Reconstituting gut microbiota-colonocyte interactions reverses diet-induced cognitive deficits: The beneficial of eucommiae cortex polysaccharides.

Rationale: Consumption of a high-fat diet (HFD) has been implicated in cognitive deficits and gastrointestinal dysfunction in humans, with the gut microbiota emerging as a pivotal mediator of these diet-associated pathologies. The introduction of plant-based polysaccharides into the diet as a therapeutic strategy to alleviate such conditions is gaining attention. Nevertheless, the mechanistic paradigm by which polysaccharides modulate the gut microbiota remains largely undefined. This study investigated the mechanisms of action of Eucommiae cortex polysaccharides (EPs) in mitigating gut dysbiosis and examined their contribution to rectifying diet-related cognitive decline. Methods: Initially, we employed fecal microbiota transplantation (FMT) and gut microbiota depletion to verify the causative role of changes in the gut microbiota induced by HFD in synapse engulfment-dependent cognitive impairments. Subsequently, colonization of the gut of chow-fed mice with Escherichia coli (E. coli) from HFD mice confirmed that inhibition of Proteobacteria by EPs was a necessary prerequisite for alleviating HFD-induced cognitive impairments. Finally, supplementation of HFD mice with butyrate and treatment of EPs mice with GW9662 demonstrated that EPs inhibited the expansion of Proteobacteria in the colon of HFD mice by reshaping the interactions between the gut microbiota and colonocytes. Results: Findings from FMT and antibiotic treatments demonstrated that HFD-induced cognitive impairments pertaining to neuronal spine loss were contingent on gut microbial composition. Association analysis revealed strong associations between bacterial taxa belonging to the phylum Proteobacteria and cognitive performance in mice. Further, introducing E. coli from HFD-fed mice into standard diet-fed mice underscored the integral role of Proteobacteria proliferation in triggering excessive synaptic engulfment-related cognitive deficits in HFD mice. Crucially, EPs effectively counteracted the bloom of Proteobacteria and subsequent neuroinflammatory responses mediated by microglia, essential for cognitive improvement in HFD-fed mice. Mechanistic insights revealed that EPs promoted the production of bacteria-derived butyrate, thereby ameliorating HFD-induced colonic mitochondrial dysfunction and reshaping colonocyte metabolism. This adjustment curtailed the availability of growth substrates for facultative anaerobes, which in turn limited the uncontrolled expansion of Proteobacteria. Conclusions: Our study elucidates that colonocyte metabolic disturbances, which promote Proteobacteria overgrowth, are a likely cause of HFD-induced cognitive deficits. Furthermore, dietary supplementation with EPs can rectify behavioral dysfunctions associated with HFD by modifying gut microbiota-colonocyte interactions. These insights contribute to the broader understanding of the modulatory effects of plant prebiotics on the microbiota-gut-brain axis and suggest a potential therapeutic avenue for diet-associated cognitive dysfunction.

6-Methyl-5-hepten-2-one promotes programmed cell death during superficial scald development in pear.

Plants possess the ability to induce programmed cell death (PCD) in response to abiotic and biotic stresses; nevertheless, the evidence on PCD initiation during pear scald development and the involvement of the scald trigger 6-methyl-5-hepten-2-one (MHO) in this process is rudimentary. Pyrus bretschneideri Rehd. cv. 'Dangshansuli' pear was used to validate such hypothesis. The results showed that superficial scald occurred after 120-d chilling exposure, which accompanied by typical PCD-associated morphological alterations, such as plasmolysis, cell shrinkage, cytosolic and nuclear condensation, vacuolar collapse, tonoplast disruption, subcellular organelle swelling, and DNA fragmentation. These symptoms were aggravated after MHO fumigation but alleviated by diphenylamine (DPA) dipping. Through transcriptome assay, 24 out of 146 PCD-related genes, which were transcribed during cold storage, were identified as the key candidate members responsible for these cellular biological alternations upon scald development. Among these, PbrCNGC1, PbrGnai1, PbrACD6, and PbrSOBIR1 were implicated in the MHO signaling pathway. Additionally, PbrWRKY2, 34 and 39 could bind to the W-box element in the promoter of PbrGnai1 or PbrSOBIR1 and activate their transcription, as confirmed by dual-luciferase, yeast one-hybrid, and transient overexpression assays. Hence, our study confirms the PCD initiation during scald development and explores the critical role of MHO in this process.

