An efficient peptide ligase engineered from a bamboo asparaginyl endopeptidase.

In recent years, a few asparaginyl endopeptidases (AEPs) from certain higher plants have been identified as efficient peptide ligases with wide applications in protein labeling and cyclic peptide synthesis. Recently, we developed a NanoLuc Binary Technology (NanoBiT)-based peptide ligase activity assay to identify more AEP-type peptide ligases. Herein, we screened 61 bamboo species from 16 genera using this assay and detected AEP-type peptide ligase activity in the crude extract of all tested bamboo leaves. From a popular bamboo species, Bambusa multiplex, we identified a full-length AEP-type peptide ligase candidate (BmAEP1) via transcriptomic sequencing. After its zymogen was overexpressed in Escherichia coli and self-activated in vitro, BmAEP1 displayed high peptide ligase activity, but with considerable hydrolytic activity. After site-directed mutagenesis of its ligase activity determinants, the mutant zymogen of [G238V]BmAEP1 was normally overexpressed in E. coli, but failed to activate itself. To resolve this problem, we developed a novel protease-assisted activation approach in which trypsin was used to cleave the mutant zymogen and was then conveniently removed via ion-exchange chromatography. After the noncovalently bound cap domain was dissociated from the catalytic core domain under acidic conditions, the recombinant [G238V]BmAEP1 displayed high peptide ligase activity with much lower hydrolytic activity and could efficiently catalyze inter-molecular protein ligation and intramolecular peptide cyclization. Thus, the engineered bamboo-derived peptide ligase represents a novel tool for protein labeling and cyclic peptide synthesis.

Immunogenicity of COVID-19 vaccines in patients with cirrhosis: A meta-analysis.

The immunogenicity of COVID-19 vaccines in patients with liver cirrhosis remains largely unknown. The purpose of this meta-analysis was to investigate the immunogenicity of COVID-19 vaccines in patients with cirrhosis and compare the humoral and cellular immune responses following complete COVID-19 vaccination between cirrhosis patients and healthy controls. A systematic literature search was conducted in PubMed, EMBASE, and Web of Science from 1 January 2020 to 22 August 2023. Sixteen studies with 2127 cirrhosis patients were included. The pooled seroconversion rate in patients with cirrhosis following complete COVID-19 vaccination was 92.4% (95% CI, 86.2%-96%, I2 = 90%) with significant between-study heterogeneity. Moreover, COVID-19 vaccination elicited a higher humoral immune response in patients of compensated cirrhosis as compared with decompensated cirrhosis (RR = 1.069, 95% CI, 1.011-1.131, I2 = 17%, p = .019). Additionally, 10 studies were included for comparison analysis of seroconversion rate between cirrhosis patients and healthy controls. The results showed that the seroconversion rate in patients with cirrhosis was slightly lower compared with healthy controls (RR = 0.972, 95% CI, 0.955-0.989, I2 = 66%, p = .001). Meanwhile, the pooled RR of cellular immune response rate for cirrhosis patients vs. healthy controls was 0.678 (95% CI, 0.563-0.817, I2 = 0, p < .0001). Our meta-analysis demonstrated that COVID-19 vaccination elicited diminished humoral and cellular immune responses in patients of cirrhosis. Patients with cirrhosis particularly decompensated cirrhosis who have completed full-doses of COVID-19 vaccination should receive continuous attention and preemptive measures.

Laryngopharyngeal Reflux and Benign Vocal Fold Lesions: A Systematic Review and Meta-analysis.

OBJECTIVE: There is a link between laryngopharyngeal reflux (LPR) and the formation of benign vocal fold lesions (BVFLs). However, previous studies have mainly focused on LPR suggested by symptoms and signs, rather than objectively diagnosed LPR via pharyngeal pH monitoring. We, therefore, conducted a Meta-analysis to evaluate the association between pharyngeal pH monitoring diagnosed LPR and the odds of BVFLs. DATA SOURCES: Relevant observational studies were identified by searching PubMed, Embase, Cochrane Library, and Web of Science. REVIEW METHODS: We evaluated between-study heterogeneity using the Cochrane Q test and estimated the I2 statistic. Random-effects models were used when significant heterogeneity was observed; otherwise, fixed-effects models were used. RESULTS: Thirteen datasets from 9 studies were included. Among them, 493 were diagnosed with LPR and 344 had BVFLs. LPR was related to a higher odds of BVFLs (odds ratio: 3.26, 95% confidence interval: 1.84-5.76, P < .001) with moderate heterogeneity (P for Cochrane Q test = .006, I2 = 57%). Subgroup analyses showed that the association was similar in studies with only pharyngeal pH monitoring (Restech), with double-probe or 3-site pH monitoring, and with 24-hour multichannel intraluminal impedance-pH monitoring (P for subgroup difference = .15). In addition, subgroup analysis showed consistent results in studies from Asia and Europe (P for subgroup analysis = .12), and the association seemed to be consistent for vocal Reinke's edema, nodules, and polyps (P for subgroup difference = .09). CONCLUSION: Pharyngeal pH monitoring diagnosed LPR is associated with the formation of BVFLs.

