Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

Relationship between Authoritative Parenting Style and Preschool Children’s Emotion Regulation:A Moderated Mediation Model

An authoritative parenting style has been shown to promote children’s emotion regulation in European-American family studies.However,little is known about how sleep problems and the child’s sibling status in Chinese families affect this relationship.Based on family system theory,this study attempts to better understand the relationship between authoritative parenting style and emotion regulation.Mothers of preschool children in Chinese kindergartens completed questionnaires about their children’s sleep habits,their authoritative parenting styles,and children’s emotion regulation.A total of 531 children participated in this study.Results showed that authoritative parenting was positively associated with emotional regulation.Sleep problems mediated the effects of authoritative parenting style on emotion regulation.The child’s sibling status moderated the mediating effects of sleep problems in authoritative parenting and emotion regulation relationships.Specifically,the relationship between the authoritative parenting style and sleep problems was significant for only children,while birth order had no significant influence on the authoritative parenting style and sleep problems in two-child families.These findings suggest that a lowauthoritative parenting style predicts low emotion regulation through sleep problems,and this depends on the child’s sibling status,indicating that children without siblings may impair emotion regulation due to increased sleep problems.

Advances in the Regulation of RpoS Protein Expression and Its Function in Bacteria

RpoS protein is a σ factor of RNA polymerase that can control the expression of a group-specific gene, thus playing a vital role in bacteria. In bacteria, RpoS expression is under strict control and is mainly regulated at three levels： transcription level, translation level and post-translational level. Environmental stress enters bacterial cells through signal transduction and leads to a series of variations in microenvironment, thereby causing changes of regulator and controlling its levels based on the direct and indirect interaction between regulator and RpoS protein. In addition, RpoS protein has played special roles in bacteria, therefore the changes of RpoS protein levels will lead to variations in expression levels of a large number of genes, thereby causing variations of bacterial response to different environmental stress and changes of certain characteristics of bacteria, which provides a new strategy for the control of bacterial diseases in the future. This paper reviewed the recent progress on the regulation of RpoS protein expression and its function in several common bacteria. Due to the functional complexity of RpoS protein, there are still a lot of unknown functions to be further identified.

Fecal-associated microbiome differences between phlegm-dampness constitution and balanced constitution

Objective: This study aimed to explore the structural and functional characteristics of the fecalassociated microbiome(FAM) between the phlegm-dampness constitution(PDC) and balanced constitution(BC), and to screen the related specific operational taxonomic unit(OTU) biomarkers.Methods: This was a cross-sectional study. After strictly identifying the constitution of subjects, their clinical index was recorded and counted. Fecal samples were collected for 16S rDNA sequencing. Alpha diversity, beta diversity, and the relative abundance of dominant bacterial taxa were used to describe the FAM structure, and the Wilcoxon rank-sum test, Metagenome Seq, and linear discriminant analysis effect size(LEf Se) were used to screen specific bacterial taxa. Specific OTUs were screened to construct receiver operating characteristic(ROC) curves.Results: Thirty-two subjects were enrolled, including 22 subjects with BC and 10 subjects with PDC.There were significant differences in cold preference, levels of aspartate transaminase, β2-microglobulin,and creatine kinase MB, and alpha diversity indices(Shannon and Shannoneven) between the two groups. In principal coordinate analysis by abund-jaccard distance measure and partial least squares discriminant analysis, bacterial communities clustered separately between the two groups. Furthermore,based on Metagenome Seq, LEf Se, and the Wilcoxon rank-sum test, a total of 43, 18, and 130 OTUs were differentially distributed between BC group and PDC group, respectively, and OTU200, OTU133, and OTU353 were screened when P≤.01. The area under the ROC curve constructed from the 3 selected OTUs was 0.93.Conclusion: The FAM structure and related functional characteristics of the PDC group differed from those of the BC group. In particular, OTU200, OTU133, and OTU353 can be used as unique markers of PDC to assist clinical diagnosis.

