Ginsenoside RG1-induced mesenchymal stem cells alleviate diabetic cardiomyopathy through secreting exosomal circNOTCH1 to promote macrophage M2 polarization.

Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.

Gestational Diabetes Mellitus Remodels the Fetal Brain Fatty Acid Profile Through Placenta-Brain Lipid Axis in C57BL/6J Mice.

BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.

Effects of Gestational Diabetes Mellitus and Selenium Deficiency on the Offspring Growth and Blood Glucose Mechanisms of C57BL/6J Mice.

This study aimed to explore the effects and mechanisms of maternal gestational diabetes mellitus (GDM) and selenium (Se) deficiency on the growth and glucose metabolism of offspring. Female C57BL/6J mice were divided into four groups as follows: a control group, a GDM group, a Se deficiency group, and a GDM with Se deficiency group. GDM animal models were established via S961. Pregnant mice fed their offspring until weaning. Then, offspring continued to be fed with a basic diet until adulthood. Body weight and fasting blood glucose were measured weekly. Se content, oxidative stress indicators, and the protein expression of the PI3K/Akt signaling pathway were detected. GDM increased susceptibility to obesity in lactating offspring, with gender differences observed in adult offspring. The effect of Se deficiency on SOD activity only appeared in female offspring during adulthood but was shown in male offspring during weaning though it disappeared during adulthood. GDM and Se deficiency increased the risk of abnormal glucose metabolism in female offspring from weaning to adulthood but gradually decreased in male offspring. The influence on the expression of PI3K/Akt signaling pathway-related proteins showed the same trend. GDM and Se deficiency affected the growth and glucose metabolism of offspring through oxidative stress and PI3K/Akt signaling pathway-related proteins, and gender differences existed.

Structural characterization and anti-oxidation activity of pectic polysaccharides from Swertia mileensis.

In this study, we isolated the pectic polysaccharide WSMP-A2b (37 kDa) from the stems and leaves of Swertia mileensis, and we investigated its compositional/structural features and antioxidant activity. FT-IR, NMR, monosaccharide composition, enzymatic hydrolysis and methylation analyses indicated that WSMP-A2b is composed of rhamnogalacturonan I (RG-I), rhamnogalacturonan II (RG-II) and homogalacturonan (HG) domains with mass ratios of 2.1:1.0:2.2. The RG-I domain is primarily substituted with α-L-1,5-arabinan and type II arabinogalactan (AG-II) side chains, as well as minor contributions of ß-D-1,4-galactan and/or type I arabinogalactan (AG-I) side chains. The HG domain was released in the form of un-esterified and partly methyl-esterified and/or acetyl-esterified oligogalacturonides with a 1 to 7 degree of polymerization after endo-polygalacturonase degradation. WSMP-A2b showed stronger antioxidant activity in vitro, in part this might due to the presence of galacturonic acid (GalA). In addition, WSMP-A2b exerted a protective effect on tert-butyl hydroperoxide (tBHP)-induced oxidative stress in INS-1 cells by reducing reactive oxygen species (ROS) production and increasing the glutathione/oxidized glutathione (GSH/GSSG) ratio. Our results provide crucial structural information on this pectic polysaccharide from Swertia mileensis, thus prompting further investigation into its structure-activity relationship.

Should the trough concentration of vancomycin be abandoned in therapeutic drug monitoring? A multicentre, retrospective study of critically ill patients without any form of dialysis.

