Transcriptome in Liver of Periparturient Dairy Cows Differs between Supplementation of Rumen-Protected Niacin and Rumen-Protected Nicotinamide.

To investigate the difference between rumen-protected niacin (RPN) and rumen-protected nicotinamide (RPM) in the transcriptome of genes relating to the lipid metabolism of the liver of periparturient dairy cows, 10 healthy Chinese Holstein cows were randomly divided into two groups and fed diets supplemented with 18.4 g/d RPN or 18.7 g/d RPM, respectively. The experiment lasted from 14 days before to 21 days after parturition. Liver biopsies were taken 21 days postpartum for transcriptomic sequencing. In addition, human LO2 cells were cultured in a medium containing 1.6 mmol/L of non-esterified fatty acids and 1 mmol/L niacin (NA) or 2 mmol/L nicotinamide (NAM) to verify the expression of the 10 genes selected from the transcriptomic analysis of the liver biopsies. The expression of a total of 9837 genes was detected in the liver biopsies, among which 1210 differentially expressed genes (DEGs) were identified, with 579 upregulated and 631 downregulated genes. These DEGs were associated mainly with lipid metabolism, oxidative stress, and some inflammatory pathways. Gene ontology (GO) enrichment analysis showed that 355 DEGs were enriched in 38 GO terms. The differences in the expression of these DEGs between RPN and RPM were predominantly related to the processes of steroid catabolism, steroid hydroxylase, monooxygenase activity, oxidoreductase activity, hemoglobin binding, and ferric iron binding, which are involved mainly in lipid anabolism and redox processes. The expressions of FADS2, SLC27A6, ARHGAP24, and THRSP in LO2 cells were significantly higher (p < 0.05) while the expressions of BCO2, MARS1, GARS1, S100A12, AGMO, and OSBPL11 were significantly lower (p < 0.05) on the NA treatment compared to the NAM treatment, indicating that NA played a role in liver metabolism by directly regulating fatty acid anabolism and transport, inflammatory factor expression, and oxidative stress; and NAM functioned more as a precursor of nicotinamide adenine dinucleotide (NAD, coenzyme I) and nicotinamide adenine dinucleotide phosphate (NADP, coenzyme II) to participate indirectly in biological processes such as ether lipid metabolism, cholesterol metabolism, energy metabolism, and other processes.

Trends in gut-heart axis and heart failure research (1993-2023): A bibliometric and visual analysis.

Background: The incidence of heart failure, the terminal stage of several cardiovascular diseases, is increasing owing to population growth and aging. Bidirectional crosstalk between the gut and heart plays a significant role in heart failure. This study aimed to analyze the gut-heart axis and heart failure from a bibliometric perspective. Methods: We extracted literature regarding the gut-heart axis and heart failure from the Web of Science Core Collection database (January 1, 1993, to June 30, 2023) and conducted bibliometric and visualization analyses using Microsoft Excel, CiteSpace, VOSviewer, and the R package "bibliometrix." Results: The final analysis included 1646 articles with an average of 35.38 citations per article. Despite some fluctuations, the number of articles published per year has steadily increased over the past 31 years, particularly since 2018. A total of 9412 authors from 2287 institutions in 86 countries have contributed to this field. The USA and China have been the most productive countries, with the Cleveland Clinic in the USA and Charité-Universitätsmedizin Berlin in Germany being the most active institutions. The cooperation between countries/regions and institutions was relatively close. Professor Tang WHW was the most productive author in the field and the journal Shocks published the highest number of articles. "Heart failure," "gut microbiota," "trimethylamine N-oxide," and "inflammation" were the most common keywords, representing the current research hotspots. The keyword burst analysis indicated that "gut microbiota" and "short-chain fatty acids" are the current frontier research topics in this field. Conclusion: Research on the gut-heart axis and heart failure is increasing. This bibliometric analysis indicated that the mechanisms associated with the gut-heart axis and heart failure, particularly the gut microbiota, trimethylamine N-oxide, inflammation, and short-chain fatty acids, will become hotspots and emerging trends in research in this field. These findings provide valuable insights into current research and future directions.

