A Comparative Analysis between Whole Chinese Yam and Peeled Chinese Yam: Their Hypolipidemic Effects via Modulation of Gut Microbiome in High-Fat Diet-Fed Mice.

Chinese yam is a "medicine food homology" food with medical properties, but little is known about its health benefits on hyperlipidemia. Furthermore, the effect of peeling processing on the efficacy of Chinese yam is still unclear. In this study, the improvement effects of whole Chinese yam (WY) and peeled Chinese yam (PY) on high-fat-diet (HFD)-induced hyperlipidemic mice were explored by evaluating the changes in physiological, biochemical, and histological parameters, and their modulatory effects on gut microbiota were further illustrated. The results show that both WY and PY could significantly attenuate the HFD-induced obesity phenotype, accompanied by the mitigative effect on epididymis adipose damage and hepatic tissue injury. Except for the ameliorative effect on TG, PY retained the beneficial effects of WY on hyperlipemia. Furthermore, 16S rRNA sequencing revealed that WY and PY reshaped the gut microbiota composition, especially the bloom of several beneficial bacterial strains (Akkermansia, Bifidobacterium, and Faecalibaculum) and the reduction in some HFD-dependent taxa (Mucispirillum, Coriobacteriaceae_UCG-002, and Candidatus_Saccharimonas). PICRUSt analysis showed that WY and PY could significantly regulate lipid transport and metabolism-related pathways. These findings suggest that Chinese yam can alleviate hyperlipidemia via the modulation of the gut microbiome, and peeling treatment had less of an effect on the lipid-lowering efficacy of yam.

Effect of structural characteristics of resistant starch prepared by various methods on microbial community and fermentative products.

Resistant starch (RS) has been extensively studied because of its beneficial effects on gut microbiota. In this study, four RSs obtained through various preparation processes were utilized for in vitro fermentation, and their structural characteristics before and after fermentation were determined using chromatography, Fourier infrared spectroscopy, and scanning electron microscopy (SEM). It was observed that these RSs can be classified into two categories based on their fermentation and structural features. The autoclaving RS (ARS) and extruding RS (ERS) were classified as Class I Microbiome Community (MC-I), characterized by a higher proportion of butyrate and its producers, including unclassified_g_Megasphaera and Megasphaera elsdenii. While microwaving RS (MRS) and ultrasound RS (URS) belonged to Class II Microbiome Community (MC-II), marked by a higher proportion of acetate and its producer, Bifidobacterium pseudocatenulatum DSM 20438. MC-I had a lower molecular weight, shorter chain length, more chains with degree of polymerization (DP) 36-100, and a more ordered structure than MC-II. Furthermore, SEM observations revealed distinct degradation patterns between MC-I and MC-II, which may be attributed to their surface structural characteristics. These findings imply that the preparation methods employed for RS can determine its multilevel structural characteristics, and consequently influence its physiological properties.

Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC-microglia interactions to induce retinal inflammation and neurodegeneration in vivo and in vitro. Mechanistically, FTO affected EC features via modulating CDK2 mRNA stability in an m6A-YTHDF2-dependent manner. FTO up-regulation under diabetic conditions was driven by lactate-mediated histone lactylation. FB23-2, an inhibitor to FTO's m6A demethylase activity, suppressed angiogenic phenotypes in vitro. To allow for systemic administration, we developed a nanoplatform encapsulating FB23-2 and confirmed its targeting and therapeutic efficiency in mice. Collectively, our study demonstrates that FTO is important for EC function and retinal homeostasis in DR, and warrants further investigation as a therapeutic target for DR patients.

Carbon emissions and low-carbon development in Olefin industry.