BACKGROUND: There are conflicts in guideline recommendations about the value and range of vancomycin trough concentration during therapeutic drug monitoring (TDM). This multicentre, retrospective study was conducted to explore the usefulness of trough concentration in specific patients who were critically ill and without any form of dialysis. METHODS: Patient information from five centres was retrospectively collected and the 24-hour area under the curve (AUC) was estimated by a Bayesian method. Patients were categorised into four groups according to trough concentration: < 10, 10-15, 15-20 and > 20 mg/L, and the corresponding AUC was analysed. A multivariable logistic regression model was used to investigate the relationship between trough concentration and AUC. RESULTS: Overall, 645 trough concentrations available from 416 patients were included in this study. The results indicated that the AUC was always < 400 mg/L∙h or > 600 mg/L∙h in the < 10 or > 20 mg/L groups, whereas the ratios of vancomycin AUC target attainment (400-600 mg/L∙h) were 48.8% and 92.3% in the 10-15 mg/L and 15-20 mg/L groups, respectively. Augmented renal clearance, low daily dose and non-q12h administration were found to be independent risk factors associated with AUC target non-attainment for patients with trough concentrations of 10-15 mg/L. CONCLUSION: Vancomycin trough concentration is a good marker of AUC for critically ill adults without any form of dialysis. However, AUC-guided TDM may be needed for patients with trough concentrations of 10-15 mg/L, especially for those with risk factors.

Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a malignancy with a hidden onset, high metastasis recurrence rate, and poor prognosis. Research on effective drugs for ICC is important for improving the prognosis of patients in the clinic. Brusatol is a quassinoid extracted from the seeds of Brucea sumatrana and has been shown to have the potential to inhibit tumor metastasis and proliferation. There has been no scientific research on the therapeutic effect of brusatol on ICC. Our study offers a novel strategy for the therapy of ICC. PURPOSE: Explore effects of brusatol treatment on ICC and clarify the possible mechanism. STUDY DESIGN: Various cell functional experiments and basic experimental techniques were applied to ICC cell lines to explore the influences of brusatol on ICC cells; this conclusion was further verified in animal models. METHODS: The anti-cancer effects of the drug on the cell, protein, and RNA level were verified by cell functional experiments, WB blotting and transcriptome sequencing experiments, respectively. Finally, the experimental results were verified using subcutaneous tumor experiments in nude mice. RESULTS: The consequences exhibited that the levels of epithelial markers of ICC cells increased after brusatol treatment, and the levels of interstitial indicators decreased, suppressing the epithelial-mesenchymal transition (EMT) process. Brusatol inhibited proliferation, induced apoptosis, and suppressed the migration and invasion abilities of Hucc-T1 and RBE oncocytes via activating PI3K/Akt pathway. It also suppressed the growth of Hucc-T1 xenografts in nude mice. CONCLUSION: Brusatol inhibits the proliferation and EMT process in ICC oncocytes by the PI3K/Akt pathway and promotes apoptosis in oncocytes.

Gating Attractor Dynamics of Frontal Cortex Under Acupuncture via Recurrent Neural Network.

Acupuncture can regulate the functions of human body and improve the cognition of brain. However, the mechanism of acupuncture manipulations remains unclear. Here, we hypothesis that the frontal cortex plays a gating role in information routing of brain network under acupuncture. To that end, the gating effect of frontal cortex under acupuncture is analyzed in combination with EEG data of acupuncture at Zusanli acupoints. In addition, recurrent neural network (RNN) is used to reproduce the dynamics of frontal cortex under normal state and acupuncture state. From low-dimensional view, it is shown that the brain networks under acupuncture state can show stable attractor cycle dynamics, which may explain the regulation effect of acupuncture. Comparing with different manipulations, we find that the attractor of low-dimensional trajectory varies under different frequencies of acupuncture. Besides, a strip gated band of neural dynamics is found by changing the frequency of stimulation and excitatory-inhibitory balance of network. This reverse engineering of brain network indicates that the differences among acupuncture manipulations are caused by interaction and separation in the neural activity space between attractors that encode acupuncture function. Consequently, our results may provide help for quantitative analysis of acupuncture, and benefit for the clinical guidance of acupuncture clinicians.

Latent Characteristics and Neural Manifold of Brain Functional Network Under Acupuncture.

