Dopamine receptor D2 confers colonization resistance via microbial metabolites.

The gut microbiome has major roles in modulating host physiology. One such function is colonization resistance, or the ability of the microbial collective to protect the host against enteric pathogens1-3, including enterohaemorrhagic Escherichia coli (EHEC) serotype O157:H7, an attaching and effacing (AE) food-borne pathogen that causes severe gastroenteritis, enterocolitis, bloody diarrhea and acute renal failure4,5 (haemolytic uremic syndrome). Although gut microorganisms can provide colonization resistance by outcompeting some pathogens or modulating host defence provided by the gut barrier and intestinal immune cells6,7, this phenomenon remains poorly understood. Here, we show that activation of the neurotransmitter receptor dopamine receptor D2 (DRD2) in the intestinal epithelium by gut microbial metabolites produced upon dietary supplementation with the essential amino acid L-tryptophan protects the host against Citrobacter rodentium, a mouse AE pathogen that is widely used as a model for EHEC infection8,9. We further find that DRD2 activation by these tryptophan-derived metabolites decreases expression of a host actin regulatory protein involved in C. rodentium and EHEC attachment to the gut epithelium via formation of actin pedestals. Our results reveal a noncanonical colonization resistance pathway against AE pathogens that features an unconventional role for DRD2 outside the nervous system in controlling actin cytoskeletal organization in the gut epithelium. Our findings may inspire prophylactic and therapeutic approaches targeting DRD2 with dietary or pharmacological interventions to improve gut health and treat gastrointestinal infections, which afflict millions globally.

Genetic diversity and genome-wide association study of 13 agronomic traits in 977 Beta vulgaris L. germplasms.

BACKGROUND: Sugar beet (Beta vulgaris L.) is an economically essential sugar crop worldwide. Its agronomic traits are highly diverse and phenotypically plastic, influencing taproot yield and quality. The National Beet Medium-term Gene Bank in China maintains more than 1700 beet germplasms with diverse countries of origin. However, it lacks detailed genetic background associated with morphological variability and diversity. RESULTS: Here, a comprehensive genome-wide association study (GWAS) of 13 agronomic traits was conducted in a panel of 977 sugar beet accessions. Almost all phenotypic traits exhibited wide genetic diversity and high coefficient of variation (CV). A total of 170,750 high-quality single-nucleotide polymorphisms (SNPs) were obtained using the genotyping-by-sequencing (GBS). Neighbour-joining phylogenetic analysis, principal component analysis, population structure and kinship showed no obvious relationships among these genotypes based on subgroups or regional sources. GWAS was carried out using a mixed linear model, and 159 significant associations were detected for these traits. Within the 25 kb linkage disequilibrium decay of the associated markers, NRT1/PTR FAMILY 6.3 (BVRB_5g097760); nudix hydrolase 15 (BVRB_8g182070) and TRANSPORT INHIBITOR RESPONSE 1 (BVRB_8g181550); transcription factor MYB77 (BVRB_2g023500); and ethylene-responsive transcription factor ERF014 (BVRB_1g000090) were predicted to be strongly associated with the taproot traits of root groove depth (RGD); root shape (RS); crown size (CS); and flesh colour (FC), respectively. For the aboveground traits, UDP-glycosyltransferase 79B6 (BVRB_9g223780) and NAC domain-containing protein 7 (BVRB_5g097990); F-box protein At1g10780 (BVRB_6g140760); phosphate transporter PHO1 (BVRB_3g048660); F-box protein CPR1 (BVRB_8g181140); and transcription factor MYB77 (BVRB_2g023500) and alcohol acyltransferase 9 (BVRB_2g023460) might be associated with the hypocotyl colour (HC); plant type (PT); petiole length (PL); cotyledon size (C); and fascicled leaf type (FLT) of sugar beet, respectively. AP-2 complex subunit mu (BVRB_5g106130), trihelix transcription factor ASIL2 (BVRB_2g041790) and late embryogenesis abundant protein 18 (BVRB_5g106150) might be involved in pollen quantity (PQ) variation. The candidate genes extensively participated in hormone response, nitrogen and phosphorus transportation, secondary metabolism, fertilization and embryo maturation. CONCLUSIONS: The genetic basis of agronomical traits is complicated in heterozygous diploid sugar beet. The putative valuable genes found in this study will help further elucidate the molecular mechanism of each phenotypic trait for beet breeding.

Effect of tea polyphenols on sturgeon myofibrillar protein structure in the in vitro anti-glycation model mediated by low temperature vacuum heating.

