Transcriptome and metabolome analyses reveal molecular mechanisms of anthocyanin-related leaf color variation in poplar (Populus deltoides) cultivars.

Introduction: Colored-leaf plants are increasingly popular for their aesthetic, ecological, and social value, which are important materials for research on the regulation of plant pigments. However, anthocyanin components and the molecular mechanisms of anthocyanin biosynthesis in colored-leaf poplar remain unclear. Consequently, an integrative analysis of transcriptome and metabolome is performed to identify the key metabolic pathways and key genes, which could contribute to the molecular mechanism of anthocyanin biosynthesis in the colored-leaf cultivars poplar. Methods: In this study, integrated metabolite and transcriptome analysis was performed to explore the anthocyanin composition and the specific regulatory network of anthocyanin biosynthesis in the purple leaves of the cultivars 'Quanhong' (QHP) and 'Zhongshanyuan' (ZSY). Correlation analysis between RNA-seq data and metabolite profiles were also performed to explore the candidate genes associated with anthocyanin biosynthesis. R2R3-MYB and bHLH TFs with differential expression levels were used to perform a correlation analysis with differentially accumulated anthocyanins. Results and discussion: A total of 39 anthocyanin compounds were detected by LC-MS/MS analysis. Twelve cyanidins, seven pelargonidins, five delphinidins, and five procyanidins were identified as the major anthocyanin compounds, which were differentially accumulated in purple leaves of QHP and ZSY. The major genes associated with anthocyanin biosynthesis, including structural genes and transcription factors, were differentially expressed in purple leaves of QHP and ZSY through RNA-sequencing (RNA-seq) data analysis, which was consistent with quantitative real-time PCR analysis results. Correlation analysis between RNA-seq data and metabolite profiles showed that the expression patterns of certain differentially expressed genes in the anthocyanin biosynthesis pathway were strongly correlated with the differential accumulation of anthocyanins. One R2R3-MYB subfamily member in the SG5 subgroup, Podel.04G021100, showed a similar expression pattern to some structural genes. This gene was strongly correlated with 16 anthocyanin compounds, indicating that Podel.04G021100 might be involved in the regulation of anthocyanin biosynthesis. These results contribute to a systematic and comprehensive understanding of anthocyanin accumulation and to the molecular mechanisms of anthocyanin biosynthesis in QHP and ZSY.

A review on the synthesis and development of alginate hydrogels for wound therapy.

Convenient and low-cost dressings can reduce the difficulty of wound treatment. Alginate gel dressings have the advantages of low cost and safe usage, and they have obvious potential for development in biomedical materials. Alginate gel dressings are currently a research area of great interest owing to their versatility, intelligent, and their application attempts in treating complex wounds. We present a detailed summary of the preparation of alginate hydrogels and a study of their performance improvement. Herein, we summarize the various applications of alginate hydrogels. The research focuses in this area mainly include designing multifunctional dressings for the treatment of various wounds and fabricating specialized dressings to assist physicians in the treatment of complex wounds (TOC). This review gives an outlook for future directions in the field of alginate hydrogel dressings. We hope to attract more research interest and studies in alginate hydrogel dressings, thus contributing to the creation of low-cost and highly effective wound treatment materials.

Effects and possible mechanisms of intermittent fasting on health and disease: a narrative review.

The imbalance between energy intake and expenditure in an environment of continuous food availability can lead to metabolic disturbances in the body and increase the risk of obesity and a range of chronic noncommunicable diseases. Intermittent fasting (IF) is one of the most popular nonpharmacological interventions to combat obesity and chronic noncommunicable diseases. The 3 most widely studied IF regimens are alternate-day fasting, time-restricted feeding, and the 5:2 diet. In rodents, IF helps optimize energy metabolism, prevent obesity, promote brain health, improve immune and reproductive function, and delay aging. In humans, IF's benefits are relevant for the aging global population and for increasing human life expectancy. However, the optimal model of IF remains unclear. In this review, the possible mechanisms of IF are summarized and its possible drawbacks are discussed on the basis of the results of existing research, which provide a new idea for nonpharmaceutical dietary intervention of chronic noncommunicable diseases.

[Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia].

Objective: To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. Methods: We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Results: Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Conclusion: Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.

Effects of protocatechuic acid on antioxidant capacity, mitochondrial biogenesis and skeletal muscle fiber transformation.

In skeletal muscle, the increased proportion of type I muscle fibers has the potential to improve muscle atrophy and prevent human metabolic diseases. Protocatechuic acid (PCA), as a kind of anthocyanin metabolite, has antioxidant and anti-inflammatory physiological activities. The purpose of this experiment was to use mice and C2C12 myotubes to examine if PCA can induce the transformation of muscle fiber and the mechanisms involved. We found that PCA significantly increased the expression of slow myosin heavy chain (MyHC), and markedly decreased the expression of fast MyHC in gastrocnemius muscle of mice and C2C12 myotubes. In addition, PCA also enhanced the antioxidant capacity and promoted mitochondrial biogenesis in mice. Importantly, the AMP-activated protein kinase (AMPK) signaling pathway was activated and AMPK inhibitor compound C attenuated the positive effect of PCA on myofiber conversion. To sum up, we revealed that PCA was able to promote the conversion of skeletal muscle fiber from type II to type I through the AMPK signaling pathway.

Effects of low-energy diet supplemented with betaine on growth performance, nutrient digestibility and serum metabolomic profiles in growing pigs.

Two experiments were carried out to evaluate the effects of betaine (BET) supplementation in diets with reduced net energy (NE) levels on growth performance, nutrient digestibility and serum metabolomic profiles in growing pigs. In Exp. 1, 24 growing pigs (initial body weight, BW, 30.83 ± 2.50 kg) were allotted to one of the four treatments (six replications with one pig per pen) in a 2 × 2 factorial arrangement, including two dietary NE levels (2475 [N-NE] or 2395 [R80-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). In Exp. 2, 72 growing pigs were used in a 2 × 3 factorial arrangement, including three dietary NE levels (2475 [N-NE], 2415 [R60-NE] or 2355 [R120-NE] kcal/kg) and two BET doses (0 or 1500 mg/kg). Pigs with initial BW of 31.44 ± 1.65 kg were divided to one of the six treatments (six replications with two pigs per pen). In Exp. 1, lowing NE concentrations increased average daily feed intake (ADFI) by 10.69% in pigs fed the diet without BET (P > 0.05). BET significant increased ADFI in N-NE diet (P < 0.05) but had no influence on ADFI in R80-NE diet (P > 0.05). BET enhanced the apparent digestibility of crude protein (CP), dry matter (DM), organic matter (OM), gross energy (GE) and ether extract (EE) in R80-NE diet (P < 0.05). In Exp. 2, lowing NE concentrations enhanced ADFI (P > 0.05) and decreased average daily gain (ADG) (P < 0.05). The reduction in feed intake by BET was further enhanced as NE concentrations decreased from 2415 to 2355 kcal/kg (P < 0.10). BET reversed the elevation of serum triglyceride, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels caused by R120-NE diet (P < 0.05). The concentrations of cholecystokinin and glucagon-like peptide 1 were increased by BET in pigs fed R120-NE diet (P < 0.05). Serum metabolomics reveals that lowing dietary NE concentrations affected mainly amino acid biosynthetic pathways (P < 0.05). BET supplementation in R120-NE diet up-regulated serum BET levels and down-regulated homocysteine, DL-carnitine and four amino acid secondary metabolites (P < 0.05). In conclusion, lowing dietary NE contents reduced the growth performance and caused metabolic abnormalities in growing pigs. However, BET decreased feed intake to a certain extent and improved the metabolic health of pigs fed low-NE diets, which may be related to the dual regulation of amino acid metabolism and the secretion of appetite related hormones by BET.

Screening of a short chain antimicrobial peptide-LKLHI and its application in hydrogels for wound healing.

Antibacterial peptides have been widely used in the field of antibacterial due to their biocompatibility. In this work, owing to quickly screen out peptides with antibacterial effects, the bacterial membranes of E. coli and S. aureus were extracted and fixed on self-made silica gel microspheres to prepare bacterial membrane chromatography stationary phase. We successfully screened antimicrobial peptides from a peptide library composed of one-bead-one-compound by bacterial membrane chromatography. The antibacterial peptide has an effective defense effect on gram-positive bacteria, gram-negative bacteria, and fungi. In addition, the antibacterial peptide has almost no hemolysis and cytotoxicity and other excellent biocompatibility and has excellent properties such as stability, broad-spectrum antibacterial, and promotion of wound healing，and HA hydrogel carrier loaded with antimicrobial peptides was prepared, which provided the application direction of antimicrobial dressings for antimicrobial peptides. In summary, this method can screen out polypeptides with antibacterial effects, and the screened-out antibacterial peptides are expected to be applied in clinical applications.

