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• Process parameters affect the cone instability and profile in flow focusing process • Recirculation flow inside the cone occurs as the viscosity ratio between the focusing and focused liquid is high • Balance of tangential shear force on cone interface dominate the size of the recirculation flow • Process parameters manipulate the size of recirculation flow A parametric study on the stability and morphology of the liquid cone in a flow focusing process is carried out through experimental and numerical methods. For the numerical simulations, we solve the Navier-Stokes equations coupled with a diffuse interface method. A scaling analysis which considers the competition between the viscous shear stress and the interfacial tension force is proposed, showing the effect of flow rates, geometrical parameters and liquid physical properties on the cone instability. The experimental and numerical results validate the scaling law and further show the effects of parameters on the cone morphology. We study the flow fields inside the liquid cone, with emphatic focus on the recirculation flow pattern which occurs at relatively high viscosity ratio between the focusing and the focused liquids. The occurrence of recirculation flow is close related to the tangential velocity distribution at both sides of the cone interface, and the change of flow rates and geometrical parameters is found to significantly affect the size of the recirculation flow. This study is expected to give a guidance to the optimization of process parameters in flow focusing system, which would contribute to the formation of a stable cone-jet structure and the production of microdroplets with high throughput. [ABSTRACT FROM AUTHOR]

Over the past two decades, the escalating prescription of opioid medications for pain management has culminated in a widespread opioid epidemic, significantly impacting public health, social dynamics, and economic stability. The urgent need for improved treatments for opioid addiction necessitates a deeper understanding of its biological underpinnings, with genetic variations playing a crucial role in individual susceptibility to opioid use disorder (OUD) and influencing clinical practices. In this study, we leverage the genetic diversity of four rat strains (ACI/N, BN/NHsd, WKY/N, and F344/N) to examine the contribution of genetic factors to oxycodone metabolism and addiction-like behaviors. We used the extended access to intravenous oxycodone self-administration procedure (12 h/day, 0.15 mg/kg/injection) to comprehensively characterize oxycodone-related behaviors and pharmacokinetics. We measured escalation of oxycodone self-administration, motivation for drug consumption, tolerance to the analgesic effects of oxycodone, withdrawal-induced hyperalgesia, and oxycodone-induced respiratory depression. Additionally, we examined oxycodone-seeking behavior after four weeks of withdrawal by reintroducing the animals to environmental and cue stimuli previously associated with oxycodone self-administration. The findings revealed notable strain differences in several behavioral measures, including oxycodone metabolism. Intriguingly, BN/NHsd and WKY/N strains exhibited similar drug intake and escalation patterns but displayed significant disparities in oxycodone and oxymorphone metabolism. Minimal sex differences were observed within strains, primarily relating to oxycodone metabolism. In conclusion, this study identifies strain differences in the behavioral responses and pharmacokinetics associated with oxycodone self-administration in rats, providing a robust foundation for identifying genetic and molecular variants associated with various facets of the opioid addiction process. • Strain differences impact oxycodone metabolism and behavior, including cue seeking. • Sex influences oxycodone pharmacokinetics. • There are complex relationships between different oxycodone-related behaviors. • Development of tolerance can differ across behavioral assays. [ABSTRACT FROM AUTHOR]

Nicotine use produces psychoactive effects, and chronic use is associated with physiological and psychological symptoms of addiction. However, chronic nicotine use is known to decrease food intake and body weight gain, suggesting that nicotine also affects central metabolic and appetite regulation. We recently showed that acute nicotine self-administration in nicotine-dependent animals produces a short-term increase in food intake, contrary to its long-term decrease of feeding behavior. As feeding behavior is regulated by complex neural signaling mechanisms, this study aimed to test the hypothesis that nicotine intake in animals exposed to chronic nicotine may increase activation of pro-feeding regions and decrease activation of pro-satiety regions to produce the acute increase in feeding behavior. FOS immunohistochemistry revealed that acute nicotine intake in nicotine self-administering animals increased activation of the pro-feeding arcuate and lateral hypothalamic nuclei and decreased activation of the pro-satiety parabrachial nucleus. Regional correlational analysis also showed that acute nicotine changes the functional connectivity of the hunger/satiety network. Further dissection of the role of the arcuate nucleus using electrophysiology found that putative POMC neurons in animals given chronic nicotine exhibited decreased firing following acute nicotine application. These brain-wide central signaling changes may contribute to the acute increase in feeding behavior we see in rats after acute nicotine and provide new areas of focus for studying both nicotine addiction and metabolic regulation. • Acute nicotine increases activation of pro-feeding brain regions in dependent rats. • Acute nicotine increases functional connectivity of nicotine and feeding regions. • Chronic and acute nicotine oppositely alter POMC neuron firing. [ABSTRACT FROM AUTHOR]

Water oxidation by cobalt complexes of flexible tetrapyrines was studied in alkaline solutions and the complex with a seven-member ring exhibited a better activity. • Synthesis and characterization of tetrapyridyl cobalt complexes. • Redox properties of tetrapyridyl cobalt complexes. • Electrocatalytic water oxidation by tetrapyridyl cobalt complexes. Effective, robust, and low-cost catalysts are highly demanded for water oxidation reaction (WOR) which is the bottleneck of water splitting. Herein reported is water oxidation catalysis of two cobalt complexes [Co(tpbn)](ClO 4) 2 (1) and [Co(tpen)](ClO 4) 2.3CH 3 CN (2) of tetrapyridyl ligands N,N,N',N'-tetrakis(2-pyridyl-methyl)-1,4-butanediamine (tpbn) and N,N,N',N'-tetrakis(2-pyridyl-methyl)-1,2-ethanediamine (tpen). 1 was a stable molecular electrocatalyst for WOR in alkaline solutions with a rate constant (k cat) of 0.97 s−1. A turnover number (TON) was estimated to be 10. Complex 2 was a much weaker catalyst than 1. The difference in the catalytic activity of 1 and 2 could be due to the flexibility of the coordination sphere of the Co center. The Co-N bonds in 1 were longer than those in 2. In comparison to the five-membered ring (N-C 2 -N-Co) in 2 , a seven-membered ring (N-C 4 -N-Co) in 1 was more flexible and easily adaptive for the incoming H 2 O or OH– groups to access the Co center, which was vital for the formation of O 2. A nucleophilic attack catalytic mechanism was proposed for WOR. This work demonstrated that the flexibility of the organic ligands and the adaptability of the coordination configuration of the metal center had a great impact on the catalytic properties of metal complexes. [ABSTRACT FROM AUTHOR]