Acupuncture can regulate the cognition of brain system, and different manipulations are the keys of realizing the curative effect of acupuncture on human body. Therefore, it is crucial to distinguish and monitor the different acupuncture manipulations automatically. In this brief, in order to enhance the robustness of electroencephalogram (EEG) detection against noise and interference, we propose an acupuncture manipulation detecting framework based on supervised ISOMAP and recurrent neural network (RNN). Primarily, the low-dimensional embedding neural manifold of brain dynamical functional network is extracted via the reconstructed geodetic distance. It is found that there exhibits stronger acupuncture-specific reconfiguration of brain network. Besides, we show that the distance travel along this manifold correlates strongly with changes of acupuncture manipulations. The low-dimensional brain topological structure of all subjects shows crescent-like feature when acupuncturing at Zusanli acupoints, and fixed-points are varying under diverse manipulation methods. Moreover, Takagi-Sugeno-Kang (TSK) classifier is adopted to identify acupuncture manipulations according to the nonlinear characteristics of neural manifolds. Compared with different classifier, TSK can further improve the accuracy of manipulation identification at 96.71%. The results demonstrate the effectiveness of our model in detecting the acupuncture manipulations, which may provide neural biomarkers for acupuncture physicians.

The association between serum selenium level and gestational diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: The relationship between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The purpose is to update and summarize previous studies to understand the relationship in more detail. METHODS: PubMed, The Cochrane Library, EMBASE, Web of science, CNKI, WANFANG DATA and Cqvip were searched for studies published up to 3 September 2021. The random-effects model was used to measure the combined estimation. The overall effect was reported in a standard mean difference (SMD) and 95% confidence interval (95% CI). All data were analysed by Review Manager 5.4. RESULTS: Twenty-seven studies involving 1588 patients with GDM and 2450 healthy pregnant women contributed to this meta-analysis. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.29; 95% CI: -1.60 to -0.97, p < 0.00001). Subgroup analyses showed that such trend was consistent within the non-European population (Asia: SMD = -1.44; 95% CI: -1.79 to -1.08, p < 0.00001; Africa: SMD = -2.62; 95% CI: -4.50 to -0.74, p = 0.006) and in the second and third trimesters (the second trimester: SMD = -1.41; 95% CI: -1.82 to -0.99, p < 0.00001; the third trimester: SMD = -1.54; 95% CI: -2.09 to -0.98, p < 0.00001), but not within the European population (SMD = -0.47; 95% CI: -1.09 to 0.16, p = 0.14) or in the first trimester (SMD = -0.52; 95% CI: -1.13 to 0.10, p = 0.10). CONCLUSIONS: This meta-analysis showed that the serum selenium level of patients with GDM was lower than that in healthy pregnant women, especially within the non-European population and in the second and third trimesters.

Intensity-Varied Closed-Loop Noise Stimulation for Oscillation Suppression in the Parkinsonian State.

This work explores the effectiveness of the intensity-varied closed-loop noise stimulation on the oscillation suppression in the Parkinsonian state. Deep brain stimulation (DBS) is the standard therapy for Parkinson's disease (PD), but its effects need to be improved. The noise stimulation has compelling results in alleviating the PD state. However, in the open-loop control scheme, the noise stimulation parameters cannot be self-adjusted to adapt to the amplitude of the synchronized neuronal activities in real time. Thus, based on the delayed-feedback control algorithm, an intensity-varied closed-loop noise stimulation strategy is proposed. Based on a computational model of the basal ganglia (BG) that can present the intrinsic properties of the BG neurons and their interactions with the thalamic neurons, the proposed stimulation strategy is tested. Simulation results show that the noise stimulation suppresses the pathological beta (12-35 Hz) oscillations without any new rhythms in other bands compared with traditional high-frequency DBS. The intensity-varied closed-loop noise stimulation has a more profound role in removing the pathological beta oscillations and improving the thalamic reliability than open-loop noise stimulation, especially for different PD states. And the closed-loop noise stimulation enlarges the parameter space of the delayed-feedback control algorithm due to the randomness of noise signals. We also provide a theoretical analysis of the effective parameter domain of the delayed-feedback control algorithm by simplifying the BG model to an oscillator model. This exploration may guide a new approach to treating PD by optimizing the noise-induced improvement of the BG dysfunction.

