms, notably, sustainability and education of the next generation of designers. Finally, we propose an expanded design justice framework that is specific to engineering design. We encourage designers in our field to adopt this framework to assist them in thinking through how their engineering design work can be used to advance justice.

During aging, the proliferation and differentiation ability of mesenchymal stem/stromal cells (MSCs) gets affected, and hence, aged MSCs are not preferred for regenerative purposes. Rapid identification of aging-associated changes within MSCs and the mechanistic pathways involved is necessary to determine optimal cell sources to treat musculoskeletal disorders in older patients. Here, in this present study, we have identified a set of phenotypic markers, namely, down-regulated expression of CD90 and upregulated expression of CD45, as age-defining markers for the bone marrow-derived MSCs. We also show that these phenotypic changes in aged MSCs correlate with their aging-mediated differentiation defects. We find that oxidative stress signaling leading to the activation of NF-κB plays an essential role in altering the phenotype and differentiation ability of the aged MSCs. We further show that treatment of aged MSCs with the conditioned medium (CM) derived from young MSCs (young-CM) restored their phenotype and differentiation potential to the young-like by ameliorating activation of NF-κB signaling in them. Similar changes could also be achieved by using an inhibitor of NF-κB signaling, showing that oxidative stress-induced NF-κB activation is the causative factor in the aging of MSCs. Additionally, we show that treating young MSCs with H2O2 mimics all the aging-mediated changes in them, underscoring the involvement of oxidative stress in the aging of MSCs. Overall, our data suggest that the altered expression of CD90 and CD45 surface markers can be used as a primary screen to identify the onset of aging in the MSCs, which can be quickly reversed by their in vitro treatment with young-CM or NF-κB inhibitor. Our study also puts the phenotypic characterization of MSCs in a clinical perspective.

Background: 5-Fluorouracil is an anti-metabolite compound used for several years as an anti-tumor drug. The development of a gastroretentive drug delivery system of 5-Fluorouracil may have advantages since they retain in the stomach for an extended time and release the drug in a sustained manner, which ultimately enhances the absorption of the drug and consequently the bioavailability. Objective: The objective of the present work was to prepare a sesame oil-entrapped gellan gum hydrogel bead for controlled stomach specific delivery of 5-Fluorouracil. Methods: Sesame oil-entrapped gellan gum hydrogel bead was prepared by ionotropic gelation method. The developed hydrogels were characterized by SEM, FTIR, DSC, and XRD. The entrapment efficiency, floating ability, swelling and drug release in vitro were also determined. Results: Electrostatic interaction between the carboxylic group of polymers and Ca++ was confirmed by FTIR analysis. The SEM photograph of the hydrogel beads portrayed an approximately spherical shaped structure. DSC thermogram and XRD spectra exhibited the molecular dispersion of the drug inside the hydrogel beads. The developed beads of 5-Fluorouracil floated in pH 1.2 buffer solutions for a prolonged time period and the duration of floating was improved significantly with increasing the concentration of oil. The developed formulations showed controlled release of drug and incorporation of oil retarded the release of the drug. Fickian and non-Fickian mechanism of drug transport was observed from the prepared hydrogel beads. Conclusion: Overall, the oil-entrapped gellan matrices could be used for the intragastric delivery of 5-Fluorouracil to treat stomach cancer.

Herein we provide new information on Cnemaspis assamensis, the only species of Cnemaspis known from north-eastern India. Based on five new samples, morphological parameters are described. The species was found to have pre-cloacal and femoral pores, not accounted for in the original description. Genetic assessment of the species was made using a 914 bp fragment of the ND2 mitochondrial gene and the species was recovered as the sister taxon of the C. podihuna clade from Sri Lanka.

The Red Mud has focused through major industrial and scientific research in industrial waste valorization. Red mud is the discarded produce of alumina extraction processes from its parent the bauxite ore. Its high alkalinity causes it to be kept in large quantities, resulting in increased deforestation. Annually, it is estimated that 64.2 MMT of red mud wastes are formed around the world, and India produces about 9MMT with less hope of being reused, posing a serious threat of pollution and contamination of both soil, ground water and the environment. Large numbers of research have shown that this bauxite solid waste can be refurbished to make construction bricks, pavement tiles, ceramic materials, but no full large-scale benign re-utilization have been made. The intent of the research is to probe in to the applications of red mud in the construction and various sectors, giving emphasis on Indian context. Other researchers' observations were considered and analyzed in terms of environmental, economic, and technical feasibility to fulfill zero waste demand due to red mud.

