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(±)‐Penindolenes A−D (1–4), the first representatives of indole terpenoids featuring a γ‐lactam skeleton, were isolated from the mangrove‐derived endophytic fungus Penicillium brocae MA‐231. Our bioactivity tests revealed their potent antimicrobial and acetylcholinesterase inhibitory activities. The biosynthetic reactions by the five enzymes PbaABCDE leading to γ‐lactam ring formation were identified with heterologous expression and in vitro enzymatic assays. Remarkably, the cytochrome P450 monooxygenase PbaB and its homolog in Aspergillus oryzae catalyzed the 2,3‐cleavage of the indole ring to generate two keto groups in 1. This is the first example of the oxidative cleavage of indole by a P450 monooxygenase. In addition, rare secondary amide bond formation by the glutamine synthetase‐like enzyme PbaD was reported. These findings will contribute to the engineered biosynthesis of unnatural, bioactive indole terpenoids. [ABSTRACT FROM AUTHOR]

Objective Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments. Methods Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured. Results A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 μM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression. Conclusions Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Thirty-two fungal polyketide derivatives, including eleven new compounds, namely (3R,5′R)-5-hydroxytalaroflavone (1), talaroisochromenols A–C (3, 5, and 11), (8R,9R,10aR)-5-hydroxyaltenuene (13), (8R,9R,10aS)-5-hydroxyaltenuene (14), (8R,9S,10aR)-5-hydroxyaltenuene (15), nemanecins D and E (25 and 26), 2,5-dimethyl-8-iodochromone (27), and talarofurolactone A (29), together with one new naturally occurring but previously synthesized metabolite, 6-hydroxy-4-methoxycoumarin (28), were isolated and identified from the deep-sea cold-seep-derived fungus Talaromyces sp. CS-258. Among them, racemic ((±)-11) or epimeric (13–15, 25, and 26) mixtures were successfully separated by chiral or gradient elution HPLC. Meanwhile, compound 27 represents a rarely reported naturally occurring iodinated compound. Their planar structures as well as absolute configurations were determined by extensive analysis via NMR, MS, single-crystal X-ray diffraction, Mosher's method, and ECD or NMR calculation (with DP4+ probability analysis). Possible biosynthetic routes of some isolated compounds, which are related to chromone or isochromone biosynthetic pathways, were put forward. The biological analysis results revealed that compounds 7, 9, 10, 18–22, 24, 30, and 31 showed broad-spectrum antibacterial activities against several human and aquatic pathogens with MIC ranges of 0.5–64 μg/mL. [ABSTRACT FROM AUTHOR]

Mutations in the X-linked MECP2 gene cause Rett syndrome (RTT), an autism spectrum disorder characterized by impaired social interactions, motor abnormalities, cognitive defects and a high risk of epilepsy. Here, we showed that conditional deletion of Mecp2 in cholinergic neurons caused part of RTT-like phenotypes, which could be rescued by re-expressing Mecp2 in the basal forebrain (BF) cholinergic neurons rather than in the caudate putamen of conditional knockout (Chat-Mecp2(-/y)) mice. We found that choline acetyltransferase expression was decreased in the BF and that α7 nicotine acetylcholine receptor signaling was strongly impaired in the hippocampus of Chat-Mecp2(-/y) mice, which is sufficient to produce neuronal hyperexcitation and increase seizure susceptibility. Application of PNU282987 or nicotine in the hippocampus rescued these phenotypes in Chat-Mecp2(-/y) mice. Taken together, our findings suggest that MeCP2 is critical for normal function of cholinergic neurons and dysfunction of cholinergic neurons can contribute to numerous neuropsychiatric phenotypes.

C53H50F2N6O10S2, monoclinic, P21/n (no. 14), a = 15.088(5) Å, b = 23.560(9) Å, c = 15.401(6) Å, β = 112.254(5)°, V = 5067(3) Å3, Z = 4, Rgt(F) = 0.0509, wRref(F2) = 0.1336, T = 298(2) K.

SUMMARY: Abscisic acid (ABA) is involved in salt and drought stress responses, but the underlying molecular mechanism remains unclear. Here, we demonstrated that the overexpression of MdMYB44‐like, an R2R3‐MYB transcription factor, significantly increases the salt and drought tolerance of transgenic apples and Arabidopsis. MdMYB44‐like inhibits the transcription of MdPP2CA, which encodes a type 2C protein phosphatase that acts as a negative regulator in the ABA response, thereby enhancing ABA signaling‐mediated salt and drought tolerance. Furthermore, we found that MdMYB44‐like and MdPYL8, an ABA receptor, form a protein complex that further enhances the transcriptional inhibition of the MdPP2CA promoter by MdMYB44‐like. Significantly, we discovered that MdPP2CA can interfere with the physical association between MdMYB44‐like and MdPYL8 in the presence of ABA, partially blocking the inhibitory effect of the MdMYB44‐like–MdPYL8 complex on the MdPP2CA promoter. Thus, MdMYB44‐like, MdPYL8, and MdPP2CA form a regulatory loop that tightly modulates ABA signaling homeostasis under salt and drought stress. Our data reveal that MdMYB44‐like precisely modulates ABA‐mediated salt and drought tolerance in apples through the MdPYL8–MdPP2CA module. Significance Statement: Under salt and drought stress, ABA promotes MdMYB44‐like gene expression, and MdPYL8 interacts with MdMYB44‐like to form a protein complex that further strengthens the transcriptional inhibition of MdMYB44‐like on the MdPP2CA promoter. Interestingly, MdPP2CA interferes with the interaction between MdMYB44‐like and MdPYL8 in the presence of ABA, thereby reducing the transcriptional inhibition of MdPP2CA by the MdMYB44‐like‐MdPYL8 complex and thus balancing ABA signaling in plants. [ABSTRACT FROM AUTHOR]

To clarify the effect of different radial cooling intensities on the formation of central cracks in large round bloom continuous casting, it is necessary to study the solidification characteristics and dynamics of P91 high‐alloy steel at different cooling rates (CRs) to improve the central defects. In this article, the solidification characteristics of P91 high‐alloy steel at different CRs are studied by using the Thermo‐Calc software, high‐temperature laser confocal microscopy, scanning electron microscopy, and optical microscopy. Meanwhile, the growth kinetics of δ‐Fe and γ‐Fe phases under different CRs are determined. The results show that the solidification path of P91 high‐alloy steel is L(L + δ‐Fe) → (L + γ‐Fe + δ‐Fe) → (δ‐Fe + γ‐Fe). The δ‐Fe and γ‐Fe phase precipitation process is divided into two stages. Stage I is the nucleation and rapid growth phase, in which a high undercooling is required. Stage II is the slow growth stage, where the undercooling decreases and remains constant. The initial growth linear velocities of the δ‐Fe phase are 0.51, 2.72, and 2.09 μm s−1 at CRs of 10, 50, and 100 °C min−1, respectively, while those of the γ‐Fe phase are 0.10, 1.42, and 1.41 μm s−1. [ABSTRACT FROM AUTHOR]