Diverse terpenoid glycosides with in vitro cytotoxicity from Glechoma longituba.

Terpenoids are the largest class of all known natural products, possessing structural diversity and numerous biological activities. Ten previously undescribed terpenoid glycosides, glechlongsides A-J (1-10), were isolated from the ethanol extract of the whole plant of Glechoma longituba, including diterpenoid glycoside and pentacyclic triterpenoid saponin. The structures of these compounds were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra. In addition, glechlongsides F-I (6-9) exhibited weak cytotoxicity against human cancer cell lines BGC-823, Be1, HCT-8, A2780, and A549 with IC50 values ranging from 3.77 to 30.95 µM, respectively.

Cholesterol-rich dietary pattern during early pregnancy and genetic variations of cholesterol metabolism genes in predicting gestational diabetes mellitus: a nested case-control study.

BACKGROUND: Higher dietary cholesterol intake during pregnancy increases risk of gestational diabetes mellitus (GDM). However, no studies have investigated interindividual variability in cholesterol metabolism and the association of genetics and diet on GDM. OBJECTIVE: ; To prospectively evaluate the joint association of cholesterol-rich dietary patterns and polymorphisms of genes coding for cholesterol metabolism pathway proteins with GDM. METHODS: A total of 1116 pregnant females from the Tongji Birth Cohort were enrolled. GDM was diagnosed according to a 75-g 2-h oral glucose tolerance test at 24-28 wk of gestation. Dietary data were collected by a validated food frequency questionnaire. The reduced-rank regression method was used to identify dietary patterns using dietary cholesterol as the response variable. Time-of-flight mass spectrometry was used for genotyping. The genetic risk score (GRS) for GDM was constructed with genetic variants in 28 cholesterol metabolism-related single-nucleotide polymorphisms (SNPs). Conditional logistic regression models were used to assess the odds ratio (OR) for GDM. RESULTS: The cholesterol-rich dietary pattern was rich in livestock and poultry meat and eggs but lower in cereals. The multivariable-adjusted ORs for GDM were 1.24 (95% confidence interval: 1.06-1.44) per SD increment of cholesterol-rich pattern scores and 1.28 (1.09-1.49) per tertile GRS. The variants of the CYP7A1 rs3808607 G→T/rs8192871 G→A/rs7833904 A→T, as well as AGGG and TTGA haplotypes of 4 CYP7A1-spanning SNPs, were significantly associated with GDM. For the joint effect, the OR was 3.53 (1.71-7.31) in the highest categories of both dietary pattern scores and GRS compared with individuals with the lowest strata without significant interaction (P for interaction = 0.101). CONCLUSIONS: Both a cholesterol-rich dietary pattern and genetic variants of cholesterol metabolism genes are associated with risk of GDM. Adherence to a cholesterol-rich dietary pattern during early pregnancy promotes the chance of GDM, especially in women with higher GRS. CLINICAL TRIAL REGISTRY: This trial was registered at http://www.chictr.org.cn (Registration number: ChiCTR1800016908). URL: =https://www.chictr.org.cn/showprojEN.html?proj=28081.

Transcriptome and metabolome analyses revealed the response mechanism of pepper roots to Phytophthora capsici infection.

