Multi-omics analysis reveals the evolutionary origin of diterpenoid alkaloid biosynthesis pathways in Aconitum.

Diterpenoid alkaloids (DAs) have been often utilized in clinical practice due to their analgesic and anti-inflammatory properties. Natural DAs are prevalent in the family Ranunculaceae, notably in the Aconitum genus. Nevertheless, the evolutionary origin of the biosynthesis pathway responsible for DA production remains unknown. In this study, we successfully assembled a high-quality, pseudochromosome-level genome of the DA-rich species Aconitum vilmorinianum (A. vilmorinianum) (5.76 Gb). An A. vilmorinianum-specific whole-genome duplication event was discovered using comparative genomic analysis, which may aid in the evolution of the DA biosynthesis pathway. We identified several genes involved in DA biosynthesis via integrated genomic, transcriptomic, and metabolomic analyses. These genes included enzymes encoding target ent-kaurene oxidases and aminotransferases, which facilitated the activation of diterpenes and insertion of nitrogen atoms into diterpene skeletons, thereby mediating the transformation of diterpenes into DAs. The divergence periods of these genes in A. vilmorinianum were further assessed, and it was shown that two major types of genes were involved in the establishment of the DA biosynthesis pathway. Our integrated analysis offers fresh insights into the evolutionary origin of DAs in A. vilmorinianum as well as suggestions for engineering the biosynthetic pathways to obtain desired DAs.

S-ketamine used during anesthesia induction increases the perfusion index and mean arterial pressure after induction: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Abnormal peripheral perfusion and postinduction hypotension are associated with postoperative adverse outcomes. S-ketamine may stimulate blood circulation by activating the sympathetic nervous system. This study aimed to identify whether S-ketamine may improve the hemodynamic profile, relative to saline. METHODS: 115 patients were assessed for eligibility for participation in this study. A total of 100 patients were included. The patients (n = 50 for each group) were randomly allocated to the Test group, treated with S-ketamine plus propofol, cisatracurium and sufentanil, and to the Control group, treated with saline plus propofol, cisatracurium, and sufentanil. Maintenance of anesthesia in both groups was accomplished with sevoflurane. The perfusion index (PI) was recorded at intervals of 1 min, and mean arterial pressure (MAP) and heart rate (HR) were collected continuously at intervals of 3 min. The number of patients with MAP < 60 mmHg was also analyzed. RESULTS: The PI remained higher in the Test group than in the Control group at the following time points: initial induction (mean difference: 1.01 [95% CI: 0.27-1.74]; P = 0.007), preintubation (mean difference: 1.46 [95% CI: 0.57-2.34]; P = 0.001) and postintubation (mean difference: 1.28 [95% CI: 0.26-2.30]; P = 0.014), before (mean difference: 2.66 [95% CI: 1.22-4.1]; P < 0.001) and after making the skin incision (mean difference: 1.03 [95% CI: 0.28-1.78]; P = 0.007). Compared with Control group, a higher MAP trend from preintubation to postincision appeared in patients assigned to S-ketamine (P = 0.003). The number of patients with MAP < 60 mmHg in the Test group was lower than Control group (10.0% vs. 34.0%, P < 0.003) in the preincision. The HR was similar throughout the test, with no statistical difference. CONCLUSIONS: During anesthesia induction and maintenance, the use of S-ketamine may improve the peripheral perfusion and blood pressure as compared to the Control group. CLINICAL TRIAL NUMBER: ChiCTR2100051167.

Invasive Aspergillus outbreak in inhalation injury: a case presentation and literature review.

BACKGROUND: Invasive pulmonary aspergillosis often occurs in patients with poor immune function, who abuse steroids or broad-spectrum antibiotics, or who use intravenous drugs. Among the Aspergillus genus of pulmonary infection, Aspergillus fumigatus is the most important pathogen, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus terreus. Inhalation injury complicated by Aspergillus infection has atypical clinical manifestations. Diagnosis is difficult, and it is easy to make mistakes in treatment. Moreover, there are few cases of burn inhalation injury complicated with pulmonary Aspergillus. CASE PRESENTATION: We report a case of severe burns combined with severe inhalation injury, early pulmonary aspergillosis, and severe respiratory failure due to treatment discontinuation. Through analyzing the processes of diagnosis and treatment in the present case and performing a literature review, we explore feasible diagnosis and treatment plans. CONCLUSIONS: Early application of a variety of diagnostic measures can be used to identify Aspergillus infection, and targeted anti-infection treatment is likely to reverse a severe adverse prognosis.

