[Systematic evaluation for efficacy of tripterygium glycosides in treating diabetic nephropathy stage IV].

To systematically evaluate the efficacy and safety of tripterygium glycosides (TG) combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV. The computer retrievals were made in Cochrane Libarary, PubMed, Embase, SCI, Sinnomed, CNKI, Chinainfo and VIP, and hand retrievals were conducted for meeting and academic papers (updated to December 30, 2014), in order to collect randomized controlled trials and quasi-randomized control trials for TG combined with ACEI/ARB preparation in treating diabetic nephropathy stage IV and set the literature inclusion and elimination standards. Eligible literatures were included and evaluated according to standards in Cochrane Handbook. RevMan 5.3 and Stata 12.0 were used for a Meta-analysis. A total of 13 randomized controlled trials and quasi-randomized control trials involving 1119 patients with diabetic nephropathy were included. The Meta analysis result showed that compared with the control group, the combination group showed better effects in reducing the 24-hour urinary protein [MD = -0.84, 95% CI (-1.02, -0.66)], raising albumin [SMD = 0.98, 95% CI (0.81, 1.16)], the total efficiency [OR = 4.23, 95% CI (2.77, 6.46)] and the significant efficiency [OR = 5.35, 95% CI (2.70, 10.60)], with no statistical difference in Serum Creatinine between Both groups [MD = -0.82, 95% CI (-4.30, 2.66), P = 0.64]. However, the risk of adverse reactions increased by 7% [RD = 0.07, 95% CI (0.03, 0.12)]. The Egger's test showed no publication bias. Tripterygium Glycosides combined with ACEI/ARB in treating diabetic nephropathy stage IV is supper than the single administration of ACEI/ARB, with a good prospect in clinical application. Nevertheless, due to the small-size and low-quality samples in this study, more high-quality and large sample-size randomized controlled trials shall be conducted to verify the findings.

Microbial consortium and its spatial distribution in a compartmentalized anaerobic reactor.

The compartmentalized anaerobic reactor (CAR) is a patent novel high-rate reactor, which consists of three compartments. The reactor has a great potential for application due to its many advantages. In this work, the microbial consortium, spatial distribution, and their relationship with performance of CAR were investigated by means of polymerase chain reaction, denaturing gradient gel electrophoresis, and fluorescence in situ hybridization. The results showed that the predominant archaea were Methanobacterium, Methanosaeta, and Methanospirillum, and the predominant bacteria were Firmicutes, Deltaproteobacteria, Spirochaetes, Actinobacteria, and Gammaproteobacteria in the microbial consortium. The methanogenic archaea (MA), the hydrogen-producing acetogenic bacteria (HAB), and the hydrolytic fermentative bacteria (HFB) were found to be predominant in the upper, middle, and bottom compartments, respectively. The results revealed that the granular sludge took on a stratified microbial structure. The HFB, HAB, and MA were located in the outer shell, middle layer, and core, respectively. The microbial populations from the bottom compartment were relatively homogeneous in the granular sludge, and from the middle and upper compartments, they were relatively heterogeneous in the granular sludge. The microbial consortia and their spatial distribution were in accordance with the organic loading rate and chemical components in the three compartments.

Diffusion law of coal gangue slurry and the application of fluidized filling technology of gangue in caving area.

In order to deeply study the basic characteristics, diffusion laws, and flow laws of coal gangue and coal gangue slurry, the basic characteristic parameters of coal gangue and coal gangue slurry were obtained through particle size distribution test, electron microscope scanning test, X-ray diffraction test, X-ray fluorescence spectrum test, and angle of repose test. The conveying performance test of coal gangue slurry was carried out, and based on this, a simulation test of coal gangue slurry caving areas was designed. The diffusion and flow laws of coal gangue slurry under the same inclination angle were summarized, and the field test of fluidization filling in the caving areas was conducted. The results show that: (1) The water-to-gangue ratio was the main controlling factor for the conveying performance of coal gangue slurry. The extensibility, slump, and bleeding rate of the coal gangue slurry increased with the increase of the water-to-gangue ratio. (2) The diffusion profile of coal gangue slurry at different dip angles was arc-shaped, and the diffusion distance of slurry increased with the increase of infiltration time. However, there were differences in the sustained diffusion ability of different dip angles. (3) At the same time interval, the spatial accumulation patterns of scattered gangue in different regions will lead to differences in the diffusion speed of the slurry. (4) Both burying and hanging pipes in the falling area can safely and efficiently fill the gangue slurry. The diffusion distance of the caving areas in the test working face was basically consistent with the diffusion distance of the slurry in the simulation test of the coal gangue slurry caving areas.

