An efficient and regioselective synthesis of fused polycyclic furo[3,4-c]indolo[2,1-a]isoquinolines through Rh(III)catalyzed cascade C−H activation/annulation/lactonization of 2-arylindoles and 4-hydroxy-2-alkynoates has been developed. This cascade reaction displays high step economy and efficiency and tolerates various functional groups. The titled polycyclic furo[3,4c]indolo[2,1-a]isoquinolines exhibit fluorescence emission.

Millimetre-wave (mmWave) technology continues to draw great interest due to its broad applications in wireless communications, radar, and spectroscopy. Compared to pure electronic solutions, photonic-based mmWave generation provides wide bandwidth, low power dissipation, and remoting through low-loss fibres. However, at high frequencies, two major challenges exist for the photonic system: the power roll-off of the photodiode, and the large signal linewidth derived directly from the lasers. Here, we demonstrate a new photonic mmWave platform combining integrated microresonator solitons and high-speed photodiodes to address the challenges in both power and coherence. The solitons, being inherently mode-locked, are measured to provide 5.8 dB additional gain through constructive interference among mmWave beatnotes, and the absolute mmWave power approaches the theoretical limit of conventional heterodyne detection at 100 GHz. In our free-running system, the soliton is capable of reducing the mmWave linewidth by two orders of magnitude from that of the pump laser. Our work leverages microresonator solitons and high-speed modified uni-traveling carrier photodiodes to provide a viable path to chip-scale, high-power, low-noise, high-frequency sources for mmWave applications.

The optical microresonator-based frequency comb (microcomb) provides a versatile platform for nonlinear physics studies and has wide applications ranging from metrology to spectroscopy. The deterministic quantum regime is an unexplored aspect of microcombs, in which unconditional entanglements among hundreds of equidistant frequency modes can serve as critical ingredients to scalable universal quantum computing and quantum networking. Here, we demonstrate a deterministic quantum microcomb in a silica microresonator on a silicon chip. 40 continuous-variable quantum modes, in the form of 20 simultaneously two-mode squeezed comb pairs, are observed within 1 THz optical span at telecommunication wavelengths. A maximum raw squeezing of 1.6 dB is attained. A high-resolution spectroscopy measurement is developed to characterize the frequency equidistance of quantum microcombs. Our demonstration offers the possibility to leverage deterministically generated, frequency multiplexed quantum states and integrated photonics to open up new avenues in fields of spectroscopy, quantum metrology, and scalable, continuous-variable-based quantum information processing.

Exosomal micro (mi)RNAs have been suggested to have important roles in abdominal obesity, and to be associated with metabolic alterations via posttranscriptional regulation of target genes. However, exosomal miRNA profiles in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have rarely been investigated. In the present study, microarray data were obtained from the Gene Expression Omnibus database with the following accession numbers: GSE68885 (exosomal miRNAs in SAT obtained from seven patients with obesity and five lean patients), GSE50574 (exosomal miRNAs in VAT obtained from seven patients with obesity and five lean patients) and GSE29718 [mRNAs in SAT (obtained from seven patients with obesity and eight lean patients) and VAT (obtained from three patients with obesity and two lean patients)]. Differentially expressed (DE)-miRNAs and differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2.0 database. Potential functions of DE-miRNA target genes were determined using the Database for Annotation, Visualization and Integrated Discovery. As a result, 10 exosomal DE-miRNAs were identified in SAT between patients with obesity and lean patients, while 58 DE-miRNAs were identified in VAT between patients with obesity and lean patients. miRNA (miR)-4517 was revealed to be a downregulated exosomal miRNA between SAT and VAT, while the other DE-miRNAs were SAT-(e.g. hsa-miR-3156-5p and hsa-miR-4460) or VAT-(e.g. hsa-miR-582-5p, hsa-miR-566 and miR-548) specific. Following overlapping with the target genes of DE-miRNAs, only one DEG [cluster of differentiation 86 (CD86)] was identified in SAT samples, whereas 25 DEGs (e.g. fibroblast growth factor 2 (FGF2), FOS like 2, AP-1 transcription factor subunit (FOSL2); and adenosine monophosphate deaminase 3 (AMPD3)] were identified in VAT samples. CD86 was revealed to be regulated by hsa-miR-3156-5p; whereas FGF2, FOSL2 and AMPD3 were revealed to be regulated by hsa-miR-582-5p, hsa-miR-566 and miR-548, respectively. Functional enrichment analysis demonstrated that these target genes may be associated with inflammation. In conclusion, exosomal miRNAs may represent underlying therapeutic targets for the treatment of abdominal obesity and metabolic disorders via regulation of inflammatory genes.

