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Abstract Background Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment. Results In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients. Conclusion Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested.

In this work, the effect of the addition of γ-polyglutamic acid (γ-PGA) on the rheology, physicochemical properties, and microstructure of fish gelatin (FG) emulsion gel was investigated. Samples of the emulsion gel were evaluated for rheological behavior and stability prior to gelation. The mechanical properties and water-holding capacity (WHC) of the emulsion were determined after gelation. The microstructure of the emulsion gel was further examined using confocal laser scanning microscopy (CLSM). The results indicated a gradual increase in the apparent viscosity and gelation temperature of the emulsion at a higher concentration of γ-PGA. Additionally, frequency scan results revealed that on the addition of γ-PGA, FG emulsion exhibited a stronger structure. The emulsion containing 0.1% γ-PGA exhibited higher stability than that of the control samples. The WHC and gel strength of the emulsion gel increased on increasing the γ-PGA concentration. CLSM images showed that the addition of γ-PGA modified the structure of the emulsion gel, and the droplets containing 0.1% γ-PGA were evenly distributed. Moreover, γ-PGA could regulate the droplet size of the FG emulsion and its size distribution. These findings suggest that the viscoelasticity and structure of FG emulsion gels could be regulated by adjusting the γ-PGA concentration. The γ-PGA-modified FG emulsion gel also exhibited improved rheology and physicochemical properties. The results showed that γ-PGA-modified FG emulsion gel may find potential applications in food, medicine, cosmetics, and other industries.

Abstract Methionine restriction (MR) provides metabolic benefits in many organisms. However, mechanisms underlying the MR-induced effect remain incompletely understood. Here, we show in the budding yeast S. cerevisiae that MR relays a signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic mitochondria to nitrogenic anabolism. In particular, decreases in cellular SAM constrain lipoate metabolism and protein lipoylation required for the operation of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete glucose oxidation with an exit of acetyl-CoA and α-ketoglutarate from the TCA cycle to the syntheses of amino acids, such as arginine and leucine. This mitochondrial response achieves a trade-off between energy metabolism and nitrogenic anabolism, which serves as an effector mechanism promoting cell survival under MR.

Gelatin emulsion was an important process for preparing gelatin films. A gelatin film with water resistance and ductility could be prepared using gelatin emulsion, whereas the prepared gelatin film has several defects (e.g., low tensile strength and poor thermal stability). This study aimed to modify gelatin emulsion through ultrasonic treatment, then gelatin film was prepared by the modified gelatin emulsion. The results showed that: under the condition of ultrasonic treatment for 12 min at 400 w, zeta potential and viscosity of gelatin emulsion were the largest; thickness, water vapor permeability (WVP) and water solubility (WS) of corresponding gelatin film were the lowest, and the tensile strength (TS), elongation at break (EAB), denaturation temperature (Tm) and enthalpy value (ΔH) of corresponding gelatin film were the highest. The above result suggested that ultrasonic treatment can be used to prepare a gelatin film with better quality by regulating the properties of gelatin emulsion, and a certain correlation was found between the properties of gelatin emulsion and the properties of gelatin film.

Background: Previous studies have suggested that point-of-care ultrasound could help to evaluate and diagnose pediatric skull fracture for the closed scalp hematoma from blunt trauma. However, relevant data in Chinese children are missing, especially in children 0–6 years old. Objectives: Our study aimed to evaluate the efficacy of point-of-care ultrasound to diagnose skull fracture in children 0–6 years old with scalp hematoma in China. Methods: We performed a prospective observational study and screened children 0–6 years old with closed scalp hematoma and a Glasgow coma scale of 14–15 at Hospital in China. Enrolled children (N = 152) were first evaluated for skull fracture with point-of-care ultrasound by the emergency physician and then received a head computed tomography scan. Results: The point-of-care ultrasound examination and computed tomography scan revealed skull fracture in 13 (8.6%) and 12 (7.9%) children, respectively. The kappa test showed a satisfactory agreement between two examinations (P

The CRISPR-Cas13 system, an RNA-guided editing tool, has emerged as a highly efficient and stable RNA editing technique. Although the CRISPR-Cas13 system has been developed in several insect species, its application in lepidopterans has not yet been reported. In the present study, we evaluated the RNA cleavage activity of the CRISPR-Cas13 system in the silkworm (Bombyx mori), a model lepidopteran insect, both ex vivo and in vivo. We established two stable silkworm BmE cell lines expressing PspCas13b and CasRx, respectively. Further analysis demonstrated that both PspCas13b and CasRx effectively down-regulated the transcription of exogenously-introduced target and endogenous genes in these cell lines. In addition, we generated two transgenic silkworm strains, one expressing CasRx and the other expressing RNA-guided CRISPR RNA targeting Sex combs reduced (Scr). Further crossing experiments showed that CasRx induced a down-regulation of Scr transcription in silkworms, which impaired systemic growth of larvae. Overall, this study demonstrated that the CRISPR-Cas13 RNA editing system works efficiently in the silkworm, providing a potential alternative approach for RNA manipulation in lepidopteran insects. [ABSTRACT FROM AUTHOR]

