Dental Pathology of the Iberian Lynx ( Lynx pardinus), Part I: Congenital, Developmental, and Traumatic Abnormalities.

The Iberian lynx is an endangered felid that has been subject to an intensive ongoing conservation program in an attempt to save it from extinction. Identification of dental pathologies could play an important role in the survival of this endangered species. The objective of this study is to evaluate the dental pathologies (congenital, developmental, and traumatic abnormalities) of this species of felid. Skulls of 88 adult specimens of the Iberian lynx ( Lynx pardinus) from the Doñana Biological Station [Estación Biológica de Doñana-Consejo Superior de Investigaciones Científicas] (EBD-CSIC), Seville, Spain, were examined macroscopically, and full-mouth dental radiographs of all specimens were performed. Presence, absence, form of teeth, number of roots, supernumerary teeth, and persistent deciduous teeth were evaluated. The presence of attrition/abrasion, tooth fractures, enamel hypoplasia/hypomineralization, endodontic disease, intrinsically stained teeth, and other traumatic findings were also evaluated. Abnormal grooves and dilacerations were the most common abnormalities seen in the roots of teeth. Two hundred and fifteen fractured teeth (11.3% of evaluated teeth) were detected, and mainly complicated fractures were noted in maxillary canine teeth (24.2% of fractured teeth) and mandibular canine teeth (16.7% of fractured teeth). Endodontic disease was present in 3.9% of the teeth examined. Intrinsic tooth staining was assessed in 8.5% of evaluated teeth. Of all teeth examined, 831 teeth (43.7% of evaluated teeth) exhibited some type of attrition/abrasion. Our study concluded that there is a high prevalence of dental fractures and attrition/abrasion with associated endodontic disease that could lead to impaired hunting ability as well as a threat to overall health and subsequent survival of this endangered species.

Dental Pathology of the Iberian Lynx ( Lynx pardinus), Part II: Periodontal Disease, Tooth Resorption, and Oral Neoplasia.

The Iberian lynx is an endangered felid that has been subject to an intensive, ongoing conservation program to save it from extinction. Identification of dental pathologies could play an important role in the survival of this endangered species. The prevalence of periodontal bone loss, tooth resorption, and oral neoplasia was evaluated in this species. Skulls of 88 adult specimens of the Iberian lynx ( Lynx pardinus) from the Doñana Biological Station (EBD-CSIC), Seville, Spain, were examined macroscopically and full-mouth dental radiographs of all specimens were performed. Different stages of periodontal disease were identified in 81.3% of teeth. Approximately two-thirds (64.8%) of the specimens examined had at least 1 tooth affected by stage 3 or 4 periodontal disease. Maxillary and mandibular incisor teeth accounted for a majority (59.4%) of teeth affected by stage 3 or 4 periodontal disease. Tooth resorption affected 12 teeth (0.63% of evaluated teeth) in 6 skull specimens (6.8% of skulls evaluated). Five of the teeth with resorptive lesions were detected on 1 skull specimen. Six teeth (50%) of those affected by tooth resorption were incisor teeth. Only 1 (1.1%) adult specimen showed signs of oral neoplasia. Our study concluded that there is a high prevalence of periodontal disease that could lead to impaired hunting ability, as well as may represent a threat to overall health and subsequent survival of this endangered species. The extremely low prevalence of tooth resorption in L pardinus could open new pathways in the discovery on the pathogenesis of tooth resorption in felids.

Spectroscopic ellipsometry as a complementary tool to characterize coatings on PDMS for CE applications.

This paper describes the use of spectroscopic ellipsometry to investigate the adsorption process of model polyelectrolytes (PDDAC and PSS) to thin-films of PDMS. A description of the information collected by ellipsometry as well as complementary information obtained by atomic force microscopy and contact angle measurements is discussed. Upon identification of the driving forces and optimum experimental conditions required for the adsorption, multilayer constructs were fabricated (ranging from 1 to 20 nm in thickness) and used to evaluate their effect on the separation of phenolic compounds by capillary electrophoresis. According to the presented results, polyelectrolyte layers of approximately 10 nm thick provided the best conditions for the separation of the selected phenolic compounds.

Electrical Conductivity and Strong Luminescence in Copper Iodide Double Chains with Isonicotinato Derivatives.

