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 m^(2)).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.

Mechanisms underlying the role of endoplasmic reticulum stress in the placental injury and fetal growth restriction in an ovine gestation model

Background Exposure to bisphenol A(BPA),an environmental pollutant known for its endocrine-disrupting properties,during gestation has been reported to increase the risk of fetal growth restriction(FGR)in an ovine model of pregnancy.We hypothesized that the FGR results from the BPA-induced insufficiency and barrier dysfunction of the placenta,oxidative stress,inflammatory responses,autophagy and endoplasmic reticulum stress(ERS).However,precise mechanisms underlying the BPA-induced placental dysfunction,and subsequently,FGR,as well as the potential involvement of placental ERS in these complications,remain to be investigated.Methods In vivo experiment,16 twin-pregnant(from d 40 to 130 of gestation)Hu ewes were randomly distributed into two groups(8 ewes each).One group served as a control and received corn oil once a day,whereas the other group received BPA(5 mg/kg/d as a subcutaneous injection).In vitro study,ovine trophoblast cells(OTCs)were exposed to 4 treatments,6 replicates each.The OTCs were treated with 400μmol/L BPA,400μmol/L BPA+0.5μg/m L tunicamycin(Tm;ERS activator),400μmol/L BPA+1μmol/L 4-phenyl butyric acid(4-PBA;ERS antagonist)and DMEM/F12 complete medium(control),for 24 h.Results In vivo experiments,pregnant Hu ewes receiving the BPA from 40 to 130 days of pregnancy experienced a decrease in placental efficiency,progesterone(P4)level and fetal weight,and an increase in placental estrogen(E2)level,together with barrier dysfunctions,OS,inflammatory responses,autophagy and ERS in type A cotyledons.In vitro experiment,the OTCs exposed to BPA for 24 h showed an increase in the E2 level and related protein and gene expressions of autophagy,ERS,pro-apoptosis and inflammatory response,and a decrease in the P4 level and the related protein and gene expressions of antioxidant,anti-apoptosis and barrier function.Moreover,treating the OTCs with Tm aggravated BPA-induced dysfunction of barrier and endocrine(the increased E2 level and decreased P4 level),OS,inflammatory responses,autophagy,and ERS.However,treating the OTCs with 4-PBA reversed the counteracted effects of Tm mentioned above.Conclusions In general,the results reveal that BPA exposure can cause ERS in the ovine placenta and OTCs,and ERS induction might aggravate BPA-induced dysfunction of the placental barrier and endocrine,OS,inflammatory responses,and autophagy.These data offer novel mechanistic insights into whether ERS is involved in BPA-mediated placental dysfunction and fetal development.

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.

Spatial-temporal changes and driving factors of eco-environmental quality in the Three-North region of China

Eco-environmental quality is a measure of the suitability of the ecological environment for human survival and socioeconomic development.Understanding the spatial-temporal distribution and variation trend of eco-environmental quality is essential for environmental protection and ecological balance.The remote sensing ecological index(RSEI)can quickly and objectively quantify eco-environmental quality and has been extensively utilized in regional ecological environment assessment.In this paper,Moderate Resolution Imaging Spectroradiometer(MODIS)images during the growing period(July-September)from 2000 to 2020 were obtained from the Google Earth Engine(GEE)platform to calculate the RSEI in the three northern regions of China(the Three-North region).The Theil-Sen median trend method combined with the Mann-Kendall test was used to analyze the spatial-temporal variation trend of eco-environmental quality,and the Hurst exponent and the Theil-Sen median trend were superimposed to predict the future evolution trend of eco-environmental quality.In addition,ten variables from two categories of natural and anthropogenic factors were analyzed to determine the drivers of the spatial differentiation of eco-environmental quality by the geographical detector.The results showed that from 2000 to 2020,the RSEI in the Three-North region exhibited obvious regional characteristics:the RSEI values in Northwest China were generally between 0.2 and 0.4;the RSEI values in North China gradually increased from north to south,ranging from 0.2 to 0.8;and the RSEI values in Northeast China were mostly above 0.6.The average RSEI value in the Three-North region increased at an average growth rate of 0.0016/a,showing the spatial distribution characteristics of overall improvement and local degradation in eco-environmental quality,of which the areas with improved,basically stable and degraded eco-environmental quality accounted for 65.39%,26.82%and 7.79%of the total study area,respectively.The Hurst exponent of the RSEI ranged from 0.20 to 0.76 and the future trend of eco-environmental quality was generally consistent with the trend over the past 21 years.However,the areas exhibiting an improvement trend in eco-environmental quality mainly had weak persistence,and there was a possibility of degradation in eco-environmental quality without strengthening ecological protection.Average relative humidity,accumulated precipitation and land use type were the dominant factors driving the spatial distribution of eco-environmental quality in the Three-North region,and two-factor interaction also had a greater influence on eco-environmental quality than single factors.The explanatory power of meteorological factors on the spatial distribution of eco-environmental quality was stronger than that of topographic factors.The effect of anthropogenic factors(such as population density and land use type)on eco-environmental quality gradually increased over time.This study can serve as a reference to protect the ecological environment in arid and semi-arid regions.