Effects of hypoxia,hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 in hepatic stellate cells

AIM: To study the effects of hypoxia, hyperoxia on the regulation of expression and activity of matrix metalloproteinase-2 (MMP-2) in hepatic stellate cells (HSC). METHODS: The expressions of MMP-2, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and membrane type matrix metalloproteinase-1 (MT1-MMP) in cultured rat HSC were detected by immunocytochemistry (ICC) and in situ hybridization (ISH). The contents of MMP-2 and TIMP-2 in culture supernatant were detected with ELISA and the activity of MMP-2 in supernatant was revealed by zymography. RESULTS: In the situation of hypoxia for 12h, the expression of MMP-2 protein was enhanced (hypoxia group positive indexes: 5.7 +/- 2.0, n=10; control: 3.2 +/- 1.0, n = 7; P【0.05), while TIMP-2 protein was decreased in HSC (hypoxia group positive indexes: 2.5 +/- 0.7, n = 10; control: 3.6 +/- 1.0, n = 7; P 【 0.05), and the activity (total A) of MMP-2 in supernatant declined obviously (hypoxia group: 7.334 +/- 1.922, n = 9; control: 17.277 +/- 7.424, n = 11; P 【 0.01). Compared the varied duration of hypoxia, the changes of expressions including mRNA and protein level as well as activity of MMP-2 were most notable in 6h group. The highest value(A(hypoxia)-A(control)) of the protein and the most intense signal of mRNA were in the period of hypoxia for 6h, along with the lowest activity of MMP-2. In the situation of hyperoxia for 12h, the contents (A(450)) of MMP-2 and TIMP-2 in supernatant were both higher than those in the control, especially the TIMP-2 (hyperoxia group: 0.0499 +/- 0.0144, n = 16; control: 0.0219 +/- 0.0098, n = 14; P 【 0.01), and so was the activity of MMP-2 (hyperoxia group: 5.252 +/- 0.771, n = 14; control: 4.304 +/- 1.083, n = 12; P 【 0.05), and the expression of MT1-MMP was increased. CONCLUSION: HSC is sensitive to the oxygen, hypoxia enhances the expression of MMP-2 and the effect is more marked at the early stage; hyperoxia mainly raises the activity of MMP-2.

Long-term acupuncture treatment has a multitargeting regulation on multiple brain regions in rats with Alzheimer＇s disease：a positron emission tomography study

The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.

Advances in molecular regulation of goat lipid metabolism and FAS structure and function regulation

Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we first introduced the molecular regulation process of goat milk fat metabolism based on the structure research of FAS.Secondly,we reviewed some key factors in FAS transcription and post-transcriptional regulation of the goat mammary gland and preliminarily constructed the expression network of the goat mammary gland FAS gene.The purpose of this paper is to systematically introduce the role of FAS in goat milk fat metabolism and to provide a reference for future studies on the mechanism of goat milk fat metabolism.

Transcriptional dysregulation in neurodegenerative diseases:who tipped the balance of Yin Yang 1 in the brain?

Yin Yang 1(YY1) is a multi-functional transcription factor that regulates gene expression in a range of cell types,including neurons.It controls neuronal differentiation,as well as neuronal specification and migration during the development of the mammalian nervous system.Besides,YY1 also mediates the transcription of genes that are required for neuronal survival.An impairment of the transcriptional function of YY1 causes neuronal death.This review summarizes recent research findings that unveil the dysfunction of YY1 in multiple neurodegenerative disorders.The expression of disease proteins perturbs the function of YY1 via distinct molecular mechanisms,including recruitment to protein aggregates,protein degradation and aberrant nuclear/cytoplasmic shuttling.Understanding the pathogenic roles of YY1 will further broaden our knowledge of the disease mechanisms in distinct neurodegenerative disorders.

Screening influencing factors of blood stasis constitution in traditional Chinese medicine

Objective To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine(TCM) constitution identification.Methods Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors(gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors(sleep time, age,and mother’s age at birth) on the constitution of the two groups were analyzed. In the singlefactor analysis, the Pearson’s chi-square test was selected for the categorical variable, and the independent sample t test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution;the binary logistic stepwise regression method was selected for the multi-factor analysis.Results The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson’s chi-square test yielded significant differences(P < 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples t test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations(P < 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types(P > 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution(P < 0.05).Conclusion Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.

