Synthesis and Characterization of Emulsifiers Based on the Maillard Reaction and Its Application in Stabilized DHA Algal Oil Nanoemulsions.

The aim of this study was to optimize the formation of sodium caseinate (CS) and gum arabic (GA) complexes through the Maillard reaction and to evaluate their effectiveness in improving the emulsification properties and stability of docosahexaenoic acid (DHA) nanoemulsions. First, the best target polysaccharides were selected, and the best modification conditions were determined using orthogonal experiments. Secondly, the response surface experiments were used to optimize the preparation process of the emulsion. The stability, in vitro digestion characteristics, and rheological characteristics of the emulsion prepared by means of CS-GA were compared with the emulsion prepared using a whey protein isolate (WPI). After the orthogonal test, the optimal modification conditions were determined to be a reaction time of 96 h, a CS-GA mass ratio of 1:2, a reaction temperature of 60 °C, and a degree of grafting of 44.91%. Changes in the infrared (IR), Raman, ultraviolet (UV), and endogenous fluorescence spectra also indicated that the complex structure was modified. The response surface test identified the optimal preparation process as follows: an emulsifier concentration of 5 g/L, an oil-phase concentration of 5 g/L, and a homogenization frequency of five, and the emulsion showed good stability. Therefore, the use of a nanoemulsion as a nanoscale DHA algal oil delivery system is very promising for extending the shelf life and improving the stability of food.

Mutated lncRNA increase the risk of type 2 diabetes by promoting ß cell dysfunction and insulin resistance.

Islet ß cell dysfunction and insulin resistance are the main pathogenesis of type 2 diabetes (T2D), but the mechanism remains unclear. Here we identify a rs3819316 C > T mutation in lncRNA Reg1cp mainly expressed in islets associated with an increased risk of T2D. Analyses in 16,113 Chinese adults reveal that Mut-Reg1cp individuals had higher incidence of T2D and presented impaired insulin secretion as well as increased insulin resistance. Mice with islet ß cell specific Mut-Reg1cp knock-in have more severe ß cell dysfunction and insulin resistance. Mass spectrometry assay of proteins after RNA pulldown demonstrate that Mut-Reg1cp directly binds to polypyrimidine tract binding protein 1 (PTBP1), further immunofluorescence staining, western blot analysis, qPCR analysis and glucose stimulated insulin secretion test reveal that Mut-Reg1cp disrupts the stabilization of insulin mRNA by inhibiting the phosphorylation of PTBP1 in ß cells. Furthermore, islet derived exosomes transfer Mut-Reg1cp into peripheral tissue, which then promote insulin resistance by inhibiting AdipoR1 translation and adiponectin signaling. Our findings identify a novel mutation in lncRNA involved in the pathogenesis of T2D, and reveal a new mechanism for the development of T2D.

Automated detection of clinical depression based on convolution neural network model.

As a common mental disorder, depression is placing an increasing burden on families and society. However, the current methods of depression detection have some limitations, and it is essential to find an objective and efficient method. With the development of automation and artificial intelligence, computer-aided diagnosis has attracted more and more attention. Therefore, exploring the use of deep learning (DL) to detect depression has valuable potential. In this paper, convolutional neural network (CNN) is applied to build a diagnostic model for depression based on electroencephalogram (EEG). EEG recordings are analyzed by three different CNN structures, namely EEGNet, DeepConvNet and ShallowConvNet, to dichotomize depression patients and healthy controls. EEG data were collected in the resting state from three electrodes (Fp1, Fz, Fp2) among 80 subjects (40 depressive patients and 40 normal subjects). After the preprocessing step, the DL structures are employed to classify the data, and their recognition performance is evaluated by comparing the classification results. The classification performance shows that depression was effectively detected using EEGNet with 93.74% accuracy, 94.85% sensitivity and 92.61% specificity. In the process of optimizing the parameters of EEGNet structure, the highest accuracy can reach 94.27%. Compared with traditional diagnostic methods, EEGNet is highly worthy for the future depression detection and valuable in terms of accuracy and speed.