Helical Micropillar Processed by One-Step 3D Printing for Solar Thermal Conversion.

Solar thermal utilization has broad applications in a variety of fields. Currently, maximizing the photo-thermal conversion efficiency remains a research hotspot in this field. The exquisite plant structures in nature have greatly inspired human structural design across many domains. In this work, inspired by the photosynthesis of helical grass, a HM type solar absorber made in graphene-based composite sheets is used for solar thermal conversion. The unique design promoted more effective solar energy into thermal energy through multiple reflections and scattering of solar photons. Notably, the Helical Micropillar (HM) is fabricated using a one-step projection 3D printing process based on a special 3D helical beam. As a result, the solar absorber's absorbance value can reach 0.83 in the 400-2500 nm range, and the surface temperature increased by ≈128.3% relative to the original temperature. The temperature rise rate of the solar absorber reached 22.4 °C min-1, demonstrating the significant potential of the HM in practical applications of solar thermal energy collection and utilization.

Preparative separation of the constituents from Ginkgo biloba L. leaves by a combination of multi-stage solvent extraction and countercurrent chromatography.

In this study, we employed a combination approach for the preparative separation of constituents from Ginkgo biloba L. leaves. It involved multi-stage solvent extractions utilizing two-phase multi-solvent systems and countercurrent chromatography (CCC) separations using three different solvent systems. The n-heptane/ethyl acetate/water (1:1:2, v/v) and n-heptane/ethyl acetate/methanol/water (HepEMWat, 7:3:7:3, v/v) solvent systems were screened out as extraction systems. The polarities of the upper and lower phases in the multi-solvent systems were adjustable, enabling the effectively segmented separation of complex constituents in G. biloba L. The segmented products were subsequently directly utilized as samples and separated using CCC with the solvent systems acetate/n-butanol/water (4:1:5, v/v), HepEMWat (5:5:5:5, v/v), and HepEMWat (9:1:9:1, v/v), respectively. As a result, a total of 11 compounds were successfully isolated and identified from a 2 g methanol extract of G. biloba L through two-stage extraction and three CCC separation processes; among them, nine compounds exhibited high-performance liquid chromatography purity exceeding 85%.

Separation of bufadienolides from Helleborus thibetanus Franch. by a combination approach involving macroporous resin column chromatography and gradient countercurrent chromatography.

In this study, a combination approach involving macroporous resin (MR) column chromatography and gradient countercurrent chromatography (CCC) was employed to enrich and purify bufadienolides from the roots and rhizomes of Helleborus thibetanus Franch. Initially, a D101 MR-packed column chromatography was utilized for fractionation and enrichment of the bufadienolides, which were effectively eluted from the column using a 60% ethanol solution. CCC was subsequently introduced to separate the enriched product using the ethyl acetate/n-butanol/water (EBuWat, 4:1:5, v/v) and EBuWat (5:0:5, v/v) solvent systems in a gradient elution mode. As results, five bufadienolides, including 6.1 mg of hellebrigenin-3-O-ß-D-glucoside (1), 2.2 mg of tigencaoside A (2), 8.3 mg of deglucohellebrin (3), 3.5 mg of 14 ß-hydroxy-3ß-[ß-D-glucopyranosyl-(1→6)-(ß-D-glucopyranosyl)oxy]-5α-bufa-20,22-dienolide (4), and 3.0 mg of 14ß-hydroxy-3ß-[(ß-D-glucopyranosyl)oxy]-5α-bufa-20,22-dienolide (5), were effectively separated from 300 mg of the enriched product. The respective high-performance liquid chromatography purities were as follows: 95.2%, 75.8%, 85.7%, 82.3%, and 92.8%. This study provides valuable insights for the efficient enrichment and separation of bufadienolides from Helleborus thibetanus Franch.

Multicomponent, Multicavity Metallacages That Contain Different Binding Sites for Allosteric Recognition.

The encapsulation of different guest molecules by their different recognition domains of proteins leads to selective binding, catalysis, and transportation. Synthetic hosts capable of selectively binding different guests in their different cavities to mimic the function of proteins are highly desirable but challenging. Here, we report three ladder-shaped, triple-cavity metallacages prepared by multicomponent coordination-driven self-assembly. Interestingly, the porphyrin-based metallacage is capable of heteroleptic encapsulation of fullerenes (C60 or C70) and coronene using its different cavities, allowing distinct allosteric recognition of coronene upon the addition of C60 or C70. Owing to the different binding affinities of the cavities, the metallacage hosts one C60 molecule in the central cavity and two coronene units in the side cavities, while encapsulating two C70 molecules in the side cavities and one coronene molecule in the central cavity. The rational design of multicavity assemblies that enable heteroleptic encapsulation and allosteric recognition will guide the further design of advanced supramolecular constructs with tunable recognition properties.

