The Effect of Macronutrient Restrictions on Gut Microbiome and Biochemical Parameters of Wistar Albino Rats

Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.

Effects of restrictions on maternal feed intake on the immune indexes of umbilical cord blood and liver Toll-like receptor signaling pathways in fetal goats during pregnancy

Background: Liver has important immune function during fetal development and after birth.However,the effect of maternal malnutrition on immune function of the fetal liver is rarely reported.In this study,twelve pregnant goats(Xiangdong black goat,at d 45 of gestation) were assigned to the control group(fed 100% of nutritional requirements) and the restriction group(fed 60% of the intake of the control group) during gestation from d 55 to100.Fetal goats were harvested at d 100 of gestation and immune indexes and amino acid profiles of the umbilical cord blood and liver Toll-like receptors(TLRs) signaling pathways were measured.Results: Maternal body weight in the restriction group was lower than the control group(P < 0.05).Maternal feed intake restriction decreased(P < 0.05) heart weight,heart index,alkaline phosphatase and serum amyloid protein A in the umbilical cord blood(UCB).Moreover,only histidine was decreased in the restricted group(P = 0.084),and there were no differences in other amino acids contents in the UCB between the two groups(P > 0.05).The TLR2 and TLR4 mRNA expression in the fetal liver in the restriction group was greater(P < 0.05) than that in the control group.Furthermore,the mRNA expression levels of myeloid differentiation primary response 88(MyD88),TNF receptor associated factor 6,nuclear factor kappa B subunit 1,NFKB inhibitor alpha,IFN-β,TGF-β,TNF-α and IL-1β in the restricted group were upregulated(P < 0.05),and the expression of TLR3(P = 0.099) tended to be higher in the restricted group.However,protein levels of TLR2,TLR4,IκBα,phosphorylated IκBα,phosphorylated IκBα/total IκBα,TRIF and MyD88 were not affected(P > 0.05) by maternal intake restriction.Conclusions: These results revealed that the restriction of maternal feed intake influenced the development of heart and hepatic protein synthesis at the acute phase of fetal goats and upregulated the mRNA expression of genes involved in MyD88-dependent signaling pathways and of target cytokines.

Assessing the Effect of Global Travel and Contact Restrictions on Mitigating the COVID-19 Pandemic

Travel restrictions and physical distancing have been implemented across the world to mitigate the coronavirus disease 2019(COVID-19)pandemic,but studies are needed to understand their effectiveness across regions and time.Based on the population mobility metrics derived from mobile phone geolocation data across 135 countries or territories during the first wave of the pandemic in 2020,we built a metapopulation epidemiological model to measure the effect of travel and contact restrictions on containing COVID-19 outbreaks across regions.We found that if these interventions had not been deployed,the cumulative number of cases could have shown a 97-fold(interquartile range 79–116)increase,as of May 31,2020.However,their effectiveness depended upon the timing,duration,and intensity of the interventions,with variations in case severity seen across populations,regions,and seasons.Additionally,before effective vaccines are widely available and herd immunity is achieved,our results emphasize that a certain degree of physical distancing at the relaxation of the intervention stage will likely be needed to avoid rapid resurgences and subsequent lockdowns.

A systematic strategy for multi-period heat exchanger network retrofit under multiple practical restrictions

A systematic strategy for retrofit of the multi-period heat exchanger network （HEN） on the basis of the multi- objective optimization is developed. In this three-stage procedure, a simplified multi-objective optimization model of the multi-period lIEN is first established and then solved to target the retrofit, aiming to minimizing the total annual cost and total annual CO2 emissions. The obtained Pareto front represents series of retrofit targets under different emission limitations, from which the most desirable one can be selected. The matching of the existing and the required heat exchangers is further implemented to finalize the retrofit, which will meet the practical retrofit requirements and matching restrictions. The application of the proposed procedure is illustrated through a case study of a HEN in a vacuum gas oil hydro-treating unit.