Engineering P-Fe2O3-CoP nanosheets for overall freshwater and seawater splitting.

Tailoring surface composition and coordinative environment of catalysts in a nano-meter region often influence their chemical performance. It is reported that CoP exhibits a low dissociation ability of H-OH, originating from the poor desorption of intermediate species. Herein, we provide a feasible method to construct P-Fe2O3-CoP nanosheets through a gas-phase phosphorization process. P doping induces the formation of interfacial structure between Fe2O3 and CoP and the generation of defective structures. The resulting P-Fe2O3-CoP nanosheets afford high freshwater/seawater oxidation activity (250/270 mV@10 mA/cm2) in 1 mol/L (M) KOH, which is even lower than commercial RuO2. Compared with CoP||CoP, P-Fe2O3||P-Fe2O3, and Co3O4||Co3O4, the assembled P-Fe2O3-CoP||P-Fe2O3-CoP exhibits the superior water/seawater electrolysis performance with 1.61/1.65 V@10 mA/cm2. The synergistic effect of P doping, defective structure, and heterojunction leads to high water oxidation efficiency and water splitting efficiency.

Nicotinamide supplementation alters plasma lipidomic profiles of peripartal dairy cows.

Fatty liver syndrome, a common health problem in dairy cows, occurs during the transition from pregnancy to lactation. If the energy supplied to the cow's body cannot meet its needs, a negative energy balance ensues, and the direct response is fat mobilization. Nicotinamide (NAM) has been reported to reduce the nonesterified fatty acid concentration of postpartum plasma. To study the biochemical adaptations underlying this physiologic dysregulation, 12 dairy cows were sequentially assigned to a NAM (45 g/day) treatment or control group. Blood samples were collected on day (D) 1 and D21 relative to parturition. Changes to the plasma lipid metabolism of dairy cows in the two groups were compared using lipidomics. There were significant increases in plasma sphingomyelins d18:1/18:0, d18:1/23:0, d18:1/24:1, d18:1/24:0, and d18:0/24:0 in the NAM group on D1 relative to parturition. In addition, fatty acids 18:2, 18:1, 18:0, 16:1, and 16:0 were obviously decreased on D21 relative to calving. This research has provided insights into how NAM supplementation improves lipid metabolism in perinatal dairy cows.

Strong interface coupling boosting hierarchical bismuth embedded carbon hybrid for high-performance capacitive deionization.

Capacitive deionization (CDI) is regarded as a promising desalination technology owing to its low cost and environmental friendliness. However, the lack of high-performance electrode materials remains a challenge in CDI. Herein, the hierarchical bismuth-embedded carbon (Bi@C) hybrid with strong interface coupling was prepared through facile solvothermal and annealing strategy. The hierarchical structure with strong interface coupling between the bismuth and carbon matrix afforded abundant active sites for chloridion (Cl-) capture, improved electrons/ions transfer and the stability of the Bi@C hybrid. As a result of these advantages, the Bi@C hybrid showed a high salt adsorption capacity (75.3 mg/g under 1.2 V), salt adsorption rate and good stability, making it a promising electrode material for CDI. Furthermore, the desalination mechanism of the Bi@C hybrid was elucidated through various characterizations. Therefore, this work provides valuable insights for the design of high-performance bismuth-based electrode materials for CDI.

The Effects of Rumen-Protected Choline and Rumen-Protected Nicotinamide on Liver Transcriptomics in Periparturient Dairy Cows.

