Industrial Process and Modern Technical Adaptations for Nylon 6 Monomer Caprolactam: A Mini Review

Caprolactam is in high demand in the new materials industry as a monomer for nylon and polyamides. Although the schemes of traditional processes such as hydroxylamine production (hydroxylamine sulphate oxime process, hydroxylamine phosphate oxime process, nitric oxide reduction process) and cyclohexanone production were still involved in the caprolactam production industry, the modern technical adaptations achieved higher atomic utilisation and higher selectivity. In this review, the basic traditional schemes for the production of caprolactam are for the first time presented. The modern technical adaptation, the rectification dehydrogenation of the by-product cyclohexane in cyclohexanone production, was highlighted to achieve an increase in atomic utilisation from 78 % to 98 %. The higher selectivity achieved with membrane separation resulted in a conversion of cyclohexanone of > 99.6 % and a selectivity of cyclohexanone oxime of > 99.5 %. In addition, the progress of the catalysts used in the modern technical adaptation was briefly discussed. This review highlights the modern process with atom economy and high selectivity

IKKβ programs to turn on the GADD45α–MKK4–JNK apoptotic cascade specifically via p50 NF-κB in arsenite response

Cross talk between NF-κB and c-Jun N-terminal kinases (JNKs) has been implicated in the cell life and death decision under various stresses. Functional suppression of JNK activation by NF-κB has recently been proposed as a key cellular survival mechanism and contributes to cancer cells escaping from apoptosis. We provide a novel scenario of the proapoptotic role of IκB kinase β (IKKβ)–NF-κB, which can act as the activator of the JNK pathway through the induction of GADD45α for triggering MKK4/JNK activation, in response to the stimulation of arsenite, a cancer therapeutic reagent. This effect of IKKβ–NF-κB is dependent on p50 but not the p65/relA NF-κB subunit, which can increase the stability of GADD45α protein through suppressing its ubiquitination and proteasome-dependent degradation. IKKβ–NF-κB can therefore either activate or suppress the JNK cascade and consequently mediate pro- or antiapoptotic effects, depending on the manner of its induction. Furthermore, the NF-κB p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-κB transcriptional activity

Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations

Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer

Function of TRP channels in monocytes/macrophages

The transient receptor potential channel (TRP channel) family is a kind of non- specific cation channel widely distributed in various tissues and organs of the human body, including the respiratory system, cardiovascular system, immune system, etc. It has been reported that various TRP channels are expressed in mammalian macrophages. TRP channels may be involved in various signaling pathways in the development of various systemic diseases through changes in intracellular concentrations of cations such as calcium and magnesium. These TRP channels may also intermingle with macrophage activation signals to jointly regulate the occurrence and development of diseases. Here, we summarize recent findings on the expression and function of TRP channels in macrophages and discuss their role as modulators of macrophage activation and function. As research on TRP channels in health and disease progresses, it is anticipated that positive or negative modulators of TRP channels for treating specific diseases may be promising therapeutic options for the prevention and/or treatment of disease

Aurora-A Interacts with AP-2α and Down Regulates Its Transcription Activity

Aurora-A is a serine/threonine protein kinase and plays an important role in the control of mitotic progression. Dysregulated expression of Aurora-A impairs centrosome separation and maturation, which lead to disrupted cell cycle progression and tumorigenesis. However, the molecular mechanism by which Aurora-A causes cell malignant transformation remains to be further defined. In this report, using transcription factors array and mRNA expression profiling array, we found that overexpression of Aurora-A suppressed transcription activity of AP-2α, a tumor suppressor that is often downregulated in variety of tumors, and inhibited expression of AP-2α-regulated downstream genes. These array-based observations were further confirmed by microwell colorimetric TF assay and luciferase reporter assay. Downregulated transcription activity of AP-2α by Aurora-A was found to be associated with reduced AP-2α protein stability, which appeared to be mediated by Aurora-A enhanced ubiquitin-dependent proteasomal degradation of AP-2α protein. Interestingly, Aurora-A-mediated AP-2α degradation was likely dependent Aurora-A kinase activity since inhibition of Aurora-A kinase activity was able to rescue Aurora-A-induced degradation of AP-2α. Moreover, we defined a physical interaction between Aurora-A and AP-2α, and such interaction might bridge the suppressive effect of Aurora-A on AP-2α protein stability. These findings provide new insights into molecular mechanism by which Aurora-A acts as an oncogenic molecule in tumor occurrence and malignant development

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets