Structure-Based Identification of Kelch-like ECH-Associated Protein 1 as a Pharmacological Target of Electrophile-Containing Catechol-O-Methyltransferase Inhibitors.

Entacapone and nitecapone are electrophile-containing catechol-O-methyltransferase (COMT) inhibitors that are used to treat Parkinson's disease in combination with L-DOPA. It is desirable to investigate whether they can covalently bind to cellular protein targets using their reactive electrophilic warheads. We identified Kelch-like ECH-associated protein 1 (KEAP1), a sensor for oxidative and electrophilic stress, as a potential pharmacological target of both drugs by performing covalent-based reverse docking. We confirmed that both drugs activate nuclear factor erythroid 2-related factor 2 (NRF2) by reversibly modifying C151 on KEAP1. Both drugs can enhance the expression of growth differentiation factor 15 (GDF15) and NRF2 downstream antioxidant response element (ARE) genes, both in vitro and in vivo. Furthermore, both drugs exhibit anti-inflammatory effects in an NRF2-dependent acute gout model. Our findings suggest that these two drugs could be repurposed for the treatment of NRF2-modulated inflammatory diseases, and the 3-methylene-acetylacetone group of nitecapone could serve as a new reversible covalent warhead.

Identification of Characteristic Bioactive Compounds in Silkie Chickens, Their Effects on Meat Quality, and Their Gene Regulatory Network.

Silkie chicken, an important chicken breed with high medicinal and nutritional value, has a long history of being used as a dietary supplement in China. However, the compounds with health-promoting effects in Silkie chickens remain unclear. In the present study, we conducted a comprehensive analysis of metabolic and lipidomic profiles to identify the characteristic bioactive compounds in Silkie chickens, using a common chicken breed as control. The results showed that the levels of 13 metabolites including estradiol, four lipid subclasses including cardiolipin (CL), eight lipid molecules, and three fatty acids including docosahexaenoic acid (C22:6) were significantly increased in Silkie chickens, which have physiological activities such as resisting chronic diseases and improving cognition. These characteristic bioactive compounds have effects on meat quality characteristics, including improving its water-holding capacity and umami taste and increasing the content of aromatic compounds and phenols. The differentially expressed genes (DEGs) between the two chicken breeds revealed the regulatory network for these characteristic bioactive compounds. Fifteen DEGs, including HSD17B1, are involved in the synthesis of characteristic metabolites. Eleven DEGs, including ELOVL2, were involved in the synthesis and transport of characteristic lipids and fatty acids. In summary, we identified characteristic bioactive compounds in Silkie chickens, and analyzed their effects on meat quality characteristics. This study provided important insight into Silkie chicken meat as a functional food.

A natural variation in OsDSK2a modulates plant growth and salt tolerance through phosphorylation by SnRK1A in rice.

Plants grow rapidly for maximal production under optimal conditions; however, they adopt a slower growth strategy to maintain survival when facing environmental stresses. As salt stress restricts crop architecture and grain yield, identifying genetic variations associated with growth and yield responses to salinity is critical for breeding optimal crop varieties. OsDSK2a is a pivotal modulator of plant growth and salt tolerance via the modulation of gibberellic acid (GA) metabolism; however, its regulation remains unclear. Here, we showed that OsDSK2a can be phosphorylated at the second amino acid (S2) to maintain its stability. The gene-edited mutant osdsk2aS2G showed decreased plant height and enhanced salt tolerance. SnRK1A modulated OsDSK2a-S2 phosphorylation and played a substantial role in GA metabolism. Genetic analysis indicated that SnRK1A functions upstream of OsDSK2a and affects plant growth and salt tolerance. Moreover, SnRK1A activity was suppressed under salt stress, resulting in decreased phosphorylation and abundance of OsDSK2a. Thus, SnRK1A preserves the stability of OsDSK2a to maintain plant growth under normal conditions, and reduces the abundance of OsDSK2a to limit growth under salt stress. Haplotype analysis using 3 K-RG data identified a natural variation in OsDSK2a-S2. The allele of OsDSK2a-G downregulates plant height and improves salt-inhibited grain yield. Thus, our findings revealed a new mechanism for OsDSK2a stability and provided a valuable target for crop breeding to overcome yield limitations under salinity stress.