Improvement of the Preliminary Test Estimator When Stochastic Restrictions are Available in Linear Regression Model

Ridge type estimators are used to estimate regression parameters in a multiple linear regression model when multicolinearity exists among predictor variables. When different estimators are available, preliminary test estimation procedure is adopted to select a suitable estimator. In this paper, two ridge estimators, the Stochastic Restricted Liu Estimator and Liu Estimator are combined to define a new preliminary test estimator, namely the Preliminary Test Stochastic Restricted Liu Estimator (PTSRLE). The stochastic properties of the proposed estimator are derived, and the performance of PTSRLE is compared with SRLE in the sense of mean square error matrix (MSEM) and scalar mean square error (SMSE) for the two cases in which the stochastic restrictions are correct and not correct. Moreover the SMSE of PTSRLE based on Wald (WA), Likelihood Ratio (LR) and Lagrangian Multiplier (LM) tests are derived, and the performance of PTSRLE is compared using WA, LR and LM tests as a function of the shrinkage parameter d with respect to the SMSE. Finally a numerical example is given to illustrate some of the theoretical findings.

Modelling the Violation of Restrictions Pertaining to Deforestation in a Given Land Right

This paper develops a model that could be used to visualize and predict the violation of restrictions in a given forest. The violation of restriction in this case is assumed to be the difference in areal extent between two forest cover scenes with time;termed “deforestation”. It analyses the relationship in forest cover changes overtime in Ganye Forest Reserve and Glide Cross Country Farm in Adamawa state, Nigeria. Cadastral maps of the forest reserve and farmland were used as the base maps, while the satellite images served as the spatio-temporal data. Landsat ETM+ images of 2003, 2008 and 2013 were used to identify, determine and estimate the violation of restrictions. The result shows that the violation of restrictions could be reliably determined for both the forest reserve and farmland and forecast made in order to predict future occurrence. It also revealed a continuous deforestation in the forest reserve, while in the farmland regeneration of forest stock was noticed. This information is very vital for forest management, planning and decision making in a viable land administration domain.

Necessary Conditions for Optimal Control of Diffusions with Hard Terminal State Restrictions

Necessary conditions are proved for certain problems of optimal control of diffusions where hard end constraints occur. The main results apply to several dimensional problems, where some of the state equations involve Brownian motions, but not the equations corresponding to states being hard restricted at the terminal time. The necessary conditions are stated in terms of weak variations. Two versions of necessary conditions are given, one version involving solutions of variational equations, the other one involving first order adjoint equations.

Restrictions and Countermeasures of Rural Vocational Education in Urban-rural Integration

Developing rural vocational education is of great significance to urban-rural integration: developing rural vocational education is helpful to cultivating new farmers for construction of new socialist countryside,favorable to improving farmers' ability of finding jobs and starting undertaking, and beneficial to transfer of rural surplus labor and acceleration of urbanization. Restrictions on development rural vocational education mainly include: low value cognition of society and social assessment of rural vocational education; out of balance of cost and expected return of rural vocational education; the quality of supply of rural vocational education failure to satisfy demand of socio-economic development; imperfect rural vocational education system. In view of these,following countermeasures and suggestions are put forward: strengthen propaganda and guidance to build environment of public opinion for rural vocational education; push forward rural vocational compulsory education system to lay social foundation for rural vocational education; reinforce policy support to assist in building rural vocational education system; improve education system to build overall framework of rural vocational education; perfect laws and regulations to establish system and norm for development of rural vocational education.

Restrictions on Purely Kinetic K-Essence

We restrict purely kinetic k-essence.Assuming that the equation of state is a power law of the kinetic energy,i.e.w=w0Xα,we find thatαmust be positive to obtain accelerated phases,constrained from the conditions for stability and causality.In this case the k-essence behaves like a phantom.We also study the evolutions of the equation of state and the speed of sound with numerical simulations.

Probability Criterion for a Dynamic Financial Model with Short-Selling Allowed

Probability criterion has its practical significance, and its investment decision-making is determined by the expected discounted wealth. In a complete, standard financial market with short-selling allowed, this paper probes into the investment decision-making with probability criterion. The upper limit of criterion function is obtained. The corresponding discounted wealth process and hedging portfolio process are provided. Finally, an illustrative example of one-dimensional constant-coefficient financial market is given.