Analytical solution of epidemic threshold for coupled information-epidemic dynamics on multiplex networks with alterable heterogeneity.

The phase transition of epidemic spreading model on networks is one of the most important concerns of physicists to theoretical epidemiology. In this paper, we present an analytical expression of epidemic threshold for interplay between epidemic spreading and human behavior on multiplex networks. The threshold formula proposed in this paper reveals the relation between the threshold on single-layer networks and that on multiplex networks, which means that the theoretical conclusions of single-layer networks can be used to improve the threshold accuracy of multiplex networks. To verify how well our formula works in different networks, we build a network model with constant total number of edges but gradually changing the heterogeneity of the network, from scale-free network to Erdos-Rényi random network. By use of theoretical analysis and computer simulations, we find that the heterogeneity of information layer behaves as a "double-edged sword" on the epidemic threshold: The strong heterogeneity can effectively improve the epidemic threshold (which means the disease outbreak requires a higher infection probability) when the awareness probability α is low, while the opposite effect takes place for high α. Meanwhile, the weak heterogeneity of the information layer is effective in suppressing the epidemic prevalence when the awareness probability is neither too high nor too low.

Dynamic tensile properties, deformation, and failure testing of impact-loaded coal samples with various water content.

Disc coal samples with different water content were tested using the split Hopkinson press bar test system. Their dynamic tensile failure process was monitored via an ultra-high-speed digital image correlation system. The deformation trend and failure characteristics as a function of the water content were analyzed, and the water content effect on dynamic mechanical properties was investigated. The results demonstrated that the dynamic stress-strain curve of the coal samples consisted of four stages. As the water content increased, the coal sample brittleness degraded, while its ductility was enhanced. Quadratic polynomial functions can describe dynamic peak stress, peak strain, and loading pressure. Under different loading pressures, the dynamic peak stress exhibited a concave bending trend as the water content increased. The coal sample's dynamic tensile strength had a strong rate correlation, and the saturated coal sample exhibited the highest rate correlation. Under high-rate loading, the inertia effect and the Stefan effect of water in coal samples hinder the initiation and propagation of coal sample cracks, improving the coal sample's strength. The research results provide a basic theoretical basis for the prevention and control of rock burst in coal mines.

Collective firing patterns of neuronal networks with short-term synaptic plasticity.

We investigate the occurrence of synchronous population activities in a neuronal network composed of both excitatory and inhibitory neurons and equipped with short-term synaptic plasticity. The collective firing patterns with different macroscopic properties emerge visually with the change of system parameters, and most long-time collective evolution also shows periodic-like characteristics. We systematically discuss the pattern-formation dynamics on a microscopic level and find a lot of hidden features of the population activities. The bursty phase with power-law distributed avalanches is observed in which the population activity can be either entire or local periodic-like. In the purely spike-to-spike synchronous regime, the periodic-like phase emerges from the synchronous chaos after the backward period-doubling transition. The local periodic-like population activity and the synchronous chaotic activity show substantial trial-to-trial variability, which is unfavorable for neural code, while they are contrary to the stable periodic-like phases. We also show that the inhibitory neurons can promote the generation of cluster firing behavior and strong bursty collective firing activity by depressing the activities of postsynaptic neurons partially or wholly.

Understanding collective behaviors in reinforcement learning evolutionary games via a belief-based formalization.