Direct reactions between CuI and isonicotinic acid (HIN) or the corresponding esters, ethyl isonicotinate (EtIN) or methyl isonicotinate (MeIN), give rise to the formation of the coordination polymers [CuI(L)]n with L=EtIN (1), MeIN (2) and HIN (3). Polymers 1-3 show similar structures based on a CuI double chain in which ethyl-, methyl isonicotinate or isonicotinic acid are coordinated as terminal ligands. Albeit, their supramolecular architecture differs considerably, affecting the distances and angles of the central CuI double chains and thereby their physical properties. Hence, the photoluminescence shows remarkable differences; 1 and 2 show a strong yellow emission, whereas 3 displays a weak emission; and 1 and 2 are semiconductors with moderate room temperature conductivities, whereas 3 has increased electrical conductivity up to 3×10(-3)  S cm(-1) . Additionally, 1 and 2 present an irreversible transition to a highly conducting phase with a conductivity almost 4 orders of magnitude higher and a quasi-metallic behaviour. Thermogravimetric analysis (TGA) coupled to a mass spectrometer and magnetic measurements point to a partial thermally induced oxidation of the carboxylate groups of the ligands with Cu(I) to Cu(0) reduction. DFT calculations have been carried out to rationalise these observations.

Coordination polymers based on diiron tetrakis(dithiolato) bridged by alkali metals, electrical bistability around room temperature, and strong antiferromagnetic coupling.

Coordination polymer chains have been formed by the direct reaction between HSC6H2Cl2SH and FeCl3·6H2O in the presence of an aqueous solution of the corresponding alkali-metal hydroxide (M = Li, Na, and K) or carbonate (M = Rb and Cs). The structures consist of dimeric [Fe2(SC6H2Cl2S)4](2-) entities bridged by [M2(THF)4] [M = K (1), Rb (2), and Cs (3); THF = tetrahydrofuran] or {[Na2(µ-H2O)2(THF)2] (5 and 5') units. The smaller size of the lithium atom yields an anion/cation ion-pair molecule, [Li(THF)4]2[Fe2(SC6H2Cl2S)4] (4), in which the dianionic moieties are held together by Cl···Cl interactions. Electrical characterization of these compounds shows a general semiconductor behavior in which the conductivity and activation energies are mainly determined by the M-Cl and M-S bond distances. Compounds 1 and 5' are interesting examples of bistability showing reversible transitions centered at ca. 350 and 290 K with very large hysteresis of ca. 60 and 35 K, respectively. All of these compounds exhibit intradimer strong antiferromagnetic Fe···Fe interactions.

Effect of different combinations of soybean-maize silage on its chemical composition, nutrient intake, degradability, and performance of Pelibuey lambs.

Sheep raising in the state of Guerrero, México, is a primary activity that is worth about US$3,251,931 annually. The objective of the present study was to evaluate the chemical composition, degradability, nutrient intake, and animal performance of Pelibuey lambs fed on different combinations of maize-soybean silages. Twenty-one combinations of maize silage (MS) and soybean silage (SS) were evaluated at day 45 post-ensiling; in each combination, MS was replaced by 5 % of SS. The 21 combinations were analysed for crude protein (CP) and chemical composition. In order to obtain a statistical criterion of potential treatments for the animal feeding test, a cluster analysis was performed based on the CP contents of all combinations at day 45 post-ensiling. From cluster analysis, four treatments were selected T1 = 100-0 % (MS/SS), T8 = 65-35 %, T12 = 45-55 %, and T16 = 25-75 %. Results indicated that cluster analysis was useful for identifying the potential treatments for animal feeding based on the crude protein content. The dry matter (DM), organic matter (OM), and acid detergent lignin (ADL) contents did not declined significantly (P > 0.05) during the fermentation of silages but CP content decreased from day 0 to 45 post-ensiling. The treatment with the highest estimated microbial crude protein synthesis was T8 and it showed the highest metabolizable energy intake, high feed efficiency with a forage-concentrate ratio of 84:16.

Fast and versatile fabrication of PMMA microchip electrophoretic devices by laser engraving.

This paper describes the effects of different modes and engraving parameters on the dimensions of microfluidic structures produced in PMMA using laser engraving. The engraving modes included raster and vector, while the explored engraving parameters included power, speed, frequency, resolution, line-width, and number of passes. Under the optimum conditions, the technique was applied to produce channels suitable for CE separations. Taking advantage of the possibility to cut-through the substrates, the laser was also used to define solution reservoirs (buffer, sample, and waste) and a PDMS-based decoupler. The final device was used to perform the analysis of a model mixture of phenolic compounds within 200 s with baseline resolution.