Long-term implications of fetal growth restriction

Fetal growth restriction(FGR),or intrauterine growth restriction(IUGR),is a complication of pregnancy where the fetus does not achieve its genetic growth potential.FGR is characterized by a pathological retardation of intrauterine growth velocity in the curve of intrauterine growth.However,the FGR definition is still debated,and there is a lack of a uniform definition in the literature.True IUGR,compared to constitutional smallness,is a pathological condition in which the placenta fails to deliver an adequate supply of oxygen and nutrients to the developing fetus.Infants with IUGR,compared to appropriately grown gestational age infants,have a significantly higher risk of mortality and neonatal complications with long-term consequences.Several studies have demonstrated how suboptimal fetal growth leads to long-lasting physiological alterations for the developing fetus as well as for the newborn and adult in the future.The long-term effects of fetal growth retardation may be adaptations to poor oxygen and nutrient supply that are effective in the fetal period but deleterious in the long term through structural or functional alterations.Epidemiologic studies showed that FGR could be a contributing factor for adult chronic diseases including cardiovascular disease,metabolic syndrome,diabetes,respiratory diseases and impaired lung function,and chronic kidney disease.In this review we discussed pathophysiologic mechanisms of FGR-related complications and potential preventive measures for FGR.

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 CRmimetics, 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.

The effect of caloric restriction on genetical pathways

Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.

Dietary Vitamin K Restriction and Effectiveness of Vitamin K Antagonists Prescribed at the CNHU-HKM University Cardiology Clinic/BENIN

Introduction: Their efficacy in preventing thrombotic and embolic events has been proven in numerous studies, but their narrow therapeutic index requires particular vigilance, especially in terms of biology. In addition, treatment-related hemorrhagic complications are not uncommon. This study explores the influence of dietary vitamin K restriction on the efficacy of antivitamin K treatment at the University Cardiology Clinic of CNHU-HKM. Methods: Cross-sectional and descriptive study that took place from 25 April to 29 August 2019. Patients’ dietary behaviors and successive INR values were collected. Information on dietary intake was obtained by 2 non-consecutive 24-hour recalls. The effectiveness of VKA treatment was assessed by the “Time in Therapeutic Range” (TTR) of the INR. VKA treatment was considered effective for a TTR greater than 65%. Results: At the end of this study, 40 patients were surveyed. The mean age of the participants was 58.05 years ± 13.32 years, with a sex ratio of 1.35. Complete arrhythmia due to atrial fibrillation was the main indication for VKA treatment (37.50%) and fluindione was the most commonly prescribed drug (77.50%). The duration of treatment was less than or equal to 2 years in 47.5% of the subjects surveyed. Before starting treatment, 85% of patients received advice on restricting vitamin K-rich foods, and 45% of patients reported “food burnout” after a period of compliance with the restriction. The majority of respondents (97.50%) complied with the restriction on vitamin K-rich foods. All respondents had high energy intakes and a poor distribution of macronutrients, with a predominance of carbohydrates and proteins. 2.5% of respondents were on effective anti-vitamin K therapy with a TTR of over 65%. Conclusion: Restriction of vitamin K-rich foods is not conducive to effective treatment with vitamin K antagonists.

