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This article details the development and evaluation of a practical solution for path-constrained proximity maneuvers of spacecraft. Whereas no velocity measurement is utilized within the feedback structure, the controller rigorously enforces actuator magnitude constraints. Specifically, the control algorithm is constructed from a potential function method repelling the spacecraft from possible collisions. The proposed controller can guarantee potential functions to be navigated to the origin and thus overcome the stubborn local minima problem. Moreover, the control capability under any given control limit can be estimated and adjusted by changing the feedback gains. The specific performance with guaranteed safety can be also explicitly calculated by designers. The results are obtained through a Lyapunov-based stability analysis to prove uniformly ultimate boundedness. Numerical simulation results illustrate the performance and features of the developed control method.

The Hippo/YAP (yes-associated protein) pathway is an important signaling pathway to control organ development and tissue homeostasis. YAP is a downstream effector of the Hippo pathway and a critical mediator of mechanic stress. Hypertensive nephropathy is characterized with glomerular sclerosis stiffness and renal fibrosis. The present study investigated the role of YAP pathway in angiotensin (Ang) II hypertensive renal injury by using YAP activation inhibitor verteporfin. Ang II increased the protein expression of YAP in renal nucleus fraction, decreased phospho-YAP, and phospho-LATS1/2 (large tumor suppressors 1 and 2) expressions in renal cytoplasmic fraction, suggesting Ang II activation of renal YAP. Ang II significantly increased systolic blood pressure (SBP), proteinuria, glomerular sclerosis, and fibrosis; treatment with verteporfin attenuated Ang II–induced proteinuria and renal injury with a mild reduction in SBP. Moreover, Ang II increased the protein expressions of inflammatory factors including tumor necrosis factor α, interleukin 1β, and monocyte chemoattractant protein-1, and profibrotic factors including transforming growth factor β, phospho-Smad3 and fibronectin. Verteporfin reversed abovementioned Ang II–induced molecule expressions. Our results for the first time demonstrate that the activation of the YAP pathway promotes hypertensive renal inflammation and fibrosis, which may promote hypertensive renal injury. YAP may be a new target for prevention and treatment of hypertensive renal diseases.

This paper addresses the attitude-maneuver control problem for a rigid-body spacecraft in the presence of attitude-constrained zones as well as input saturation. More specifically, attitude-constra...

It has been shown that the inflammatory cytokine tumor necrosis factor α (TNFα) plays a role in the development of hypertension and end-stage renal diseases. We hypothesize that TNFα contributes to endothelial dysfunction and cardiac and vascular injury in deoxycorticosterone acetate (DOCA)/salt-hypertensive mice. The wild-type or TNFα-deficient mice were uninephrectomized and implanted with DOCA pellet treatment for 5 weeks; the mice were given either tap water or 1% NaCl drinking water. DOCA mice developed hypertension (systolic blood pressure (SBP): 167±5 vs. 110±4 mmHg in control group, p<0.05), cardiac and vascular hypertrophy, and the impairment of endothelium-dependent relaxation to acetylcholine (EDR). TNFα deficiency improved EDR and lowered cardiac and vascular hypertrophy with a mild reduction in SBP (152±4 vs. 167±5 mmHg in DOCA group, p<0.05) in DOCA mice. The mRNA expressions of the inflammatory cytokines, including TNFα, interleukin 1β (IL1β), monocyte chemotactic protein 1 (MCP1), and monocyte/macrophage marker F4/80 were significantly increased in the aorta of DOCA-hypertensive mice; TNFα deficiency reduced these inflammatory gene expressions. DOCA-hypertensive mice also exhibited an increase in the vascular oxidative fluorescence intensities, the protein expressions of gp91phox and p22phox, and the fibrotic factors transforming growth factor β and fibronectin. TNFα deficiency reduced oxidative stress and fibrotic protein expressions. The DOCA mice also showed a decrease in the protein expression of eNOS associated with increased miR155 expression; TNFα deficiency prevented a decrease in eNOS expression and an increase in miR155 expression in DOCA mice. These results support the idea that TNFα significantly contributes to vascular inflammation, vascular dysfunction, and injury in hypertension.