To investigate the effects of rumen-protected choline (RPC) and rumen-protected nicotinamide (RPM) on liver metabolic function based on transcriptome in periparturient dairy cows, 10 healthy Holstein dairy cows with similar parity were allocated to RPC and RPM groups (n = 5). The cows were fed experimental diets between 14 days before and 21 days after parturition. The RPC diet contained 60 g RPC per day, and the RPM diet contained 18.7 g RPM per day. Liver biopsies were taken 21 days after calving for the transcriptome analysis. A model of fat deposition hepatocytes was constructed using the LO2 cell line with the addition of NEFA (1.6 mmol/L), and the expression level of genes closely related to liver metabolism was validated and divided into a CHO group (75 µmol/L) and a NAM group (2 mmol/L). The results showed that the expression of a total of 11,023 genes was detected and clustered obviously between the RPC and RPM groups. These genes were assigned to 852 Gene Ontology terms, the majority of which were associated with biological process and molecular function. A total of 1123 differentially expressed genes (DEGs), 640 up-regulated and 483 down-regulated, were identified between the RPC and RPM groups. These DEGs were mainly correlated with fat metabolism, oxidative stress and some inflammatory pathways. In addition, compared with the NAM group, the gene expression level of FGF21, CYP26A1, SLC13A5, SLCO1B3, FBP2, MARS1 and CDH11 in the CHO group increased significantly (p < 0.05). We proposed that that RPC could play a prominent role in the liver metabolism of periparturient dairy cows by regulating metabolic processes such as fatty acid synthesis and metabolism and glucose metabolism; yet, RPM was more involved in biological processes such as the TCA cycle, ATP generation and inflammatory signaling.

Driving forces and recovery potential of the macrophyte decline in East Taihu Lake.

Macrophytes are of key importance to the structure and ecological services of shallow lakes and are sensitive to anthropogenic and natural perturbations. Ongoing eutrophication and hydrological regime change affect macrophytes through changes in water transparency and water level, which lead to a dramatic decrease in bottom light availability. Here an integrated dataset (2005-2021) of multiple environmental factors is used to demonstrate the driving forces and recovery potential of the macrophyte decline in East Taihu Lake by using a critical indicator, which is the ratio of the Secchi disk depth to the water depth (SD/WD). The macrophyte distribution area showed a remarkable decrease from 136.1 ± 9.7 km2 (2005-2014) to 66.1 ± 6.5 km2 (2015-2021). The macrophyte coverage in the lake and in the buffer zone decreased by 51.4% and 82.8%, respectively. The structural equation model and correlation analysis showed that the distribution and coverage of macrophytes decreased with the decrease in the SD/WD over time. Moreover, an extensive hydrological regime change, which caused a sharp decrease in SD and an increase in the water level, is likely to be the driving force that brought about the decline of macrophytes in this lake. The proposed recovery potential model shows that the SD/WD has been low in recent years (2015-2021), and that this SD/WD cannot ensure the growth of submerged macrophytes and is unlikely to ensure the growth of floating-leaved macrophytes, especially in the buffer zone. The approach developed in the present study provides a basis for the assessment of macrophyte recovery potential and the management of ecosystems in shallow lakes that suffer from macrophyte loss.

Fabrication of Ru/WO3-W2N/N-doped carbon sheets for hydrogen evolution reaction.

Recent experimental analysis indicates WO3-based nanostructures exhibit poor hydrogen evolution reactivity, particularly in alkaline medium, arising from the low electron transfer rate. It is imperative to tune the composition and structure of WO3 to boost the cleavage of H-OH bond. Here, we construct Ru/WO3-W2N/N-doped carbon sheets (Ru/WO3-W2N/NC) using m-WO3 nanosheets as precursors with the aid of RuCl3, Tris (hydroxymethyl) aminomethane, and dopamine. Structural investigation reveals the formation of N-doped carbon sheets, Ru nanoparticles, and WO3-W2N. As a result, hydrogen evolution reactivity is greatly improved on Ru/WO3-W2N/N-doped carbon sheets with 64 mV at 10 mA/cm2 in 1 mol/L (M) KOH, outperforming most of WO3-based electrocatalysts in previous literatures. Meanwhile, it facilitates the generation of H2 in 0.5 M H2SO4 with the excellent activity of 110 mV at 10 mA/cm2. Our work provides an efficient strategy to tailor the electronic structure of WO3 to catalyze acidic and alkaline hydrogen evolution reaction.