Paeoniae Radix Alba (PRA), as a Traditional Chinese Medicine, is widely used in Chinese cuisine due to high health-benefits and nutrition, but the effect of different polarity of solvents on the extraction of antioxidant and hypoglycemic constituents, as well as the major active compounds remain unclear. In this research, 40, 70, and 95% ethanol were firstly applied to extract the polyphenols from PRA, the extraction yields, total phenolics, and total flavonoids content, free radical scavenging ability, α-glucosidase inhibition ability, and anti-glycation ability of extracts were evaluated spectroscopically. The oxidative damage protection, hypoglycemic activity, and alleviation on peripheral nerve damage were evaluated by H2O2-induced HepG2 cells and hyperglycemic zebrafish models. UPLC-QTOF-MS/MS was used to identify the major chemical constituents. The results showed that 40, 70, and 95% ethanol exhibited insignificant difference on the extraction of phenolics and flavonoids from PRA. All extracts showed promising DPPH⋅ and ABTS⋅+ scavenging ability, α-glucosidase inhibition and anti-glycation ability. In addition, PRA extracts could restore the survival rate of HepG2 cells induced by H2O2, and alleviate the oxidative stress by reducing the content of MDA and increasing the levels of SOD, CAT, and GSH-Px. The 70% ethanol extract could also mitigate the blood glucose level and peripheral motor nerve damage of hyperglycemic zebrafish. Thirty-five compounds were identified from 70% ethanol extract, gallotannins, gallic acid and its derivatives, and paeoniflorin and its derivatives were the dominant bioactive compounds. Above results could provide important information for the value-added application of PRA in functional food and medicinal industry.

Radix Paeonia Alba (RPA) is often used as food and medicine. This study aimed to enrich and identify the antioxidant and hypoglycemic bioactive compounds from RPA. The results indicated that the ethyl acetate fraction (EAF) showed the highest total phenolic content, DPPH, ABTS+ scavenging ability, and α-glucosidase inhibition ability (IC50 = 7.27 μg/ml). The EAF could alleviate H2O2-induced oxidative stress in HepG2 cells by decreasing the MDA and ROS levels, improving cell apoptosis, increasing the enzyme activity of GPX-Px, CAT, SOD, Na+/K+-ATP, and Ca2+/Mg2+-ATP, and stimulating T-AOC expression, which also enhanced the glucose uptake of insulin-resistant HepG2 cells. In addition, the EAF significantly reduced the fasting blood glucose level and improved glucose tolerance in diabetic mice. An HPLC-QTOF-MS/MS analysis displayed that procyanidin, digallic acid isomer, methyl gallate, tetragalloylglucose isomer, dimethyl gallic acid, and paeoniflorin were the major compounds in the EAF. These findings are meaningful for the application of the EAF in the medicinal or food industry to prevent and treat oxidative stress and diabetes mellitus.

Bioaffinity ultrafiltration combined with LC-Orbitrap-MS/MS was applied for the first time to achieve rapid screening and identification of tyrosinase inhibitory peptides (TYIPs) from grass carp scale gelatin hydrolysates. The binding mode of TYIPs with tyrosinase was investigated by molecular docking technology. The whitening effect of TYIPs was further studied by evaluating the tyrosinase activity and melanin content in mouse B16F10 cells. Four new TYIPs were screened from hydrolysates, among which DLGFLARGF showed the strongest tyrosinase inhibition with an IC50 value of 3.09 mM. Molecular docking showed that hydrogen bonds were the main driving force in the interaction between the peptide DLGFLARGF and tyrosinase. The addition of DLGFLARGF significantly inhibited the tyrosinase activity and melanin production of B16F10 melanoma cells. These results suggest that DLGFLARGF is a promising skin whitening agent for the treatment of potential pigment-related diseases.

The aim of this study was to explore the effects of an emerging and efficient heating technology, superheated steam (SS), on the allergenicity and molecular structure of ovomucoid (OVM). OVM was treated with 120–200 °C of SS for 2 to 10 min. The allergenicity (IgG/IgE binding abilities and cell degranulation assay) and molecular structure (main functional groups and amino acids modification) changes were investigated. The IgG-binding ability of OVM decreased and the releases of β-hex and TNF-γ were inhibited after SS treatment, indicating that the protein allergenicity was reduced. Significant increases in oxidation degree, free SH content and surface hydrophobicity were observed in SS-treated OVM. The protein dimer and trimer appeared after SS treatment. Meanwhile, obvious changes occurred in the primary structure. Specifically, serine can be readily modified by obtaining functional groups from other modification sites during SS treatment. Moreover, the natural OVM structure which showed resistance to trypsin digestion was disrupted, leading to increased protein digestibility. In conclusion, SS-induced OVM aggregation, functional groups and amino acids modifications as well as protein structure alteration led to reduced allergenicity and increased digestibility.