BACKGROUND: Phytophthora root rot caused by the oomycete Phytophthora capsici is the most devastating disease in pepper production worldwide, and current management strategies have not been effective in preventing this disease. Therefore, the use of resistant varieties was regarded as an important part of disease management of P. capsici. However, our knowledge of the molecular mechanisms underlying the defense response of pepper roots to P. capsici infection is limited. METHODS: A comprehensive transcriptome and metabolome approaches were used to dissect the molecular response of pepper to P. capsici infection in the resistant genotype A204 and the susceptible genotype A198 at 0, 24 and 48 hours post-inoculation (hpi). RESULTS: More genes and metabolites were induced at 24 hpi in A204 than A198, suggesting the prompt activation of defense responses in the resistant genotype, which can attribute two proteases, subtilisin-like protease and xylem cysteine proteinase 1, involved in pathogen recognition and signal transduction in A204. Further analysis indicated that the resistant genotype responded to P. capsici with fine regulation by the Ca2+- and salicylic acid-mediated signaling pathways, and then activation of downstream defense responses, including cell wall reinforcement and defense-related genes expression and metabolites accumulation. Among them, differentially expressed genes and differentially accumulated metabolites involved in the flavonoid biosynthesis pathways were uniquely activated in the resistant genotype A204 at 24 hpi, indicating a significant role of the flavonoid biosynthesis pathways in pepper resistance to P. capsici. CONCLUSION: The candidate transcripts may provide genetic resources that may be useful in the improvement of Phytophthora root rot-resistant characters of pepper. In addition, the model proposed in this study provides new insight into the defense response against P. capsici in pepper, and enhance our current understanding of the interaction of pepper-P. capsici.

Magnesium Status, Genetic Variants of Magnesium-Related Ion Channel Transient Receptor Potential Membrane Melastatin 6 (TRPM6) and the Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women: A Nested Case-Control Study.

SCOPE: Magnesium plays an important role in regulating glucose metabolism. The study attempts to explore association between magnesium status and single nucleotide polymorphisms (SNPs) of gene involved in magnesium absorption-transient receptor potential membrane melastatin 6 (TRPM6) and gestational diabetes mellitus (GDM) risk METHODS AND RESULTS: A nested case-control study including 170 GDM cases and matched 340 controls is conducted based on Tongji Birth Cohort. Dietary, serum, and urine magnesium are evaluated before the diagnosis of GDM. Compared to the lowest tertile, women in the highest tertile of serum magnesium are at a lower risk of GDM (adjusted odds ratio [aOR] 0.42, 95% confidence intervals [CI] 0.21-0.84). Serum magnesium is inversely associated with insulin and homeostatic model assessment of insulin resistance (ß = -0.05, p = 0.002; ß = -0.04, p = 0.001, respectively). The aOR for GDM in carriers of the CT or CC genotypes of TRPM6 rs2274924 compared with carriers of the TT genotype is 2.76 (95% CI 1.78-4.26). Dietary magnesium is positively associated with serum magnesium (ß = 0.02, p = 0.004), but not with GDM risk. CONCLUSION: Serum magnesium and the TRPM6 rs2274924 polymorphism are associated with the risk of GDM.

The efficacy of different nimodipine administration route for treating subarachnoid hemorrhage: A network meta-analysis.

BACKGROUND: A systematic review and network meta-analysis (NMA) were conducted to explore the optimal administration route of nimodipine for treatment subarachnoid hemorrhage. METHODS: Electronic databases (Pubmed, Embase, Web of Science and Cochrane databases) were systematically searched to identify randomized controlled trials evaluating different administration route of nimodipine (intravenous and enteral) versus placebo for treatment subarachnoid hemorrhage. Outcomes included case fatality at 3 months, poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), incidence of delayed cerebral ischemia (DCI), delayed ischemic neurological deficit. A random-effect Bayesian NMA was conducted for outcomes of interest, and results were presented as odds ratios (ORs) and 95% credible intervals. The NMA was performed using R Software with a GeMTC package. A Bayesian NMA was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS: Nine randomized controlled trials met criteria for inclusion and finally included in this NMA. There was no statistically significant between intravenous and enteral in terms of case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P > .05). Both intravenous and enteral could reduce case fatality, the occurrence of DCI, delayed ischemic neurologic deficit and poor outcomes (P < .05). The SUCRA shows that enteral ranked first, intravenous ranked second and placebo ranked the last for case fatality, the occurrence of DCI and poor outcomes. The SUCRA shows that intravenous ranked first, enteral ranked second and placebo ranked the last for delayed ischemic neurologic deficit. CONCLUSIONS: It is possible that both enteral and intravenous nimodipine have comparable effectiveness in preventing poor outcomes, DCI, and delayed ischemic neurological deficits. However, further investigation may be necessary to determine the exact role of intravenous nimodipine in current clinical practice.

Spatio-temporal evolution of acoustic emission events and initiation of stress fields in the fracturing of rock mass around a roadway under cyclic high-stress loading.

