Hirschsprung's disease: m6A methylase VIRMA suppresses cell migration and proliferation by regulating GSK3ß.

BACKGROUND: N6-methyladenosine (m6A) is the most abundant mRNA modification in mammals, participating in various biological processes. VIRMA is a key methyltransferase involved in m6A modification. However, the role of VIRMA in Hirschsprung's disease (HSCR) remains unclear. This study aims to investigate the function of VIRMA in HSCR and identify its corresponding regulatory mechanisms. METHODS: The expression of VIRMA and GSK3ß in colon tissues of HSCR was examined using RT-qPCR, Western blot, and Immunohistochemistry. Immunofluorescence detected localization of VIRMA and GSK3ß. Cell proliferation was measured by CCK8 and EdU assays, and cell migration was evaluated via cell migration and wound healing assays. The stability of GSK3ß mRNA was assessed using the actinomycin D assay and the overall level of m6A in cells was assessed by colorimetric assay. RESULTS: VIRMA was significantly downregulated in narrow-segment colon tissue. Silencing of VIRMA inhibited cell proliferation and migration. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß. GSK3ß was significantly upregulated in narrow-segment colon tissues. Accordingly, our findings showed that GSK3ß mediated the VIRMA-driven cell migration and proliferation. CONCLUSION: VIRMA can inhibit cell migration and proliferation by upregulating the expression of GSK3ß, contributing to the onset of HSCR. IMPACT: The expressions of VIRMA were significantly reduced in HSCR, while GSK3ß expression was increased in HSCR, and can be used as a molecular marker. VIRMA overexpression promoted the proliferation and migration of SH-SY5Y and HEK-293T cells. VIRMA can inhibit the degradation of GSK3ß mRNA and increase the expression of GSK3ß.

Antioxidant Dipeptides Enhance Osmotic Stress Tolerance by Regulating the Yeast Cell Wall and Membrane.

This study aimed to investigate the role of the yeast cell wall and membrane in enhancing osmotic tolerance by antioxidant dipeptides (ADs) including Ala-His (AH), Thr-Tyr (TY), and Phe-Cys (FC). Results revealed that ADs could improve the integrity of the cell wall by restructuring polysaccharide structures. Specifically, FC significantly (p < 0.05) reduced the leakage of nucleic acid and protein by 2.86% and 5.36%, respectively, compared to the control. In addition, membrane lipid composition played a crucial role in enhancing yeast tolerance by ADs, including the increase of cell membrane integrity and the decrease of permeability by regulating the ratio of unsaturated fatty acids. The up-regulation of gene expression associated with the cell wall integrity pathway (RLM1, SLT2, MNN9, FKS1, and CHS3) and fatty acid biosynthesis (ACC1, HFA1, OLE1, ERG1, and FAA1) further confirmed the positive impact of ADs on yeast tolerance against osmotic stress.

Surgical prediction of neonatal necrotizing enterocolitis based on radiomics and clinical information.

PURPOSE: To assess the predictive value of radiomics for surgical decision-making in neonatal necrotizing enterocolitis (NEC) when abdominal radiographs (ARs) do not suggest an absolute surgical indication for free pneumoperitoneum. METHODS: In this retrospective study, we finally included 171 newborns with NEC and obtained their ARs and clinical data. The dataset was randomly divided into a training set (70%) and a test set (30%). We developed machine learning models for predicting surgical treatment using clinical features and radiomic features, respectively, and combined these features to build joint models. We assessed predictive performance of the different models by receiver operating characteristic curve (ROC) analysis and compared area under curve (AUC) using the Delong test. Decision curve analysis (DCA) was used to assess the potential clinical benefit of the models to patients. RESULTS: There was no significant difference in AUC between the clinical model and the four radiomic models (P > 0.05). The XGBoost joint model had better predictive efficacy and stability (AUC, training set: 0.988, test set: 0.959). Its AUC in the test set was significantly higher than that of the clinical model (P < 0.05). DCA showed that the XGBoost joint model achieved higher net clinical benefit compared to the clinical model in the threshold probability range (0.2-0.6). CONCLUSION: Radiomic features based on AR are objective and reproducible. The joint model combining radiomic features and clinical signs has good surgical predictive efficacy and may be an important method to help primary neonatal surgeons assess the surgical risk of NEC neonates.

Improving the emulsifying capacity of brewers' spent grain arabinoxylan by carboxymethylation.