Mitochondrial Dynamics Mediated by DRP1 and MFN2 Contributes to Cisplatin Chemoresistance in Human Ovarian Cancer SKOV3 cells.

Cisplatin (DDP) is the first-line chemotherapeutic agent for ovarian cancer. However, the development of DDP resistance seriously influences the chemotherapeutic effect and prognosis of ovarian cancer. It was reported that DDP can directly impinge on the mitochondria and activate the intrinsic apoptotic pathway. Herein, the role of mitochondrial dynamics in DDP chemoresistance in human ovarian cancer SKOV3 cells was investigated. In DDP-resistant SKOV3/DDP cells, mitochondrial fission protein DRP1 was down-regulated, while mitochondrial fusion protein MFN2 was up-regulated. In accordance with the expression of DRP1 and MFN2, the average mitochondrial length was significantly increased in SKOV3/DDP cells. In DDP-sensitive parental SKOV3 cells, downregulation of DRP1 and upregulation of mitochondrial fusion proteins including MFN1,2 and OPA1 occurred at day 2~6 under cisplatin stress. Knockdown of DRP1 or overexpression of MFN2 promoted the resistance of SKOV3 cells to cisplatin. Intriguingly, weaker migration capability and lower ATP level were detected in SKOV3/DDP cells. Respective knockdown of DRP1 in parental SKOV3 cells or MFN2 in SKOV3/DDP cells using siRNA efficiently reversed mitochondrial dynamics, migration capability and ATP level. Moreover, MFN2 siRNA significantly aggravated the DDP-induced ROS production, mitochondrial membrane potential disruption, expression of pro-apoptotic protein BAX and Cleaved Caspase-3/9 in SKOV3/DDP cells. In contrast, DRP1 siRNA alleviated DDP-induced ROS production, mitochondrial membrane potential disruption, expression of pro-apoptotic protein BAX and Cleaved Caspase-3/9 in SKOV3 cells. Thus, these results indicate that mitochondrial dynamics mediated by DRP1 and MFN2 contributes to the development of DDP resistance in ovarian cancer cells, and will also provide a new strategy to prevent chemoresistance in ovarian cancer by targeting mitochondrial dynamics.

Management of a pregnant patient with chylomicronemia from a novel mutation in GPIHBP1: a case report.

BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive lipid disorder often associated with recurrent episodes of pancreatitis. It is documented in most cases with FCS due to the mutations of key proteins in lipolysis, including LPL, APOC2, APOA5, LMF1 and GPIHBP1. CASE PRESENTATION: We report the successful management of a 35-year-old pregnant woman carrying a novel homozygous frameshift mutation c.48_49insGCGG (p.P17A fs*22) in the GPIHBP1 gene with previous severe episodes of acute pancreatitis triggered by pregnancy, resulting in adverse obstetrical outcomes. With careful monitoring, the patient underwent an uneventful pregnancy and delivered a baby with no anomalies. CONCLUSIONS: The case report contributes to the understanding of GPIHBP1-deficient familial chylomicronemia syndrome (FCS) and highlights gestational management of FCS patient.

Path loss modeling and verification of implantable human-body communication based on a point source field.

BACKGROUND: Deep brain stimulation is a method of nerve regulation that uses human body conductance characteristics; signals are diffused and transmitted through human tissues to regulate diseases. OBJECTIVE: We analyzed the distribution and the transmission mechanism of implantable electrical signals from a point source field in the human body using the point source field implanting channel model. METHODS: The model was established using a mathematical modeling method, with reasonable boundary conditions and assumptions. Further, we established an equivalent numerical solution model to verify its accuracy and compared the model to published experimental results to evaluate its consistency. RESULTS: The analysis results of the two models revealed that both had errors of < 1%. A comparison of the experimental results to published experimental data revealed that the error between the two was < 4 dB, and the model displayed excellent consistency. CONCLUSIONS: Our proposed model is accurate and exhibits good consistency with published experimental results. We therefore conclude that the proposed model is reliable.