The binding mechanism between tea polyphenols and sturgeon myofibrillar protein (SMP) in the early stage (0, 2, 4 min), middle stage (6, 10 min) and late stage (15 min) of low temperature vacuum heating (LTVH) in an in vitro anti-glycation model was investigated. The result indicated that the protein cross-linking during LTVH treatment were mainly induced by tea polyphenols. The loss rate of free arginine (Arg) and free lysine (Lys) of SMP at the late stage of LTVH treatment (15 min) was 73.95 % and 83.16 %, respectively. The hydrophobic force and disulfide bond were the main force between tea polyphenols and SMP in the middle and late stage of LTVH treatment. The benzene ring and phenolic hydroxyl group of tea polyphenols can interact with the amino acid residues of SMP, which was exothermic and entropy-increasing. This study provides new insights in the interaction mechanisms between tea polyphenols-protein during heat treatment process.

Preventive strategies for feeding intolerance among patients with severe traumatic brain injury: A cross-sectional survey.

Objectives: This study aimed to investigate the application status of preventive measures for feeding intolerance in patients with severe traumatic brain injury (STBI) in China and analysis the differences and their causes. Methods: A cross-sectional survey was conducted. From December 2019 to January 2020, ICU nurses and physicians of 89 hospitals in China were surveyed by using a questionnaire on preventive strategies for feeding intolerance in patients with STBI. The questionnaire included two parts: the general information of participants (10 items) and application of preventive measures for feeding intolerance in STBI patients (18 items). Results: Totally 996 nurses and physicians completed the questionnaire. Among various methods, gastrointestinal symptoms(85.0%) and injury severity (71.4%) were mostly used to assess gastrointestinal functions and risk of feeding intolerance among STBI patients, respectively. Initiating enteral nutrition (EN) within 24-48 h (61.5%), nasogastric tubes (91.2%), 30°-45° of head-of-bed elevation (89.5%), continuous feeding by pump (72.9%), EN solution temperature of 38-40 °C (65.5%), <500 ml initial volume of EN solution (50.0%), monitoring gastric residual volume with a syringe (93.7%), and assessing gastric residual volume every 4 h (51.5%) were mostly applied for EN delivery among STBI patients. Prokinetic agents (73.3%), enema (73.6%), probiotics (79.0%), antacid agents (84.1%), and non-nutritional preparations as initial EN formula (65.6%) were commonly used for preventing feeding intolerance among STBI patients. Conclusions: The survey showed that nurses and clinicians in China have a positive attitude towards preventive strategies for feeding intolerance. However, some effective new technologies and methods have not been timely applied in clinical practice. We suggest that managers, researchers, clinicians, nurses, and other health professionals should collaborate to explore effective and standard preventive strategies for feeding intolerance among patients with STBI.

Improving oxidative stability and release behavior of docosahexaenoic acid algae oil by microencapsulation.

BACKGROUND: Spray-dried docosahexaenoic acid algae oil (DHA AO) microcapsules were prepared using whey protein isolate and glucose syrup (WPI + GS), or sodium starch octenylsuccinate and glucose syrup (SSOS + GS), or whey protein isolate and lactose (WPI + L). The effect of the formulations on encapsulation properties, oxidative protection and in vitro oil release pattern of the resulting microencapsulates was investigated. RESULTS: A high encapsulation efficiency of over 98% of DHA AO was obtained for microcapsules with all three wall materials. Among the wall materials, SSOS + GS exhibited a better micro-particulation ability reflected by more uniform size and smoother surface of the formed microcapsules and no agglomerates. DHA AO microcapsules with all the wall materials showed good protection of the oil from oxidation during storage with an increasing order of WPI + GS, SSOS + GS and WPI + L. Moreover, microencapsulation significantly increased the release of DHA AO in the intestinal phase of the in vitro digestion process with an increasing order of SSOS + GS, WPI + GS and WPI + L, indicating the increased stability of the oil in the highly acidic gastric environment and the enhanced lipid digestibility in the small intestine. CONCLUSIONS: The results suggest that it is possible to transform a highly oxidizable liquid functional food ingredient such as DHA AO into a stable and easy-to-handle solid powder through spray drying with properly selected wall materials. © 2020 Society of Chemical Industry.

[Comparative Observation on Electroacupuncture and Manual Acupuncture in Rabbits with Facial Nerve Injury by Electron Microscope].

OBJECTIVE: To observe the effect of manual acupuncture and electroacupuncture (EA) on ultrastructure of facial nerve Schwann cells, myelin sheath and mitochondria in facial nerve injury rabbits, so as to explore its mechanism underlying improving facial palsy. METHODS: A total of 50 New Zealand rabbits were randomly divided into normal, sham-operation, model, MA and EA groups (n=10 in each group). Facial nerve injury model was made by clamping the facial nerve for 5 min using a pair of forceps. Manual needle stimulation (mild reinforcing-reducing) or EA (continuous wave, 20 Hz) was applied to "Dicang" (ST 4), "Xiaguan" (ST 7), "Taiyang" (EX-HN 5) and "Yangbai" (GB 14) on the injured sides for 4 weeks, 30 min each day. The facial nerve motion score was performed every 7 days. The ultrastructure of facial nerve was observed by electron microscope after 28 days' treatment. RESULTS: There were no significant differences in behavioral score and ultrastructure in normal and sham-operation groups (P<0.05). Compared with the normal group, facial nerve motion scores, ultrastructural morphological changes and the number of axons per unit area, myelin sheath thickness and axon area were worse in the model group (P<0.05). After treatment, facial nerve motion scores, ultrastructural morphological changes and the number of axons per unit area, myelin sheath thickness and axon area in the two treatment groups were better than those in the model group (P<0.05), and EA worked better than MA (P<0.05). CONCLUSIONS: In the treatment of facial nerve injury, EA can promote axoplasmic mitochondrial proliferation, myelin sheath recovery and axonal regeneration more effectively than MA, which may be one of the mechanisms that EA therapy is superior to MA.

