[Protective effects of galacto-oligosaccharide and polydextrose on Caco-2 intestinal cell barrier injury model].

OBJECTIVE: To explore the protective effect of different ratios of galactose oligosaccharide(GOS) and polydextrose(PDX) on intestinal cell barrier damage model of Caco-2. METHODS: The same batch of Caco-2 cells were cultured to form a cell barrier model and randomly divided into damaged model group without calcium, calcium-containing blank control group(1.8 mmol/L Ca~(2+)), low-ratio/low-dose group(1.8 mmol/L Ca~(2+)+2 mg/mL GOS+2 mg/mL PDX) and low-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+4 mg/mL GOS+4 mg/mL PDX), low-ratio/high-dose group(1.8 mmol/L Ca~(2+)+8 mg/mL GOS+8 mg/mL PDX) and high-ratio/low-dose group(1.8 mmol/L Ca~(2+)+0.8 mg/mL GOS+3.2mg/mL PDX), high-ratio/medium-dose group(1.8 mmol/L Ca~(2+)+1.6 mg/mL GOS+6.4 mg/mL PDX), high-ratio/high-dose group(1.8 mmol/L Ca~(2+)+3.2mg/mL GOS+12.8 mg/mL PDX), a total of 8 groups, three parallel groups were performed in each group. The Trans Epithelial Electrical Resistance value and apparent permeability coefficient value of each group were determined after 4 d culture, and the morphology of tight junction proteins ZO-1, Occludin and Claudin-1 were observed by immunofluorescence method, and the expression levels of inflammatory related factors in each group were determined by protein microarray method. RESULTS: Compared with damaged model group, TEER ratio in calcium-containing blank control group was significantly increased(P<0.05), while Papp value was significantly decreased(P<0.05);Compared with calcium-containing blank control group, TEER ratio in low-ratio/medium-dose group and high-ratio/high-dose group was significantly increased(P<0.05) while Papp value was significantly decreased(P<0.05), and they could significantly down-regulate some inflammatory response related cytokines. The cell barrier was intact in all groups except for the compact junction protein structure in the model group. CONCLUSION: Compared with Ca~(2+) alone, the combination of two prebiotics can enhance the density of Caco-2 cell barrier and reduced the permeability of cell bypass. And it can significantly reduce the expression level of some inflammatory cytokines and effectively protect the intestinal cell barrier.

Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace.

Introduction: Brain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose. Methods: In this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated. Results: The results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy. Discussion: The MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets' learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.

Combination of Walnut Peptide and Casein Peptide alleviates anxiety and improves memory in anxiety mices.

Introduction: Anxiety disorders continue to prevail as the most prevalent cluster of mental disorders following the COVID-19 pandemic, exhibiting substantial detrimental effects on individuals' overall well-being and functioning. Even after a search spanning over a decade for novel anxiolytic compounds, none have been approved, resulting in the current anxiolytic medications being effective only for a specific subset of patients. Consequently, researchers are investigating everyday nutrients as potential alternatives to conventional medicines. Our prior study analyzed the antianxiety and memory-enhancing properties of the combination of Walnut Peptide (WP) and Casein Peptide (CP) in zebrafish. Methods and Results: Based on this work, our current research further validates their effects in mice models exhibiting elevated anxiety levels through a combination of gavage oral administration. Our results demonstrated that at 170 + 300 mg human dose, the WP + CP combination significantly improved performances in relevant behavioral assessments related to anxiety and memory. Furthermore, our analysis revealed that the combination restores neurotransmitter dysfunction observed while monitoring Serotonin, gamma-aminobutyric acid (GABA), dopamine (DA), and acetylcholine (ACh) levels. This supplementation also elevated the expression of brain-derived neurotrophic factor mRNA, indicating protective effects against the neurological stresses of anxiety. Additionally, there were strong correlations among behavioral indicators, BDNF (brain-derived neurotrophic factor), and numerous neurotransmitters. Conclusion: Hence, our findings propose that the WP + CP combination holds promise as a treatment for anxiety disorder. Besides, supplementary applications are feasible when produced as powdered dietary supplements or added to common foods like powder, yogurt, or milk.

The effects of Ascophyllum nodosum, Camellia sinensis-leaf extract, and their joint interventions on glycolipid and energy metabolism in obese mice.

