A comparison of urgent-start of hemodialysis vs urgent initiation of peritoneal dialysis: a meta-analysis study.

OBJECTIVE: To investigate the effects of urgent-start HD(USHD) and urgent-start PD(USPD) on dialysis patients and provide references for relevant clinical practice. METHODS: A literature search was conducted in Chinese and English databases (PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP) and the cutoff date for which was July 30, 2023. Studies comparing USHD and USPD were included and I2 statistics and Q tests were used to determine heterogeneity among them. Risk ratios (RR) with 95% confidence intervals (CI) were computed for count data. RESULTS: Nine studies met the inclusion criteria. The all-cause mortality rate was 0.173 (0.070, 0.277) for USPD versus 0.214 (0.142, 0.286) for USHD, indicating that USPD had a protective effect against all-cause mortality compared to USHD (RR = 0.76, 95% CI 0.63-0.91). Patients receiving USPD had lower risks of infection-related mortality (RR = 0.19; 95% CI 0.05-0.76), bacteremia (RR = 0.38; 95% CI 0.18-0.80), and composite complications (RR = 0.54; 95% CI 0.41-0.71). However, no significant differences were found between USHD and USPD for cardiovascular mortality (RR = 0.68; 95% CI 0.28-1.68) or cancer mortality (RR = 0.44; 95% CI 0.15-1.29). CONCLUSION: Compared to USHD, USPD has better protective effects against all-cause mortality, infection-related mortality, bacteremia, and composite complications. However, more high-quality research is still needed to further investigate the impacts of the two dialysis modalities on patients.

The diagnosis and treatment of pediatric clinical myocarditis in China: a multicenter retrospective study.

This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: • Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: • To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.

Clinical characteristics of pediatric hypertension: a multicenter study in China.

OBJECTIVES: Hypertension in children has attracted increasing attention. However, clinical-based studies investigating characteristics and secular trends of pediatric hypertension remain limited. This study aimed to investigate the clinical characteristics and secular trends of different types of hypertension among hospitalized children in China. METHODS: This retrospective analysis was based on medical records from nine tertiary children's hospitals in China during 2010∼2020. A total of 5847 pediatric inpatients (aged <18 years) with the diagnosis of hypertension were enrolled. Information on the clinical characteristics of each patient was obtained from their first admission records. RESULTS: During the past decade, secondary hypertension sustained to be the dominant type of hypertension in children, with the proportion increased from 51.2% during 2010∼2015 to 59.8% during 2016∼2020. The main causes of secondary hypertension were neurologic disorders in children aged 0∼2 years, which changed to renal diseases after 3 years of age. Compared with primary hypertension, secondary hypertension was common in girls (43.1 vs. 23.3%) and children under 5 years of age (32.2 vs. 2.1%). Moreover, over four-fifths of primary hypertensive individuals had obesity and obesity-related comorbidities, and the proportion of clusters of one or more comorbidities increased in the past decade (79.7 → 85.2%). CONCLUSION: Secondary hypertension sustained to be the dominant type of hypertension among children, especially in girls. Renal diseases were the most common causes of secondary hypertension in children, followed by rheumatic immune diseases. For primary hypertension, over four-fifths of inpatients had obesity and obesity-related diseases, and the proportion kept rising.

Case report: Catecholamine cardiomyopathy in children with neuroblastoma.

Introduction: Many endocrine diseases, such as neuroblastoma (NB), can be linked with acquired cardiomyopathy and heart failure. Neuroblastoma's cardiovascular manifestations are typically hypertension, electrocardiogram (ECG) changes, and conduction disturbances. Case Presentation: A 5-year-old 8-month-old girl was admitted to the hospital with ventricular hypertrophy and hypertension (HT) and heart failure. She had no previous history of HT. On color doppler echocardiography, the left atrium and left ventricle were enlarged. The left ventricular ejection fraction (EF) was as low as 40%, and the ventricular septum and left ventricular free wall were thickened. The internal diameters of both coronary arteries were widened. Abdominal computed tomography scan (CT) demonstrated an 8.7 cm × 7.1 cm × 9.5 cm tumor behind the left peritoneum. In urine catecholamines analysis, free-norepinephrine (f-NE), free-dopamine (f-DA), free-normetanephrine (f-NMN), free-3-methoxytyramine (f-3MT), vanillylmandelic acid (VMA), and homovanillic acid (HVA) levels were all greater than the normal range for 24 h except free-metanephrine (f-MN) and free-epinephrine (f-E). Based on these findings, we diagnosed her as NB complicated by catecholamine cardiomyopathy manifested by hypertrophic cardiomyopathy (HCM). Oral metoprolol, spironolactone, captopril and amlodipine furosemide, and intravenously injected sodium nitroprusside and phentolamine were employed for treating HT. After the tumor resection, the blood pressure (BP) and urinary catecholamine levels were all restored. After a follow-up of 7 months, echocardiography indicated normalization of ventricular hypertrophy and function. Conclusion: This is a rare report showing catecholamine cardiomyopathy in NB children. Tumor resection leads to a return to normal of the catecholamine cardiomyopathy manifested as HCM.