Vanillin downregulates NNMT and attenuates NNMT­related resistance to 5­fluorouracil via ROS­induced cell apoptosis in colorectal cancer cells.

Chemoresistance is the main cause of poor prognosis in colorectal cancer (CRC). Nicotinamide N­methyltransferase (NNMT) is a metabolic enzyme that is upregulated in various tumor types. It has been reported that NNMT inhibits apoptosis and enhances resistance to 5­fluorouracil (5­Fu) via inhibition of the apoptosis signal regulating kinase 1 (ASK1)­p38 MAPK pathway in CRC cells. A natural product library was screened, and it was found that vanillin, also known as 4­hydroxy­3­methoxybenzaldehyde, a plant secondary metabolite found in several essential plant oils, mainly Vanilla planifolia, Vanilla tahitensis, and Vanilla pompon, may be a promising anticancer compound targeted to NNMT. The aim of the present study was to explore the effect of vanillin on promoting apoptosis and attenuating NNMT­induced resistance to 5­Fu in CRC. Lentiviral vectors of short hairpin RNA and small interfering RNA were transfected into HT­29 cells to construct NNMT­knockdown HT­29 cell lines. Vectors containing an open reading frame of NNMT were stably transfected into SW480 cells to induce NNMT overexpression in SW480 cell lines. Vanillin was found to inhibit the mRNA and protein expression levels of NNMT following the inhibition of NNMT activity in HT­29 cell lines. Vanillin was able to reverse NNMT­induced increased cell proliferation, decreased cell apoptosis and resistance to 5­Fu by inhibiting NNMT expression. Furthermore, it increased cell apoptosis by activating the ASK1­p38 MAPK pathway, which could be inhibited by NNMT. In addition, vanillin increased cell apoptosis by promoting mitochondrial damage and reactive oxygen species. In vivo, the combination of vanillin with 5­Fu yielded a notable synergy in inhibiting tumor growth and inducing apoptosis. Considering that vanillin is an important flavor and aromatic component used in foods worldwide, vanillin is deemed to be a promising anticancer candidate by inhibiting NNMT and may attenuate NNMT­induced resistance to 5­Fu in human CRC therapy with few side effects.

Protective Effects of the King Oyster Culinary-Medicinal Mushroom, Pleurotus eryngii (Agaricomycetes), Polysaccharides on ß-Amyloid-Induced Neurotoxicity in PC12 Cells and Aging Rats, In Vitro and In Vivo Studies.

Pleurotus eryngii (PE) contains polysaccharides and vitamins, and has been reported to have antidepression properties. P. eryngii polysaccharides (PEP) are one of the main components. Modulation of ß-amyloid-induced neurotoxicity has emerged as a possible therapeutic approach to ameliorate the onset and progression of Alzheimer's disease (AD). The present study aimed to evaluate the protective effect of PEP on ß-amyloid-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells and aging rats. After 28 weeks' treatment, exposure of PC12 cells to P. eryngii polysaccharides significantly elevated cell viability, decreased the levels of intracellular calcium, and attenuated the ß-amyloid-mediated cell apoptosis. In aging rats, P. eryngii polysaccharides could decrease the production of APP in the brain by an action that is associated with a lowering of the iNOS, and COX-2 level. Our findings indicated that P. eryngii polysaccharides had potential neuroprotective actions against ß-amyloid-induced neurotoxicity, which might be through modulating calcium channels, or downstream molecules involved in inflammation.

Effects of dietary crude protein level and N-carbamylglutamate supplementation on nutrient digestibility and digestive enzyme activity of jejunum in growing pigs.

