Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Mother Images in Carol Ann Duffy＇s Poetry

＂Mother＂ is sometimes associated with ＂other＂. The same is true in some of Carol Ann Duffy＇s poems, in which some mothers are described as institutionalized in the patriarchal society and considered as ＂the other＂, losing self-identity. Duffy also describes women fighting against the patriarchal control generation after generation until they are finally free. Some mothers exhibit their own potentials as mothers, either able to or unable to fulfill the duties of both material and spiritual caretakers of the family.

Mom's the Word—Great gift ideas for mothers of all ages

Every day should be spent showing Mom how much you appreciate her.However,for any days you might have missed,you can make it up to her with the perfect Mother’s Day gift.Whether she’s a new mother,step- mother,grandmother or like a mother she’s sure to love our top picks.Happy Mother’s Day Mom!

Percutaneous transsplenic embolization of esophageal and gastrio-fundal varices in 18 patients

AIM: Clinical application and potential complication of percutaneous transsplenic varices embolization (PTSVE) of esophageal or gastrio-fundal varices in patients with hepatocellular carcinoma (HCC) complicated with portal vein cancerous thrombosis (PVCT).METHODS: 18 patients with HCC complicated with PVCT and esophageal or gastrio-fundal varices who underwent PTSVE were collected. The rate of success, complication, mortality of the procedure and postoperative complication were recorded and analyzed.RESULTS: PTSVE were successfully performed in 16 of 18cases, and the rate of success was 89%. After therapy erythrocyte counts decreased in all of the natunts. 5 of patients needed blood transfusion, 2 patients requiredsurgical intervention because of and 11 patients with ascites were alleviated by diuresis. Among these 18patients, the procedure-related mortality was 11% (2/18),one died of acute hepatic failure on the forth day after procedure, another died of acute renal failure on the fifth day. The patients were follow up for 112 mon exceptone. 13of them died of their tumors but none of them experienced variceal bleeding.CONCLUSION: PTSVE is a relatively safe and effective method to treat esophageal or gastrio-fundal varices in HCCpatients with PVCT when percutaneous transhepatic varices embolization (PTHVE) of varices is impossible.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

Phosphorylated tau as a toxic agent in synaptic mitochondria: implications in aging and Alzheimer’s disease

During normal aging,there is a decline in all physiological functions in the organism.One of the most affected organs is the brain,where neurons lose their proper synaptic function leading to cognitive impairment.Aging is one of the main risk factors for the development of neurodegenerative diseases,such as Alzheimer’s disease.One of the main responsible factors for synaptic dysfunction in aging and neurodegenerative diseases is the accumulation of abnormal proteins forming aggregates.The most studied brain aggregates are the senile plaques,formed by Aβpeptide;however,the aggregates formed by phosphorylated tau protein have gained relevance in the last years by their toxicity.It is reported that neurons undergo severe mitochondrial dysfunction with age,with a decrease in adenosine 5′-triphosphate production,loss of the mitochondrial membrane potential,redox imbalance,impaired mitophagy,and loss of calcium buffer capacity.Interestingly,abnormal tau protein interacts with several mitochondrial proteins,suggesting that it could induce mitochondrial dysfunction.Nevertheless,whether tau-mediated mitochondrial dysfunction occurs indirectly or directly is still unknown.A recent study of our laboratory shows that phosphorylated tau at Ser396/404(known as PHF-1),an epitope commonly related to pathology,accumulates inside mitochondria during normal aging.This accumulation occurs preferentially in synaptic mitochondria,which suggests that it may contribute to the synaptic failure and cognitive impairment seen in aged individuals.Here,we review the main tau modifications promoting mitochondrial dysfunction,and the possible mechanism involved.Also,we discuss the evidence that supports the possibility that phosphorylated tau accumulation in synaptic mitochondria promotes synaptic and cognitive impairment in aging.Finally,we show evidence and argue about the presence of phosphorylated tau PHF-1 inside mitochondria in Alzheimer’s disease,which could be considered as an early event in the neurodegenerative process.Thus,phosphorylated tau PHF-1 inside the mitochondria could be considered such a potential therapeutic target to prevent or attenuate age-related cognitive impairment.

A unified constitutive model for multiphase precipitation and multi-stage creep ageing behavior of Al−Li−S4 alloy

A unified constitutive model is presented to predict the recently observed“multi-stage”creep behavior of Al−Li−S4 alloy.The corresponding microstructural variables related to the yield strength and creep deformation of the alloy during the creep ageing process,including dislocations and multiple precipitates,have been characterized in detail by X-ray diffraction(XRD)and transmission electron microscopy(TEM).For the yield strength,the model considers the multiphase strengthening behavior of the alloy based on strengthening mechanisms,which includes shearable T1 precipitate strengthening,non-shearable T1 precipitate strengthening andθ′precipitate strengthening.Based on creep deformation mechanism,the“multi-stage”creep behavior of the alloy is predicted by introducing the effects of interacting microstructural variables,including the radius of multiple precipitates,dislocation density and solute concentration,into the creep stress−strain model.It is concluded that the results calculated by the model are in a good agreement with the experimental data,which validates the proposed model.

