On-chip Brillouin lasers based on 10 million-Q chalcogenide resonators without direct etch process

We present a new device platform which defines on-chip chalcogenide waveguide/resonators without directly etching chalcogenide. Using our platform, we have demonstrated chalcogenide ring resonators with record high Q-factor exceeding 1.1x107 which is 10 times larger than previous record on on-chip chalcogenide resonators. A ring cavity is designed and fabricated for Stimulated Brillouin lasing on our platform. Thanks to the high-Q factor, Brillouin lasing with threshold power of 1 mW is demonstrated. This value is more than an order of magnitude improvement than previous world record for on-chip chalcogenide Brillouin lasers. We also developed an efficient and flexible method for resonator waveguide coupling with our device platform. Coupling between a resonator and a waveguide can be varied from under coupled region to over-coupled regio

Gene duplication of type-B ARR transcription factors systematically extends transcriptional regulatory structures in Arabidopsis

Many of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, we examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures.1

Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation

BackgroundEzetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.MethodsWe fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.ResultsIn OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe’s mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.ConclusionThis study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism

Rapid Hepatobiliary Excretion of Micelle-Encapsulated/Radiolabeled Upconverting Nanoparticles as an Integrated Form

In the field of nanomedicine, long term accumulation of nanoparticles (NPs) in the mononuclear phagocyte system (MPS) such as liver is the major hurdle in clinical translation. On the other hand, NPs could be excreted via hepatobiliary excretion pathway without overt tissue toxicity. Therefore, it is critical to develop NPs that show favorable excretion property. Herein, we demonstrated that micelle encapsulated Cu-64-labeled upconverting nanoparticles (micelle encapsulated Cu-64-NOTA-UCNPs) showed substantial hepatobiliary excretion by in vivo positron emission tomography (PET) and also upconversion luminescence imaging (ULI). Ex vivo biodistribution study reinforced the imaging results by showing clearance of 84% of initial hepatic uptake in 72 hours. Hepatobiliary excretion of the UCNPs was also verified by transmission electron microscopy (TEM) examination. Micelle encapsulated Cu-64-NOTA-UCNPs could be an optimal bimodal imaging agent owing to quantifiability of Cu-64, ability of in vivo/ex vivo ULI and good hepatobiliary excretion property.

Universal light-guiding geometry for on-chip resonators having extremely high Q-factor

By providing an effective way to leverage nonlinear phenomena in integrated devices, high-Q optical resonators have led to recent advances in on-chip photonics. However, developing fabrication processes to shape any new material into a resonator with extremely smooth surfaces on a chip has been an exceptionally challenging task. Here, we describe a universal method to implement ultra-high-Q resonators with any new material having desirable properties that can be deposited by physical vapor deposition. Using this method light-guiding cores with surface roughness on the molecular-scale are created automatically on pre-patterned substrates. Its efficacy has been verified using As2S3, a chalcogenide glass that has high-nonlinearity. The Q-factor of the As2S3 resonator so-developed approached the propagation loss record achieved in chalcogenide fibers which were limited by material losses. Owing to the boosted Q-factor, lasing by stimulated Brillouin scattering has been demonstrated with 100 times lower threshold power than the previous record. © 2020, The Author(s).1

Universal light-guiding geometry for on-chip resonators having extremely high Q-factor

By providing an effective way to leverage nonlinear phenomena in integrated devices, high-Q optical resonators have led to recent advances in on-chip photonics. However, developing fabrication processes to shape any new material into a resonator with extremely smooth surfaces on a chip has been an exceptionally challenging task. Here, we describe a universal method to implement ultra-high-Q resonators with any new material having desirable properties that can be deposited by physical vapor deposition. Using this method light-guiding cores with surface roughness on the molecular-scale are created automatically on pre-patterned substrates. Its efficacy has been verified using As2S3, a chalcogenide glass that has high-nonlinearity. The Q-factor of the As2S3 resonator so-developed approached the propagation loss record achieved in chalcogenide fibers which were limited by material losses. Owing to the boosted Q-factor, lasing by stimulated Brillouin scattering has been demonstrated with 100 times lower threshold power than the previous record.This work was supported by Samsung Research Funding & Incubation Center of Samsung Electronics under Project Number SRFC-IT1801-03

Hypertension, renin-angiotensin-aldosterone-system-blocking agents, and COVID-19

Background There have been concerns regarding the safety of renin-angiotensin-aldosterone-system (RAAS)-blocking agents including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) during the coronavirus disease 2019 (COVID-19) pandemic. This study sought to evaluate the impact of hypertension and the use of ACEI/ARB on clinical severity in patients with COVID-19. Methods A total of 3,788 patients aged 30 years or older who were confirmed with COVID-19 with real time reverse transcription polymerase chain reaction were identified from a claims-based cohort in Korea. The primary study outcome was severe clinical events, a composite of intensive care unit admission, need for ventilator care, and death. Results Patients with hypertension (n = 1,190, 31.4 %) were older and had higher prevalence of comorbidities than those without hypertension. The risk of the primary study outcome was significantly higher in the hypertension group, even after multivariable adjustment (adjusted odds ratio [aOR], 1.67; 95 % confidence interval [CI], 1.04 to 2.69). Among 1,044 patients with hypertensive medical treatment, 782 (74.9 %) were on ACEI or ARB. The ACEI/ARB subgroup had a lower risk of severe clinical outcomes compared to the no ACEI/ARB group, but this did not remain significant after multivariable adjustment (aOR, 0.68; 95 % CI, 0.41 to 1.15). Conclusions Patients with hypertension had worse COVID-19 outcomes than those without hypertension, while the use of RAAS-blocking agents was not associated with increased risk of any adverse study outcomes. The use of ACE inhibitors or ARBs did not increase the risk of adverse COVID-19 outcomes, supporting current guidance to continue these medications when indicated.This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (grant number 2019R1C1C1006611)