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Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines. [ABSTRACT FROM AUTHOR]

Numerous clinical disorders have been linked to the etiology of dysregulated NLRP3 (NACHT, LRR, and PYD domain‐containing protein 3) inflammasome activation. Despite its potential as a pharmacological target, modulation of NLRP3 activity remains challenging. Only a sparse number of compounds have been reported that can modulate NLRP3 and none of them have been developed into a commercially available drug. In this research, we identified three potent NLRP3 inflammasome inhibitors, gymnoasins A‐C (1–3), with unprecedented pentacyclic scaffolds, from an Antarctic fungus Pseudogymnoascus sp. HDN17‐895, which represent the first naturally occurring naphthopyrone‐macrolide hybrids. Additionally, biomimetic synthesis of gymnoasin A (1) was also achieved validating the chemical structure and affording ample amounts of material for exhaustive bioactivity assessments. Biological assays indicated that 1 could significantly inhibited in vitro NLRP3 inflammasome activation and in vivo pro‐inflammatory cytokine IL‐1β release, representing a valuable new lead compound for the development of novel therapeutics with the potential to inhibit the NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

A new alkaloid named aspergilalkaloid A (1) with pyridoindole hydroxymethyl piperazine dione structure along with six known compounds 2-7 were isolated from deep-sea derived fungus Aspergillus sp. HDN20-1401. The structure including absolute configuration was elucidated by extensive NMR analyses, HRESIMS, ECD calculation, and theoretical NMR calculation with DP4+ analysis. All isolated compounds were tested for antimicrobial and anticancer activity. Aspergilalkaloid A (1) showed inhibitive activity against Bacillus cereus with MIC value of 12.5 μM and weak activity against MRCNS. [ABSTRACT FROM AUTHOR]

Four new polyketides, namely furantides A–B (1–2), talamin E (3) and arugosinacid A (4), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3, with an IC50 value of 6.79 µM, was better than vitamin C. [ABSTRACT FROM AUTHOR]

Dimeric indole‐containing diketopiperazines (di‐DKPs) are a diverse group of natural products produced through cytochrome P450‐catalyzed C–C or C–N coupling reactions. The regio‐ and stereoselectivity of these reactions plays a significant role in the structural diversity of di‐DKPs. Despite their pivotal role, the mechanisms governing the selectivity in fungi are not fully understood. Employing bioinformatics analysis and heterologous expression experiments, five undescribed P450 enzymes (AmiP450, AcrP450, AtP450, AcP450, and AtuP450) responsible for the regio‐ and stereoselective dimerization of diketopiperazines (DKPs) in fungi are identified. The function of these P450s is consistent with phylogenetic analysis, highlighting their dominant role in controlling the dimerization modes. Combinatorial biosynthesis‐based pathway reconstitution of non‐native gene clusters expands the chemical space of fungal di‐DKPs and reveals that the regioselectivity is influenced by the substrate. Furthermore, multiple sequence alignment and molecular docking of these enzymes demonstrate a C‐terminal variable region near the substrate tunnel entrance in AtuP450 that is crucial for its regioselectivity. These findings not only reveal the secret of fungal di‐DKPs diversity but also deepen understanding of the mechanisms and catalytic specificity involved in P450‐catalyzed dimerization reactions. [ABSTRACT FROM AUTHOR]

Heterologous biosynthesis has become an effective means to activate fungal silent biosynthetic gene clusters (BGCs) and efficiently utilize fungal genetic resources. Herein, thirteen labdane diterpene derivatives, including five undescribed ones named talarobicins A–E (3–7), were discovered via heterologous expression of a silent BGC (labd) in Aspergillus nidulans. Their structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as electronic circular dichroism (ECD) calculations. These labdanes belong to four skeleton types, and talarobicin B (4) is the first 3,18-dinor-2,3:4,18-diseco-labdane diterpene with the cleavage of the C2–C3 bond in ring A and the decarboxylation at C-3 and C-18. Talarobicin B (4) represents the key intermediate in the biosynthesis of penioxalicin and compound 13. The combinatorial heterologous expression and feeding experiments revealed that the cytochrome P450 enzymes LabdC, LabdE, and LabdF were responsible for catalyzing various chemical reactions, such as oxidation, decarboxylation, and methylation. All of the compounds are noncytotoxic, and compounds 2 and 8 displayed inhibitory effects against methicillin-resistant coagulase-negative staphylococci (MRCNS) and Bacillus cereus. [ABSTRACT FROM AUTHOR]

