Expression and clinical significance of <i>Pax6</i> gene in retinoblastoma

AIM: To discuss the expression and clinical significance of <i>Pax6 </i>gene in retinoblastoma(Rb). <p>METHODS: Totally 15 cases of fresh Rb organizations were selected as observation group and 15 normal retinal organizations as control group. Western-Blot and reverse transcriptase polymerase chain reaction(RT-PCR)methods were used to detect <i>Pax6</i> protein and <i>Pax6 </i>mRNA expressions of the normal retina organizations and Rb organizations. At the same time, Western Blot method was used to detect the <i>Pax6</i> gene downstream MATH5 and BRN3b differentiation gene protein level expression. After the comparison between two groups, the expression and clinical significance of <i>Pax6</i> gene in Rb were discussed. <p>RESULTS: In the observation group, average value of mRNA expression of <i>Pax6</i> gene was 0.99±0.03; average value of <i>Pax6</i> gene protein expression was 2.07±0.15; average value of BRN3b protein expression was 0.195±0.016; average value of MATH5 protein expression was 0.190±0.031. They were significantly higher than the control group, and the differences were statistically significant(<i>P</i><0.05). <p>CONCLUSION: Abnormal expression of <i>Pax6</i> gene is likely to accelerate the occurrence of Rb

Higher Sensitivity to Thyroid Hormones may be Linked to Maintaining the Healthy Metabolic Condition in Population with Obesity: New Insight from NHANES

Introduction: Obesity contributes to the pathogenesis of diverse metabolic diseases, and yet the mechanism underlying metabolically healthy obesity (MHO) remains elusive. Thyroid hormones and sensitivity to them have a major impact on human metabolism. Our study investigated whether MHO is associated with thyroid hormone sensitivity. Methods: Thyroid hormone indices, including the thyroid stimulating hormone (TSH) index (TSHI), the thyrotroph thyroxine sensitivity index (TTSI), the thyroid feedback quantile-based index (TFQI), and the parametric thyroid feedback quantile-based Index (PTFQI), were calculated based on a non-institutionalized U.S. sample in the National Health and Nutrition Examination Survey (NHANES, 2007–2012). Participants were divided into four groups (metabolically healthy non-obesity [MHNO], metabolically unhealthy non-obesity [MUNO], MHO, and metabolically unhealthy obesity [MUO]) according to their body mass index and metabolic profiles. Linear regression, logistic regression, and restricted cubic splines were used to study the association between thyroid hormone indices and metabolic phenotypes. Results: A total of 4,857 participants (49.6% men; mean age, 42.6 years) were included. Of these, 1,539 had obesity and 235 were identified as having MHO. Compared with the MHNO group, participants with MHO had a lower level of TSH, TSHI, TTSI, TFQI, and PTFQI (all P 0.05). Among the participants with obesity, TSH, TSHI, TTSI, TFQI, and PTFQI were positively associated with metabolic abnormality (all P < 0.05). Discussion/Conclusion: The MHO population exhibited higher thyroid hormone sensitivity among various obesity phenotypes, even when compared to those with MHNO. A positive association was observed between metabolic abnormality and thyroid hormone sensitivity, while the trend of TSH was observed to be consistent with sensitivity to thyroid hormone indices in discriminating metabolic abnormality. Hence, TSH has potential as a convenient index for detecting sensitivity to thyroid hormone and further metabolic conditions

Effects of inhomogeneous activity of players and noise on cooperation in spatial public goods games

We study the public goods game in the noisy case by considering the players with inhomogeneous activity teaching on a square lattice. It is shown that the introduction of the inhomogeneous activity of teaching of the players can remarkably promote cooperation. By investigating the effects of noise on cooperative behavior in detail, we find that the variation of cooperator density $\rho_C$ with the noise parameter $\kappa$ displays several different behaviors: $\rho_C$ monotonically increases (decreases) with $\kappa$; $\rho_C$ firstly increases (decreases) with $\kappa$ and then it decreases (increases) monotonically after reaching its maximum (minimum) value, which depends on the amount of the multiplication factor $r$, on whether the system is homogeneous or inhomogeneous, and on whether the adopted updating is synchronous or asynchronous. These results imply that the noise plays an important and nontrivial role in the evolution of cooperation.Comment: 4 pages, 4 figure

Trimodal Therapy: A Tumor Vascularâ Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia (Adv. Sci. 8/2018)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145503/1/advs201870048.pd