Objectives: Obesity is often associated with glucolipid and/or energy metabolism disorders. Ascophyllum nodosum extract (seaweed extract, SE) and Camellia sinensis-leaf extract (tea extract, TE) have been reported to promote positive metabolic effects through different mechanisms. We investigated the effects of SE and TE on metabolic homeostasis in diet-induced obese mice and discussed their functional characteristics. Methods: Male C57BL/6J mice fed with high-fat diets for 8 weeks were established as obese models and subsequently divided into different intervention groups, followed by SE, TE, and their joint interventions for 10 weeks. Body weight and food intake were monitored. Fasting glucose and oral glucose tolerance tests were interspersed during the experiment. After the intervention, the effects on obesity control were assessed based on body composition, liver pathology section, blood lipids and glucose, respiratory exchange ratio (RER), energy expenditure (EE1, EE2, and EE3), inflammatory factors, lipid anabolism enzymes, and gut flora of the obese mice. Results: After continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower ~4.93 g, vs. HFD 38.02 g), peri-testicular fat masses (lower ~0.61 g, vs. HFD 1.92 g), and perirenal fat masses (lower ~0.21 g, vs. HFD mice 0.70 g). All interventions prevented diet-induced increases in plasma levels of glucose, adiponectin, leptin, and the inflammatory factors IL-1ß and TNF-α. The RER was modified by the interventions, while the rhythm of the RER was not. Blood lipids (total cholesterol, triglycerides, and LDL) decreased and were associated with lower lipid anabolism enzymes. In addition, the SE and TE interventions altered the structure and abundance of specific flora. Different interventions inhibited the growth of different genera positively associated with obesity (Escherichia-Shigella, Helicobacter, etc.) and promoted the growth of Akkermansia and Bacteroides, thus affecting the chronic inflammatory state. Conclusion: SE and TE both have synergistic effects on weight control and glucolipid metabolism regulation by improving insulin sensitivity and reducing lipid synthesis-related enzyme expression, whereas the combination of SE and TE (3:1) has a better effect on regulating energy metabolism and inhibiting chronic inflammation.

Effects of Poria cocos extract and protein powder mixture on glucolipid metabolism and rhythm changes in obese mice.

Herein, we explored the effects of Poria cocos extract, protein powder mixture, and their combined intervention on weight loss in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice were selected and fed a HFD for 8 weeks; obese mice that were successfully modeled were divided into modeling and five intervention groups, and given the corresponding treatment for 10 weeks. Body weight, fat, and muscle tissue, blood glucose, lipids, inflammatory factors, and other glucose and lipid metabolism-related indicators were measured to evaluate the effect of P. cocos and protein powder intervention on weight loss in obese mice. The body weight of the intervention group was reduced compared with the HFD group. Fat content of mice in F3PM group decreased significantly (p < .05). Levels of blood glucose, lipids, adiponectin, leptin, and inflammatory factors, including interleukin-1 ß and tumor necrosis factor- α showed improvement. Lipoprotein lipase (lower about 2.97 pg/ml, vs. HFD mice 10.65 mmoL/ml) and sterol regulatory element-binding transcription factor (lower about 1413.63 pg/ml, vs. HFD mice 3915.33 pg/ml) levels in liver tissue were decreased. The respiratory exchange rate (RER) of mice in the HFD and subject intervention groups had no circadian rhythm and was maintained at approximately 0.80. The protein powder mixture (PM) group had the lowest RER (p < .05), the P. cocos extract (FL) and F1PM groups had similar RER to the HFD group (p < .05), and the F2PM group had a higher RER than the HFD group (p < .05). And food intake and energy metabolism returned to circadian rhythm, with an increase in the dose of P. cocos extract, the feeding rhythms of F1PM, F2PM, and F3PM were closer to that of the normal diet (ND) group. Feeding intervention with P. cocos and protein powder improved fat distribution, glucolipid metabolism, and energy metabolism, with the combination of F3PM showing more diverse benefits.

Formula Milk Supplementation and Bone Acquisition in 4-6 Years Chinese Children: A 12-Month Cluster-Randomized Controlled Trial.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4-6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20-30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (-7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (-15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

[Fetal electrocardiogram signal extraction and analysis method combining fast independent component analysis algorithm and convolutional neural network].

