Copper-Catalyzed Multicomponent Reaction of DABCO·(SO₂)₂, Alcohols, and Aryl Diazoniums for the Synthesis of Sulfonic Esters

A Cu-catalyzed multicomponent cascade reaction of DABCO·(SO₂)₂ (DABSO), alcohol, and aryl diazonium tetrafluoroborate was developed which afforded sulfonic esters in moderate to good chemical yields. In this reaction, the SO₂ surrogate DABSO was used for the first time in the synthesis of sulfonic aliphatic esters. This multicomponent reaction was carried out under mild conditions and tolerated a wide range of substrates, which provides a new and efficient strategy for the synthesis of sulfonic esters

Table1_Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.DOCX

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.</p

Copper-Catalyzed Multicomponent Reaction of DABCO·(SO₂)₂, Alcohols, and Aryl Diazoniums for the Synthesis of Sulfonic Esters

A Cu-catalyzed multicomponent cascade reaction of DABCO·(SO₂)₂ (DABSO), alcohol, and aryl diazonium tetrafluoroborate was developed which afforded sulfonic esters in moderate to good chemical yields. In this reaction, the SO₂ surrogate DABSO was used for the first time in the synthesis of sulfonic aliphatic esters. This multicomponent reaction was carried out under mild conditions and tolerated a wide range of substrates, which provides a new and efficient strategy for the synthesis of sulfonic esters

Bacteria That Make a Meal of Sulfonamide Antibiotics: Blind Spots and Emerging Opportunities

The release of sulfonamide antibiotics into the environment is alarming because the existence of these antibiotics in the environment may promote resistance in clinically relevant microorganisms, which is a potential threat to the effectiveness of antibiotic therapies. Controllable biodegradation processes are of particular significance for the inexpensive yet effective restoration of sulfonamide-contaminated environments. Cultivation-based techniques have already made great strides in successfully isolating bacteria with promising sulfonamide degradation abilities, but the implementation of these isolates in bioremediation has been limited by unknown microbial diversity, vast population responsiveness, and the impact of perturbations from open and complex environments. Advances in DNA sequencing technologies and metagenomic analyses are being used to complement the information derived from cultivation-based procedures. In this Review, we provide an overview of the growing understanding of isolated sulfonamide degraders and identify shortcomings of the prevalent literature in this field. In addition, we propose a technical paradigm that integrates experimental testing with metagenomic analysis to pave the way for improved understanding and exploitation of these ecologically important isolates. Overall, this Review aims to outline how metagenomic studies of isolated sulfonamide degraders are being applied for the advancement of bioremediation strategies for sulfonamide contamination

Table2_Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.DOCX

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.</p

Table3_Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.DOCX

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.</p

Table5_Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.XLSX

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.</p

Table4_Whole-genome characterization of large-cell lung carcinoma: A comparative analysis based on the histological classification.DOCX

Background: According to the 2015 World Health Organization classification, large cell neuroendocrine carcinoma (LCNEC) was isolated from Large-cell lung cancer (LCLC) tumors, which constitutes 2%–3% of non-small cell lung cancer (NSCLC). However, LCLC tumors are still fairly vaguely defined at the molecular level compared to other subgroups.Materials and Methods: In this study, whole-genome sequencing (WGS) was performed on 23 LCLC and 15 LCNEC tumor specimens. Meanwhile, data from the TCGA (586 LUADs and 511 LUSCs) and U Cologne (120 SCLCs) were analyzed and compared.Results: The most common driver mutations were found in TP53 (13/23, 57%), FAM135B (8/23, 35%) and FAT3 (7/23, 30%) in LCLC, while their counterparts in LCNEC were TP53 (13/15, 87%), LRP1B (6/15, 40%) and FAT1 (6/15, 40%). Notably, FAM135B mutations only occurred in LCLC (P = 0.013). Cosmic signature analysis revealed widespread defective DNA mismatch repair and tobacco-induced mutations in both LCLC and LCNEC. Additionally, LCNEC had a higher incidence of chromosomal copy number variations (CNVs) and structural variations (SVs) compared with LCLC, although the differences were not statistically significant. Particularly, chromothripsis SVs was significantly associated with CNVs. Furthermore, mutational landscape of different subtypes indicated differences between subtypes, and there seems to be more commonalty between our cohort and SCLC than with other subtypes. SMARCA4 mutations may be specific driver gene alteration in our cohort.Conclusion: Our results support that LCLC and LCNEC tumors follow distinct tumorigenic pathways. To our knowledge, this is the first genome-wide profiling comparison of LCLC and LCNEC.</p

Partnership of Arthrobacter and Pimelobacter in Aerobic Degradation of Sulfadiazine Revealed by Metagenomics Analysis and Isolation

In this study, metagenomic analyses were combined with cultivation-based techniques as a nested approach to identify functionally significant bacteria for sulfadiazine biodegradation within enrichment communities. The metagenomic investigations indicated that our previously isolated sulfadiazine degrader, Arthrobacter sp. D2, and another Pimelobacter bacterium concomitantly occurred as most abundant members in the community of an enrichment culture that performed complete sulfadiazine mineralization for over two years. Responses of the enriched populations to sole carbon source alternation further suggested the ability of this Pimelobacter member to grow on 2-amino­pyrimidine, the most prominent intermediate metabolite of sulfadiazine. Taking advantage of this propensity, additional cultivation procedures have enabled the successful isolation of Pimelobacter sp. LG209, whose genomic sequences exactly matched that of the dominant Pimelobacter bacterium in the sulfadiazine enrichment culture. Integration of metagenomic investigations with the physiological characteristics of the isolates conclusively demonstrated that the sulfadiazine mineralization in a long-running enrichment culture was prominently mediated by primary sulfadiazine-degrading specialist strain Arthrobacter sp. D2 in association with the 2-amino­pyrimidine-degrading partner strain Pimelobacter sp. LG209. Here, we provided the first mechanistic insight into microbial interactions in steady sulfadiazine mineralization processes, which will help develop appropriate bioremediation strategies for sulfadiazine-contaminated hotspot sites

MOESM1 of Metabolic engineering of Saccharomyces cerevisiae for efficient production of glucaric acid at high titer

Additional file 1: Table S1. Primers used in this study. Figure S1. MIOX4 activity of the episomal expression plasmid in the wild-type strain and opi1 mutant strain with myo-inositol. All experiments were performed in triplicates and the error bar represented mean Âą standard deviation. Figure S2. myo-inositol residue in shake flask (A) and fed-batch (B) cultures when fed 60 mM (10.8 g/L) myo-inositol to the culture. All experiments were performed in triplicates and the error bar represented mean Âą standard deviation