Modulation of pectin on intestinal barrier function via changes in microbial functional potential and bile acid metabolism.

Weaning is one of the major factors that cause stress and intestinal infection in infants and in young animals due to an immature intestine and not fully developed immune functions. Pectin (PEC), a prebiotic polysaccharide, has attracted considerable attention in intestinal epithelial signaling and function via modulation of the microbial community. A total of 16 weaned piglets (21-d-old) were randomly assigned into two groups: control group and PEC group. Supplementation of 5% pectin improved intestinal mucosal barrier function by modulating the composition of the bile acid pool in piglets. Specifically, piglets in PEC group had less serum D-lactate content and alkaline phosphatase activity. In the ileum, dietary pectin increased the number of crypt PAS/AB-positive goblet cells and the mRNA expressions of MUC2, ZO-1, and Occludin. Piglets in PEC group displayed a decreased abundance of Enterococcus (2.71 vs. 65.92%), but the abundances of Lactobacillus (30.80 vs. 7.93%), Streptococcus (21.41 vs. 14.81%), and Clostridium_sensu_stricto_1 (28.34 vs. 0.01%) were increased. Elevated concentrations of bile acids especially hyocholic acid species (HCAs) including HCA, HDCA, and THDCA were also observed. Besides, correlation analysis revealed that dietary pectin supplementation may have beneficial effects through stimulation of the crosstalk between gut microbes and bile acid synthesis within the enterohepatic circulation. Thus, dietary pectin supplementation exhibited a further positive effect on the healthy growth and development of weaned piglets. These findings suggest pectin supplementation as the prebiotic is beneficial for gut health and improvement of weaned stress via regulating microbiota and bile acid metabolism.

Combined effects of sodium butyrate and xylo-oligosaccharide on growth performance, anti-inflammatory and antioxidant capacity, intestinal morphology and microbiota of broilers at early stage.

This study aimed to evaluate the individual and combined effects of chemically protected sodium butyrate (CSB) and xylo-oligosaccharide (XOS) on performance, anti-inflammatory and antioxidant capacity, intestinal morphology and microbiota of broilers. A total of 280 one-day-old Arbor Acres broilers were randomly distributed into 5 treatments: basal diet (CON), basal diet supplemented with 100 mg/kg aureomycin and 8 mg/kg enramycin (ABX), 1000 mg/kg CSB (CSB), 100 mg/kg XOS (XOS), and mixture of 1000 mg/kg CSB and 100 mg/kg XOS (MIX), respectively. On d 21, ABX, CSB, and MIX decreased feed conversion ratio compared with CON (CON: ABX: CSB: MIX = 1.29: 1.22: 1.22: 1.22), whereas body weight of CSB and MIX was increased by 6.00% and 7.93%, and average daily gain was increased by 6.62% and 8.67% at 1-21 d, respectively (P < 0.05). The main effect analysis showed that both CSB and XOS treatments increased ileal villus height and villus height to crypt depth ratio (VCR) (P < 0.05). Moreover, broilers in ABX showed lower 21.39% ileal crypt depth and higher 31.43% VCR than those in CON (P < 0.05). Dietary CSB and XOS were added individually or collectively increased total antioxidant capacity and superoxide dismutase, and anti-inflammatory cytokines interleukin-10 and transforming growth factor-ß, whereas decreased malondialdehyde, and proinflammatory cytokines IL-6 and tumor necrosis factor-α content in serum (P < 0.05). Meanwhile, MIX showed the best effect of antioxidant and anti-inflammatory capacity among the 5 groups (P < 0.05). There was an interaction between CSB and XOS treatments on increasing cecal acetic acid, propionic acid, butyric acid and total short-chain fatty acid (SCFA) (P < 0.05), and the one-way ANOVA showed that propionic acid in CSB was 1.54 times that of CON, whereas butyric acid and total SCFAs in XOS were 1.22 times and 1.28 times that of CON, respectively (P < 0.05). Furthermore, dietary combination of CSB and XOS changed phyla Firmicutes and Bacteroidota, and increased genera Romboutsia and Bacteroides (P < 0.05). In conclusion, dietary CSB and XOS improved growth performance of broilers, and the combined addition of them had the best effect on anti-inflammatory and antioxidant capacity, and intestinal homeostasis of broilers in current study, indicating that it may be a potential natural alternative to antibiotics.

