Enantioconvergent Cu-catalysed N-alkylation of aliphatic amines.

Chiral amines are commonly used in the pharmaceutical and agrochemical industries1. The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods1,2. Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version3-5. Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning.

Cu(I)-Catalyzed Chemo- and Enantioselective Desymmetrizing C-O Bond Coupling of Acyl Radicals.

Transition-metal-catalyzed enantioselective functionalization of acyl radicals has so far not been realized, probably due to their relatively high reactivity, which renders the chemo- and stereocontrol challenging. Herein, we describe Cu(I)-catalyzed enantioselective desymmetrizing C-O bond coupling of acyl radicals. This reaction is compatible with (hetero)aryl and alkyl aldehydes and, more importantly, displays a very broad scope of challenging alcohol substrates, such as 2,2-disubstituted 1,3-diols, 2-substituted-2-chloro-1,3-diols, 2-substituted 1,2,3-triols, 2-substituted serinols, and meso primary 1,4-diols, providing enantioenriched esters characterized by challenging acyclic tetrasubstituted carbon stereocenters. Partnered by one- or two-step follow-up transformations, this reaction provides a convenient and practical strategy for the rapid preparation of chiral C3 building blocks from readily available alcohols, particularly the industrially relevant glycerol. Mechanistic studies supported the proposed C-O bond coupling of acyl radicals.

Copper-Catalyzed Enantioconvergent Radical C(sp3)-N Cross-Coupling of Activated Racemic Alkyl Halides with (Hetero)aromatic Amines under Ambient Conditions.

The enantioconvergent C(sp3)-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N-alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp3)-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

The effect of endoscopic ultrasound on the precise selection of endoscopic treatment for submucosal tumors in the upper gastrointestinal tract.

OBJECTIVE: To summarize and discuss the guiding role of endoscopic ultrasound (EUS) in selecting endoscopic treatments for submucosal tumors (SMTs) in the upper gastrointestinal tract. METHODS: A retrospective investigation was conducted on 156 SMT patients who received endoscopic resection guided by EUS in the endoscopy center of the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from May 2019 to September 2021. Next, the size, pathological type, and distribution of lesions were analyzed; the correlation of the tumor origin with distribution of lesions and selection of treatments was explored; and the consistency of preoperative EUS diagnosis and postoperative pathological diagnosis was summarized and analyzed. RESULTS: The tumor diameters of the included SMT patients ranged from 0.3 to 4 cm, with a mean diameter of 0.95 cm; the lesions were mostly located in the esophagus, gastric fundus or fundic cardia and gastric body. As for the pathological types, liomyoma was the most common tumor in the esophagus, liomyoma and mesenchymoma were mainly located in the fundic cardia and gastric body, and heterotopic pancreas was mostly discovered in the gastric sinus. Among 38 esophageal SMT patients, some with lesions originating from muscularis mucosa and submucosa under EUS mainly underwent endoscopic submucosal dissection (ESD) and endoscope band ligation (EBL); while others with lesions originated from muscularis propria mainly received submucosal tunneling endoscopic resection (STER). Of 115 gastric SMT patients under EUS, some with lesion origins from the muscularis mucosa and submucosa mainly underwent endoscopic submucosal excavation (ESE), while others from muscularis propria mainly underwent ESE, ESD, and endoscopic full-thickness resection (EFTR). Besides, 3 duodenal SMT patients with lesion origins from submucosa and muscularis propria under EUS were given ESD and ESE, respectively. Additionally, 121 cases showed a consistency between the EUS diagnosis and the postoperative pathological nature, and the consistency rate was 84.6%. CONCLUSION: Clarifying the origin layer, size, growth pattern, and pathological nature of the lesion through preoperative EUS can guide the precise selection of endoscopic treatments, thereby ensuring a safe, effective, and complete surgical outcomes and reducing complications.

[Effects of light quality on growth and icariin flavonoid content of Epimedium pseudowushanense under different light intensity].