Olefin industry as a vital part in economic development is facing a problem of high CO2 emission. In this work, for the global and China's olefin industry under different development scenario, the carbon emission is predicted after the revealing of carbon footprint in different olefin routes. The results show that the carbon footprint of the natural gas liquids (NGLs)-derived route is highly lower than that of the oil- and coal-derived routes. The carbon emission from the global olefin industry in 2015 is 553 million ton CO2 (MtCO2). In 2030, it will be ranged between 739 and 924 MtCO2 under different scenarios. Under sustainable development scenario, 15% reduction space is existed, whereas 6% growth is observed under the hybrid-development scenario compared to the business-as-usual situation. In the case of China, its carbon emission is 120 MtCO2 in 2015. Its potential carbon emission in 2030 will increase to 264-925 MtCO2, depending on the rest new capacity from low-carbon or high-carbon routes. The large gap implies the significant influence of the development route choice. However, if most new capacity is from the existed planned olefin projects, the carbon emission will be ranged between 390 and 594 MtCO2. Finally, the low-carbon roadmaps as well as polices are proposed for sustainable development of olefin industry.

Identification and molecular binding mechanism of novel pancreatic lipase and cholesterol esterase inhibitory peptides from heat-treated adzuki bean protein hydrolysates.

Heat-treated adzuki bean protein hydrolysates exhibit lipid-reducing properties; however, few studies have reported pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory effects and elucidated the underlying mechanisms. In this study, we accomplished the identification of antiobesity peptides through peptide sequencing, virtual screening, and in vitro experiments. Furthermore, the mechanisms were investigated via molecular docking. The findings reveal that the action of pepsin and pancreatin resulted in the transformation of intact adzuki bean protein into smaller peptide fragments. The < 3 kDa fraction exhibited a high proportion of hydrophobic amino acids and displayed superior inhibitory properties for both PL and CE. Five novel antiobesity peptides (LLGGLDSSLLPH, FDTGSSFYNKPAG, IWVGGSGMDM, YLQGFGKNIL, and IFNNDPNNHP) were identified as PL and CE inhibitors. Particularly, IFNNDPNNHP exhibited the most robust biological activity. These peptides exerted their inhibitory action on PL and CE by occupying catalytic or substrate-binding sites through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking.

The implications of lipid mobility, drug-enhancers (surfactants)-skin interaction, and TRPV1 activation on licorice flavonoid permeability.

Licorice flavonoids (LFs) are derived from perennial herb licorice and have been attaining a considerable interest in cosmetic and skin ailment treatments. However, some LFs compounds exhibited poor permeation and retention capability, which restricted their application. In this paper, we systematically investigated and compared the enhancement efficacy and mechanisms of different penetration enhancers (surfactants) with distinct lipophilicity or "heat and cool" characteristics on ten LFs compounds. Herein, the aim was to unveil how seven different enhancers modified the stratum corneum (SC) surface and influence the drug-enhancers-skin interaction, and to relate these effects to permeation enhancing effects of ten LFs compounds. The enhancing efficacy was evaluated by enhancement ratio (ER)permeation, ERretention, and ERcom, which was conducted on the porcine skin. It was summarized that heat capsaicin (CaP) and lipophilic Plurol® Oleique CC 497 (POCC) caused the most significance of SC lipid fluidity, SC water loss, and surface structure alterations, thereby resulting in a higher permeation enhancing effects than other enhancers. CaP could completely occupied drug-skin interaction sites in the SC, while POCC only occupied most drug-skin interactions. Moreover, the enhancing efficacy of both POCC and CaP was dependent on the log P values of LFs. For impervious LFs with low drug solubility, enhancing their drug solubility could help them permeate into the SC. For high-permeation LFs, their permeation was inhibited ascribed to the strong drug-enhancer-skin strength in the SC. More importantly, drug-surfactant-skin energy possessed a good negative correlation with the LFs permeation amount for most LFs molecules. Additionally, the activation of transient receptor potential vanilloid 1 (TRPV1) could enhance LFs permeation by CaP. The study provided novel insights for drug permeation enhancement from the viewpoint of molecular pharmaceutics, as well as the scientific utilization of different enhancers in topical or transdermal formulations.

Whole-Grain Highland Barley Attenuates Atherosclerosis Associated with NLRP3 Inflammasome Pathway and Gut Microbiota in ApoE-/- Mice.