The inhibition of Nelumbo nucifera leaf (NNL) extract and its fractions on the formation of advanced glycation end-products (AGEs) was evaluated with different models. Changes in the conformational structure of bovine serum albumin (BSA) were analyzed by fluorescence spectrometry. Effect of ethyl acetate fraction (EAF) on the glycation sites and glycation degree of BSA was investigated by Nano LC-Orbitrap-MS/MS due to its strongest inhibitory ability. Results indicated that EAF could effectively inhibit the formation of AGEs by scavenging reactive radicals and attenuating the conformational change of BSA induced by glycation. Phenolics and flavonoids were the major contributors. Eleven (11 lysines) and ten (9 lysines and 1 arginine) glycation sites were identified from glycated BSA with and without EAF, respectively. Addition of EAF could not reduce the number of glycation sites of BSA, but could significantly decrease the glycation degree of most glycated peptides and alter the location of glycation.

This article contains peptides mapping, mass spectrometry and processed data related to the research “Identification and quantification of the phosphorylated ovalbumin by high resolution mass spectrometry under dry-heating treatment” [1]. Fourier transform ion cyclotron mass spectrometry (FTICR MS) was used to investigate the specific phosphorylation sites and the degree of phosphorylation (DSP) at each site. Specifically, phosphorylated peptides were monitored through mass shift on the FTICR MS spectrum. DSP was evaluated through the relative abundance levels of the FTICR MS spectrometry. From these data, the calculation method of DSP was exemplified.

Epidemiological studies showed the association between air pollution and dementia. A soluble fraction of particulate matters including polycyclic aromatic hydrocarbons (PAHs) is suspected to be involved with the adverse effects of air pollution on the central nervous system of humans. It is also reported that exposure to benzopyrene (B[a]P), which is one of the PAHs, caused deterioration of neurobehavioral performance in workers. The present study investigated the effect of B[a]P on noradrenergic and serotonergic axons in mouse brains. In total, 48 wild-type male mice (10 weeks of age) were allocated into 4 groups and exposed to B[a]P at 0, 2.88, 8.67 or 26.00 µg/mice, which is approximately equivalent to 0.12, 0.37 and 1.12 mg/kg bw, respectively, by pharyngeal aspiration once/week for 4 weeks. The density of noradrenergic and serotonergic axons was evaluated by immunohistochemistry in the hippocampal CA1 and CA3 areas. Exposure to B[a]P at 2.88 µg/mice or more decreased the density of noradrenergic or serotonergic axons in the CA1 area and the density of noradrenergic axons in the CA3 area in the hippocampus of mice. Furthermore, exposure to B[a]P dose-dependently upregulated Tnfα at 8.67 µg/mice or more, as well as upregulating Il-1β at 26 µg/mice, Il-18 at 2.88 and 26 µg/mice and Nlrp3 at 2.88 µg/mice. The results demonstrate that exposure to B[a]P induces degeneration of noradrenergic or serotonergic axons and suggest the involvement of proinflammatory or inflammation-related genes with B[a]P-induced neurodegeneration. [ABSTRACT FROM AUTHOR]

Douchi is a type of Chinese traditional fermented food that is an important source of protein and is used in flavouring ingredients. The end product is affected by the microbial community present during fermentation, but exactly how microbes influence the fermentation process remains poorly understood. We used an Illumina MiSeq approach to investigate bacterial and fungal community diversity during both douchi-koji making and fermentation. A total of 181,443 high quality bacterial 16S rRNA sequences and 221,059 high quality fungal internal transcribed spacer reads were used for taxonomic classification, revealing eight bacterial and three fungal phyla. Firmicutes, Actinobacteria and Proteobacteria were the dominant bacterial phyla, while Ascomycota and Zygomycota were the dominant fungal phyla. At the genus level, Staphylococcus and Weissella were the dominant bacteria, while Aspergillus and Lichtheimia were the dominant fungi. Principal coordinate analysis showed structural separation between the composition of bacteria in koji making and fermentation. However, multivariate analysis of variance based on unweighted UniFrac distances did identify distinct differences (p

A new steroidal saponin, named pumilum A (1), and a new phenolic glycoside, threo-1-(4′-hydroxy-2′-methoxyphenyl)-2-(2′′,4′′-dihydroxyphenyl)-1,3-propanediol-4′-O-β-D-glucopyranoside (7) were isolated from the methanolic extract of the bulbs of Lilium pumilum DC, along with five known steroidal saponins. Their chemical structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical methods. In addition, the inhibitory activity of all the isolates on Na+/K+ ATPase was evaluated.