Skeletal Transformation of Oxindoles into Quinolinones Enabled by Synergistic Copper/Iminium Catalysis.

We describe a synergistic Cu/secondary amine catalysis for skeletal transformation of an oxindole core into a quinolinone skeleton, which generates several structurally new pyridine-fused quinolinones. The synergistic reactions allow expansion of a five-membered lactam ring by radical cation-triggered C-C bond cleavage and enable a further intramolecular cyclization with the aim to construct totally distinct core skeletons.

Efficient Treatment of Oily Sludge via Fast Microwave-Assisted Pyrolysis, Followed by Thermal Plasma Vitrification.

Oily sludge, as a critical hazardous waste, requires appropriate treatment for resource recovery and harmfulness reduction. Here, fast microwave-assisted pyrolysis (MAP) of oily sludge was conducted for oil removal and fuel production. The results indicated the priority of the fast MAP compared with the MAP under premixing mode, with the oil content in solid residues after pyrolysis reaching below 0.2%. The effects of pyrolysis temperature and time on product distribution and compositions were examined. In addition, pyrolysis kinetics can be well described using the Kissinger-Akahira-Sunose (KAS) and the Flynn-Wall-Ozawa (FWO) methods, with the activation energy being 169.7-319.1 kJ/mol in the feedstock conversional fraction range of 0.2-0.7. Subsequently, the pyrolysis residues were further treated by thermal plasma vitrification to immobilize the existing heavy metals. The amorphous phase and the glassy matrix were formed in the molten slags, resulting in bonding and, hence, immobilization of heavy metals. Operating parameters, including working current and melting time, were optimized to reduce the leaching concentrations of heavy metals, as well as to decrease their volatilization during vitrification.

[Network pharmacological analysis and experimental verification of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium].

To explore the mechanism of anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium based on network pharmacology and inflammatory or pain mouse models. The effective components of Zanthoxyli Pericarpium were screened out by TCMSP database. And their potential corresponding targets were predicted by PharmMapper software. The possible targets relating to inflammation and pain were mainly collected through DrugBank, TTD and DisGeNET databases. The "active ingredient-gene-disease" network diagram was constructed by Cytoscape 3.7.0 software. The network pharmacology results showed 5 potential effective compounds, which were related to 29 targets; 132 targets relating to inflammation and pain were screened out in the DrugBank, TTD and DisGeNET databases. The network analysis results indicated that the phosphatidylinositol 3-kinase catalytic subunit gamma isoform(PIK3 CG) gene may be the key to the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium. The anti-inflammatory and analgesic effects of essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium were explored through the mouse model of inflammation induced by xylene or carrageenan and the mouse model of pain induced by acetic acid or formalin. The experimental results showed that essential oil extract and dichloromethane extract of Zanthoxyli Pericarpium could reduce xylene-induced ear swelling and carrageenan-induced paw swelling and decrease the number of writhing responses in mice induced by acetic acid and the licking foot time of mice in phase Ⅱ induced by formalin. Western blot results showed that Zanthoxyli Pericarpium extract could inhibit the expressions of PIK3 CG, phosphonated nuclear factor kappaB(p-NF-κB) and phosphonated p38(p-p38 MAPK) protein. The present study showed the anti-inflammatory and analgesic effect of Zanthoxyli Pericarpium through multiple components and targets, so as to provide a pharmacodynamic basis for the study of Zanthoxyli Pericarpium and its mechanism.

LncRNA MIR22HG inhibits growth, migration and invasion through regulating the miR-10a-5p/NCOR2 axis in hepatocellular carcinoma cells.

Despite the rapidly identified numbers of lncRNA in humans, exploration of the molecular mechanisms of lncRNA is lagging, because the molecular mechanisms of lncRNA can be various and complex in different conditions. In this study, we found a new molecular mechanism for a versatile molecule, MIR22HG. MIR22HG is an lncRNA that contributes to the initiation and progression of many human cancers, including hepatocellular carcinoma (HCC). We report that MIR22HG was downregulated in 120 HCC samples compared with adjacent nontumor liver tissues. More interestingly, decreased expression of MIR22HG in HCC could predict poor prognosis of HCC patients. Knockdown of MIR22HG promoted the growth, migration and invasion of HCC cells. In exploring the molecular mechanism of MIR22HG, we found that MIR22HG functioned as a tumor suppressor in hepatocellular carcinomas, in part through serving as a competing endogenous RNA to modulate the miRNA-10a-5p level. Moreover, NCOR2 was verified to act as the downstream target gene of MIR22HG/miR-10a-5p. In addition, the MIR22HG/miRNA-10a-5p/NCOR2 axis inhibited the activation of the Wnt/ß-catenin pathway. Together, our results demonstrated that MIR22HG inhibited HCC progression in part through the miR-10a-5p/NCOR2 signaling axis and might act as a new prognostic biomarker for HCC patients.