Ischemic stroke can induce neurogenesis. However, most stroke-generated newborn neurons cannot survive. It has been shown that MR-409, a potent synthetic agonistic analog of growth hormone–releasing hormone (GHRH), can protect against some life-threatening pathological conditions by promoting cell proliferation and survival. The present study shows that long-term treatment with MR-409 (5 or 10 μg/mouse/d) by subcutaneous (s.c.) injection significantly reduces the mortality, ischemic insult, and hippocampal atrophy, and improves neurological functional recovery in mice operated on for transient middle cerebral artery occlusion (tMCAO). Besides, MR-409 can stimulate endogenous neurogenesis and improve the tMCAO-induced loss of neuroplasticity. MR-409 also enhances the proliferation and inhibits apoptosis of neural stem cells treated with oxygen and glucose deprivation–reperfusion. The neuroprotective effects of MR-409 are closely related to the activation of AKT/CREB and BDNF/TrkB pathways. In conclusion, the present study demonstrates that GHRH agonist MR-409 has remarkable neuroprotective effects through enhancing endogenous neurogenesis in cerebral ischemic mice.

Epilepsy is characterized by recurrent seizures that have a variety of manifestations. The severity of, and risks for patients associated with, seizures are largely linked to the duration of seizures. Methods that determine seizure duration based on seizure onsets could be used to help mitigate the risks associated with what might be extended seizures by guiding timely interventions.Using long-term intracranial electroencephalography (iEEG) recordings, this article presents a method for predicting whether a seizure is going to be long or short by analyzing the seizure onset. The definition of long and short depends on each patient's seizure distribution. By analyzing 2954 seizures from 10 patients, patient-specific classifiers were built to predict seizure duration given the first few seconds from the onset.The proposed methodology achieved an average area under the receiver operating characteristic curve (AUC) performance of 0.7 for the 5 of 10 patients with above chance prediction performance (p value from 0.04 to 10Our results imply that the duration of seizures can be predicted from the onset in some patients. This could form the basis of methods for predicting status epilepticus or optimizing the amount of electrical stimulation delivered by seizure control devices.

Background N-methyl-d-aspartate receptors (NMDARs) have been demonstrated to play central roles in stroke pathology and recovery, including dual roles in promoting either neuronal survival or death with their different subtypes and locations. Purpose We have previously demonstrated that pseudoginsenoside-F11 (PF11) can provide long-term neuroprotective effects on transient and permanent ischemic stroke-induced neuronal damage. However, it is still needed to clarify whether NMDAR-2A (NR2A)-mediated pro-survival signaling pathway is involved in the beneficial effect of PF11 on permanent ischemic stroke. Material and Methods PF11 was administrated in permanent middle cerebral artery occlusion (pMCAO)-operated rats. The effect of PF11 on oxygen-glucose deprivation (OGD)-exposed primary cultured neurons were further evaluated. The regulatory effect of PF11 on NR2A expression and the activation of its downstream AKT-CREB pathway were detected by Western blotting and immunofluorescence in the presence or absence of a specific NR2A antagonist NVP-AAM077 (NVP) both in vivo and in vitro. Results PF11 dose- and time-dependently decreased calpain1 (CAPN1) activity and its specific breakdown product α-Fodrin expression, while the expression of Ca2+/calmodulin-dependent protein kinase II alpha (CaMKII-α) was significantly upregulated in the cortex and striatum of rats at 24 h after the onset of pMCAO operation. Moreover, PF11 prevented the downregulation of NR2A, p-AKT/AKT, and p-CREB/CREB in both in vivo and in vitro stroke models. Finally, the results indicated treatment with NVP can abolish the effects of PF11 on alleviating the ischemic injury and activating NR2A-mediated AKT-CREB signaling pathway. Conclusions Our results demonstrate that PF11 can exert neuroprotective effects on ischemic stroke by inhibiting the activation of CAPN1 and subsequently enhancing the NR2A-medicated activation of AKT-CREB pathway, which provides a mechanistic link between the neuroprotective effect of PF11 against cerebral ischemia and NR2A-associated pro-survival signaling pathway.

