In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an ...uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance.
A copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes is realized, providing diverse tetrasubstituted chiral allenes. The utilization of the copper/chiral N,N,P‐ligand is crucial for the enantiocontrol over the allenyl radicals, which is difficult due to their elongated linear configuration that necessitates the stereo‐differentiation of remote motifs away from the reaction site.
Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the ...transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also impor- tant for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA （abscisic acid） and GAs （gibberellins） are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions （crosstalk） of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node.
The development of enantioconvergent cross‐coupling of racemic alkyl halides directly with heteroarene C(sp2)−H bonds has been impeded by the use of a base at elevated temperature that leads to ...racemization. We herein report a copper(I)/cinchona‐alkaloid‐derived N,N,P‐ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)−H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α‐chiral alkylated azoles, such as 1,3,4‐oxadiazoles, oxazoles, and benzodoxazoles as well as 1,3,4‐triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)−H bond and the involvement of alkyl radical species under the reaction conditions.
The use of a cinchona‐alkaloid‐derived N,N,P‐ligand leads to the direct enantioconvergent coupling of racemic alkyl bromides with azole C(sp2)−H bonds by copper catalysis. The key to success is the ligand‐enabled facile oxidative addition at approximately room temperature that suppresses product racemization at elevated temperature. This method provides a range of enantioenriched α‐chiral alkylated azoles.
In contrast with the well‐established C(sp2)−SCF3 cross‐coupling to forge the Ar−SCF3 bond, the corresponding enantioselective coupling of readily available alkyl electrophiles to forge chiral ...C(sp3)−SCF3 bond has remained largely unexplored. We herein disclose a copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of a range of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands through tuning electronic and steric effects for the simultaneous control of the reaction initiation and enantioselectivity. This strategy can successfully realize two types of asymmetric radical reactions, including enantioconvergent C(sp3)−SCF3 cross‐coupling of racemic benzyl halides and three‐component 1,2‐carbotrifluoromethylthiolation of arylated alkenes under mild reaction conditions. It therefore provides a highly flexible platform for the rapid assembly of an array of enantioenriched SCF3‐containing molecules of interest in organic synthesis and medicinal chemistry.
A copper‐catalyzed enantioselective radical C(sp3)−SCF3 coupling of secondary/tertiary benzyl radicals with the easily available (Me4N)SCF3 reagent was developed to afford enantioenriched trifluoromethylthiolated molecules. The key to the success lies in the utilization of chiral phosphino‐oxazoline‐derived anionic N,N,P‐ligands for the reaction initiation and enantioselectivity.
The digestive system cancers are leading cause of cancer‐related death worldwide, and have high risks of morbidity and mortality. More and more long non‐coding RNAs (lncRNAs) have been studied to be ...abnormally expressed in cancers and play a key role in the process of digestive system tumour progression. Plasmacytoma variant translocation 1 (PVT1) seems fairly novel. Since 1984, PVT1 was identified to be an activator of MYC in mice. Its role in human tumour initiation and progression has long been a subject of interest. The expression of PVT1 is elevated in digestive system cancers and correlates with poor prognosis. In this review, we illustrate the various functions of PVT1 during the different stages in the complex process of digestive system tumours (including oesophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and pancreatic cancer). The growing evidence shows the involvement of PVT1 in both proliferation and differentiation process in addition to its involvement in epithelial to mesenchymal transition (EMT). These findings lead us to conclude that PVT1 promotes proliferation, survival, invasion, metastasis and drug resistance in digestive system cancer cells. We will also discuss PVT1's potential in diagnosis and treatment target of digestive system cancer. There was a great probability PVT1 could be a novel biomarker in screening tumours, prognosis biomarkers and future targeted therapy to improve the survival rate in cancer patients.
Rolipram specifically inhibits phosphodiesterase (PDE) 4, thereby preventing inactivation of the intracellular second messenger cyclic adenosine monophosphate (cAMP). Rolipram has been shown to play ...a neuroprotective role in some central nervous system (CNS) diseases. However, the role of PDE4 and the potential protective effect of rolipram on the pathophysiological process of intracerebral haemorrhage (ICH) are still not entirely clear. In this study, a mouse model of ICH was established by the collagenase method. Rolipram reduced brain oedema, blood-brain barrier (BBB) leakage, neuronal apoptosis and inflammatory cytokine release and improved neurological function in our mouse model of ICH. Moreover, rolipram increased the levels of cAMP and silent information regulator 1 (SIRT1) and upregulated the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, these effects of rolipram could be reversed by the SIRT1 inhibitor sirtinol. In conclusion, rolipram can play a neuroprotective role in the pathological process of ICH by activating the cAMP/AMPK/SIRT1 pathway.
Cisplatin is commonly applied as anticancer agent for various cancers, including ovarian cancer. Unfortunately, the drug resistance frequently occurred which obstructing the effect of cisplatin on ...tumors. The goal of our research was to investigate the reversal actions and the potential mechanisms of sulforaphane (SFN) on cisplatin resistance in ovarian carcinoma.