To study fracture mechanisms and initiation of stress fields in the rock mass around a roadway subjected to cyclic stress, a series of loading and unloading tests were conducted on the rock mass around the roadway by using high-precision acoustic emission (AE) monitoring. The results show that intense AE activities occur in a specimen during cyclic load-holding at different levels. With the increase in the number of cycles, the overall stability of the specimen gradually decreases. In the cyclic loading and unloading process, the specimen exhibits a Kaiser effect. As the number of cycles increases, more AE events occur in the unloading stage and a Felicity effect is manifest. The spatial distribution of AE events is related to the stress regime and structure of the specimen, crack propagation in the roadway exhibits directionality due to effects of the principal stress. High stress is conducive to microcrack initiation and propagation in the specimen, which accelerates damage accumulation and macrofracture formation in a rock mass. The research provides a reference for roadway support work and disaster prevention and control in deep mines.

Permeability Prediction of Nanoscale Porous Materials Using Discrete Cosine Transform-Based Artificial Neural Networks.

The permeability of porous materials determines the fluid flow rate and aids in the prediction of their mechanical properties. This study developed a novel approach that combines the discrete cosine transform (DCT) and artificial neural networks (ANN) for permeability analysis and prediction in digital rock images, focusing on nanoscale porous materials in shale formations. The DCT effectively captured the morphology and spatial distribution of material structure at the nanoscale and enhanced the computational efficiency, which was crucial for handling the complexity and high dimensionality of the digital rock images. The ANN model, trained using the Levenberg-Marquardt algorithm, preserved essential features and demonstrated exceptional accuracy for permeability prediction from the DCT-processed rock images. Our approach offers versatility and efficiency in handling diverse rock samples, from nanoscale shale to microscale sandstone. This work contributes to the comprehension and exploitation of unconventional resources, especially those preserved in nanoscale pore structures.

Developing High-Power-Density Electromagnetic Devices with Nanocrystalline and Amorphous Magnetic Materials.

With the increasing demand for smaller, lighter, and more affordable electromagnetic devices, there is a growing trend toward developing high-power-density transformers and electrical machines. While increasing the operating frequency is a straightforward approach to achieving high power density, it can lead to significant power loss within a limited volume, resulting in excessive temperature rise and device degradation. Therefore, it is crucial to design high-power-density electromagnetic devices that exhibit low power loss and efficient thermal dissipation to address these challenges. Advanced techniques, such as the utilization of novel and advanced electromagnetic materials, hold great promise for overcoming these issues. Specifically, nanocrystalline and amorphous magnetic materials have emerged as highly effective solutions for reducing power loss and increasing efficiency in electromagnetic devices. This paper aims to provide an overview of the application of nanocrystalline and amorphous magnetic materials in transformers and electrical machines, along with key technologies and the major challenges involved.

Effects of brain-derived neurotrophic factor and adeno-associated viral vector on morphine-induced condition through target concentration changes in the ventral tegmental area and nucleus accumbens.

Morphine remains the standard analgesic for severe pain. However, the clinical use of morphine is limited by the innate tendency of opiates to become addictive. Brain-derived neurotrophic factor (BDNF) is a growth factor that is protective against many mental disorders. This study aimed to evaluate the protective function of BDNF on morphine addiction based on the behavioural sensitisation (BS) model and assess potential changes in downstream molecular tropomyosin-related kinase receptor B (TrkB) and cyclic adenosine monophosphate response element binding protein (CREB) expression caused by overexpression of BDNF. We divided 64 male C57BL/6 J mice into saline, morphine, morphine plus adeno-associated viral vector (AAV), and morphine plus BDNF groups. After administering the treatments, behavioural tests were conducted during the development and expression phases of BS, followed by a western blot analysis. All data were analysed by one- or two-way analysis of variance. The overexpression of BDNF in the ventral tegmental area (VTA) caused by BDNF-AAV injection decreased the total distance of locomotion in mice who underwent morphine-induced BS and increased the concentrations of BDNF, TrkB, and CREB in the VTA and nucleus accumbens (NAc). BDNF exerts protective effects against morphine-induced BS by altering target gene expression in the VTA and NAc.

Molecular dynamics-based analysis of the factors influencing the CO2 replacement of methane hydrate.