Objective: Hypertension is associated with a low-grade systemic inflammation in cardiovascular system. Macrophage infiltration may initiate an inflammatory process that contributes to vascular and ventricular remodeling in hypertensive human and mice. The present study investigated the effect of chemical depletion of macrophage using liposome encapsulated clodronate (LEC) on cardiac hypertrophy and remodeling in angiotensin (Ang) II hypertensive mice.Methods: C57BL/6 mice received an Ang II (1.1 mg/kg/day with a minipump) infusion for 2 weeks to induce hypertension. Endothelium-dependent relaxation (ED) was examined by organ bath, hematoxylin and staining and Masson-Trichrome staining were used to evaluate aorta and cardiac hypertrophy and fibrosis.Results: Ang II infusion significantly increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and impaired EDR accompanied by increased macrophage infiltration in the heart. Treatment with LEC significantly lowered Ang II-induced cardiac hypertrophy and fibrosis and cardiac macrophage infiltration, and improved EDR with a mild reduction in SBP. Ang II increased the expression of inflammatory cytokines tumor necross factor alpha and interleukin 1 beta and profibrotic factors transforming growth factor beta 1 and fibronectin in the heart, with was reduced by LEC treatment. Treatment with LEC prevented Ang II-induced the phosphorphorylation of ERK1/2 and c-Jun-N-terminal kinase.Conclusions: Our study suggests that cardiac macrophage may be critical for hypertensive cardiac hypertrophy and remodeling, the underlying mechanisms may involve initial heart inflammation and the activation of hypertrophic MAPKs pathway.

A novel adaptive control solution for pose tracking problems of spacecraft proximity operations subject to not only motion constraints but also parameter uncertainties is proposed in this paper. Sp...

This paper addresses the approaching trajectory control problem for the final phase of non-cooperative spacecraft proximity operations in the presence of disturbances and even input saturation. As a stepping stone, a novel line-of-sight tracking model is developed to describe attitude maneuver towards the target in the proximity. Then, a two-stage artificial potential function is employed to enable the pursuer spacecraft to comply the safety trajectory during approaching the target. In each stage, gradients of potential function are analyzed and the local minimum problem associated with potential function can be addressed. Furthermore, a saturated control law is proposed to ensure a reliable real-time tracking measurement of the target, and the controller rigorously enforces safe path and actuator magnitude constraints. The associated stability proof is accomplished through Lyapunov method. Simulations are carried out to evaluate the effectiveness of the proposed method.

Background and Purpose: CAPN1 (calpain1)—an intracellular Ca 2+ -regulated cysteine protease—can be activated under cerebral ischemia. However, the mechanisms by which CAPN1 activation promotes cerebral ischemic injury are not defined. Methods: In the present study, we used adeno-associated virus-mediated genetic knockdown and pharmacological blockade (MDL-28170) of CAPN1 to investigate the role of CAPN1 in the regulation of the autophagy-lysosomal pathway and neuronal damage in 2 models, rat permanent middle cerebral occlusion in vivo model and oxygen-glucose–deprived primary neuron in vitro model. Results: CAPN1 was activated in the cortex of permanent middle cerebral occlusion–operated rats and oxygen-glucose deprivation–exposed neurons. Genetic and pharmacological inhibition of CAPN1 significantly attenuated ischemia-induced lysosomal membrane permeabilization and subsequent accumulation of autophagic substrates in vivo and in vitro. Moreover, inhibition of CAPN1 increased autophagosome formation by decreasing the cleavage of the autophagy regulators BECN1 (Beclin1) and ATG (autophagy-related gene) 5. Importantly, the neuron-protective effect of MDL-28170 on ischemic insult was reversed by cotreatment with either class III-PI3K (phosphatidylinositol 3-kinase) inhibitor 3-methyladenine or lysosomal inhibitor chloroquine (chloroquine), suggesting that CAPN1 activation-mediated impairment of autophagic flux is crucial for cerebral ischemia-induced neuronal damage. Conclusions: The present study demonstrates for the first time that ischemia-induced CAPN1 activation impairs lysosomal function and suppresses autophagosome formation, which contribute to the accumulation of substrates and aggravate the ischemia-induced neuronal cell damage. Our work highlights the vital role of CAPN1 in the regulation of cerebral ischemia–mediated autophagy-lysosomal pathway defects and neuronal damage.