Fetal electrocardiogram (ECG) signals provide important clinical information for early diagnosis and intervention of fetal abnormalities. In this paper, we propose a new method for fetal ECG signal extraction and analysis. Firstly, an improved fast independent component analysis method and singular value decomposition algorithm are combined to extract high-quality fetal ECG signals and solve the waveform missing problem. Secondly, a novel convolutional neural network model is applied to identify the QRS complex waves of fetal ECG signals and effectively solve the waveform overlap problem. Finally, high quality extraction of fetal ECG signals and intelligent recognition of fetal QRS complex waves are achieved. The method proposed in this paper was validated with the data from the PhysioNet computing in cardiology challenge 2013 database of the Complex Physiological Signals Research Resource Network. The results show that the average sensitivity and positive prediction values of the extraction algorithm are 98.21% and 99.52%, respectively, and the average sensitivity and positive prediction values of the QRS complex waves recognition algorithm are 94.14% and 95.80%, respectively, which are better than those of other research results. In conclusion, the algorithm and model proposed in this paper have some practical significance and may provide a theoretical basis for clinical medical decision making in the future.

Effects of Coix seed extract, Lactobacillus paracasei K56, and their combination on the glycolipid metabolism in obese mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism through different modes of action. We tested the effects of CSE, Lactobacillus paracasei K56, and their combination to determine whether they have synergistic effects on glycolipid metabolism of obese mice. We fed male C57BL/6J mice with high-fat diet for 8 weeks to establish an obesity model. The obesity mice were selected and divided into five groups: the model control group and four intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31-4.41 g, vs. HFD 42.25 g, p < 0.01), and epididymal (lower about 0.58-0.92 g, vs. HFD 2.50 g, p < 0.01) and perirenal fat content (lower about 0.24-0.42 g, vs. HFD 0.88 g, p < 0.05); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. K56 + CSE-combined intervention groups were more effective in lowering blood glucose, IL-1ß, and TNF-α levels than the CSE and K56 alone interventions. The content of fatty acid synthase and SREBP-1c protein in liver tissue was lower. The combination has synergistic effects on weight control, fat reduction, and blood glucose regulation by improving the chronic inflammatory state and reducing the content of lipid synthesis-related enzymes of obese mice, which can hinder chronic disease progression. PRACTICAL APPLICATION: Coix seed extract can be used in obese people to regulate abnormal glucose and lipid metabolism and delay the development of chronic diseases.

Effects of Coix Seed Extract, Bifidobacterium BPL1, and Their Combination on the Glycolipid Metabolism in Obese Mice.

Coix seed extract (CSE) and probiotics have been reported to regulate glycolipid metabolism via different modes of action. We tested the effects of CSE, Bifidobacterium BPL1, and their combination to determine their effects on glycolipid metabolism in obese mice. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. Obese mice were selected and divided into four groups: the model control group and three intervention groups. After 10 weeks of continuous gavage intervention, the mice in the intervention groups exhibited lower body weight (lower about 2.31 g, vs. HFD mice 42.23 g) and epididymal (lower about 0.37 g, vs. HFD mice 2.5 g) and perirenal fat content (lower about 0.47 g, vs. HFD mice 0.884 g); decreased fasting blood glucose, total cholesterol, triglycerides, and VLDL; and increased HLDL, respiratory exchange ratio, energy expenditure, and amount of exercise performed. CSE, BPL1 and their combination can effectively control the weight gain in obese mice, reduce fat content, and regulate blood lipids and abnormal blood sugar. These results may be related to reduce the chronic inflammatory states, improve energy metabolism, exercise, relieve insulin sensitivity, and reduce lipid synthesis via the intervention of CSE, BPL1 and their combination. Compared with the single use of CSE alone, the combination of CSE + BPL1 can better exert the regulation function of intestinal flora, and change in the abundance of bacteria that could improve the level of inflammatory factors, such as increasing Bifidobacterium, reducing Lactococcus. Compared with the use of BPL1 alone, the combination of CSE and BPL1 can better regulate pancreatic islet and improve blood sugar. CSE may act directly on body tissues to exert anti-inflammatory effects. BPL1 and CSE + BPL1 may improve the structure and function of the intestinal flora, and reduce tissue inflammation.

Fetal Electrocardiogram Signal Extraction Based on Fast Independent Component Analysis and Singular Value Decomposition.