Aging is a gradual and unavoidable physiological phenomenon that manifests in the natural maturation process and continues to progress from infanthood to adulthood. Many elderly people suffer from aging-associated hematological and nonhematological disorders. Recent advances in regenerative medicine have shown new revolutionary paths of treating such diseases using stem cells; however, aging also affects the quality and competence of stem and progenitor cells themselves and ultimately directs their death or apoptosis and senescence, leading to a decline in their regenerative potential. Recent research works show that extracellular vesicles (EVs) isolated from different types of stem cells may provide a safe treatment for aging-associated disorders. The cargo of EVs comprises packets of information in the form of various macromolecules that can modify the fate of the target cells. To harness the true potential of EVs in regenerative medicine, it is necessary to understand how this cargo contributes to the rejuvenation of aged stem and progenitor populations and to identify the aging-associated changes in the macromolecular profile of the EVs themselves. In this review, we endeavor to summarize the current knowledge of the involvement of EVs in the aging process and delineate the role of EVs in the reversal of aging-associated phenotypes. We have also analyzed the involvement of the molecular cargo of EVs in the generation of aging-associated disorders. This knowledge could not only help us in understanding the mechanism of the aging process but could also facilitate the development of new cell-free biologics to treat aging-related disorders in the future.

Cancer has recently been the second leading cause of death worldwide, trailing only cardiovascular disease. Cancer stem cells (CSCs), represented as tumor-initiating cells (TICs), are mainly liable for chemoresistance and disease relapse due to their self-renewal capability and differentiating capacity into different types of tumor cells. The intricate molecular mechanism is necessary to elucidate CSC's chemoresistance properties and cancer recurrence. Establishing efficient strategies for CSC maintenance and enrichment is essential to elucidate the mechanisms and properties of CSCs and CSC-related therapeutic measures. Current approaches are insufficient to mimic theiin vivo/ichemical and physical conditions for the maintenance and growth of CSC and yield unreliable research results. Biomaterials are now widely used for simulating the bone marrow microenvironment. Biomaterial-based three-dimensional (3D) approaches for the enrichment of CSC provide an excellent promise for future drug discovery and elucidation of molecular mechanisms. In the future, the biomaterial-based model will contribute to a more operative and predictive CSC model for cancer therapy. Design strategies for materials, physicochemical cues, and morphology will offer a new direction for future modification and new methods for studying the CSC microenvironment and its chemoresistance property. This review highlights the critical roles of the microenvironmental cues that regulate CSC function and endow them with drug resistance properties. This review also explores the latest advancement and challenges in biomaterial-based scaffold structure for therapeutic approaches against CSC chemoresistance. Since the recent entry of extracellular vesicles (EVs), cell-derived nanostructures, have opened new avenues of investigation into this field, which, together with other more conventionally studied signaling pathways, play an important role in cell-to-cell communication. Thus, this review further explores the subject of EVs in-depth. This review also discusses possible future biomaterial and biomaterial-EV-based models that could be used to study the tumor microenvironment (TME) and will provide possible therapeutic approaches. Finally, this review concludes with potential perspectives and conclusions in this area.

Sketching is often used as a tool during idea generation in the early stages of engineering design. At the same time, the rapid increase in remote engineering and design work paves the way for an increased reliance on digital design tools and technologies throughout the design process. Sketch quality and quantity have been shown to be linked to design perceptions and design outcomes. Additionally, sketch quality and style have been linked with the gender of the sketcher. Thus, there are financial, social, and ethical motivations for understanding how digital design tools influence sketching during early stages of engineering design. In this study, we investigate the influence of hand sketching on a tablet as compared to pencil or pen and paper on early stage sketching for concept generation. We also assess the influence of gender on sketching attributes. We ask three mixed gender groups of participants (using pen, pencil, and a tablet) to sketch concepts in response to an open-ended design prompt. We hypothesize that participants using tablet and pencil will produce fewer drawings than those using pen due to their ability to erase and focus on perfecting drawings, and we expect participants using the tablet to produce cleaner drawings with smoother strokes due to the tablet’s ability to auto-smooth lines. Based on prior literature, we posit that women and gender minorities will produce fewer sketches and use the feathering style of sketching more than men. We find that sketch quality is highest for pencil drawings and lower for tablet and pen drawings. We also find that concept novelty is negatively correlated with how understandable the concept is. Participants reported that experiences of drawing on paper and on the tablet differ in terms of missing the feeling of friction on the tablet and finding that too many features in a tool can be distracting during concept generation. Interestingly, participants from all groups mentioned that they were not good at sketching. Finally, we find several interesting results with respect to gender differences in sketching performance: namely, women and other gender minorities produced a higher quantity of sketches but did not have any difference in their sketch quality or style.

