Environmental chemical TCPOBOP exposure alters milk liposomes and offspring growth trajectories in mice.

Exposure to environmental endocrine disruptors (EEDs) has become a global health concern, and EEDs are known to be potent inducers of constitutive androstane receptor (CAR). 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP, hereafter abbreviated as TC), a specific ligand for CAR, has been considered as a potential EED. Here, we analyzed the effect of TC exposure to female mice on the histological morphology of their alveoli in the basic unit of lactation. We quantified differences in the milk metabolome of the control and TC-exposed group while assessing the correlations between metabolites and neonatal growth. Mammary histological results showed that TC exposure inhibited alveolar development. Based on the milk metabolomic data, we identified a total of 1505 differential metabolites in both the positive and negative ion mode, which indicated that TC exposure affected milk composition. As expected, the differential metabolites were significantly enriched in the drug metabolism pathway. Further analyses revealed that differential metabolites were significantly enriched in multiple lipid metabolic pathways, such as fatty acid biosynthesis, suggesting that most differential metabolites were concentrated in lipids. Simultaneously, a quantitative analysis showed that TC exposure led to a decrease in the relative abundance of total milk lipids, affecting the proportion of some lipid subclasses. Notably, a portion of lipid metabolites were associated with neonatal growth. Taken together, these findings suggest that TC exposure may affect milk lipidomes, resulting in the inability of mothers to provide adequate nutrients, ultimately affecting the growth and health of their offspring.

Constitutive Androstane Receptor Agonist, TCPOBOP: Maternal Exposure Impairs the Growth and Development of Female Offspring in Mice.

Environmental chemicals, which are known to impact offspring health, have become a public concern. Constitutive activated receptor (CAR) is activated by various environmental chemicals and participates in xenobiotic metabolism. Here, we described the effects of maternal exposure to the CAR-specific ligand 1,4-bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP, TC) on offspring health outcomes. Maternal TC exposure exhibited a stronger inhibition of body weight in 3-week-old and 8-week-old first-generation (F1) offspring female mice compared to controls. Further, maternal TC exposure obtained a strong increase in hepatic drug-metabolizing enzyme expression in 3-week-old female mice that persisted into 8-week-old adulthood. Interestingly, we observed distorted intestinal morphological features in 8-week-old F1 female mice in the TC-exposed group. Moreover, maternal TC exposure triggered a loss of intestinal barrier integrity by reducing the expression of intestinal tight junction proteins. Accordingly, maternal exposure to TC down-regulated serum triglyceride levels as well as decreased the expression of intestinal lipid uptake and transport marker genes. Mechanistically, maternal TC exposure activated the intestinal inflammatory response and disrupted the antioxidant system in the offspring female mice, thereby impeding the intestinal absorption of nutrients and seriously threatening offspring health. Altogether, these findings highlight that the effects of maternal TC exposure on offspring toxicity could not be ignored.

Environmental chemical TCPOBOP disrupts milk lipid homeostasis during pregnancy and lactation.

Humans are exposed to different kinds of environmental contaminants or drugs throughout their lifetimes. The widespread presence of these compounds has raised concerns about the consequent adverse effects on lactating women. The constitutive androstane receptor (CAR, Nr1i3) is known as a xenobiotic sensor for environmental pollution or drugs. In this study, the model environmental chemical 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene, TCPOBOP (TC), which is a highly specific agonist of CAR, was used to investigate the effects of exogenous exposure on lactation function and offspring health in mice. The results revealed that TC exposure decreased the proliferation of mammary epithelial cells during pregnancy. This deficiency further compromised lobular-alveolar structures, resulting in alveolar cell apoptosis, as well as premature stoppage of the lactation cycle and aberrant lactation. Furthermore, TC exposure significantly altered the size and number of milk lipid droplets, suggesting that TC exposure inhibits milk lipid synthesis. Additionally, TC exposure interfered with the milk lipid metabolism network, resulting in the inability of TC-exposed mice to efficiently secrete nutrients and feed their offspring. These findings demonstrated that restricted synthesis and secretion of milk lipids would indirectly block mammary gland form and function, which explained the possible reasons for lactation failure and retarded offspring growth.

Melatonin Attenuates Dextran Sodium Sulfate Induced Colitis in Obese Mice.

Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.

High-Protein Diet Induces Hyperuricemia in a New Animal Model for Studying Human Gout.

Hyperuricemia is a central risk factor for gout and increases the risk for other chronic diseases, including cardiometabolic disease, kidney disease, and hypertension. Overproduction of urate is one of the main reasons for hyperuricemia, and dietary factors including seafoods, meats, and drinking are contributed to the development of it. However, the lack of a suitable animal model for urate metabolism is one of the main reasons for the delay and limitations of hyperuricemia research. Combining evolutionary biological studies and clinical studies, we conclude that chicken is a preferred animal model for hyperuricemia. Thus, we provided chickens a high-protein diet (HPD) to evaluate the changes in the serum urate levels in chickens. In our study, the HPD increased the serum urate level and maintained it at a long-term high level in chickens. Long-term high serum urate levels induced an abnormal chicken claw morphology and the precipitation of monosodium urate (MSU) in joint synovial fluid. In addition, a long-term HPD also decreased the glomerular filtration rate and induced mild renal injury. Most importantly, allopurinol and probenecid displayed the positive effects in decreasing serum urate and then attenuated hyperuricemia in chicken model. These findings provide a novel model for hyperuricemia and a new opportunity to further investigate the effects of long-term hyperuricemia on other metabolic diseases.