Fetal electrocardiograms (FECGs) provide important clinical information for early diagnosis and intervention. However, FECG signals are extremely weak and are greatly influenced by noises. FECG signal extraction and detection are still challenging. In this work, we combined the fast independent component analysis (FastICA) algorithm with singular value decomposition (SVD) to extract FECG signals. The improved wavelet mode maximum method was applied to detect QRS waves and ST segments of FECG signals. We used the abdominal and direct fetal ECG database (ADFECGDB) and the Cardiology Challenge Database (PhysioNet2013) to verify the proposed algorithm. The signal-to-noise ratio of the best channel signal reached 45.028 dB and the issue of missing waveforms was addressed. The sensitivity, positive predictive value and F1 score of fetal QRS wave detection were 96.90%, 98.23%, and 95.24%, respectively. The proposed algorithm may be used as a new method for FECG signal extraction and detection.

Nutrient combinations exhibit universal antianxiety, antioxidant, neuro-protecting, and memory-improving activities.

Anxiety disorders are the most common mental disorders and, without proper treatment, may lead to severe conditions: e.g., somatic disorders or permanent damage to central nervous system. Although there are drugs in clinical trials, this study focuses on exploring the efficacy of nutrients in treating these diseases. We built different zebrafish models and screened several nutrient combinations for their antianxiety, antioxidant, neuro-protecting, and memory-improving activities. Our results showed that the combinations of nutrients (e.g., Walnut Peptides + Theanine at 14.2 + 33.3 µg/ml) have similar or better activities than the positive control drugs. In addition, we discovered that the effects of the nutrients in the above four aspects were universal and highly related. This study is noteworthy as it suggested that nutrients could be healthier and greener drug alternatives and provide similar or better universal treatments for anxiety and related conditions.

The combined use of gamma-aminobutyric acid and walnut peptide enhances sleep in mice.

BACKGROUND: γ-aminobutyric acid (GABA) is a naturally occurring non-protein amino acid in the nervous system and has a wide range of physiological functions in the body. Walnut peptide (WP) contains high levels of arginine, aspartic acid, and glutamate, and has been shown to improve cognitive deficits and memory impairment in mice, while restoring antioxidant enzyme levels and reducing brain inflammatory mediators. METHODS: This study investigated the effects of GABA and WP, either alone or in combination, on sleep disturbances in mice. The pentobarbital-prolonged sleep test, pentobarbital-threshold sleep test, and barbital-induced sleep test were conducted to assess the effects of GABA and WP on sleep quality by gavage for 30 days as follows: GABA (102.25 mg/kg), WP (102.25 mg/kg), GABA (33.95, 102.25, 306.75 mg/kg)/WP (102.25 mg/kg) mixture. Furthermore, neurotransmitter tests were performed using mice brain tissue to investigate the possible mechanisms of GABA and WP on sleep status. RESULTS: The results showed that the combined use of GABA and WP significantly increased sleep duration compared with single administration of either WP or GABA. Increasing doses of GABA in mice treated with combined GABA and WP elevated the sleep rate to 50.00%, 64.28%, and 64.28%, respectively, compared to mice treated with GABA alone (35.71%) or mice treated with WP alone (28.57%). In mice that received a combination of GABA and WP orally, the latency time was significantly decreased after 30 days compared to control mice (P<0.05). Additionally, in mice treated with GABA, WP, or the combination of GABA and WP, the concentrations of GABA and acetylcholine (Ach) in the brain were significantly elevated and the concentration of serotonin (5-HT) was decreased compared to untreated mice. CONCLUSIONS: These results demonstrated that the combined administration of GABA and WP could prolong the sleep duration, increase sleep rate, and shorten the sleep latency more effectively than the administration of either GABA or WP alone. The mechanisms of action may be related to the regulation of neurotransmitters in the brain tissue by the combination of GABA and WP.

L-theanine and Neumentix mixture improves sleep quality and modulates brain neurotransmitter levels in mice.