Nitrogen-containing aromatics have potential applications in surface functionalization, corrosion inhibition, and carbon-nitride materials. Reflection− absorption infrared spectroscopy (RAIRS), X-ray photoelectron spectroscopy (XPS), near-edge X-ray absorption fine structure (NEXAFS), and temperatureprogrammed reaction/desorption (TPR/D) have been employed to study the system of 2,4-C 5 NH 3 Br 2 /Cu(100). Our experimental results indicate that 2,4-C 5 NH 3 Br 2 is adsorbed predominantly in molecular form on Cu(100) at 100 K; however, a tiny fraction of the adsorbed molecules is subjected to debromination. The 2,4-C 5 NH 3 Br 2 undergoes partial C−Br dissociation below 400 K, forming C 5 NH 3 Br intermediate. Although after breaking both the C−Br bonds (>400 K), 2,4-pyridyne (C 5 NH 3 ) can be formed, the possibility of Ullmann coupling reaction cannot be excluded. The NEXFAS study shows a ∼ 35°average inclination of the aromatic plane, with respect to the surface, in a packed 2,4-pyridyne adsorption layer. Thermal decomposition of the C 5 NH 3 or its coupling reaction products on the Br/Cu(100) surface mainly occurs at a temperature higher than 550 K, generating H 2 , HCN, HBr, and (CN) 2 .

ABSTRACT. We examined the distribution of major allelic variants of CYP2C9 and CYP2C19 in the Mongolian population of China and compared it with that of other populations. The polymorphisms of CYP2C9 (including the CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles) and CYP2C19 (including the CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles) were analyzed in 280 healthy unrelated Chinese Mongolian subjects, using a PCR-RFLP assay. The frequencies of CYP2C9*1, *2 and *3 alleles were 0.97, 0.00 and 0.03, respectively. The frequencies of CYP2C19*1, *2 and *3 alleles were 0.72, 0.24 and 0.04, respectively. We did not find any differences in the allelic distribution of these two genes between age groups. However, the genotype frequency of CYP2C9 *1/*3 was significantly higher in males than in females. Compared with other populations, we found that the allele frequencies of the CYP2C9*2 and CYP2C9*3 allelic variants in this Mongolian population of China were similar to those reported

X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, and temperature-programmed reaction/desorption have been employed to investigate the adsorption and reaction pathways of CH2=CHCOOH and CH3CHFCOOH on Cu(100) and oxygen-precovered Cu(100) [O/Cu(100)]. In the case of CH2=CHCOOH on O/Cu(100), CH2=CHCOO is the surface intermediate detected between 110 K and 400 K. CH2=CHCOO is adsorbed vertically and can change adsorption sites at a higher temperature. The propenoate (acrylate) decomposes at higher temperatures (>500 K), with formation of >C=C=O (ketenylidene) surface species and gaseous products. On Cu(100), CH2=CHCOOH is adsorbed in dimer form and can dissociate to generate CH2=CHCOO and CH3CHCOO intermediates on the surface. The CH3CHCOO continuously recombines with the H from deprotonation of CH2=CHCOOH, resulting in the formation CH3CH2COO. The co-existing CH2=CHCOO and CH3CH2COO further decompose at ∼550 K to evolve reaction products, but without >C=C=O being detected. On O/Cu(100), CH3CHFCOOH readily deprotonates to form CH3CHFCOO at 120 K. This intermediate reacts on the surface at ∼460 K to evolve gaseous products, also producing CH2=CHCOO. In the case of Cu(100), deprotonation of CH3CHFCOOH occurs at ∼250 K, forming CH3CHFCOO. Without oxygen on the surface, this intermediate decomposes into HF and CH2=CHCOO at ∼455 K.

BMS-690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development. The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction (34%) of metabolism. It is also a substrate of P-glycoprotein (P-gp) in vitro. To assess the effect of ketoconazole on BMS-690514 pharmacokinetics, 17 healthy volunteers received 200 mg BMS-690514 alone followed by 100 mg BMS-690514 with ketoconazole (400 mg once daily for 4 days). The AUC(∞) of 100 mg BMS-690514 concomitantly administered with ketoconazole was similar to that of 200 mg BMS-690514 alone. The dose-normalized C(max) and AUC(∞) of BMS-690514 from the 100-mg BMS-690514/400-mg ketoconazole treatment increased by 55% and 127%, respectively, relative to those from 200 mg BMS-690514 alone. Prediction of the drug-drug interaction (DDI) using a population-based simulator (Simcyp) indicated that, in addition to CYP3A4 inhibition, the inhibition of P-gp by ketoconazole in the intestine, liver, and kidneys must be invoked to fully account for the DDI observed. This finding suggests that the inhibition of P-gp by ketoconazole, along with its effect on CYP3A4, needs to be considered when designing a DDI study of ketoconazole with a victim drug that is a dual substrate.