Getting started with open-hardware: development and control of microfluidic devices.

Understanding basic concepts of electronics and computer programming allows researchers to get the most out of the equipment found in their laboratories. Although a number of platforms have been specifically designed for the general public and are supported by a vast array of on-line tutorials, this subject is not normally included in university chemistry curricula. Aiming to provide the basic concepts of hardware and software, this article is focused on the design and use of a simple module to control a series of PDMS-based valves. The module is based on a low-cost microprocessor (Teensy) and open-source software (Arduino). The microvalves were fabricated using thin sheets of PDMS and patterned using CO2 laser engraving, providing a simple and efficient way to fabricate devices without the traditional photolithographic process or facilities. Synchronization of valve control enabled the development of two simple devices to perform injection (1.6 ± 0.4 µL/stroke) and mixing of different solutions. Furthermore, a practical demonstration of the utility of this system for microscale chemical sample handling and analysis was achieved performing an on-chip acid-base titration, followed by conductivity detection with an open-source low-cost detection system. Overall, the system provided a very reproducible (98%) platform to perform fluid delivery at the microfluidic scale.

Comparative study of the safety of regadenoson between patients with mild/moderate chronic obstructive pulmonary disease and asthma.

PURPOSE: To compare the safety of regadenoson, a selective agonist of A2A adenosine receptors, combined with low-level exercise, between subjects with mild/moderate chronic obstructive pulmonary disease (COPD) and asthma referred for myocardial perfusion imaging (MPI). METHODS: We studied 116 patients, of whom 67 had COPD and 49 asthma (62 % men, mean age 68.3 ± 11.3 years, range 31 - 87 years). Patient demographics, past medical history, medications, clinical symptoms during stress and changes in blood pressure (BP) and heart rate (HR) were evaluated. RESULTS: Both groups were comparable with regard to hypertension, dyslipidaemia, diabetes and medications with the exception of a higher rate of use of anticholinergics in patients with COPD and of antileukotrienes in asthmatics (58.2 % vs. 28.6 % and 1.5 % vs. 14.3 %, respectively; all p < 0.01). There was a higher incidence of dyspnoea in COPD patients and of headache and feeling hot in asthmatic patients (40.3 % vs. 22.4 %, 6 % vs. 18.4 % and 10.4 % vs. 26.5 %, respectively; all p < 0.05). Although there was no difference in the incidence of other adverse events, we observed a higher frequency in asthmatics of flushing, dry mouth, sweating and fatigue (1.5 % vs. 6.1 %, 14.9 % vs. 24.5 %, 0 % vs. 4.1 % and 37.3 % vs. 49 %, respectively). Adverse events were self-limiting, except in three patients who suffered persistent dyspnoea (2 of 67 COPD patients; 1 of 49 asthma patients) requiring theophylline administration. We observed no significant changes in BP among either group, but there was a tendency towards a higher increase in systolic BP in COPD patients following regadenoson administration (148.3 ± 27.6 vs. 154.6 ± 31.0 mmHg, p = 0.056). CONCLUSION: This study showed a good safety profile in our series of COPD and asthma patients undergoing MPI. Regadenoson was well tolerated by all patients, with dyspnoea, headache and feeling hot showing differences between groups.

Coordination polymers containing manganese(II)-azido layers connected by dipyridyl-tetrazine and 4,4'-azobis(pyridine) linkers.

Two new polynuclear manganese(II) complexes [Mn(dptz)(N(3))(2)](n) (1) and [Mn(azpy)(N(3))(2)](n) (2) (where dptz = dipyridyl-tetrazine and azpy = 4,4'-azobis(pyridine)) have been synthesized by self-assembly of the ligand azide, together with dptz and azpy as secondary spacers. The compounds are characterized by single-crystal X-ray diffraction analyses and variable-temperature magnetic measurements. The structural analyses reveal that in complex 1, which is the first reported Mn(II) complex with the ligand dptz, two µ(1,3) bridging azides connect neighboring manganese ions in a zigzag manner to generate a neutral two-dimensional (2D) sheet which is further connected by the dptz ligands to form a three-dimensional (3D) framework. By contrast, complex 2 contains dimeric [Mn(2)(µ(1,1)-N(3))(2)](2+) fragments linked to four identical motifs by means of four single µ(1,3)-N(3) bridges, that generates a neutral 2D Mn(II)-azide sheet which is further interconnected by azpy ligands to neighboring manganese ions forming an unprecedented 3D network. Variable-temperature (2-300 K) magnetic susceptibility measurements show the presence of predominantly antiferromagnetic coupling for both complexes that has been reproduced with a regular antiferromagnetic S = 5/2 chain (J) with interchain interactions (j) modeled with the molecular field approximation with J = -7.1 cm(-1) and j' = -0.8 cm(-1) for 1 and J = -4.2 cm(-1) and j' = 0.1 cm(-1) for 2.