Impact of submerged macrophytes on growth and 2-MIB release risk of Pseudanabaena sp.: From field monitoringa to cultural experiments.

The off-flavor compound 2-methylisoborneol (2-MIB) is generally associated with the proliferation and metabolism of filamentous cyanobacteria in shallow freshwater ecosystems. Here field monitoring in East Taihu Lake from July to October 2021, along with cultural experiments, was conducted to determine the impact of submerged macrophytes on the growth and 2-MIB production of filamentous cyanobacteria. Pseudanabaena sp. was identified as the 2-MIB producer with the highest detection rate (100%) and correlation coefficient (R=0.68, p < 0.001). The 2-MIB concentration and algal growth in the macrophyte-dominated zones were markedly decreased compared with those in the phytoplankton-dominated zone. Five submerged macrophytes classified into flat-leaf type (Vallisneria natans and Potamogeton crispus) and thin-leaf type (Hydrilla verticillata, Ceratophyllum demersum, and Myriophyllum spicatum) exhibited strong inhibition effects against Pseudanabaena sp.: Overall inhibition efficiencies (IEs) of 92.7% ± 6.8% and 92.7% ± 8.4% for cell growth and 2-MIB production were achieved, respectively. Moreover, the thin-leaf macrophytes exhibited significant higher IEs for cell growth (94.0% vs. 84.7%) and 2-MIB production (99.4% vs. 82.6%) than the flat-leaf macrophytes and can be selected as pioneer species in controlling odor problems. Nutrient uptake, increasing water clarity, shading effects, and allelopathic effects of the submerged macrophytes were found to be the dominant inhibition mechanisms.

Analysis of Risk Factors in Patients With Peripheral Vertigo or Central Vertigo.

INTRODUCTION: This study was aimed to determine risk factors for central vertigo (CV) in patients with isolated vertigo accompanied by hearing loss or not. PATIENTS AND METHODS: Patients with CV or peripheral vertigo (PV) who were admitted to our hospital between January 2014 and July 2016 were retrospectively reviewed. All patients underwent thorough physical examination with detailed medical histories recorded, including smoking, hypertension, diabetes, cardiovascular disease, and stroke history. Logistic regression estimated odds ratio (OR) of the risk factors. RESULTS: Eighty-seven patients were enrolled into the study, including 41 cases of CV and 46 cases of PV. There was significant difference in sex, age above 60, hypertension, diabetes, smoking, and stroke history between the 2 groups. The patients without any risk factors did not have CV. The risk for CV in the patients with ≥3 risk factors was greater (OR, 11.43; 95% confidence interval, 3.27-39.93; P<0.001) than the patients with 1 risk factor. The risk for CV in the patients with 2 risk factors was similar (OR, 0.833; 95% confidence interval, 0.17-4.28; P=0.825) to the patients with 1 risk factor. CONCLUSION: The patients with isolated vertigo (accompanied by hearing loss or not) and 3 or more risk factors are at higher risk for CV. They should have a comprehensive neurological examination and be closely followed up.

MiRNAs participate in the diagnosis, pathogenesis and therapy of Parkinson's disease.

MicroRNAs (miRNAs), one kind of post-transcriptional modification, mediate transcriptional silencing of various metabolic enzymes that are involved in various life processes, including Parkinson's disease. At present, the pathogenesis of Parkinson's disease is not clear, although many studies suggest that miRNAs play a very important role in the progress of Parkinsonism. This paper reviews the biological characteristics of miRNAs and summarizes the progress of miRNAs in reference to the diagnosis and pathogenesis of Parkinson's disease. It even considers miRNAs as a potential target for Parkinson's disease therapy.