Plasma Protein Biomarkers of Healthy Dietary Patterns: Results from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study.

BACKGROUND: Molecular mechanisms underlying the benefits of healthy dietary patterns are poorly understood. Identifying protein biomarkers of dietary patterns can contribute to characterizing biological pathways influenced by food intake. OBJECTIVES: This study aimed to identify protein biomarkers associated with four indexes of healthy dietary patterns: Healthy Eating Index-2015 (HEI-2015); Alternative Healthy Eating Index-2010 (AHEI-2010); DASH diet; and alternate Mediterranean Diet (aMED). METHODS: Analyses were conducted on 10,490 Black and White men and women aged 49-73 y from the ARIC study at visit 3 (1993-1995). Dietary intake data were collected using a food frequency questionnaire, and plasma proteins were quantified using an aptamer-based proteomics assay. Multivariable linear regression models were used to examine the association between 4955 proteins and dietary patterns. We performed pathway overrepresentation analysis for diet-related proteins. An independent study population from the Framingham Heart Study was used for replication analyses. RESULTS: In the multivariable-adjusted models, 282 out of 4955 proteins (5.7%) were significantly associated with at least one dietary pattern (HEI-2015: 137; AHEI-2010: 72; DASH: 254; aMED: 35; P value < 0.05/4955 = 1.01 × 10-5). There were 148 proteins that were associated with only one dietary pattern (HEI-2015: 22; AHEI-2010: 5; DASH: 121; aMED: 0), and 20 proteins were associated with all four dietary patterns. Five unique biological pathways were significantly enriched by diet-related proteins. Seven out of 20 proteins associated with all dietary patterns in the ARIC study were available for replication analyses, and 6 out of these 7 proteins were consistent in direction and significantly associated with at least 1 dietary pattern in the Framingham Heart Study (HEI-2015: 2; AHEI-2010: 4; DASH: 6; aMED: 4; P value < 0.05/7 = 7.14 × 10-3). CONCLUSIONS: A large-scale proteomic analysis identified plasma protein biomarkers that are representative of healthy dietary patterns among middle-aged and older US adult population. These protein biomarkers may be useful objective indicators of healthy dietary patterns.

Yeast hydrolysate attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage in weaned piglets.

BACKGROUND: Intestinal inflammation is the main risk factor causing intestinal barrier dysfunction and lipopolysaccharide (LPS) can trigger inflammatory responses in various eukaryotic species. Yeast hydrolysate (YH) possesses multi-biological effects and is received remarkable attention as a functional ingredient for improving growth performance and promoting health in animals. However, there is still inconclusive on the protective effects of dietary YH supplementation on intestinal barrier of piglets. This study was conducted to investigate the attenuate effects of YH supplementation on inflammatory responses and intestinal barrier injury in piglets challenged with LPS. METHODS: Twenty-four piglets (with an average body weight of 7.42 ± 0.34 kg) weaned at 21 days of age were randomly assigned to one of two dietary treatments (12 replications with one pig per pen): a basal diet or a basal diet containing YH (5 g/kg). On the 22nd d, 6 piglets in each treatment were intraperitoneally injected with LPS at 150 µg/kg BW, and the others were injected with the same amount of sterile normal saline. Four hours later, blood samples of each piglet were collected and then piglets were euthanized. RESULTS: Dietary YH supplementation increased average daily feed intake and average daily gain (P < 0.01), decreased the ratio of feed intake to gain of piglets (P = 0.048). Lipopolysaccharide (LPS) injection induced systemic inflammatory response, evidenced by the increase of serum concentrations of haptoglobin (HP), adrenocorticotropic hormone (ACTH), cortisol, and interleukin-1ß (IL-1ß). Furthermore, LPS challenge resulted in inflammatory intestinal damage, by up-regulation of the protein or mRNA abundances of tumor necrosis factor-α (TNF-α), IL-1ß, toll-like receptors 4 (TLR4) and phosphor-nuclear factor-κB-p65 (p-NFκB-p65) (P < 0.01), and down-regulation of the jejunal villus height, the protein and mRNA abundances of zonula occludens-1 (ZO-1) and occludin (OCC; P < 0.05) in jejunal mucosa. Dietary YH supplementation decreased the impaired effects of ACTH, cortisol, HP, IL-1ß and diamine oxidase in serum (P < 0.05). Moreover, YH supplementation also up-regulated the jejunal villus height, protein and mRNA abundances of ZO-1 and OCC (P < 0.05), down-regulated the mRNA expressions of TNF-α and IL-1ß and the protein abundances of TNF-α, IL-1ß, TLR4 and p-NFκB-p65 in jejunal mucosa in LPS-challenged pigs (P < 0.01). CONCLUSION: Yeast hydrolysate could attenuate inflammatory response and intestinal barrier injury in weaned piglets challenged with LPS, which was associated with the inhibition of TLR4/NF-κB signaling pathway activation.