In this study, the growth index including plant height, compound leaf area, specific leaf area, leaf water content, number of branches, and leaf biomass per plant and the icariin flavonoids such as epimedin A, epimedin B, epimedin C and icariin of Epimedium pseudowushanense were determined on 30 d and 60 d under light intensity(18.2±2.5) µmol·m~(-2)·s~(-1)(L1) and(90.9 ±2.5) µmol·m~(-2)·s~(-1)(L2), and white light as control, red light, blue light and yellow light were used as three light quality treatments, to study the effect of light quality on the growth and flavonoids accumulation of E. pseudowushanense. The E. pseudowushanense was sui-table for growth under L1 light intensity, the blue light treatment significantly reduced the leaf area, but had little effect on the stem height, the red light treatment and the yellow light treatment had no obvious effect on the stem height and leaf area, but the yellow light treatment significantly increased the germination of new branches, and had a sustained promoting effect, and the biomass was significantly higher than the white light treatment at 60 d. The content of icariin flavonoids in red light, blue light and yellow light treatment was higher than that in white light treatment at 30 d and 60 d under L1 light intensity, while yellow light treatment promoted the synthesis of icariin flavonoids to the largest extent, which was 1.8 and 1.9 times of white light treatment(30 d and 60 d).Under L2 light intensity, the effect of strong light on promoting stem germination became the main factor, while the yellow light treatment showed no significant effect on promoting stem germination, and the red light treatment exhibited a significant effect on reducing leaf area. Icariin flavonoids under red light, blue light and yellow light treatment were all lower than that under white light treatment, that is, the effect of white light treatment on the synthesis of icariin flavonoids is better than red light, blue light and yellow light treatment. When the time of strong light treatment was longer, the degradation range of icariin flavonoids in other light treatment appeared, while red light treatment promotes the synthesis of icariin flavonoids. Therefore, the influence of light quality on E. pseudowushanense is quite different under different light intensity, no matter from growth index or flavonoid content index. The results support that the biomass and icariin flavonoid content can be increased by providing appropriate red and yellow light.

Retrospective analysis of population-based causes of death and life expectancy in urban Western China from 2003 to 2012.

BACKGROUND: Hitherto, a population-based analysis of the cause of death in urban areas of Western China has not been undertaken over an extended period. The aims of this study were to calculate the overall and annual cause-specific mortality rates by age and sex in urban areas of Western China from 2003 to 2012 and to evaluate the quality of the data. METHODS: We used Excel software, cause-of-death registrations, and International Classification of Diseases, 10th revision, codes to calculate the overall and yearly cause-specific crude mortality rates by age and sex, the Chinese age-standardized mortality rate, and life expectancies. RESULTS: In the Jiulongpo District from 2003 to 2012, there was an increase in the number of death case reports in the census-registered population, a decrease in the number of omitted deaths, and rise in the crude mortality rate. Except for 2003, the Chinese age-standardized mortality rate was the lowest in 2012 (330.83/100,000) and highest in 2005 (390.08/100,000). Life expectancy increased from 78.36 years in 2005 to 81.67 years in 2012. CONCLUSIONS: With the development of its social economy, the Chinese government and public attach greater importance to cause-of-death surveillance. The quality of cause-of-death registrations has gradually increased, crude mortality rates have risen, the Chinese age-standardized mortality rate has fallen, and life expectancies have increased.

[Progress of effects of light on plant flavonoids].

As an important secondary metabolites of medicinal plant, flavonoids plays a very important role on itself including light protection and antioxidant. Light is one of the important environmental factors which impacts the secondary metabolites of plant and has a significant impact on biological synthesis of flavonoids. This paper reviews the recent progress of the effects of light on flavonoids on the plants focusing from light intensity and light quality, and summarizes briefly functions of the phenylalanine ammonia lyase (PAL) in plant secondary metabolism and the upstream key enzyme chalcone synthase (CHS) in flavonoid biosynthetic pathway.

[Research on photosynthetic and eco-physiological characteristics of Epimedium pseudowushannense in different growing age].