Light travels in a zero-index medium without accumulating a spatial phase, resulting in perfect spatial coherence. Such coherence brings several potential applications, including arbitrarily shaped waveguides, phase-mismatch-free nonlinear propagation, large-area single-mode lasers, and extended superradiance. A promising platform to achieve these applications is an integrated Dirac-cone material that features an impedance-matched zero index. Although an integrated Dirac-cone material eliminates ohmic losses via its purely dielectric structure, it still entails out-of-plane radiation loss, limiting its applications to a small scale. We design an ultra-low-loss integrated Dirac cone material by achieving destructive interference above and below the material. The material consists of a square array of low-aspect-ratio silicon pillars embedded in silicon dioxide, featuring easy fabrication using a standard planar process. This design paves the way for leveraging the perfect spatial coherence of large-area zero-index materials in linear, nonlinear, and quantum optics., Zero-index media: ultra-low loss Calculations suggest that a new design of engineered medium can simultaneously yield a refractive index of zero and low optical loss at the telecommunications wavelength of 1550 nm. The development could lead to applications in nonlinear and quantum optics benefiting from an infinite coherence length. The approach of Tian Dong and coworkers from China and the US is to embed an array of silicon pillars (about 180 nm in radius and 1100 nm high) into a matrix of silicon dioxide to create a Dirac-cone photonic-crystal slab. Importantly, if the pillar height is chosen correctly any upwards and downwards radiation out of the slab can be made to destructively interfere thus reducing propagation loss to a level of 0.15 dB/mm. The slab should be possible to fabricate using standard processes.

The spread of misinformation in social media outlets has become a prevalent societal problem and is the cause of many kinds of social unrest. Curtailing its prevalence is of great importance and machine learning has shown significant promise. However, there are two main challenges when applying machine learning to this problem. First, while much too prevalent in one respect, misinformation, actually, represents only a minor proportion of all the postings seen on social media. Second, labeling the massive amount of data necessary to train a useful classifier becomes impractical. Considering these challenges, we propose a simple semi-supervised learning framework in order to deal with extreme class imbalances that has the advantage, over other approaches, of using actual rather than simulated data to inflate the minority class. We tested our framework on two sets of Covid-related Twitter data and obtained significant improvement in F1-measure on extremely imbalanced scenarios, as compared to simple classical and deep-learning data generation methods such as SMOTE, ADASYN, or GAN-based data generation.