Association between SLC2A9 Genetic Variants and Risk of Hyperuricemia in a Uygur Population.

EN: Summary]This study aimed to test the effects of five single nucleotide polymorphisms within SLC2A9 on uric acid level in a special ethnic population, the Uygurs in Xinjiang, China. According to our inclusion and exclusion criteria, Uygur adults from Xinjiang constituted the study population. There were 1053 Uygur adults with hyperuricemia and 1373 normal Uygur adults who served as controls. Five single nucleotide polymorphisms within SLC2A9 (rs938557, rs7679916, rs7349721, rs13101785, and rs13137343) were selected with the HapMap dataset and TaqMan assays. We found that, in normouricemia group, rs938557 was significantly correlated with uric acid (ß=11.39±3.74, P=0.0024) adjusting for age, gender and BMI; rs7679916 and rs13137343 were marginally associated with uric acid concentration (ß=5.77±3.09, P=0.0626; ß= 5.99±3.08, P=0.0520). In the hyperuricemia group, no SNP was found to possibly influence uric acid concentration. None of these SNPs showed significant association with hyperuricemia after controlling for age, gender and BMI. There were significant or marginal correlations between certain single nucleotide polymorphisms in the SLC2A9 region and uric acid concentration in Uygur normouricemia samples. In turn, some of these single nucleotide polymorphisms in SLC2A9 may increase the risk of hyperuricemia.

Mitochondrial Fission Is Required for Blue Light-Induced Apoptosis and Mitophagy in Retinal Neuronal R28 Cells.

Light emitting diodes (LEDs) are widely used to provide illumination due to their low energy requirements and high brightness. However, the LED spectrum contains an intense blue light component which is phototoxic to the retina. Recently, it has been reported that blue light may directly impinge on mitochondrial function in retinal ganglion cells (RGCs). Mitochondria are high dynamic organelles that undergo frequent fission and fusion events. The aim of our study was to elucidate the role of mitochondrial dynamics in blue light-induced damage in retinal neuronal R28 cells. We found that exposure to blue light (450 nm, 1000 lx) for up to 12 h significantly up-regulated the expression of mitochondrial fission protein Drp1, while down-regulating the expression of mitochondrial fusion protein Mfn2 in cells. Mitochondrial fission was simultaneously stimulated by blue light irradiation. In addition, exposure to blue light increased the production of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP), and induced apoptosis in R28 cells. Notably, Drp1 inhibitor Mdivi-1 and Drp1 RNAi not only attenuated blue light-induced mitochondrial fission, but also alleviated blue light-induced ROS production, MMP disruption and apoptosis in cells. Compared with Mdivi-1 and Drp1 RNAi, the antioxidant N-acetyl-L-cysteine (NAC) only slightly inhibited mitochondrial fission, while significantly alleviating apoptosis after blue light exposure. Moreover, we examined markers for mitophagy, which is responsible for the clearance of dysfunctional mitochondria. It was found that blue light stimulated the conversion of LC3B-I to LC3B-II as well as the expression of PINK1 in R28 cells. Mdivi-1 or Drp1 RNAi efficiently inhibited the blue light-induced expression of PINK1 and co-localization of LC3 with mitochondria. Thus, our data suggest that mitochondrial fission is required for blue light-induced mitochondrial dysfunction and apoptosis in RGCs.

Association of serum uric acid levels with osteoporosis and bone turnover markers in a Chinese population.

