A Pseudo-Surfactant Chemical Permeation Enhancer to Treat Otitis Media via Sustained Transtympanic Delivery of Antibiotics.

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable noninvasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, can compromise gelation, formulation stability, and drug diffusion. To overcome this challenge, differing interactions between CPEs and the hydrogel system are explored, especially those with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and those with methyl laurate (ML), a nonionic counterpart with a similar length alkyl chain. Notably, the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM), which is not possible with the use of SDS. Ciprofloxacin and ML are shown to form a pseudo-surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70-fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest-performing formulation. Beyond improved efficacy and biocompatibility, this single-CPE formulation significantly accelerates its progression toward clinical deployment.

Assembly and analysis of the genome of Notholithocarpus densiflorus.

Tanoak (Notholithocarpus densiflorus) is an evergreen tree in the Fagaceae family found in California and southern Oregon. Historically, tanoak acorns were an important food source for Native American tribes, and the bark was used extensively in the leather tanning process. Long considered a disjunct relictual element of the Asian stone oaks (Lithocarpus spp.), phylogenetic analysis has determined that the tanoak is an example of convergent evolution. Tanoaks are deeply divergent from oaks (Quercus) of the Pacific Northwest and comprise a new genus with a single species. These trees are highly susceptible to "sudden oak death" (SOD), a plant pathogen (Phytophthora ramorum) that has caused widespread deaths of tanoaks. In this study, we set out to assemble the genome and perform comparative studies among a number of individuals that demonstrated varying levels of susceptibility to SOD. First, we sequenced and de novo assembled a draft reference genome of N. densiflorus using cobarcoded library processing methods and an MGI DNBSEQ-G400 sequencer. To increase the contiguity of the final assembly, we also sequenced Oxford Nanopore long reads to 30× coverage. To our knowledge, the draft genome reported here is one of the more contiguous and complete genomes of a tree species published to date, with a contig N50 of ∼1.2 Mb, a scaffold N50 of ∼2.1 Mb, and a complete gene score of 95.5% through BUSCO analysis. In addition, we sequenced 11 genetically distinct individuals and mapped these onto the draft reference genome, enabling the discovery of almost 25 million single nucleotide polymorphisms and ∼4.4 million small insertions and deletions. Finally, using cobarcoded data, we were able to generate a complete haplotype coverage of all 11 genomes.

Investigation of AFeO3 (A=Ba, Sr) Perovskites for the Oxidative Dehydrogenation of Light Alkanes under Chemical Looping Conditions.

Oxidative dehydrogenation (ODH) of light alkanes to produce C2-C3 olefins is a promising alternative to conventional steam cracking. Perovskite oxides are emerging as efficient catalysts for this process due to their unique properties such as high oxygen storage capacity (OSC), reversible redox behavior, and tunability. Here, we explore AFeO3 (A=Ba, Sr) bulk perovskites for the ODH of ethane and propane under chemical looping conditions (CL-ODH). The higher OSC and oxygen mobility of SrFeO3 perovskite contributed to its higher activity but lower olefin selectivity than its Ba counterpart. However, SrFeO3 perovskite is superior in terms of cyclic stability over multiple redox cycles. Transformations of the perovskite to reduced phases including brownmillerite A2Fe2O5 were identified by X-ray diffraction (XRD) as a cause of performance degradation, which was fully reversible upon air regeneration. A pre-desorption step was utilized to selectively tune the amount of lattice oxygen as a function of temperature and dwell time to enhance olefin selectivity while suppressing CO2 formation from the deep oxidation of propane. Overall, SrFeO3 exhibits promising potential for the CL-ODH of light alkanes, and optimization through surface and structural modifications may further engineer well-regulated lattice oxygen for maximizing olefin yield.