Initial Rifting Age of the Nearly N–S Rifts in Southern Tibetan Plateau:New Evidence from the Age limit of the Early Sediments

Objective The nearly parallel N-S-trending rifts in southern Tibet represent the E-W extension of the Tibet Plateau. Most data which constrained the age of the extensional deformation come from isotopic dating of the dikes probably related to the activity of the nearly N-S faulting and micas from hydrothermal activity and the low- temperature thermochronology of plateau uplift. Previous research shows that there are at least three different ideas about the age of the rifts： （1） older than 16-12 Ma, （2） 14- 10 Ma, and （3） 8-4 Ma （Fig. la）. For the old sedimentary strata represented the beginning of the rifting, the dating of the sediments helps to better define the initial rifting age.

Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice

AIM：To identify the pathological role of amyloid beta（Aβ） deposition in retinal degeneration,and explore Aβ deposition on the retinal pigment epithelium cells（RPE） layer and the associated structural and functional changes in Alzheimer＇s disease transgenic mice.METHODS：RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic（NTG） mice over 20 months old were examined.Histological changes were investigated via hematoxylin and eosin（H＆E） staining and transmission electron microscopy（TEM） examination,whereas the expression of amyloid precursor protein（APP）,Aβ,Zonula occludens-1（ZO-1） and Ionized calcium binding adaptor molecule-1（IBA-1） were investigated using immunohistochemistry and immunofluorescence techniques.All of the obtained results were quantitatively and statistically analyzed.RESULTS：In aged transgenic mice,an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice.The RPE demonstrated some vacuole changes,shortened basal infoldings and basal deposition in histopathological examination and TEM tests,wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence.Furthermore,IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch＇s membrane（Br M） complex,which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice.The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts.CONCLUSION：The observed Aβ deposition in the RPE layer may cause RPE dysfunction,which is associated with microglia cells infiltration into the retina of aged transgenic mice,suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

Biliverdin Reductase-A correlates with inducible nitric oxide synthasein in atorvastatin treated aged canine brain

Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment （80 mg/day for 14.5 months） to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosative stress levels. We hypothesize that biliverdin reductase-A-dependent inducible nitric oxide synthase regulation strongly contributes to the cognitive improvement observed following atorvastatin treatment.

Mothers’ Knowledge of Health Caring for Premature Infants after Discharge from Neonatal Intensive Care Units in the Gaza Strip, Palestine

Background: Preterm labor is one of the most public health problems related to neonates admitted to Neonatal Intensive Care Unit (NICU). Poor knowledge among mothers about the care requirements of a preterm neonate is immediate cause for post-discharge medical problems in premature and neonates readmission to NICU. Hence, this study aims to evaluate mothers’ knowledge of caring for premature infants post-discharge from Neonatal Intensive Care Units in the Gaza strip. Methods: A Quantitative-based cross-sectional designs study was used to survey 120 mothers of preterm neonates at the time of preterm neonates discharge by face-to-face interview at Al-Shifa medical complex and Nasser hospital between February and June 2018. Results: The results showed that only about 58.4% of mothers of premature babies had good knowledge about health care needed for premature infants after discharge from NICU. Furthermore, there was no statistically significant difference between the level of knowledge and mother’s sociodemographic characteristics (P-values > 0.05). Conclusion: Mothers’ knowledge of premature infants care was not at the optimal level, which might put the newborns at risk. Therefore, the study emphasizes the necessity of thoughtful exchange of health information between team members and mothers and establishing pre- and post-discharge plans with mothers to start their healthy transition of preterm neonate to home and to ameliorate family concerns.

Tectonic Environments of the Yan-Liao Rift during Earth's Middle Age(1.7～0.75 Ga): Evidence from Mafic Dyke Swarms in Eastern Hebei, North China

During the past decade,generations of Precambrian mafic dykes/sills have been investigated and revealed in the North China Craton(NCC).Researchers identified more than 20 episodes of Precambrian dyke swarms,

Effect of insulin on hyperkalemia during anhepatic stage of liver transplantation

AIM:To investigate the effectiveness of insulin on decreasing serum potassium concentration during anhepatic stage of orthotopic liver transplantation. METHODS:Sixteen patients with serum potassium concentrations greater than 4.0 mmol/L at the onset of anhepatic stage were randomized into two groups.The patients in control group (n=8) received no treatment, while those in treatment group (n=8) received an intravenous bolus injection of regular insulin (20U) 10 min into the anhepatic stage,followed by a glucose infusion (500mL 50g/L dextrose) over 15 min. RESULTS:In control group,potassium concentration underwent no changes whereas in treatment group,it decreased from 4.8±0.48 mmol/L to 4.19±0.55 mmol/L (mean±SD) within 15 min and to 3.62±0.45 mmol/L 60 min after the therapy.The potassium concentration was lower in treatment group than in control group within 30 min of treatment (3.94±0.57 vs 4.47±0.42 mmol/L, respectively;P<0.05),and increased similarly 30 s after graft reperfusion in both groups of patients,but remained lower in treatment group (5.81±2.78 vs 7.44±1.75 mmol/L, respectively;P<0.05).The potassium concentration returned to pre-reperfusion levels within 5 min after graft reperfusion. CONCLUSION:In patients undergoing orthotopic liver transplantation,the administration of insulin rapidly decreases serum potassium concentration even in the absence of the liver,suggesting an important contribution by extrahepatic tissues in insulin-stimulated uptake of potassium.