Collective behaviors by self-organization are ubiquitous in nature and human society and extensive efforts have been made to explore the mechanisms behind them. Artificial intelligence (AI) as a rapidly developing field is of great potential for these tasks. By combining reinforcement learning with evolutionary game (RLEG), we numerically discover a rich spectrum of collective behaviors-explosive events, oscillation, and stable states, etc., that are also often observed in the human society. In this work, we aim to provide a theoretical framework to investigate the RLEGs systematically. Specifically, we formalize AI-agents' learning processes in terms of belief switches and behavior modes defined as a series of actions following beliefs. Based on the preliminary results in the time-independent environment, we investigate the stability at the mixed equilibrium points in RLEGs generally, in which agents reside in one of the optimal behavior modes. Moreover, we adopt the maximum entropy principle to infer the composition of agents residing in each mode at a strictly stable point. When the theoretical analysis is applied to the 2×2 game setting, we can explain the uncovered collective behaviors and are able to construct equivalent systems intuitively. Also, the inferred composition of different modes is consistent with simulations. Our work may be helpful to understand the related collective emergence in human society as well as behavioral patterns at the individual level and potentially facilitate human-computer interactions in the future.

GPR30-mediated estrogenic regulation of actin polymerization and spatial memory involves SRC-1 and PI3K-mTORC2 in the hippocampus of female mice.

AIMS: The G-protein-coupled estrogen receptor GPR30 (also referred to as GPER) has been implicated in the estrogenic regulation of hippocampal plasticity and spatial memory; however, the molecular mechanisms are largely unclear. METHODS: In this study, we initially examined the levels of GPR30 in the hippocampus of postnatal, ovariectomy (OVX)- and letrozole (LET)-treated female mice. Under G1, G15, and/or OVX treatment, the spatial memory, spine density, levels of ERα, ERß, and SRC-1, selected synaptic proteins, mTORC2 signals (Rictor and p-AKT Ser473), and actin polymerization dynamics were subsequently evaluated. Furthermore, G1, G15, and/or E2 combined with SRC-1 and/or PI3K inhibitors, actin cytoskeleton polymerization modulator JPK, and CytoD treatments were used to address the mechanisms that underlie GPR30 regulation in vitro. Finally, mTORC2 activator A-443654 (A4) was used to explore the role of mTORC2 in GPR30 regulation of spatial memory. RESULTS: The results showed that high levels of GPR30 were detected in the adult hippocampus and the levels were downregulated by OVX and LET. OVX induced an impairment of spatial memory, and changes in other parameters previously described were reversed by G1 and mimicked by G15. Furthermore, the E2 effects on SRC-1 and mTORC2 signals, synaptic proteins, and actin polymerization were inhibited by G15, whereas G1 effects on these parameters were inhibited by the blockade of SRC-1 or PI3K; the levels of synaptic proteins were regulated by JPK and CytoD. Importantly, G15-induced actin depolymerization and spatial memory impairment were rescued by mTORC2 activation with A4. CONCLUSIONS: Taking together, these results demonstrated that decreased GPR30 induces actin depolymerization through SRC-1 and PI3K/mTORC2 pathways and ultimately impairs learning and memory, indicating its potential role as a therapeutic target against hippocampus-based, E2-related memory impairments.

Nuclear and membrane estrogen receptor antagonists induce similar mTORC2 activation-reversible changes in synaptic protein expression and actin polymerization in the mouse hippocampus.

AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERß) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2. Then, we examined the changes in hippocampal SRC-1 expression, mTORC2 signaling (rictor and phospho-AKTSer473), actin polymerization (phospho-cofilin and profilin-1), synaptic protein expression (GluR1, PSD95, spinophilin, and synaptophysin), CA1 spine density, and synapse density. RESULTS: All of the examined parameters except synaptophysin expression were significantly decreased by MPP/PHTPP and G15 treatment. MPP/PHTPP and G15 induced a similar decrease in most parameters except p-cofilin, GluR1, and spinophilin expression. The ER antagonist-induced decreases in these parameters were significantly reversed by mTORC2 activation, except for the change in SRC-1, rictor, and synaptophysin expression. CONCLUSIONS: nERs and mER contribute similarly to the changes in proteins and structures associated with synaptic plasticity, and mTORC2 may be a novel target of hippocampal-dependent dementia such as Alzheimer's disease as proposed by previous studies.

