Isolated unilateral brachial plexus injury following carbon monoxide intoxication: a case report and literature review

Carbon monoxide (CO) is a gas that has no odor or color, making it difficult to detect until exposure leads to coma or death. CO poisoning is one of the most common and deadly poisonings around the world. CO poisoning is a common and often fatal form of poisoning worldwide. A toxic effect of CO is tissue hypoxia, which leads to systemic complications. Additionally, there may be severe neurological symptoms and delayed complications following CO poisoning. However, peripheral neuropathy is relatively rare after CO poisoning. Previously, only one case of unilateral plexopathy after CO poisoning, accompanied by rhabdomyolysis and cognitive dysfunction, has been reported. In this report, an isolated unilateral brachial plexopathy following CO intoxication is described. A key mechanism in this case may be CO-induced spinal cord ischemia. Immediate administration of hyperbaric oxygen therapy (HBOT) is crucial to prevent peripheral neuropathy after acute CO intoxication. Hyperbaric oxygen therapy (HBOT) should be administered immediately after acute CO intoxication to prevent peripheral neuropathy. Additionally, peripheral neuropathy following acute CO intoxication may benefit from consistent rehabilitation training

Turning a Sesquiterpene Synthase into a Di- and Sesterterpene Synthase

The sesquiterpene synthase 7-epi-α-eudesmol synthase is widespread in streptomycetes. Several active site residues that were identified by an alignment of their amino acid sequence to the sequence of the structurally known selina-4(15),7(11)-diene synthase were targeted by site-directed mutagenesis. In these experiments, the active site cavity was widened through exchange of large with small residues, resulting in the discovery of two key residues for which such exchanges turned 7-epi-α-eudesmol synthase into a di- or sesterterpene synthase

1,2-or 1,3-Hydride Shifts: What Controls Guaiane Biosynthesis?

A systematic computational study addressing the entire chemical space of guaianes in conjunction with an analysis of all known compounds shows that 1,3-hydride shifts are rare events in guaiane biosynthesis. As demonstrated here, 1,3-hydride shifts towards guaianes can only be realized for two stereochemically well defined out of numerous possible stereoisomeric skeletons. One example is given by the mechanism of guaia-4(15)-en-11-ol synthase from California poplar, an enzyme that yields guaianes with unusual stereochemical properties. The general results from DFT calculations were experimentally verified through isotopic-labeling experiments with guaia-4(15)-en-11-ol synthase

The enzyme mechanism of patchoulol synthase

Different mechanisms for the cyclisation of farnesyl pyrophosphate to patchoulol by the patchoulol synthase are discussed in the literature. They are based on isotopic labelling experiments, but the results from these experiments are contradictory. The present work reports on a reinvestigation of patchoulol biosynthesis by isotopic labelling experiments and computational chemistry. The results are in favour of a pathway through the neutral intermediates germacrene A and alpha-bulnesene that are both reactivated by protonation for further cyclisation steps, while previously discussed intra- and intermolecular hydrogen transfers are not supported. Furthermore, the isolation of the new natural product (2S,3S,7S,10R)-guaia-1,11-dien-10-ol from patchouli oil is reported

Influence of CO₂ Curing on the Alkali-Activated Compound Mineral Admixtures’ Corrosion Resistance to NaCl Dry–Wet Alternations

In this study, the influence of CO2 curing on the corrosion resistance of reinforced alkali-activated compounds is investigated. Fly ash (FA) and blast furnace slag powder (BFS) are used as mineral admixtures. The specimens were subjected to dry–wet alternations with 3% NaCl, used to simulate a concrete structure under a corrosion environment. The ultrasonic velocity, mass loss rate, and electrical characteristics (such as electrical resistance, AC impedance spectra, and corrosion area rates determined by Tafel curves) are utilized to determine the degree of corrosion. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) are used to analyze the corrosion mechanism. Results show that the corrosion resistance is decreased by the addition of FA but improved by CO2 curing. When CO2 curing is provided, the addition of BFS shows a higher enhancing effect on the corrosion resistance than that of FA. The equivalent circuit diagram of reinforced alkali-activated compound mineral admixtures obtained by AC impedance spectra is composed of three electrical elements (electrical resistance and capacitance in parallel) in series. The X-ray diffraction results show that adding BFS and CO2 curing can decrease the rust’s iron oxides on the steel bars’ surface. Finally, as found in the SEM photos, BFS and CO2 curing can effectively improve the compactness of specimens. Meanwhile, the roughness of hydration is increased by CO2 curing

Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements

The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS) were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems

The Sesquiterpene Synthase PtTPS5 Produces (1<i>S</i>,5<i>S</i>,7<i>R</i>,10<i>R</i>)-Guaia-4(15)-en-11-ol and (1<i>S</i>,7<i>R</i>,10<i>R</i>)-Guaia-4-en-11-ol in Oomycete-Infected Poplar Roots

