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Dysregulation of cholesterol homeostasis is associated with many diseases such as cardiovascular disease and cancer. Liver X receptors (LXRs) are major upstream regulators of cholesterol homeostasis and are activated by endogenous cholesterol metabolites such as 27-hydroxycholesterol (27HC). LXRs and various LXR ligands such as 27HC have been described to influence several extra-hepatic biological systems. However, disparate reports of LXR function have emerged, especially with respect to immunology and cancer biology. This would suggest that, similar to steroid nuclear receptors, the LXRs can be selectively modulated by different ligands. Here, we use RNA-sequencing of macrophages and single-cell RNA-sequencing of immune cells from metastasis-bearing murine lungs to provide evidence that LXR satisfies the 2 principles of selective nuclear receptor modulation: (1) different LXR ligands result in overlapping but distinct gene expression profiles within the same cell type, and (2) the same LXR ligands differentially regulate gene expression in a highly context-specific manner, depending on the cell or tissue type. The concept that the LXRs can be selectively modulated provides the foundation for developing precision pharmacology LXR ligands that are tailored to promote those activities that are desirable (proimmune), but at the same time minimizing harmful side effects (such as elevated triglyceride levels).

Sow litter sizes have increased over recent decades, increasing the need for cross-fostering. The objective of this study was to determine the effect of the number of source litters used to create cross-fostered litters on piglet pre-weaning mortality (PWM) and weaning weight. A RCBD was used with 26 blocks of 5 litters (total 130 litters/1820 piglets), all litters consisted of 14 piglets. Blocking factors were farrowing day, sow parity, body condition score, and functional teat number, and the average and CV of piglet birth weight. Five cross-fostering treatments were compared: 0%, 1 source (all piglets remaining on the birth sow); 100%, 1 source (all piglets moved from birth to a different sow); 100%, 6+ sources (piglets from ≥ 6 birth sows used to form a litter on a different sow); 50%, 2 sources (7 piglets remaining with birth sow, 7 from one other sow); 50%, 4+ sources (7 piglets remaining with the birth sow, 7 from ≥ 3 other sows). The single-source litters were selected from those with > 14 piglets at birth, with excess piglets removed. For other treatments, piglets were selected to meet blocking factors. Piglets were weighed 24 h after birth and at weaning (19.5 ± 0.50 d); all PWM was recorded. Weight data were analyzed using PROC MIXED of SAS; PWM data were analyzed using PROC GLIMMIX of SAS. Models included Treatment and sow within block. There was no effect (P > 0.05) of treatment on weaning weights. Pre-weaning mortality was greater (P < 0.05) for the 0%, 1 source compared to the 50%, 2 source treatment, with the others being intermediate and generally not statistically different (Table 1). In conclusion, cross-fostering and/or mixing litters had no effect on weaning weights, but pre-weaning mortality was highest for the non-fostered treatment.

Litter sizes of commercial sows have increased recently, often resulting in the number of piglets exceeding the sow functional teat number. The objective of this study was to determine the effects of litter size after cross-fostering on piglet pre-weaning mortality (PWM) and growth. A RCBD was used with 13 blocks of 3 litters (total 39 litters/561 piglets); blocking factors were farrowing day, sow parity, body condition score, and functional teat number. Three Litter Size treatments (LS) relative to sow functional teat number were compared: Under (2 piglets below); Equal (same number of piglets); Over (2 piglets above). Piglets were weighed 24 h after birth and allotted to LS to create litters with similar gender ratio and average and CV of birth weight. Weaning was at 19.5 ± 0.50 d, weights and PWM were recorded. Piglet weight data were analyzed using PROC MIXED of SAS; PWM data were analyzed using PROC GLIMMIX of SAS. Models included LS and sow within block. Litter sizes averaged 12.1, 14.1, and 16.1 for the Under, Equal, and Over treatments, respectively (P ≤ 0.05). The Under treatment tended (P = 0.07) to have greater weaning weights compared to the Equal and Over treatments (Table 1). The Under treatment had lower (P ≤ 0.05) PWM than the Over treatment, with the Equal treatment being intermediate and not different to the other 2 (P > 0.05; Table 1). In conclusion, reducing litter size after cross-fostering to two piglets below the number of functional teats of the sow decreased PWM and tended to increase weaning weights.