Effects of maternal methyl donor intake during pregnancy on ileum methylation and function in an intrauterine growth restriction pig model

Background Intrauterine growth retardation(IUGR)affects intestinal growth,morphology,and function,which leads to poor growth performance and high mortality.The present study explored whether maternal dietary methyl donor(MET)supplementation alleviates IUGR and enhances offspring’s growth performance by improving intestinal growth,function,and DNA methylation of the ileum in a porcine IUGR model.Methods Forty multiparous sows were allocated to the control or MET diet groups from mating until delivery.After farrowing,8 pairs of IUGR and normal birth weight piglets from 8 litters were selected for sampling before suckling colostrum.Results The results showed that maternal MET supplementation tended to decrease the IUGR incidence and increased the average weaning weight of piglets.Moreover,maternal MET supplementation significantly reduced the plasma concentrations of isoleucine,cysteine,urea,and total amino acids in sows and newborn pig-lets.It also increased lactase and sucrase activity in the jejunum of newborn piglets.MET addition resulted in lower ileal methionine synthase activity and increased betaine homocysteine S-methyltransferase activity in the ileum of newborn piglets.DNA methylation analysis of the ileum showed that MET supplementation increased the methyla-tion level of DNA CpG sites in the ileum of newborn piglets.Down-regulated differentially methylated genes were enriched in folic acid binding,insulin receptor signaling pathway,and endothelial cell proliferation.In contrast,up-regulated methylated genes were enriched in growth hormone receptor signaling pathway and nitric oxide biosyn-thetic process.Conclusions Maternal MET supplementation can reduce the incidence of IUGR and increase the weaning litter weight of piglets,which may be associated with better intestinal function and methylation status.

Concerns about the application of resistance exercise with blood-flow restriction and thrombosis risk in hemodialysis patients

Background:Hemodialysis(HD) per se is a risk factor for thrombosis.Considering the growing body of evidence on blood-flow restriction(BFR) exercise in HD patients,identification of possible risk factors related to the prothrombotic agent D-dimer is required for the safety and feasibility of this training model.The aim of the present study was to identify risk factors associated with higher D-dimer levels and to determine the acute effect of resistance exercise(RE) with BFR on this molecule.Methods:Two hundred and six HD patients volunteered for this study(all with a glomerular filtration rate of <15 mL/min/1.73 m2).The RE+BFR session consisted of 50% arterial occlusion pressure during 50 min sessions of HD(intradialytic exercise).RE repetitions included concentric and eccentric lifting phases(each lasting 2 s) and were supervised by a strength and conditioning specialist.Results:Several variables were associated with elevated levels of D-dimer,including higher blood glucose,citrate use,recent cardiovascular events,recent intercurrents,higher inflammatory status,catheter as vascular access,older patients(>70 years old),and HD vintage.Furthermore,RE+BFR significantly increases D-dimer after 4 h.Patients with borderline baseline D-dimer levels(400-490 ng/mL) displayed increased risk of elevating D-dimer over the normal range(≥500 ng/mL).Conclusion:These results identified factors associated with a heightened prothrombotic state and may assist in the screening process for HD patients who wish to undergo RE+BFR.D-dimer and/or other fibrinolysis factors should be assessed at baseline and throughout the protocol as a precautionary measure to maximize safety during RE+BFR.

Changes and Restrictions

The development of the United States of America in its history over the past more than 200 years demonstrates that, the strategic line of thought of this nation is rather clear. In other words, America is a "nation that is never content. " This can be seen from its development from thirteen colonies to a big power stretching cross two oceans, then the only superpower in today’s world. The words and deeds of U. S. important political figures and public opinions as well reveal that at pre-

Effect of water restrictions on the physiological parameters,psychological behavior and brain c-Fos expression in rat

