Experimental recordings in hippocampal slices indicate that astrocytic dysfunction may cause neuronal hyper-excitation or seizures. Considering that astrocytes play important roles in mediating local ...uptake and spatial buffering of K+ in the extracellular space of the cortical circuit, we constructed a novel model of an astrocyte-neuron network module consisting of a single compartment neuron and 4 surrounding connected astrocytes and including extracellular potassium dynamics. Next, we developed a new model function for the astrocyte gap junctions, connecting two astrocyte-neuron network modules. The function form and parameters of the gap junction were based on nonlinear regression fitting of a set of experimental data published in previous studies. Moreover, we have created numerical simulations using the above single astrocyte-neuron network module and the coupled astrocyte-neuron network modules. Our model validates previous experimental observations that both Kir4.1 channels and gap junctions play important roles in regulating the concentration of extracellular potassium. In addition, we also observe that changes in Kir4.1 channel conductance and gap junction strength induce spontaneous epileptic activity in the absence of external stimuli.
This study investigated the effects of Bacillus subtilis HW2 on the growth performance, immune response, endoplasmic reticulum (ER) stress, and intestinal health in broilers with necrotic enteritis. ...Three hundred 1-day-old male Cobb 500 broilers (33.88 ± 2.34 g) were randomly allocated to 5 groups including non-infected control (NC group), basal diet + necrotic enteritis challenge (NE group), basal diet + 1 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (L-Pro group), basal diet + 5 × 106 CFU/g B. subtilis HW2 + necrotic enteritis challenge (M-Pro group), and basal diet + 1 × 107 CFU/g B. subtilis HW2 + necrotic enteritis challenge (H-Pro group), with 6 replicates per group. All broilers except NC group were orally given with sporulated coccidian oocysts at day 14 and Clostridium perfringens from days 19 to 21. Results showed that L-Pro and M-Pro groups improved growth performance and intestinal morphology in necrotic enteritis-challenged broilers, and L-Pro, M-Pro, and H-Pro groups improved intestinal barrier function and immune response and decreased ER stress in necrotic enteritis-challenged broilers. Analysis of the gut microbiota revealed that L-Pro group increased the abundances of Alistipes, Coprobacter, Barnesiella, and Limosilactobacillus, decreased Erysipelatoclostridium abundance on day 42 in necrotic enteritis-challenged broilers. M-Pro group increased Turicibacter abundance on day 28 and the abundances of Alistipes, Barnesiella, and Limosilactobacillus on day 42 in necrotic enteritis-challenged broilers. H-Pro group decreased Romboutsia abundance on day 28 and unidentified_Clostridia abundance on day 42 in necrotic enteritis-challenged broilers. Analysis of short-chain fatty acids (SCFAs) revealed higher isobutyric acid and isovaleric acid levels in L-Pro and M-Pro groups than NE group. Correlation analysis revealed the correlations between the biochemical parameters and gut microbiota as well as SCFAs, especially Romboutsia, Barnesiella, Coprobacter, isobutyric acid, and isovaleric acid. Overall, our results indicated that B. subtilis HW2 supplementation could ameliorate necrotic enteritis infection-induced gut injury. The optimal dietary supplementation dosage of Bacillus subtilis HW2 was 5 × 106 CFU/g.
To assess the diagnostic value of the Copenhagen index for ovarian malignancy.
PubMed, Web of Science, the Cochrane Library, Embase, CBM, CNKI, and WanFang databases were searched throughout June ...2021. Statistical analyses were performed using Stata 12, Meta-DiSc, and RevMan 5.3. The pooled sensitivity, specificity, and diagnostic odds ratio were calculated, the summary receiver operating characteristic curve was drawn, and the area under the curve was calculated.
Ten articles, including 11 studies with a total of 5266 patients, were included. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.82 95% CI (0.80-0.83), 0.88 95% CI (0.87-0.89), and 57.31 95% CI (32.84-100.02), respectively. The area under the summary receiver operating characteristics curve and the Q index were 0.9545 and 0.8966, respectively.
Our systematic review shows that the sensitivity and specificity of the Copenhagen index are high enough for it to be used in a clinical setting to provide accurate ovarian cancer diagnosis without considering menopausal status.
Guidelines for initiating colorectal cancer (CRC) screening are based on family history but do not consider lifestyle, environmental, or genetic risk factors. We developed models to determine risk of ...CRC, based on lifestyle and environmental factors and genetic variants, and to identify an optimal age to begin screening.