Antiproliferative Evaluation of Novel 4-Imidazolidinone Derivatives as Anticancer Agent Which Triggers ROS-Dependent Apoptosis in Colorectal Cancer Cell.

Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and more therapies are needed to treat CRC. To discover novel CRC chemotherapeutic molecules, we used a series of previously synthesized novel imidazolidin-4-one derivatives to study their anticancer role in several cancer cell lines. Among these compounds, compound 9r exhibited the best anticancer activity in CRC cell lines HCT116 and SW620. We further investigated the anticancer molecular mechanism of compound 9r. We found that compound 9r induced mitochondrial pathway apoptosis in HCT116 and SW620 cells by inducing reactive oxygen species (ROS) production. Moreover, the elevated ROS generation activated the c-Jun N-terminal kinase (JNK) pathway, which further accelerated apoptosis. N-acetylcysteine (NAC), an antioxidant reagent, suppressed compound 9r-induced ROS production, JNK pathway activation, and apoptosis. Collectively, this research synthesized a series of imidazolidin-4-one derivatives, evaluated their anticancer activity, and explored the molecular mechanism of compound 9r-induced apoptosis in CRC cells. The present results suggest that compound 9r has a potential therapeutic role in CRC. Hence, it deserves further exploration as a lead compound for CRC treatment.

Analysis of Anti-Arrhythmic Impacts of Crocin through Estimation of Expression of Cx43 in Myocardial Infarction Using a Rat Animal Model.

Arrhythmia is an important cause of death after myocardial infarction (MI). Different substances have been evaluated for their anti-arrhythmic effect in MI. This study was performed to evaluate the anti-arrhythmic impacts of crocin in an MI animal model (rat) by estimation of the expression of connexin 43 (Cx43). Fifty male Sprague-Dawley rats were grouped into 5 groups, each composed of 10 rats. The first group was regarded as the normal control group and the second one was considered as the MI group, which was caused by ligation of the left anterior descending artery. The other three groups received crocin 50 or 10 mg/kg/day or metoprolol 100 mg/kg/day for 1 week, following ligation of the left anterior descending artery. Evaluated outcomes were cardiac Cx43 expression, arrhythmia incidence, histological findings, and myocyte resting potential. Crocin-treated MI groups showed a significantly lower arrhythmia score than the non-treated MI group, 10 mg/kg/day (1.85 ± 0.55, p < 0.01) and 50 mg/kg/day (1.70 ± 0.33, p < 0.01). Groups that received crocin 10 mg/kg/day (66.30 ± 2.59, p < 0.01), crocin 50 mg/kg/day (68.10 ± 2.43, p < 0.01), and metoprolol 100 mg/kg/day (-63.54 ± 0.63 mV, p < 0.01) significantly prevented depolarization in comparison with the non-treated MI group. Expression of Cx43 mRNA in crocin 10 mg/kg/day (1.54 ± 0.24, p < 0.01), crocin 50 mg/kg/day (1.73 ± 0.09, p < 0.01), and metoprolol 100 mg/kg/day (1.75 ± 0.14, p < 0.01) treatment groups was significantly higher in comparison with the non-treated MI group. Crocin showed a preventive effect on the arrhythmogenic impact of MI in an experimental model of ischemic injury through an increase in expression of Cx43.

Microscopic Imaging Technology Assisted Dynamic Monitoring and Restoration of Micron-Level Cracks in the Painted Layer of Terracotta Warriors and Horses of the Western Han Dynasty.