ELECTRON SPIN RESONANCE DATING FOR THE AGE OF PEKING-MAN, LOC.1, ZHOUKOUDIAN, BEIJING

In this paper, we used ESR dating method to measure the accumulative dose of the fossil teeth samples, which are contemporaneous with the Peking-Man. The internal annual dose rate of samples are got by neutron activation analysis and the environmental annual dose rate by highly sensitive TL dosimeters to be embedded in cave deposits in the site. The results of ESR dating are corresponded with the dating results obtained by U-series, FT, TL and paleomagnetic stratigraphical methods on the 3rd, 4th, 7th and 10th layers. Calculation of using different models, the close-equilibrium model, the linear uranium accumulation model and radon loss-linear uranium accumulation model, for travertine, deer teeth and rhinoceros tooth, we obtained the age of the First Peking- Man in the nth layer is 578 ka and gave ages of other layers, from the 1st to the 13th layer in Peking- Man site.

Age related changes in pancreatic beta cells: A putativeextra-cerebral site of Alzheimer's pathology

Frequent concomitant manifestation of type 2 diabetesmellitus (T2DM) and Alzheimer's disease (AD) hasbeen recently demonstrated by epidemiological studies.This might be due to functional similarities between β-cells and neurons, such as secretion on demand ofhighly specific molecules in a tightly controlled fashion.An additional similarity represents the age-relatedalteration of hyperphosphorylated tau in AD patients.Similarly, alterations have been identified in β-cells of T2DM patients. The islet amyloid polypeptide has beenassociated with β-cell apoptosis. As a consequence ofincreasing age, the accumulation of highly modified proteins together with decreased regenerative potentialmight lead to increasing rates of apoptosis. Moreover, reduction of β-cell replication capabilities results in reduction of β-cell mass in mammals, simultaneously withimpaired glucose tolerance. The new challenge is tolearn much more about age-related protein modifications. This can lead to new treatment strategies forreducing the incidence of T2DM and AD.

China’s National Image in Western Travel Writings in the Age of Discovery

Western travel writings about China provided material driving and theoretical guidance for the Age of Discovery, and became the main spiritual motive of the Westerners voyage to the East. In the Age of Discovery, the image of China in the eyes of Western envoys, merchants and missionaries begun to fade away from traditional mythological and psychedelic colors, and the image of cultural elements such as material, spirit and history become clear. These Western travelers tried to shape the image of China as a state of civilization and wisdom, a state of moral order, and a state of wealth and power. On the basis of the continued description of the kingship and wealth of the Middle Ages, they constructed an overall image of China as a powerful state of civilization and wealth, thus forming a new frame of reference for cognition of China.

Association of Television Watching Practices of Mothers on Overweight and Obesity of Their Under-5 Offspring in Urban Bangladesh

Childhood overweight and obesity, is an emerging public health concern in developing countries like Bangladesh. However, regular television watching by child’s mother and its impact on excess weight gain or overweight and obesity to their offspring is not reported elsewhere. The aim of the present analysis was to determine the socio-demographic characteristics among overweight and obese children based on those mothers who watch television regularly and compare this finding with malnourished and well-nourished under-5 children. A total of 20,800 under-5 children were enrolled during 1996 to 2012 in the Diarrheal Disease Surveillance System (DDSS) of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). Mean weight-for-age z-score (–1.61 vs. –2.30;mean difference: ?0.69;p < 0.001), height-for-age z-score (–1.42 vs. –1.99;–0.57;<0.001), weight-for-height z-score (–1.59 vs. –1.07;–0.53;<0.001), BMI-for-age z-score (–1.09 vs. –1.61, –0.52;<0.001) differed significantly between the children whose mother did and did not watch television regularly. Under-5 children whose mother watched television regularly (2%) compared to those who did not (1%), had 2.28 [(95% CI-1.61 - 3.24) p < 0.001] times increased odds of being overweight and obese. Television watching of mothers is associated with childhood overweight and obesity and is one of the most public health concerns in Bangladesh. These changes may be in part of better socio-economic condition, changes in life style behaviour and dietary pattern.

Zhu Xianmo——The Man Who Harnessed the Power of China’s Mother Rive

THE Yellow River is the second longest river in China and called the cradle of Chinese civilization. With a drainage area totaling 750,000 square kilometers, it runs 5,464 kilometers through nine provinces and autonomous regions before emptying into the Bohai Sea.