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The continuous emergence of resistant bacteria has become a major worldwide health threat. The current development of new antibacterials has lagged far behind. To discover reagents to fight against resistant bacteria, we initiated a chemical approach by synthesizing and screening a small molecule library, reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of structurally diverse natural products, many of which were isolated from plants that have been used as traditional medicine for millennia. Specifically, we adapted an evolutionarily conserved biosynthetic strategy and developed a concise and unified diversity synthesis pathway. Using this pathway, we synthesized 120 polycyclic indolines that contain 26 distinct skeletons and a wide variety of functional groups. A tricyclic indoline, Of1, was discovered to selectively potentiate the activity of β-lactam antibiotics in multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin-sensitive S. aureus. In addition, we found that Of1 itself does not have antiproliferative activity but can resensitize several MRSA strains to the β-lactam antibiotics that are widely used in the clinic, such as an extended-spectrum β-lactam antibiotic amoxicillin/clavulanic acid and a first-generation cephalosporin cefazolin. These data suggest that Of1 is a unique selective resistancemodifying agent for β-lactam antibiotics, and it may be further developed to fight against resistant bacteria in the clinic.

A Global Navigation Satellite System (GNSS)/Inertial Navigation System (INS)/Light Detection and Ranging (LiDAR)-Simultaneous Localization and Mapping (SLAM) integrated navigation system based on graph optimization is proposed and implemented in this paper. The navigation results are obtained by the information fusion of the GNSS position, Inertial Measurement Unit (IMU) preintegration result and the relative pose from the 3D probability map matching with graph optimizing. The sliding window method was adopted to ensure that the computational load of the graph optimization does not increase with time. Land vehicle tests were conducted, and the results show that the proposed GNSS/INS/LiDAR-SLAM integrated navigation system can effectively improve the navigation positioning accuracy compared to GNSS/INS and other current GNSS/INS/LiDAR methods. During the simulation of one-minute periods of GNSS outages, compared to the GNSS/INS integrated navigation system, the root mean square (RMS) of the position errors in the North and East directions of the proposed navigation system are reduced by approximately 82.2% and 79.6%, respectively, and the position error in the vertical direction and attitude errors are equivalent. Compared to the benchmark method of GNSS/INS/LiDAR-Google Cartographer, the RMS of the position errors in the North, East and vertical directions decrease by approximately 66.2%, 63.1% and 75.1%, respectively, and the RMS of the roll, pitch and yaw errors are reduced by approximately 89.5%, 92.9% and 88.5%, respectively. Furthermore, the relative position error during the GNSS outage periods is reduced to 0.26% of the travel distance for the proposed method. Therefore, the GNSS/INS/LiDAR-SLAM integrated navigation system proposed in this paper can effectively fuse the information of GNSS, IMU and LiDAR and can significantly mitigate the navigation error, especially for cases of GNSS signal attenuation or interruption.

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“Diazo” not needed: The title reaction results in the rearrangement of oxonium ylides, which were prepared from readily available homopropargylic allylic ethers instead of diazo compounds, through two different mechanisms: a concerted 2,3‐sigmatropic rearrangement, or a stepwise 1,4‐allyl migration followed by a Claisen rearrangement (see scheme).

Previously we discovered a tricyclic indoline, N-[2-(6-bromo-4-methylidene-2,3,4,4a,9,9a-hexahydro-1H-carbazol-4a-yl)ethyl]-4-chlorobenzene-1-sulfonamide (1, Of1), from bioinspired synthesis of a highly diverse polycyclic indoline alkaloid library, that selectively resensitizes methicillin-resistant Staphylococcus aureus strains to β-lactam antibiotics. Herein, we report a thorough structure–activity relationship investigation of 1, which identified regions of 1 that tolerate modifications without compromising activity and afforded the discovery of a more potent analogue with reduced mammalian toxicity.