Epimedium is a widely used medicinal plants. Due to excessive use of wild resources and resource constraints, artificial cultivation is the only way to achieve sustainable use of resources. E. pseudowushannense is intended to achieve the first cultivated species, but plant production technology is not yet fully mature.The diurnal variation of photosynthetic and eco-physiological characteristics of E. pseudowushannense in different growing age was studied by the CI-340 Portable Photosynthesis System under natural conditions. The net photosynthetic rate (Pn), stomatal conductance (C), intercellular CO2 concentration (Ci), photosynthetically active radiation (PAR), relative humidity (RH), air temperature (Ta), apparent mesophyll conductance (ALMC), transpiration rate (E), leaf temperature (Tl), water use efficiency (WUE) and other photosynthetic physiological factors and environmental factors were measured. The obtained data was analyzed by correlation analysis, path analysis and stepwise multiple-regression analysis to explore the relationship between net photosynthetic rate and physiological and ecological factors. The results show that： ①The daily variation of the Pn, E, ALMC, C of E. pseudowushannense in different growing age took on"two peak type", the Pn was with an obvious midday depression phenomenon at noon.②The Pn, ALMC and C of annuals' were significantly higher than biennial or three-year; but the Ci was basically a three-year > biennial> annual.③The correlation analysis, path analysis and stepwise regression analysis showed that ALMC, Ci, Ta might played important role in the Pn and ranked as ALMC>Ci>Ta.

Short-term ethanol exposure causes imbalanced neurotrophic factor allocation in the basal forebrain cholinergic system: a novel insight into understanding the initial processes of alcohol addiction.

Alcohol ingestion affects both motor and cognitive functions. One brain system that is influenced by ethanol is the basal forebrain (BF) cholinergic projection system, which projects to diverse neocortical and limbic areas. The BF is associated with memory and cognitive function. Our primary interest is the examination of how regions that receive BF cholinergic projections are influenced by short-term ethanol exposure through alterations in the mRNA levels of neurotrophic factors [nerve growth factor/TrkA, brain-derived neurotrophic factor/TrkB, and glial-derived neurotrophic factor (GDNF)/GDNF family receptor α1]. Male BALB/C mice were fed a liquid diet containing 5 % (v/v) ethanol. Pair-fed control mice were maintained on an identical liquid diet, except that the ethanol was isocalorically substituted with sucrose. Mice exhibiting signs of ethanol intoxication (stages 1-2) were used for real-time reverse transcription-polymerase chain reaction analyses. Among the BF cholinergic projection regions, decreased levels of GDNF mRNA and increased levels of TrkB mRNA were observed in the basal nucleus, and increased levels of TrkB mRNA were observed in the cerebral cortex. There were no significant alterations in the levels of expression of relevant neurotrophic factors in the septal nucleus and hippocampus. Given that neurotrophic factors function in retrograde/anterograde or autocrine/paracrine mechanisms and that BF cholinergic projection regions are neuroanatomically connected, these findings suggested that an imbalanced allocation of neurotrophic factor ligands and receptors is an initial phenomenon in alcohol addiction. The exact mechanisms underlying this phenomenon in the BF cholinergic system are unknown. However, our results provide a novel notion for the understanding of the initial processes in alcohol addiction.

Structure-based computational study of the hydrolysis of New Delhi metallo-ß-lactmase-1.

New Delhi metallo-ß-lactmase-1 (NDM-1) is an enzyme that confers antibiotic resistance to bacteria and is thus a serious threat to human health. Almost all clinically available ß-lactam antibiotics can be hydrolyzed by NDM-1. To determine the mechanism behind the wide substrate diversity and strong catalytic ability of NDM-1, we explored the molecular interactions between NDM-1 and different ß-lactam antibiotics using computational methods. Molecular dynamics simulations and binding free energy calculations were performed on enzyme-substrate (ES) complex models of NDM-1-Meropenem, NDM-1-Nitrocefin, and NDM-1-Ampicillin constructed by molecular docking. Our computational results suggest that mutant residues Ile35 and Lys216, and active site loop L1 residues 65-73 in NDM-1 play crucial roles in substrate recognition and binding. The results of our study provide new insights into the mechanism behind the enhanced substrate binding and wider substrate spectrum of NDM-1 compared with its homologous enzymes CcrA and IMP-1. These insights may be useful in the discovery and design of specific and potent inhibitors against NDM-1.