The efficacy and mechanism of highland barley in the treatment of atherosclerosis have received little attention. Herein, we aimed to explore whether highland barley supplementation can prevent atherosclerosis progression and improve gut microbiota disorder in apolipoprotein E knockout (ApoE-/-) mice. Male ApoE-/- mice were fed a high-fat diet with whole-grain highland barley (WHB) or refined highland barley for 18 weeks. WHB substantially inhibited the formation of atherosclerotic plaques, reduced serum tumor necrosis factor-α, and downregulated the expression of NLRP3 in the aorta. Furthermore, the 16S rRNA analysis revealed that highland barley supplementation helped to restore the dysregulation of the gut microbiota, as evidenced by an increase in the relative abundance of specific beneficial bacteria known for their anti-inflammatory properties, such as Lachnospiraceae, Lactobacillus, Muribaculaceae, and Bifidobacterium. Highland barley supplementation might alleviate atherosclerotic plaque formation by modulating the NLRP3 inflammasome pathway and the synthesis of anti-inflammatory metabolites by the gut microbiota.

Pulmonary hypertension- a novel phenotypic hypothesis of Kabuki syndrome: a case report and literature review.

BACKGROUND: Pediatric pulmonary hypertension (PH) is a serious and rare disease that is often derived from genetic mutations. Kabuki syndrome (KS) is a chromosomal abnormality disease that has its origin in the mutation of lysine methyltransferase 2D(KMT2D). Recent evidence has shown that KMT2D mutations are associated with pediatric pulmonary disorders. However, the relationship between the clinical courses of PH and the KMT2D mutation is reported in extremely few cases. Therefore, in this paper, a case was presented and previous literature was reviewed for better understanding of the correlation between pediatric PH and KMT2D mutations. CASE PRESENTATION: A 3-year-old girl was transferred to our center for severe cough, shortness of breath, fatigue and fever. Physical examination revealed facial deformities and growth retardation. Echocardiography showed a small atrial septal defect (ASD), and right heart catheterization indicated a significant increase in pulmonary vascular pressure and resistance. The genetic test suggested that she had a KMT2D gene mutation. The patient was finally diagnosed with KS. She was given targeted drugs to reduce pulmonary vascular pressure, but the effect was unsatisfactory. CONCLUSIONS: KS can be complicated with multiple organ malformations and dysfunction. With the progress of next generation sequencing, an increasing number of new phenotypes related to KMT2D mutations have been reported. A bold hypothesis is proposed in this article, that is, PH may be a new phenotype associated with KMT2D mutations. It is suggested that KS and PH should be differentiated from each other to avoid delayed diagnosis and treatment in clinical practice. There is no specific drug for KS treatment. The prognosis of children with inherited PH is usually poor, and lung transplantation may increase their survival rates.

Correction: Heat-treated foxtail millet protein delayed the development of pre-diabetes to diabetes in mice by altering gut microbiota and metabolomic profiles.

Correction for 'Heat-treated foxtail millet protein delayed the development of pre-diabetes to diabetes in mice by altering gut microbiota and metabolomic profiles' by Han Wang et al., Food Funct., 2023, 14, 4866-4880, https://doi.org/10.1039/D3FO00294B.

Effects on Diabetic Mice of Consuming Lipid Extracted from Foxtail Millet (Setaria italica): Gut Microbiota Analysis and Serum Metabolomics.