Chemoselective Mono- and Difluorination of 1,3-Dicarbonyl Compounds.

By altering the amount of Selectfluor, the highly selective mono- and difluorination of 1,3-dicarbonyl compounds has been achieved, affording a variety of 2-fluoro- and 2,2-difluoro-1,3-dicarbonyl compounds in good to excellent yields. The reaction can be readily performed in aqueous media without any catalyst and base, which features practical and convenient fluorination. Importantly, a gram-scale reaction, transformation of 2-fluoro-1,3-diphenylpropane-1,3-dione to 4-fluoro-1,3,5-triphenyl-1H-pyrazole, and chlorination and bromination of 1,3-dicarbonyl compounds are realized to further exhibit its synthetic utility.

Asymmetric Synthesis of 1,3-Oxazolidine Derivatives with Multi-Component Reaction and Research of Kinetic Resolution.

An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The plausible mechanism was proposed and a kinetic resolution of epoxides process was confirmed.

Utilizing different types of biomass materials to modify steel slag for the preparation of composite materials used in the adsorption and solidification of Pb in solutions and soil.

This study utilized discarded steel slag (SS) as raw material and prepared modified steel slag materials (SS-SBC, SS-NBC, SS-BHA) through modification with biomass materials such as straw biochar (SBC), nutshell biochar (NBC), and biochemical humic acid (BHA). These materials were then applied for the removal of Pb from both solution and soil. The physical and chemical properties of the materials were analyzed using characterization techniques such as SEM, EDS, XRD, and BET. The specific surface area of the modified materials increased from the original 3.8584 m2/g to 34.7133 m2/g, 181.7329 m2/g, and 7.7384 m2/g, respectively. The study then explored the influence of different adsorption conditions on the adsorption capacity of Pb in solution, determining the optimal conditions as follows: initial concentration of 200 mg/L, adsorbent mass of 0.04 g, temperature of 15 °C, and pH = 2. To further investigate the adsorption process, kinetic and isotherm models were established. The results indicated that the adsorption process for all three materials followed a pseudo-second-order kinetic model and Freundlich isotherm model, suggesting a multi-layer chemical adsorption. Thermodynamic analysis revealed that the adsorption process was an exothermic spontaneous reaction. Soil cultivation experiments were conducted to explore the effects of different material addition amounts and cultivation times on the passivation of Pb-polluted soil. Analysis of heavy metal forms in the soil revealed that the addition of modified materials reduced the acid-extractable form of Pb in the soil and increased the residual form, which is beneficial for reducing the migration of Pb in the soil. FT-IR and XPS analyses were employed to study the functional groups, element composition, and valence states before and after adsorption passivation of Pb by the three materials. The results confirmed that the adsorption mechanisms of SS-SBC, SS-NBC, and SS-BHA mainly involved electrostatic adsorption, ion and ligand exchange, and surface precipitation. This study not only provides a new material for adsorbing and immobilizing heavy metals in soil and water but also offers a new approach for the resource utilization of steel slag waste.

SYN1 variant causes X-linked neurodevelopmental disorders: a case report of variable clinical phenotypes in siblings.

The SYN1 gene encodes synapsin I, variants within the SYN1 gene are linked to X-linked neurodevelopmental disorders with high clinical heterogeneity, with reflex epilepsies (REs) being a representative clinical manifestation. This report analyzes a Chinese pedigree affected by seizures associated with SYN1 variants and explores the genotype-phenotype correlation. The proband, a 9-year-old boy, experienced seizures triggered by bathing at the age of 3, followed by recurrent absence seizures, behavioral issues, and learning difficulties. His elder brother exhibited a distinct clinical phenotype, experiencing sudden seizures during sleep at the age of 16, accompanied by hippocampal sclerosis. Whole exome sequencing (WES) confirmed a pathogenic SYN1 variant, c.1647_1650dup (p. Ser551Argfs*134), inherited in an X-linked manner from their mother. Notably, this variant displayed diverse clinical phenotypes in the two brothers and one previously reported case in the literature. Retrospective examination of SYN1 variants revealed an association between truncating variants and the pathogenicity of REs, and non-truncating variants are more related to developmental delay/intellectual disability (DD/ID). In summary, this study contributes to understanding complex neurodevelopmental disorders associated with SYN1, highlighting the clinical heterogeneity of gene variants and emphasizing the necessity for comprehensive genetic analysis in elucidating the pathogenic mechanisms of such diseases.

The Construction of Furocoumarins through Iron-Catalyzed Relay Annulation of Oxime Esters with 4-Hydroxycoumarins.