Electrical bistability around room temperature in an unprecedented one-dimensional coordination magnetic polymer.

The synthesis, crystal structure, and physical properties of an unprecedented one-dimensional (1D) coordination polymer containing [Fe2(S2C6H2Cl2)4](2-) entities bridged by dicationic [K2(µ-H2O)2(THF)4](2+) units are described. The magnetic properties show that the title compound presents pairwise Fe-Fe antiferromagnetic interactions that can be well reproduced with a S = 1/2 dimer model with an exchange coupling, J = -23 cm(-1). The electrical conductivity measurements show that the title compound is a semiconductor with an activation energy of about 290 meV and two different transitions, both with large hysteresis of about 60 and 30 K at 260-320 K and 350-380 K, respectively. These two transitions are assumed to be due to slight structural changes in the cation-anion interactions. Differential Scanning Calorimetry confirms the presence of both transitions. This compound represents the first sample of a coordination polymer showing electrical bistability.

Semiconductive and magnetic one-dimensional coordination polymers of Cu(II) with modified nucleobases.

Four new copper(II) coordination complexes, obtained by reaction of CuX2 (X = acetate or chloride) with thymine-1-acetic acid and uracil-1-propionic acid as ligands, of formulas [Cu(TAcO)2(H2O)4]·4H2O (1), [Cu(TAcO)2(H2O)2]n (2), [Cu3(TAcO)4(H2O)2(OH)2]n·4H2O (3), and [Cu3(UPrO)2Cl2(OH)2(H2O)2]n (4) (TAcOH = thymine-1-acetic acid, UPrOH = uracil-1-propionic acid) are described. While 1 is a discrete complex, 2-4 are one-dimensional coordination polymers. Complexes 2-4 present dc conductivity values between 10(-6) and 10(-9) S/cm(-1). The magnetic behavior of complex 2 is typical for almost isolated Cu(II) metal centers. Moderate-weak antiferromagnetic interactions have been found in complex 3, whereas a combination of strong and weak antiferromagnetic interactions have been found in complex 4. Quantum computational calculations have been done to estimate the individual "J" magnetic coupling constant for each superexchange pathway in complexes 3 and 4. Compounds 2-4 are the first known examples of semiconductor and magnetic coordination polymers containing nucleobases.

Coordination chemistry of 6-thioguanine derivatives with cobalt: toward formation of electrical conductive one-dimensional coordination polymers.

In this work we have synthetized and characterized by X-ray diffraction five cobalt complexes with 6-thioguanine (6-ThioGH), 6-thioguanosine (6-ThioGuoH), or 2'-deoxy-6-thioguanosine (2'-d-6-ThioGuoH) ligands. In all cases, these ligands coordinate to cobalt via N7 and S6 forming a chelate ring. However, independently of reagents ratio, 6-ThioGH provided monodimensional cobalt(II) coordination polymers, in which the 6-ThioG(-) acts as bridging ligand. However, for 2'-d-6-ThioGuoH and 6-ThioGuoH, the structure directing effect of the sugar residue gives rise to mononuclear cobalt complexes which form extensive H-bond interactions to generate 3D supramolecular networks. Furthermore, with 2'-d-6-ThioGuoH the cobalt ion remains in the divalent state, whereas with 6-ThioGuoH oxidation occurs and Co(III) is found. The electrical and magnetic properties of the coordination polymers isolated have been studied and the results discussed with the aid of DFT calculations, in the context of molecular wires.

Unmanned platform for long-range remote analysis of volatile compounds in air samples.