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure.

Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light-12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.

Optimization and characterization of exopolysaccharides with a highly branched structure extracted from Leuconostoc citreum B-2.

The fermentation conditions for exopolysaccharides (EPS) with a highly branched structure extracted from Leuconostoc citreum B-2 were optimized by response surface methodology (RSM). The results showed that under the optimal fermentation conditions of sucrose, yeast extract and pH of 99.80 g/L, 5.94 g/L and 6.12, respectively, the B-2 EPS yield was 59.33 ±â€¯1.34 g/L, which was 5.93 times greater than that from the initial nonoptimized conditions. Chemical composition analysis showed that the carbon, hydrogen, nitrogen and sulfur contents of the B-2 pure EPS (P-EPS) were 39.05 ±â€¯0.25%, 7.19 ±â€¯0.08%, 0.72 ±â€¯0.03% and 0%, respectively. The content of uronic acid was high, reaching 20.94 ±â€¯6.30%. B-2 EPS had certain 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (·OH), superoxide anion (O2-), hydrogen peroxide (H2O2), nitroso radical (NO2-) scavenging abilities and reducing power. The degradation temperature of the B-2 EPS was 313 °C, indicating that B-2 EPS have high thermal stability. The emulsification effect on vegetable oils was better than that of hydrocarbons. The EPS produced by Leu. citreum B-2 was activated in different concentrations of sucrose-supplemented skimmed milk, which caused the skimmed milk to have different degrees of solidification. Moreover, B-2 EPS promoted the growth of probiotic bacteria, especially Lactobacillus delbrueckii.

Purification, characterization and mode of action of enterocin, a novel bacteriocin produced by Enterococcus faecium TJUQ1.

Enterococcus faecium TJUQ1 with high bacteriocin-producing ability was isolated from pickled Chinese celery. In this study, enterocin TJUQ1 was purified by ammonium sulfate precipitation, reversed-phase chromatography (Sep-Pak C8) and cation-exchange chromatography. The activity of the purified bacteriocin was 44,566.41 ± 874.69 AU/mg, which corresponds to a purification fold of 35.89 ± 2.34. The molecular mass was 5520 Da by MALDI-TOF MS and Tris-Tricine SDS-PAGE. The result of LC-MS/MS showed that the bacteriocin shared 59.15% identity with enterocin produced by E. faecium GN (accession no. O34071). PCR amplification revealed that E. faecium TJUQ1 possesses a gene encoding enterocin B with 60% identity to enterocin B. Circular dichroism (CD) spectroscopy showed that the molecular conformation was 32.6% helix, 19.5% beta, 12.9% turn and 35.0% random. The stability of enterocin TJUQ1 was measured. After exposure at 121 °C for 15 min, the residual antimicrobial activity of enterocin TJUQ1 was 85.95 ± 1.32%. The antimicrobial activity of enterocin TJUQ1 was still active over a pH range of 3-11. Enterocin TJUQ1 was inactivated after exposure to proteolytic enzymes but was not inactivated by lipase or amylase. These results showed that enterocin TJUQ1 was a novel class II bacteriocin. Enterocin TJUQ1 showed wide antibacterial activity against food-borne gram-negative and gram-positive pathogens, such as Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Salmonella enterica. The MIC was 5.26 ± 0.24 µg/mL against L. monocytogenes CMCC 1595. SEM and TEM were used to observe the changes in the morphological and intracellular organization of L. monocytogenes CMCC 1595 cells treated with enterocin TJUQ1. The results demonstrated that enterocin TJUQ1 increased extracellular electrical conductivity, facilitated pore formation, triggered the release of UV-absorbing materials, ATP and LDH, and even caused cell lysis in L. monocytogenes CMCC 1595 cells. Based on the characterization, the wide inhibitory spectrum and mode of action determined so far, enterocin TJUQ1 is a potential preservative for the food industry.

Determination of glucansucrase encoding gene in Leuconostoc mesenteroides.

A glucansucrase encoding gene was cloned into pET-28a(+) vector and expression in Escherichia coli BL21(DE3). An about 160 kDa recombinant glucansucrase was purified with a yield of 50.73% and a 4.02-fold increase in activity. The 1464 amino acid residue enzyme belongs to the GH70 subfamily and shares 90% similarity with Leuconostoc sp. glucansucrase. The optimal temperature and pH were 30 °C and pH 5.5, and 80% of activity was retained after incubation at 10-30 °C and pH 5-7. Enzyme activity was strongly activated by Ca2+ and Mn2+ and inhibited by various metal ions and chemical agents, and a high affinity for sucrose (Km = 11.6 mM, Vmax = 8.1 mmol/(mL·min)). Circular dichroism (CD) and Raman spectra collectively indicated a high proportion of random coil structure.