An iron-catalyzed relay annulation protocol was disclosed, which utilizes oxime esters and 4-hydroxycoumarins as the readily available starting materials and showcases broad substrate scope and good functional group tolerance. This method allows the simultaneous generation of two C-C and one C-O bonds and two rings in one step, affording structurally new furocoumarins in moderate to good yields.

Modular Assembly of 2-Aminoaniline Derivatives by Merging Hydroxylamine-Passerini and Hetero-Cope Rearrangement.

A metal-free three-component protocol that combines a hydroxylamine-Passerini reaction and hetero-Cope rearrangement was realized, which enables the modular assembly of a wide range of structurally new and interesting 2-aminoanilines bearing an α-hydroxyamide substructure.

Relay Annulation of Ammonium Ylides with Oxindole-Derived α,ß-Unsaturated Ketimines: Catalytic Construction of Spiro-polycyclic Oxindoles.

An ammonium ylide-based relay annulation was disclosed, which uses DABCO as the catalyst and oxindole-derived α,ß-unsaturated ketimines and γ-bromo-crotonates as the starting materials. This method enables the rapid assembly of a series of structurally novel spiro-polycyclic oxindoles containing a bicyclo[4.1.0]heptane moiety through simultaneous generation of three new bonds and two rings in one step under mild reaction conditions.

1,5-Hydrogen atom transfer of α-iminyl radical cations: a new platform for relay annulation for pyridine derivatives and axially chiral heterobiaryls.

The exploitation of new reactive species and novel transformation modes for their synthetic applications have significantly promoted the development of synthetic organic methodology, drug discovery, and advanced functional materials. α-Iminyl radical cations, a class of distonic ions, exhibit great synthetic potential for the synthesis of valuable molecules. For their generation, radical conjugate addition to α,ß-unsaturated iminium ions represents a concise yet highly challenging route, because the in situ generated species are short-lived and highly reactive and they have a high tendency to cause radical elimination (ß-scission) to regenerate the more stable iminium ions. Herein, we report a new transformation mode of the α-iminyl radical cation, that is to say, 1,5-hydrogen atom transfer (1,5-HAT). Such a strategy can generate a species bearing multiple reactive sites, which serves as a platform to realize (asymmetric) relay annulations. The present iron/secondary amine synergistic catalysis causes a modular assembly of a broad spectrum of new structurally fused pyridines including axially chiral heterobiaryls, and exhibits good functional group tolerance. A series of mechanistic experiments support the α-iminyl radical cation-induced 1,5-HAT, and the formation of several radical species in the relay annulations. Various synthetic transformations of the reaction products demonstrate the usefulness of this relay annulation protocol for the synthesis of significant molecules.

Characterization and Transcriptome Analysis of Maize Small-Kernel Mutant smk7a in Different Development Stages.

The kernel serves as a storage organ for various nutrients and determines the yield and quality of maize. Understanding the mechanisms regulating kernel development is important for maize production. In this study, a small-kernel mutant smk7a of maize was characterized. Cytological observation suggested that the development of the endosperm and embryo was arrested in smk7a in the early development stage. Biochemical tests revealed that the starch, zein protein, and indole-3-acetic acid (IAA) contents were significantly lower in smk7a compared with wild-type (WT). Consistent with the defective development phenotype, transcriptome analysis of the kernels 12 and 20 days after pollination (DAP) revealed that the starch, zein, and auxin biosynthesis-related genes were dramatically downregulated in smk7a. Genetic mapping indicated that the mutant was controlled by a recessive gene located on chromosome 2. Our results suggest that disrupted nutrition accumulation and auxin synthesis cause the defective endosperm and embryo development of smk7a.

Deconstructive Insertion of Oximes into Coumarins: Modular Synthesis of Dihydrobenzofuran-Fused Pyridones.

In the presence of a copper catalyst, a series of oximes undergo deconstructive insertion into coumarins to afford structurally interesting dihydrobenzofuran-fused pyridones in moderate to good yields with good functional group compatibility. The reaction likely involves a radical relay annulation, leading to the ring opening of the lactone moiety of the coumarins, and simultaneous formation of three new bonds. The investigation of photoluminescent properties reveals that several obtained compounds may have potential as fluorescent materials.

Two new lignans from Zanthoxylum armatum.

Zanthoxylum armatum, its peels possessed better special flavour, as well as various bioactivities, such as anti-inflammatory, anti-microbial and anti-tumour. In our chemical investigation on the peels of Z. armatum, two new lignans (1 and 2) and three known lignans (3-5) were isolated by silica gel column chromatography, ODS column and preparative HPLC and their structures were established as zanthlignans A and B (1-2), (-)-asarinin (3), phylligenin (4) and planispine A (5) through various spectroscopic techniques including UV, IR, HR-ESI-MS, NMR and CD methods.