Three experiments were conducted to investigate the effects of dietary crude protein (CP) level and N-carbamylglutamate (NCG) supplementation on apparent total tract digestibility (ATTD) and ileal digestibility of nutrients and digestive enzyme activity of jejunum in growing pigs. In experiment 1, 10 Duroc × Landrace × Yorkshire barrows (initial BW: 48.7 kg) were allotted to a three-period switchback design with five experimental diets and two replicate pigs per diet in each period. Diets were categorized as high CP (HP, 18% CP), moderate low CP (MLP, 15% CP), very low CP (VLP, 12% CP), and MLP and VLP with 0.1% NCG supplementation. Feces and urine were collected from day 6 to day 11 after a 5-d adaptation period. The DE, ME, and ATTD of GE, OM, CP, NDF, ADF, and P decreased (P < 0.01) with a reduction of dietary CP, but no effect of dietary treatments on pig daily N retention was detected. The NCG supplementation increased (P < 0.01) DE and ATTD of ADF of the VLP diet. In experiment 2, 10 jejunal-cannulated Duroc × Landrace × Yorkshire barrows (initial BW: 44.5 kg) were fed five diets for three periods as experiment 1. Jejunal fluid was collected on days 6 and 8 after a 5-d adaptation period. The digestive enzymes activity was not affected by dietary CP level, except for α-amylase, for which there was a decrease (P < 0.01) in pigs fed VLP diets compared to HP and MLP diets. In experiment 3, 12 ileal-cannulated Duroc × Landrace × Yorkshire barrows (initial BW: 46.7 kg) were allotted to a three-period switchback design with six diets and two replicate pigs per diet in each period. The six experimental diets consisted of five experimental diets as experiment 1 and one N-free diet. Ileal digesta was collected from day 6 to day 8 after a 5-d adaptation period. Results indicated that apparent ileal digestibility (AID) of CP and P and ileal digestibility of Arg, His, Ile, Leu, Phe, and all dispensable AA, except Pro, decreased (P < 0.01) in pigs fed VLP diet compared to HP and MLP diets, but AID of GE, OM, EE, NDF, and ADF were not affected. The supplementation of NCG in the VLP diet increased (P < 0.01) the AID of CP and ileal digestibility of Arg, His, Leu, Phe, Val, Ser, and Tyr. In conclusion, reducing dietary CP level decreased nutrient digestibility, but improved the efficiency of dietary N utilization and reduced N emission. Moderate reduction of dietary CP level had a minimal effect on nutrient digestibility and digestive enzyme activity. Additionally, NCG supplementation plays a beneficial effect on nutrient digestion only if the dietary CP level is extremely lowered.

Modulation Effect of Acupuncture on Functional Brain Networks and Classification of Its Manipulation With EEG Signals.

Acupuncture manipulation is the key of Chinese medicine acupuncture therapy. In clinical practice, different acupuncture manipulations are required to achieve different therapeutic effects, which means it is crucial to distinguish different acupuncture manipulations. In this paper, we proposed a classification framework for different acupuncture manipulations, which employed the graph theory and machine learning method. Multichannel EEG signals evoked by acupuncture at "Zusanli" acupoint were recorded from healthy humans by two acupuncture manipulations: twirling-rotating (TR) and lifting-thrusting (LT). Phase locking value was used to estimate the phase synchronization of pair-wise EEG channels. It was found that acupunctured by TR manipulation exhibit significantly higher synchronization degree than acupunctured by LT manipulation. With the construction of functional brain network, the topological features of graph theory were extracted. Taken the network features as inputs, machine learning classifiers were established to classify acupuncture manipulations. The highest accuracy can achieve 92.14% with support vector machine. By further optimizing the network features utilized in machine learning classifiers, it was found that the combination of node betweenness and small world network index is the most effective factor for acupuncture manipulations classification. These findings suggested that our approach provides new ideas for automatically identify acupuncture manipulations from the perspective of functional brain networks and machine learning methods.

Effects of L-lysine·H2SO4 product on the intestinal morphology and liver pathology using broiler model.