We collected data from 9748 CRC cases and 10,590 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colorectal Transdisciplinary study, from 1992 through 2005. Half of the participants were used to develop the risk determination model and the other half were used to evaluate the discriminatory accuracy (validation set). Models of CRC risk were created based on family history, 19 lifestyle and environmental factors (E-score), and 63 CRC-associated single-nucleotide polymorphisms identified in genome-wide association studies (G-score). We evaluated the discriminatory accuracy of the models by calculating area under the receiver operating characteristic curve values, adjusting for study, age, and endoscopy history for the validation set. We used the models to project the 10-year absolute risk of CRC for a given risk profile and recommend ages to begin screening in comparison to CRC risk for an average individual at 50 years of age, using external population incidence rates for non-Hispanic whites from the Surveillance, Epidemiology, and End Results program registry.
In our models, E-score and G-score each determined risk of CRC with greater accuracy than family history. A model that combined both scores and family history estimated CRC risk with an area under the receiver operating characteristic curve value of 0.63 (95% confidence interval, 0.62–0.64) for men and 0.62 (95% confidence interval, 0.61–0.63) for women; area under the receiver operating characteristic curve values based on only family history ranged from 0.53 to 0.54 and those based only E-score or G-score ranged from 0.59 to 0.60. Although screening is recommended to begin at age 50 years for individuals with no family history of CRC, starting ages calculated based on combined E-score and G-score differed by 12 years for men and 14 for women, for individuals with the highest vs the lowest 10% of risk.
We used data from 2 large international consortia to develop CRC risk calculation models that included genetic and environmental factors along with family history. These determine risk of CRC and starting ages for screening with greater accuracy than the family history only model, which is based on the current screening guideline. These scoring systems might serve as a first step toward developing individualized CRC prevention strategies.
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Intestinal inflammation is a primary contributor to poor growth performance during poultry production. Chlorogenic acid (CGA) is a natural phenolic acid that exhibits superior anti-inflammatory ...activity and improved intestinal health. To investigate the protective effects and molecular mechanisms of CGA during intestinal inflammation in lipopolysaccharide (LPS)-challenged broilers, we randomly divided 288 one-day-old male Cobb broilers into 4 groups: a control group fed a basal diet (CON group), a basal diet + LPS group (LPS group), and 2 basal diet groups fed 500 or 750 mg/kg CGA + LPS (CGA_500 or CGA_750 groups). Broilers were injected with LPS or saline at 15, 17, 19, and 21 d old. Chlorogenic acid supplementation improved the growth performance of LPS-challenged broilers by increasing average daily gain (ADG) and reducing feed/gain (F/G) ratios (P < 0.05). CGA also improved intestinal barrier function in LPS-challenged boilers by enhancing jejunum morphology and integrity, decreasing intestinal permeability, and increasing occludin 3, zonula occludens-1, and mucin 2 expression (P < 0.05). CGA supplementation also improved systemic and jejunum antioxidant capacity by significantly enhancing glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities (P < 0.05), and reducing malonaldehyde (MDA) and protein carbonyl (PCO) levels (P < 0.05). Chlorogenic acid supplementation reduced systemic and jejunum pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, and IL-12) and increased anti-inflammatory cytokines (IL-10) in LPS-challenged broilers (P < 0.05) by inhibiting the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway (P < 0.05). In addition, the protective effects of CGA toward intestinal inflammation and apoptosis appeared to be correlated with inhibited endoplasmic reticulum (ER) stress (P < 0.05). In summary, CGA supplementation improved intestinal morphology and integrity by inhibiting TLR4/NF-κB and ER stress pathways, which potentially reduced oxidative stress and inflammation, and ultimately improved the growth performance of LPS-challenged broilers.
Epilepsy has been found to be modulated by the astrocyte systems in experiments, and tremendous modeling studies have unveiled the roles of astrocyte cellular functions such as the calcium and ...potassium channels in the epileptic seizures. However, little attention has been paid to the structure changes of astrocytes in the epileptic seizures in the scale of networks. This paper first constructs a neuron–astrocyte network model to explain the experimental observation that astrocytes mainly induce epilepsy by blocking the channels of the astrocyte gap junction in the network scale. Such model is used to discuss potential seizure induction process in the network by changing the connection intensity of the astrocyte gap junction. The simulation results show that a decrease of the gap junction intensity changes the firing pattern of the population of neurons from slow periodical firing to high-frequency epileptic seizures, featuring epileptic patterns of depolarization blocks. This further verifies that epileptic seizures are experimentally induced via the channel block of the astrocyte gap junctions. Because of the heterogeneous structure of the real neuron–astrocyte network, the effect of changing astrocyte network structures on the seizure activities is then studied in two typical network structures: the regular neighboring connection and the random connection. The results show that an increase of the number of regular connections of the regular neighboring astrocyte network could inhibit the induction and spread of the epileptic seizures. The epileptic inhibition can be achieved similarly by increasing the connection probability of the random astrocyte network. These findings further provide evidence for the experimental phenomena of the protective response of gliosis to epilepsy with increasing gap junctions. Above all, the simulation results suggest a potential pathway of epilepsy treatment by targeting the astrocyte gap junctions.
