Bisphosphonate nephrotoxicity

Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function

The Effect of Bounded Rationality on Human Cooperation with Voluntary Participation

The evolution of human cooperation is an important issue concerning social science. A deep understanding of human bounded rationality is a prerequisite for promoting collective cooperation and solving social dilemmas. Here we construct an asymmetric micro-dynamic based on bounded rationality from a micro perspective by combining behavioral economics and cognitive psychology with evolutionary game theory. Asynchronously updated Monte Carlo simulations were conducted where individuals were located on a square lattice to play a voluntary public goods game. The results showed that “free riding” behaviors can be effectively suppressed in most situations. The cooperation level can be obviously enhanced in a population comprising easily satisfied cooperators and greedy defectors. Moreover, essential conditions for the stability of the system are further discussed at the microscopic level, and altruistic behavior can be explained that an individual with lower expectations for or underestimation of a single game is more likely to cooperate. We argue that, compared to traditional approaches, the integration of interdisciplinary ideas should be taken more seriously

The Effect of Bounded Rationality on Human Cooperation with Voluntary Participation

The evolution of human cooperation is an important issue concerning social science. A deep understanding of human bounded rationality is a prerequisite for promoting collective cooperation and solving social dilemmas. Here we construct an asymmetric micro-dynamic based on bounded rationality from a micro perspective by combining behavioral economics and cognitive psychology with evolutionary game theory. Asynchronously updated Monte Carlo simulations were conducted where individuals were located on a square lattice to play a voluntary public goods game. The results showed that “free riding” behaviors can be effectively suppressed in most situations. The cooperation level can be obviously enhanced in a population comprising easily satisfied cooperators and greedy defectors. Moreover, essential conditions for the stability of the system are further discussed at the microscopic level, and altruistic behavior can be explained that an individual with lower expectations for or underestimation of a single game is more likely to cooperate. We argue that, compared to traditional approaches, the integration of interdisciplinary ideas should be taken more seriously

Strategy intervention in spatial voluntary public goods games

It is well known that punishment has been considered to enhance cooperation based on empirical and theoretical studies. An important question arises over the existence of the “second-order” problems, which result from the interactions between individuals. In this paper, we propose strategy intervention as a new mechanism in spatial voluntary public goods game, in which individuals only know their own payoffs. By virtue of centralized institution, the defectors may reserve amounts of probabilities to contribute to the common pool with a certain amount of investments. The centralized institution is established costly by all the participants to enforce the intervention rather than peer punishment. We find that the number of cooperators (defectors) decreases (increases) with weak intervention, which contrasts our intuition. Loners vanish and cooperation emerges significantly, as the level of intervention reaches a threshold. We give an accurate range of intervention leading to full cooperation, and demonstrate that at partial cooperation state, proper intervention can remarkably increase income accumulations of individuals, between which there exists smaller income gap in contrast to typical models. We highlight the significance of intervention enforced by a higher authority for maintaining social stability

Simulated microgravity using a rotary culture system compromises the <i>in vitro</i> development of mouse preantral follicles

Growing cells in simulated weightlessness condition might be a highly promising new technique to maintain or generate tissue constructs in a scaffold-free manner. There is limited evidence that microgravity condition may affect development of ovarian follicles. The objective of the present study was to investigate the effects of simulated microgravity on the in vitro development of mouse preantral follicles.Ovarian tissue from 14-day-old mice, or preantral follicles mechanically isolated from 14-day-old mouse ovaries were cultured at a simulated microgravity condition generated using a rotating wall vessel apparatus. Follicle survival was assessed quantitatively using H&E staining. Follicle diameter and oocyte diameter were measured under an inverted microscope. Ultrastructure of oocytes was evaluated using transmission electron microscopy. We observed that simulated microgravity compromised follicle survival in vitro, downregulated PCNA and GDF-9 expressions, and caused ultrastructural abnormalities in oocytes.This study showed for the first time that three-dimensional culture condition generated by simulated microgravity is detrimental to the initial stage development of mouse preantral follicles in vitro. The experimental setup provides a model to further investigate the mechanisms involved in the in vitro developmental processes of oocytes/granulosa cells under the microgravity condition