Characterization and difference of lipids and metabolites from Jianhe White Xiang and Large White pork by high-performance liquid chromatography-tandem mass spectrometry.

The quality of pork, such as intramuscular fat (IMF) content and flavor, can affect the acceptance of the consumer. Many studies have reported on the pork quality of Chinese local and commercial pigs (for example Large White (LW) pigs). The Jianhe White Xiang (JWX) pig, one of the Chinese Xiang pigs, is known for its high IMF and pork flavor. However, studies investigating the characterization and difference of lipids and metabolites between the JWX and LW pork are limited. Herein, we performed metabolomic and lipidomic profiling of JWX and LW pork by high-performance liquid chromatography-tandem mass spectrometry. The IMF and meat redness (a*) of the JWX pork were significantly higher than those of the LW pork. Metabolomic profiling revealed that 118 out of 501 polar metabolites, such as carnitine, amino acids, sugar, and dipeptide, were significantly different between the two types of pork. Additionally, the screened metabolites were mainly related to carnitine synthesis, phospholipid metabolism, sugar metabolism, and amino acid metabolism. Lipidomic profiling identified 100 of 376 lipids, which contained carnitine, diglyceride, triglyceride (TG), sphingomyelin, cardiolipin, fatty acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which were significantly different between the two types of pork under the positive and negative ion modes (variable importance in projection (VIP) > 1, p < 0.05, and fold change (FC) > 2 or FC < 0.5). All of the different TG substances were up-regulated in the JWX pork, and their carbon chain length was longer than that of the residual TGs. In addition, the JWX pork had more double bonds of PC and PE substances than LW pork. Thus, our findings provide comprehensive metabolomic and lipidomic profiles between the JWX and LW pork and a basic understanding on increasing the pork quality.

Enantioselective Behavior of Flumequine Enantiomers and Metabolites' Identification in Sediment.

The enantioselective adsorption, degradation, and transformation of flumequine (FLU) enantiomers in sediment were investigated to elucidate the enantioselective environmental behaviors. The results of adsorption test showed that stereoselective differences of FLU enantiomers in sediment samples and the adsorbing capacity of S-(-)-FLU and R-(+)-FLU are higher than the racemate, and the pH values of the sediment determined the adsorption capacity. Enantioselective degradation behaviors were found under nonsterilized conditions and followed pseudo-first-order kinetic. The R-(+)-FLU was preferentially degraded, and there was significant enantioselectivity of the degradation of FLU. It can be concluded that the microorganism was the main reason for the stereoselective degradation in sediments. The physicochemical property of sediments, such as pH value and organic matter content, can affect the degradation rate of FLU. In addition, the process of transformation of FLU enantiomers in water-sediment system had enantioselective behavior, and R-(+)-FLU was preferential transformed. Meanwhile, the main metabolites of FLU in the sediment were decarboxylate and dihydroxylation products. This study contributes the evidence of comprehensively assessing the fate and risk of chiral FLU antibiotic and enantioselective behavior in the environment.

Integrated Lipidomic and Metabolomics Analysis Revealing the Effects of Frozen Storage Duration on Pork Lipids.

Frozen storage is an important strategy to maintain meat quality for long-term storage and transportation. Lipid oxidation is one of the predominant causes of the deterioration of meat quality during frozen storage. Untargeted lipidomic and targeted metabolomics were employed to comprehensively evaluate the effect of frozen duration on pork lipid profiles and lipid oxidative products including free fatty acids and fatty aldehydes. A total of 688 lipids, 40 fatty acids and 14 aldehydes were successfully screened in a pork sample. We found that ether-linked glycerophospholipids, the predominant type of lipids, gradually decreased during frozen storage. Of these ether-linked glycerophospholipids, ether-linked phosphatidylethanolamine and phosphatidylcholine containing more than one unsaturated bond were greatly influenced by frozen storage, resulting in an increase in free polyunsaturated fatty acids and fatty aldehydes. Among these lipid oxidative products, decanal, cis-11,14-eicosenoic acid and cis-5,8,11,14,17-dicosapentaenoic acid can be considered as potential indicators to calculate the freezing time of unknown frozen pork samples. Moreover, over the three-month frozen storage, the first month was a rapid oxidation stage while the other two months were a slow oxidation stage.