Administration of alpha-ketoglutarate improves epithelial restitution under stress injury in early-weaning piglets.

Alpha-ketoglutarate (AKG) is an important cellular metabolite that participates in energy production and amino acid metabolism. However, the protective effects and mechanism of AKG on mucosal lesions have not been well understood. This study was conducted to investigate the effects of dietary AKG supplementation on epithelial restitution in early-weaning piglets under Escherichia coli lipopolysaccharide (LPS) induction. A total of 32 weaned piglets were used in a 2 × 2 factorial design; the major factors were dietary treatment (basal diet or AKG diet) and inflammatory challenge (LPS or saline). The results showed that AKG supplementation improved the growth performance and intestinal morphology in the LPS-induced early-weaning piglets. Compared with the basal diet, the AKG diet remarkably decreased the concentration and mRNA expression of intestinal inflammatory cytokines (IL-1ß, IL-6, and IL-12) in the LPS-induced piglets. Moreover, AKG administration upregulated the mRNA expression of nutrient-sensing transporters (GLUT-2, SGLT-1, PEPT-1, I-FABP2) in the small intestine of both saline- and LPS-treated piglets, and improved the distribution and expression of tight-junction genes andproteins (ZO-1, Occludin, Claudins, E-cadherin). Collectively, our findings indicate that AKG has the potential to alleviate intestinal inflammatory response and improve epithelial restitution and nutrient-sensing ability under stress injury in early-weaning piglets, and it also provides an experimental basis for enteral use of AKG in swine production and clinical application to prevent intestinal epithelial damage.

In Silico Insight into Potential Anti-Alzheimer's Disease Mechanisms of Icariin.

Herbal compounds that have notable therapeutic effect upon Alzheimer's disease (AD) have frequently been found, despite the recent failure of late-stage clinical drugs. Icariin, which is isolated from Epimedium brevicornum, is widely reported to exhibit significant anti-AD effects in in vitro and in vivo studies. However, the molecular mechanism remains thus far unclear. In this work, the anti-AD mechanisms of icariin were investigated at a target network level assisted by an in silico target identification program (INVDOCK). The results suggested that the anti-AD effects of icariin may be contributed by: attenuation of hyperphosphorylation of tau protein, anti-inflammation and regulation of Ca(2+) homeostasis. Our results may provide assistance in understanding the molecular mechanism and further developing icariin into promising anti-AD agents.

Dietary supplementation with L-glutamate and L-aspartate alleviates oxidative stress in weaned piglets challenged with hydrogen peroxide.

This study was to evaluate the protective roles of L-glutamate (Glu) and L-aspartate (Asp) in weaned piglets challenged with H2O2. Forty weaned piglets were assigned randomly into one of five groups (8 piglets/group): (1) control group (NC) in which pigs were fed a corn- and soybean meal-based diet and received intraperitoneal administration of saline; (2) H2O2 group (PC) in which pigs were fed the basal diet and received intraperitoneal administration of 10 % H2O2 (1 ml/kg body weight once on days 8 and repeated on day 11); (3) PC + Glu group (PG) in which pigs were fed the basal diet supplemented with 2.0 % Glu before intraperitoneal administration of 10 % H2O2; (4) PC + Asp group (PA) in which pigs were fed the basal diet supplemented with 1.0 % Asp before intraperitoneal administration of 10 % H2O2; (5) PC + Glu + Asp group (PGA) in which pigs were fed the basal diet supplemented with 2.0 % Glu plus 1.0 % Asp before intraperitoneal administration of 10 % H2O2. Measured parameters included daily feed intake (DFI), average daily gain (ADG), feed conversion rate (FCR), and serum anti-oxidative enzyme activities (catalase, superoxide dismutase, glutathione peroxidase-1), serum malondialdehyde and H2O2 concentrations, serum amino acid (AA) profiles, and intestinal expression of AA transporters. Dietary supplementation with Glu, Asp or their combination attenuated the decreases in DFI, ADG and feed efficiency, the increase in oxidative stress, the alterations of serum AA concentrations, and the changed expression of intestinal AA transporters in H2O2-challenged piglets. Thus, dietary supplementation with Glu or Asp alleviates growth suppression and oxidative stress, while restoring serum the amino acid pool in H2O2-challenged piglets.