Dynamic deflection deformation is a crucial index which can reflect the healthy operation of bridges; due to their limitations, monitoring technologies (e.g., sensors, automatic total stations, and GPS) cannot perform high-frequency and whole-process non-contact dynamic deformation monitoring. Therefore, taking the Jinan Fenghuangshan Road Bridge as an example, this paper developed key low-cost and high-precision close-range photogrammetry technology and combined this with GB-RAR technology to remotely monitor bridge dynamic deformation. The results indicate that the measurement accuracy pertaining to the technology, which is based on an isometric virtual surface, is approximately 0.5 mm when the monitoring distance is 250 m, which can meet the accuracy requirements of bridge deformation monitoring. A vehicle's dynamic load is transmitted in the form of a stress wave inside the bridge, and with regard to span, the wave is most significant in the 1/2 to 1/4 range. This study observes that the maximum deflection deformation of the bridge is 47.2 mm, which is within the allowable deformation range of the General Specifications for Design of Highway Bridges and Culverts. The research results herein provide technical support and data reference for safety monitoring, and for the reinforcement and maintenance of bridges such as the Fenghuangshan Road Bridge. [ABSTRACT FROM AUTHOR]

Coumarins, isocoumarins and their derivatives are polyketides abundant in fungal metabolites. Although they were first discovered over 50 years ago, the biosynthetic process is still not entirely understood. Herein, we report the activation of a silent nonreducing polyketide synthase that encodes a C7-methylated isocoumarin, similanpyrone B (1), in a marine-derived fungus Simplicillium lamellicola HDN13-430 by heterologous expression. Feeding studies revealed the host enzymes can change 1 into its hydroxylated derivatives pestapyrone A (2). Compounds 1 and 2 showed moderate radical scavenging activities with ED50 values of 67.4 µM and 104.2 µM. Our discovery fills the gap in the enzymatic elucidation of naturally occurring C7-methylated isocoumarin derivatives. [ABSTRACT FROM AUTHOR]

Phycocyanobilin (PCB) is the bioactive chromophore attached to Phycocyanin (PC) that is of special interest for nutraceutical and therapeutic applications. However, the production of PCB from the heterologous host Escherichia coli is still very low. To facilitate subsequent application of PCB, improving its production in microbial hosts is still a challenge to be solved. In this paper, a strategy involving fusion-expression of apo-proteins with signal peptides was adopted to improve PCB production in E. coli. First, we reconstructed the PCB biosynthesis pathway in E. coli and then optimized its culture media. Subsequently, one PC α (CpcA) subunit and one PC β (CpcB) subunit, which can capture free PCB, were introduced and increased the yield of PCB. Finally, CpcA was fused with seven signal peptides to generate recombinant proteins, among which, the signal peptide N20 fused with CpcA protein drastically improved PCB production in E. coli, providing a maximum flask output of 8.47 ± 0.18 mg/L. The results of this study demonstrate that PCB distribution and transporting manners in E. coli could affect the heterologous production efficiency. By fusing apo-proteins with signal peptides, the secretion of phycocyanin was refined and the production of PCB was successfully enhanced by 3.7-fold, compared with the starting strain (1.80 ± 0.12 mg/L). This work provided an alternative method for improving the production of PCB and other phycobilins. [ABSTRACT FROM AUTHOR]

It is well-known that structures composed of super high-rise buildings accumulate damages gradually due to ultra-long loads, material aging, and component defects. Thus, the bearing capacity of the structures can be significantly decreased. In addition, these effects may cause inestimable life and property losses upon strong winds, earthquakes, and other heavy loads. Hence, it is necessary to develop real-time health monitoring methods for super high-rise buildings to deeply understand the running state during operation, timely discover potential safety potentials, and to provide reference data for reinforcement design. Along these lines, in this work, the built super high-rise buildings (Yunding Building) and super high-rise buildings (the Main Tower of the Shandong International Financial Center), under construction, were selected as the research objects. The overall dynamic deformation laws of super high-rise buildings were monitored by using ground-based real aperture radar (GB-RAR) technology for its advantages in non-contact measurement, remote monitoring, and real-time display of observation results. Denoising of the observation data was also carried out based on wavelet analysis. The visualization of the space state of the Yunding Building was realized based on handheld LiDAR technology. From the acquired results, it was demonstrated that the measuring accuracy of GB-RAR could reach the submillimeter level, while the noises under a natural state of wavelet analysis were eliminated well. The maximum deformation values of the Yunding Building and the Main Tower of Shandong International Financial Center under their natural state were 9.63 mm and 16.46 mm, respectively. Under sudden wind loads, the maximum deformation of the Yunding Building could be as high as 895.79 mm. The overall motion state switched between an S-shaped pattern, hyperbolic-type, and oblique line, presented the characteristics of nonlinear elastic deformation. [ABSTRACT FROM AUTHOR]