Chronic heat stress induces the disorder of gut transport and immune function associated with endoplasmic reticulum stress in growing pigs.

Although high temperatures influence gut health, data on underlying mechanisms remains scant. Using a pig model, this study performed a global analysis on how chronic heat stress affects the transport and immune function of the gut through transcriptome, proteome, microbial diversity and flow cytometry. A total of 27 pigs with similar body weights were assigned into 3 groups, control (Con) group (23 °C), chronic heat stressed (HS) group (33 °C), and pair-fed (PF) group, in a controlled environment for 21 days. Our results showed that pigs in the HS group had reduced growth performance and diminished height of ileal villi (P < 0.01). Transcriptome and proteome analyses demonstrated notable modification of expression of nutrients and ion transport-related transporters and gut mechanical barrier-related genes by chronic heart stress (P < 0.05), suggesting damage of transport functions and the gut barrier. Chronic heat stress-induced endoplasmic reticulum stress also increased the synthesis of misfolded proteins, leading to upregulation of misfolded protein degradation and synthesis, as well as vesicle transport disorder (P < 0.05). Energy supply processes were enhanced in the mitochondrion (P < 0.05) to maintain biological processes with high energy demands. Furthermore, chronic heat stress activated complement cascade response-related genes and proteins in the gut mucosa (P < 0.05). Our flow cytometry assays showed that the proportion of gut lymphocytes (CD4+ T cells, T cells, B cells in Peyer's patch lymphocytes and CD4+ CD25+ T cells in intraepithelial lymphocytes) were significantly altered in the HS group pigs (P < 0.05). In addition, the occurrence of gut microbial dysbiosis in the HS group pigs was characterized by increased potential pathogens (e.g., Asteroleplasma, Shuttleworthia, Mycoplasma) and suppression of beneficial bacteria (e.g., Coprococcus and Aeriscardovia), which are associated with gut immune function. Altogether, our data demonstrated that chronic heat stress induced gut transport and immune function disorder associated with endoplasmic reticulum stress in growing pigs.

A high-performance porous flexible composite film sensor for tension monitoring.

Flexible, lightweight sensors with a wide strain-sensing range are showing increasing significance in structural health monitoring compared with conventional hard sensors, which typically have a small strain range, are heavyweight, and have a large volume. In this work, salt particle precipitation and mechanical coating methods are used to fabricate porous graphene nanoplatelet (GNP)/polydimethylsiloxane (PDMS) flexible sensors for tension monitoring in structural health applications. The signal transformation through the Back Propagation (BP) algorithm is integrated to provide monitoring data that are comparable with other sensors. The results reveal that the flexible sensors with a low content of GNPs (0.1-0.25 wt%) possess better flexibility, allowing tensile strains over 200% to be measured. In addition, due to the enhanced deformation capacity of the pore structures, they can achieve high sensitivity (1-1000) under 65% strain, and a fast response time (70 ms) under 10% strain at 60 mm min-1. They also show high performance in the fatigue test (20 000 cycles) under 5% strain, and can effectively respond to bending and torsion. In addition, the sensors show an obvious response to temperature. Overall, the prepared flexible composite sensors in this work have the advantages of a wide strain-sensing range, a full-coverage conductive network, and being lightweight, and show potential for structural health monitoring in the near future.

Mucin O-glycan-microbiota axis orchestrates gut homeostasis in a diarrheal pig model.