Wide-Size Range and High Robustness Self-Assembly Micropillars for Capturing Microspheres.

Capillary force driven self-assembly micropillars (CFSA-MP) holds immense promise for the manipulation and capture of cells/tiny objects, which has great demands of wide size range and high robustness. Here, we propose a novel method to fabricate size-adjustable and highly robust CFSA-MP that can achieve wide size range and high stability to capture microspheres. First, we fabricate a microholes template with an adjustable aspect ratio using the spatial-temporal shaping femtosecond laser double-pulse Bessel beam-assisted chemical etching technique, and then the micropillars with adjustable aspect ratio are demolded by polydimethylsiloxane (PDMS). We fully demonstrated the advantages of the Bessel optical field by using the spatial-temporal shaping femtosecond laser double-pulse Bessel beams to broaden the height range of the micropillars, which in turn expands the size range of the captured microspheres, and finally achieving a wide range of capturing microspheres with a diameter of 5-410 µm. Based on the inverted mold technology, the PDMS micropillars have ultrahigh mechanical robustness, which greatly improves the durability. CFSA-MP has the ability to capture tiny objects with wide range and high stability, which indicates great potential applications in the fields of chemistry, biomedicine, and microfluidics.

Multi-dimensional preparation of Thymus quinquecostatus Celak. by normal-phase flash chromatography coupled to counter-current chromatography.

In this study, a multi-dimensional chromatography system was developed by integrating normal-phase flash chromatography and counter-current chromatography to isolate flavonoids, phenylpropanoids, and thymol from the aerial parts of Thymus quinquecostatus Celak. In the online multi-dimensional switching system, a normal-phase flash chromatograph packed with 1.2 g of dry homogeneous silica gel mixture (containing 600 mg of methanol extract) was connected to counter-current chromatography via a six-port valve. Two two-dimensional separations were performed using n-heptane-ethyl acetate-methanol-water (6:4:6:4, v/v) and ethyl acetate-water solvent systems sequentially to separate the constituents of Thymus quinquecostatus Celak. The upper phase of the former solvent system was utilized as both elution solvent for flash chromatography and the stationary phase for counter-current chromatography, while the lower phase of the latter solvent system containing 10 mM trifluoroacetic acid was employed as elution solvent for flash chromatography and one mobile phase in pH gradient counter-current chromatography. Thymol (7) and xanthomicrol (8), two hydrophobic ingredients, were purified in the initial two-dimensional separation. The subsequent two-dimensional separation yielded six hydrophilic compounds, namely dihydrokaempferol-7-O-D-glucopyranoside (1), lithospermic acid (2), luteolin-7-O-glucuronide (3), rosmarinic acid (4), messerschmidin (5) and apigenin-7-O-D-glucuronide (6). This study represents the first documented use of online multi-dimensional normal-phase flash chromatography coupled to counter-current chromatography for separating constituents from Thymus quinquecostatus Celak.

High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism.

BACKGROUND: Aberrant tryptophan (Trp)-kynurenine (Kyn) metabolism has been implicated in the pathogenesis of human disease. In particular, populations with long-term western-style diets are characterized by an excess of Kyn in the plasma. Host-gut microbiota interactions are dominated by diet and are essential for maintaining host metabolic homeostasis. However, the role of western diet-disturbed gut microbiota-colonocyte interactions in Trp metabolism remains to be elucidated. RESULTS: Here, 4-week-old mice were fed with a high-fat diet (HFD), representing a typical western diet, for 4 weeks, and multi-omics approaches were adopted to determine the mechanism by which HFD disrupted gut microbiota-colonocyte interplay causing serum Trp-Kyn metabolism dysfunction. Our results showed that colonocyte-microbiota interactions dominated the peripheral Kyn pathway in HFD mice. Mechanistically, persistent HFD-impaired mitochondrial bioenergetics increased colonic epithelial oxygenation and caused metabolic reprogramming in colonites to support the expansion of Proteobacteria in the colon lumen. Phylum Proteobacteria-derived lipopolysaccharide (LPS) stimulated colonic immune responses to upregulate the indoleamine 2,3-dioxygenase 1 (IDO1)-mediated Kyn pathway, leading to Trp depletion and Kyn accumulation in the circulation, which was further confirmed by transplantation of Escherichia coli (E.coli) indicator strains and colonic IDO1 depletion. Butyrate supplementation promoted mitochondrial functions in colonocytes to remodel the gut microbiota in HFD mice, consequently ameliorating serum Kyn accumulation. CONCLUSIONS: Our results highlighted that HFD disrupted the peripheral Kyn pathway in a gut microbiota-dependent manner and that the continuous homeostasis of gut bacteria-colonocytes interplay played a central role in the regulation of host peripheral Trp metabolism. Meanwhile, this study provided new insights into therapies against western diet-related metabolic disorders. Video Abstract.