BACKGROUND: Lysine is used widely in livestock production due to the shortage of feed protein resources. L-lysine·H2SO4 contains L-lysine sulphate as well as fermentation co-products which contain other amino acids and phosphorus. However, there are few articles about L-lysine·H2SO4 product regarding intestinal morphology and liver pathology of broiler chickens. In this article, we focus on the absorption and metabolism of L-lysine·H2SO4 revealed in the variation of intestinal morphology and liver pathology to determine the tolerance of chicks for L-lysine·H2SO4. METHODS: To evaluate the tolerance of broilers for L-lysine·H2SO4, 240 one day old broilers were allocated randomly to one of five dietary treatments which included corn-soybean diets containing 0, 1%, 4%, 7% or 10% L-lysine·H2SO4 (L-lysine content = 55%). RESULTS: Supplementation of 1% L-lysine·H2SO4 in the diet had no negative effects. However, 4%, 7% or 10% L-lysine·H2SO4 supplementation produced negative responses on broiler performance, carcass characteristics, blood biochemistry, and particularly on intestinal morphology and liver pathology compared with broilers fed the control diet. CONCLUSION: Our results show that supplementation with 1% L-lysine·H2SO4 had no negative effects on performance, carcass characteristics, blood biochemistry, intestinal morphology and liver pathology in broilers, but supplementation with 4%, 7% or 10% L-lysine·H2SO4 produced a negative response, particularly with respect to intestinal morphology and liver pathology.

Modulation of Spectral Power and Functional Connectivity in Human Brain by Acupuncture Stimulation.

Acupuncture, as an external stimulation, can produce clinical effects via the central nervous system. In order to investigate the modulatory efficacy of acupuncture on brain activity, multichannel EEG signals evoked by acupuncture at "Zusanli" acupoint were recorded from healthy humans in three states: pre-acupuncture, acupuncture, and post-acupuncture. Power spectral density is first used to analyze the EEG power change during acupuncture process. It is found that EEG power significantly increased in the delta and alpha bands under acupuncture and high power level remained in alpha band after acupuncture. Then, we calculated phase lag index to quantify the phase synchronization of pair-wise channels. In acupuncture state, delta and alpha bands exhibit significantly higher synchronization degree than pre-acupuncture state. Additionally, post-effect of acupuncture can be observed in alpha band as high synchronization degree remains in post-acupuncture state. Moreover, functional brain networks converted from synchronization matrix in each band are reconstructed. Acupuncture increases long-range connections between left and right hemispheres and changes the position of main nodes. Graph theory metrics are extracted to explore the change of functional connectivity in different states. The result shows the functional networks in delta and alpha bands are small world networks (SWN) and acupuncture improves the SWN efficiency of functional network.

Colletotrilactam A-D, novel lactams from Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla.

Four novel lactams, colletotrilactam A-D (1-4), along with six known compounds (5-10) were isolated from the culture broth of Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla. The structures of these compounds were elucidated by comprehensive NMR spectroscopy. Isolates were tested for monoamine oxidase (MAO) inhibitory activity and compound 9 showed potent MAO inhibitory activity with IC50 value of 8.93±0.34µg/mL, when the IC50 value of iproniazid as a standard was 1.80±0.5µg/mL.

Reconstruction of neuronal input through modeling single-neuron dynamics and computations.

Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is.

Closed-Loop Control of Tremor-Predominant Parkinsonian State Based on Parameter Estimation.

A significant feature of Parkinson's disease (PD) is the inability of the thalamus to respond faithfully to sensorimotor information from the cerebral cortex. This may be the result of abnormal oscillations in the basal ganglia (BG). Deep brain stimulation (DBS) is regarded as an effective method to modulate these pathological brain rhythmic activities. However, the selection of DBS parameters is challenging because the mechanism is not well understood. This work proposes the design of a closed-loop control strategy to automatically adjust the parameters of a DBS waveform based on a computational model. By estimating the synaptic input from BG to the thalamic neuron model as feedback variable, we designed and compared various control algorithms to counteract the effects of pathological oscillatory inputs. We then obtained optimal DBS parameters to modulate the tremor-predominant Parkinsonian state. We showed that even a simple proportional controller provides higher fidelity of thalamic relay of sensorimotor information and lower energy expenditure, as compared with classical open-loop DBS. Integral action further enhances DBS performance. Additionally, a positive bias voltage further improves the relay ability of the thalamus with decreased stimulation energy expenditure. These findings were conducive to the development of a more effective DBS to further improve the treatment of the PD.