This paper describes a long-range remotely controlled CE system built on an all-terrain vehicle. A four-stroke engine and a set of 12-V batteries were used to provide power to a series of subsystems that include drivers, communication, computers, and a capillary electrophoresis module. This dedicated instrument allows air sampling using a polypropylene porous tube, coupled to a flow system that transports the sample to the inlet of a fused-silica capillary. A hybrid approach was used for the construction of the analytical subsystem combining a conventional fused-silica capillary (used for separation) and a laser machined microfluidic block, made of PMMA. A solid-state cooling approach was also integrated in the CE module to enable controlling the temperature and therefore increasing the useful range of the robot. Although ultimately intended for detection of chemical warfare agents, the proposed system was used to analyze a series of volatile organic acids. As such, the system allowed the separation and detection of formic, acetic, and propionic acids with signal-to-noise ratios of 414, 150, and 115, respectively, after sampling by only 30 s and performing an electrokinetic injection during 2.0 s at 1.0 kV.

Dynamic magnetic materials based on the cationic coordination polymer [Cu(btix)2]n(2n+) [btix = 1,4-bis(triazol-1-ylmethyl)benzene]: tuning the structural and magnetic properties through anion exchange.

A three-dimensional coordination polymer, [Cu(btix)(2)(BF(4))(2)](n) [btix = 1,4-bis(triazol-1-ylmethyl)benzene], with antiferromagnetic interactions occurring via the organic ligand, has been prepared and characterized. It has been shown to permit the exchange of anionic species in the crystalline network with modification of the magnetic properties. Coordinated BF(4)(-) can be reversibly exchanged by different anions with (NO(3)(-) and Cl(-)) or without (PF(6)(-) and ClO(4)(-)) dynamic response of the organic ligand, which acts as the only linker between the metal centers. Interestingly, an irreversible exchange occurs with N(3)(-) anions to generate a new coordination polymer, [Cu(btix)(N(3))(2)](n), whose structure has been determined ab initio by powder X-ray diffraction, revealing a totally different connectivity between the Cu(II) centers. These structural transformations are accompanied by a change of the magnetic properties, which have been detected by electron paramagnetic resonance and magnetic susceptibility measurements.

Electrical conductivity and luminescence in coordination polymers based on copper(I)-halides and sulfur-pyrimidine ligands.

The solvothermal reactions between pyrimidinedisulfide (pym(2)S(2)) and CuI or CuBr(2) in CH(2)Cl(2):CH(3)CN lead to the formation of [Cu(11)I(7)(pymS)(4)](n) (pymSH = pyrimidine-2(1H)-thione) (1) and the dimer [Cu(II)(µ-Br)(Br)L](2) (L = 2-(pyrimidin-2-ylamino)-1,3-thiazole-4-carbaldehyde) (2). In the later reaction, there is an in situ S-S, S-C(sp(2)), and C(sp(2))-N multiple bond cleavage of the pyrimidinedisulfide resulting in the formation of 2-(pyrimidin-2-ylamino)-1,3-thiazole-4-carbaldehyde. Interestingly, similar reactions carried out just with a change in the solvent (H(2)O:CH(3)CN instead of CH(2)Cl(2):CH(3)CN) give rise to the formation of coordination polymers with rather different architectures. Thus, the reaction between pym(2)S(2) and CuI leads to the formation of [Cu(3)I(pymS)(2)](n) (3) and [CuI(pym(2)S(3))] (pym(2)S(3) = pyrimidiltrisulfide) (4), while [Cu(3)Br(pymS)(2)](n) (5) is isolated in the reaction with CuBr(2). Finally, the solvothermal reactions between CuI and pyrimidine-2-thione (pymSH) in CH(2)Cl(2):CH(3)CN at different ratios, 1:1 or 2:1, give the polymers [Cu(2)I(2)(pymSH)(2)](n) (6) and [Cu(2)I(2)(pymSH)](n) (7), respectively. The structure of the new compounds has been determined by X-ray diffraction. The studies of the physical properties of the novel coordination polymers reveal that compounds 3 and 5 present excellent electrical conductivity values at room temperature, while compounds 1, 3, and 5-7 show luminescent strong red emission at room temperature.

Acute social stress increases biochemical and self report markers of stress without altering spatial learning in humans.