BACKGROUND: Post-weaning diarrhea in piglets reduces growth performance and increases mortality, thereby causing serious economic losses. The intestinal epithelial cells and microbiota reciprocally regulate each other in order to maintain intestinal homeostasis and control inflammation. However, a relative paucity of research has been focused on the host-derived regulatory network that controls mucin O-glycans and thereby changes gut microbiota during diarrhea in infancy. At the development stage just after birth, the ontogeny of intestinal epithelium, immune system, and gut microbiota appear similar in piglets and human infants. Here, we investigated the changes of mucin O-glycans associated with gut microbiota using a diarrheal post-weaned piglet model. RESULTS: We found that diarrhea disrupted the colonic mucus layer and caused aberrant mucin O-glycans, including reduced acidic glycans and truncated glycans, leading to an impaired gut microenvironment. Subsequently, the onset of diarrhea, changes in microbiota and bacterial translocation, resulting in compromised epithelial barrier integrity, enhanced susceptibility to inflammation, and mild growth faltering. Furthermore, we found the activation of NLRP3 inflammasome complexes in the diarrheal piglets when compared to the healthy counterparts, triggered the release of proinflammatory cytokines IL-1ß and IL-18, and diminished autophagosome formation, specifically the defective conversion of LC3A/B I into LC3A/B II and the accumulation of p62. Additionally, selective blocking of the autophagy pathway by 3-MA led to the reduction in goblet cell-specific gene transcript levels in vitro. CONCLUSIONS: We observed that diarrheal piglets exhibited colonic microbiota dysbiosis and mucosal barrier dysfunction. Our data demonstrated that diarrhea resulted in the activation of inflammasomes and autophagy restriction along with aberrant mucin O-glycans including reduced acidic glycans and truncated glycans. The results suggested the mucin O-glycans-microbiota axis is likely associated with diarrheal pathogenesis. Our study provides novel insights into the pathophysiology of early-weaning-induced diarrheal disease in piglets and potentially understanding of disease mechanisms of diarrhea for human infants. Understanding the molecular pathology and pathogenesis of diarrhea is a prerequisite for the development of novel and effective therapies. Our data suggest that facilitating O-glycan elongation, modifying the microbiota, and developing specific inhibitors to some key inflammasomes could be the options for therapy of diarrhea including human infants. Video abstract.

A strategy for accurately and sensitively quantifying free and esterified fatty acids using liquid chromatography mass spectrometry.

Fatty acid (FA) composition of foods dictates a diversity of aspects regarding food quality, ranging from product shelf life, sensory properties to nutrition. There is a challenge to quantitate FAs using liquid chromatography-mass spectrometry due to poor ionization efficiency and matrix effects. Here, an isotopic-tagged derivatization strategy was established to accurately and sensitively quantify free and esterified FAs. After derivatization reaction, the detection sensitivity of FAs was remarkably improved and the limit of quantitation was lower than 100 ng/L. The quantitative errors caused by matrix effects were diminished benefiting from isotope-derivatized internal standards. The established quantitation strategy was successfully applied to verify both free and esterified FA contents in meat after different post-harvest procedures, finding that free polyunsaturated FAs increased significantly during freezing process.

Multi-Omics Uncover Neonatal Cecal Cell Development Potentials.

Although, the cecum plays vital roles in absorption of water, electrolytes, and other small molecules, and harbors trillions of commensal bacteria to shape large intestine immune functions, it is unknown the cecum development potentials at single cell level during the very crucial neonatal developmental period. Using singe cell RNA-seq and proteomics, we have characterized six major types of cecal cells: undifferentiated cells; immune cells (Ims); cecumocytes (CCs); goblet, Paneth like cells (PLCs), and enteroendocrine cells (EECs) with specific markers. CCs mature with a gradual decrease in proportion of cells; however, Ims develop with a continuing increase in proportion of cells. Meanwhile, goblet and EEC cells reduced in proportion of cells from do to d14 or d21; PLCs increased in proportion of cells from d0 to d7 then decreased at d14 and d21. The cells exhibit specific development and maturation trends controlled by transcriptional factors, ligand-receptor pairs, and other factors. As piglets grow, cecal content and mucosal microbial diversity increases dramatically with population of beneficial microbiota, such as lactobacillus. Moreover, cecal mucosal-associated and cecal content microbiota are positively correlated and both show significant correlation with different types of cecal cells and plasma metabolites. This is the first presentation of neonatal cecal cell development and maturation naturally at single cell level with transcript, protein, microbiota and metabolism perspectives. Furthermore, this study provides an important tool for the determination of novel interventions in cecal drug delivery and metabolism studies.