Stu-miR827-Targeted StWRKY48 Transcription Factor Negatively Regulates Drought Tolerance of Potato by Increasing Leaf Stomatal Density

Stomata are specialized portals in plant leaves to modulate water loss from plants to the atmosphere by control of the transpiration, thereby determining the water-use efficiency and drought resistance of plants. Despite that the stomata developmental progression is well-understood at the molecular level, the experimental evidence that miRNA regulates stomata development is still lacking, and the underlying mechanism remains elusive. This study demonstrates the involvement of stu-miR827 in regulating the drought tolerance of potato due to its control over the leaf stomatal density. The expression analysis showed that stu-miR827 was obviously repressed by drought stresses and then rapidly increased after rewatering. Suppressing the expression of stu-miR827 transgenic potato lines showed an increase in stomatal density, correlating with a weaker drought resistance compared with wildtype potato lines. In addition, StWRKY48 was identified as the target gene of stu-miR827, and the expression of StWRKY48 was obviously induced by drought stresses and was greatly upregulated in stu-miR827 knockdown transgenic potato lines, suggesting its involvement in the drought stress response. Importantly, the expression of genes associated with stomata development, such as SDD (stomatal density and distribution) and TMM (too many mouths), was seriously suppressed in transgenic lines. Altogether, these observations demonstrated that suppression of stu-miR827 might lead to overexpression of StWRKY48, which may contribute to negatively regulating the drought adaptation of potato by increasing the stomatal density. The results may facilitate functional studies of miRNAs in the process of drought tolerance in plants

Optimization of Critical Factors Affecting Dynamic Membrane Formation in a Gravity-Driven Self-Forming Dynamic Membrane Bioreactor towards Low-Cost and Low-Maintenance Wastewater Treatment

Self-forming dynamic membrane (SFDM) formation is affected by a variety of operating conditions. However, previous studies have only focused on individual influencing factors and a systematic analysis of important factors is lacking. In this study, an aerobic self-forming dynamic membrane bioreactor (SFDMBR) was developed for the treatment of domestic wastewater with the critical factors that affect the effective formation of SFDM optimized, and the operational performances under optimized formation conditions confirmed. The results indicated that SFDM could be formed within 5 min using 48 μm stainless-steel mesh as the supporting material at a sludge concentration of 5–6 g/L and a gravity waterhead of 15 cm. And the SFDM formed could maintain a stable flux of 30–50 LMH, and the removals of COD, SCOD, and NH4+-N were 93.28%, 82.85%, and 95.46%, respectively. Furthermore, the cake layer resistance (reversible fouling) contributed to 95.93% of the total filtration resistance, thus a simple physical cleaning can effectively restore the flux indicating a low-maintenance requirement. This study provides valuable insights into the optimization and application of the SFDMBR process

Comparing Performance of Deep Convolution Networks in Reconstructing Soliton Molecules Dynamics from Real-Time Spectral Interference

Deep neural networks have enabled the reconstruction of optical soliton molecules with more complex structures using the real-time spectral interferences obtained by photonic time-stretch dispersive Fourier transformation (TS-DFT) technology. In this paper, we propose to use three kinds of deep convolution networks (DCNs), including VGG, ResNets, and DenseNets, for revealing internal dynamics evolution of soliton molecules based on the real-time spectral interferences. When analyzing soliton molecules with equidistant composite structures, all three models are effective. The DenseNets with layers of 48 perform the best for extracting the dynamic information of complex five-soliton molecules from TS-DFT data. The mean Pearson correlation coefficient (MPCC) between the predicted results and the real results is about 0.9975. Further, the ResNets in which the MPCC achieves 0.9906 also has the better ability of phase extraction than VGG which the MPCC is about 0.9739. The general applicability is demonstrated for extracting internal information from complex soliton molecule structures with high accuracy. The presented DCNs-based techniques can be employed to explore undiscovered mechanisms underlying the distribution and evolution of large numbers of solitons in dissipative systems in experimental research