Electrolyte-Salts Regulated Hydrogen-Bonding Configuration and Interphase Formation Achieving Highly Stable Anode for Rechargeable Aqueous Sodium-Ion Batteries.

Hydrogen evolution reactions that cause the alkalization of aqueous electrolytes generally frustrate the structural stability and cycling performance of NaTi2(PO4)3/C anode material for rechargeable aqueous sodium-ion batteries (ASIBs). Herein, a novel highly concentrated electrolyte with a large hydrogen-evolution overpotential and hydroxide-capture ability is rationally established by incorporating a bifunctional Mg(Ac)2 additive into a concentrated NaAc aqueous solution. The highly concentrated electrolyte salts (4m NaAc+3m Mg(Ac)2) favor regulation on hydrogen-bonding configurations and kinetically shift the hydrogen evolution potential to a lower value of -1.37 V (vs Ag/AgCl). The Mg(Ac)2 additive plays particular roles in spontaneously capturing hydroxide ions generated during hydrogen evolution reactions on anode surfaces and simultaneously forming a protective Mg(OH)2-like interphase. As a result, the unique electrolyte significantly improves the structural stability and cycling performance of NaTi2(PO4)3/C anode (94.8% capacity retention after 100 cycles at 100 mA·g-1). The effect of salt concentration on hydrogen bonding configurations of aqueous electrolytes is investigated with Raman spectroscopy and FTIR spectroscopy. The interphase is identified by coupling EDS mapping, X-ray photoelectron spectroscopy, and X-ray diffraction. This work provides a new strategy for improving the cycling stability of aqueous sodium-ion batteries.

PKP2 induced by YAP/TEAD4 promotes malignant progression of gastric cancer.

Gastric cancer (GC) exhibits significant heterogeneity and its prognosis remains dismal. Therefore, it is essential to investigate new approaches for diagnosing and treating GC. Desmosome proteins are crucial for the advancement and growth of cancer. Plakophilin-2 (PKP2), a member of the desmosome protein family, frequently exhibits aberrant expression and is strongly associated with many tumor types' progression. In this study, we found upregulation of PKP2 in GC. Further correlation analysis showed a notable association between increased PKP2 expression and both tumor stage and poor prognosis in individuals diagnosed with gastric adenocarcinoma. In addition, our research revealed that the Yes-associated protein1 (YAP1)/TEAD4 complex could stimulate the transcriptional expression of PKP2 in GC. Elevated PKP2 levels facilitate activation of the AKT/mammalian target of rapamycin signaling pathway, thereby promoting the malignant progression of GC. By constructing a mouse model, we ultimately validated the molecular mechanism and function of PKP2 in GC. Taken together, these discoveries suggest that PKP2, as a direct gene target of YAP/TEAD4 regulation, has the potential to be used as an indication of GC progression and prognosis. PKP2 is expected to be a promising therapeutic target for GC.

Platycodin D2 enhances P21/CyclinA2-mediated senescence of HCC cells by regulating NIX-induced mitophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) cells usually show strong resistance to chemotherapy, which not only reduces the efficacy of chemotherapy but also increases the side effects. Regulation of autophagy plays an important role in tumor treatment. Cell senescence is also an important anti-cancer mechanism, which has become an important target for tumor treatment. Therefore, it is of great clinical significance to find anti-HCC drugs that act through this new mechanism. Platycodin D2 (PD2) is a new saponin compound extracted from the traditional Chinese medicine Platycodon grandiflorum. PURPOSE: Our study aimed to explore the effects of PD2 on HCC and identify the underlying mechanisms. METHODS: First, the CCK8 assay was used to detect the inhibitory effect of PD2 on HCC cells. Then, different pathways of programmed cell death and cell cycle regulators were measured. In addition, we assessed the effects of PD2 on the autophagy and senescence of HCC cells by flow cytometry, immunofluorescence staining, and Western blotting. Finally, we studied the in vivo effect of PD2 on HCC cells by using a mouse tumor-bearing model. RESULTS: Studies have shown that PD2 has a good anti-tumor effect, but the specific molecular mechanism has not been clarified. In this study, we found that PD2 has no obvious toxic effect on normal hepatocytes, but it can significantly inhibit the proliferation of HCC cells, induce mitochondrial dysfunction, enhance autophagy and cell senescence, upregulate NIX and P21, and downregulate CyclinA2. Gene silencing and overexpression indicated that PD2 induced mitophagy in HCC cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence. CONCLUSIONS: These results indicate that PD2 induces HCC cell death through autophagy and aging. Our findings provide a new strategy for treating HCC.

Evidence of a large current of transcranial alternating current stimulation directly to deep brain regions.