BACKGROUND: L-theanine (L-THE), a natural amino acid found in green tea, has been shown to improve anxiety and sleep. Neumentix proprietary spearmint extract (PSE), which is commonly found in beverage flavoring a pharmaceutical, also has a wide range of health benefits, including cognitive performance improvement. METHODS: Four experiments tested the effects of L-THE and PSE on sleep: a direct sleeping test, pentobarbital-induced sleeping test, sub-hypnotic pentobarbital-induced sleeping test, and sodium barbital-induced sleeping test. Presence of neurotransmitters in brain tissue was detected by liquid chromatography mass spectroscopy (HP LC-MS) during these studies. RESULTS: Pentobarbital-induced sleeping and sodium barbital-induced sleeping tests examined the potential effect of L-THE/PSE mixture on synergistic sleep, while neurotransmitter levels in the brain were determined by the high performance liquid chromatography/mass spectroscopy (HPLC/MS) method. L-THE and L-THE/PSE mixture showed increased sleep duration and shortened sleep latency when co-administrated with pentobarbital or sodium barbital. The mixture also increased sleeping rate when co-administrated with the pentobarbital at sub-hypnotic dose. Additionally, the L-THE, PSE and L-THE/PSE mixture significantly increased the concentrations of acetylcholine (Ach), γ-aminobutyric acid (GABA), and decreased the concentration of serotonin (5-HT) in the brain. CONCLUSIONS: These data demonstrated that L-THE/PSE mixture regulates sleep disorders via the GABA receptor and neurotransmitter systems.

Network analysis of population flow among major cities and its influence on COVID-19 transmission in China.

Large-scale and diffuse population flow amplifies the localized COVID-19 outbreak into a widespread pandemic. Network analysis provides a new methodology to uncover the topology and evolution of the population flow and understand its influence on the early dynamics of COVID-19 transmission. In this paper, we simulated 42 transmission scenarios to show the distribution of the COVID-19 outbreak across China. We predicted some original (Guangzhou, Shanghai, Shenzhen) had higher total aggregate population outflows than Wuhan, indicating larger spread scopes and faster growth rates of COVID-19 outbreak. We built an importation risk model to identify some major cities (Dongguan and Foshan) with the highest total importation risk values and the highest standard deviations, indicating the core transmission chains (Dongguan-Shenzhen, Foshan-Guangzhou). We built the population flow networks to analyze their Spatio-temporal characteristics and identify the influential sub-groups and spreaders. By removing different influential spreaders, we identified Guangzhou can most influence the network's topological characteristics, and some major cities' degree centrality was significantly decreased. Our findings quantified the effectiveness of travel restrictions on delaying the epidemic growth and limiting the spread scope of COVID-19 in China, which helped better derive the geographical COVID-19 transmission related to population flow networks' structural features.

Building the COVID-19 Collaborative Emergency Network: a case study of COVID-19 outbreak in Hubei Province, China.

The purpose of this study is to uncover and optimize the structure and performance of the collaborative network that emerged in response to COVID-19 in Hubei Province, China. This study reconstructed the Hubei Public Health Emergency Response Network as the actual collaborative network and built COVID-19 Collaborative Emergency Network as a planned task-oriented collaborative network. Based on the data sets of the inter-organizational collaboration collected from the content analysis, this study explored the core tasks of the participating actors and their relationships during the COVID-19 emergency response, and built six sub-networks to accomplish six core tasks. Network analysis was used with the Pajek software to compare the structural characteristics and performance of the planned network with the actual one and six sub-networks, and identified the central actors, key bridges, and brokers in networks and sub-networks separately. Findings suggested that COVID-19 Collaborative Emergency Network had a more tightly, central, and connective structure than Hubei Public Health Emergency Response Network, because it had more participating actors (i.e., databases and AI systems), more powerful and strong collaborative relationships with research institutions and non-profit organizations. With practical-based recommendations for inter-organizational collaboration, this study concluded that COVID-19 Collaborative Emergency Network could significantly enhance the local capacity of Hubei Province for emergency collaboration, which provided insights for building and optimizing COVID-19 collaborative networks in other provinces of China, even other countries.

Dramatic Enhancement of Power Conversion Efficiency in Polymer Solar Cells by Conjugating Very Low Ratio of Triplet Iridium Complexes to PTB7.

Various low ratios of triplet iridium complexes (0, 0.5, 1, 1.5, 2.5, and 5 mol%) are conjugated to the backbone of the famous champion donor polymer PTB7. At the same conditions, the power conversion efficiency for polymer containing 1% of Ir increases by 45%, 39%, and 31% in three batches of devices compared with control Ir-free PTB7.