Vesicovaginal fistulas (VVFs), abnormal openings between the vagina and bladder, disrupt the lives of over 3 million people worldwide due to resulting incontinence and infections. VVFs are commonly treated with surgery after the fistula has had time to heal over several months. In low-resource areas, immediate incontinence often leads to ostracization from the community and can be devastating for the patient. To address this problem, we have designed a three-tiered silicone plug consisting of a bladder-dwelling disk, a midfistula disk, and a vagina-dwelling cross-shaped tapered plug, all supported on a central stem. The system is designed to occlude the fistula and enable full continence until the patient is able to access surgery. This proof-of-concept device withstands typical expulsion forces from the bladder and does not leak under typical bladder filling or urination pressures. The maximum device expulsion force is 3.69 N and it is watertight up to 9.8 kPa. It is designed to be easily deployed by trained community members.

Coping with population growth, houses are built to meet the hike. The prerequisites for concrete and steel reinforcements have surged up globally since last 3 to 4decades. Shortage of natural building materials, increased wastes from coal based industries to augment carbon foot print has worried the engineers to reuse their wastes (such as fibres, powders, granules, etc.) as building materials ingredient. Glass fibre has improved flexural capabilities with fly ash dosages in cement concrete and alternately helps in restricting environmental degradation. Present research aims at investigating the impact of glass fiber (at 1%, 2% and 3% addition) and fly ash (dosages of 10% and 20% over the existing fly ash in PPC). The ingredients and microstructure of composites are found by either X-ray fluorescent spectroscopy or scanning electron microscope. Experimental evaluation results of the blended composite concrete parameters of RCC are experimentally evaluated and compared have shown that concrete with 10% cement substitution with fly ash and 3% fibre showed optimum compressive strength performance than the concrete without fibre and fly ash and also chemically resistant against commonly used M-20 grade of Concrete.

An increasing number of proteins have been demonstrated in recent years to adopt multiple three-dimensional folds with different functions. These metamorphic proteins are characterized by having two or more folds with significant differences in their secondary structure, where each fold is stabilized by a distinct local environment. So far, about 90 metamorphic proteins have been identified in the Protein Databank (PDB), but we and others hypothesize that a far greater number of metamorphic proteins remain undiscovered. In this work, we introduce a computational model to predict metamorphic behavior in proteins using only knowledge of the sequence. In this model, secondary structure prediction programs are used to calculatediversity indices, which are measures of uncertainty in predicted secondary structure at each position in the sequence; these are then used to assign protein sequences as likely to be metamorphic vs. monomorphic (i.e. having just one-fold). We constructed a reference dataset to train our classification method, which includes a novel compilation of 140 likely-monomorphic proteins, and a set of 201 metamorphic proteins taken from the literature. Our model is able to classify proteins as metamorphic vs. monomorphic with a Matthews correlation coefficient of ∼0.4 and true positive / true negative rates of ∼65% / 80%, suggesting that it is possible to predict metamorphic behavior in proteins using only sequence information.Statement of SignificanceThis paper introduces the diversity index as a descriptor to distinguish metamorphic proteins, which possess multiple stable folds, from monomorphic proteins that possess only one fold. The diversity index is designed to measure uncertainty in computationally predicted secondary structure, which we hypothesize is elevated for metamorphic proteins. We tested our hypothesis by training a binary classifier using the diversity index and an annotated dataset of metamorphic and monomorphic proteins, and found an optimal Matthews correlation coefficient of 0.4, supporting the hypothesis and demonstrating for the first time that it is possible to predict metamorphic behavior in proteins using only sequence information. The sequence-based classifier has broader applicability compared to methods that rely on making comparison to experimentally measured structures.