Deep brain regions such as hippocampus, insula, and amygdala are involved in neuropsychiatric disorders, including chronic insomnia and depression. Our recent reports showed that transcranial alternating current stimulation (tACS) with a current of 15 mA and a frequency of 77.5 Hz, delivered through a montage of the forehead and both mastoids was safe and effective in intervening chronic insomnia and depression over 8 weeks. However, there is no physical evidence to support whether a large alternating current of 15 mA in tACS can send electrical currents to deep brain tissue in awake humans. Here, we directly recorded local field potentials (LFPs) in the hippocampus, insula and amygdala at different current strengths (1 to 15 mA) in 11 adult patients with drug-resistant epilepsy implanted with stereoelectroencephalography (SEEG) electrodes who received tACS at 77.5 Hz from 1 mA to 15 mA at 77.5 Hz for five minutes at each current for a total of 40 min. For the current of 15 mA at 77.5 Hz, additional 55 min were applied to add up a total of 60 min. Linear regression analysis revealed that the average LFPs for the remaining contacts on both sides of the hippocampus, insula, and amygdala of each patient were statistically associated with the given currents in each patient (p < 0.05-0.01), except for the left insula of one subject (p = 0.053). Alternating currents greater than 7 mA were required to produce significant differences in LFPs in the three brain regions compared to LFPs at 0 mA (p < 0.05). The differences remained significant after adjusting for multiple comparisons (p < 0.05). Our study provides direct evidence that the specific tACS procedures are capable of delivering electrical currents to deep brain tissues, opening a realistic avenue for modulating or treating neuropsychiatric disorders associated with hippocampus, insula, and amygdala.

Unlock the C-N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation.

The C-N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence of trifluoromethanesulfonic acid (TfOH). The method enables the practical synthesis of valuable enamides without the use of any metal reagent. In addition, this transamidation protocol can also be expanded to the reactions of sulfonamides, and the late-stage functionalization on sulfonamide drugs such as Celecoxib and Valdecoxib has been verified. Moreover, the participation of water in assisting the transamidation process has been identified by the isotope labeling experiments using D2O, disclosing a new possibility in designing catalytic tactic to other transamidation reactions.

Cascade [3 + 2] Annulation of 1,3-Dicarbonyl Compounds and Ethyl Secondary Amines for Pyrrole Synthesis via Poly C(sp3)-H Bond Functionalization.

The synthesis of polyfunctionalized pyrroles via the cascade reactions of 1,3-dicarbonyl compounds and two molecules of ethyl secondary amines has been realized via simple iodine catalysis in the presence of Dess-Martin periodinane (DMP). The formation of the target pyrrole products involves the formation of one new C-C and two new C-N bonds via the major functionalization of six C(sp3)-H bonds, presenting a highly novel and efficient synthetic protocol toward pyrrole scaffolds.

Transition-Metal-Free C-H Trifluoromethylthiolation of N,N-Disubstituted Enaminones To Access CF3S-Functionalized Enaminones and Their Application in the Synthesis of CF3S-Heteroaryls.

The α-C-H trifluoromethylthiolation of N,N-disubstituted enaminones has been achieved with simple and cheap CF3SO2Na as the CF3S source. The reactions were run at mild temperature (0 °C to rt) using POCl3 as the only reducing reagent. The work represents the first example on the synthesis of α-trifluoromethylthio enaminones via direct C-H functionalization. In addition, the resulting CF3S-functionalized enaminones have been proven as useful building blocks in the synthesis of various CF3S-functionalized heteroaromatic compounds by simple annulation reactions.

Iridium-catalyzed reduction of o-hydroxyl phenyl enaminones for the synthesis of propiophenones and their application in 3-methyl chromone synthesis.

A method of reducing o-hydroxyphenyl enaminones with silane as the reductant to provide o-hydroxyl propiophenones has been achieved with iridium catalysis. The reduction reactions were found to proceed via the assistance of the hydroxyl group in the phenyl ring. In addition, the o-hydroxyl propiophenone products were used for the easy synthesis of 3-methyl chromones by directly incorporating N,N-dimethyl formamide dimethyl acetal (DMF-DMA) without using any catalyst.

Hyperbaric oxygen therapy alleviates intestinal dysfunction following traumatic brain injury via m6A regulation.

Hyperbaric oxygen (HBO) therapy can attenuate neurological impairment after traumatic brain injury (TBI) and alleviate intestinal dysfunction. However, the role and mechanism of HBO therapy in intestinal dysfunction following TBI remain unclear. Herein, by establishing a mouse model of controlled cortical impact (CCI), we found that HBO therapy reduced histopathological lesions and decreased the levels of inflammatory and oedema proteins in the intestinal tissues of mice 10 days after TBI. We also showed that HBO therapy improved microbiome abundance and probiotic (particularly g_Bifidobacterium) colonisation in mice post-CCI. Then, we identified that the m6A level imcreased notably in injured cortical tissue of CCI+HBO group compared with the CCI group following CCI. Thus, our results suggested that HBO therapy could alleviate TBI-induced intestinal dysfunction and m6A might participate in this regulation process, which provides new insights for exploring the specific mechanism and targets of HBO in the treatment of intestinal dysfunction after TBI, thereby improving the therapeutic effect of HBO.

Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions. METHODS: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity. RESULTS: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively. CONCLUSION: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

The correlation between anti-phospholipase A2 receptor antibodies and hypercoagulability in patients with idiopathic membranous nephropathy.

BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Diagnostic accuracy of qualitative and quantitative magnetic resonance imaging-guided contrast-enhanced ultrasound (MRI-guided CEUS) for the detection of prostate cancer: a prospective and multicenter study.

PURPOSE: To evaluate the diagnostic value of MRI-guided contrast-enhanced ultrasound (CEUS) for prostate cancer (PCa) diagnosis, and characteristics of PCa in qualitative and quantitative CEUS. MATERIAL AND METHODS: This prospective and multicenter study included 250 patients (133 in the training cohort, 57 in the validation cohort and 60 in the test cohort) who underwent MRI, MRI-guided CEUS and prostate biopsy between March 2021 and February 2023. MRI interpretation, qualitative and quantitative CEUS analysis were conducted. Multitree extreme gradient boosting (XGBoost) machine learning-based models were applied to select the eight most important quantitative parameters. Univariate and multivariate logistic regression models were constructed to select independent predictors of PCa. Diagnostic value was determined for MRI, qualitative and quantitative CEUS using the area under receiver operating characteristic curve (AUC). RESULTS: The performance of quantitative CEUS was superior to that of the qualitative CEUS and MRI in predicting PCa. The AUC was 0.779 (95%CI 0.70-0.849), 0.756 (95%CI 0.638-0.874) and 0.759 (95%CI 0.638-0.879) of qualitative CEUS, and 0.885 (95%CI 0.831-0.940), 0.802 (95%CI 0.684-0.919) and 0.824 (95%CI 0.713-0.936) of quantitative CEUS in training, validation and test cohort, respectively. Compared with quantitative CEUS, MRI achieved less well performance for AUC 0.811 (95%CI 0.741-0.882, p = 0.099), 0.748 (95%CI 0.628-0.868, p = 0.539) and 0.737 (95%CI 0.602-0.873, p = 0.029), respectively. Moreover, the highest specificity of 80.6% was obtained by quantitative CEUS. CONCLUSION: We developed a reliable method of MRI-guided CEUS that demonstrated enhanced performance compared to MRI. The qualitative and quantitative CEUS characteristics will contribute to improved diagnosis of PCa.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Intracerebral lentiviral ABCD1 gene therapy in an early disease onset ALD mouse model.

X-linked adrenoleukodystrophy (ALD) is a genetic disorder of the ABCD1 gene. We aimed to treat ALD via direct intracerebral injection of lentiviral ABCD1 (LV.ABCD1). Lentiviral vectors (LVs) were injected into the brain of wild type mice to access toxicities and biodistribution. Confocal microscopy illustrated supraphysiological ABCD1 expression surrounding the injection sites, and LVs were also detected in the opposite site of the unilaterally injected brain. In multi-site bilateral injections (4, 6, 8, and 9 sites), LV.ABCD1 transduced most brain regions including the cerebellum. Investigation of neuronal loss, astrogliosis and microglia activation did not detect abnormality. For efficacy evaluation, a novel ALD knockout (KO) mouse model was established by deleting exons 3 to 9 of the ABCD1 gene based on CRISPR/Cas9 gene editing. The KO mice showed behavioral deficit in open-field test (OFT) and reduced locomotor activities in rotarod test at 6 and 7 months of age, respectively. We treated 3-month-old KO mice with bilateral LV.ABCD1 injections into the external capsule and thalamus. ABCD1 expression was detected 15 days later, and the impaired motor ability was gradually alleviated. Our studies established an early onset ALD model and illustrated neurological improvement after LV.ABCD1 intracerebral injection without immunopathological toxicity.

Helicobacter pylori-induced aberrant demethylation and expression of GNB4 promotes gastric carcinogenesis via the Hippo-YAP1 pathway.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. METHODS: The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. RESULTS: GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746-179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo-YAP1 pathway in both in vitro and in vivo models. CONCLUSIONS: Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

Effectiveness and Accuracy of MRI-Ultrasound Fusion Targeted Biopsy Based on PI-RADS v2.1 Category in Transition/Peripheral Zone of the Prostate.