Hereditary tyrosinemia type 1 (HT1; OMIM# 276700) is a genetic metabolism disorder caused by disease-causing variants in the fumarylacetoacetate hydrolase (FAH) gene encoding the last enzyme of the ...tyrosine catabolic pathway. Herein, we describe the clinical features and genetic characteristics of HT1 in a five years and seven months old Chinese patient.
After clinical diagnosis of the proband with HT1, genetic testing was performed by Sanger sequencing of the FAH gene in all family members. Functional analysis of the disease-causing variant was performed by cDNA sequencing to understand the effect of the variant on FAH transcript. To further predict the variant effect, we used Human Splicing Finder (HSF) and PyMol in silico analysis.
We identified a novel previously undescribed intronic variant in the FAH gene (c.914-1G>A). It was detected in a child who was homozygous for the variant and had the clinical presentation of HT1. cDNA sequencing showed that this splice-junction variant affected the transcription of FAH by formation of two different transcripts. Our observations and laboratory experiments were in line with in silico methods.
Our study provides new insight into the HT1 variant spectrum and a better understanding of this disease in the Chinese population. This will be useful for molecular diagnosis in our country in cases where premarital screening, prenatal diagnosis and preimplantation genetic diagnosis are planned.
The agriculture industry has faced various challenges nowadays. This research is the first part of a project that presents the designing process, kinematic modelling, and parameterization of a 4-DOF ...SCARA-type robotic arm specifically designed for work in an agricultural field in terms of seeding, watering, fertilizing, weeding, harvesting, and transporting. The designing of parameters, such as optimum degrees of freedom and component configuration, was done. The kinematic model was calculated using the Denavit-Hartenberg method. The structure of robot was developed for inertia reduction, smooth motion, and torque minimization. The results show that the working space, maximum front access, and side access of developed robotic arm were 11.4 m
, 2.9 m, and 2.4 m, respectively. The results indicate that the robot has sufficient surface coverage for defined farm work.
This paper presents a new compact on-chip current-sensing circuit to enable current-mode buck regulators operating at a high switching frequency for reducing the inductor profile. A dynamically ...biased shunt feedback technique is developed in the proposed current sensor to push nondominant poles to higher frequencies, thereby improving the speed and stability of the current sensor under a wide range of load currents. A feedforward gain stage in the proposed current sensor also increases the dc loop-gain magnitude and thus enhances the accuracy of the current sensing. A current-mode buck regulator with the proposed current sensor has been implemented in a standard 0.35-μm CMOS process. Measurement results show that the proposed current sensor can achieve 95% sensing accuracy and <;; 50-ns settling time. The buck converter can thus operate properly at the switching frequency of 2.5 MHz with the duty cycle down to 0.3. The output ripple voltage of the regulator is <;; 43 mV with a 4.7-μF off-chip capacitor and a 2.2-μH off-chip inductor. The power efficiency of the buck regulator achieves above 80% over the load current ranging from 25 to 500 mA.
This paper presents a multi-MHz buck regulator for portable applications using an auto-selectable peak- and valley-current control (ASPVCC) scheme. The proposed ASPVCC scheme can enable the ...current-mode buck regulator to reduce the settling-time requirement of the current sensing by two times. In addition, the dynamically biased shunt feedback technique is employed to improve the sensing speed and the sensing accuracy of both the peak and valley current sensors. With both ASPVCC scheme and advanced current sensors, the buck regulator can thus operate at high switching frequencies with a wide range of duty ratios for reducing the required off-chip inductance. The proposed current-mode buck regulator was fabricated in a standard 0.35-μm CMOS process and occupies a small chip area of 0.54 mm 2 . Measurement results show that the buck regulator can deliver a maximum output current of 500 mA, operate at 5 MHz with a wide duty-ratio range of about 0.6, use a small-value off-chip inductor of 1 μH, and achieve the peak power efficiency of 91%.
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