Regulation on the Protection of Fossils Issued by the State Council of the People's Republic of China:Scientists' Researches Protected Legally—Further Explanation

With large-scale engineering projects being carried out in China, a large number of fossil localities have been discovered and excavated by responsible agencies, but still some important fossils of great value have been removed and smuggled into foreign countries. In the last three years, more than 1345 fossil specimens have been intercepted by Customs in Shenzhen, Shanghai, Tianjin, Beijing and elsewhere, and more than 5000 fossils, most of which are listed as key fossils,

Ideal Point Method Applied in Forest Harvest Regulation

Ideal point method is one of the methods to solve multi-objective problem. It is applied to forest harvest regu-lation, and showed very good results by analyzing changes of quantitative indexes of forest resource structure before andafter the regulation. This method can be applied as one of the mathematical tools in forest harvest regulation.

Environmental regulation and firms'performance:a quasi-natural experiment from China

This paper investigates whether environmental regulation affects firm's performance including productivity,wage and employment using firm-level data in 1996-2007.The identification uses Two Control Zones(TCZ)policy implemented by the Chinese government in 1998,in which tougher environmental regulations were imposed in TCZ cities but not others.By difference-indifferences estimation,we find that tougher environmental regulation leads to larger increase on both total factor productivity and wage,and firms tend to employ fewer workers under pressure of environmental protection.Heterogeneous tests show that the impacts are better for nonpollution intensive firms,non-exporters and SOEs.Finally,we find that R&D input and exiting firms among industry are the driving forces for enhancing TFP and increasing wage and unemployment.

China＇s Electricity Industry at the Crossroads： New Challenges for Developing the Right Model of Regulation

China is facing important challenges stemming from increasing rates of urbanization and aging population. To pursue its ＂harmonious society＂ objective without disrupting its path to development major overhauls are necessary in education, health, social security and above all in public services, particularly in electricity. China＇s electricity industry is at the crossroads. To meet the challenges, new models of regulation should be developed and applied. This paper examines the current state of the Chinese electricity industry and the burden it imposes on its public finances. It also reviews and critically examines the existing FIT （Europe） and RPS （USA） models of regulation and of promotion of renewable energies and advances on whether they are advantageous for China. It is argued that the electricity industry has already undergone important reforms but cross subsidies still exist, equivalent to 1.5% of China＇s GDP. Drastic rate rebalancing policies will create sustainability problems and a deterioration of China＇s public finances. To avoid such negative results, China has to further reform its electricity industry gradually and use wisely FIT-type programs to bring renewables into the grid and fulfill the Kyoto Protocol

Regulations on Foreign Exchange System of the People′s RepubliC of China(PartⅡ)

Chapter VI Supervision and Management ●Article 33 The foreign exchange administration agencies shall carry out their responsibilities in accordance with laws and regulations and have the power to take the following measures: (1) Make on-the-spot inspection of financial institutions con- ducting foreign exchange operations;

Implementation Regulations for China's Labor Contract Law

1.Introduction On January 1,2008,the Labor Contract Law of the People's Republic of China(LCL)became effective,resulting in wide- spread changes in labor policy for all companies and other af- fected organizations.As is the case with legislating in China, many details were left for resolution in implementing regulations,

GPCR/endocytosis/ERK signaling/S2R is involved in the regulation of the internalization,mitochondria-targeting and-activating properties of human salivary histatin 1

Human salivary histatin 1(Hst1)exhibits a series of cell-activating properties,such as promoting cell spreading,migration,and metabolic activity.We recently have shown that fluorescently labeled Hst1(F-Hst1)targets and activates mitochondria,presenting an important molecular mechanism.However,its regulating signaling pathways remain to be elucidated.We investigated the influence of specific inhibitors of G protein-coupled receptors(GPCR),endocytosis pathways,extracellular signal-regulated kinases1/2(ERK1/2)signaling,p38 signaling,mitochondrial respiration and Na+/K+-ATPase activity on the uptake,mitochondria-targeting and-activating properties of F-Hst1.We performed a si RNA knockdown(KD)to assess the effect of Sigma-2 receptor(S2R)/Transmembrane Protein 97(TMEM97)—a recently identified target protein of Hst1.We also adopted live cell imaging to monitor the whole intracellular trafficking process of F-Hst1.Our results showed that the inhibition of cellular respiration hindered the internalization of F-Hst1.The inhibitors of GPCR,ERK1/2,phagocytosis,and clathrin-mediated endocytosis(CME)as well as siRNA KD of S2R/TMEM97 significantly reduced the uptake,which was accompanied by the nullification of the promoting effect of F-Hst1 on cell metabolic activity.Only the inhibitor of CME and KD of S2R/TMEM97 significantly compromised the mitochondria-targeting of Hst1.We further showed the intracellular trafficking and targeting process of F-Hst1,in which early endosome plays an important role.Overall,phagocytosis,CME,GPCR,ERK signaling,and S2R/TMEM97 are involved in the internalization of Hst1,while only CME and S2R/TMEM97 are critical for its subcellular targeting.The inhibition of either internalization or mitochondria-targeting of Hst1 could significantly compromise its mitochondria-activating property.