Hydrogen sulfide improves salt tolerance through persulfidation of PMA1 in Arabidopsis.

KEY MESSAGE: A new interaction was found between PMA1 and GRF4. H2S promotes the interaction through persulfidated Cys446 of PMA1. H2S activates PMA1 to maintain K+/Na+ homeostasis through persulfidation under salt stress. Plasma membrane H+-ATPase (PMA) is a transmembrane transporter responsible for pumping protons, and its contribution to salt resistance is indispensable in plants. Hydrogen sulfide (H2S), a small signaling gas molecule, plays the important roles in facilitating adaptation of plants to salt stress. However, how H2S regulates PMA activity remains largely unclear. Here, we show a possible original mechanism for H2S to regulate PMA activity. PMA1, a predominant member in the PMA family of Arabidopsis, has a non-conservative persulfidated cysteine (Cys) residue (Cys446), which is exposed on the surface of PMA1 and located in cation transporter/ATPase domain. A new interaction of PMA1 and GENERAL REGULATORY FACTOR 4 (GRF4, belongs to the 14-3-3 protein family) was found by chemical crosslinking coupled with mass spectrometry (CXMS) in vivo. H2S-mediated persulfidation promoted the binding of PMA1 to GRF4. Further studies showed that H2S enhanced instantaneous H+ efflux and maintained K+/Na+ homeostasis under salt stress. In light of these findings, we suggest that H2S promotes the binding of PMA1 to GRF4 through persulfidation, and then activating PMA, thus improving the salt tolerance of Arabidopsis.

Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling.

Diabetes has become a significant disease threatening human health and social development. Food intervention is considered an essential strategy to prevent early diabetes development sustainably. The natural product, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG), commonly found in fruits and diets, has many potential antihypoglycemic, antibacterial, and antitumor activities. We found that PGG can promote glucose uptake in whole-organism zebrafish screening, which help in downregulating the glucose levels. We investigated the metabolome and transcriptome changes in zebrafish exposed to high glucose and PGG intervention. The differential genes and metabolites were screened out based on the comparisons of blank, hyperglycemic, and the PGG-exposed groups of zebrafish larvae. Combined with RT-qPCR validation, we found that PGG mainly restored four genes (fthl27, LOC110438965, plat, and aacs) and six metabolites abnormally invoked by high glucose. These validated genes are related with the key metabolites sphingosine and (R)-3-hydroxybutanoate involving the pathways of apelin, apoptosis, necroptosis, and butanoate metabolism. Our findings provided a new mechanistic basis for understanding the hypoglycaemic function of the commonly present dietary molecule (PGG) and offered a new perspective for the rational utilization of PGG to regulate metabolic disorders.

Metabolic exploration of the developmental abnormalities and neurotoxicity of Esculentoside B, the main toxic factor in Phytolaccae radix.

P: radix is a perennial herb, and its extracts have various biological properties that make it a potential candidate for the treatment of tumors, edema, and lymphatic stasis. However, the main factor contributing to its toxicity are not clear. Here, we used a zebrafish toxicological model to study the main toxicity factor of P. radix and explore the potential mechanisms involved. The results revealed that Esculentoside B was the major toxic factor of P. radix. Exposure of zebrafish larvae to Esculentoside B caused developmental abnormalities, neurotoxicity and altered locomotor behavior. The combination of AChE activity and the expression levels of genes relevant to CNS development demonstrated that Esculentoside B is neurotoxic to zebrafish larvae, impairs their CNS development, and that AChE may be a toxic target of Esculentoside B. Metabolomic analysis has revealed that Esculentoside B exposure can disrupt D-Amino acid metabolism, protein export, autophagy, and mTOR signaling pathways in zebrafish larvae. These findings provide insights into the molecular mechanisms underlying EsB-induced neurotoxicity in zebrafish, which can facilitate further research and development of P. radix for safe consumption.