Arabinoxylan derived from brewers' spent grain was carboxymethylated, and the emulsifying capacity of carboxymethylated arabinoxylans (CMAX) with different degrees of substitution (DS) was investigated. Results showed that carboxymethylation greatly enhanced the emulsifying capacity and emulsion stability of CMAX compared to the initial arabinoxylan. CMAX developed decreased ζ-potential, higher hydrophilicity, and improved interfacial adsorption capacity. Consequently, the denser and stronger interface on the oil droplet was formed, and the stabilizing mechanism was altered. Moreover, CMAX with lower DS could effectively stabilize emulsions during storage at a concentration of 0.5 % and pH between 6 and 7. Higher DS, however, led to poorer emulsion stability and greater flocculation as a result of the fragile interface formed by excess intermolecular ionic force. The research found CMAX potential in emulsion stabilizing and further applications in food processing.

Insights into spirotetramat-induced thyroid disruption during zebrafish (Danio rerio) larval development: An integrated approach with in vivo, in vitro, and in silico analyses.

Spirotetramat (SPT), a tetronic acid-derived insecticide, is implicated in reproductive and lipid metabolism disorders, as well as developmental toxicity in fish. While these effects are documented, the precise mechanisms underlying its developmental toxicity are not fully elucidated. In this study, zebrafish embryos (2 h post-fertilization, hpf) were exposed to four concentrations of SPT (0, 60, 120, and 240 µg/L) until 21 dpf (days post-fertilization). We delved into the mechanisms by examining its potential disruption of the thyroid endocrine system, employing in vivo, in vitro, and in silico assays. The findings showed notable developmental disturbances, including reduced hatching rates, shortened body lengths, and decelerated heart rates. Additionally, there was an increase in malformations and a decline in locomotor activity. Detailed analyses revealed that SPT exposure led to elevated thyroid hormone levels, perturbed the hypothalamic-pituitary-thyroid (HPT) axis transcript levels, amplified deiodinase type I (Dio1) and deiodinase type II (Dio2) activities, and both transcriptionally and proteomically upregulated thyroid receptor beta (TRß) in larvae. Techniques like molecular docking and surface plasmon resonance (SPR) confirmed SPT's affinity for TRß, consistent with in vitro findings suggesting its antagonistic effect on the T3-TR complex. These insights emphasize the need for caution in using tetronic acid-derived insecticides.

Characterization, Expression, and Functional Analysis of the Northern Snakehead (Channa argus) Hepcidin.

Hepcidin, an antimicrobial peptide (AMP), is a well-conserved molecule present in various species such as fish, amphibians, birds, reptiles, and mammals. It exhibits broad-spectrum antimicrobial activity and holds a significant role in the innate immune system of host organisms. The northern snakehead (Channa argus) has become a valuable freshwater fish in China and Asia. In this investigation, the cDNA encoding the hepcidin gene of northern snakehead was cloned and named caHep. The amino acid sequences and protein structure of caHep are similar to those of hepcidins from other fish. The eukaryotic expression product of the caHep gene showed broad-spectrum antibacterial activity. Scanning electron microscope analysis indicated that the caHep peptide inhibited bacterial growth by damaging their cell membranes. Lipopolysaccharide (LPS) injection induced significant expression of caHep, implying the involvement of caHep in the innate immune response of northern snakeheads. This investigation showed that the caHep peptide is potentially a robust antibacterial drug against bacterial diseases in aquaculture animals.

Mechanism of selenite tolerance during barley germination: A combination of tissue selenium metabolism alterations and ascorbate-glutathione cycle modulation.

Selenite is widely used to increase Selenium (Se) content in cereals, however excessive selenite may be toxic to plant growth. In this study, barley was malted to elucidate the action mechanism of selenite in the generation and detoxification of oxidative toxicity. The results showed that high doses (600 µM) of selenite radically increased oxidative stress by the elevated accumulation of superoxide and malondialdehyde, leading to phenotypic symptoms of selenite-induced toxicity like stunted growth. Barley tolerates selenite through a combination of mechanisms, including altering Se distribution in barley, accelerating Se efflux, and increasing the activity of some essential antioxidant enzymes. Low doses (150 µM) of selenite improved barley biomass, respiratory rate, root vigor, and maintained the steady-state equilibrium between reactive oxygen species (ROS) and antioxidant enzyme. Selenite-induced proline may act as a biosignal to mediate the response of barley to Se stress. Furthermore, low doses of selenite increased the glutathione (GSH) and ascorbate (AsA) concentrations by mediating the ascorbate-glutathione cycle (AsA-GSH cycle). GSH intervention and dimethyl selenide volatilization appear to be the primary mechanisms of selenite tolerance in barley. Thus, results from this study will provide a better understanding of the mechanisms of selenite tolerance in crops.

