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RNA interference-based gene silencing drugs are attracting attention for treating various diseases. Lipid nanoparticles (LNPs) are carriers that efficiently deliver small interfering RNA (siRNA) to the cytoplasm of target cells. Recently, we developed potent and well-tolerated biodegradable LNPs with asymmetric ionizable lipids. Here, we evaluated the effect of LNPs on immune cells in mice. After intravenous administration, LNPs were efficiently incorporated into several tissue-resident macrophages, including liver macrophages, through an apolipoprotein E (ApoE)-independent mechanism. Administration of LNP-encapsulated siRNA against Irf5, encoding the transcription factor critical for inflammatory responses, sharply reduced its expression in macrophages in vivo, and persisted for as long as 7 days. The therapeutic potential of Irf5 siRNA-loaded LNPs in inflammatory diseases was tested in a concanavalin A (Con A)-induced hepatitis model, whose pathogenic mechanisms are dependent on cytokine secretion from macrophages. We found that Con A-induced liver injury was significantly attenuated after LNP injection. Serum aspartate transaminase, alanine aminotransferase, and inflammatory cytokine levels were significantly reduced in mice injected with Irf5 siRNA-loaded LNPs compared to those injected with control siRNA-loaded LNPs. Our results suggest that administering biodegradable LNPs to deliver siRNA is a promising strategy for treating inflammatory disorders.

IRF5 is a potential target for therapy in systemic lupus erythematosus (SLE). Here the authors show using mouse SLE-like models that genetic or chemical inhibition of IRF5 after SLE onset could be more effective than, or an add on for, currently utilised type I interferon inhibition.

Ryosuke Kawanishi,1 Kaori Yamamoto,2 Yoko Tobetto,2 Kayo Nomura,2 Michihisa Kato,2 Ritsuko Go,2 Yasuo M Tsutsumi,3 Katsuya Tanaka,3 Yoshitsugu Takeda4 1Department of Anesthesiology, Tokushima University Hospital, Tokushima, 2Division of Anesthesiology, Tokushima Red Cross Hospital, Komatsushima, 3Department of Anesthesiology, Institute of Health Bioscience, University of Tokushima Graduate School, Tokushima, 4Division of Orthopedics, Tokushima Red Cross Hospital, Komatsushima, Japan Purpose: To determine the effects of intravenous and perineural dexamethasone on the duration of interscalene brachial plexus block (ISB) with ropivacaine in patients undergoing arthroscopic shoulder surgery. Patients and methods: In this prospective, randomized, placebo-controlled trial, patients presenting for arthroscopic shoulder surgery with an ISB were randomized to receive ropivacaine 0.75% (group C), ropivacaine 0.75% plus perineural dexamethasone 4 mg (group Dperi), or ropivacaine 0.75% plus intravenous dexamethasone 4 mg (group Div). The primary outcome was the duration of analgesia, defined as the time between performance of the block and the first request for analgesic. Results: Thirty-nine patients were randomized. The median times of sensory block in groups C, Dperi, and Div were 11.2 hours (interquartile range [IQR] 8.0–15.0 hours), 18.0 hours (IQR 14.5–19.0 hours), and 14.0 hours (IQR 12.7–15.1 hours), respectively. Significant differences were observed between groups Dperi and C (P=0.001). Kaplan–Meier analysis for the first analgesic request showed significant differences between groups Dperi and C (P=0.005) and between groups Dperi and Div (P=0.008), but not between groups C and Div. Conclusion: Perineural but not intravenous administration of 4 mg of dexamethasone significantly prolongs the duration of effective postoperative analgesia resulting from a single-shot ISB with ropivacaine 0.75%. Keywords: ropivacaine, interscalene nerve block, dexamethasone, postoperative pain, perineural

A strain-balanced, AllnAs/InGaAs/InP quantum cascade laser structure, designed for light emission at 4.0 [micro]m using nonresonant extraction design approach, was grown by molecular beam epitaxy. Laser devices were processed in buried heterostructure geometry. An air-cooled laser system incorporating a 10-mm x 11.5-[micro]m laser with antireflection-coated front facet and high-reflection-coated back facet delivered over 2 W of single-ended optical power in a collimated beam. Maximum continuous-wave room temperature wall plug efficiency of 5.0% was demonstrated for a high-reflection-coated 3.65-mm x 8.7-[micro]m laser mounted on an aluminum nitride submount. high power | midinfrared doi/ 10.1073/pnas.1013250107

Background: Jelebu is one of Negeri Sembilan districts of Malaysia, famous for its wide variety of D. zibethinus. It is also recognized as the top hotspot area for consumers looking for genuine Durian Kampung. This study aimed at discovering and recording significant morphological data in identification and classification of D. zibethinus fruit in Jelebu. Methods: Fifty-three accessions of durian were observed from January 2020 to September 2020 in accordance with Malaysia's Department of Agriculture guidelines. Result: Forty-one parameters were compiled and divided into two primary morphological data sets: external and internal structures. Size, shape, color and aril characteristics of fruits were several engrossing parameters for identifying and classifying D. zibethinus varieties. Fruit weight varies between 665 g and 2.7 kg, depending on size. The results also revealed six different variants in the fruit shape and color. Aril characteristics included a variety of aril color and thickness ranging from 0.23 cm to 1.17 cm. Therefore, this research revealed that external and internal morphological data from durian fruits were valuable for recognizing and categorizing D. zibethinus Jelebu variants. [ABSTRACT FROM AUTHOR]