Early postnatal maternal separation causes alterations in the expression of ß3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity.

The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague-Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3h each day during the 10-15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), ß3-adrenergic receptor (ß3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through ß3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the ß3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

A quantum mechanics/molecular mechanics study on the hydrolysis mechanism of New Delhi metallo-ß-lactamase-1.

New Delhi metallo-ß-lactamase-1 (NDM-1) has emerged as a major global threat to human health for its rapid rate of dissemination and ability to make pathogenic microbes resistant to almost all known ß-lactam antibiotics. In addition, effective NDM-1 inhibitors have not been identified to date. In spite of the plethora of structural and kinetic data available, the accurate molecular characteristics of and details on the enzymatic reaction of NDM-1 hydrolyzing ß-lactam antibiotics remain incompletely understood. In this study, a combined computational approach including molecular docking, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations was performed to characterize the catalytic mechanism of meropenem catalyzed by NDM-1. The quantum mechanics/molecular mechanics results indicate that the ionized D124 is beneficial to the cleavage of the C-N bond within the ß-lactam ring. Meanwhile, it is energetically favorable to form an intermediate if no water molecule coordinates to Zn2. Moreover, according to the molecular dynamics results, the conserved residue K211 plays a pivotal role in substrate binding and catalysis, which is quite consistent with previous mutagenesis data. Our study provides detailed insights into the catalytic mechanism of NDM-1 hydrolyzing meropenem ß-lactam antibiotics and offers clues for the discovery of new antibiotics against NDM-1 positive strains in clinical studies.

Impact of body mass index on atrial fibrillation recurrence: a meta-analysis of observational studies.

BACKGROUND: Obesity is associated with increased risk of atrial fibrillation (AF). Several trials exploring the impact of elevated body mass index (BMI) on the catheter ablation of AF have been published and yield conflicting results. We thus conducted a meta-analysis to explore the association between elevated BMI and AF recurrence in patients undergoing catheter ablation. METHODS: A systematic review and meta-analysis was performed. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled. RESULTS: Six observational studies including 2,358 patients were included. Of those, four studies were prospective cohort studies, and two were retrospective studies. Elevated BMI increased the risk of AF recurrence compared to normal BMI by 31%, where the difference between the two arms was statistically significant (RR = 1.308, 95% CI: 1.036-1.651, P = 0.02). Compared to normal BMI group, the overweight group had a 27% increased risk of AF recurrence (RR = 1.270, 95% CI 0: 961-1.679, P = 0.093) and the obese group had a significantly increased risk of AF recurrence (RR = 1.378, 95% CI: 1.006-1.887, P = 0.045). When compared to the overweight group, the obese group has a 12% increased risk of AF recurrence (RR = 1.116, 95% CI: 0.866-1.438, P = 0.397). CONCLUSIONS: Elevated BMI is associated significantly with AF recurrence in patients undergoing catheter ablation. There is a graded relationship between elevated BMI and increased risk of AF recurrence.

Cu-catalysed enantioselective radical heteroatomic S-O cross-coupling.

The transition-metal-catalysed cross-coupling reaction has established itself as one of the most reliable and practical synthetic tools for the efficient construction of carbon-carbon/heteroatom (p-block elements other than carbon) bonds in both racemic and enantioselective manners. In contrast, development of the corresponding heteroatom-heteroatom cross-couplings has so far remained elusive, probably due to the under-investigated and often challenging heteroatom-heteroatom reductive elimination. Here we demonstrate the use of single-electron reductive elimination as a strategy for developing enantioselective S-O coupling under Cu catalysis, based on both experimental and theoretical results. The reaction manifests its synthetic potential by the ready preparation of challenging chiral alcohols featuring congested stereocentres, the expedient valorization of the biomass-derived feedstock glycerol, and the remarkable catalytic 4,6-desymmetrization of inositol. These results demonstrate the potential of enantioselective radical heteroatomic cross-coupling as a general chiral heteroatom-heteroatom formation strategy.