Pneumonia, lymphocytes and C-reactive protein are valuable tests for predicting surgical intervention in necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is one of the important causes of neonatal death, and proper timing of operation is of critical significance. This study aimed to explore the high-risk factors for NEC requiring surgical intervention and to provide a reference for its clinical diagnosis and treatment. Methods: Clinical and radiological evidence of NEC neonates admitted to Zhujiang Hospital of Southern Medical University and Zhongshan Boai Hospital from January 2010 to October 2022 were retrospectively analyzed. Patients were divided into surgical group and conservative group according to whether they underwent surgery or not. Univariate analysis of the clinical data of the two groups was conducted, and multivariate logistic regression analysis was then performed for statistically significant results in the univariate analysis. Results: 267 infants were included in this study, of which 90 patients underwent surgical intervention for NEC and 177 conservation treatment. The univariate analysis showed that the gestational age, pneumonia, leukocytes, lymphocytes, erythrocytes, platelets, C-reactive protein, and blood glucose were statistically significant in the surgical group compared to the conservative group (All P < 0.05). Furthermore, the results of multivariate logistic regression analysis showed that compared to the conservative group, patients in the surgical group had a higher proportion of pneumonia (OR = 2.098; 95% CI: 1.030-4.272; P = 0.041), lower lymphocyte values (OR = 0.749; 95% CI: 0.588-0.954; P = 0.019), and higher C-reactive protein values (OR = 1.009; 95% CI: 1.003-1.016; P = 0.004). Conclusions: Pneumonia, decreased lymphocytes, and elevated C-reactive protein are potential high-risk factors for neonates with NEC requiring surgical intervention and may have potential clinical implications for predicting surgical risk.

Mechanisms of Antioxidant Dipeptides Enhancing Ethanol-Oxidation Cross-Stress Tolerance in Lager Yeast: Roles of the Cell Wall and Membrane.

High concentrations of ethanol could cause intracellular oxidative stress in yeast, which can lead to ethanol-oxidation cross-stress. Antioxidant dipeptides are effective in maintaining cell viability and stress tolerance under ethanol-oxidation cross-stress. In this study, we sought to elucidate how antioxidant dipeptides affect the yeast cell wall and membrane defense systems to enhance stress tolerance. Results showed that antioxidant dipeptide supplementation reduced cell leakage of nucleic acids and proteins by changing cell wall components under ethanol-oxidation cross-stress. Antioxidant dipeptides positively modulated the cell wall integrity pathway and up-regulated the expression of key genes. Antioxidant dipeptides also improved the cell membrane integrity by increasing the proportion of unsaturated fatty acids and regulating the expression of key fatty acid synthesis genes. Moreover, the addition of antioxidant dipeptides significantly (p < 0.05) increased the content of ergosterol. Ala-His (AH) supplementation caused the highest content of ergosterol, with an increase of 23.68 ± 0.01% compared to the control, followed by Phe-Cys (FC) and Thr-Tyr (TY). These results revealed that the improvement of the cell wall and membrane functions of antioxidant dipeptides was responsible for enhancing the ethanol-oxidation cross-stress tolerance of yeast.

Laboratory tidal microcosm deciphers responses of sediment archaeal and bacterial communities to microplastic exposure.

Microplastics (MPs) are 1-5 mm plastic particles that are serious global contaminants distributed throughout marine ecosystems. However, their impact on intertidal sediment microbial communities is poorly understood. In this study, we conducted a 30-day laboratory tidal microcosm experiment to investigate the effects of MPs on microbial communities. Specifically, we used the biodegradable polymers polylactic acid (PLA) and polybutylene succinate (PBS), as well as the conventional polymers polyethylene terephthalate (PET), polycarbonate (PC), and polyethylene (PE). Treatments with different concentrations (1-5%, w/w) of PLA- and PE-MPs were also included. We analyzed taxonomic variations in archaeal and bacterial communities using 16S rRNA high-throughput sequencing. PLA-MPs at concentrations of 1% (w/w) rapidly altered microbiome composition. Total organic carbon and nitrite nitrogen were the key physicochemical factors and urease was the major enzyme shaping MP-exposed sediment microbial communities. Stochastic processes predominated in microbial assembly and the addition of biodegradable MPs enhanced the contribution of ecological selections. The major keystone taxa of archaea and bacteria were Nitrososphaeria and Alphaproteobacteria, respectively. MPs exposure had less effect on archaeal functions while nitrogen cycling decreased in PLA-MPs treatments. These findings expanded the current understanding of the mechanism and pattern that MPs affect sediment microbial communities.