A synthesis of 3,3-diarylazetidines from N-Boc-3-aryl-3-azetidinols using Friedel–Crafts arylation conditions with AlCl3 is described. A series of substituted diarylazetidines were readily prepared...

Phosphoenolpyruvate carboxylase (PEPC) is the key enzyme for fixing atmospheric carbon dioxide in C4 and CAM plants, and in anaplerotic metabolism in most plants. It is regulated by reversible phosphorylation, and allosteric activation or inhibition. The regulatory role of phosphorylation at N-terminal serine residue (S15) is documented earlier. In this study PEPC was cloned from maize and engineered to generate phosphomimic mutant enzyme by conversion of the codon for Serine 15 to aspartate (PEPCS15D). In vitro study with recombinant wild-type PEPC and phosphomimic PEPCS15D showed that both the enzymes are active catalytically. Kinetics analysis showed that PEPCS15D enzyme has comparatively lower Km value over WT PEPC, thus implying higher affinity towards its substrate PEP than the wild type PEPC. However, both WT PEPC and mutant PEPCS15D showed similar regulation with the allosteric activator (Glycine) and allosteric inhibitors (l-Aspartate or l-Malate). Thus, the engineered phosphomimic mutant PEPCS15D with high affinity for PEP will be useful to engineer rice and other C3 plants for enhancing photosynthesis and minimizing respiratory CO2 loss.

Designers routinely create informal “thinking” sketches to explore a design space, “talking” sketches to communicate design ideas during the early phases of the design process, and “learning” prototypes to test potential concepts. This study presents two new tools to assess novice designers’ sketch attributes and prototyping reflections in the context of an introductory design course. First, it proposes a rubric for assessing the quality of early-stage design sketches including line smoothness, proportion, and understandability. Of particular note is the contribution of assessing understandability as a metric for sketches as communication tools. This study also presents a tool to capture designer reflections after each iteration of a prototype. Not only does this record what is learned about a design but also designers’ personal and emotional reactions to the process. Sketching-related results show a positive correlation between sketch quality and understandability, indicating the importance of sketch quality especially when designers use sketches to communicate. Results also indicate that early-stage sketch quantity, but not quality, is linked with design outcomes. This study also finds a link between the frequency of sketching and higher maximum sketch quality scores (i.e., at least one highly rated sketch) as well as a correlation between individuals’ maximum sketch quality scores and overall design outcomes. Preliminary results around prototyping indicate that reflection on both the technical and emotional aspects of prototyping may be a worthwhile area of further study. Finally, several results point to novice designers’ lack of consistent focus on users in their prototyping reflections and presentations.

Herein we describe a new species of Cyrtodactylus from Lunglei District in the state of Mizoram, India. Based on morphology and ND2 gene sequences, the species was found to be a member of the Cyrtodactylus khasiensis group. The species can be identified by its moderate size (adult SVL 64.9–75.1 mm) with rounded, bluntly conical and feebly keeled dorsal tubercles in 24–28 longitudinal rows; 32–40 paravertebral tubercles between the level of the axilla and the level of the groin; 37–43 mid-ventral scale rows; 3–5 precloacal pores in males and 5–7 pitted precloacal scales in females; 16–18 subdigital lamellae under IV toe; no single row of transversely enlarged subcaudal scales; dorsal markings are dark brown, irregular and distinct; tail with alternating dark and light bands.

Proteins that can reversibly alternate between distinctly different folds under native conditions are described as being metamorphic. The "metamorphome" is the collection of all metamorphic proteins in the proteome, but it remains unknown the extent to which the proteome is populated by this class of proteins. We propose that uncovering the metamorphome will require a synergy of computational screening of protein sequences to identify potential metamorphic behavior and validation through experimental techniques. This perspective discusses computational and experimental approaches that are currently used to predict and characterize metamorphic proteins as well as the need for developing improved methodologies. Since metamorphic proteins act as molecular switches, understanding their properties and behavior could lead to novel applications of these proteins as sensors in biological or environmental contexts.