[Relationship between germ cell apoptosis and Sertoli cell vimentin in prepubertal rats induced by local exposure to heat].

OBJECTIVE: To explore the relationship between germ cell apoptosis and the expression as well as the distribution of Sertoli cell vimentin induced by local exposure to heat. METHODS: Local short-term exposure of prepubertal male rats testis to heat (43 degrees C for 15 min). Histochemical method was used to observe morphological characteristics of seminiferous tubule. The distribution and expression of Sertoli cell cytoskeletons were analyzed by immunohistochemistry and germ cell apoptosis was evaluated by TUNEL technique at different hour-intervals. RESULTS: After 2 h and 4 h heat exposure, the disattachment phenomenon between Sertoli cell and spermatogonia occurred. Spermatogonia arranged in disorder and displaced away from the basement membrane of seminiferous tubules. Immunohistochemical staining showed that vimentin positive staining was seen radiating from the Sertoli cell perinuclear region with apical "spoke-like" pattern in controls. There was an intense vimentin immunoreactivity surrounding Sertoli cell nuclei along with the collapse of the apical extensions in 2 h group, but no significant difference compared with the controls. The expressions of vimentin in 12 h and 24 h groups were higher than those of the controls (P <0.01), respectively. TUNEL showed that incidence of apoptosis was observed to increases markedly in 12 h and 24 h groups, but it was found that the incidences of apoptotic events were decreased in these two groups compared with the controls. CONCLUSION: The changes of expression and distribution of Sertoli cell vimentin filaments correlate with the increased germ cell apoptosis. Local heat may disrupt spermatogenesis by injuring Sertoli cell directly.

Adrenoceptor-Mediated Post- and Pre-Synaptic Regulations of the Reticulospinal Neurons in Rat Caudal Pontine Reticular Nucleus.

The central noradrenergic system participates in diverse nervous functions. Nevertheless, our knowledge of the action of adrenoceptors in motor regulation is still lacking. Intriguingly, reticulospinal neurons in the caudal pontine reticular nucleus (PnC) receive fairly dense noradrenergic innervation and play an important role in motor control. Here, after demonstrating the expression of α1- and α2-adrenoceptors in the PnC, we found that noradrenaline elicited a post-synaptic effect (inward or outward whole-cell current at -70 mV holding) on PnC reticulospinal neurons. The α1- and α2-adrenoceptors were co-expressed in individual PnC reticulospinal neurons to mediate an inward and an outward current component at -70 mV holding, respectively, which, when superposed, produced the overall post-synaptic effects of noradrenaline (NA). More importantly, the activation of post-synaptic α1- or α2-adrenoceptors indeed exerted opposing modulations (excitation vs. inhibition) on the firing activities of individual PnC reticulospinal neurons. Furthermore, the activation and inhibition of the Na+-permeable non-selective cationic conductance (NSCC) were demonstrated to be coupled to α1- and α2-adrenoceptors, respectively. Additionally, the activation of α2-adrenoceptors activated K+ conductance. Pre-synaptically, the α2-adrenoceptors were expressed to attenuate the miniature excitatory postsynaptic current (mEPSC) in PnC reticulospinal neurons, but not to affect the miniature inhibitory postsynaptic current (mIPSC). Consistently, the evoked EPSC in PnC reticulospinal neurons was suppressed after the activation of pre-synaptic α2-adrenoceptors. Thus, the excitatory input and post-synaptic dynamics of PnC reticulospinal neurons are indeed intricately modulated by the activation of α1- and α2-adrenoceptors, through which motor control may be regulated in an adaptive manner by the central noradrenergic system.

Controlling herding in minority game systems.