Millet and its components have received much extensive attention for their health benefits in mitigating metabolic diseases. Foxtail millet is rich in phytochemicals, including oil. However, the hypoglycemic capacity of foxtail millet oil has yet to be fully investigated. The present study explored the effects of consuming this oil as the lipid extract of foxtail millet (LEFM) on intestinal microbiota composition and metabolic function in diabetic mice. After eight weeks of LEFM supplementation, the blood glucose, insulin resistance index, and lipid accumulation of diabetic mice were significantly decreased. In addition, LEFM feeding modulated gut microbiota composition, reduced the abundance of harmful bacteria (Escherichia-Shigella, Peptococcus, and norank_f_Oscillospiraceae), induced a bloom of probiotics, especially short-chain fatty acid (SCFA)-producing bacteria (Adlercreutzia, Faecalibaculum, and Bifidobacterium), and increased SCFAs concentration. LEFM treatment altered serum metabolite levels, for instance, greatly increasing the levels of l-carnitine and l-glutamine and reducing S-acetyldihydrolipoamide-E and sphingosine. Overall, improvements in gut microbiota and metabolic function were associated with the hypoglycemic potential of LEFM.

Heat-treated foxtail millet protein delayed the development of pre-diabetes to diabetes in mice by altering gut microbiota and metabolomic profiles.

Millet protein has gained much attention for its beneficial effects in mitigating metabolic diseases. However, most individuals pass through a prediabetic phase before developing full-blown diabetes, and whether millet protein has hypoglycemic effects on prediabetic mice remains unclear. In the present study, heat-treated foxtail millet protein (HMP) supplementation significantly decreased fasting blood glucose and serum insulin levels, alleviated insulin resistance, and improved impaired glucose tolerance in prediabetic mice. In addition, HMP altered the intestinal flora composition, as evidenced by the reduction in the abundance of Dubosiella and Marvinbryantia and the increase in the content of Lactobacillus, Bifidobacterium, and norank_f_Erysipelotrichaceae. Moreover, HMP supplementation dramatically regulated the levels of serum metabolites (i.e., LysoPCs, 11,14,17-eicosatrienoic acid, and sphingosine) and related metabolic pathways, such as sphingolipid metabolism and pantothenate and CoA biosynthesis. In conclusion, the improvement of gut microbiota and serum metabolic profiles was related to the hypoglycemic potential of HMP in prediabetes.

Structural, functional and mechanistic insights uncover the role of starch in foxtail millet cultivars with different congee-making quality.

Ten foxtail millet cultivars with different congee-making quality were investigated for relationships between starch structures, functional properties and congee-making qualities. Swelling power, pasting peak viscosity (PV) and setback (SB), gel hardness and resilience, and gelatinization onset (To), peak (Tp) and range (R) temperature were correlated with congee-making performance significantly. Good eating-quality cultivars with these parameters were in the range of 15.41-18.58 %, 3095-3279 cp, 1540-1745 cp, 430-491 g, 0.47-0.57, 64.43-65.28 °C, 69.97-70.32 °C and 23.38-24.52 °C, respectively. Correlation analysis showed that amylose, amylopectin B2 chains and A21 were essential parameters controlling the functional properties. Amylose molecules with linear molecular morphology would cause crystal defects and a wide range of molecular weight distribution. Additionally, they were more prone to re-association, which influenced the PV, SB, To, Tp and gel hardness. B2 chains impacted the gelatinization temperature range (R), gel resilience and swelling behavior by affecting the alignment of double helices and the size of starch particles and pores. Starch with more binding sites of bound water (A21) tended to leach from the swelling granules easily and contributed to higher values of PV. The content of amylose, B2 chains and A21 of good eating-quality cultivars were 16.19-18.46 %, 11.60-11.69 % and 96.50-97.02 %, respectively.

Gamma-aminobutyric acid (GABA): a comprehensive review of dietary sources, enrichment technologies, processing effects, health benefits, and its applications.

Gamma-aminobutyric acid (GABA) is a naturally occurring potential bioactive compound present in plants, microorganisms, animals, and humans. Especially, as a main inhibitory neurotransmitter in the central nervous system, GABA possesses a broad spectrum of promising bioactivities. Thus, functional foods enriched with GABA have been widely sought after by consumers. However, the GABA levels in natural foods are usually low, which cannot meet people's demand for health effects. With the increasing public awareness on the food securities and naturally occurring processes, using enrichment technologies to elevate the GABA contents in foods instead of exogenous addition can enhance the acceptability of health-conscious consumers. Herein, this review provides a comprehensive insight on the dietary sources, enrichment technologies, processing effects of GABA, and its applications in food industry. Furthermore, the various health benefits of GABA-enriched foods, mainly including neuroprotection, anti-insomnia, anti-depression, anti-hypertensive, anti-diabetes, and anti-inflammatory are also summarized. The main challenges for future research on GABA are related to exploring high GABA producing strains, enhancing the stability of GABA during storage, and developing emerging enrichment technologies without affecting food quality and other active ingredients. A better understanding of GABA may introduce new windows for its application in developing functional foods.

