The knowledge of drug concentrations in bilayer headgroups, core, and at the interface between them is a prerequisite for quantitative modeling of drug interactions with many membrane-bound transporters, metabolizing enzymes and receptors, which have the binding sites located in the bilayer. This knowledge also helps understand the rates of trans-bilayer transport because balanced interactions of drugs with the bilayer strata lead to high rates, while excessive affinities for any stratum cause a slowdown. Experimental determination of bilayer location is so tedious and costly that the data are only available for some fifty compounds. To extrapolate these valuable results to more compounds at a higher throughput, surrogate phases have been used to obtain correlates of the drug affinities for individual strata. We introduced a novel system, consisting of a diacetyl phosphatidylcholine (DAcPC) solution with the water content of the fluid bilayer as the headgroup surrogate and n-hexadecane (C16) representing the core. The C16/DAcPC partition coefficients were measured for 113 selected compounds, containing structural fragments that are frequently occurring in approved drugs. The data were deconvoluted into the ClogP-based fragment solvation characteristics and processed using a solvatochromic correlation. Increased H-bond donor ability and excess molar refractivity of compounds promote solvation in the DAcPC phase as compared to bulk water, contrary to H-bond acceptor ability, dipolarity/polarizability, and volume. The results show that aromates have more balanced distribution in bilayer strata, and thus faster trans-bilayer transport, than similar alkanes. This observation is in accordance with the frequent occurrence of aromatic rings in approved drugs and with the role of rigidity of drug molecules in promoting intestinal absorption. Bilayer locations, predicted using the C16/DAcPC system, are in excellent agreement with available experimental data, in contrast to other surrogate systems.

Surrogate phases have been widely used as correlates for modeling transport and partitioning of drugs in biological systems, taking advantage of chemical similarity between the surrogate and the phospholipid bilayer as the elementary unit of biological phases, which is responsible for most of transport and partitioning. Solvation in strata of the phospholipid bilayer is an important drug characteristics because it affects the rates of absorption and distribution, as well as the interactions with the membrane proteins having the binding sites located inside the bilayer. The bilayer core can be emulated by n-hexadecane (C16), and the headgroup stratum is often considered a hydrophilic phase because of the high water content. Therefore, we tested the hypothesis that the C16/water partition coefficients (P) can predict the bilayer locations of drugs and other small molecules better than other surrogate systems. Altogether 514 PC16/W values for nonionizable (458) and completely ionized (56) compounds were collected from the literature or measured, when necessary. With the intent to create a fragment-based prediction system, the PC16/W values were factorized into the fragment solvation parameters (f) and correction factors based on the ClogP fragmentation scheme. A script for the PC16/W prediction using the ClogP output is provided. To further expand the prediction system and reveal solvation differences, the fC16/W values were correlated with their more widely available counterparts for the 1-octanol/water system (O/W) using solvatochromic parameters. The analysis for 50 compounds with known bilayer location shows that the available and predicted PC16/W and PO/W values alone or the PC16/O values representing their ratio do not satisfactorily predict the preference for drug accumulation in bilayer strata. These observations indicate that the headgroups stratum, albeit well hydrated, does not have solvation characteristics similar to water and is also poorly described by the O/W partition characteristics.

Polymorphisms of BMP15 gene exon 2 and its relationship with prolificacy of goats were detected by PCR-SSCP and DNA sequencing methods in Chinese two local goat breeds. The results showed that the product amplified by the primers displayed polymorphisms. Three genotypes (AA, BB and AB) were detected in Funiu white goats, and their frequency was 0.071, 0.715, 0.214, respectively. Two genotypes (AB and BB) were detected in Taihang black goats, and their frequency was 0.342 and 0.658, respectively. Sequencing revealed that four mutations (456T→G, 466C→G, 510C→T, 511T→C) occurred in genotype BB of Funiu white goat, which resulted in amino acid substitution of V155G and S171P. No mutation was detected in Taihang black goat. The Funiu white goat with genotype BB had 0.91 or 0.82 kids, more than those with AB or AA, respectively. The difference of the least squares means for litter size between BB and AB was not significant (p>0.05) in Taihang black goat. It is concluded that the BMP15 gene may be a major gene which affects the prolificacy in Funiu white goats. This study could provide basic molecular data on the reproductive characteristics of local breeds of Henan province in China, and a scientific basis for the conservation and utilization of those two goat breeds.

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Novel polymethacrylate-functionalized octaphenylsilsesquioxanes (OPS) macromonomer was designed and synthesized, which was employed as nanofiller and cross-linker to copolymerize with MMA to produce OPS/PMMA hybrid nanocomposites with OPS contents ranging from 0 to 1.18 mol %. The synthesis route was that, OPS was brominated to yield polybromo-OPS, and polybromo-OPS was then reacted with BuLi and CO 2 to obtain polycarboxyl-OPS. After that, the carboxyls were converted to chlorocarbonyl groups, and the esterification reaction of polychlorocarbonyl-OPS with 2-hydroxyethyl methacrylate led to polymethacrylate-OPS. Their chemical structures were characterized by means of FTIR, 1 H NMR and 13 C NMR spectra. Moreover, after cleavage of C-Si bond by KF/H 2 O 2 , the position and number of functional groups on the benzene rings of OPS macromonomers and the molecular weight of PMMA in the nanocomposite were investigated in detail by LC-MS and GPC methods, respectively. The prepared OPS macromonomer can result into PMMA significantly improved thermal-chemical stability and apparently increased glass transition temperature. For example, the nanocomposites are insoluble in any common organic solvents due to the formation of three-dimensional networks. Compared to the pure PMMA, the OPS/PMMA nanocomposite with OPS content of only 0.94 mol % exhibits increased 5%-mass-loss temperature and glass transition temperature by 104 and 21 °C, respectively.

To explore the feasibility of dietary Chinese herbal residue (CHR) supplementation in swine production with the objective of valorization, we examined the effects of dietary supplementation with CHR or fermented CHR products on the colonic ecosystem (i.e., microbiota composition, luminal bacterial metabolites, and expression of genes related to the intestinal barrier function in weaned piglets). We randomly assigned 120 piglets to one of four dietary treatment groups: a blank control group, CHR group (dose of supplement 4 kg/t), fermented CHR group (dose of supplement 4 kg/t), and a positive control group (supplemented with 0.04 kg/t virginiamycin, 0.2 kg/t colistin, and 3000 mg/kg zinc 0.04 kg/t virginiamycin, 0.2 kg/t colistin, and 3000 mg/kg zinc oxide). Our results indicate that dietary supplementation with CHR increased (P < 0.05) the mRNA level corresponding to E-cadherin compared with that observed in the other three groups, increased (P < 0.05) the mRNA level corresponding to zonula occludens-1, and decreased (P < 0.05) the quantity of Bifidobacterium spp. When compared with the blank control group. Dietary supplementation with fermented CHR decreased (P < 0.05) the concentration of indole when compared to the positive control group; increased (P < 0.05) the concentrations of short-chain fatty acids compared with the values measured in the CHR group, as well as the mRNA levels corresponding to interleukin 1 alpha, interleukin 2, and tumor necrosis factor alpha. However, supplementation with fermented CHR decreased (P < 0.05) interleukin 12 levels when compared with the blank control group. Collectively, these findings suggest that dietary supplementation with CHR or fermented CHR modifies the gut environment of weaned piglets.

Supplementary Figure S1. Rarefaction curves of samples (n = 8) clustered at 97% sequence identity. OTU, operational taxonomic unit; CON, Control group; EF, Group II (7.5 • 10 8 cfu Enterococcus faecalis/kg diet).

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