Morphological evidence of an altered process of synaptic transcytosis in adult rats exposed to ethanol.

AIMS: The effects of ethanol exposure on synaptic structure were investigated in the nucleus of solitary tract (NST) in rats, using the horse-radish peroxidase (HRP) method. METHODS: Eight-week-old experimental rats were allowed free access to a liquid diet containing ethanol for 3 weeks, while controls were given an isocaloric diet. Some of the control and experimental animals were given an injection of wheat germ agglutinin conjugated with HRP (WGA-HRP) into the vagus nerve toward the end of the treatment period. After the treatment, the neuropil region of the NST was examined under an electron microscope. RESULTS: We observed that a few terminals were characterized by deep indentation of axodendritic membranes into the post-synaptic neurons. This appeared to be similar to that commonly seen in exocrine glands. Interestingly, the indented portion often contained various sizes of vacuoles and flattened cisternae. HRP-reaction product (RP) transported to terminals was recognized easily as an electron-dense lysosomal substance when lead citrate staining was omitted. Terminals containing HRP-RP also revealed quite a similar structure with indentation of axodendritic membranes as described earlier. The results are considered to confirm that terminals forming 'apocrine-like structures' observed in the ethanol-fed animals with no injection of WGA-HRP originate from afferent fibers of the vagus nerve. CONCLUSION: The present study suggests the possibility that the alteration of the synaptic structure induced by ethanol exposure can lead to the neuronal transcytosis of materials including proteins which is different from the normal vesicular exocytosis involved in chemical synaptic transmission.

Regional differences of high-quality development level for manufacturing industry in China.

The development of China's manufacturing industry is still facing the challenge of regional imbalance. To solve the problem of development imbalance, it is necessary to realize regional development. First, we must analyze the development characteristics of different regions. To this end, we consider the requirements of the new development era and design an evaluation index system for the high-quality development level of the manufacturing industry from the dimensions of innovation, green, and efficiency. Then construct a novel hybrid model which combines the grey incidence clustering model and AP algorithm for panel data in this paper. According to the statistical data from 2014 to 2018, we find out the high-quality development of China's manufacturing industry is characterized by obvious regional differences, different development stages and different constraints.

Comparison of inhibitory effects and mechanisms of lactonic sophorolipid on different pathogenic bacteria.

Crude sophorolipids (SLs) have been proven to perform varying degrees of inhibitory effects on different pathogenic bacteria. However, systematic comparative studies of pure lactonic sophorolipid (LSL) among different types of bacteria are few. In this study, the antibacterial effects and mechanisms of LSL on pathogenic bacteria of Staphylococcus aureus, Lactobacillus sp., Pseudomonas aeruginosa, and Escherichia coli were investigated. Bacteriostatic circle, antibacterial rate, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) of LSL on different pathogenic bacteria were measured. Then, the antibacterial mechanisms of LSL on S. aureus and P. aeruginosa were explored using ultrastructural observation, cell membrane permeability analysis, intracellular ATP content determination, and extracellular UV absorption detection. With the minimum MIC and MBC values of 0.05 and 0.20 mg/ml, LSL exhibited the best inhibitory effect against S. aureus, followed by P. aeruginosa. LSL showed no significant inhibitory effect on E. coli and Lactobacillus sp. For both S. aureus and P. aeruginosa, LSL achieved bacteriostatic and bactericidal effects by destroying the cell wall, increasing the permeability of the cell membrane and leading to the flow out of intracellular contents. However, the action mode and action intensity of LSL on the cell wall and membrane of these two bacteria were significantly different. LSL had a greater influence on the cell membrane of S. aureus by "leaking," while it exhibited a stronger effect on the cell wall of P. aeruginosa by "blasting." These results contributed to a better understanding of the relationship between LSL and different bacterial cell structures, further suggesting the conclusion that LSL might be used for the targeted treatment of special pathogenic bacteria.

Apolipoprotein C3 and circulating mediators of preadipocyte proliferation in states of lipodystrophy.