Cross-fostering of piglets is a common commercial practice, however, there is limited information on optimum methods. The objective of this study was to evaluate the effects of within-litter birth weight variation after cross-fostering on piglet pre-weaning mortality (PWM) and growth. A RCBD was used with 47 blocks of 6 litters (total 282 litters/3,948 piglets); blocking factors were farrowing day, sow parity, body condition score, and functional teat number. Piglets were allotted at 24 h after birth according to Birth Weight Category (BWC) [L (< 1.0 kg), M (1.0 to 1.5 kg), or H (1.5 to 2.0 kg)] to 6 Litter Composition (LC) treatments with 14 piglets/litter: Uniform (14 L, M or H); Mixed L+M (7 L, 7 M); Mixed M+H (7 M, 7 H); Mixed L+M+H (3 L, 6 M, 5 H). Piglets were weaned at 18.7 ± 0.64 d and PWM was recorded. Piglet birth and weaning weights were analyzed using PROC MIXED of SAS; PWM were analyzed using PROC GLIMMIX of SAS; models included BWC, LC, the interaction, and sow within block. There were LC by BWC interactions (P < 0.05) for PWM and weaning weights. For L piglets, there was no effect (P > 0.05) of LC on PWM (22.8, 26.7, and 28.4% for Uniform, Mixed L+M, and Mixed L+M+H treatments, respectively). For H piglets, PWM was lower (P < 0.05) in Mixed L+M+H compared to Uniform or Mixed M+H litters (1.7, 9.6, and 5.8%, respectively). For M piglets, PWM was lower (P < 0.05) in Mixed L+M than Uniform or Mixed M+H litters (7.1, 12.2, and 14.6%, respectively); Mixed L+M+H were intermediate (10.0%; P > 0.05). Weaning weights generally followed a similar but opposite pattern for all BWC. In conclusion, increasing the average weight of littermates generally decreased weaning weights and increased PWM within each BWC.

Low blood glucose levels at the start of farrowing have been associated with increased farrowing duration and stillbirth rate. This study evaluated changes in sow blood glucose (BG) on the day of farrowing and investigated relationships between sow and litter parameters and BG. The study was carried out over 12 h from 0600h (time of last feeding) on the day sows were induced to farrow (d 115 of gestation) as a cross-sectional survey using 42 sows/gilts of which 32 farrowed. Blood samples (1.2 μL) were collected from an ear vein of each sow every 2 h from 0600 h; glucose was measured using a glucometer (Accuchek Aviva; Roche Diabetes Care, Inc., Indianapolis, IN). Sow parameters recorded included parity, body condition score (BCS: 1 = extremely thin to 5 = extremely fat), number of piglets born, total litter birth weight, and farrowing duration. Linear relationships between sow parameters and BG were developed using PROC REG of SAS. Sows that farrowed had similar (P > 0.05) BG to those that did not (84.4 vs. 86.8 mg/dL; SEM 1.76). Regression relationships between sow parameters and BG were generally weak (adjusted R2 ≤ 0.20). There was no effect (P > 0.05) of time after feeding, time after start of farrowing, or time interval between piglet births on BG. Average BG levels increased linearly (P < 0.05) with sow BCS (7.6 mg/dL/BCS; SE 2.63) but decreased linearly (P < 0.05) with sow parity (-2.5 mg/dL/litter; SE 0.96), litter size (-0.8 mg/dL/piglet; SE 0.28), litter weight (-0.06 mg/dL/kg; SE 0.26), and farrowing duration (-1.8 mg/dL/h; SE 0.82). In contrast to previous research, changes in BG from last feed to start of farrowing (which ranged from 0 to 9 h) and relationship with other sow and litter parameters were relatively limited.

Blood glucose levels in piglets at birth are potentially associated with survival, however, there has been limited research to quantify these and to establish any associations with piglet characteristics. This study, which evaluated the effects of a number of piglet characteristics on blood glucose levels at birth, was conducted as a cross-sectional survey involving 32 litters. Litter was the experimental unit; piglet was a sub-sample of litter. At birth, piglets were weighed and assigned a vitality score [1 = high vitality; 2 = low vitality (limited mobility and/or respiration)]. Piglets were then dried with a cellulose-based desiccant, and blood samples were collected from half of the piglets in each litter with a vitality score of 1 (n = 226) and all piglets with a vitality score of 2 (n = 7). Samples (1.2 μL) were collected from the vena subcutanea abdominis; blood glucose was measured using a glucometer (Accuchek Aviva; Roche Diabetes Care, Inc., Indianapolis, IN). Effects of piglet characteristics and relationships with blood glucose levels were analyzed using PROC MIXED, PROC GLIMMIX, and PROC REG of SAS, as appropriate. There were no effects (P > 0.05) of piglet birth weight or gender on blood glucose levels. Piglets with a vitality score of 2 had higher (P < 0.05) blood glucose levels than those with a score of 1. Blood glucose levels increased linearly (P < 0.05) with birth order (0.8 mg/dL for each piglet increase). In conclusion, blood glucose levels at birth were higher for piglets with low compared to high vitality and for those born later in the birth order. Further research is needed to establish relationships between blood glucose levels in piglets at birth and subsequent survival.