Nitric oxide induces S-nitrosylation of CESA1 and CESA9 and increases cellulose content in Arabidopsis hypocotyls.

Nitric oxide (NO), a small signaling gas molecule, participates in several growth and developmental processes in plants. However, how NO regulates cell wall biosynthesis remains unclear. Here, we demonstrate a positive effect of NO on cellulose content that may be related to S-nitrosylation of cellulose synthase 1 (CESA1) and CESA9. Two S-nitrosylated cysteine (Cys) residues, Cys562 and Cys641, which are exposed on the surface of CESA1 and CESA9 and located in the cellulose synthase catalytic domain, were identified to be S-nitrosylated. Meanwhile, Cys641 was located on the binding surface of CESA1 and CESA9, and Cys562 was very close to the binding surface. Cellulose synthase complexes (CSCs) dynamics are closely associated with cellulose content. S-nitrosylation of CESA1 and CESA9 improved particles mobility and thus increased the accumulation of cellulose in Arabidopsis hypocotyl cells. An increase in hemicellulose content as well as an alteration in pectin content facilitated cell wall extension and contributed to cell growth, finally promoting elongation of Arabidopsis hypocotyls. Overall, our work provides a path to investigate the way NO affects the cellulose content of plants.

Stacking-BERT model for Chinese medical procedure entity normalization.

Medical procedure entity normalization is an important task to realize medical information sharing at the semantic level; it faces main challenges such as variety and similarity in real-world practice. Although deep learning-based methods have been successfully applied to biomedical entity normalization, they often depend on traditional context-independent word embeddings, and there is minimal research on medical entity recognition in Chinese Regarding the entity normalization task as a sentence pair classification task, we applied a three-step framework to normalize Chinese medical procedure terms, and it consists of dataset construction, candidate concept generation and candidate concept ranking. For dataset construction, external knowledge base and easy data augmentation skills were used to increase the diversity of training samples. For candidate concept generation, we implemented the BM25 retrieval method based on integrating synonym knowledge of SNOMED CT and train data. For candidate concept ranking, we designed a stacking-BERT model, including the original BERT-based and Siamese-BERT ranking models, to capture the semantic information and choose the optimal mapping pairs by the stacking mechanism. In the training process, we also added the tricks of adversarial training to improve the learning ability of the model on small-scale training data. Based on the clinical entity normalization task dataset of the 5th China Health Information Processing Conference, our stacking-BERT model achieved an accuracy of 93.1%, which outperformed the single BERT models and other traditional deep learning models. In conclusion, this paper presents an effective method for Chinese medical procedure entity normalization and validation of different BERT-based models. In addition, we found that the tricks of adversarial training and data augmentation can effectively improve the effect of the deep learning model for small samples, which might provide some useful ideas for future research.

The interaction of CFLAR with p130Cas promotes cell migration.

CASP8 and FADD Like Apoptosis Regulator (CFLAR) is a key anti-apoptotic regulator for resistance to apoptosis mediated by Fas and TRAIL. In addition to its anti-apoptotic function, CFLAR is also an important mediator of tumor growth. High level of CFLAR expression correlates with a more aggressive tumor. However, the mechanism of CFLAR signaling in malignant progression is not clear. Here we report a novel CFLAR-associated protein p130Cas, which is a general regulator of cell growth and cell migration. CFLAR-p130Cas association is mediated by the DED domain of CFLAR and the SD domain of p130Cas. Immunofluorescence observation showed that CFLAR had the colocalization with p130Cas at the focal adhesion of cell membrane. CFLAR overexpression promoted p130Cas phosphorylation and the formation of focal adhesion complex. Moreover, the enhancement of cell migration induced by CFLAR overexpression was obviously inhibited by p130Cas siRNA. In silico analysis on human database suggests high expressions of CFLAR or/and p130Cas are associated with poor prognosis of patients with lung cancer. Together, our results suggest a new mechanism for CFLAR involved in tumor development via association with p130Cas.

Effects of Social Support and Loneliness on the Irrational Consumption Tendencies of Healthcare Products among the Elderly: A Structural Equation Model.