Targeted delivery of nutraceuticals derived from food for the treatment of obesity and its related complications.

Nutraceuticals which are abundant in foods have attracted much attention due to their bioactive activities of anti-obesity, anti-hyperlipidemia and anti-atherosclerosis. Unfortunately, the poor bioavailability severely undermines their envisioned benefits. Therefore, there is an urgent need to develop suitable delivery systems to promote the benefits of their biological activity. Targeted drug delivery system (TDDS) is a novel drug delivery system that can selectively concentrate drugs on targets in the body, improve the bioavailability of agents and reduce side effects. This emerging drug delivery system provides a new strategy for the treatment of obesity with nutraceuticals and would be a promising alternative to be widely used in the food field. This review summarizes the recent studies on the application in the targeted delivery of nutraceuticals for treating obesity and its related complications, especially the available receptors and their corresponding ligands for TDDS and the evaluation methods of the targeting ability.

4'-OH as the Action Site of Lipids and MRP1 for Enhanced Transdermal Delivery of Flavonoids.

To date, the transdermal delivery study mainly focused on the drug delivery systems' design and efficacy evaluation. Few studies reported the structure-affinity relationship of the drug with the skin, further revealing the action sites of the drugs for enhanced permeation. Flavonoids attained a considerable interest in transdermal administration. The aim is to develop a systematic approach to evaluate the substructures that were favorable for flavonoid delivery into the skin and understand how these action sites interacted with lipids and bound to multidrug resistance protein 1 (MRP1) for enhanced transdermal delivery. First, we investigated the permeation properties of various flavonoids on the porcine skin or rat skin. We found that 4'-OH (hydroxyl group on the carbon 4' position) rather than 7-OH on the flavonoids was the key group for flavonoid permeation and retention, while 4'-OCH3 and -CH2═CH2-CH-(CH3)2 were unfavorable for drug delivery. 4'-OH could decrease flavonoids' lipophilicity to an appropriate log P and polarizability for better transdermal drug delivery. In the stratum corneum, flavonoids used 4'-OH as a hand to specifically grab the C═O group of the ceramide NS (Cer), which increased the miscibility of flavonoids and Cer and then disturbed the lipid arrangement of Cer, thereby facilitating their penetration. Subsequently, we constructed overexpressed MRP1 HaCaT/MRP1 cells by permanent transfection of human MRP1 cDNA in wild HaCaT cells. In the dermis, we observed that 4'-OH, 7-OH, and 6-OCH3 substructures were involved in H-bond formation within MRP1, which increased the flavonoid affinity with MRP1 and flavonoid efflux transport. Moreover, the expression of MRP1 was significantly enhanced after the treatment of flavonoids on the rat skin. Collectively, 4'-OH served as the action site for increased lipid disruption and enhanced affinity for MRP1, which facilitate the transdermal delivery of flavonoids, providing valuable guidelines for molecular modification and drug design of flavonoids.

Comparison of the generation of α-glucosidase inhibitory peptides derived from prolamins of raw and cooked foxtail millet: In vitro activity, de novo sequencing, and in silico docking.