Cracks are one of the most common issues affecting colored pottery relics; these can be divided into macroscopic cracks, recognizable by the human eye, and micron cracks, which cannot be observed by the naked eye. The gradual development of micron cracks eventually leads to large-scale cracks and the shedding of the coating layer. The repair of such micron cracks poses a key technical difficulty in restoring painted pottery remnants from the Western Han Dynasty. We attempt to solve this problem by reporting on a method that entails the use of a water-borne fluoropolymer material as the adhesive agent, as well as ultra-depth-of-field, digital microscopic imaging technology to build an operating platform for an optical imaging monitoring system. By making simulated ceramic samples, we systematically investigated the influences of water-borne fluoropolymer on chromaticity, adhesion, contact angle, surface morphology, and thermal stability of the paint layer. The results indicate that the color of the painted layer, when treated with the water-borne fluoropolymer, did not change, and the adhesion and contact angle of the painted layer were improved. Additionally, the outcomes of the SEM analysis show that the adhesion and hydrophobicity of the painted layer were improved because the water-borne fluoropolymer filled up the porous structure of the painted layer and covered the pigment particles. These findings demonstrate that aqueous, water-borne fluoropolymer can be used as an adhesive agent for micron cracks. Meanwhile, via the operating platform of the optical imaging monitoring system, the micron cracks of the painted terracotta warriors and horses from the Western Han Dynasty were successfully repaired using the water-borne fluoropolymer. The results imply that the microstructure, size, and geometric spaces of the cracks can be obtained directly utilizing microscopic imaging technology. The dynamic monitoring and imaging system described above can be employed to assist prosthetists in visualizing micro-repair operations in real time, assist with fine visual operations during the repair process, and realize dynamic video recording of the entire repair process. Our work provides a simple visualization method to repair micron-scale cracks in painted pottery relics by applying modern fluoropolymer and ultra-depth-of-field digital microscopic imaging technology.

An Essential Role of Gelatin in the Formation Process of Curling in Long Historical Photos.

Curling disease in long historical photos significantly affects the presentation of cultural heritage information. However, people lack attention to the formation process and microstructural changes of photo curling. In this article, a long historical photo (1912-1949 AD) collected by the Second Historical Archives of China was taken as the research object, and the formation process and cause of the curling were further explored. Firstly, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), X-ray energy disperse spectrometer (EDS), and other instruments were used to analyze the material composition of the long historical photo. It was found that the photographic paper was made of gelatin, barium sulfate, and plant fiber layers. Then, the effects of hygrothermal environments on curling and contraction in the gelatin layer and simulated photographic paper were explored. Meanwhile, the formation process and main influence factors of the curling were preliminarily revealed. The morphological analysis by SEM was carried out to identify the inner correlation between the microstructure and curling of photos. Finally, the possible formation cause of photo curling was analyzed. This study provides a scientific basis and experimental data for the preservation and restoration of long historical photos based on gelatin.

The Protective Role of Cirsilineol against Ovalbumin-Induced Allergic Rhinitis in Mice by Suppression of Inflammation and Oxidative Stress.

Allergic rhinitis (AR) is a common type of inflammatory disease with symptoms including rhinorrhea, fatigue, sneezing, and disturbed sleep. AR affects nearly 40% of peoples worldwide with the increased numbers of new cases. In this work, the study was conducted to disclose the anti-inflammatory and antiallergic properties of cirsilineol against the ovalbumin (OVA)-sensitized AR in mice. AR was provoked in BALB/c mice through the OVA challenge 30 days along with 10 and 20 mg/kg of cirsilineol treatment. The nasal symptoms, i.e., rubbing and sneezing was monitored after the final OVA challenge. The status of OVA-specific IgE, PGD2, and LTC4 was investigated using assay kits. The status of pro-inflammatory markers also examined using assay kits. The levels of oxidative markers, SOD activity, and pro-inflammatory markers in the spleen mononuclear cells (SMEs) were studied by using respective assay kits. The mRNA expression of TXNIP was assessed using RT-PCR study. The 10 and 20 mg/kg of cirsilineol treatment effectively decreased the sneezing and nasal rubbings in OVA-provoked mice. Cirsilineol also decreased the IgE, PGD2, and LTC4 status in the AR animals. The status of pro-inflammatory markers, i.e., IL-4, IL-5, IL-6, IL-33 and TNF-α was found to be decreased in the cirsilineol administered AR mice. Cirsilineol effectively reduced the ROS and MDA and improved SOD in the OVA-challenged SMCs. The mRNA expression of TXNIP was appreciably suppressed by the cirsilineol treatment. Altogether, these findings proved the beneficial actions of cirsilineol against the OVA-triggered AR in mice. The additional studies on the cirsilineol could lead to the development of new drug for AR management.

A Myocardial Segmentation Method Based on Adversarial Learning.

