CD38 Deficiency Protects Mouse Retinal Ganglion Cells Through Activating the NAD+/Sirt1 Pathway in Ischemia-Reperfusion and Optic Nerve Crush Models.

Purpose: The purpose of this study was to investigate the protective effect of CD38 deletion on retinal ganglion cells (RGCs) in a mouse retinal ischemia/reperfusion (I/R) model and an optic nerve crush (ONC) model, and to elucidate the underlying molecular mechanisms. Methods: Retinal I/R and ONC models were constructed in mice. PCR was used to identify the deletion of CD38 gene in mice, hematoxylin and eosin (H&E) staining was used to evaluate the changes in retinal morphology, and electroretinogram (ERG) was used to evaluate the changes in retinal function. The survival of RGCs and activation of retinal macroglia were evaluated by immunofluorescence staining. The expression of Sirt1, CD38, Ac-p65, Ac-p53, TNF-α, IL-1ß, and Caspase3 proteins in the retina was further evaluated by protein imprinting. Results: In retinal I/R and ONC models, CD38 deficiency reduced the loss of RGCs and activation of macroglia and protected the retinal function. CD38 deficiency increased the concentration of NAD+, reduced the degree of acetylation of NF-κB p65 and p53, and reduced expression of the downstream inflammatory cytokines TNFα, IL-1ß, and apoptotic protein Caspase3 in the retina in the ONC model. Intraperitoneal injection of the Sirt1 inhibitor EX-527 partially counteracted the effects of CD38 deficiency, suggesting that CD38 deficiency acts at least in part through the NAD+/Sirt1 pathway. Conclusions: CD38 plays an important role in the pathogenesis of retinal I/R and ONC injury. CD38 deletion protects RGCs by attenuating inflammatory responses and apoptosis through the NAD+/Sirt1 pathway.

Age-Aware Utility Maximization in Relay-Assisted Wireless Powered Communication Networks.

This article investigates a relay-assisted wireless powered communication network (WPCN), where the access point (AP) inspires the auxiliary nodes to participate together in charging the sensor, and then the sensor uses its harvested energy to send status update packets to the AP. An incentive mechanism is designed to overcome the selfishness of the auxiliary node. In order to further improve the system performance, we establish a Stackelberg game to model the efficient cooperation between the AP-sensor pair and auxiliary node. Specifically, we formulate two utility functions for the AP-sensor pair and the auxiliary node, and then formulate two maximization problems respectively. As the former problem is non-convex, we transform it into a convex problem by introducing an extra slack variable, and then by using the Lagrangian method, we obtain the optimal solution with closed-form expressions. Numerical experiments show that the larger the transmit power of the AP, the smaller the age of information (AoI) of the AP-sensor pair and the less the influence of the location of the auxiliary node on AoI. In addition, when the distance between the AP and the sensor node exceeds a certain threshold, employing the relay can achieve better AoI performance than non-relaying systems.

Synergistic effects of multiple myeloma cells and tumor-associated macrophages on vascular endothelial cells in vitro.

Angiogenesis is a prerequisite for multiple myeloma development. Tumor cells can stimulate angiogenesis by secreting vascular endothelial growth factor A (VEGFA), but we previously reported that tumor angiogenesis was not significantly reduced when VEGFA expression was inhibited in myeloma cells. Tumor-associated macrophages (TAMs) are important components of the tumor microenvironment and have been reported to be involved in the regulation of angiogenesis. In this study, we performed in vitro macrophage coculture studies and studies with RPMI 8226 and TAMs cell-conditioned media to explore their effects on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Our results showed that M2 macrophages and RPMI 8226 cells could synergistically promote HUVEC proliferation, migration, and tube formation, and that VEGFA depletion in both cell types suppressed HUVEC tube formation ability. Conversely, M1 macrophages inhibited the tube formation in HUVECs. Mechanistically, M2 macrophage secretion of VEGFA may affect vascular endothelial growth factor receptor 1 signaling to regulate angiogenesis. In summary, our results suggest that macrophage clearance or inducing of transformation of M2 macrophages into M1 macrophages are potential treatment strategies for multiple myeloma.

Optimal Design of Hierarchical Cloud-Fog&Edge Computing Networks with Caching.

This paper investigates the optimal design of a hierarchical cloud-fog&edge computing (FEC) network, which consists of three tiers, i.e., the cloud tier, the fog&edge tier, and the device tier. The device in the device tier processes its task via three computing modes, i.e., cache-assisted computing mode, cloud-assisted computing mode, and joint device-fog&edge computing mode. Specifically, the task corresponds to being completed via the content caching in the FEC tier, the computation offloading to the cloud tier, and the joint computing in the fog&edge and device tier, respectively. For such a system, an energy minimization problem is formulated by jointly optimizing the computing mode selection, the local computing ratio, the computation frequency, and the transmit power, while guaranteeing multiple system constraints, including the task completion deadline time, the achievable computation capability, and the achievable transmit power threshold. Since the problem is a mixed integer nonlinear programming problem, which is hard to solve with known standard methods, it is decomposed into three subproblems, and the optimal solution to each subproblem is derived. Then, an efficient optimal caching, cloud, and joint computing (CCJ) algorithm to solve the primary problem is proposed. Simulation results show that the system performance achieved by our proposed optimal design outperforms that achieved by the benchmark schemes. Moreover, the smaller the achievable transmit power threshold of the device, the more energy is saved. Besides, with the increment of the data size of the task, the lesser is the local computing ratio.