Vascular calcification on the risk of kidney stone: a meta-analysis.

BACKGROUND: The association between vascular calcification (VC) and kidney stone is still inconclusive. Therefore, we conducted a meta-analysis to estimate the risk of kidney stone disease in subjects with VC. METHODS: To identify publications from related clinical studies, we performed a search on PubMed, Web of Science, Embase, and Cochrane Library databases from their inceptions until 1 September 2022. According to obvious heterogeneity, a random-effects model was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Subgroup analysis was conducted trying to dissect the effects of VC in different segments and population regions in predicting kidney stone risk. RESULTS: Seven articles were included with a total number of 69,135 patients, of which 10,052 have vascular calcifications and 4728 have kidney stones. There was a significantly higher risk of kidney stone disease in participants with VC versus control (OR = 1.54, 95% CI: 1.13-2.10). Sensitivity analysis confirmed the stability of the results. VC can be separated into abdominal, coronary, carotid, and splenic aortic calcification while pooled analysis of abdominal aorta calcification did not indicate a significant higher kidney stone risk. An obvious higher risk of kidney stone was observed in Asian VC patients (OR = 1.68, 95% CI: 1.07-2.61). CONCLUSION: Combined evidence of observational studies suggested patients with VC may be associated with an increased risk of kidney stone disease. Despite the predictive value was relatively low, it is still worth noting that patients with VC are under the threat of kidney stone disease.

Association of the gut microbiome with kidney function and damage in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: The gut microbiome is altered in chronic kidney disease (CKD), potentially contributing to CKD progression and co-morbidities, but population-based studies of the gut microbiome across a wide range of kidney function and damage are lacking. METHODS: In the Hispanic Community Health Study/Study of Latinos, gut microbiome was assessed by shotgun sequencing of stool (n = 2,438; 292 with suspected CKD). We examined cross-sectional associations of estimated glomerular filtration rate (eGFR), urinary albumin:creatinine (UAC) ratio, and CKD with gut microbiome features. Kidney trait-related microbiome features were interrogated for correlation with serum metabolites (n = 700), and associations of microbiome-related serum metabolites with kidney trait progression were examined in a prospective analysis (n = 3,635). RESULTS: Higher eGFR was associated with overall gut microbiome composition, greater abundance of species from Prevotella, Faecalibacterium, Roseburia, and Eubacterium, and microbial functions related to synthesis of long-chain fatty acids and carbamoyl-phosphate. Higher UAC ratio and CKD were related to lower gut microbiome diversity and altered overall microbiome composition only in participants without diabetes. Microbiome features related to better kidney health were associated with many serum metabolites (e.g., higher indolepropionate, beta-cryptoxanthin; lower imidazole propionate, deoxycholic acids, p-cresol glucuronide). Imidazole propionate, deoxycholic acid metabolites, and p-cresol glucuronide were associated with prospective reductions in eGFR and/or increases in UAC ratio over ~6 y. CONCLUSIONS: Kidney function is a significant correlate of the gut microbiome, while the relationship of kidney damage with the gut microbiome depends on diabetes status. Gut microbiome metabolites may contribute to CKD progression.