Congenital heart defects (CHD) are structural imperfections of the heart or large blood vessels that are detected around birth and their symptoms vary wildly, with mild case patients having no obvious symptoms and serious cases being potentially life-threatening. Using cardiovascular magnetic resonance imaging (CMRI) technology to create a patient-specific 3D heart model is an important prerequisite for surgical planning in children with CHD. Manually segmenting 3D images using existing tools is time-consuming and laborious, which greatly hinders the routine clinical application of 3D heart models. Therefore, automatic myocardial segmentation algorithms and related computer-aided diagnosis systems have emerged. Currently, the conventional methods for automatic myocardium segmentation are based on deep learning, rather than on the traditional machine learning method. Better results have been achieved, however, difficulties still exist such as CMRI often has, inconsistent signal strength, low contrast, and indistinguishable thin-walled structures near the atrium, valves, and large blood vessels, leading to challenges in automatic myocardium segmentation. Additionally, the labeling of 3D CMR images is time-consuming and laborious, causing problems in obtaining enough accurately labeled data. To solve the above problems, we proposed to apply the idea of adversarial learning to the problem of myocardial segmentation. Through a discriminant model, some additional supervision information is provided as a guide to further improve the performance of the segmentation model. Experiment results on real-world datasets show that our proposed adversarial learning-based method had improved performance compared with the baseline segmentation model and achieved better results on the automatic myocardium segmentation problem.

A Novel Imidazopyridine Derivative Exhibits Anticancer Activity in Breast Cancer by Inhibiting Wnt/ß­catenin Signaling.

BACKGROUND: Breast cancer exhibits poor prognosis and high relapse rates following chemotherapy therapeutics. Thus, this study aims to develop effective novel agents regulating the core molecular pathway of breast cancer such as Wnt/ß-catenin signaling. METHODS: The present study screened a novel inhibitor, called "C188", using MTT assay. The molecular formula of C188 is C21H15FN4O3 and the molecular weight is 390. Flow cytometry and Western blotting were employed to assess cell cycle arrest after treatment with C188. Wound-healing and transwell assays were applied to measure the cell migration and invasion viability. The regulatory effects of C188 on Wnt/ß­catenin signaling and localization of ß­catenin in the nucleus were investigated by Western blotting and immunofluorescence. RESULTS: We found that C188 significantly suppressed proliferation and growth in a dose- and time-dependent manner in breast cancer cells, but not in normal breast cells. The inhibitory effect was caused by cell cycle arrest at the G1-phase which is induced by C188 treatment. Additionally, C188 dramatically inhibited cell migration of breast cancer cells in a dose-dependent manner. The migration inhibition was attributed to the suppression of Wnt/ß­catenin signaling and localization of ß­catenin in the nucleus mediated by regulating phosphorylation of ß­catenin and its subsequent stability. Furthermore, the target genes, including Axin 2, c-JUN, and c-Myc, were downregulated due to the decrease of ß­catenin in the nucleus after exposure to C188. CONCLUSION: C188 treatment resulted in the downregulation of cyclin D which led to cell cycle arrest at the G1 phase, and the inhibition of cell migration, indicating that C188 may be an effective novel therapeutic candidate as a potential treatment for human breast cancer.

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis.

BACKGROUND: Cancer remains a major clinical challenge because of the lack of effective drug for its treatment. To find out novel cancer chemotherapeutic molecules, we explored the anticancer effect of novel imidazopyridine compound 9i and also investigated the underlying molecular mechanism. METHODS: Human cervical cancer cell (HeLa) viability was measured by an MTT assay after treatment with compound 9i. Clonogenicity of HeLa cells was investigated by an in vitro colony formation assay. Cell death was visualized by propidium iodide (PI) staining. Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and mitochondrial membrane potential in HeLa cells. The expression level of apoptosis-related proteins was also determined by western blot. RESULTS: Compound 9i suppressed HeLa cell viability in a time- and dose-dependent manner. Compound 9i induced mitochondrial outer membrane permeabilization (MOMP), activated caspase cascade, and finally resulted in apoptosis. CONCLUSION: Compound 9i induces mitochondrial pathway-mediated apoptosis in human cervical cancer cells, suggesting that 9i could be a potential lead compound to be developed as a cancer therapeutic molecule.

Acylation of the antimicrobial peptide CAMEL for cancer gene therapy.