Vascular endothelial insulin signaling is critical for the maintenance of vascular and metabolic homeostasis. We have previously shown that in hypertensive Dahl rats, impaired vascular insulin action is linked to angiotensin II activation of the NFκB inflammatory pathway. Macrophage polarization (M1) has implicated in hypertensive and metabolic diseases. Here, we investigated the effect of macrophage depletion using liposome-encapsulated clodronate (LEC) on endothelial insulin resistance and cardiovascular remodeling in Dahl salt-sensitive (DS) rats. High salt intake (HS) for 5 weeks increased systolic blood pressure (SBP: 192±5 vs. 144±4 mmHg in NS, p<0.05), aortic and cardiac hypertrophy, cardiac fibrosis, and impaired acetylcholine- and insulin-induced vasorelaxation, accompanied by impaired insulin activation of endothelial nitric oxide synthases (eNOS)/NO signaling. HS rats had a significant increase in CD68 (a monocyte/macrophage marker) expression in the aorta and the heart. LEC reduced SBP (168±5 mmHg, p<0.05) and cardiovascular injury and improved acetylcholine- and insulin-mediated vasorelaxation and insulin signaling molecules with a reduction in the macrophage infiltration in the aorta and the heart. HS rats also manifested an increase in the aortic expressions of inflammatory cytokines, including the ratio of phosphorylated inhibitory kappa B (Iκb)/Iκb, tumor necrosis factor α, and phosphorylated c-Jun N-terminal kinase (JNK) and oxidative stress, which were reduced in HS/LEC rats. Our results suggest that in salt-sensitive hypertension, macrophage may importantly contribute to endothelial insulin resistance, vascular inflammation, and injury. These findings support the idea that macrophages may be a new target for immunotherapy of vasculopathy in hypertensive and metabolic disorders.

Materials with a zero refractive index support electromagnetic modes that exhibit stationary phase profiles. While such materials have been realized across the visible and near-infrared spectral range, radiative and dissipative optical losses have hindered their development. We reduce losses in zero-index, on-chip photonic crystals by introducing high-Q resonances via resonance-trapped and symmetry-protected states. Using these approaches, we experimentally obtain quality factors of 2.6*10^3 and 7.8*10^3 at near-infrared wavelengths, corresponding to an order-of-magnitude reduction in propagation loss over previous designs. Our work presents a viable approach to fabricate zero-index on-chip nanophotonic devices with low-loss., Comment: 35 pages, 16 figures

The attitude tracking control problem of a rigid spacecraft with actuator saturation is investigated in this paper. A finite-time attitude tracking control scheme is presented by incorporating sliding mode control (SMC) and adaptive technique. Specifically, a novel time-varying sliding mode manifold is first developed that aims at regulating the attitude tracking error to equilibrium point within a certain finite time. Moreover, it can be specified a priori by the designer according to the mission requirement. Subsequently, an adaptive controller is derived by using the SMC in conjunction with adaptive technique. The designed controller is capable of ensuring that the state trajectories reach to sliding regime within a finite time, and hence that attitude tracking error can converge to zero in a finite time with the aid of the developed sliding dynamics, despite the presence of exogenous disturbances, unknown inertia properties and saturation nonlinearities. Finally, the simulation experiments are carried out to demonstrate the effectiveness of the proposed control scheme.

Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert neuroprotective effects on ischemic stroke induced by permanent and transient middle cerebral artery occlusion in experimental animals. The aim of the present study was to investigate the effect of PF11 on thromboembolic stroke in rats and its possible mechanisms on thromboinflammation. PF11 (4, 12, 36 mg/kg) was injected intravenously (i.v.) once a day for 3 consecutive days to male Wistar rats followed by embolic middle cerebral artery occlusion (eMCAO). The results showed that PF11 significantly reduced the cerebral infarction volume, brain edema and neurological deficits induced by eMCAO. Meanwhile, the thromboinflammation in the ischemic hemisphere was observed at 24 h after eMCAO, as indicated by the increased number of microvascular thrombus and inflammatory response. Moreover, eMCAO resulted in the up-regulation of platelet glycoprotein Ibα (GPIbα) and VI (GPVI), as well as the activation of contact-kinin pathway. Notably, PF11 significantly reversed all these changes. Furthermore, PF11 prevented the eMCAO-induced loss of tight junction proteins and up-regulation of matrix metalloproteinase-9 (MMP-9), thus leading to the alleviation of blood-brain barrier (BBB) damage. In conclusion, the present study revealed that thromboinflammation was induced in the ischemic hemisphere of rats after eMCAO and PF11 exerted marked protective effects against thromboembolic stroke by attenuating thromboinflammation and preventing BBB damage. This research further identifies the potential therapeutic role of PF11 for ischemic stroke.