BACKGROUND: In recent years, with the development of the social economy and an improvement in health consciousness, the levels of demand and consumption for healthcare products have been increasing rapidly among the elderly. However, the irrational consumption of healthcare products has caused widespread concern, as it can generate economic losses and have negative effects on psychological health. Therefore, it is critical to identify the variables that can reduce tendencies toward irrational consumption in the area of healthcare products. This study aimed to explore the relationship between the irrational consumption tendencies of healthcare products, social support, and loneliness among elderly people in Hangzhou, China. METHODS: In 2021, a cross-sectional survey involving 485 elderly people from three districts in Hangzhou, China, was conducted. Descriptive statistics were calculated for socioeconomic status and demographic characteristics, level of loneliness, social support, and irrational consumption tendencies. A structural equation model was used to test the impact of social support on the irrational consumption tendencies of healthcare products among the elderly and to explore the mediating effects of loneliness. RESULTS: The findings reveal that the average levels of social support and loneliness among the elderly were 30.63 points (total = 44 points) and 6.88 points (15 points), respectively. The average scores of the four subscales of irrational consumption tendencies, which were named susceptibility to persuasion, interpersonal influences, pursuit of added value, and fears of aging were 2.48, 2.93, 2.48, and 3.17 points (5 points), respectively. Social support had a significant effect on irrational consumption tendencies, and loneliness played a partial mediating role between social support and irrational consumption tendencies. CONCLUSIONS: A relationship model was constructed to examine the association between loneliness, social support, and irrational consumption tendencies among older people in relation to healthcare products. From a social support and psychological perspective, advice and countermeasures are proposed to prevent the irrational consumption of healthcare products among older people.

Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS.

Alcohol is an essential element in human culture. However, alcoholism has contributed to numerous health issues, including alcoholic fatty liver and sudden death. We found that the alkaloid lotusine possessed hepato- and neuroprotection against alcohol injuries. Lotusine showed comparable protective effects to puerarin, a widely recognized antagonist against alcohol damage. To better understand the metabolic response to alcohol injury and antagonist molecules, we applied sensitive zebrafish and LC-ESI-MS to collect metabolites related to alcohol, puerarin and lotusine exposure. LC-MS identified 119 metabolites with important physiological roles. Differential metabolomic analysis showed that alcohol caused abnormal expression of 82 metabolites (60 up-regulated and 22 down-regulated). These differential metabolites involved 18 metabolic pathways and modules, including apoptosis, necroptosis, nucleotide and fatty acid metabolism. Puerarin reversed seven metabolite variations induced by alcohol, which were related to necroptosis and sphingolipid metabolism. Lotusine was found to repair five metabolites disorders invoked by alcohol, mainly through nucleotide metabolism and glutathione metabolism. In phenotypic bioassay, lotusine showed similar activities to puerarin in alleviating behavioral abnormalities, neuroapoptosis and hepatic lipid accumulation induced by alcohol exposure. Our findings provided a new antagonist, lotusine, for alcohol-induced damage and explored the roles in repairing abnormal metabolism.

D-chiro-Inositol facilitates adiponectin biosynthesis and activates the AMPKα/PPARs pathway to inhibit high-fat diet-induced obesity and liver lipid deposition.

D-chiro-Inositol (DCI) is a natural cyclohexanol isomer that widely exists in all living beings, which can effectively prevent glucose and lipid metabolism disorders in mammals. This study revealed the DCI elevated adiponectin levels to reduce obesity and hepatic lipid deposition in high-fat diet (HFD) fed mice. Twelve weeks of DCI supplementation (50 and 100 mg per kg body weight per day) lowered body weight and serum triglyceride, total cholesterol, insulin, and fasting glucose levels. Histopathology analysis revealed that DCI inhibited hepatic steatosis and adipocyte expansion. Remarkably, DCI significantly increased serum adiponectin levels and upgraded the expressions of adiponectin receptors (AdipoR1 and AdipoR2) in the liver. The results of western blot and qRT-PCR showed that DCI impeded the inhibitory effect of HFD on liver AMPKα and PPARs activities through activating AdipoRs and regulated downstream fatty acid metabolism. In addition, we analyzed the concentration difference of DCI in mouse liver and adipose tissue by the HRLC-MS/MS technology, indicating the preference of DCI in different tissues. Therefore, DCI relieved liver lipid deposition and hyperlipidemia potentially by promoting adiponectin synthesis in white adipose tissue and activating the AdipoR-AMPKα/PPARs pathway in the liver.