Recent evidence shows that uric acid is protective against some neurological diseases, but can be detrimental in many metabolic and cardiovascular disorders. In this study, we examined the association between serum uric acid levels and bone metabolism in Chinese males and postmenopausal females. A total of 943 males and 4256 postmenopausal females were recruited in Shanghai. The levels of serum uric acid and bone turnover markers (BTMs) were detected along with other biochemical traits. In addition, the fat distribution was calculated through MRI and image analysis software, and bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry. For postmenopausal females, the prevalence of osteoporosis was significantly lower in the hyperuricemia group compared with the normouricemic group (P=4.65E-06). In females, serum uric acid level was significantly associated with osteoporosis, with odds ratio (OR) and 95% confidence interval (95% CI) of 0.844 [0.763; 0.933] (P=0.0009) after adjusting for age, body mass index, HbA1c, lean mass, visceral and subcutaneous fat areas, albumin, 25-hydroxyvitamin D3 [25(OH)D3], and parathyroid hormone (PTH). In females, serum uric acid level was positively correlated with the BMD of the femoral neck (ß±SE: 0.0463±0.0161; P=0.0042), total hip (ß±SE: 0.0433±0.0149; P=0.0038) and L1-4 (ß±SE: 0.0628±0.0165; P=0.0001) after further adjusting for age, BMI, HbA1c, lean mass, VFA, SFA, albumin, 25(OH)D3 and PTH. Regarding BTMs, serum uric acid level was negatively correlated with N-terminal procollagen of type I collagen (PINP) in females (ß±SE: -0.1311±0.0508; P=0.0100). In summary, our results suggest that uric acid has a protective effect on bone metabolism independent of body composition in Chinese postmenopausal females.

Mangiferin ameliorates insulin resistance by inhibiting inflammation and regulatiing adipokine expression in adipocytes under hypoxic condition.

Adipose tissue hypoxia has been recognized as the initiation of insulin resistance syndromes. The aim of the present study was to investigate the effects of mangiferin on the insulin signaling pathway and explore whether mangiferin could ameliorate insulin resistance caused by hypoxia in adipose tissue. Differentiated 3T3-L1 adipocytes were incubated under normal and hypoxic conditions, respectively. Protein expressions were analyzed by Western blotting. Inflammatory cytokines and HIF-1-dependent genes were tested by ELISA and q-PCR, respectively. The glucose uptake was detected by fluorescence microscopy. HIF-1α was abundantly expressed during 8 h of hypoxic incubation. Inflammatory reaction was activated by up-regulated NF-κB phosphorylation and released cytokines like IL-6 and TNF-α. Glucose uptake was inhibited and insulin signaling pathway was damaged as well. Mangiferin substantially inhibited the expression of HIF-1α. Lactate acid and lipolysis, products released by glycometabolism and lipolysis, were also inhibited. The expression of inflammatory cytokines was significantly reduced and the damaged insulin signaling pathway was restored to proper functional level. The glucose uptake of hypoxic adipocytes was promoted and the dysfunction of adipocytes was relieved. These results showed that mangiferin could not only improve the damaged insulin signaling pathway in hypoxic adipocytes, but also ameliorate inflammatory reaction and insulin resistance caused by hypoxia.

Association of bone turnover markers with glucose metabolism in Chinese population.

The association between type 2 diabetes (T2DM) and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance (NGT), impaired glucose regulation (IGR) or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers (BTMs) and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin (N-MID), N-terminal procollagen of type I collagen (PINP) and ß-cross-linked C-telopeptide of type I collagen (ß-CTX) were significantly decreased in the T2DM group compared to the NGT group (P<0.01). When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and ß-CTX were included in one logistic model, N-MID (OR [95% CI]: 0.954 [0.932; 0.976]; P=0.0001) was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-ß. PINP was significantly associated with HOMA-ß, GUTT-ISI, Stumvoll first-phase insulin secretion index (STU-1) and Stumvoll second-phase insulin secretion index (STU-2), but ß-CTX was associated only with HOMA-ß (ß±SE: 0.1331±0.0311; P=1.95×10-5) and GUTT-ISI (ß±SE: 0.0727±0.0229; P=0.0015). In males, N-MID was significantly correlated with HOMA-ß (ß±SE: 0.3439±0.0633; P=7.75×10-8), GUTT-ISI (ß±SE: 0.1601±0.0531; P=0.0027) and STU-1 (ß±SE: 0.2529±0.1033; P=0.0146). Significant associations were also detected between ß-CTX and HOMA-ß (ß±SE: 0.2736±0.0812; P=0.0009). This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.