Ginsenoside metabolite compound k alleviates adjuvant-induced arthritis by suppressing T cell activation.

Ginsenoside metabolite compound K (CK) is the degradation product of ginsenosides in the intestine by bacteria and has many pharmacological activities including anti-inflammatory effects. Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease characterized by chronic synovial inflammation and articular damage in multiple joints. However, the effect of CK on RA remains unclear. In this study, the effect of CK on adjuvant arthritis (AA) and the underlying mechanisms that focused on T cell activation were investigated. Complete Freund's adjuvant was used to induce AA rats. After the onset of arthritis, rats were given CK (10, 40, and 160 mg/kg) or MTX (0.5 mg/kg). To evaluate the severity of arthritis, arthritis index and paw swelling were evaluated every 3 days. Histopathology of joint and spleen were assayed. Subsets of T cells including CD4+CD62L+ (naïve T cells), CD4+CD25+ (activated T cells), and CD4+CD25 + Foxp3+ cells (Treg) and CD25 expression were assayed by flow cytometry. Proliferation of T cell was evaluated by (3)H-TdR. IL-2 level was assayed by ELISA. We found that CK attenuated arthritis index and paw swelling, restored the histopathological change of joint and spleen, downregulated the percentage of activated T cells, and upregulated naïve T cells and Treg cells in spleen. CK significantly suppressed T cell activation (as indicated by T cell proliferation, CD25 expression, and IL-2 production). In conclusion, our results suggest that CK alleviates autoimmune arthritis by suppressing T cell activation.

[Metabolite changes in the greasy tongue coating of patients with chronic gastritis].

OBJECTIVE: To explore the changes in metabolites in the greasy tongue coating in patients with chronic gastritis. METHODS: Forty chronic gastritis patients presenting with greasy tongue coating, 30 chronic gastritis patients presenting with non-greasy tongue coating, and 20 healthy control persons presenting with light red tongues and thin white coating were enrolled, and the tongue coating was detected by combining artificial diagnosis and the Z-BOX Tongue Digital Analyzer's diagnosis. Samples of all the tongue coatings were collected before treatment. The metabolic fingerprinting of the tongue coating samples was obtained using ultra-performance liquid chromatography and mass spectrometry (UPLC-MS), and the metabolic components in the tongue coating samples were detected. After this, principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify potential metabolic markers. Finally, the components were identified using the Chemspider and HMDB searching. RESULTS: UPLC-MS results were analyzed by OPLS-DA and showed that the metabolites among the three groups were distributed in different regions. The different potential metabolic markers between the patients with or without greasy coating were 3-ketolactose, 2-deoxy-D-ribose, UDP-D-galactose metarhodopsin, ascorbate, picolinate and histidine. The different potential metabolic markers between the greasy coating group and the normal group were 3-ketolactose, UDP-D-galactose, leukotriene A4 and vitamin D(2). CONCLUSION: The metabolites of the greasy coating group, the non-greasy coating group and the normal group show significant differences in energy metabolism, mainly of glucose metabolism. This demonstrated that glucose metabolism may be one of the mechanisms leading to the formation of greasy coating.

Application of multilabel learning using the relevant feature for each label in chronic gastritis syndrome diagnosis.

Background. In Traditional Chinese Medicine (TCM), most of the algorithms are used to solve problems of syndrome diagnosis that only focus on one syndrome, that is, single label learning. However, in clinical practice, patients may simultaneously have more than one syndrome, which has its own symptoms (signs). Methods. We employed a multilabel learning using the relevant feature for each label (REAL) algorithm to construct a syndrome diagnostic model for chronic gastritis (CG) in TCM. REAL combines feature selection methods to select the significant symptoms (signs) of CG. The method was tested on 919 patients using the standard scale. Results. The highest prediction accuracy was achieved when 20 features were selected. The features selected with the information gain were more consistent with the TCM theory. The lowest average accuracy was 54% using multi-label neural networks (BP-MLL), whereas the highest was 82% using REAL for constructing the diagnostic model. For coverage, hamming loss, and ranking loss, the values obtained using the REAL algorithm were the lowest at 0.160, 0.142, and 0.177, respectively. Conclusion. REAL extracts the relevant symptoms (signs) for each syndrome and improves its recognition accuracy. Moreover, the studies will provide a reference for constructing syndrome diagnostic models and guide clinical practice.