35 research outputs found
Access to Optically Active Aryl Halohydrins Using a Substrate-Tolerant Carbonyl Reductase Discovered from Kluyveromyces thermotolerans
By genome data mining, a carbonyl reductase tool box
was designed
and developed for chiral alcohol synthesis. On the basis of systematic
comparison of the specific activity and substrate tolerance toward
α-chloroacetophenone among reductases in this tool box, KtCR,
a highly substrate-/product-tolerant carbonyl reductase from Kluyveromyces thermotolerans, was identified. The
reduction of a series of substituted aryl ketones was investigated
using this newly mined biocatalyst. Almost all of the ketones tested
were asymmetrically reduced into corresponding chiral alcohols in
99% ee. Substrates with substituents adjacent to the carbonyl group
or those with substituents on the para position of the phenyl ring
were easier to reduce. For α-choloacetophenone as a representative
substrate, as much as 154 g/L (1.0 M) of the substrate was asymmetrically
reduced within merely 12 h by lyophilized cells of Escherichia coli/pET28-KtCR, resulting in an isolated
yield of 92%, an enantiopurity of >99% ee, and a total turnover
number
of 5000, which was five times higher than the highest record reported
so far. These results indicate the great potential of KtCR in practical
synthesis of valuable aryl halohydrins as versatile chiral synthons
Reactivity of Bis(3,5-dimethylpyrazol-1-yl)methyllithium with S or CS<sub>2</sub>, Followed by Reaction with Fe<sub>3</sub>(CO)<sub>12</sub> and Ar<sub>3</sub>SnCl or RX: Unexpected Formation of (3,5-Dimethylpyrazol-1-yl)dithioformate Derivatives
Reaction of bisÂ(3,5-dimethylpyrazol-1-yl)Âmethyllithium
with sulfur at â70 °C, followed by reaction with Fe<sub>3</sub>(CO)<sub>12</sub> and triaryltin chlorides, yielded trinuclear
butterfly cluster complexes. When the triaryltin chlorides were replaced
by organic halides, unexpected (3,5-dimethylpyrazol-1-yl)Âdithioformate
derivatives were obtained. In addition, treatment of bisÂ(3,5-dimethylpyrazol-1-yl)Âmethane
with <i>n</i>-BuLi at 0 °C resulted in partial decomposition
to yield a carbene intermediate and a 3,5-dimethylpyrazolate anion.
The carbene intermediate readily dimerized, and reaction of the anion
with carbon disulfide, and subsequently with Fe<sub>3</sub>(CO)<sub>12</sub> and organic halides, also gave the dithioformate derivatives
Enantioselective Synthesis of Both Axially and Planar Chiral Ferrocenes via Axial-to-Planar Diastereoinduction
Ferrocenes
with planar chirality have emerged as an important class
of scaffolds for ligands in asymmetric catalysis; however, ferrocene
molecules with polychiral structures have not been well explored.
Herein, both axially and planar chiral ferrocenes were synthesized
via palladium/chiral norbornene cooperative catalysis and axial-to-planar
diastereoinduction. In this work, chiral norbornene was used to stereoselectively
control the aromatic axial chirality, and further selectivity induced
C(sp2)âH activation for ferrocene planar chirality.
Based on density functional theory calculations, the catalytic model
of chiral norbornene with the substrate and the axial-to-planar diastereoinduction
process were confirmed
Table_1_Characteristics of Carbapenem-Resistant Enterobacteriaceae in Ready-to-Eat Vegetables in China.xlsx
<p>Vegetables harboring bacteria resistant to antibiotics are a growing food safety issue. However, data concerning carbapenem-resistant Enterobacteriaceae (CRE) in ready-to-eat fresh vegetables is still rare. In this study, 411 vegetable samples from 36 supermarkets or farmer's markets in 18 cities in China, were analyzed for CRE. Carbapenemase-encoding genes and other resistance genes were analyzed among the CRE isolates. Plasmids carrying carbapenemase genes were studied by conjugation, replicon typing, S1-PFGE southern blot, restriction fragment length polymorphism (RFLP), and sequencing. CRE isolates were also analyzed by pulsed-field gel electrophoresis (PFGE). Ten vegetable samples yielded one or more CRE isolates. The highest detection rate of CRE (14.3%, 4/28) was found in curly endive. Twelve CRE isolates were obtained and all showed multidrug resistance: Escherichia coli, 5; Citrobacter freundii, 5; and Klebsiella pneumoniae, 2. All E. coli and C. freundii carried bla<sub>NDM</sub>, while K. pneumoniae harbored bla<sub>KPCâ2</sub>. Notably, E. coli with bla<sub>NDM</sub> and ST23 hypervirulent Klebsiella pneumoniae (hvKP) carrying bla<sub>KPCâ2</sub> were found in the same cucumber sample and clonal spread of E. coli, C. freundii, and K. pneumoniae isolates were all observed between vegetable types and/or cities. IncX3 plasmids carrying bla<sub>NDM</sub> from E. coli and C. freundii showed identical or highly similar RFLP patterns, and the sequenced IncX3 plasmid from cucumber was also identical or highly similar (99%) to the IncX3 plasmids from clinical patients reported in other countries, while bla<sub>KPCâ2</sub> in K. pneumoniae was mediated by similar F35:A-:B1 plasmids. Our results suggest that both clonal expansion and horizontal transmission of IncX3- or F35:A-:B1-type plasmids may mediate the spread of CRE in ready-to-eat vegetables in China. The presence of CRE in ready-to-eat vegetables is alarming and constitutes a food safety issue. To our knowledge, this is the first report of either the C. freundii carrying bla<sub>NDM</sub>, or K. pneumoniae harboring bla<sub>KPCâ2</sub> in vegetables. This is also the first report of ST23 carbapenem-resistant hvKP strain in vegetables.</p
Image_4_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.tif
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p
Image_3_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.tif
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p
Table_2_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.xlsx
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p
Table_7_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.xlsx
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p
Table_6_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.xlsx
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p
Table_4_Molecular and clinical features of papillary thyroid cancer in adult patients with a non-classical phenotype.xlsx
PurposeGenotyping is fundamental in papillary thyroid cancer (PTC) and helps to enhance diagnosis and prognosis and determine appropriate treatments. The phenotype-genotype association in PTC was previously studied, with BRAF V600E characterizing classic PTC and tall-cell PTC and RAS mutations characterizing follicular-variant PTC. In clinic, some non-classical histological subtypes of PTC were also identified, however, their genotype remains unclear. In this study, we collected samples of these non-classical PTC after the exclusion of classic phenotypes and examined their phenotypes, genotype and the relationship between phenotype and genotype.MethodsWe screened out non-classical PTC by excluding classical PTC from 1,059 different thyroid samples, and a total of 24 cases was obtained and described from the morphological features, which is rare in differentiated PTC. DNA/RNA sequencing was performed using 18 available samples to describe the genetic features.ResultsPTC with the non-classical phenotype were characterized cuboidal to low columnar tumor cells with subtle nuclear features of PTC and without discernible nuclear elongation, concurrently with dense microfollicles, delicate papillae or solid nodules with delicate fibrovascular cores. They were associated with lymphatic vessel invasion (PConclusionsOur study retrospectively screened a large cohort of different thyroid tissue samples, and presented the histopathological and genetic features of a non-classical phenotype of PTC from 24 patients. It may contribute to diagnose in PTC, and patients of these non-classical phenotype may benefit from targeted therapy, compared to a natural patient cohort without selection.</p