Foxtail millet prolamin has been demonstrated to have anti-diabetic effects. In this study, we compared the generation of anti-α-glucosidase peptides derived from prolamins of raw and cooked foxtail millet (PRFM and PCFM). PRFM and PCFM hydrolysates (PRFMH and PCFMH) both exhibited α-glucosidase inhibitory activity. After ultrafiltration according to molecular weight (Mw), the fraction with Mw < 3 kDa in PCFMH (PCFMH<3) showed higher α-glucosidase inhibitory activity than that in PRFMH (PRFMH<3). The composition of α-glucosidase inhibitory peptides identified by de novo sequencing in PCFMH<3 and PRFMH<3 was compared by virtual screening, combining biological activity, net charge, grand average of hydropathicity (GRAVY), and key hydrophobic amino acids (Met, Pro, Phe, and Leu). We found that the proportion of peptides with excellent α-glucosidase binding force in PCFMH<3 was higher than in PRFMH<3. Overall, cooking may positively affect the generation of peptides that perform well in inhibiting α-glucosidase derived from foxtail millet prolamin.

A comparison between partially peeled hulless barley and whole grain hulless barley: beneficial effects on the regulation of serum glucose and the gut microbiota in high-fat diet-induced obese mice.

Though the hypoglycemic effect of whole grain hulless barley (Hordeum vulgare L.) has been documented, whether glucose metabolism would be improved by hulless barley with moderate peeling is still unclear. The purpose of this study was to compare the differences in glucose metabolism and gut microbiota between partially (10%) peeled hulless barley (PHB) and whole grain hulless barley (WHB) intervention in obese mice induced by a high-fat diet. The results showed that both PHB and WHB interventions significantly improved the impaired glucose tolerance, fat accumulation in fat and liver tissues, and the impaired intestinal barrier in mice. The dysbiosis of gut microbiota was improved and the relative abundance of some beneficial bacteria such as genera Lactobacillus, Bifidobacterium, Ileibacterium, and norank_f__Mutibaculaceae was increased by both, PHB and WHB, interventions. Spearman correlation analysis revealed that the abundance of Bifidobacterium was negatively correlated with the area under the blood glucose curve. In conclusion, our results provide evidence that hulless barley improved the gut microbiota and impaired glucose tolerance in mice, and also showed that there was little loss of hypoglycemic effect even when hulless barley was moderately peeled.

Effects of heat-treated starch and protein from foxtail millet (Setaria italica) on type 2 diabetic mice.

Foxtail millet and its components have hypoglycemic effects on mice, but the role of starch and protein in millet in these effects is unclear. The present study investigated the impact of heat-treated foxtail millet starch and protein on type 2 diabetic mice and the underlying mechanisms, including the influence of gut microbiota and serum metabolic profile. In diabetic mice, the consumption of heat-treated foxtail millet starch and protein reduced, respectively, fasting blood glucose 18.52% and 26.33% and insulin levels 12.22% and 15.96%. In addition, heat-treated foxtail millet starch and protein altered the gut microbiota composition, enriched the abundance of probiotics and short-chain fatty acids producing bacteria, reduced harmful bacteria, and increased fecal short-chain fatty acids concentration. Heat-treated foxtail millet protein had greater effects on gut microbiota composition, whereas heat-treated foxtail millet starch had greater effects on metabolic function. The hypoglycemic potential of heat-treated foxtail millet starch and protein was associated with the modulation of both gut microbiota and serum metabolic profile.

Ultrasound-triggered piezocatalytic composite hydrogels for promoting bacterial-infected wound healing.

Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection. As such, it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness. Here, based on ultrasound-triggered piezocatalytic therapy, a multifunctional hydrogel is designed to promote bacteria-infected wound healing. Under ultrasonic vibration, the surface of barium titanate (BaTiO3, BT) nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species (ROS) owing to the established strong built-in electric field, endowing the hydrogel with superior antibacterial efficacy. This modality shows intriguing advantages over conventional photodynamic therapy, such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers. Moreover, the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide (THM), N-(3-aminopropyl)methacrylamide hydrochloride (APMH) and oxidized hyaluronic acid (OHA) exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing. Notably, compared with the widely reported mussel-inspired adhesive hydrogels, OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized, giving it long-term and repeatable adhesion performance. Importantly, this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria, markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.