Xylooligosaccharide-mediated gut microbiota enhances gut barrier and modulates gut immunity associated with alterations of biological processes in a pig model.

Xylooligosaccharide (XOS) has tremendous prebiotic potentials for gut health, but the relevant mechanisms are unclear. Herein, we confirmed the positive effects of dietary XOS enhancing gut barrier in a pig model via suppressing the expression of pro-inflammatory cytokines (IL-6 and IL-8). Meanwhile, XOS increased beneficial microbes Lactobacillus and decreased potential pathogenic bacteria. Moreover, XOS augmented microbiota-derived metabolites (mainly butyrate, propionate, and secondary bile acid) to strengthen the gut barrier and regulate gut immunity through activating host G-protein coupled receptors 109a or inhibiting histone deacetylases. Furthermore, XOS attenuated IgA-production and antigen cross-presentation processes. In addition, XOS supplementation led to the alteration of cell proliferation, remodeling of the energy metabolism, activation processes of serial genes or proteins, increased molecular chaperones, and the enhanced ubiquitin-proteasome pathway in cecal cells. Collectively, these results suggest that XOS enhances gut barrier and modulates gut immunity by optimizing gut microbiota and their metabolites, which is associated with alterations of biological processes.

Porous polyvinyl alcohol/graphene oxide composite film for strain sensing and energy-storage applications.

In this study, a flexible porous polyvinyl alcohol (PVA)/graphene oxide (GO) composite film was developed and tested for flexible strain sensing and energy-storage applications. Morphology and mechanical properties were studied; tensile strength and Young's modulus increased by 225% and 86.88%, respectively, at 0.5 wt% GO. The PVA/GO film possesses exceptional sensing ability to various mechanical strains, such as tension, compression, bending, and torsion. For example, the gauge factor of the PVA/GO film as a tensile-strain sensor was measured as 2.46 (246%). Under compression loads, the PVA/GO composite film showed piezoresistive and capacitive strain-sensing characteristics. Under 5 kPa of compression load, the relative resistance increased by 81% with a 100 msec response time; the relative capacitance increased by 160% with a 120 msec response time. The PVA/GO strain sensor exhibited high durability and reliability over 20 × 103cycles of tensile strain and bending at 3.33 Hz. Moreover, the PVA/GO composite film showed good electrochemical properties due to its porous structure; the maximum capacitance was 124.7 F g-1at 0.5 wt% GO. After 20 × 103charging-discharging cycles, the capacitance retention rate was 94.45%, representing high stable capacitance performance. The results show that electrically conductive porous PVA nanocomposite films are promising candidates for strain sensing and energy-storage devices.

Isotope-Coded Chemical Derivatization Method for Highly Accurately and Sensitively Quantifying Short-Chain Fatty Acids.

Short-chain fatty acids (SCFAs) are major gut microbiota-derived metabolites, which can reshape the intestine and regulate gut immunity. The application of conventional GC methods has been hampered for quantifying low-concentrated SCFAs, such as in serum, saliva, and digesta of germ-free animals. Herein, we established a LC-MS method to quantify SCFAs after 5-(dimethylamino)-1-carbohydrazide-isoquinoline (DMAQ) derivatization. The DMAQ derivatization significantly enhanced the detection sensitivity and improved separation of SCFAs. 2-methylbutyric acid and 3-methylbutyric acid were separately quantitated. Moreover, the matrix effect was diminished using DMAQ-13C/15N-tagged SCFAs as internal standards. The established quantitation method was successfully applied in the analysis of plasma and cecum digesta collected from neonatal piglets, revealing that significant increases in biological SCFA contents in cecum digesta were closely related to the variation of gut microbial diversity. The established quantitation method is capable of sensitively and comprehensively quantifying SCFAs that may provide insights into underlying gut-microbiota functions.

Multi-omics unravel the compromised mucosal barrier function linked to aberrant mucin O-glycans in a pig model.