BACKGROUND: MRI-ultrasound fusion targeted biopsy (MRI-TBx) improves the clinically significant prostate cancer (csPCa) detection with fewer cores. However, whether systematic biopsy-guided by transrectal ultrasound (TRUS-SBx) can be omitted when undergoing MRI-TBx in transition zone (TZ) and peripheral zone (PZ) remains unclear. PURPOSE: To assess the performance and effectiveness of MRI-TBx based on PI-RADS v2.1 for csPCa diagnosis in TZ and PZ, respectively. STUDY TYPE: Retrospective. SUBJECTS: A total of 309 selected cases (median age 70 years) with 356 lesions who underwent both MRI-TBx and TRUS-SBx were enrolled. FIELD STRENGTH/SEQUENCE: A 3.0 T, multiparametric MRI (mp-MRI) including T2-weighted turbo-spin echo imaging (T2WI), diffusion-weighted spin-echo echo planar imaging (DWI), dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging (DCE). ASSESSMENT: Mp-MRI was assessed by two radiologists using PI-RADS v2.1. The csPCa detection rates provided by MRI-TBx, TRUS-SBx and combined biopsy in TZ and PZ were calculated, respectively. STATISTICAL TESTS: McNemar test was used to compare the csPCa detection rates in TZ and PZ, respectively. The frequencies and distribution of all detected prostate cancers by different biopsy methods were also compared. P < 0.05 was considered statistically significant. RESULTS: Among 356 lesions in 309 patients, 208 (68 in TZ, 140 in PZ) were pathologically confirmed as csPCa. In TZ, there were significant differences for csPCa detection with PI-RADS 3 between combined biopsy and TRUS-SBx (23.5% vs. 15.3%), MRI-TBx (23.5% vs. 16.3%), respectively. MRI-TBx detected 23% (19/83) cases missed by TRUS-SBx in which 68% (13/19) were csPCa. In PZ, there were no statistical differences between MRI-TBx and combined biopsy with PI-RADS 3-5 (P = 0.21, 0.25, 0.07, respectively). In 9% (14/152) cases only detected by MRI-TBx, 86% (12/14) were clinically significant. Five percent (7/152) of cases only detected by TRUS-SBx were completely nonclinically significant. DATA CONCLUSION: MRI-TBx played a positive role on csPCa diagnosis in TZ, but combined biopsy might be the best choice especially in the subgroup PI-RADS 3. In PZ, MRI-TBx had an advantage over TRUS-SBx for csPCa detection. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Cascade in Situ Iodination, Chromone Annulation, and Cyanation for Site-Selective Synthesis of 2-Cyanochromones.

A facile cascade reaction for the site selective synthesis of 2-cyanochromones is described. By using simple o-hydroxyphenyl enaminones and potassium ferrocyanide trihydrate (K4[Fe(CN)6]3·3H2O) as starting materials and I2/AlCl3 as promoters, the products are furnished via tandem chromone ring formation and C-H cyanation. The in situ formation of 3-iodochromone and a formal 1,2-hydrogen atom transfer (HAT) process account for the unconventional site selectivity. In addition, the synthesis of 2-cyanoquinolin-4-one has been realized by employing corresponding 2-aminophenyl enaminone as substrate.

Synergistic Visible Light and Pd-Catalyzed C-H Alkylation of 1-Naphthylamines with α-Diazoesters.

The combination of visible light irradiation and Pd-catalysis has been practically employed for the C-H alkylation reactions of naphthylamines and α-diazo esters, leading to the synthesis of α-naphthyl functionalized acetates via C-C bond construction under mild reaction conditions and under solvent-free conditions. The light irradiation has been proven to play a pivotal role in the reactions, probably by promoting the generation of active carbene species from α-diazo esters.

Catalyst-Free Cascade Annulation of Enaminones and Aryl Diazonium Tetrafluoroboronates for Cinnoline Synthesis and the Anti-Inflammatory Activity Study.

A simple and concise method for the synthesis of cinnolines has been developed by the reactions of readily available enaminones and aryl diazonium tetrafluoroboronates. The reactions run efficiently to provide cinnolines with broad diversity in the substructure by heating in dimethyl sulfoxide without using any catalyst or additive. In addition, the primary investigation of the anti-inflammatory activity of these products leads to the observation of p-chlorobenzoyl (3f) and p-nitrobenzoyl (3j) cinnolines as attractive anti-inflammatory compounds in vitro.

Three-Component Fusion to Pyrazolo[5,1-a]isoquinolines via Rh-Catalyzed Multiple Order Transformation of Enaminones.

A facile and practical method for the synthesis of fused tricyclic pyrazolo[5,1-a]isoquinolines has been realized via the reactions of enaminones, hydrazine hydrochloride, and internal alkynes. By means of Rh catalysis, the extraordinary high-order bond functionalization, including the transformation of aryl C-H, ketone C═O, and alkenyl C-N bonds in the enaminones, marks the major feature of the cascade reactions. The results disclose the individual advantage of enaminones in the design of novel and efficient synthetic methods.