The A2780 and IGROV1 cells and their cisplatin resistance cells A2780/CP70 and IGROV1-R10 were used in this study. Cell viability was detected by CCK-8. The DNA repair was measured by comet assay. The cisplatin transporter proteins were measured with western blotting. The concentration of intracellular cisplatin was detected by HPLC. The luciferase activity assay was applied to determine the target site of miR-30a-3p on the 3′UTR of ERCC1 and ATP7A. A2780/CP70 and IGROV1-R10 xenograft mouse model were established to confirm the antineoplastic action of SFN combined with cisplatin.
SFN reversed the resistance of A2780/CP70 and IGROV1-R10 ovarian carcinoma cells to cisplatin through inducing DNA damage and accumulation of intracellular cisplatin. SFN treatment notably increased miR-30a-3p expression, which was decreased in cisplatin-resistant cells. Moreover, overexpressed miR-30a-3p enhanced the sensitivity of A2780/CP70 and IGROV1-R10 cells to cisplatin treatment, and inhibiting miR-30a-3p activity abated the reversal actions of SFN on cisplatin resistance. The luciferase assay findings showed that miR-30a-3p binds to ERCC1 and ATP7A which are the key regulators for DNA repair and cisplatin transportation.
Our findings indicated that SFN could enhance cisplatin sensitivity of ovarian carcinoma cells through up-regulating miR-30a-3p to induce DNA damage and accumulation of intracellular cisplatin.
•Sulforaphane (SFN) reverses cisplatin resistance in ovarian cancer cells.•SFN and cisplatin combination inhibits DNA repair in ovarian cancer cells.•SFN and cisplatin combination increases cisplatin levels in ovarian cancer cells.•SFN up-regulates miR-30a-3p to induce DNA damage in ovarian cancer cells.•SFN up-regulates miR-30a-3p to increase cisplatin levels in ovarian cancer cells.
This study was performed to examine the epidemiological features of maxillofacial fracture, including the incidence, causes, age and sex distribution, methods of treatment, and prognosis, in a local ...area.A retrospective study was performed to investigate the epidemiological characteristics of 829 patients with maxillofacial fractures treated in a hospital in northern China from August 2011 to July 2019. Sex, age, etiology, fracture site, and treatment method were obtained from the medical records.The average age of all 829 patients was 36.1 years, and most patients were in the 20- to 29-year age group. The male to female ratio was 3.04:1.00. Traffic accidents were the main cause of the maxillofacial fractures. The mandible was the most commonly fractured bone, and the parasymphysis was the most frequently affected site. Head injury was the most common associated injury. Open surgery with internal fixation was the first-choice treatment for most cases.Traffic accidents were the main cause of maxillofacial fractures, followed by falling. Open surgery with internal fixation was the leading treatment choice. Both functional and esthetic outcomes should be considered in the treatment of maxillofacial fractures.
MicroRNAs (miRNAs) are small non-protein-codingRNAs that function as negative gene expression regulators. miRNA-210 (miR-210) has recently been recognized in the pathogenesis of osteonecrosis ...associated with angiogenesis. Herein we aimed to explore the clinical significance of miR-210 treatment for postmenopausal osteoporosis. The expression of miR-210 was detected in bone marrow mesenchymal stem cells (BMSCs) in vitro and miR-210 significantly promoted the expression of vascular edothelial growth factor (VEGF) in BMSCs in a time-dependent manner (p<0.05). And miR-210 suppressed PPARγ expression but increased the expression of ALP and osterix, demonstrating that miR-210 inhibited adipocyte differentiation and promoted osteoblast differentiation of BMSCs in vitro. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and VEGF in 17β-estradiol (E2) treated osteoblasts were significantly increased in a dose- and time-dependent manner (p<0.05). And E2 inducted the VEGF expression through the PI3K/AKT signaling pathway in osteoblasts. Taken together, these data implied that miR-210 played an important role in ameliorating the estrogen deficiency caused-postmenopausal osteoporosis through promotion the VEGF expression and osteoblast differentiation.
Reliable power transmission requires the safe operation of high‐voltage cable. A number of high‐voltage cable failures caused by aluminium sheath corrosion has been reported these years. However, ...neither discussion on factors influencing corrosion rate nor specification describing corrosion inhibiting method has been presented. Thus, it is crucial to address the research gap in evaluating corrosion rate of aluminium sheath in various corrosive environments. Here, the effect of chlorides on aluminium sheath corrosion is analyzed. Using scanning electron microscopy (SEM) and energy dispersive spectrometer (EDS), the corroded surface is investigated. Titration experiment is performed to quantify the chlorides content in buffer layer of cable. Polarization curves are employed to analyze the corrosion rate of aluminium sheath in different chlorides content environment. Surface analysis result shows that chlorine‐rich phase can be observed on the corroded surface. Titration experiment result reveals that buffer layer used in high voltage cable is one of the sources of chlorides content which varies from 0.7 to 4.2 wt%. Finally, polarization curve shows that when chloride content increases from 0.6 to 1.8 wt%, the pitting potential left shifts from −0.689 to −0.742 V. The corrosion resistance of aluminium sheath deteriorates significantly with the increase of chlorides content.
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