Drugs of abuse, including morphine and cocaine, can reduce hippocampal neurogenesis (HN). Whereas promotion of HN is being increasingly recognized as a promising strategy for treating morphine and cocaine addiction. The present study is focused on exploring the changes of HN during methamphetamine (METH) administration and further clarify if HN is involved in METH-associated reward memory. After successfully establishing the conditioned place preference (CPP) paradigm to simulate the METH-associated reward memory in C57BL/6 mice, we observed that HN was significantly inhibited during METH (2 mg/kg, i. p.) administration and returned to normal after the extinction of METH CPP, as indicated by the immunostaining of bromodeoxyuridine (BrdU) and doublecortin (DCX) in the hippocampus. To promote/inhibit HN levels, 7,8-dihydroxyflavone (DHF), a small tyrosine kinase receptor B (TrkB) agonist and temozolomide (TMZ), an alkylating agent, were administered intraperitoneally (i.p.), respectively. The data showed that either DHF (5 mg/kg, i. p.) or TMZ (25 mg/kg, i. p.) pre-treatment before METH administration could significantly prolong extinction and enhance reinstatement of the reward memory. Notably, DHF treatment after METH administration significantly facilitated extinction and inhibited METH reinstatement, while TMZ treatment resulted in opposite effects. The present study indicated that METH administration could induce a temporal inhibitory effect on HN. More importantly, promotion of HN after the acquisition of METH-associated reward memory, but not inhibition of HN or promotion of HN before the acquisition of reward memory, could facilitate METH extinction and inhibit METH reinstatement, indicating the beneficial effect of HN on METH addiction by erasing the according reward memory.

Drug addiction is one of the leading causes of mortality worldwide. Despite great advances were achieved in understanding the neurobiology of drug addiction, the therapeutic options are severely limited, with poor effectiveness and serious side effects. The neuropeptide oxytocin (OXT) is well known for its effects on uterine contraction, sexual/maternal behaviors, social affiliation, stress and learning/memory by interacting with the OXT receptor and other neuromodulators. Emerging evidence suggests that the acute or chronic exposure to drugs can affect the OXT system. Additionally, OXT administration can ameliorate a wide range of abused drug-induced neurobehavioral changes. Overall, OXT not only suppresses drug reward in the binge stage of drug addiction, but also reduces stress responses and social impairments during the withdrawal stage and, finally, prevents drug/cue/stress-induced reinstatement. More importantly, clinical studies have also shown that OXT can exert beneficial effects on reducing substance use disorders of a series of drugs, such as heroin, cocaine, alcohol, cannabis and nicotine. Thus, the present review focuses on the role of OXT in treating drug addiction, including the preclinical and clinical therapeutic potential of OXT and its analogs on the neurobiological perspectives of drugs, to provide a better insight of the efficacy of OXT as a clinical addiction therapeutic agent.

With the continuous development of the construction industry, the utilization rate of construction waste recycling is still at a low level. Therefore, the government has issued relevant policies to reduce construction waste and take measures for resource utilization. Based on the estimation of the output of construction waste in Wuhan in the past ten years, the current utilization level of construction waste in Wuhan is obtained. In combination with the current policy and Wuhan city construction waste recycling enterprise’s game, it is concluded that the government needs to enhance the construction waste recycling enterprise of rewards and punishments, so as to improve the utilization of construction waste.