Pathogen infection often leads to the enhanced formation of specialized plant metabolites that act as defensive barriers against microbial attackers. In this study, we investigated the formation of potential defense compounds in roots of the Western balsam poplar (Populus trichocarpa) upon infection with the generalist root pathogen Phytophthora cactorum (Oomycetes). P. cactorum infection led to an induced accumulation of terpenes, aromatic compounds, and fatty acids in poplar roots. Transcriptome analysis of uninfected and P. cactorum-infected roots revealed a terpene synthase gene PtTPS5 that was significantly induced upon pathogen infection. PtTPS5 had been previously reported as a sesquiterpene synthase producing two unidentified sesquiterpene alcohols as major products and hedycaryol as a minor product. Using heterologous expression in Escherichia coli, enzyme assays with deuterium-labeled substrates, and NMR analysis of reaction products, we could identify the major PtTPS5 products as (1S,5S,7R,10R)-guaia-4(15)-en-11-ol and (1S,7R,10R)-guaia-4-en-11-ol, with the former being a novel compound. The transcript accumulation of PtTPS5 in uninfected and P. cactorum-infected poplar roots matched the accumulation of (1S,5S,7R,10R)-guaia-4(15)-en-11-ol, (1S,7R,10R)-guaia-4-en-11-ol, and hedycaryol in this tissue, suggesting that PtTPS5 likely contributes to the pathogen-induced formation of these compounds in planta

The Sesquiterpene Synthase PtTPS5 Produces (1S,5S,7R,10R)-Guaia-4(15)-en-11-ol and (1S,7R,10R)-Guaia-4-en-11-ol in Oomycete-Infected Poplar Roots

Pathogen infection often leads to the enhanced formation of specialized plant metabolites that act as defensive barriers against microbial attackers. In this study, we investigated the formation of potential defense compounds in roots of the Western balsam poplar (Populus trichocarpa) upon infection with the generalist root pathogen Phytophthora cactorum (Oomycetes). P. cactorum infection led to an induced accumulation of terpenes, aromatic compounds, and fatty acids in poplar roots. Transcriptome analysis of uninfected and P. cactorum-infected roots revealed a terpene synthase gene PtTPS5 that was significantly induced upon pathogen infection. PtTPS5 had been previously reported as a sesquiterpene synthase producing two unidentified sesquiterpene alcohols as major products and hedycaryol as a minor product. Using heterologous expression in Escherichia coli, enzyme assays with deuterium-labeled substrates, and NMR analysis of reaction products, we could identify the major PtTPS5 products as (1S,5S,7R,10R)-guaia-4(15)-en-11-ol and (1S,7R,10R)-guaia-4-en-11-ol, with the former being a novel compound. The transcript accumulation of PtTPS5 in uninfected and P. cactorum-infected poplar roots matched the accumulation of (1S,5S,7R,10R)-guaia-4(15)-en-11-ol, (1S,7R,10R)-guaia-4-en-11-ol, and hedycaryol in this tissue, suggesting that PtTPS5 likely contributes to the pathogen-induced formation of these compounds in planta

Origin of the 3-methylglutaryl moiety in caprazamycin biosynthesis

BACKGROUND: Caprazamycins are liponucleoside antibiotics showing bioactivity against Gram-positive bacteria including clinically relevant Mycobacterium tuberculosis by targeting the bacterial MraY-translocase. Their chemical structure contains a unique 3-methylglutaryl moiety which they only share with the closely related liposidomycins. Although the biosynthesis of caprazamycin is understood to some extent, the origin of 3-methylglutaryl-CoA for caprazamycin biosynthesis remains elusive. RESULTS: In this work, we demonstrate two pathways of the heterologous producer Streptomyces coelicolor M1154 capable of supplying 3-methylglutaryl-CoA: One is encoded by the caprazamycin gene cluster itself including the 3-hydroxy-3-methylglutaryl-CoA synthase Cpz5. The second pathway is part of primary metabolism of the host cell and encodes for the leucine/isovalerate utilization pathway (Liu-pathway). We could identify the liu cluster in S. coelicolor M1154 and gene deletions showed that the intermediate 3-methylglutaconyl-CoA is used for 3-methylglutaryl-CoA biosynthesis. This is the first report of this intermediate being hijacked for secondary metabolite biosynthesis. Furthermore, Cpz20 and Cpz25 from the caprazamycin gene cluster were found to be part of a common route after both individual pathways are merged together. CONCLUSIONS: The unique 3-methylglutaryl moiety in caprazamycin originates both from the caprazamycin gene cluster and the leucine/isovalerate utilization pathway of the heterologous host. Our study enhanced the knowledge on the caprazamycin biosynthesis and points out the importance of primary metabolism of the host cell for biosynthesis of natural products. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12934-022-01955-6

Functional characterisation of twelve terpene synthases from actinobacteria

Fifteen type I terpene synthase homologs from diverse actinobacteria that were selected based on a phylogenetic analysis of more than 4000 amino acid sequences were investigated for their products. For four enzymes with functions not previously reported from bacterial terpene synthases the products were isolated and their structures were elucidated by NMR spectroscopy, resulting in the discovery of the first terpene synthases for (+)-δ-cadinol and (+)-α-cadinene, besides the first two bacterial (−)-amorpha-4,11-diene synthases. For other terpene synthases with functions reported from bacteria before the products were identified by GC–MS. The characterised enzymes include a new epi-isozizaene synthase with monoterpene synthase side activity, a 7-epi-α-eudesmol synthase that also produces hedycaryol and germacrene A, and four more sesquiterpene synthases that produce mixtures of hedycaryol and germacrene A. Three phylogenetically related enzymes were in one case not expressed and in two cases inactive, suggesting pseudogenisation in the respective branch of the phylogenetic tree. Furthermore, a diterpene synthase for allokutznerene and a sesterterpene synthase for sesterviolene were identified