Search

Propofol is widely used for the induction and maintenance of anesthesia, which causes a rapid loss of consciousness. However, the mechanisms underlying the hypnosis effect of propofol are still not fully understood. The thalamic reticular nucleus (TRN) is crucial for regulating wakefulness, sleep rhythm generation, and sleep stability, while the role of TRN in the process of propofol-induced anesthesia is still unknown. Here, we investigated the function of the anterior TRN in propofol general anesthesia. Our results demonstrated that the neural activity of anterior TRN is suppressed during propofol anesthesia, whereas it is robustly activated from anesthesia by recording the calcium signals using fiber photometry technology. The results showed that the activation of anterior TRN neurons by chemogenetic and optogenetic methods shortens the emergency time without changing the induction time. Conversely, chemogenetic or optogenetic inhibition of the TRN neurons leads to a delay in the recovery time. Our study showed that anterior TRN is crucial for behavioral arousal without affecting the induction time of propofol anesthesia.

The discovery of new, safe, and effective pesticides is one of the main means for modern crop protection and parasitic disease control. During the search for new insecticidal secondary metabolites from endophytes in Stemona sessilifolia (a traditional Chinese medicine with a long history as an insecticide), 10 new insecticidal endostemonines A-J (1-10) were identified from an endophytic Streptomyces sp. BS-1. Their structures were determined by comprehensive spectroscopic analysis. Endostemonines A-J represent the first reported naturally occurring pyrrole-2-carboxylic ester derivatives, which consisted of different fatty acid chains at the C-2 of pyrrole ring were produced by traditional Chinese medicine endophytic microbes. All new tested compounds exhibited strong lethal activity against Aphis gossypii (LC50 value range of 3.55-32.00 mg/L after 72 h). This research highlighted the discovery of pesticide natural products from insecticidal medicinal plant endophytes for the first time, paving a new pathway for the development of pest control.

Treating cerebral ischemia continues to be a clinical challenge. Studies have shown that the neurovascular unit (NVU), as the central structural basis, plays a key role in cerebral ischemia. Here, we report that anthocyanin, a safe and natural antioxidant, could inhibit apoptosis and inflammation to protect NVU in rats impaired by middle cerebral artery occlusion/reperfusion (MCAO/R). Administration of anthocyanin significantly reduced infarct volume and neurological scores in MCAO/R rats. Anthocyanin could also markedly ameliorate cerebral edema and reduce the concentration of Evans blue (EB) by inhibiting MMP-9. Moreover, anthocyanin alleviated apoptotic injury resulting from MCAO/R through the regulation of Bcl-2 family proteins. The levels of inflammation-related molecules including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which were over-expressed with MCAO/R, were decreased by anthocyanin. In addition, Nuclear factor-kappa B (NF-κB) and the NLRP3 inflammasome pathway might be involved in the anti-inflammatory effect of anthocyanin. In conclusion, anthocyanin could protect the NVU through multiple pathways, and play a protective role in cerebral ischemia/reperfusion injury.

Daunorubicin (DNR) is a representative anthracycline with anti-tumor bioactivity. Its convergent biosynthetic pathway has promoted the research on pursuing novel anthracyclines by combinatorial biosynthesis. SnoaL is a special polyketide cyclase that catalyzes the closure of nogalonic acid methyl ester with the C9-S stereochemistry. In this study, the gene cluster of DNR was cloned, and snoaL was integrated into the DNR biosynthetic pathway for the substitution of dnrD in Streptomyces coeruleobidus DM, which resulted in the production of epi-aklaviketone. The biosynthetic pathway of NDP-4-deacetyl-L-chromose B was then expressed in the engineered strain, which led to the production of corresponding glycosylated anthracycline compounds. Finally, the bioactivities of these engineering strains were evaluated.

Daunorubicin (DNR) is an important anthracycline antibiotic. Its biosynthesis pathway has been well understood, however, the regulation of DNR biosynthesis needs further investigations. An ORF cloned between drrB and dnrX from the genome of a DNR producer, Streptomyces coeruleobidus DM, was named dauW and designated as an orthologous gene with dnrW and drrD. Several plasmids were constructed for over-expression and/or disruption of dauW in DM. Complete disruption of dauW can significantly increase the yield of DNR. We also found that the transcription level of dnrI, a major regulatory protein in the biosynthesis of DNR, and the self-resistance level were improved in dauW knock-out mutant. These results suggested that dauW may be a down-regulatory gene for DNR biosynthesis. Antibiotics productivity in S. coeruleobidus could be improved via regulation of the transcription of dnrI, a SARP regulator. The production of DNR in a high-producer and the yield of epi-DNR in an engineering strain were also increased by disruption of dauW.