Supplemental Digital Content is available in the text, Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) at the colonic mucosa and submucosa. Shen-Ling-Bai-Zhu-San (SLBZS) is one of the most common formulations of traditional Chinese medicine (TCM) for the treatment of UC. However, its effects and safety remain uncertain. This protocol is described for a systematic review to investigate the beneficial effects and safety of SLBZS for UC. Methods: We will systematically search for eligible studies in PubMed, the Cochrane library, Embase, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), and Wanfang Data (WAN FANG) until August 2018. The primary outcomes are the induction of remission and the maintenance of remission. The summary results will be pooled using the random-effects model or fixed-effects model according to the heterogeneity of the included studies. Results: The results will be submitted to a peer-reviewed journal for publication. Conclusion: The conclusion of our systematic review will provide evidence to judge whether SLBZS is an effective intervention for patient with UC. PROSPERO registration number: PROSPERO CRD 42018100477.

Monocyte/macrophage recruitment is closely associated with the degree of hypertensive renal injury. Here we investigated the direct role of macrophage using Liposome encapsulated clodronate (LEC) to deplete monocyte/macrophage in Ang II-induced hypertensive renal injury. C57BL/6 mice were treated with a pressor dose of angiotensin II (Ang, 1.4 mg/kg/day by mini-pump) plus LEC or the PBS-liposome for two weeks. Ang II mice developed hypertension (186 ± 5 vs. 110 ± 4 mmHg in control, p+ cells) and the protein expression of renal tumor necrosis factor α and interleukin β1, which were significantly reduced in Ang II mice treated with LEC. Ang II increased renal oxidative stress (as demonstrated by increased oxidative fluorescence densities, NADPH oxidative activity and the protein expression of NADPH oxidase subunits gp91phox and p22phox) and the expression of profibrotic factors transform growth factor β1 and fibronectin. Ang II also inhibited the phosphorylation of endothelial nitric oxide synthesis (eNOS, ser1177). LEC revised most of the changes in the Ang II-induced molecules as mentioned above. Our results suggest that renal macrophage is a main mediator to contribute to Ang II-induced hypertensive renal injury and fibrosis, the underlying mechanisms may involve reduction in macrophage-drove renal inflammation and restoration of the balance between renal oxidative stress and eNOS. These findings may lead us to develop a novel therapy directed at targeting the infiltration of macrophages or the macrophages-derived cytokines for treatment of hypertensive renal diseases.

The objective of this study was to illustrate the role of enhancer zeste homolog 2 (EZH2) overexpression in the proliferation, progression, and prognosis of cervical cancer. We detected EZH2 and Ki-67 expression levels using immunohistochemical (IHC) studies in 20 normal cervical tissues, 50 cervical intraepithelial neoplasia (including 25 low-grade intraepithelial lesions and 25 high-grade intraepithelial lesions), and 101 cervical cancer tissues. The relationships between EZH2 expression and Ki-67 expression, conventional clinicopathologic characteristics of cervical cancer, and patient outcomes were evaluated. The effect of EZH2 expression on cancer-specific survival was assessed by multivariate Cox regression analysis. Positive expression of EZH2 was detected in 10% (2/20) of the normal cervical tissues, 52% (13/25) of the low-grade squamous intraepithelial lesions, 64% (16/25) of the high-grade squamous intraepithelial lesions, and 68.3% (69/101) of the cervical cancer tissues. The expression of Ki-67 was positively correlated with EZH2 expression: 5% (1/20) in normal cervical tissues, 48% (12/25) in low-grade squamous intraepithelial lesions, 52% (13/25) in high-grade squamous intraepithelial lesions, and 57.4% (58/101) in cervical cancer tissues. Overexpression of EZH2 was adversely associated with clinical stage, histologic differentiation, infiltration depth, and lymph node metastasis (P