The benefits of large reserves, wide distribution, and high combustion energy density of natural gas hydrates are of great practical importance to alleviate the energy tension, enhance the existing energy system in China and reduce the greenhouse effect. The CO2 replacement method is a critical way to develop natural gas hydrate, while traditional experimental methods are difficult to reveal the microscopic mechanism of the replacement system. An MD (molecular dynamics) technique was utilized in this work to simulate the process of carbon dioxide replacement of gas hydrates. This simulation investigates the effects of temperature, pressure, and CO2 purity during the CO2 replacement process. CO2, different concentrations of CO2/H2O, and CO2/NH3 are used as the injected fluid. The simulation results show that the influence of temperature on the CO2 replacement of natural gas hydrate is more significant than that of pressure. Within the temperature and pressure range specified in the simulation, H2O inhibits the replacement of CO2, owing to the inhibitory effect increasing as the concentration of H2O increases; NH3 promotes the process of CO2 replacement under the temperature conditions of 250 K and 260 K, and the promotion effect becomes more significant as the concentration of NH3 increases. However, adding NH3 inhibits the CO2 replacement process with hydrate when the temperature lifts to 270 K. These findings provide new ideas to improve the efficiency of the CO2 replacement method and provide theoretical insight for the engineering exploitation of hydrates.

Prevalence and clinical characteristics of T2DM patients with OTUD3 gene rs78466831 SNP at a single academic center in China.

Background: A novel, rare OTUD3 c.863G>A (rs78466831) in humans has been reported associated with diabetes, but the prevalence and clinical characteristics of T2DM patients with rs78466831 have not been reported before. Objective: To investigate the prevalence and clinical characteristics of T2DM patients with rs78466831 and provide a basis for clinical diagnosis and treatment. Methods: OTUD3 gene rs78466831 SNP was detected by Sanger sequencing in all the collected specimens of laboratory-confirmed T2DM patients and healthy people. Clinical characteristics indexes inconsisting of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and a body mass index (BMI), T2DM-associated chronic complications (myocardial infarction, cerebrovascular disease, retinopathy, arterial plaque, peripheral neuropathy and nephropathy) were obtained from the clinical laboratory information systems and electronic medical record system. Clinical characteristic indicators were compared between the wild-type and variant (rs78466831) patients with T2DM. Results: The prevalence of rs78466831 in the T2DM patients group was significantly higher than the healthy control in our academic center. The general characteristic indicators were not significantly different between the wild-type and rs78466831 patients with T2DM, except the family history of diabetes. Clinical laboratory indicators including HbA1c, FBG, OGTT, TC, HDL-C, LDL-C and CP had no significant difference between the two groups. The therapeutic drug and target achievement rates were not significantly different between the two groups. The incidence of diabetic retinopathy in the variant group was significantly higher than the wild-type group. Conclusions: The OTUD3 gene rs78466831 was associated with T2DM and may be a biological risk factor of diabetes retinopathy.

An Analytical Model for Hysteretic Pressure-Sensitive Permeability of Nanoporous Media.

Hysteretic pressure-sensitive permeability of nanohybrids composed of substantial nanopores is critical to characterizing fluid flow through nanoporous media. Due to the nanoscale effect (gas slippage), complex and heterogeneous pore structures of nanoporous media, the essential controls on permeability hysteresis of nanohybrids are not determined. In this study, a hysteretic pressure sensitive permeability model for nitrogen flow through dry nanoporous media is proposed. The derived model takes into account the nanoscale effect and pore deformation due to effective stress. The model is validated by comparing it with the experimental data. The results show that the calculated permeability and porosity are consistent with the measured results with the maximum relative error of 6.08% and 0.5%, respectively. Moreover, the hysteretic pressure-sensitive permeability of nanohybrids is related to effective stress, gas slippage, pore microstructure parameters, grain quadrilateral angle, and the loss rate of grain quadrilateral angle. The nanoscale effect is crucial to the permeability of nanoporous media. In addition, as impacted by the comprehensive impact of multiple relevant influential parameters, permeability during the pressure unloading process is not a monotonous function but presents complicated shapes. The proposed model can explain, quantify, and predict the permeability hysteresis effect of nanoporous media reasonably well.

The Transverse Bearing Characteristics of the Pile Foundation in a Calcareous Sand Area.

