Inhaled Nanoformulated mRNA Polyplexes for Protein Production in Lung Epithelium

Noninvasive aerosol inhalation is an established method of drug delivery to the lung, and remains a desirable route for nucleic‐acid‐based therapeutics. In vitro transcribed (IVT) mRNA has broad therapeutic applicability as it permits temporal and dose‐dependent control of encoded protein expression. Inhaled delivery of IVT‐mRNA has not yet been demonstrated and requires development of safe and effective materials. To meet this need, hyperbranched poly(beta amino esters) (hPBAEs) are synthesized to enable nanoformulation of stable and concentrated polyplexes suitable for inhalation. This strategy achieves uniform distribution of luciferase mRNA throughout all five lobes of the lung and produces 101.2 ng g^?1 of luciferase protein 24 h after inhalation of hPBAE polyplexes. Importantly, delivery is localized to the lung, and no luminescence is observed in other tissues. Furthermore, using an Ai14 reporter mouse model it is identified that 24.6% of the total lung epithelial cell population is transfected after a single dose. Repeat dosing of inhaled hPBAE‐mRNA generates consistent protein production in the lung, without local or systemic toxicity. The results indicate that nebulized delivery of IVT‐mRNA facilitated by hPBAE vectors may provide a clinically relevant delivery system to lung epithelium.     

Ultrasonication study for suspending single-walled carbon nanotubes in water

A systematic calorimetry-based technique was developed to standardize single-walled carbon nanotube (SWNT) dispersion protocol. Simple calorimetric experiments were performed to benchmark the performance of the ultra-dismembrator. Temperature profiles for the sonication period were utilized to estimate energy input to the system. Energy loss profile was generated for the ultradismembrator in use and a calibration relationship was formulated that could standardize the sonication process. The standardized protocol was used to prepare aqueous SWNT suspensions-sonicating SWNTs in a varied range of input energy (18-100 kJ) in water. SWNT mass fractions suspended for each energy input was accurately measured and the suspended SWNT samples were characterized for morphology, surface potential, cluster size and structure, and chemical functionality using high resolution transmission electron microscopy (HRTEM), electrophoresis, dynamic and static light scattering (DLS/SLS), and Raman spectroscopy. The study demonstrated that suspended mass of SWNTs increased up to 18 kJ of energy input with no further increase upon continued energy input. The physicochemical properties showed similar trend for energy input. The aggregate cluster size, surface potential behavior, as well as the Raman defect properties plateaued after the initial energy input. The significant changes observed were limited to morphological properties, i.e., shorter length, debundled, and sharp edged SWNTs and fractal cluster formation (lower D(f)) with increased input energy.     

Novel water-soluble polymer coatings control NPK release rate,improve soil quality and maize productivity

We investigated different combinations of polymers (5% each) (i) starch, gelatin (polymer coating; PC-1), (ii) polyvinyl alcohol (PVA), gum Arabica (PC-2), (iii) PVA, gelatin (PC-3), (iv) starch, gum Arabica (PC-4), (v) gelatin, gum Arabica (PC-5), (vi) starch, PVA (PC-6), for coating NPK (17, 17:17) in a fluidized bed granulator. Morphological characterization indicated a uniform coating of all formulations on NPK granules. A slow release of N (PC-3), P (PC-6), and K (PC-3) was observed in water. In soil, high mineral N (63%), plant-available P (72%), and K (24%) were observed in PC-3, PC-5, and PC-6, respectively than uncoated fertilizer. Microbial biomass NPK was also higher in these treatment. This resulted in higher maize yield (66%), N (114%), P (164%), and K (137%) uptakes and apparent N (267%), P (196%), and K (358%) recoveries from applied fertilizer in these treatments. Among these, PC-3 resulted in an increase of 115% shoot N, 169% P and 138% K uptakes and 268% apparent N, 206% P and 361% K recoveries than uncoated fertilizer. Hence, coating of NPK with this biodegradable polymer combination controlled N, P, and K release and synchronized these nutrients availabilities with maize nutrients demand therefore resulted in higher maize crop yield and nutrient utilization efficiencies.     

Symmetry analysis of MHD Casson fluid flow for heat and mass transfer near a stagnation point over a linearly stretching sheet with variable viscosity and thermal conductivity

In this article, the impacts of variable viscosity and thermal conductivity on magnetohydrodynamic, heat transfer, and mass transfer flow of a Casson fluid are analyzed on a linearly stretching sheet inserted in a permeable medium along with heat source/sink and viscous dissipation. To reduce the ascendant partial differential equations into ordinary differential equations, Lie group transformation is utilized. Further, the fourth-order Runge–Kutta strategy is utilized to solve the ordinary differential equations numerically. The numerical results obtained for various parameters by employing coding in MATLAB programming are investigated and considered through graphical representation and tables. We anatomize the impacts of distinctive parameters on velocity, temperature, and concentration distributions.     

Investigation on the Antioxidant Activity of Leaves, Peels, Stems Bark, and Kernel of Mango (Mangifera indica L.)