Objective In order to characterize the feature of stress response induced by stressor with both physical and psychological natures, the effect of water restriction performed in different experimental modes on the physiological parameters, psychological behavioral manifestations and brain c-Fos expressions were observed and compared. Methods 58 male Wistar rats were used and randomly divided into three experimental groups （n=18 for each） and a control group （n=4）. In control group, the rats were allowed to access drinking water freely at all experimental period. In the experimental groups the water supply to the rats was restricted. In timed water supply （TW） group, the water was supplied twice a day, 10 min for each in fixed hours every day. In empty bottle-served （EB） and water-restricted （WR） groups, the water was served only once a day for 10 min, either in the early morning or evening, and in the other time point scheduled for water supply only an empty bottle without water was provided in the EB group and nothing was given in the WR group. The quantities of drank water and eaten food, weight-gaining, and behavior score were observed every day. The serum level of corticosterone was assayed and the rats were sacrificed with fixative perfusion of 3 d, 7 d or 14 d respectively, following water restriction （n=6 for each time point in each group）. The brain c-Fos expressions were examined with immunohistochemistry. Results The slowing down of weight-gaining, rise of serum corticosterone level, occurrence of psychological behavioral manifestations of unpeaceful restlessness such as exploring and attacking, enhance of c-Fos expression in the subfomical organ （SFO）, median preoptic nucleus （MnPO）, area postrema （AP）, hypothalamic paraventricular nucleus （PVN）, supraoptic nucleus （SON）, medial （MeA） and central （CeA） amygdaloid nucleus and ventrolateral septum （LSV） were noticed in both EB and WR groups, except the nucleus of solitary tract （NTS） in which the Fos expression was decreased. The changes of Fos expression in most of nuclei in EB group began at day 3, at least persisted till day 7, and backed down at day 14. While in WR group, similar changes started at day 7 and reached its peak at day 14. In TW group, only the concentration of corticosterone at day 7 was slightly increased and the rest indexes observed were unchanged. Conclusion The results indicate that water restriction induces physical as well as psychological stress responses. And the water restrictions experimentally executed in different modes result in different manifestations of behavioral response and brain immediately early gene expression in discrete brain nuclei/regions.

Cooperative UAV search strategy based on DMPC-AACO algorithm in restricted communication scenarios

Improvement of integrated battlefield situational awareness in complex environments involving dynamic factors such as restricted communications and electromagnetic interference(EMI)has become a contentious research problem.In certain mission environments,due to the impact of many interference sources on real-time communication or mission requirements such as the need to implement communication regulations,the mission stages are represented as a dynamic combination of several communication-available and communication-unavailable stages.Furthermore,the data interaction between unmanned aerial vehicles(UAVs)can only be performed in specific communication-available stages.Traditional cooperative search algorithms cannot handle such situations well.To solve this problem,this study constructed a distributed model predictive control(DMPC)architecture for a collaborative control of UAVs and used the Voronoi diagram generation method to re-plan the search areas of all UAVs in real time to avoid repetition of search areas and UAV collisions while improving the search efficiency and safety factor.An attention mechanism ant-colony optimization(AACO)algorithm is proposed for UAV search-control decision planning.The search strategy is adaptively updated by introducing an attention mechanism for regular instruction information,a priori information,and emergent information of the mission to satisfy different search expectations to the maximum extent.Simulation results show that the proposed algorithm achieves better search performance than traditional algorithms in restricted communication constraint scenarios.

Quadratic Loss of Isotonic Normal Means under Simultaneous Order Restrictions

For two normal populations with unknown means μ and unknown variances σ2, assume that there are simple order restrictions among the means and variances: μ1 < μ2 and σ12 >σ22 > 0. This case is said to be simultaneous order restriction by Shi (Maximum likelihood estimation of means and variances from normal populations under simultaneous order restrictions, J. Multivariate Anal., 50(1994), 282-293.) and an iterative algorithm of computing the order restricted maximum likelihood estimates of μi and σi2 was given in that paper. This paper shows that the restricted maximum likelihood estimate of μi has smaller mean square loss than the usual estimate xi under some conditions.