OBJECTIVES: Spatial learning is shown to be influenced by acute stress in both human and other animals. However, the intricacies of this relationship are unclear. Based on prior findings we hypothesized that compared to a control condition, a social stress condition would not affect spatial learning performance despite elevated biochemical markers of stress. METHODS: The present study tested the effects of social stress in human males and females on a subsequent spatial learning task. Social stress induction consisted of evaluative stress (the Trier Social Stress Test, TSST) compared to a placebo social stress. RESULTS: Compared to the placebo condition, the TSST resulted in significantly elevated cortisol and alpha amylase levels at multiple time points following stress induction. In accord, cognitive appraisal measures also showed that participants in the TSST group experienced greater perceived stress compared to the placebo group. However, there were no group differences in performance on a spatial learning task. CONCLUSION: Our findings suggest that unlike physiological stress, social stress does not result in alterations in spatial learning in humans. It is possible that moderate social evaluative stress in humans works to prevent acute stress-mediated alterations in hippocampal learning processes..

Present and future of lipid nanoparticle-mRNA technology in phenylketonuria disease treatment.

Phenylketonuria (PKU) is a metabolic rare disease characterized by a failure of the body to clear out the high levels of Phenylalanine (Phe), leading to devastating neurological defects and growth retardation. PKU was discovered in 1934 by AsbjrØrn FØlling, and even though there have been continuous efforts from the scientific community to find therapeutic approaches to modulate the high levels of phenylalanine found in the body of the PKU patients, an efficient therapy still needs to be developed. Current standard of care includes low phenylalanine diets, but the strict restrictions for patients and families makes it very difficult to adequately being implemented. FDA has approved two drugs to help reduce Phe levels in PKU patients: an enzyme substitution therapy, Palynziq® (PEGylated recombinant phenylalanine ammonia lyase), and Kuvan®, a supplemental tetrahydrobiopterin (BH4) cofactor that enhances residual enzyme activity. Both treatments are restricted to certain PKU patients' population, and, therefore, there are still high unmet needs for most of the patients. The present review will focus on current advancements in lipid nanoparticles (LNP)-mRNA technologies and their potential in treating the root cause of PKU, a therapeutic approach that will be analyzed in the context of other promising therapeutic approaches that are been developed for PKU.

Obesity and oral health in Mexican children and adolescents: systematic review and meta-analysis.

CONTEXT: A relationship between obesity and poor oral health has been reported. OBJECTIVE: To investigate the association between overweight/obesity and oral health in Mexican children and adolescents. DATA SOURCES: A literature search was conducted of 13 databases and 1 search engine for articles published from 1995 onward. DATA ANALYSIS: A total of 18 publications were included. Evidence was inconclusive and varied according to sociodemographic factors or outcome measuring tools. The Decayed, Missing, and Filled Teeth and Filled Teeth Surfaces indices and the decayed extracted filled teeth index outcomes were included in a random effects model meta-analysis. Pooled estimates showed no statistically significant oral health differences (measured via the decayed extracted filled teeth or the Decayed, Missing, and Filled Teeth Surfaces indexes) among body mass index (BMI) categories. However, pooled estimates of 6 studies showed that children with higher BMI had worse oral health in permanent teeth (measured via the Decayed Missing Filled Teeth Index) than children with lower BMI (overall mean difference, -0.42; 95%CI, -0.74, -0.11). CONCLUSION: Whether there is an association between poor oral health and high BMI is inconclusive; however, both co-exist among Mexican children. Therefore, health promotion and prevention efforts should address common risk factors and broader risk social determinants shared between noncommunicable diseases.

Synthesis and bioactivity of readily hydrolysable novel cationic lipids for potential lung delivery application of mRNAs.

Lipid nanoparticles (LNPs) mediated mRNA delivery has gained prominence due to the success of mRNA vaccines against Covid-19, without which it would not have been possible. However, there is little clinical validation of this technology for other mRNA-based therapeutic approaches. Systemic administration of LNPs predominantly targets the liver, but delivery to other organs remains a challenge. Local approaches remain a viable option for some disease indications, such as Cystic Fibrosis, where aerosolized delivery to airway epithelium is the preferred route of administration. With this in mind, novel cationic lipids (L1-L4) have been designed, synthesized and co-formulated with a proprietary ionizable lipid. These LNPs were further nebulized, along with baseline control DOTAP-based LNP (DOTAP+), and tested in vitro for mRNA integrity and encapsulation efficiency, as well as transfection efficiency and cytotoxicity in cell cultures. Improved biodegradability and potentially superior elimination profiles of L1-L4, in part due to physicochemical characteristics of putative metabolites, are thought to be advantageous for prospective therapeutic lung delivery applications using these lipids.