Early weaning stress (EWS) in piglets is associated with intestinal dysfunction. Here, utilizing a pig EWS model to mimic early-life stress (ELS) in humans, we investigated the mechanism of ELS-induced intestinal diseases through integrated multi-omics analyses of proteome, glycome, and microbiome. Our results demonstrated that EWS resulted in disrupted the ileal barrier integrity by reducing tight junction-related gene expression and interfering with cell-cell adhesion paralleled the increased proportion of pathogens such as Escherichia_Shigella and Helicobacter. Furthermore, Proteome data revealed that the accumulation of unfolded proteins and insufficient unfolded protein response (UPR) process caused by EWS led to ER stress. Data from proteome and glycome found that EWS induced aberrant mucin O-glycans, including truncated glycans, reduction in acidic glycans, and increased in fucosylated glycans. In addition, correlation test by taking fucose and inflammatory response into account suggested that enhancement of fucose expression might be a compensatory host response. Taken together, these results extend the comprehensive knowledge of the detrimental impacts and pathogenesis of EWS and help to provide intervention targets for ELS-induced intestinal diseases in the future.

A fluorescent pH probe for evaluating the freshness of chicken breast meat.

A fluorescent probe, Nap-MOR, based on the naphthalimide fluorophore, was designed and developed for pH measurement in aqueous solutions. Nap-MOR had a close linear relationship between fluorescence intensity and pH, in the range 4.5-8, which covers the full range of pH found in normal fresh, defective and spoiled meat. pH measurement with Nap-MOR was free from interference by a wide range of ions and biochemicals found in meat and the results were not significantly different in comparison with a pH meter. Therefore, Nap-MOR is a robust and convenient way to evaluate the freshness of chicken breast meat by measuring its pH.

Quantitative proteomics reveals tissue-specific toxic mechanisms for acute hydrogen sulfide-induced injury of diverse organs in pig.

Hydrogen sulfide (H2S) is a highly toxic gas in many environmental and occupational places. It can induce multiple organ injuries particularly in lung, trachea and liver, but the relevant mechanisms remain poorly understood. In this study, we used a TMT-based discovery proteomics to identify key proteins and correlated molecular pathways involved in the pathogenesis of acute H2S-induced toxicity in porcine lung, trachea and liver tissues. Pigs were subjected to acute inhalation exposure of up to 250 ppm of H2S for 5 h for the first time. Changes in hematology and biochemical indexes, serum inflammatory cytokines and histopathology demonstrated that acute H2S exposure induced organs inflammatory injury and dysfunction in the porcine lung, trachea and liver. The proteomic data showed 51, 99 and 84 proteins that were significantly altered in lung, trachea and liver, respectively. Gene ontology (GO) annotation, KEGG pathway and protein-protein interaction (PPI) network analysis revealed that acute H2S exposure affected the three organs via different mechanisms that were relatively similar between lung and trachea. Further analysis showed that acute H2S exposure caused inflammatory damages in the porcine lung and trachea through activating complement and coagulation cascades, and regulating the hyaluronan metabolic process. Whereas antigen presentation was found in the lung but oxidative stress and cell apoptosis was observed exclusively in the trachea. In the liver, an induced dysfunction was associated with protein processing in the endoplasmic reticulum and lipid metabolism. Further validation of some H2S responsive proteins using western blotting indicated that our proteomics data were highly reliable. Collectively, these findings provide insight into toxic molecular mechanisms that could potentially be targeted for therapeutic intervention for acute H2S intoxication.

A naphthimide fluorescent probe for the detection of selenols in selenium-enriched Tan sheep.

An "off-on" fluorescent probe, Nap-DNB, which is based on naphthimide, was designed and developed for the detection of biological selenols in vitro. We have adopted a combination of a low-pH detection environment and reaction sites that are more difficult to destroy to avoid the interference of a large number of biological thiols in biological samples. Nap-DNB can completely respond to selenocysteine within 15 mins, with a detection limit of 92 nM. Nap-DNB was successfully used for the detection of selenols in the serum, liver, and longissimus dorsi of selenium-enriched Tan sheep. Through comparison, we found that the detection of selenols by the Nap-DNB is similar to that by thioredoxin reductase and glutathione peroxidase in a commercial kit method. Nap-DNB can be used for the detection of selenols in selenium-enriched Tan sheep.