Brij-58 supplementation enhances menaquinone-7 biosynthesis and secretion in Bacillus natto.

Menaquinone-7 is a form of vitamin K2 that has been shown to have numerous healthy benefits. In this study, several surfactants were investigated to enhance the production of menaquinone-7 in Bacillus natto. Results showed that Brij-58 supplementation influenced the cell membrane via adsorption, and changed the interfacial tension of fermentation broth, while the changes in the state and the composition of the cell membrane enhanced the secretion and biosynthesis of menaquinone-7. The total production and secretion rate of menaquinone-7 increased by 48.0% and 56.2% respectively. During fermentation, the integrity of the cell membrane decreased by 82.9% while the permeability increased by 158% when the maximum secretory rate was reached. Furthermore, Brij-58 supplementation induced the stress response in bacteria, resulting in hyperpolarization of the membrane, and increased membrane ATPase activity. Finally, changes in fatty acid composition increased membrane fluidity by 30.1%. This study provided an effective strategy to enhance menaquinone-7 yield in Bacillus natto and revealed the mechanism of Brij-58 supplementation in menaquinone-7 production. KEY POINTS: • MK-7 yield in Bacillus natto was significantly increased by Brij-58 supplementation. • Brij-58 could be adsorbed on cell surface and change fermentation environment. • Brij-58 supplementation could affect the state and composition of the cell membrane.

1,4-α-Glucosidase from Fusarium solani for Controllable Biosynthesis of Silver Nanoparticles and Their Multifunctional Applications.

In the study, monodispersed silver nanoparticles (AgNPs) with an average diameter of 9.57 nm were efficiently and controllably biosynthesized by a reductase from Fusarium solani DO7 only in the presence of ß-NADPH and polyvinyl pyrrolidone (PVP). The reductase responsible for AgNP formation in F. solani DO7 was further confirmed as 1,4-α-glucosidase. Meanwhile, based on the debate on the antibacterial mechanism of AgNPs, this study elucidated in further depth that antibacterial action of AgNPs was achieved by absorbing to the cell membrane and destabilizing the membrane, leading to cell death. Moreover, AgNPs could accelerate the catalytic reaction of 4-nitroaniline, and 86.9% of 4-nitroaniline was converted to p-phenylene diamine in only 20 min by AgNPs of controllable size and morphology. Our study highlights a simple, green, and cost-effective process for biosynthesizing AgNPs with uniform sizes and excellent antibacterial activity and catalytic reduction of 4-nitroaniline.

Proteomic analysis reveals the adaptation of Vibrio splendidus to an iron deprivation condition.

Vibrio splendidus is a ubiquitous Gram-negative marine bacterium that causes diseases within a wide range of marine cultured animals. Since iron deprivation is the frequent situation that the bacteria usually encounter, we aimed to explore the effect of iron deprivation on the proteomic profile of V. splendidus in the present study. There were 425 differentially expressed proteins (DEPs) responded to the iron deprivation condition. When the cells were grown under iron deprivation condition, the oxidation‒reduction processes, single-organism metabolic processes, the catalytic activity, and binding activity were downregulated, while the transport process, membrane cell component, and ion binding activity were upregulated, apart from the iron uptake processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that various metabolism pathways, biosynthesis pathways, energy generation pathways of tricarboxylic acid cycle, and oxidative phosphorylation were downregulated, while various degradation pathways and several special metabolism pathways were upregulated. The proteomic profiles of cells at a OD600 ≈ 0.4 grown under iron deprivation condition showed high similarity to that of the cells at a OD600 ≈ 0.8 grown without iron chelator 2,2'-bipyridine. Correspondingly, the protease activity, the activity of autoinducer 2 (AI-2), and indole content separately catalyzed by LuxS and TnaA, were measured to verify the proteomic data. Our present study gives basic information on the global protein profiles of V. splendidus grown under iron deprivation condition and suggests that the iron deprivation condition cause the cell growth enter a state of higher cell density earlier. KEY POINTS: • Adaptation of V. splendidus to iron deprivation was explored by proteomic analysis. • GO and KEGG of DEPs under different iron levels or cell densities were determined. • Iron deprivation caused the cell enter a state of higher cell density earlier.