Effect of type 2 diabetes on coronary artery ectasia: smaller lesion diameter and shorter lesion length but similar adverse cardiovascular events.

BACKGROUND: Coronary artery ectasia (CAE) is a rare finding in coronary angiography and associated with poor clinical outcomes. Unlike atherosclerosis, diabetes mellitus (DM) is not commonly associated with CAE. This study aims to investigate the effect of type 2 diabetes mellitus (DM2) on coronary artery ectasia, especially the differences in angiographic characteristics and clinical outcomes. METHODS: Patients with angiographically confirmed CAE from 2009 to 2015 were included. Quantitative coronary angiography (QCA) was performed to measure the diameter and length of the dilated lesion. The primary endpoint was the maximum diameter and maximum length of the dilated lesion at baseline coronary angiography. The secondary endpoint was 5-year major adverse cardiovascular events (MACE), which was a component of cardiovascular death and nonfatal myocardial infarction (MI). Propensity score weighting (PSW) and propensity score matching (PSM) were used to balance covariates. Kaplan-Meier method and Cox regression were performed to assess the clinical outcomes. RESULTS: A total of 1128 patients were included and 258 were combined with DM2. In the DM2 group, the maximum diameter of dilated lesion was significantly lower (5.26 mm vs. 5.47 mm, P = 0.004) and the maximum length of the dilated lesion was significantly shorter (25.20 mm vs. 31.34 mm, P = 0.002). This reduction in dilated lesion diameter (5.26 mm vs. 5.41 mm, P = 0.050 in PSW; 5.26 mm vs. 5.46 mm, P = 0.007 in PSM, respectively) and length (25.17 mm vs. 30.17 mm, P = 0.010 in PSW; 25.20 mm vs. 30.81 mm, P = 0.012 in PSM, respectively) was consistently observed in the propensity score analysis. A total of 27 cardiovascular deaths and 41 myocardial infarctions occurred at 5-year follow-up. Compared with non-DM group, there were similar risks of MACE (6.02% vs. 6.27%; HR 0.96, 95% CI 0.54-1.71, P = 0.894), cardiovascular death (2.05% vs. 2.61%; HR 0.78, 95% CI 0.29-2.05, P = 0.605) and MI (4.07% vs. 3.72%; HR 1.11, 95% CI 0.54-2.26, P = 0.782) in patients with DM2. Consistent result was observed in multivariable regression. CONCLUSIONS: Compared to non-DM patients, patients with CAE and type 2 diabetes were associated with a smaller diameter and shorter length of dilated vessels, suggesting the important effect of DM2 on the pathophysiological process of CAE. Similar risks of MACE were found during 5-year follow up among diabetic and non-DM patients.

Development and Validation of a Nomogram for Predicting the Risk of Adverse Cardiovascular Events in Patients with Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is a rare finding and is associated with poor clinical outcomes. However, prognostic factors are not well studied and no prognostication tool is available. In a derivation set comprising 729 consecutive CAE patients between January 2009 and June 2014, a nomogram was developed using Cox regression. Total of 399 patients from July 2014 to December 2015 formed the validation set. The primary outcome was 5-year major adverse cardiovascular events (MACE), a component of cardiovascular death and nonfatal myocardial infarction. Besides the clinical factors, we used quantitative coronary angiography (QCA) and defined QCA classification of four types, according to max diameter (< or ≥5 mm) and max length ratio (ratio of lesion length to vessel length, < or ≥1/3) of the dilated lesion. A total of 27 cardiovascular deaths and 41 nonfatal myocardial infarctions occurred at 5-year follow-up. The nomogram effectively predicted 5-year MACE risk using predictors including age, prior PCI, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and QCA classification (area under curve [AUC] 0.75, 95% CI 0.68-0.82 in the derivation set; AUC 0.71, 95% CI 0.56-0.86 in the validation set). Patients were classified as high-risk if prognostic scores were ≥155 and the Kaplan-Meier curves were well separated (log-rank p < 0.001 in both sets). Calibration curve and Hosmer-Lemeshow test indicated similarity between predicted and actual 5-year MACE survival (p = 0.90 in the derivation and p = 0.47 in the validation set). This study developed and validated a simple-to-use method for assessing 5-year MACE risk in patients with CAE.