Reviewing literature revealed that the studies on the bearing characteristics of pile foundations mainly focuses on clay, ordinary sand, loess, saline soil, and other areas. However, few studies on the bearing characteristics of the pile foundation in calcareous sand were conducted. Besides, existing traditional studies ignored the variation of soil compression modulus with depth, and the effect of void ratio on the transverse bearing characteristics of the pile foundation in a calcareous sand area were not well understood. In response of these problems, this study conducted a theoretical investigation on the transverse bearing characteristics of the pile foundation in a calcareous sand area. The transverse bearing characteristics of the pile foundation were derived based on the Pasternak foundation model and the Winkler foundation model, incorporating the heterogeneous distribution of compressive modulus with buried depth. The calculation results of the Pasternak foundation model are closer to the observed results than the Winkler foundation model. Therefore, the following research on the transverse bearing characteristics of the pile foundation in the calcareous sand area adopts the Pasternak foundation model. Then, the effects of the pile length, pile diameter, pile elastic modulus, horizontal load, bending moment, and void ratio on the transverse bearing characteristics of the pile foundation in a calcareous sand area were thoroughly analyzed. Furthermore, the difference between the transverse bearing characteristics of the pile foundation in a calcareous sand area and a quartz sand area was discussed. Results show that the horizontal displacement of the pile top in a calcareous sand area is greater than the quartz sand area under the same conditions.

Dietary tributyrin intervention improves the carcass traits, organ indices, and blood biomarker profiles in broilers under the isocaloric diets administration.

The objective of the current study was to investigate the effect of dietary tributyrin (TB) intervention on carcass traits, visceral and immune organ indices, and blood biomarker profiles in Arbor Acres (AA) broilers under the isocaloric diets administration. A total of 432-day-old healthy AA broiler chickens were assigned to 4 treatments, with 12 replicates per treatment and 9 birds per cage, for 42 d. The dietary treatments were a basal diet (control) and the basal diet supplemented with a TB product (Eucalorie) at doses of 0.50 g/kg (TB1), 1.0 g/kg (TB2), and 2.0 g/kg (TB3). The results showed that dietary TB treatment quadratically improved the average daily gain and average daily feed intake in the second (22-42 d) and overall (0-42 d) feeding periods (P < 0.05) while decreasing the feed conversion ratio in the second feeding period (P < 0.05). Dietary TB treatment improved the carcass traits, as evidenced by a higher eviscerated carcass rate and lower abdominal fat yield than those in the control group (P < 0.05). The breast meat yield rate was quadratically improved in response to dietary TB administration (P < 0.05). Dietary TB treatment improved the kidney, spleen, thymus, and bursa indices (P < 0.05) and reduced the lung indices compared with those in the control group (P < 0.05). In particular, the spleen and thymus indices were improved quadratically in response to dietary TB administration (P < 0.05). Dietary TB treatment improved the white and red blood cell counts, platelet count, hemoglobin and hematocrit at d 21, and platelet count at d 42 (P < 0.05), with those in the TB3 group being most affected. Dietary TB administration quadratically decreased the plasma content of uric acid at both d 21 and d 42 as well as that of creatine kinase at d 42 (P < 0.05), while it quadratically increased the plasma albumin/globulin ratio at both d 21 and d 42 (P < 0.05). Collectively, these results demonstrated that dietary TB intervention improved the growth performance, carcass traits, selected visceral and immune organ indices, and some blood biochemical markers under the isocaloric diets administration, which may facilitate better economic profit returns in poultry industry application.

Specific Role for GSK3α in Limiting Long-Term Potentiation in CA1 Pyramidal Neurons of Adult Mouse Hippocampus.

Glycogen synthase kinase-3 (GSK3) mediates phosphorylation of several hundred proteins, and its aberrant activity is associated with an array of prevalent disorders. The two paralogs, GSK3α and GSK3ß, are expressed ubiquitously and fulfill common as well as unique tasks throughout the body. In the CNS, it is established that GSK3 is involved in synaptic plasticity. However, the relative roles of GSK3 paralogs in synaptic plasticity remains controversial. Here, we used hippocampal slices obtained from adult mice to determine the role of each paralog in CA3-CA1 long-term potentiation (LTP) of synaptic transmission, a form of plasticity critically required in learning and memory. Conditional Camk2a Cre-driven neuronal deletion of the Gsk3a gene, but not Gsk3b, resulted in enhanced LTP. There were no changes in basal synaptic function in either of the paralog-specific knockouts, including several measures of presynaptic function. Therefore, GSK3α has a specific role in serving to limit LTP in adult CA1, a postsynaptic function that is not compensated by GSK3ß.

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences.

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease (CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction (CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas: (1) mechanisms underlying age-related cardiac remodeling; (2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women; (3) we select a few polyphenol or polyamine rich compounds as the CR-mimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.