Selenium Uptake, Translocation, and Metabolization Pattern during Barley Malting: A Comparison of Selenate, Selenite, and Selenomethionine.

Selenium (Se) is an essential trace element for human and animal health. Understanding the uptake and translocation of Se in crops is critical from the perspective of Se biofortification. In this study, barley was malted to investigate the uptake, translocation, and metabolism of exogenous Se including Na2SeO4, Na2SeO3, and selenomethionine (Se-Met). The results showed that the uptake rates of different forms of Se in barley decreased in the following order: Se-Met > Na2SeO3 > Na2SeO4, with the peak uptake occurring at the end of the steeping stages. In the early stages of germination, Se was mainly distributed in the husk and endosperm. Exogenous Se upregulated the transcription levels of Se transport and metabolic enzyme genes in the barley to varying degrees, which promoted Se transformation in various tissues, and improved Se bioeffectiveness. Compared to the Na2SeO3 and Se-Met groups, more Se was transferred from husk and endosperm to acrospire and rootlets in the Na2SeO4 group during the germination stage. Na2SeO4 and Se-Met stimulated the development of rootlets, and accelerated Se metabolism, resulting in a higher Se loss rate. Thus, these comparative findings provide new insights into Se uptake, transformation, and metabolization in barley.

Enhancing the foaming properties of brewer's spent grain protein by ultrasound treatment and glycation reaction.

The denaturation state and relatively poor solubility of brewer's spent grain protein (BSGP) have limited its industrial application. Ultrasound treatment and glycation reaction were applied to improve the structural and foaming properties of BSGP. The results showed that all ultrasound, glycation, and ultrasound-assisted glycation treatments increased the solubility and surface hydrophobicity of BSGP while decreasing its zeta potential, surface tension and particle size. Meanwhile, all these treatments resulted in a more disordered and flexible conformation of BSGP, as observed by CD spectroscopy and SEM. After grafting, the result of FTIR spectroscopy confirmed the covalent binding of -OH between maltose and BSGP. Ultrasound-assisted glycation treatment further improved the free SH and S-S content, which might be due to -OH oxidation, indicating that ultrasound promoted the glycation reaction. Furthermore, all these treatments significantly increased the foaming capacity (FC) and foam stability (FS) of BSGP. Notably, BSGP treated with ultrasound showed the best foaming properties, increasing the FC from 82.22% to 165.10% and the FS from 10.60% to 131.20%, respectively. In particular, the foam collapse rate of BSGP treated with ultrasound-assisted glycation was lower than that of ultrasound or traditional wet-heating glycation treatment. The enhanced hydrogen bonding ability and hydrophobic interaction between protein molecules caused by ultrasound and glycation might be responsible for the improved foaming properties of BSGP. Thus, ultrasound and glycation reactions were efficient methods for producing BSGP-maltose conjugates with superior foaming properties.

Structure, chemical stability and antioxidant activity of melanoidins extracted from dark beer by acetone precipitation and macroporous resin adsorption.

Melanoidins contribute to the sensory and functional properties of dark beers. The structure, stability, and antioxidant activity of acetone precipitation extracted melanoidins (APE-M) and macroporous resin adsorption extracted melanoidins (MAE-M) from dark beer were investigated. The structural properties of melanoidins were characterized using Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), scanning electron microscopy (SEM), and the solution storage stability, thermal behavior and antioxidant activity of melanoidins in dark beers were evaluated. MAE-M revealed more sophisticated structures than APE-M, including more concrete characteristics of Maillard reaction (MR) products in FTIR (1550-1500 cm-1), more ordered secondary structure in CD spectra, and thinner slices as well as more microspheres in SEM. The solution storage stability assay showed that certain factors, including 55 °C, 5 % v/v ethanol, UV light, and H2O2 solution, accelerated the degradation of melanoidins. The moderate extraction process of MAE-M performed a minor enthalpy change (-92.28 Jg-1) in the DSC-TG test than that of APE-M (-319.41 Jg-1). Furthermore, the ABTS and DPPH radical scavenging activities and the FRAP assay demonstrated that the antioxidant activity of MAE-M was almost twice that of APE-M. In general, MAE was more effective in extracting beer melanoidins while maintaining its accurate structure and profitable antioxidant activity than APE.

The Expression Pattern of Insulin-Like Growth Factor Subtype 3 (igf3) in the Orange-Spotted Grouper Epinephelus coioides and Its Function on Ovary Maturation.