Iminyl radical-triggered relay annulation for the construction of bridged aza-tetracycles bearing four contiguous stereogenic centers.

Bridged tetracyclic nitrogen scaffolds are found in numerous biologically active molecules and medicinally relevant structures. Traditional methods usually require tedious reaction steps, and/or the use of structurally specific starting materials. We report an unprecedented, iminyl radical-triggered relay annulation from oxime-derived peresters and azadienes, which shows good substrate scope and functional group compatibility, and can deliver various bridged aza-tetracyclic compounds with complex molecular topology and four contiguous stereogenic centers (dr > 19 : 1) in a single operation. This transformation represents the first example of trifunctionalization of iminyl radicals through simultaneous formation of one C-N and two C-C bonds. DFT calculation studies were conducted to obtain an in-depth insight into the reaction pathways, which revealed that the reactions involved an interesting 1,6-hydrogen atom transfer process.

[4 + 3] Cycloaddition of aromatic α,ß-unsaturated aldehydes and ketones with epoxides: one-step approach to synthesize seven-membered oxacycles catalyzed by Lewis acid.

A novel intermolecular [4 + 3] cycloaddition method to construct 1,4-dioxide seven-membered oxacycles was developed. This one-step method was carried out in the presence of catalytic amount of (C(2)H(5))(2)OBF(3) under mild conditions. Seven-membered oxacycles and some natural compounds could be easily synthesized via this protocol. Control experiments were carried out and possible mechanism for the reaction was proposed. Asymmetric reactions were proceeded and 3e was obtained with moderate ee value.

Exploration on asymmetric synthesis of flavanone catalyzed by (S)-pyrrolidinyl tetrazole.

An improved method of the synthesis of flavanones catalyzed by pyrrolidine and BF(3) ·Et(2) O has been developed and a lot of flavanones could be easily synthesized via this method. The asymmetric synthesis of flavanone from benzaldehyde and 5-fluoro-2-hydroxyacetophenone has been studied and flavanone with moderate enantioselectivity was obtained in one step.

LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma.

Metastasis is a core hallmark of cancer that leads to high mortality of cancer patients, especially in hepatocellular carcinoma (HCC). However, the underlying mechanisms of long noncoding RNAs (lncRNAs) in HCC metastasis remain largely unknown. We found that ID2-AS1 expression decreased in metastatic HCC cell lines and HCC tissues, and lower ID2-AS1 expression predicted reduced overall survival in HCC patients. ID2-AS1 significantly suppressed the migration, invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ID2-AS1 regulated the transcription of its adjacent gene inhibitor of DNA binding 2 (ID2) by blocking the binding of histone deacetylase 8 (HDAC8) on the ID2 enhancer. Furthermore, ID2-AS1 and ID2 suppressed the Twist-induced epithelial-mesenchymal transition (EMT) in HCC cells. In addition, ID2 expression was also significantly decreased in HCC tissues and was positively correlated with ID2-AS1 in HCC tissues and HCC cell lines. Taken together, our findings demonstrated that ID2-AS1 regulated adjacent ID2 transcription by manipulating chromatin modification and that the newly identified ID2-AS1/ID2 axis suppressed HCC metastasis by regulating EMT processes. Our findings provide insights into the molecular mechanisms underlying the metastasis of HCC cells.

An LTR Retrotransposon-Derived Long Noncoding RNA lncMER52A Promotes Hepatocellular Carcinoma Progression by Binding p120-Catenin.

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts. However, the role of these LTR-activated transcripts, especially long non-coding RNAs (lncRNA), in cancer development remains largely unexplored. Here, we identified a novel lncRNA derived from MER52A retrotransposons (lncMER52A) that was exclusively expressed in hepatocellular carcinoma (HCC). HCC patients with higher lncMER52A had advanced TNM stage, less differentiated tumors, and shorter overall survival. LncMER52A promoted invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, lncMER52A stabilized p120-catenin and triggered the activation of Rho GTPase downstream of p120-catenin. Furthermore, we found that chromatin accessibility was crucial for the expression of lncMER52A. In addition, YY1 transcription factor bound to the cryptic MER52A LTR promoter and drove lncMER52A transcription in HCC. In conclusion, we identified an LTR-activated lncMER52A, which promoted the progression of HCC cells via stabilizing p120-catenin and activating p120-ctn/Rac1/Cdc42 axis. LncMER52A could serve as biomarker and therapeutic target for patients with HCC. SIGNIFICANCE: A novel long noncoding RNA lncMER52 modulates cell migration and invasion via posttranslational control of p120-catenin protein stability. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/976/F1.large.jpg.