In order to deeply study the mechanism of prestressed anchor anti-slide pile, an indoor model experimental device was developed, and a finite difference and particle flow numerical analysis model of slope anchor cable anti-slide pile was established based on the reinforcement project of prestressed anchor cable anti-slide pile in a mountain road slope. Based on the analysis of the force and displacement characteristics of the anti-slide pile, the influence of the prestress of the anchor cable, the inclination angle of the anchor cable, the width and column spacing of the anti-slide pile and the inclination angle of the landslide, the height and nature of the filling soil on the force and deformation characteristics of the pile are discussed, and some design parameters are optimized. Results show that the larger the prestress of the anchor cable, the smaller the displacement of the pile body, but the excessive stress is not conducive to the safety of the pile body. The optimal tension should be 50–70% of the designed tension of the anchor cable. With the increase in the inclination angle of the anchor cable, the displacement of the pile decreases first and then increases, and there is an optimal inclination angle of the anchor cable. In the double row piles, with the increase in pile spacing, the front row piles gradually change from supporting the soil between the double row piles to supporting the sliding body with the back row piles, and the double row piles are plum-shaped. When the pile spacing is 2.5 times the pile diameter, the force of the front and rear piles is the most reasonable. In the process of soil arching evolution, the influence of cohesion on the soil arching effect is greater than that of the internal friction angle. [ABSTRACT FROM AUTHOR]

To resolve insufficient traditional bolt supports due to the complexity of geological conditions, the optimal design of an expanded head bolt was investigated by using theoretical calculations and experiments. The results show that the drawing capacity of an expanded head bolt is affected by the bearing capacity of front and rear ends, side bearing capacity, and side friction resistance. For a circular anchor bolt, stepped anchor bolt, and semi-ellipsoidal anchor bolt, with an increase in the front section's radius, the lateral friction resistance of the inner anchor section is gradually shared by the bearing force of the front end of the inner anchor section; the bearing effect of the front end of the inner anchor section is enhanced; and the pulling performance of the anchor bolt is enhanced. Therefore, the pulling force of the circular anchor bolt is at the maximum, followed by the stepped anchor bolt, and the semi-ellipsoidal bolt is at the minimum. The increase in the rear section can provide greater lateral friction resistance and end-bearing force. Compared with cylindrical enlarged head anchors, the circular, stepped, and semi-elliptic enlarged head anchors have a smaller front section but a larger rear section, and the reduction in the front section's bearing capacity is less than the increase in the side bearing capacity and rear-end bearing capacity; thus, the cylindrical bolt has the lowest pulling force. Compared with the front radius, the back radius has more influence on the drawing ability of the enlarged head anchor. The longer the inner anchorage section, the larger the distribution range in the compression zone that is formed in the soil body and the smaller the range in the tension zone that is formed in the rear. The increase in the length of the inner anchorage section is conducive to improving the reinforcement effect of the soil in front of the anchorage section in the bolt. Therefore, this parameter plays an important role in the redistribution of the soil in front of the force. The ultimate pull-out force of a circular table-shaped tensile bolt is the highest, followed by the stepped bolt, and the semi-elliptic bolt comes in third, with the cylindrical bolt exhibiting the lowest pull-out force; the circular table-shaped enlarged head anchor constitutes the best style design. [ABSTRACT FROM AUTHOR]

Six angucyclines including three unreported compounds (1–3) were isolated from Streptomyces sp. XS-16 by overexpressing the native global regulator of SCrp (cyclic AMP receptor). The structures were characterized based on nuclear magnetic resonance (NMR) and spectrometry analysis and assisted by electronic circular dichroism (ECD) calculations. All compounds were tested for their antitumor and antimicrobial activities, and compound 1 showed different inhibitory activities against various tumor cell lines with IC50 values ranging from 0.32 to 5.33 μM. [ABSTRACT FROM AUTHOR]