Melatonin synthesis genes N-acetylserotonin methyltransferases evolved into caffeic acid O-methyltransferases and both assisted in plant terrestrialization.

Terrestrialization is one of the most momentous events in the history of plant life, which leads to the subsequent evolution of plant diversity. The transition species, in this process, had to acquire a range of adaptive mechanisms to cope with the harsh features of terrestrial environments compared to that of aquatic habitat. As an ancient antioxidant, a leading regulator of ROS signaling or homeostasis, and a presumed plant master regulator, melatonin likely assisted plants transition to land and their adaption to terrestrial ecosystems. N-acetylserotonin methyltransferases (ASMT) and caffeic acid O-methyltransferases (COMT), both in the O-methyltransferase (OMT) family, catalyze the core O-methylation reaction in melatonin biosynthesis. How these two enzymes with close relevance evolved in plant evolutionary history and whether they participated in plant terrestrialization remains unknown. Using combined phylogenetic evidence and protein structure analysis, it is revealed that COMT likely evolved from ASMT by gene duplication and subsequent divergence. Newly emergent COMT gained a significantly higher ASMT activity to produce greater amounts of melatonin for immobile plants to acclimate to the stressful land environments after evolving from the more environmentally-stable aquatic conditions. The COMT genes possess more conserved substrate-binding sites at the amino acid level and more open protein conformation compared to ASMT, and getting a new function to catalyze the lignin biosynthesis. This development directly contributed to the dominance of vascular plants among the Earth's flora and prompted plant colonization of land. Thus, ASMT, together with its descendant COMT, might play key roles in plant transition to land. The current study provides new insights into plant terrestrialization with gene duplication contributing to this process along with well-known horizontal gene transfer.

Full Utilization of Lignocellulose with Ionic Liquid Polyoxometalates in a One-Pot Three-Step Conversion.

The lignin-first concept is a new innovation for full utilization of lignocellulose into value-added chemicals. Ionic liquid (IL) polyoxometalates [MIMPS]2 H4 P2 Mo18 O62 [MIMPS=1-(3-sulfonic group) propyl-3-methyl imidazolium] are reported to be active in the cleavage of ß-O-4, α-O-4, and 4-O-5 bonds in three kinds of lignin models and also efficient for converting native lignocellulose. The three components in soft or hard lignocellulose were depolymerized in a one-pot three-step treatment. For soft lignocellulose (pine), lignin was first decomposed into guaiacol and phenol with yields of 15.3 and 12.9 % at 98.6 % delignification efficiency at 130 °C for 14 h. Meanwhile, hemicellulose and cellulose were intact during the delignifying process and were subsequently hydrolyzed to 3.5 % xylose at 100 % hemicellulose conversion efficiency at 150 °C for 14 h and 36.4 % glucose at 100 % cellulose conversion efficiency at 170 °C for 12 h, respectively. For hard lignocellulose (poplar), the yields of guaiacol and phenol were 10.1 and 8.7 % at 91.9 % delignification efficiency at 130 °C for 14 h, whereas 12.9 % xylose at 90.4 % hemicellulose conversion efficiency at 150 °C for 12 h and 32.9 % glucose at 100 % cellulose conversion efficiency at 170 °C for 12 h were obtained. [MIMPS]2 H4 P2 Mo18 O62 achieved the full utilization of lignocellulose with total conversion in the lignin-first strategy and also showed the easy separation as a result of temperature-reversibility with ten recycling runs.

A Polyoxometalate-Based Microfluidic Device for Liquid-Phase Oxidation of Glycerol.

Peroxidation of glycerol has been carried out in a polyoxometalate (POM)-based microfluidic reactor, which was fabricated on a capillary by using a layer-by-layer strategy. Lactic acid (LA) is produced selectively in high yield with a TOF as high as 20 000 h-1 , compared to a TOF of 200 h-1 in batch mode. This POM microfluidic reactor is readily prepared, scalable, highly stable, reusable, and also potentially applicable to selective oxidation of other bio-wastes.