China's Constitution:Guarantee for People's Rights

The Communist Party of China, which represents the fundamental interests of the broadest possible masses of the people, has always attached much importance to the rights of the people and the safeguard measures. As early as in the New Democratic Revolution period, it adopted in Ruijin, Jiangxi Province, an Outline Constitution of the All-China Soviet Republic in January 1934. The document stipulated that all workers, peasants, soldiers and other labor populace and their families, irrespective of their gender, ethnic group or religion, are equal before the law of the Soviet and enjoy the right to work, supervision, education and the freedom

China's Regulations on Cultural Exchanges with Foreign Countries

China's cultural exchanges with foreign countries follow cen- tralized administration by the Ministry of Culture.On June 27,1997,the Ministry of Culture promul- gated the Regulations on Foreign Cultural and Artistic Performances and Exhibi-

Huu S. TIEU Request for FDA to Establish Regenerating Human Cells as Law on December 13, 2016 President Barack H. Obama Signed the 21st Century CURES Act into FDA Regulation and Law

Background and Aims: On November 24, 2009, Huu S. TIEU and Golden Sunrise Pharmaceutical, Inc. (Golden Sunrise) applied for the Technology and Innovation to be reviewed and evaluated by the U.S. Food and Drug Administration (FDA). In the review and evaluation, it was requested by Golden Sunrise designated the new indications for this application under Serious or Life-threatening conditions or diseases. Discussions followed with the FDA, Huu S. TIEU, and Golden Sunrise for FDA approval on new products and new indications on existing new Medical Technology and Innovation. It was agreed in Year-2015 that the FDA would take the request for new indications to the United States Congress to establish into FDA regulation and law. At that time the following was the FDA Guidance—“Emergency Use of a Test Article” is exempt from prior Institutional Review Board or Advisory Committee evaluation and approval, provided that such emergency use is reported to the Institutional Review Board within five working days after use. Expedited Institutional Review Board or Advisory Committee approval is not permitted in emergency use. There has been no funding to the authors for the writing or publication of this article. Methods: It was requested by Huu S. TIEU and Golden Sunrise in documents given to the FDA to have Serious or Life-threatening conditions or diseases indication be recognized by law. On August 08, 2015, the FDA responding to this request took the documentation produced by Golden Sunrise to the United States Congress on behalf of Golden Sunrise and Huu S. TIEU. This article encompasses the FDA regulatory method as well as the discussion and results of the establishment of the FDA and the 21st Century Cures Act. Results: On December 13, 2016, H.R.34—114th United States Congress (2015-2016) 21st Century CURES Act was signed into law by President Barack H. Obama which included the Serious or Life-threatening indication to be written into the CURES Act. In summary, the 21st Century Cures Act is a landmark piece of legislation that enjoyed broad bipartisan support in United States Congress. The main goals of the Act are impactful and should transform future cancer, neurologic, and precision medicine or drug research as well as aid individuals with mental health is intended to facilitate the prompt approval of new agents and devices, clinicians should be aware of the types of data behind an approval and take this into consideration when developing illnesses and opioid dependence. However, some of the wording within the CURES Act regarding the drug and device approval process may bring pause to health care providers including pharmacists. Although this wording and implementing care plans and counseling patients. The 21st Century Cures Act was incorporated into laws and regulations by the FDA under § 3072 of the Act grants the Commissioner of Food and Drugs the authority to appoint and set the annual rate of pay for outstanding and qualified candidates to scientific, technical, or professional positions that support the development, review, and regulation of medical products.