Calorie restriction potentiates epigallocatechin-3-gallate-mediated Nrf2 activation in hepatocytes of aged rats

Objective:To explore the combinatorial effect of epigallocatechin-3-gallate(EGCG)and calorie restriction on activation of nuclear factor erythroid 2-related factor 2(Nrf2),a transcription factor involved in the antioxidant defense system of aged rats.Methods:Aged male Wistar rats were calorie-restricted and treated with EGCG orally for 45 days.The initial body weight of aged rats was recorded,and the final body weight was measured at the end of the experimental period.Serum lipid and lipoprotein status,oxidative stress markers such as free radicals and malondialdehyde levels,and reduced glutathione were assessed.In addition,RT-PCR and Western blotting analyses were performed.Results:Calorie restriction potentiated the effect of EGCG on enhancing antioxidant status,improving the levels of serum lipid and lipoproteins,upregulating Nrf2 and Bcl2,and downregulating Keap1,cullin3,Bax and cytochrome c in aged rats.Conclusions:Calorie restriction can promote EGCG-mediated Nrf2 activation in aged rats.This preliminary finding paves the way for a combinatory approach to replenishing the antioxidant status during aging,thereby reducing the risk for age-associated degenerative diseases.

Effect of Sleep Hygiene Orientation on Social Cognition Impairments Due to Chronic Sleep Restriction in Mexican Medical Residents

Introduction: Sleep is critical to human physiological function, cognitive performance, and emotional regulation. Healthcare personnel, especially physicians, are chronically exposed to long working hours, which are often accompanied by decreased sleep time. Clinical evidence indicates that these conditions affect their cognitive function and professional practice, but researchers in the field have not sufficiently explored the possible effects of reductions in sleep time on social cognition. Objective: The aim of this is to further explore the effects of sleep restriction among medical residents, the specific impairments in social cognition that it produces, and the effects of a sleep hygiene orientation on those impairments. Method: There were 124 medical residents (50 males, 74 females) who completed a daily sleep/work log, a battery of sleep tests/questionnaires, and neuropsychological evaluations. The participants then received a short course (8 hours) on basic concepts of sleep hygiene and sleep psychoeducation. Once the course was completed, participants filled out the questionnaires again. Results: The results indicate that sleep disturbances in medical residents were associated with severe neurocognitive and social cognition impairments. After the sleep hygiene intervention, neuropsychological function and sleep parameters improved, awareness increased, and social cognition performance significantly improved. Conclusion: Using sleep psychoeducation and sleep hygiene intervention in medical residents is a simple strategy to mitigate the effects of sleep restriction.

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.

Unenumerated Rights Clauses and the System of Restriction on Fundamental Rights——Another Construction Plan for Article 51 of the Constitution of PRC

According to constitutional jurisprudence in China,Article 51 of the Constitution is an unenumerated restrictive clause.Such theoretical construction fails to justify the differentiated restrictions established in the Constitution and makes it difficult to explain the constitutional status of human dignity. Article 51 implies the possibility of other theoretical constructions. It is not an unenumerated restriction clause but an unenumerated rights clause. It aims to provide guarantees for general freedom of action not enumerated in the Constitution rather than restricting fundamental rights. The actual benefit of this kind of theoretical construction lies in that it can establish the basis of the constitutional text for general freedom of action and promote the people’s correct understanding of the model of restriction on fundamental rights established by the Constitution of PRC.

Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.

The Restriction on Educational Quality in Rural Schools

In order to understand the educational quality in rural schools,I went deep into Huangjia Middle School(situatedin Northern China)to make the research.In this article,I focus on the restrictions on educational qualitys,which is one of themain themes about rural education.The factors influencing quality in rural schools are analyzed in this article.It is concludedthat educational quality depends on the relationship of teaching and learning and its supporting context.

Intermittent energy restriction in type 2 diabetes: A short discussion of medication management

AIM To discuss type 2 diabetes mellitus(T2DM) medication changes required during the popular 5:2 intermittent energy restriction(IER) diet. METHODS A search was conducted in MEDLINE, EMBASE, AMED, CINAHL and Cochrane library for original research articles investigating the use of very low calorie diets(VLCD) in people with T2 DM. The search terms used included "VLCD" or "very low energy diet" or "very low energy restriction" or "IER" or "intermittent fasting" or "calorie restriction" or "diabetes mellitus type 2" and "type 2 diabetes". Reference lists of selected articles were also screened for relevant publications. Only research articles written in English, which also included an explanation of medication changes were included. A recent pilot trial using the 5:2 IER method, conducted by our research group, will also be summarized.RESULTS A total of 8 studies were found that investigated the use of VLCD in T2 DM and discussed medication management. Overall these studies indicate that the use of a VLCD for people with T2 DM usually require the cessation of medication to prevent hypoglycemia. Therefore, the 5:2 IER method will also require medication changes, but as seen in our pilot trial, may not require total cessation of medication, rather a cessation on the 2 IER days only. CONCLUSION Guidelines outlined here can be used in the initial stages of a 2-d IER diet, but extensive blood glucose monitoring is still required to make the necessary individual reductions to medications in response to weight loss.

