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Tuberculosis (TB) is a life-threatening disease resulting in an estimated 10 million new infections and 1.8 million deaths annually, primarily in underdeveloped countries. The economic burden of TB has been estimated as approximately 12 billion USD annually in direct and indirect costs. Additionally, multi-drug-resistant (MDR) and extreme-drug-resistant (XTR) TB strains resulting in about 250 000 deaths annually are now widespread, increasing pressure on the identification of new anti-TB agents that operate by a novel mechanism of action. Chrysomycin A is a rare C-aryl glycoside first discovered over 60 years ago. In a recent highthroughput screen, we found that chrysomycin A has potent anti-TB activity, with minimum inhibitory concentration (MIC) = 0.4 μg/mL against MDR-TB strains. However, chrysomycin A is obtained in low yields from fermentation of Streptomyces, and the mechanism of action of this compound is unknown. To facilitate the mechanism of action and preclinical studies of chrysomycin A, we developed a 10-step, scalable synthesis of the isolate and its two natural congeners polycarcin V and gilvocarcin V. The synthetic sequence was enabled by the implementation of two sequential C−H functionalization steps as well as a late-stage C-glycosylation. In addition, >10 g of the advanced synthetic intermediate has been prepared, which greatly facilitated the synthesis of 33 new analogues to date. The structure−activity relationship was subsequently delineated, leading to the identification of derivatives with superior potency against MDR-TB (MIC = 0.08 μg/mL). The more potent derivatives contained a modified carbohydrate residue which suggests that further optimization is additionally possible. The chemistry we report here establishes a platform for the development of a novel class of anti-TB agents active against drug-resistant pathogens.

Three‐dimensional (3D) graphene hydrogel (GH) architectures are of great interest in applications towards electronics, environmental fields, catalysis devices, and sensors. However, due to the structure constraints of graphene, only macropore and low specific surface areas are obtained. Conjugated microporous polymers always possess a micro‐ and mesopore structure simultaneously, but the conductivity is very poor. However, both the conductivity and the pore parameter are important factors affecting the performance of capacitor. Here, we propose a facile and highly efficient method to improve the microstructure of GH, enlarging the conductivity of CMPs, simultaneously. Porphyrin‐based conjugated microporous polymer (CMP) gels were integrated tightly on the surface of GH via a room‐temperature oxidative homocoupling reaction, resulting a new composite (GH‐CMP) with excellent conductivity, enlarged BET surface area, and hierarchical pore structure. The fabricated GH‐CMP was used as the electrode material for capacitors. The hierarchical pore structure is beneficial for mass transfer, facilitates the diffusion, and further enhances the specific capacitance. The resultant supercapacitor electrodes presented a high capacitance of 208 F g−1 at 20 mA g−1 and an excellent cycle stability with a retained capacitance of about 92.6 % after 10 000 cycles at 2 A g−1. The integration of CMPs and GH makes graphene hydrogel films an ideal electrode material for supercapacitors.

HFD (high-fat diet) induces obesity and metabolic disorders, which is associated with the alteration in gut microbiota profiles. However, the underlying molecular mechanisms of the processes are poorly understood. In this study, we used the simple model organism honey bee to explore how different amounts and types of dietary fats affect the host metabolism and the gut microbiota. Excess dietary fat, especially palm oil, elicited higher weight gain, lower survival rates, hyperglycemic, and fat accumulation in honey bees. However, microbiota-free honey bees reared on high-fat diets did not significantly change their phenotypes. Different fatty acid compositions in palm and soybean oil altered the lipid profiles of the honey bee body. Remarkably, dietary fats regulated lipid metabolism and immune-related gene expression at the transcriptional level. Gene set enrichment analysis showed that biological processes, including transcription factors, insulin secretion, and Toll and Imd signaling pathways, were significantly different in the gut of bees on different dietary fats. Moreover, a high-fat diet increased the relative abundance of Gilliamella, while the level of Bartonella was significantly decreased in palm oil groups. This study establishes a novel honey bee model of studying the crosstalk between dietary fat, gut microbiota, and host metabolism.

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