Resource allocation takes place in various types of real-world complex systems such as urban traffic, social services institutions, economical and ecosystems. Mathematically, the dynamical process of resource allocation can be modeled as minority games. Spontaneous evolution of the resource allocation dynamics, however, often leads to a harmful herding behavior accompanied by strong fluctuations in which a large majority of agents crowd temporarily for a few resources, leaving many others unused. Developing effective control methods to suppress and eliminate herding is an important but open problem. Here we develop a pinning control method, that the fluctuations of the system consist of intrinsic and systematic components allows us to design a control scheme with separated control variables. A striking finding is the universal existence of an optimal pinning fraction to minimize the variance of the system, regardless of the pinning patterns and the network topology. We carry out a generally applicable theory to explain the emergence of optimal pinning and to predict the dependence of the optimal pinning fraction on the network topology. Our work represents a general framework to deal with the broader problem of controlling collective dynamics in complex systems with potential applications in social, economical and political systems.

Immunolocalization of estrogen receptor beta in the hypothalamic paraventricular nucleus of female mice during pregnancy, lactation and postnatal development.

Previous studies have shown that estrogen receptor beta (ERbeta) is the predominant estrogen receptor in the hypothalamic paraventricular nucleus (PVN) of mouse, mediating estrogen regulation of the neuroendocrine activities of the PVN, but the exact roles that ERbeta plays in the PVN remain unclear. In this study, we used immunocytochemistry to investigate the expression of ERbeta in the maternal PVN of mice during pregnancy (pregnant days 8, 10, 12, 15 and 18), lactation (postpartum days 1, 4 and 8) as well as in the PVN of the females from postnatal days 1, 3, 5, 7, 9, 15, 30 and 70. We found out that ERbeta was predominantly localized in the magnocellular divisions of PVN. In the pregnant female brain, generally, the ERbeta was lower than that of the postnatal development, the lowest level was found at gestational days 10-12; then from gestational day 18 to postpartum day 1, it increased to higher levels, followed by a decrease from postpartum day 4. During the postnatal development, the highest level of ERbeta was found at early postnatal days (before postnatal day 15), thereafter, it decreased to a lower level. The above results indicate that circulating sex steroids may differentially regulate the expression of ERbeta in the PVN of mice. It also suggests that this receptor may play important roles in the regulation of parturition and in the development, food intake and body weight increases of the newborns by acting on the neuropeptides, which were also detected in the PVN.

Distribution and differences of estrogen receptor beta immunoreactivity in the brain of adult male and female rats.

Studies have shown that estrogen plays important roles in regulating neural structure and function in the brain, but the mechanism remains unclear. The actions of estrogen were thought to be mediated by a single estrogen receptor until the identification of another estrogen receptor, namely estrogen receptor-beta (ER-beta). Here we report a comprehensive study of the localization of ER-beta immunoreactivity and differences in the brains of adult male and female rats on the basis of a nickel ammonium sulfate-enhanced immunocytochemical method using a polyclonal antiserum sc-8974. The results of these studies revealed: (1) ER-beta immunoactive material was mainly localized in the neuronal nucleus, but it was also detectable in the cytoplasm and neuronal processes; (2) in both male and female rats, high levels of ER-beta immunopositive signals were detected in the anterior olfactory nucleus, cerebral cortex, Purkinje cells, vertical limb of the diagonal band, red nucleus, locus ceruleus, and motor trigeminal nucleus. Moderate levels were found in the medial septum, lateral amygdaloid nucleus, substantia nigra, and central gray. Weak signals were localized in other subregions of the hypothalamus and amygdaloid complex; (3) there was an obvious difference of ER-beta immunoreactivity between male and female rats, and its intracellular distribution also showed a sex difference. The above results provide the first detailed evidence that ER-beta protein is widely distributed in both male and female rat brains, but that distinctive sex differences also exist. Estrogen may exert its function in different brain regions in a gender-specific manner.

Controlling collective dynamics in complex minority-game resource-allocation systems.