Quantitative Evaluation of Sustainable Development and Eco-Environmental Carrying Capacity in Water-Deficient Regions:A Case Study in the Haihe River Basin,China

Quantitative assessment of development sustainability could be a challenge to regional management and planning, especially for areas facing great risks of water shortage. Surface-water decline and groundwater over-pumping have caused serious environmental problems and limited economic development in many regions all around the world. In this paper, a framework for quantitatively evaluating development sustainability was established with water-related eco-environmental carrying capacity （EECC） as the core measure. As a case study, the developed approach was applied to data of the Haihe River Basin, China, during 1998 through 2007. The overall sustainable development degree （SDD） is determined to be 0.39, suggesting that this rate of development is not sustainable. Results of scenario analysis revealed that overshoot, or resource over- exploitation, of the Basin＇s EECC is about 20% for both population and economy. Based on conditions in the study area in 2007, in order to achieve sustainable development, i.e., SDD〉0.70 in this study, the EECC could support a population of 108 million and gross domestic product （GDP） of 2.72 trillion CNY. The newly developed approach in quantifying ecoenvironmental carrying capacity is anticipated to facilitate sustainable development oriented resource management in waterdeficient areas.

Land cover change and eco-environmental quality response of different geomorphic units on the Chinese Loess Plateau

Land cover in the Chinese Loess Plateau has undergone dramatic changes since the late 1980s.Revealing the trend in land cover change and eco-environmental quality response of different geomorphic units in this stage is a realistic requirement for promoting sustainable development of the Chinese Loess Plateau.Based on the data of geomorphic units and land cover in 1990,2000,2010 and 2018 of the Chinese Loess Plateau,we studied the trend of land cover change and eco-environmental quality response of different geomorphic units by using a significance index of land cover change,a proportion index of land cover change and an eco-environmental response model.The results indicated that from 1990 to 2018,the areas of forestland and construction land substantially increased,whereas those of cropland,grassland,wetland and unused land considerably decreased.Land cover change exhibited large geomorphic differences,and the main conversion of land cover was from cropland into other land types.Unstable trend of land cover change in the loess tablelands and sandy loess hills declined,whereas the unstable trends in the other geomorphic units enhanced.Eco-environmental quality varied among different geomorphic units.The expansion of construction land and degradation of forestland,grassland and wetland resulted in the deterioration of eco-environmental quality.The conversion of cropland and unused land into forestland and grassland,and the conversion of grassland into forestland were the main factors that drove the improvement of eco-environmental quality.The findings of this study may provide theoretical reference and support decision making for the optimization of land use structure and the improvement of eco-environmental quality on the Chinese Loess Plateau.

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.

Protective effects of estrogens and caloric restriction during aging on various rat testis parameters

Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR （40%）. Results： Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes： gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion： Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species （ROS） produced in large quanti- ties in the aged testis.

Insertion Mutagenesis of Trichoderma atroviride by Restriction Enzyme-mediated DNA integration

Restriction enzyme-mediated integration(REMI) of DNA has been recently received attention as a new technique for the generation of mutants by transformation in fungi. Trichoderma atroviride strain T23 was transformed with linearized plasmid pV2, conferring resistance to hygromycin B, in the presence of restriction enzyme used to linearize the plasmid. A total of 172 regeneration transformants were detected by successive inoculation for seven times subcultivation on fresh PDA plate containing hygromycin B. The plasmid was integrated stably into the chromosome DNA, which was confirmed by PCR and southern analysis. The difference between 172 transformants and the parent strain was confirmed in colonial color, sporulation and growth rate. The results showed that the significant difference appeared in above mentioned characters between transformants and parent strain is sporulation capability. Transformants TC6, TD5, TE7, TF1 and TK1 produced higher amounts of conidia than the parent strain T23. In addition, transformants TK1and TC6 showed stronger inhibition to the growth rate of the cucumber wilt pathogen (Fusarium oxyporum) in vitro.