Missense Genetic Variation of ICAM1 and Incident Heart Failure.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF. METHODS AND RESULTS: We identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in the Atherosclerosis Risk in Communities (ARIC) study. Of the 3 missense variants, rs5491 was common in Black participants (minor allele frequency [MAF] > 20%) and rare in other race/ethnic groups (MAF < 5%). In Black participants, the presence of rs5491 was associated with higher levels of circulating ICAM-1 at 2 timepoints separated by 8 years. Among Black participants in MESA (n = 1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HR = 2.30; [95% CI 1.25-4.21; P = 0.007]). The other ICAM1 missense variants (rs5498 and rs1799969) were associated with ICAM-1 levels, but there were no associations with HF. In ARIC, rs5491 was significantly associated with incident HF (HR = 1.24 [95% CI 1.02 - 1.51]; P = 0.03), with a similar direction of effect for HFpEF that was not statistically significant. CONCLUSIONS: A common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.

Long-Term Dietary Supplementation with Betaine Improves Growth Performance, Meat Quality and Intramuscular Fat Deposition in Growing-Finishing Pigs.

This study was designed to investigate the effects of dietary betaine supplementation on growth performance, meat quality and muscle lipid metabolism of growing-finishing pigs. Thirty-six crossbred pigs weighing 24.68 ± 0.97 kg were randomly allotted into two treatments consisting of a basal diet supplemented with 0 or 1200 mg/kg betaine. Each treatment included six replications of three pigs per pen. Following 119 days of feeding trial, dietary betaine supplementation significantly enhanced average daily gain (ADG) (p < 0.05) and tended to improve average daily feed intake (ADFI) (p = 0.08) and decreased the feed intake to gain ratio (F/G) (p = 0.09) in pigs during 100~125 kg. Furthermore, a tendency to increase ADG (p = 0.09) and finial body weight (p = 0.09) of pigs over the whole period was observed in the betaine diet group. Betaine supplementation significantly increased a*45 min and marbling and decreased b*24 h and cooking loss in longissimus lumborum (p < 0.05), tended to increase intramuscular fat (IMF) content (p = 0.08), however had no significant influence on carcass characteristics (p > 0.05). Betaine supplementation influenced the lipid metabolism of pigs, evidenced by a lower serum concentration of low-density lipoprotein cholesterol (p < 0.05), an up-regulation of mRNA abundance of fatty acid synthase and acetyl-CoA carboxylase (p < 0.05), and a down-regulation of mRNA abundance of lipolysis-related genes, including the silent information regulators of transcription 1 (p = 0.08), peroxisome proliferator-activated receptorα (p < 0.05), peroxisome proliferator-activated receptor gamma coactivator-1α (p = 0.07) and carnitine palmitoyl transferase 1 (p < 0.05) in longissimus lumborum. Moreover, betaine markedly improved the expression of microRNA-181a (miR-181a) (p < 0.05) and tended to enhance miR-370 (p = 0.08). Overall, betaine supplementation at 1200 mg/kg could increase the growth performance of growing-finishing pigs. Furthermore, betaine had a trend to improve meat quality and IMF content via increasing lipogenesis and down-regulating the abundance of genes associated with lipolysis, respectively, which was associated with the regulation of miR-181a and miR-370 expression by betaine.

Eugenol promotes appetite through TRP channels mediated-CaMKK2/AMPK signaling pathway.

Eugenol is a major component of clove oil. A recent study found that inhalation of eugenol promoted the appetite of mice. However, whether oral ingestion of eugenol promoted appetite is unclear and its mechanism await study. Here, mice were divided into four treatments (n = 20) and fed a basal diet supplemented with 0%, 0.005%, 0.01% and 0.02% eugenol for 4 weeks. In addition, mice (n = 7) were injected intraperitoneally with 3 mg/kg body weight eugenol. Our data showed that feeding mice with 0.01% and 0.02% eugenol promoted their appetite. In addition, the short-term intraperitoneal injection of eugenol enhanced the feed intake in mice within 1 h. Further studies found that dietary eugenol increased orexigenic factors expression and decreased anorexigenic factors expression in mice. We then carried out N38 cell experiments to explore the transient receptor potential (TRP) channels-dependent mechanism of eugenol in promoting appetite. We found that eugenol activated the TRP channels mediated-CaMKK2/AMPK signaling pathway in the hypothalamus and N38 cells. Besides, the inhibition of TRPV1 and AMPK eliminated the upregulation of eugenol on the agouti-related protein level in N38 cells. In conclusion, the study suggested that eugenol promotes appetite through TRPV1 mediated-CaMKK2/AMPK signaling pathway.