Effects of pro-inflammatory cytokines and antioxidants expression in the jejunum of mice induced by hydrogen peroxide.

Inflammation-induced jejunal cell death and oxidative stress have been observed in inflammatory bowel disease (IBD), but now, there is still no systematic animal model of jejunal oxidative stress for the evaluation of potential therapies. Thus, the purpose of this study was to evaluate the dynamic changes of pro-inflammatory cytokines and antioxidant expression on the jejunal inflammation. In this study, Hydrogen peroxide(H2O2, 10 ml/kg)was administrated intragastrically to mice in a single dose of 1%, 3%, or 5%. The incidence of death, histomorphometry, inflammatory cytokines (including TNF-α,IL-1ß,and IL-5), and antioxidant genes were measured via RT-PCR. During the whole period, a massive infiltration of neutrophils was observed in the jejunum. Intragastric administration of H2O2 significantly up-regulated the expression of TNF-α,IL-1ß, and IL-5 (P<0.05). Meanwhile, 5% H2O2 induced an acute stress in mice which lasted up to 3 days, while 3% H2O2 induced a chronic injury in the jejunum that lasted 7 days. In the early stage, H2O2 markedly enhanced expression of antioxidant genes and all of the doses used progressively decreased the expression of antioxidant genes in a time-dependent manner. These findings suggested that intragastric administration of 3% H2O2 induces relatively stable oxidative stress in the jejunum.

Low-protein diets affect ileal amino acid digestibility and gene expression of digestive enzymes in growing and finishing pigs.

The objective of this study was to evaluate effects of dietary crude protein (CP) intake on ileal amino acid digestibilities and expression of genes for digestive enzymes in growing and finishing pigs. In Experiment 1, 18 growing pigs (average initial BW = 36.5 kg) were assigned randomly into one of three treatments (n = 6/treatment group) representing normal (18 % CP), low (15 % CP), and very low (12 % CP) protein intake. In Experiment 2, 18 finishing pigs (average initial BW = 62.3 kg) were allotted randomly into one of three treatments (n = 6/treatment group), representing normal (16 % CP), low (13 % CP) and very low (10 % CP) protein intake. In both experiments, diets with low and very low CP were supplemented with crystalline amino acids to achieve equal content of standardized ileal digestible Lys, Met, Thr, and Trp, and were provided to pigs ad libitum. Daily feed intake, BW, and feed/gain ratios were determined. At the end of each experiment, all pigs were slaughtered to collect pancreas, small-intestine samples, and terminal ileal chymes. Samples were used for determining expression of genes for digestive enzymes and ileal amino acid digestibilities. Growing pigs fed the 12 % CP and 15 % CP diets had lower final body weight (P < 0.01) and ADG (P < 0.0001) when compared with pigs fed the 18 % dietary CP diet. Growing pigs fed with the 12 % CP diet showed higher digestibilities for CP (P < 0.05), DM (P < 0.05), Lys (P < 0.0001), Met (P < 0.01), Cys (P < 0.01), Thr (P < 0.01), Trp (P < 0.05), Val (P < 0.05), Phe (P < 0.05), Ala (P < 0.05), Cys (P < 0.01), and Gly (P < 0.05) than those fed the 18 % CP diet. Finishing pigs fed the 16 % CP diet had a higher (P < 0.01) final body weight than those fed the 10 % CP diet. mRNA levels for digestive enzymes (trypsinogen, chymotrypsin B, and dipeptidases-II and III) differed among the three groups of pigs (P < 0.05), and no difference was noted in the genes expression between control group and lower CP group. These results indicated that a reduction of dietary CP by a six-percentage value limited the growth performance of growing-finishing pigs and that a low-protein diet supplemented with deficient amino acids could reduce the excretion of nitrogen into the environment without affecting weight gain.

