Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma

Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.

具有非线性颗粒链的弯曲弹性波超材料中的二极管行为

本文研究了非线性弹性波超材料的带隙和非互易传播特性,该结构由双振子弯曲颗粒链组成.采用增量谐波平衡方法推导了具有分数项的非线性波方程.考虑了不同的弯曲角度和振幅比对非线性弹性波带隙的影响.通过Runge-Kutta方法数值计算和实验研究证实了超材料的带隙和二极管行为.本研究为非线性声子晶体和具有不同弯曲方向的力学超材料提供了新的应用.

Active feedback control of sound radiation in elastic wave metamaterials immersed in water with fluid-solid coupling

Due to their potential properties unlike traditional materials and structures,elastic wave metamaterials have received significant interests in recent years.With the coupling between the acoustic and vibration,their mechanical characteristics can be tuned by the active feedback control system at low frequency ranges in which the traditional passive control is limited.This work illustrates that the superior performances of the effective mass density and sound pressure level(SPL)of an elastic wave metamaterial can be significantly changed by the active control,in which the periodic array of local resonators and orthogonal stiffeners are included.Significantly,based on the locally resonant mechanism,the negative density occurs over a frequency range.Due to the effects of lattice constant,structural damping and other parameters,the SPL with the function of fluid-solid coupling are illustrated and discussed.

Sound Transmission Comparisons of Active Elastic Wave Metamaterial Immersed in External Mean Flow

Using the active feedback control system on the elastic wave metamaterial,this research concentrates on the sound transmission with the dynamic effective model.The metamaterial is subjected to an incident pressure and immersed in the external mean flow.The elastic wave metamaterial consists of double plates and the upper and lower four-link mechanisms are attached inside.The vertical resonator is attached by the active feedback control system and connected with two four-link mechanisms.Based on the dynamic equivalent method,the metamaterial is equivalent as a single-layer plate by the dynamic effective parameter.With the coupling between the fluid and structure,the expression of the sound transmission loss(STL)is derived.This research shows the influence of effective mass density on sound transmission properties,and the STL in both modes can be tuned by the acceleration and displacement feedback constants.In addition,the dynamic response and the STL are also changed obviously by different values of structural damping,incident angle(i.e.,the elevation and azimuth angles)and Mach number of the external fluid with the mean flow property.The results for sound transmission by two methods are compared,i.e.,the virtual work principle for double plates and the dynamic equivalent method corresponding to a single one.This paper is expected to be helpful for understanding the sound transmission properties of both pure single-and double-plate models.

Improving native human sperm freezing protection by using a modified vitrification method

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice.However,it has been shown to have a negative impact on sperm function and structure.Vitrification as a successful alternative method has been proved to have better protective effects on human embryos,but vitrification of spermatozoa is still subject to low recovery rates.In this study,a modified vitrification method for native spermatozoa was developed.A total of 28 semen samples were included;each sample was divided into three equal parts and assigned to fresh,slow freezing,and vitrification groups.Sperm vitality,motility,morphology,DNA integrity,and acrosome reaction were assessed for each of the groups.The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing;vitrification achieves a higher recovery rate(P<0.05),motility(P<0.05),morphology(P<0.05),and curve line velocity(P<0.05)than slow freezing.Furthermore,DNA fragmentation was decreased(P<0.05)and better acrosome protection(P<0.05)was exhibited in the spermatozoa after vitrification.Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster,indicating that spermatozoa are better preserved through vitrification.In conclusion,while both slow freezing and vitrification have negative effects on sperm function and structure,the vitrification protocol described here had a relatively better recovery rate(65.8%)and showed improved preservation of several sperm quality parameters compared with slow freezing.

Nonreciprocal Head-on Collision Between Two Nonlinear Solitary Waves in Granular Metamaterials with an Interface

In this work,the head-on collision and transmission with nonreciprocal properties of opposite propagating solitary waves are studied,in which the interface between different granular chains is considered.Due to the discontinuity of two periodic granular systems,the transmitted and reflected solitary waves are produced.The head-on collision appears at the interface and the reductive perturbation method is applied to derive the generated solitary waves.According to the derivation and numerical simulation,we can find that the transmitted and reflected solitary waves can propagate with the same speed when they locate at the same chain.Moreover,the influences of both the arrangement and prestress are discussed.It is found that the amplitude and velocity of solitary waves become larger because of a bigger prestress,which result in the nonreciprocal collision and transmission in the granular mechanical metamaterials.This study is expected to be helpful for the design and application of elastic wave metamaterials and mechanical diodes with nonlinear solitary waves.