Resource allocation takes place in various kinds of real-world complex systems, such as traffic systems, social services institutions or organizations, or even ecosystems. The fundamental principle underlying complex resource-allocation dynamics is Boolean interactions associated with minority games, as resources are generally limited and agents tend to choose the least used resource based on available information. A common but harmful dynamical behavior in resource-allocation systems is herding, where there are time intervals during which a large majority of the agents compete for a few resources, leaving many other resources unused. Accompanying the herd behavior is thus strong fluctuations with time in the number of resources being used. In this paper, we articulate and establish that an intuitive control strategy, namely pinning control, is effective at harnessing the herding dynamics. In particular, by fixing the choices of resources for a few agents while leaving the majority of the agents free, herding can be eliminated completely. Our investigation is systematic in that we consider random and targeted pinning and a variety of network topologies, and we carry out a comprehensive analysis in the framework of mean-field theory to understand the working of control. The basic philosophy is then that, when a few agents waive their freedom to choose resources by receiving sufficient incentives, the majority of the agents benefit in that they will make fair, efficient, and effective use of the available resources. Our work represents a basic and general framework to address the fundamental issue of fluctuations in complex dynamical systems with significant applications to social, economical, and political systems.

Emergence of grouping in multi-resource minority game dynamics.

Complex systems arising in a modern society typically have many resources and strategies available for their dynamical evolutions. To explore quantitatively the behaviors of such systems, we propose a class of models to investigate Minority Game (MG) dynamics with multiple strategies. In particular, agents tend to choose the least used strategies based on available local information. A striking finding is the emergence of grouping states defined in terms of distinct strategies. We develop an analytic theory based on the mean-field framework to understand the "bifurcations" of the grouping states. The grouping phenomenon has also been identified in the Shanghai Stock-Market system, and we discuss its prevalence in other real-world systems. Our work demonstrates that complex systems obeying the MG rules can spontaneously self-organize themselves into certain divided states, and our model represents a basic and general mathematical framework to address this kind of phenomena in social, economical and political systems.

The structure, density and settlability of anammox granular sludge in high-rate reactors.

Microscopic observation and settling test were carried out to investigate the structure, density and settlability of anammox granules taken from a high-rate upflow anaerobic sludge blanket (UASB) reactor. The results showed that the anammox granules were irregular in shape and uneven on surface, and their structure included granule, subunit, microbial cell cluster and single cell. The gas pockets were often observed in the anammox granules, and they originated from the obstruction of gas tunnel by extracellular polymer substances (EPSs) and the inflation of produced dinitrogen gas. The volume of gas pockets became larger with the increasing diameter of anammox granules, which led to the decreasing density and the floatation of anammox granules. The diameter of anammox granules should be controlled at less than 2.20mm to avoid the granule floatation. A hypothesized mechanism for the granulation and floatation of anammox biomass was proposed.

Performance of high-loaded ANAMMOX UASB reactors containing granular sludge.

The performance of high-loaded anaerobic ammonium oxidizing (ANAMMOX) upflow anaerobic sludge bed (UASB) reactors was investigated. Two ANAMMOX reactors (R1 with and R2 without effluent recycling, respectively) were fed with relatively low nitrite concentration of 240 mg-N L(-1) with subsequent progressive increase in the nitrogen loading rate (NLR) by shortening the hydraulic retention time (HRT) till the end of the experiment. A super high-rate performance with nitrogen removal rate (NRR) of 74.3-76.7 kg-N m(-3) day(-1) was accomplished in the lab-scale ANAMMOX UASB reactors, which was 3 times of the highest reported value. The biomass concentrations in the reactors were as high as 42.0-57.7 g-VSS L(-1) with the specific ANAMMOX activity (SAA) approaching to 5.6 kg-N kg-VSS(-1) day(-1). The high SAA and high biomass concentration were regarded as the key factors for the super high-rate performance. ANAMMOX granules were observed in the reactors with settling velocities of 73-88 m h(-1). The ANAMMOX granules were found to contain a plenty of extracellular polymers (ECPs) such as 71.8-112.1 mg g-VSS(-1) of polysaccharides (PS) and 164.4-298.2 mg g-VSS(-1) of proteins (PN). High content of hemachrome (6.8-10.3 µmol g-VSS(-1)) was detected in the ANAMMOX granules, which is supposed to be attributed to their unique carmine color.