Obtaining ideal gene delivery vectors is still a major goal in cancer gene therapy. CAMEL, a short hybrid antimicrobial peptide, can kill cancer cells by membrane lysis. In this study, we constructed a series of non-viral vectors by attaching fatty acids with different chain lengths to the N-terminus of CAMEL. Our results showed that the cellular uptake and transfection efficiency of acyl-CAMEL started to significantly increase from a chain length of 12 carbons. C18-CAMEL was screened for gene delivery because it had the highest transfection efficiency. Surprisingly, C18-CAMEL/plasmid complexes displayed strong endosomal escape activity after entering cells via endocytosis. Importantly, C18-CAMEL could deliver p53 plasmids to cancer cells and significantly inhibited cell proliferation by the expression of p53. In addition, the C18-CAMEL/p53 plasmid complexes and the MDM2 inhibitor nutlin-3a showed significantly synergistic anticancer activity against MCF-7 cells expressing wild-type p53. Conclusively, our study demonstrated that conjugation of stearic acid to antimicrobial peptides is a simple and successful approach for constructing efficient and economical non-viral vectors for cancer gene therapy.

DNA branched junctions induced the enhanced fluorescence recovery of FAM-labeled probes on rGO for detecting Pb2.

The reduced graphene oxide (rGO) could strongly adsorb and quench the fluorescence of dye-labeled single-stranded DNA (ssDNA); thus, it is widely applied in fluorescent sensors. However, these sensors may suffer from a limited sensitivity due to the low fluorescence recovery when adding the complementary DNA (cDNA) sequence. In this work, the powerful DNA branched junctions were constructed to improve the fluorescence recovery of FAM-labeled probe on rGO. In the presence of target Pb2+, the ribonucleotide (rA) in the substrate was cleaved specifically and the catalytic hairpin assembly of three metastable hairpins was further initiated, accompanied by the formation of DNA branched junctions. Then, the liberated Pb2+ could be recyclable. Impressively, the DNA branched junctions not only hybridize with the FAM-labeled probes with a high efficiency, but also are significantly undesirable for the rGO. Thus, a high fluorescence recovery of FAM-labeled probe on rGO was expected. The integration of the high fluorescence recovery and dual-cycle signal amplification endows the sensing strategy with a good performance for Pb2+ detection, including low detection limit (0.17 nM), good selectivity, and satisfactory practical applicability. The proposed DNA branched junctions offer a novel avenue to improve the fluorescence recovery of the dye-labeled probes on rGO for biological analysis.

Facile and Scalable Conservation of Chinese Ancient Paintings Using Water-Borne Fluoropolymer.

In China, alum-gelatin aqueous solution is historically used to prevent falling off of mineral pigments from paintings and to enhance strength of their paper matrices in the restoration process. However, after a long period of time of preservation, alum-gelatin aqueous solution applied to paintings will hydrolyze and produce free acid, which accelerates aging. To resolve this issue, instead of using alum-gelatin aqueous solution, here we report a new method of using a water-borne fluoropolymer coating to protect paintings. This coating is applied to simulated paintings, and their influences are systematically examined on the antipeeling property of pigment, mechanical properties, thermal stability, chromaticity, surface morphology, and water contact angle. Our results show that the applied coating slightly affects the appearance of the painting without falling off of pigment observed. Moreover, the coating increases the tensile strength and folding endurance of the paper because the polymer fills into the porous structure of paper fibers and covers pigment particles from SEM analysis. The treated painting retains moderate hydrophilicity, which facilitates removal of degradation substances from the paintings by water cleaning and the subsequent mounting procedure. Moreover, this coating is successfully applied to repairing a set of real ancient Chinese paintings of Yuan Dynasty (1271∼1368 A.D.), with practical acceptance. Our work provides a facile yet effective solution to conservation of ancient paintings by applying the modern fluoropolymers.

A Derivate of Benzimidazole-Isoquinolinone Induces SKP2 Transcriptional Inhibition to Exert Anti-Tumor Activity in Glioblastoma Cells.

We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.

Diversity-Oriented Synthesis of Imidazo-Dipyridines with Anticancer Activity via the Groebke-Blackburn-Bienaymé and TBAB-Mediated Cascade Reaction in One Pot.

A facile and metal-free one-pot protocol for the synthesis of fused imidazopyridine scaffolds has been developed. This novel protocol combines the Groebke-Blackburn-Bienaymé reaction (GBBR) with a sequential TBAB-mediated cyclization cascade. Biological evaluation demonstrated that compound 6a inhibits human prostate cancer cell DU-145 proliferation with an IC50 of 1.6 µM. The molecular mechanism study indicates that 6a significantly suppresses the oncogenic Erk kinase phosphorylation at 3 µM.