Bioactive polyphenols, cartenoids, and anthocyanins present in fruits and vegetables are receiving much attention because of their potential antioxidant activity. This study was conducted to determine antioxidant activity of leaves, peels, stem bark, and kernel of mango varieties langra and chonsa. Total phenolic (TPC) and total flavonoid contents (TFCs) in segments of langra ranged from 63.89 to 116.80 mg GAE/g DW and 45.56 to 90.89 mg CE/g DW, respectively, and that of chonsa were 69.24 to 122.60 mg GAE/g DW and 48.43 to 92.55 mg CE/g DW, respectively. The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and linoleic inhibition capacity in segments of langra ranged from 53.30% to 61.10% and 40.0% to 47.20%, respectively, whereas for chonsa; 56.40% to 66.0% and 48.1% to 49.0%, respectively. The reducing potentials of different segments of langra and chonsa at concentration of 10 mg/mL were 0.512 to 0.850 and 0.595 to 0.665 mV, respectively. Comparison between both varieties showed chonsa exhibited better antioxidant activity. Data were analyzed by analysis of variance (ANOVA) using completely randomised design (CRD) under factorial.     

Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes

B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T‐cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non‐Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose‐dependent and time‐controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells. Here, the design, synthesis, and biological evaluation of a lipid nanoparticle (LNP) system that can encapsulate mRNA, navigate to the spleen, transfect B lymphocytes, and induce more than 60 pg of protein expression per million B cells within the spleen is described. Importantly, this LNP induces more than 85% of total protein production in the spleen, despite LNPs being observed transiently in the liver and other organs. These results demonstrate that LNP composition alone can be used to modulate the site of protein induction in vivo, highlighting the critical importance of designing and synthesizing new nanomaterials for nucleic acid delivery.     

Synthesis and Antimicrobial Activity of p-tetranitrocalix[4]arene Derivative

The present study demonstrates the synthesis and antimicrobial activity of the p-tetranitrocalix[4]arene (3). The microbial activity was determined against a variety of microorganisms, i.e., Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus ATCC 10231, Streptococcus viridans ATCC 12392, Escherichia coli ATCC 8739, as well as some fungal species including Aspergillus niger ATCC 16404, Aspergillus flavus ATCC 90906, and Candida albicans ATCC 32333. Kirby-Bauer well agar diffusion method was employed for the determination of antimicrobial activity. All the microorganisms were applied to a selective agar medium (Mueller Hinton Agar) for growth. It was observed that compound 3 is considerably effective against selected microorganisms. The MIC values were also evaluated. Thus, from the results it could be deduced that compound 3 may be a valuable addition to the therapeutic index.     

Design for the Ecological Age: Rethinking the Role of Sustainability in Architectural Education

While sustainability has become a mainstream concern in design thinking and practice, the debate is fragmented and the concept of sustainable architecture remains contested. We interpret this as symptomatic of a widening gap between architectural academe and the world of practice. Inspired by the “pluralist imagination,” we propose a meta-framework based on analyses of competing discourses at three levels: conceptual, performance, and pedagogical. With the intention of inspiring a critical attitude among designers, the value of such a framework lies in its ability to promote dialogue across theoretical boundaries in order to impede both notions of theoretical determinism and panacean interpretations of proliferating sustainable practices.     

Synthesis of novel hollow microflowers (NHMF) of Nb3O7F,their optical and hydrogen storage properties

A two step, facile surfactant free hydrothermal route was adopted to synthesize Nb₃O₇F novel hollow microflowers (NHMF). Time dependent experiments were performed which suggested Nb₃O₇F-NHMF were formed due to Ostwald-ripening process. Raman spectroscopy was conducted to understand different vibrational modes of Nb₃O₇F-NHMF. Its characteristic band at 692 cm⁻¹ was observed which is associated to NbO₆ octahedron sharing. The bandgap of 3.2 eV was calculated by using UV-VIS-NIR absorption spectrum. Considering importance of layered structures in energy storage applications, hydrogen storage ability of Nb₃O₇F-NHMF were measured for the first time. The maximum values of hydrogen absorption for Nb₃O₇F-NHMF at 373 K and 473 K were 0.789 wt.% and 1.08 wt.%, respectively. The hydrogen storage measurements revealed the potential of Nb₃O₇F-NHMF as prospective material for energy storage applications.     

Phosphorylated nanocellulose fibrils/PVA nanocomposite membranes for biogas upgrading at higher pressure

ABSTRACT

High moisture uptake and excellent mechanical properties of cellulose nano-fibril (CNF) make it an interesting material to use as an additive in facilitated transport membranes. The objective of this work is to develop novel phosphorylated nanocellulose fibrils (PCNF)/polyvinyl alcohol (PVA) nanocomposite membranes for biogas upgrading. Results showed that the thickness of membrane increases with increasing concentration of PCNF. The addition of PCNF to pristine PVA membranes has beneficial effect for CO₂/CH₄ separation. However, maximum performance was achieved with 1 wt.% PCNF in 2% PVA at pH 12. Furthermore, increasing feed pressure caused a decrease in both permeability and selectivity.