Adipogenesis is a complex process controlled by intrinsic and extrinsic factors that regulate preadipocyte proliferation, adipogenic capacity and maturation of metabolic function. Here we show that insulin and IGF-1 receptors are essential for mature adipocyte survival and that deletion of both IR and IGF1R specifically in fat using a tamoxifen inducible-AdipoQ-Cre (Ai-DKO) leads to rapid and severe loss of adipocytes in all depots, associated with a metabolic syndrome characterized by hypertriglyceridemia, hyperglycemia, hyperinsulinemia, fatty liver, and pancreatic beta cell proliferation. In this model, this pathological phenotype reverses over a few weeks, in large part, due to preadipocyte proliferation and adipose tissue regeneration. Incubation of preadipocytes with serum from the Ai-DKO mice in vitro stimulates cell proliferation, and this effect can be mimicked by conditioned media from liver slices of Ai-DKO mice, but not by media of cultured Ai-DKO adipocytes, indicating a hepatic origin of the growth factor. Proteomic analysis of serum reveals apolipoprotein C3 (APOC3), a protein secreted by liver, as one of the most upregulated proteins in the Ai-DKO mice. In vitro, purified and delipidated APOC3 stimulates preadipocyte proliferation, however, knockdown of hepatic APOC3 in vivo in Ai-DKO mice is not sufficient to block adipose regeneration. Thus, lipodystrophy is associated with presence of increased preadipocyte-stimulating growth factors in serum. Our study indicates that APOC3 is one contributing factor to preadipocyte proliferation, however, other still-unidentified circulating growth factors are also likely present in Ai-DKO mice. Identification of these factors may provide a new approach to regulation of adipose mass in health and disease.

Copper-Catalyzed anti-Selective Radical 1,2-Alkylarylation of Terminal Alkynes.

A copper-catalyzed highly anti-selective radical 1,2-alkylarylation of terminal alkynes with aryl boronic acids and alkyl bromides has been established. The reaction exhibits high compatibility with a wide range of terminal alkynes and diverse aryl boronic acids, thus providing facile access to various stereodefined trisubstituted alkenes in high yield under mild reaction conditions. Preliminary mechanistic investigations support the formation of alkyl radicals and their subsequent addition to alkynes in the reaction.

Circular RNA ERBB2 Contributes to Proliferation and Migration of Airway Smooth Muscle Cells via miR-98-5p/IGF1R Signaling in Asthma.

BACKGROUND: Asthma belongs to chronic inflammatory respiratory diseases characterized by airway inflammation and remodeling. Circular RNAs (circRNAs) are promising therapeutic targets for various diseases, including asthma. In this work, we aim to investigate the role of circular RNA Erb-B2 receptor tyrosine kinase 2 (circERBB2) during progression of asthma. METHODS: Human airway smooth muscle cells (ASMCs) were treated with platelet-derived growth factor BB (PDGF-BB) to mimic cell remodeling. The expression of circERBB2, microRNA-98-5p (miR-98-5p), and insulin-like growth factor 1 receptor (IGF1R) was measured by qRT-PCR. Cell proliferation, migration and apoptosis were determined by cell counting-8 (CCK-8), transwell, and flow cytometry. Protein levels of PCNA, MMP-9, IGF1R were evaluated using Western blotting. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA). Luciferase reporter gene experiment was adopted to evaluate the targeting relationship between miR-98-5p with circERBB2 and IGF1R. Interaction between RNAs was determined by RNA pulldown and RIP assay. RESULTS: The depletion of circERBB2 attenuated the proliferation, migration, and levels of inflammatory factors induced by PDGF-BB and cell apoptosis. CircERBB2 was identified to directly interact with miR-98-5p, and overexpression of miR-98-5p abolished the function of circERBB2 on PDGF-BB-stimulated ASMCs. IGF1R was identified as a target of miR-98-5p, and knockdown of IGF1R relieved the PDGF-BB-induced ASMCs proliferation and migration. CONCLUSION: Our work disclosed that knockdown of circERBB2 suppressed PDGF-BB-caused proliferation, migration and inflammatory response of ASMCs, through regulating miR-98-5p/IGF1R signaling, presented circERBB2 as a promising therapeutic target for asthma.