Four Kinds of Polymer Microspheres Prepared by the Seed Swelling Method Used to Purify the Industrial Production of Phytol.

Four monodisperse porous polymer microspheres were successfully prepared by seed emulsion polymerization and used as stationary phases for HPLC and preparative high-performance liquid chromatography (Prep-HPLC). All four polymer microspheres(polystyrene-polystyrene (PS-PS), polystyrene-poly(glycidyl methylate) (PS-PGMA), polystyrene-poly(methyl methylate) and poly(glycidyl methylate)-poly(glycidyl methylate) were used for filling HPLC empty columns. According to the analysis results of the HPLC column, PS-PS and PS-PGMA microspheres were screened out as the stationary phase of Prep-HPLC. The industrial-grade phytol was successfully separated and purified, and the purity of the final phytol was as high as 99%. The two types of polymer microspheres have been applied to industrial-grade phytol purification and have been used in factories.

Identification of Dietary Supplements Associated with Blood Metabolites in the Hispanic Community Health Study/Study of Latinos Cohort Study.

BACKGROUND: Metabolomics approaches have been widely used to define the consumption of foods but have less often been used to study exposure to dietary supplements. OBJECTIVES: To identify dietary supplements associated with metabolite levels and to examine whether these metabolites predicted incident diabetes risk. METHODS: We studied 3972 participants from a prospective cohort study of 18-74-y-old Hispanic/Latino adults. At a baseline examination, we ascertained use of dietary supplements using recall methods and concurrently, a serum metabolomic panel. After adjustment for potential confounders, we identified dietary supplements associated with metabolites. We then examined the association of these metabolites with incident diabetes at the 6-y study examination. RESULTS: We observed a total of 110 dietary supplement-metabolite associations that met the criteria for statistical significance adjusted for age, sex, field center, Hispanic/Latino background, body mass index, diet, smoking, physical activity, and number of medications (adjusted P < 0.05). This included 13 metabolites uniquely associated with only one dietary supplement ingredient. Vitamin C had the most associated metabolites (n = 15), including positive associations with oxalate, tartronate, threonate, and isocitrate, which were each in turn protective for the risk of incident diabetes. Vitamin C was also associated with higher N-acetylvaline level, which was an unfavorable diabetes risk factor. Other findings related to branched chain amino acid related compounds including α-hydroxyisovalerate and 2-hydroxy-3-methylvalerate, which were inversely associated with thiamine or riboflavin intake and also predicted higher diabetes risk. Vitamin B12 had an inverse association with γ-glutamylvaline, levels of which were positively associated with the risk of diabetes. CONCLUSIONS: Our data point to potential metabolite changes associated with vitamin C and B vitamins, which may have favorable metabolic effects. Knowledge of blood metabolites that can be modified by dietary supplement intake may aid understanding the health effects of dietary supplements and identify potential biological mediators.

Metabolomic Markers of Ultra-Processed Food and Incident CKD.

