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The experiment aimed to investigate the effects of microbial preparations on the growth and intestinal microbiota of crucian carp. Three hundred evenly sized crucian carp were randomly divided into five groups, with three replicates in each group, and 20 fish in each replicate. The group A was fed a feed containing mixed lactic acid bacteria preparations, the group B was fed a feed containing mixed Clostridium butyricum preparations, the group C was fed a feed containing a mixture of lactic acid bacteria and Clostridium butyricum preparations, the group D was fed a feed containing a mixture of lactic acid bacteria, Clostridium butyricum preparations, and 3 mg/g nano-selenium. The control group (CK group) was fed a basic feed. The experimental period lasted for 28 days. The results showed that the weight gain rate of crucian carp in the group A, group B, and group D was higher than that in the CK group ( P<0.05). The condition factor and feed coefficient of crucian carp in the group A were higher than those in the CK group ( P<0.05). The hepatopancreas SOD activity of crucian carp in the group D was higher than that in the CK group ( P<0.05), and the hepatopancreas LZM activity in the group B was higher than that in the CK group ( P<0.05). The abundance of Fusobacteria in the intestines of crucian carp in the group A significantly increased, while the abundance of Bacteroidetes in the intestines of crucian carp in the group B significantly increased. The study indicates that adding lactic acid bacteria, Clostridium butyricum, and nano-selenium to the feed can promote the growth of crucian carp, alter the community structure of the intestinal microbiota, and inhibit harmful bacteria in the intestines. [ABSTRACT FROM AUTHOR]

Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs. [ABSTRACT FROM AUTHOR]