Optimization and partial characterization of ca-independent α-amylase from Bacillus amyloliquefaciens BH1.

Strain Bacillus amyloliquefaciens BH1 was evaluated for the generation of α-amylase. Culture conditions and medium components were optimized by a statistical approach for the optimal generation of α-amylase with response surface methodology (RSM) method. The Plackett-Burman (PB) design was executed to select the fermentation variables and Central composite design (CCD) for optimizing significant factors influencing production. The optimum levels for highest generation of α-amylase activity (198.26 ± 3.54 U/mL) were measured. A 1.69-fold improve generation was acquired in comparison with the non-optimized. Partial characterization of the α-amylase indicated optimal pH and temperature at 7.0 and 40 °C, respectively. Crude α-amylase maintained a constant pH range 5.0-8.0 and 30-70 °C. The α-amylase was independent of Ca2+, and the activity was inhibited by Fe3+, Co2+, Cu2+, and Hg2+. The thermo and pH stability of the α-amylase indicate its extensive application in the food and pharmaceutical industries.

Purification, characterization and antioxidant activity of dextran produced by Leuconostoc pseudomesenteroides from homemade wine.

An exopolysaccharide (EPS) was produced by Leuconostoc pseudomesenteroides DRP-5 isolated from homemade wine. The EPS was obtained with ethanol extraction, which was further purified by chromatography of Sephadex G-100 to get a purified fraction. The monosaccharide composition of the EPS was glucose, and its molecular weight (Mw) was 6.23 × 106 Da, as determined by gas chromatography (GC) and high-performance size-exclusion chromatography (HPSEC). Fourier transform infrared spectra (FT-IR) and nuclear magnetic resonance spectra (NMR) showed that the EPS was a linear glucan with α-(1→6)-linked glucosidic bonds. The water holding capacity (WHC), water solubility index (WSI) and emulsifying activity (EA) of DRP-5 EPS were 296.76 ±â€¯18.93%, 98.62 ±â€¯3.57% and 87.22 ±â€¯2.18%, respectively. DRP-5 EPS have a higher degradation temperature of 278.36 °C, suggesting high thermal stability of the EPS. Also, DRP-5 EPS was found to have moderate 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical, superoxide anion radical, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical, Fe2+ scavenging activities and reducing power. All these characteristics suggest that DRP-5 EPS might have potential applications in the pharmaceutical, cosmetic and food industries.

Well-Defined Nanographene-Rhenium Complex as an Efficient Electrocatalyst and Photocatalyst for Selective CO2 Reduction.

Improving energy efficiency of electrocatalytic and photocatalytic CO2 conversion to useful chemicals poses a significant scientific challenge. We report on using a colloidal nanographene to form a molecular complex with a metal ion to tackle this challenge. In this work, a well-defined nanographene-Re complex was synthesized, in which electron delocalization over the nanographene and the metal ion significantly decreases the electrical potential needed to drive the chemical reduction. We show the complex can selectively electrocatalyze CO2 reduction to CO in tetrahydrofuran at -0.48 V vs NHE, the least negative potential reported for a molecular catalyst. In addition, the complex can absorb a significant spectrum of visible light to photocatalyze the chemical transformation without the need for a photosensitizer.

Basal Plane Fluorination of Graphene by XeF2 via a Radical Cation Mechanism.

Graphene fluorination with XeF2 is an attractive method to introduce a nonzero bandgap to graphene under mild conditions for potential electro-optical applications. Herein, we use well-defined graphene nanostructures as a model system to study the reaction mechanism of graphene fluorination by XeF2. Our combined experimental and theoretical studies show that the reaction can proceed through a radical cation mechanism, leading to fluorination and sp(3)-hybridized carbon in the basal plane.

Wacker-type oxidation of internal alkenes using Pd(Quinox) and TBHP.

The Pd-catalyzed TBHP-mediated Wacker-type oxidation of internal alkenes is reported. The reaction uses 2-(4,5-dihydro-2-oxazolyl)quinoline (Quinox) as ligand and TBHP(aq) as oxidant to deliver single ketone constitutional isomer products in a predictable fashion from electronically biased olefins. This methodology is showcased through its application on an advanced intermediate in the total synthesis of the antimalarial drug artemisinin.

Concise total synthesis of (-)-8-epigrosheimin.

A highly efficient route was developed to synthesize (-)-8-epigrosheimin in four steps from aldehyde 2 based on a substrate-controlled method. The key steps of the synthesis included (1) a stereo- and regioselective allylation addition, (2) an intramolecular translactonization, and (3) an aldehyde-ene cyclization.