There is a growing movement in engineering and industry for students and practitioners to learn to embrace failure and develop resilience. The design process is naturally full of iteration and failures that can inherently be leveraged as learning opportunities for students. This study establishes a set of failure-related interventions implemented in an introductory design course, and then examines potential links to students’ experiences and attitudes towards failure. These interventions included a failure-themed “speaker seminar” series, a virtual gallery of design mistakes (“mistake museum”), and the introduction of a prototype logger for students to intentionally reflect on each iteration of their own design projects, including what went wrong and what was learned from the iteration. Students found these interventions to be effective in gaining perspective on failure and learning to embrace it. Students’ perceptions of the openness to failure of the class, perceptions of the field of design’s openness to failure, and perceptions of their major’s openness to failure all changed significantly, while their perceptions of their own openness to failure and their academic institution’s openness to failure were unchanged over the duration of the design course. Students also self-reported that the reflective processes of logging prototypes made them feel more comfortable with failure.

It is well recognized that the world needs to develop interdisciplinary problem solvers and creative thinkers to address the problems of the future. Training in the fields of Science, Technology, Engineering, Art, and Math (STEAM) is essential for understanding the complexity of the world around us and for identifying and tackling critical technical and social issues. To that end, many programs have been launched all around the world to expose students to STEAM fields and to encourage them to pursue STEAM careers. Hands-on, project-based learning has been shown to get more students engaged with STEAM and help them learn key skills for the future. However, most STEAM education programs target students in upper-middle or high school. If students are nurtured at earlier ages to love thinking critically, solving problems, and building, they are more likely to pursue STEAM fields. This paper describes the implementation of project-based STEAM curriculum with elementary school students from ages 6–13. It includes a detailed discussion of curriculum design, case studies of specific student work, subjective analysis of engagement level with various projects, and discussion of lessons learned. The paper also discusses how the makerspace environment where the students execute their projects has been set up to be accessible for students in this age range. Additionally, the paper describes how a hands-on STEAM curriculum that traditionally relies on in-person feedback, materials, and access to peers as teammates can be maintained while having students learning remotely. Educational techniques for hands-on learning while physical distancing due to the COVID-19 pandemic are discussed.

Summary Affordances offered by new media platforms are perceived as revolutionary instruments for removing the inequities of access to health promotion and communication. However, the production and dissemination of health promotional material on digital platforms does not necessarily translate into uniform access across diverse demographics. This article addresses the lacuna when it comes to analyzing Health Promotion initiatives in India, with a specific focus on the governmental publicity carried out on social media during the four phases of COVID-19 national lockdown between 24 March and 31 May 2020. Our intervention examines how governmental social media health promotion in India played a key role in shaping the ‘outbreak narrative’ during the lockdown across different levels of social and economic privilege. Through a combination of quantitative data analysis and qualitative interview methods, this article analyzes the circulation and impact of official publicity in online and offline spaces, during the COVID-19 lockdown in India. Resultant findings allow for a comprehensive assessment of whether such publicity contributed to democratized citizen science discourses: enabling social protection measures for vulnerable majorities or potentially reified the existing privileges of the economically and socially affluent minority. We find that health promotion campaigns during a pandemic must focus on reaching the widest possible audience in the most efficient manner. Specifically, in the Indian context, health promotion through mass-media like Television and Radio, and participatory media platforms needed to be implemented in tandem with new media platforms, to achieve required engagement with vulnerable communities on key health issues.

Lizards have been around since the time of the dinosaurs, but climate change poses a threat to their existence on earth as they are highly sensitive to temperature fluctuations. They feed on nocturnal insects and occasionally are cannibalistic, eat rice grain, appreciate sugar, and at times seeds of wild plants and rarely hibiscus flowers. The present study reports the femoral gland secretion of two species of Gekkonids Hemidactylus aquilonius and Hemidactylus flaviviridis from Assam using gas chromatography and mass spectrometry techniques. In Hemidactylus aquilonius esters (35%) and alkanes (25%) were predominant whereas alkanes (53%), esters (21%) and halides (11%) were the major constituents of femoral gland secretion of Hemidactylus flaviviridis. In conclusion, this is the first report on the femoral gland secretion from the genus Hemidactylus in Assam.

“All we women need to be well organized and willful to fulfil both the roles successfully.”–Jimmy Kaul, CEO, Shopotox(“7 working, mother entrepreneurs share tips on work-life balance”, Jain 2017)Du...