Summary Aims Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert wide-ranging neuroprotective properties. The aim of this study was to investigate the effect and potential mechanisms of PF11 on the autophagic/lysosomal pathway following ischemic stroke. Methods Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). Cerebral ischemia outcome, TUNEL staining, Fluoro-Jade B staining were carried out 24 hours poststroke. The autophagic/lysosomal-related proteins were measured. Results A single administration of PF11 significantly decreased the infarct area, reduced the brain water content, and improved neurological functions, even 4 hours after the onset of pMCAO. Meanwhile, PF11 lessened the ischemic insult-mediated loss of neurons and activation of astrocytes and microglia. Furthermore, PF11 attenuated pMCAO-induced accumulations of autophagosomes and apoptosis. We further observed a remarkable effect of PF11 in reversing the ischemic insult-induced accumulation of autophagosomes (LC3-II) and abnormal aggregation of autophagic proteins (SQSTM1 and ubiquitin). Furthermore, PF11 was capable of improving lysosomal function and lysosome/autophagosome fusion following pMCAO, and this change was reversed by the lysosomal inhibitor chloroquine. Also, the improvement of ischemic outcome and the antiapoptotic effect induced by PF11 was reversed by CQ. Conclusion These findings indicate that the autophagic flux is impaired in a rat model of pMCAO, and that PF11 exerts an excellent protective effect against ischemic stroke by alleviating autophagic/lysosomal defects.

Yonkenafil is a novel phosphodiesterase type 5 (PDE5) inhibitor. Here we evaluated the effect of yonkenafil on ischemic injury and its possible mechanism of action. Male Sprague-Dawley rats underwent middle cerebral artery occlusion, followed by intraperitoneal or intravenous treatment with yonkenafil starting 2h later. Behavioral tests were carried out on day 1 or day 7 after reperfusion. Nissl staining, Fluoro-Jade B staining and electron microscopy studies were carried out 24h post-stroke, together with an analysis of infarct volume and severity of edema. Levels of cGMP-dependent Nogo-66 receptor (Nogo-R) pathway components, hsp70, apaf-1, caspase-3, caspase-9, synaptophysin, PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and nerve growth factor (NGF)/tropomyosin-related kinase A (TrkA) were also measured after 24h. Yonkenafil markedly inhibited infarction and edema, even when administration was delayed until 4h after stroke onset. This protection was associated with an improvement in neurological function and was sustained for 7d. Yonkenafil enlarged the range of penumbra, reduced ischemic cell apoptosis and the loss of neurons, and modulated the expression of proteins in the Nogo-R pathway. Moreover, yonkenafil protected the structure of synapses and increased the expression of synaptophysin, BDNF/TrkB and NGF/TrkA. In conclusion, yonkenafil protects neuronal networks from injury after stroke.

The fast recovery diodes (FRDs) are widely used in high frequency and high power applications. The forward characteristics of the FRDs, such as the forward voltage drop, are very important to determine the property of the FRDs. The forward characteristics of the FRD always greatly depend on the temperature. Here, in this paper, we researched some FRDs with special structures by simulation and proposed a new structure to farther improve the temperature coefficient of the FRDs. It is found that, a diode with low P+ emitter efficiency, and a P+ buried layer at anode junction has a better forward temperature coefficient. It proposes a guiding way to design the FRDs which are worked in the positive temperature coefficient (PTC) area.

Thyroid cancer is a malignant neoplasm originated from thyroid cells. It can be classified into papillary carcinomas (PTCs) and anaplastic carcinomas (ATCs). Although ATCs are in an very aggressive status and cause more death than PTCs, their difference is poorly understood at molecular level. In this study, we focus on the transcriptome difference among PTCs, ATCs and normal tissue from a published dataset including 45 normal tissues, 49 PTCs and 11 ATCs, by applying a machine learning method, maximum relevance minimum redundancy, and identified 9 genes (BCL2, MRPS31, ID4, RASAL2, DLG2, MY01B, ZBTB5, PRKCQ and PPP6C) and 1 miscRNA (miscellaneous RNA, LOC646736) as important candidates involved in the progression of thyroid cancer. We further identified the protein-protein interaction (PPI) sub network from the shortest paths among the 9 genes in a PPI network constructed based on STRING database. Our results may provide insights to the molecular mechanism of the progression of thyroid cancer.