SWIPT-Aware Fog Information Processing: Local Computing vs. Fog Offloading.

This paper studies a simultaneous wireless information and power transfer (SWIPT)-aware fog computing by using a simple model, where a sensor harvests energy and receives information from a hybrid access point (HAP) through power splitting (PS) receiver architecture. Two information processing modes, local computing and fog offloading modes are investigated. For such a system, two optimization problems are formulated to minimize the sensor's required power for the two modes under the information rate and energy harvesting constraints by jointly optimizing the time assignment and the transmit power, as well as the PS ratio. The closed-form and semi-closed-form solutions to the proposed optimization problems are derived based on convex optimization theory. Simulation results show that neither mode is always superior to the other one. It also shows that when the number of logic operations per bit associated with local computing is less than a certain value, the local computing mode is a better choice; otherwise, the fog offloading mode should be selected. In addition, the mode selection associated with the positions of the user for fixed HAP and fog server (FS) is also discussed.

[Rapid cloning and functional characterization of hypericin synthase gene].

Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, commonly known as St. John's wort. Hypericin has attracted a growing attention of the pharmaceutical industry because of its potential application to various therapies, including the treatment of depression and remarkable antiviral and photodynamic activities, hyp-1 gene encodes for phenolic coupling protein which catalyzes in vitro direct and specific conversion of emodin to hypericin which, however, has not formed common opinion so far. Six pairs of primers specific to hyp-1 gene were synthesized. The rapid cloning of hyp-1 gene was performed based on step-by-step extension of a short region of the gene through a series of PCR reactions. All cloned sequences were confirmed by DNA sequencing. A vector named pET32ahyp containing hyp-1 gene was constructed and was transformed into E. coli to induce heterologous expression. SDS-PAGE and Western blot results showed the recombinant Hyp-1 protein was expressed successfully in E. coli. The soluble fraction was used to test the function of the recombinant Hyp-1. Hypericin was detected by LC-MS/MS with emodin as a substrate under in vitro conditions. The above results corroborated the Hyp-1 function, a confusing question, which lay a material foundation for the synthesis of hypericin by synthetic biotechnology.

Improvement of amorpha-4,11-diene production by a yeast-conform variant of Vitreoscilla hemoglobin.

Amorpha-4,11-diene is the precursor of the antimalarial compound artemisinin. The effect of Vitreoscilla hemoglobin (VHb) and its yeast-conform variant (VHbm) on amorpha-4,11-diene production in engineered Saccharomyces cerevisiae was investigated. First, the VHb gene was mutated to the yeast-conform variant VHbm based on step-by-step extension of a short region of the gene through a series of polymerase chain reactions (PCR). The artificial VHbm gene contained codons preferred by the yeast translation machinery. Two yeast expression vectors containing VHb or VHbm gene were constructed and introduced into the amorpha-4,11-diene-producing strain S. cerevisiae WK1 to form WK1[VHb] and WK1[VHbm], respectively. Western blot and CO-difference spectrum absorbance assay showed that VHb and VHbm were successfully expressed. In shake flasks, VHbm expression conferred higher cell growth than VHb expression. GC-MS results indicated the amorpha-4,11-diene production in WK1[VHbm] and WK1[VHb] was 3- and 2-fold higher than that in WK1, respectively. This suggests that VHb might improve the amorpha-4,11-diene production in engineered S. cerevisiae.

[Study on pharmacokinetics of oridonin in mice].

OBJECTIVE: To develop a HPLC method for the determination of plasma concentration of oridonin (ORI) and study the pharmacokinetics of ORI in mice. METHOD: Blood was sampled from mice which were injected ORI by 10 mg x kg(-1) at different time intervals, and the concentration of ORI was determined by HPLC. The pharmacokinetic parameters were accessed by 3P97. RESULT: The calibration curve was linear (r = 0.998 7) within the range of 0.202-20.0 mg x L(-1) for ORI in plasma. The average recoveries were more than 93%. The within-day and between-day precisions were no more than 9%. After i.v. oridonin in mice, the plasma concentration-time course fitted well to two-compartment model. The pharmacokinetic equation was C = 16.192 5e(-0.554 6t) + 5.475 7e(-0.016 3t). The pharmacokinetic parameters were below: t1/2alpha 1.249 9 min, t1/2beta 42.638 4 min, K21 0.152 3 min(-1), K12 0.359 3 min(-1), K10 0.0592 min(-1), AUC 366.035 0 microg x min x mL(-1), CL 0.0273 L x min(-1) x kg(-1), V(c)0.461 5 L x kg(-1). CONCLUSION: The method can be used to determine the concentration and to investigate the pharmacokinetics of ORI in mice. ORI was absorbed and distributed very fast in mice. The effect of ORI was rapid. The elimination was the main process.