A Tumor Vascularâ Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

Vascularâ targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)â based nanosystem for rationally designed, interlocking trimodal cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxiaâ activated prodrug (HAP), and HIFâ 1α siRNA (siHIFâ 1α) (3) is reported. The VTPâ induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a topoisomerase II inhibitor) for chemotherapy. However, the hypoxiaâ induced HIFâ 1α acts as a â hidden brake,â through downregulating CYP450 (the dominant HAPâ activating reductases), to substantially hinder AQ4N activation. siHIFâ 1α is rationally adopted to suppress the HIFâ 1α expression upon hypoxia and further enhance AQ4N activation. This trimodal nanosystem significantly delays the growth of PCâ 3 tumors in vivo compared to the control nanoparticles carrying VP, AQ4N, or siHIFâ 1α alone or their pairwise combinations. This multimodal nanoparticle design presents, the first example exploiting VTP to actively induce hypoxia for enhanced HAP activation. It is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAPâ activating reductases (CYP450), and this can be well overcome by GO nanoparticleâ mediated siHIFâ 1α intervention.Vascularâ targeted photodynamic therapy (VTP) is integrated with hypoxiaâ activated prodrug (AQ4N) and HIFâ 1α siRNA (siHIFâ 1α) for interlocking trimodal therapy. The VTPâ induced aggravated hypoxia is exploited for efficient AQ4N activation for chemotherapy. HIFâ 1α induced by hypoxia acts as a â hidden brake,â through downregulating CYP450 reductases, to hinder AQ4N activation. siHIFâ 1α is rationally adopted to suppress HIFâ 1α expression upon VTP to enhance AQ4N activation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/1/advs661-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/2/advs661.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145505/3/advs661_am.pd

Thromboxane A2 Activates YAP/TAZ Protein to Induce Vascular Smooth Muscle Cell Proliferation and Migration

The thromboxane A2 receptor (TP) has been implicated in restenosis after vascular injury, which induces vascular smooth muscle cell (VSMC) migration and proliferation. However, the mechanism for this process is largely unknown. In this study, we report that TP signaling induces VSMC migration and proliferation through activating YAP/TAZ, two major downstream effectors of the Hippo signaling pathway. The TP-specific agonists [1S-[1α,2α(Z),3β(1E,3S*),4 α]]-7-[3-[3-hydroxy-4-(4-iodophenoxy)-1-butenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (I-BOP) and 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619) induce YAP/TAZ activation in multiple cell lines, including VSMCs. YAP/TAZ activation induced by I-BOP is blocked by knockout of the receptor TP or knockdown of the downstream G proteins Gα12/13. Moreover, Rho inhibition or actin cytoskeleton disruption prevents I-BOP-induced YAP/TAZ activation. Importantly, TP activation promotes DNA synthesis and cell migration in VSMCs in a manner dependent on YAP/TAZ. Taken together, thromboxane A2 signaling activates YAP/TAZ to promote VSMC migration and proliferation, indicating YAP/TAZ as potential therapeutic targets for cardiovascular diseases

Topographic beta spiral and onshore intrusion of the Kuroshio Current

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 45 (2018): 287–296, doi:10.1002/2017GL076614.The Kuroshio intrusion plays a vitally important role in carrying nutrients to marginal seas. However, the key mechanism leading to the Kuroshio intrusion remains unclear. In this study we postulate a mechanism: when the Kuroshio runs onto steep topography northeast of Taiwan, the strong inertia gives rise to upwelling over topography, leading to a left-hand spiral in the stratified ocean. This is called the topographic beta spiral, which is a major player regulating the Kuroshio intrusion; this spiral can be inferred from hydrographic surveys. In the world oceans, the topographic beta spirals can be induced by upwelling generated by strong currents running onto steep topography. This is a vital mechanism regulating onshore intruding flow and the cross-shelf transport of energy and nutrients from the Kuroshio Current to the East China Sea. This topographic beta spiral reveals a long-term missing link between the oceanic general circulation theory and shelf dynamic theory.Strategic Priority Research Program of the Chinese Academy of Sciences Grant Numbers: XDA11020104, XDA110203052; National Natural Science Foundation of China (NSFC) Grant Numbers: 41576023, 41376030, 41476019; Foundation for Innovative Research Groups of NSFC Grant Number: 41421005; NSFC-Shandong Joint Fund for Marine Science Research Centers Grant Number: U1406401; Aoshan Sci-Tec Innovative Project of Qingdao National Laboratory for Marine Science and Technology Grant Number: 2016ASKJ02; National Key Research and Development Program of China Grant Numbers: 2017YFC1404000, 2016YFC1401601; National Key research and development Plan Sino-Australian Center for Healthy Coasts Grant Number: 2016YFE01015002018-07-1