Associations of serum D-dimer and glycosylated hemoglobin levels with third-trimester fetal growth restriction in gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)is a special type of diabetes that commonly occurs in women during pregnancy and involves impaired glucose tolerance and abnormal glucose metabolism;GDM is diagnosed for the first time during pregnancy and can affect fetal growth and development.AIM To investigate the associations of serum D-dimer(D-D)and glycosylated hemoglobin(HbA1c)levels with third-trimester fetal growth restriction(FGR)in GDM patients.METHODS The clinical data of 164 pregnant women who were diagnosed with GDM and delivered at the Obstetrics and Gynecology Hospital of Fudan University from January 2021 to January 2023 were analyzed retrospectively.Among these women,63 whose fetuses had FGR were included in the FGR group,and 101 women whose fetuses had normal body weights were included in the normal body weight group(normal group).Fasting venous blood samples were collected from the elbow at 28-30 wk gestation and 1-3 d before delivery to measure serum D-D and HbA1c levels for comparative analysis.The diagnostic value of serum D-D and HbA1c levels for FGR was evaluated by receiver operating characteristic analysis,and the influencing factors of third-trimester FGR in GDM patients were analyzed by logistic regression.RESULTS Serum fasting blood glucose,fasting insulin,D-D and HbA1c levels were significantly greater in the FGR group than in the normal group,while the homeostasis model assessment of insulin resistance values were lower(P<0.05).Regarding the diagnosis of FGR based on serum D-D and HbA1c levels,the areas under the curves(AUCs)were 0.826 and 0.848,the cutoff values were 3.04 mg/L and 5.80%,the sensitivities were 81.0%and 79.4%,and the specificities were 88.1%and 87.1%,respectively.The AUC of serum D-D plus HbA1c levels for diagnosing FGR was 0.928,and the sensitivity and specificity were 84.1%and 91.1%,respectively.High D-D and HbA1c levels were risk factors for third-trimester FGR in GDM patients(P<0.05).CONCLUSION D-D and HbA1c levels can indicate the occurrence of FGR in GDM patients in the third trimester of pregnancy to some extent,and their combination can be used as an important index for the early prediction of FGR.

Measuring the Social Net Benefits of COVID-19 Restrictions: The Case of Reduced Vehicle Use in a Pollution-Prone Region of Utah

A number of natural experiments have recently found that COVID-19 restrictions imposed in nations worldwide are correlated with short-term reductions—in some cases dramatic reductions—in mobile-source air pollutants. Noticeably absent from these studies are estimates of the social net benefits associated with the changes in human behavior underlying the pandemic-induced effects. Using readily available data provided by the state of Utah and the U.S. Environmental Protection Agency’s Co-Benefits Risk Assessment Health Impacts Screening and Mapping Tool (COBRA), we find that daily social net benefit was positive during a pandemic-induced shutdown from March to April, 2020 in Utah’s Wasatch Front region solely when COBRA’s “high” health benefit estimate from combined reductions in PM2.5 and NOx concentrations are weighed against the region’s “low” vehicle-trip cost estimate. All other scenarios correspond with negative net benefit estimates, i.e., when high and low benefit estimates of reductions solely in PM2.5 concentrations as well as for combined reductions in PM2.5 and NOx concentrations are weighed against the region’s high vehicle-trip cost estimate. Generally speaking, social net benefits are higher for two of the Wasatch Front’s four counties.

Urban Land Use Efficiency and Contributing Factors in the Yangtze River Delta Under Increasing Environmental Restrictions in China

Evaluating urban land use efficiency(ULUE) provides insights into the interactions between land use systems and their external environment. Specifically, changes in ULUE are important for monitoring urban transformation in developing countries. In this study, using a traditional input-output index model, we incorporated slack-based measurements and undesirable outputs into a SBM-UN(slack-based measure-undesirable) model to investigate ULUE within the context of increasing environmental restrictions in China. The model was used to estimate the ULUE of 26 cities in the highly developed urban agglomeration of the Yangtze River Delta from 2000 to2018. The average ULUE in the Yangtze River Delta was relatively low compared to that of developed city regions in the European Union(EU) and North America and exhibited a U-shaped curve over the study period. Incorporating undesirable outputs, such as environmental pollution, into the model reduced ULUE by 19.06%. ULUE varied spatially, with the kernel density estimation exhibiting a bimodal distribution. Efficiency decomposition analysis showed that scale efficiency made a greater contribution to ULUE than pure technical efficiency. Based on our findings, recommended approaches to improve ULUE include optimizing factor allocation, reducing undesirable outputs, and increasing the effective output per land unit. The study suggests that ULUE and the SBM-UN model are useful planning tools for sustainable urban development.

SREBP2 restricts osteoclast differentiation and activity by regulating IRF7 and limits inflammatory bone erosion

Osteoclasts are multinucleated bone-resorbing cells,and their formation is tightly regulated to prevent excessive bone loss.However,the mechanisms by which osteoclast formation is restricted remain incompletely determined.Here,we found that sterol regulatory element binding protein 2(SREBP2)functions as a negative regulator of osteoclast formation and inflammatory bone loss.Cholesterols and SREBP2,a key transcription factor for cholesterol biosynthesis,increased in the late phase of osteoclastogenesis.