This experiment was conducted to investigate the effects of dietary supplementation of α-glycerol monolaurate (α-GML) on the growth performance, nutrient digestibility, serum profiles, intestinal morphology, and gut microbiota of weaned piglets. A total of 96 healthy 28-d-old (Duroc × Landrace × Yorkshire) weaned piglets with body weight of 8.34 ± 0.05 kg were randomly divided into 2 treatment groups with 6 replicate pens and 8 piglets per pen. The control group was fed a basal diet and the experimental group was fed the basal diet supplemented with 1,000 mg/kg α-GML. The experiment lasted for 28 d. Dietary supplementation with α-GML had no effect on average daily gain, average daily feed intake, or gain to feed ratio in piglets (P > 0.05); however, it reduced (P < 0.05) diarrhea rate of piglets on days 15 to 28. The apparent total tract digestibility of dry matter (DM), crude protein (CP), ether extract (EE), and gross energy (GE) on day 14, and DM, organic matter, CP, EE, and GE on day 28 increased (P < 0.05) with α-GML supplementation. Moreover, higher (P < 0.05) glutathione peroxidase activity and interleukin-10 (IL-10) concentration, and lower (P < 0.05) malondialdehyde and tumor necrosis factor-α concentrations were observed in piglets supplemented with α-GML compared with the control group on day 14. Compared with the control group, the villus height/crypt depth in the duodenum and villus height in the jejunum and ileum were significantly greater (P < 0.05) in the α-GML group. Dietary α-GML supplementation significantly increased (P < 0.05) the relative abundance of Firmicutes, while decreasing (P < 0.05) Bacteroidota and Campilobacterota in the cecal contents; significantly increased (P < 0.05) the relative proportion of Lactobacillus and Blautia species, reduced (P < 0.05) Eubacterium_rectale_ATCC_33656, Campylobacter, and uncultured_bacterium_Alloprevotella species. Thus, dietary α-GML supplementation at 1,000 mg/kg reduces diarrhea rate, improves intestinal morphology, nutrient digestibility, antioxidant capacity, and immune status, and ameliorates gut microbiota in weaned piglets.

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a “selective starvation” strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution. Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure–activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter.

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Solubility data were measured for omeprazole sulfide in ethanol, 95 mass-% ethanol, ethyl acetate, isopropanol, methanol, acetone, n-butanol and n-propanol in the temperature range from 280.35 to 319.65 K by employing the gravimetric method. The solubilities increase with temperature and they are in good agreement with the calculated solubility of the modified Apelblat equation and the λh equation. The experimental solubility and correlation equation in this work can be used as essential data and model in the purification process of omeprazole sulfide. The thermodynamic properties of the solution process, including the Gibbs energy, enthalpy, and entropy were calculated using the van’t Hoff equation.

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Summary Toll-like receptor 8 (TLR8) is a pattern recognition receptor that senses RNA degradation products and initiates immune responses. TLR8 overactivation is associated with autoimmune diseases. Herein, we describe the evaluation and validation of TLR8 antagonists in HEK-Blue cells via secreted embryonic alkaline phosphatase (SEAP) assay, WST assay, ITC and immunoblotting. These assays can facilitate the development of TLR8 antagonists; this protocol can also be adapted to analyze agonists and antagonists for other TLRs. For complete details on the use and execution of this protocol, please refer to Hu et al. (2018) .