Pyrrolidine Dithiocarbamate Inhibits NF-KappaB Activation and Upregulates the Expression of Gpx1, Gpx4, Occludin, and ZO-1 in DSS-Induced Colitis.

Inflammatory bowel disease (IBD) correlates with oxidative stress, inflammation, and alteration in several signal pathways, including nuclear transcription factor-kappaB (NF-κB). Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, has been widely demonstrated to exhibit an antioxidant and anti-inflammatory function. This study aimed to test the hypothesis that NF-κB inhibitor PDTC confers a beneficial role in a colitis model induced by dextran sodium sulfate (DSS) in mouse. The results showed that DSS decreased daily weight gain, induced colonic inflammation, suppressed the expression of antioxidant enzymes and tight junctions, and activated NF-κB and nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathways. PDTC significantly upregulated (P < 0.05) Gpx1, Gpx4, occludin, and ZO-1 expressions in the DSS-induced colitis model. Meanwhile, PDTC reversed (P < 0.05) the activation of NF-κB signal pathway caused by DSS treatment. In conclusion, PDTC could serve as an adjuvant therapy for the patient with IBD.

Screening Ingredients from Herbs against Pregnane X Receptor in the Study of Inductive Herb-Drug Interactions: Combining Pharmacophore and Docking-Based Rank Aggregation.

The issue of herb-drug interactions has been widely reported. Herbal ingredients can activate nuclear receptors and further induce the gene expression alteration of drug-metabolizing enzyme and/or transporter. Therefore, the herb-drug interaction will happen when the herbs and drugs are coadministered. This kind of interaction is called inductive herb-drug interactions. Pregnane X Receptor (PXR) and drug-metabolizing target genes are involved in most of inductive herb-drug interactions. To predict this kind of herb-drug interaction, the protocol could be simplified to only screen agonists of PXR from herbs because the relations of drugs with their metabolizing enzymes are well studied. Here, a combinational in silico strategy of pharmacophore modelling and docking-based rank aggregation (DRA) was employed to identify PXR's agonists. Firstly, 305 ingredients were screened out from 820 ingredients as candidate agonists of PXR with our pharmacophore model. Secondly, DRA was used to rerank the result of pharmacophore filtering. To validate our prediction, a curated herb-drug interaction database was built, which recorded 380 herb-drug interactions. Finally, among the top 10 herb ingredients from the ranking list, 6 ingredients were reported to involve in herb-drug interactions. The accuracy of our method is higher than other traditional methods. The strategy could be extended to studies on other inductive herb-drug interactions.

Effects of reducing dietary protein on the expression of nutrition sensing genes (amino acid transporters) in weaned piglets.

The effects of crude protein (CP) levels in the diet on the mRNA expression of amino acid (AA) transporters were studied in a 45-d trial. Eighteen piglets with an initial body weight (BW) of 9.57 kg were assigned to three groups (14%, 17%, and 20% CP in the diet) in a completely randomized design (six replicates per treatment). Diets were supplemented with crystalline AA to achieve equal standardized ileal digestible contents of Lys, Met plus Cys, Thr, and Trp, and were provided ad libitum. After 45 d, all piglets were slaughtered to collect small intestine samples. Compared with the values in the 14% CP group, the expressions of ASCT2, 4F2hc, and ATB(0) mRNA in the jejunum were increased by 23.00%, 12.00%, 6.00% and 48.00%, 47.00%, 56.00% in the 17% and 20% CP groups, respectively. These results indicate that a 14% CP diet supplemented with crystalline AA may not transport enough AA into the body and maintain growth performance of piglets. However, a reduction of dietary 17% CP may reduce the excretion of nitrogen into the environment while supporting the development of piglets. Therefore, the 17% CP level is more suitable than 14% CP level.