BACKGROUND: High ultra-processed food consumption is associated with higher risk of CKD. However, there is no biomarker for ultra-processed food, and the mechanism through which ultra-processed food is associated with CKD is not clear. Metabolomics can provide objective biomarkers of ultra-processed food and provide important insights into the mechanisms by which ultra-processed food is associated with risk of incident CKD. Our objective was to identify serum metabolites associated with ultra-processed food consumption and investigate whether ultra-processed food-associated metabolites are prospectively associated with incident CKD. METHODS: We used data from 3751 Black and White men and women (aged 45-64 years) in the Atherosclerosis Risk in Communities study. Dietary intake was assessed using a semiquantitative 66-item food frequency questionnaire, and ultra-processed food was classified using the NOVA classification system. Multivariable linear regression models were used to identify the association between 359 metabolites and ultra-processed food consumption. Cox proportional hazards models were used to investigate the prospective association of ultra-processed food-associated metabolites with incident CKD. RESULTS: Twelve metabolites (saccharine, homostachydrine, stachydrine, N2, N2-dimethylguanosine, catechol sulfate, caffeine, 3-methyl-2-oxovalerate, theobromine, docosahexaenoate, glucose, mannose, and bradykinin) were significantly associated with ultra-processed food consumption after controlling for false discovery rate <0.05 and adjusting for sociodemographic factors, health behaviors, eGFR, and total energy intake. The 12 ultra-processed food-related metabolites significantly improved the prediction of ultra-processed food consumption (difference in C statistics: 0.069, P <1×10 -16 ). Higher levels of mannose, glucose, and N2, N2-dimethylguanosine were associated with higher risk of incident CKD after a median follow-up of 23 years. CONCLUSIONS: We identified 12 serum metabolites associated with ultra-processed food consumption and three of them were positively associated with incident CKD. Mannose and N2, N2-dimethylguanosine are novel markers of CKD that may explain observed associations between ultra-processed food and CKD. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_03_08_CJN08480722.mp3.

Establishing a Prediction Model for the Efficacy of Platinum-Based Chemotherapy in NSCLC Based on a Two Cohorts GWAS Study.

Platinum drugs combined with other agents have been the first-line treatment for non-small cell lung cancer (NSCLC) in the past decades. To better evaluate the efficacy of platinum-based chemotherapy in NSCLC, we establish a platinum chemotherapy response prediction model. Here, a total of 217 samples from Xiangya Hospital of Central South University were selected as the discovery cohort for a genome-wide association analysis (GWAS) to select SNPs. Another 216 samples were genotyped as a validation cohort. In the discovery cohort, using linkage disequilibrium (LD) pruning, we extract a subset that does not contain correlated SNPs. The SNPs with p < 10-3 and p < 10-4 are selected for modeling. Subsequently, we validate our model in the validation cohort. Finally, clinical factors are incorporated into the model. The final model includes four SNPs (rs7463048, rs17176196, rs527646, and rs11134542) as well as two clinical factors that contributed to the efficacy of platinum chemotherapy in NSCLC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.726.

Eugenol Alleviates TGEV-Induced Intestinal Injury via Suppressing ROS/NLRP3/GSDMD-Dependent Pyroptosis.

Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEV-induced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced intestinal epithelial cell pyroptosis and reduces intestinal injury in TGEV-infected piglets. Mechanistically, eugenol reduces the activation of NLRP3 inflammasome, thereby inhibiting TGEV-induced intestinal epithelial cell pyroptosis. In addition, eugenol scavenges TGEV-induced reactive oxygen species (ROS) increase, which in turn prevents TGEV-induced NLRP3 inflammasome activation and pyroptosis. Overall, eugenol protects the intestine by reducing TGEV-induced pyroptosis through inhibition of NLRP3 inflammasome activation, which may be mediated through intracellular ROS levels. These findings propose that eugenol may be an effective strategy to prevent TGEV infection.

Models of ultrasonic radiomics and clinical characters for lymph node metastasis assessment in thyroid cancer: a retrospective study.

Background: Preoperative prediction of cervical lymph node metastasis in papillary thyroid carcinoma provided a basis for tumor staging and treatment decision. This study aimed to investigate the utility of machine learning and develop different models to preoperatively predict cervical lymph node metastasis based on ultrasonic radiomic features and clinical characteristics in papillary thyroid carcinoma nodules. Methods: Data from 400 papillary thyroid carcinoma nodules were included and divided into training and validation group. With the help of machine learning, clinical characteristics and ultrasonic radiomic features were extracted and selected using randomforest and least absolute shrinkage and selection operator regression before classified by five classifiers. Finally, 10 models were built and their area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, positive predictive value and negative predictive value were measured. Results: Among the 10 models, RF-RF model revealed the highest area under curve (0.812) and accuracy (0.7542) in validation group. The top 10 variables of it included age, seven textural features, one shape feature and one first-order feature, in which eight were high-dimensional features. Conclusions: RF-RF model showed the best predictive performance for cervical lymph node metastasis. And the importance features selected by it highlighted the unique role of higher-dimensional statistical methods for radiomics analysis.