HSPA4 Is a Biomarker of Placenta Accreta and Enhances the Angiogenesis Ability of Vessel Endothelial Cells

Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.     

Molecular and Physiological Responses of Citrus sinensis Leaves to Long-Term Low pH Revealed by RNA-Seq Integrated with Targeted Metabolomics

Low pH-induced alterations in gene expression profiles and organic acids (OA) and free amino acid (FAA) abundances were investigated in sweet orange [Citrus sinensis (L.) Osbeck cv. Xuegan] leaves. We identified 503 downregulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OA biosynthesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen compounds, proteins, and FAAs in leaves, which might be conducive to maintaining energy homeostasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses to phosphate starvation, including phosphate recycling, lipid remodeling, and phosphate transport, thus enhancing leaf acid-tolerance. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid, and pyroglutamic acid), but it impaired the pentose phosphate pathway and V_E and secondary metabolite biosynthesis and downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase, and 2-alkenal reductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.     

Nitric Oxide Signalling in Descending Vasa Recta after Hypoxia/Re-Oxygenation

Reduced renal medullary oxygen supply is a key factor in the pathogenesis of acute kidney injury (AKI). As the medulla exclusively receives blood through descending vasa recta (DVR), dilating these microvessels after AKI may help in renoprotection by restoring renal medullary blood flow. We stimulated the NO-sGC-cGMP signalling pathway in DVR at three different levels before and after hypoxia/re-oxygenation (H/R). Rat DVR were isolated and perfused under isobaric conditions. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (10⁻⁶ mol/L) impaired cGMP degradation and dilated DVR pre-constricted with angiotensin II (Ang II, 10⁻⁶ mol/L). Dilations by the soluble guanylyl cyclase (sGC) activator BAY 60-2770 as well as the nitric oxide donor sodium nitroprusside (SNP, 10⁻³ mol/L) were equally effective. Hypoxia (0.1% O₂) augmented DVR constriction by Ang II, thus potentially aggravating tissue hypoxia. H/R left DVR unresponsive to sildenafil, yet sGC activation by BAY 60-2770 effectively dilated DVR. Dilation to SNP under H/R is delayed. In conclusion, H/R renders PDE5 inhibition ineffective in dilating the crucial vessels supplying the area at risk for hypoxic damage. Stimulating sGC appears to be the most effective in restoring renal medullary blood flow after H/R and may prove to be the best target for maintaining oxygenation to this vulnerable area of the kidney.     

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/βcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.     

Proactive multipath routing with a predictive mechanism in software‐defined networks

With the growth of network traffic volume, link congestion cannot be avoided efficiently with conventional routing protocols. By utilizing the single shortest‐path routing algorithm from link state advertisement information, standard routing protocols lack of global awareness and are difficult to be modified in a traditional network environment. Recently, software‐defined network (SDN) provided innovative architecture for researchers to program their own network protocols. With SDN, we can divert heavy traffic to multiple paths in order to resolve link congestion. Furthermore, certain network traffics come in periodic fashion such as peak hours at working days so that we can leverage forecasting for resource management to improve its performance. In this paper, we propose a proactive multipath routing with a predictive mechanism (PMRP) to achieve high‐performance congestion resolution. PMRP has two main concepts: (a) a proactive mechanism where PMRP deploys M/M/1 queue and traffic statistics to simulate weighted delay for possible combinations of multipaths placement of all subnet pairs, and leverage genetic algorithm for accelerating selection of optimized solution, and (b) a predictive mechanism whereby PMRP uses exponential smoothing for demand traffic volumes and variance predictions. Experimental results show a 49% reduction in average delay as compared with single shortest routing, and a 16% reduction in average delay compared with utilization & topology‐aware multipath routing (UTAMP). With the predictive mechanism, PMRP can decrease an additional 20% average delay. Furthermore, PMRP reduces 93% of flow table usage on average as compared with UTAMP.     

盘管外融冰问题的数学模型及数值分析

本文分析了盘管外融冰问题并建立其数学模型;利用该模型模拟了盘管外融冰过程,并对模拟结果进行了分析。分析表明,该模型比较合理,更加接近蓄冷槽内融冰过程的实际情况;循环水量对融冰持续时间有较大影响。所得结论可为今后蓄冷系统的优化计算分析提供理论根据。     

Linear Study of a Large-orbit Coaxial-waveguide Cyclotron Autoresonance Maser Amplifier

A linear theory based on Maxwell-Vlasov equations and the Laplace transform is presented to describe the large-orbit coaxial-waveguide cyclotron autoresonance maser (CARM) amplifier. A 35-GHz, TE_5,1-mode large-orbit coaxial-waveguide CARM amplifier is specifically analyzed. Good agreement between the linear theory and the nonlinear simulations is found in the exponentially growing region of the wave. Results show that the operating magnetic field and the electron-beam energy and average radius substantially affect the power, and especially, a small beam current may be unsuitable to a large-orbit CARM amplifier operation.     

Optimization of optical design for developing an LED lens module

In this study, a procedure for optimization of an LED lens module design based on 3 LED light sources was divided into two phases. For preliminary optimization of the dimensions of the LED lens module in Stage I, an optical analysis with orthogonal arrays and TracePro (an optical design package) combined with analysis of variance was conducted to investigate relationships between the multiple optical quality characteristics (viewing angle and average illuminance) and dimension parameters and find the initial optimal parameter combination of the LED lens module. In Stage II, the initial optimal parameter combination determined in Stage I was employed to develop an orthogonal array L₂₅(5⁶) for optical simulation. The experimental data of the orthogonal array were used to train and test the back-propagation neural network to develop an optical quality predictor, which was integrated into the genetic algorithms and the particle swarm optimization in order to find the optimal parameter combination that conformed to optical quality. From the experimental results, the proposed optimization procedure contributes to a precise viewing angle to achieve the goal of optical quality and improved the average illuminance in development of the product. The procedure to optimize the optical design developed in this study can be applied to design all types of LED lens modules and improve the optical design and technology of the LED lens industry.     

Investigation of growth behavior of Al-Cu intermetallic compounds in Cu wire bonding

In this work, we investigate the intermetallic compound formation in Cu wire bonded device. Voids near the Cu side at the bond interface are clearly seen. Nevertheless, these voids do not seem to interfere with the function of the unit. High temperature storage test (HTST) results show that there are Al₂Cu and AlCu in the damaged unit while Al₂Cu and Al₄Cu₉ appear in the good unit. The results clearly show that the Al layer is exhausted in the damaged unit while those with Al₄Cu₉ on the Cu side pass HTST with unconsumed Al. Theoretical calculations indicate that AlCu and Al₄Cu₉ are energetically more favorable than Al₂Cu, which is consistent with the reported IMC forming sequence. Formation energy of AlCu is compatible but slightly lower to that of Al₄Cu₉, suggesting AlCu tends to be the most stable phase among all. The reason why the Al layer is completely consumed in one case and some Al layer remains in the other is due to the fact that the formation of AlCu requires more than twice the amount of Al than Al₄Cu₉ for the same amount of Cu consumed. The complete consumption of Al is proposed as the reason responsible for the failure of the damaged unit.