A new insulin-like growth factor (Igf) subtype 3 (igf3) has recently been found in the bony fish orange-spotted grouper (Epinephelus coioides). However, the role of igf3 in the maturation of the ovary and sex differentiation in E. coioides is currently unknown. We examined the ovarian localization and receptor binding of the novel ortholog Igf3 using qRT-PCR, and Western blotting, combined with in situ hybridization and immunohistochemistry methods. Results demonstrated the presence of igf3 mRNA and protein in mature oocytes. Furthermore, Igf3 protein expression was not detected in testis, brain, kidney and liver homogenates. The calculated molecular weight of Igf3 was 22 kDa, which was consistent with the deduced amino acid sequence from the full-length open reading frame. The immunoreactivity showed that Igf3 was strongly present in the follicle staining fully-grown stage. The igf3 mRNA expression level was significantly positively correlated with ovarian follicular maturation. Meanwhile, Igf3 increased germinal-vesicle breakdown in a time- and dose-dependent manner. In vitro, treatment of primary ovarian cells with Igf3 up-regulated significantly the mRNA expression level of genes related to sex determination and reproduction such as forkhead boxl2 (foxl2), dosage-sensitive sex reversal adrenal hypoplasia critical region on chromosome x gene 1 (dax1), cytochrome P450 family 19 subfamily member 1 a (cyp19a1a), cytochrome P450 family 11 subfamily a member 1 a (cyp11a1a) and luteinizing hormone receptor 1 (lhr1). Overall, our results demonstrated that igf3 promotes the maturation of the ovary and plays an important role in sex differentiation in E. coioides.

Urbanization alters soil bacterial communities in southern China coastal cities.

Urbanization carries essential influences to ecosystem of soil bacteria in coastal cities. Comprehending the patterns and drivers of bacterial diversity are essential to understanding how soil ecosystems respond to environmental change. This study aimed to explore how soil bacterial community (SBC) response to distinct urbanization of coastal cities on composition, assembly process and potential function in Guangdong province, south China. 72 samples from 24 sample sites within 3 cities were included in the study. Soil chemical properties were analyzed, and the bacterial community were investigated by high-throughout sequencing. Proteobacteria and Acidobacteria were the main phyla. Assembly processes remained in stochastic processes and co-occurrence network of SBC kept stable, while urbanization altered SBC by influencing the dominant phyla. The indicators of communities in coastal city soils were the genera gamma_proteobacterium and beta_proteobacterium. Urbanized extent was the non-negligible factor which affected soil bacterial community, despite the total carbon was still the most vital. The impact of urbanization on bacterial communities might follow a non-linear pattern. Faprotax function prediction showed different urbanized coastal city soils share similar metabolic potential. Our study improved our understanding of the response of soil bacterial communities to urbanization in subtropical coastal cities and offered a useful strategy to monitor the ecology risk toward the soil under urbanization.

[Analysis of variant of GLI3 gene in a child featuring autosomal dominant Pallister-Hall syndrome].

OBJECTIVE: To explore the clinical and genetic characteristics of a child with Pallister-Hall syndrome (PHS). METHODS: DNA was extracted from peripheral blood sample from the child and subjected to whole exome sequencing. Suspected variants were verified by Sanger sequencing of his family members. RESULTS: Genetic testing revealed that the child has harbored a heterozygous c.3320_3330delGGTACGAGCAG (p.G1107Afs×18) variant of the GLI3 gene. Neither parent was found to carry the same variant. CONCLUSION: The c.3320_3330delGGTACGAGCAG (p.G1107Afs×18) frameshift variant of the GLI3 gene probably underlay the pathogenesis of PHS in this child. Genetic testing should be considered for patients featuring hypothalamic hamartoma and central polydactyly.

Hypoglycemic Effects of Novel Panax notoginseng Polysaccharide in Mice with Diet-Induced Obesity.

In the study, the structural features and hypoglycemic effects of a polysaccharide Pan from the root of Panax notoginseng were investigated. The molecular weight of Pan was 8.27 kDa. Structural analysis indicated that Pan mainly consisted of →3)-ß-L-Rhap-(1→, →3,6)-ß-D-Galf-(1→ and →6)-ß-D-Galf-(1→ residues with acetyl groups. Pan exhibited good antioxidant activity. Pan could slow down the body weight and the content of blood glucose in the high-fat diet-induced mice, further suppress GLUT-2 and SGLT-1 expression in the intestines, and enhance p-IRS and p-AMPK expression in the livers, finally exhibiting hypoglycemic effects. The results could supply a direction for further research on polysaccharides as components for the control of hyperglycemia induced by obesity and diabetes.