Because of intimidating toxicity of ammonia, development of ultra-sensitive, as well as portable and energy efficient ammonia sensor is of paramount importance. Here, we report a simple as well as cost-effective synthesis protocol of graphite– poly-amino benzene sulfonic acid (Graphite -PABS) nanocomposite via an in-situ chemical oxidative polymerization pathway. The ammonia sensing characteristics of graphite – PABS composite based sensors on low cost plastic substrate has been investigated in the concentration range of 10–100 ppm of ammonia in air at room temperature. While the sensitivity for sensors comprising only PABS is about 136.38%, the graphite -PABS nanocomposites demonstrated an appreciably high value of about 282.5% towards 100 ppm of ammonia. The sensors have not only demonstrated high sensitivity, selectivity and fast recovery; they are operable at room temperature and hence consume considerably low power compared to the conventional metal-oxide sensors. Furthermore, we have fitted the response and recovery transients of conductance of graphite/PABS based cost effective sensor using two sites Langmuir adsorption kinetics to explain the plausible ammonia sensing mechanism of graphite loaded PABS sensor. Low concentration ammonia sensing characteristics of this newly synthesized graphite/PABS composite on the plastic substrate is first demonstrated by our group.

The introduction of inorganic metal oxide nanoparticles in a polymer matrix is found to significantly modulate its optical, electrical and electrochemical properties. Here, we report the one-pot synthesis of SnO2-polycarbazole (PCz) nano composite via solution phase technique (in situ chemical oxidative polymerization route) for the first time. The morphological and compositional analyses of these organic-inorganic hybrid nano composites were done by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), the Fourier transform infrared (FTIR) spectroscopy and ultraviolet-visible (UV–visible) spectroscopy. The successful loading of SnO2 nanoparticles by PCz was apparent from FESEM micrographs. UV-Visible spectroscopy revealed that optical property of the pristine PCz was significantly revamped after incorporation of SnO2 nanoparticles. The Synergetic interactions between polycarbazole and tin oxide nanoparticles were apparent from the FTIR and XRD spectra. Thermal stability of the material estimated by Thermo gravimetric (TGA) analysis; which shows thermal strength is significantly increased after incorporation of SnO2 nanoparticles in the PCz matrix. The I-V curve shows good ohmic contact of the material with tin electrode and electrical conductivity of the material is significantly altered with varying the loading percentage of SnO2 nano particles in PCz matrix.

A series of nitrate ester analogues of the acetaminophen derivative SCP-1 were prepared by triflic acid catalyzed O-acylation of SCP-1 with chloroalkanoyl chlorides followed by nitration with silver nitrate. The chloroesters and corresponding nitrate esters were obtained in high yields. Preliminary hepatotoxicity studies revealed nitrate esters 5b (MD-38) and 5c (MD-39) to be well tolerated by human hepatocytes and had little effect on the three cytochrome P450 enzymes tested (CYP3A4, CYP2E1 and CYP2D6). In addition, the nitrate ester 5c (MD-39) exhibited antipyretic activity similar to acetaminophen.

Retinoic acid (RA), an active metabolite of vitamin A, plays a critical role in the morphogenesis and differentiation of various tissues, especially in the central nervous system. RA is the most commonly used morphogen for the differentiation of human embryonic stem cells (hESCs) into neuronal progenitor cells (NPCs), an abundant source of healthy neuronal tissues for regenerative therapy. During the differentiation process, the activity of RA is governed by the involvement of RA receptor subtypes (RAR α, β, and γ) and their isoforms in the nucleus. However, little is known about the involvement of specific RAR subtypes during neuronal differentiation in humans. It is essential to elucidate the dynamic function of different RAR subtypes and their influence on the phenotypic outcome. Here in this study, we used TTNPB, an analog and stabilized form of retinoic acid that potently and selectively activates retinoic acid receptors. Here we determined the optimum concentration of TTNPBfor the efficient generation of early NPCs from hESCs. Using the optimized concentration of -TTNPB, we found that RARα is the functionally dominant subtype and controls the RA-mediated neurogenesis of hESCs. Importantly, we also found that the RARγ subtype also played a role in neuronal differentiation. In contrast, the RARβ subtype negatively correlates with neuronal differentiation. Therefore, pharmacological inhibition of RARβ in the TTNPB-mediated differentiation process could be used as a strategy to generate a large number of NPCs in vitro. In summary, our results show that RARα and RARγ play a vital role in the TTNPB-mediated neuronal differentiation of hESCs, -whereas RARβ acts as a negative regulator.