Impairment of rigidity sensing caused by mutant TP53 gain of function in osteosarcoma

Osteosarcoma(OS)is the most common primary malignant pediatric bone tumor and is characterized by high heterogeneity.Studies have revealed a wide range of phenotypic differences among OS cell lines in terms of their in vivo tumorigenicity and in vitro colony-forming abilities.However,the underlying molecular mechanism of these discrepancies remains unclear.The potential role of mechanotransduction in tumorigenicity is of particular interest.To this end,we tested the tumorigenicity and anoikis resistance of OS cell lines both in vitro and in vivo.We utilized a sphere culture model,a soft agar assay,and soft and rigid hydrogel surface culture models to investigate the function of rigidity sensing in the tumorigenicity of OS cells.Additionally,we quantified the expression of sensor proteins,including four kinases and seven cytoskeletal proteins,in OS cell lines.The upstream core transcription factors of rigidity-sensing proteins were further investigated.We detected anoikis resistance in transformed OS cells.The mechanosensing function of transformed OS cells was also impaired,with general downregulation of rigidity-sensing components.We identified toggling between normal and transformed growth based on the expression pattern of rigidity-sensing proteins in OS cells.We further uncovered a novel TP53 mutation(R156P)in transformed OS cells,which acquired gain of function to inhibit rigidity sensing,thus sustaining transformed growth.Our findings suggest a fundamental role of rigidity-sensing components in OS tumorigenicity as mechanotransduction elements through which cells can sense their physical microenvironment.In addition,the gain of function of mutant TP53 appears to serve as an executor for such malignant programs.

具有乳头状核特征的非浸润性甲状腺滤泡性肿瘤临床病理特征分析

目的:探讨具有乳头状核特征的非浸润性甲状腺滤泡性肿瘤(non-invasive follicular thyroid neoplasm with papillary-like nu⁃clear features,NIFTP)的临床病理学特征。方法:回顾性分析2012年1月至2017年12月蚌埠医学院第一附属医院7例NIFTP患者的临床表现、组织形态学、免疫组织化学、分子遗传和预后特征,并复习相关文献。结果:7例NIFTP患者中,男性3例,女性4例,年龄36~54岁,中位年龄50岁;肿瘤直径0.2~3.0 cm,中位直径1.2 cm。单发结节4例,双发结节2例,多发结节1例。7例形态学表现为包膜完整、边界清晰,无血管和包膜浸润;肿瘤细胞核大、拥挤,部分可见核沟、核内假包涵体及毛玻璃样核,具有甲状腺乳头状癌(papillary thyroid carcinoma,PTC)的核特征。免疫组织化学缺乏特异性表达,诊断价值有限,Ki-67增殖指数低。荧光定量PCR检测KRAS和NRAS基因突变2例,均无BRAF V600E突变。5例随访21~74个月,无复发和转移,2例失访。结论:NIFTP是一种极低度恶性潜能的甲状腺交界性肿瘤,具有特定形态学表现和惰性生物学行为,RAS基因突变检测有助于诊断。

Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes:current perspectives and future challenges

Exosomes are small intracellular membrane-based vesicles with different compositions that are involved in several biological and pathological processes. The exploitation of exosomes as drug delivery vehicles offers important advantages compared to other nanoparticulate drug delivery systems such as liposomes and polymeric nanoparticles; exosomes are non-immunogenic in nature due to similar composition as body's own cells. In this article, the origin and structure of exosomes as well as their biological functions are outlined. We will then focus on specific applications of exosomes as drug delivery systems in pharmaceutical drug development. An overview of the advantages and challenges faced when using exosomes as a pharmaceutical drug delivery vehicles will also be discussed.

CMOS-compatible all-optical modulator based on the saturable absorption of graphene

Graphene resting on a silicon-on-insulator platform offers great potential for optoelectronic devices.In the paper,we demonstrate all-optical modulation on the graphene-silicon hybrid waveguides(GSHWs)with tens of micrometers in length.Owing to strong interaction between graphene and silicon strip waveguides with compact light confinement,the modulation depth reaches 22.7%with a saturation threshold down to 1.38 pJ per pulse and a 30-μm-long graphene pad.A response time of 1.65 ps is verified by a pump-probe measurement with an energy consumption of 2.1 pJ.The complementary metal-oxide semiconductor compatible GSHWs with the strip configuration exhibit great potential for ultrafast and broadband all-optical modulation,indicating that employing two-dimensional materials has become a complementary technology to promote the silicon photonic platform.

Real-time observation of frequency Bloch oscillations with fibre loop modulation

Bloch oscillations(BOs)were initially predicted for electrons in a solid lattice to which a static electric field is applied.The observation of BOs in solids remains challenging due to the collision scattering and barrier tunnelling of electrons.Nevertheless,analogies of electron BOs for photons,acoustic phonons and cold atoms have been experimentally demonstrated in various lattice systems.Recently,BOs in the frequency dimension have been proposed and studied by using an optical micro-resonator,which provides a unique approach to controlling the light frequency.However,the finite resonator lifetime and intrinsic loss hinder the effect from being observed practically.Here,we experimentally demonstrate BOs in a synthetic frequency lattice by employing a fibre-loop circuit with detuned phase modulation.We show that a detuning between the modulation period and the fibre-loop roundtrip time acts as an effective vector potential and hence a constant effective force that can yield BOs in the modulation-induced frequency lattices.With a dispersive Fourier transformation,the pulse spectrum can be mapped into the time dimension,and its transient evolution can be precisely measured.This study offers a promising approach to realising BOs in synthetic dimensions and may find applications in frequency manipulations in optical fibre communication systems.

On-chip ultrafast pulse generation based on graphene-silicon hybrid waveguides

On-chip ultrafast mode-locking lasers are basic building blocks for the realization of a chip-based optical frequency comb.In this paper,an ultrafast saturable absorber made up of a graphene pad on top of a silicon waveguide is applied to implement an ultrafast pulse laser.Benefiting from the small mode area of the graphene/silicon hybrid waveguide,the saturable pulse energy is reduced by two orders of magnitude compared with the fiber.A mode-locked pulse with a duration of 542 fs and a repetition rate of 54.37 MHz is realized.Pump–probe measurement shows that the carrier relaxation process of free carrier recombination with atomic-thin graphene/silicon junctions is three orders of magnitude faster than silicon,which plays a fundamental role in pulse narrowing.The chip-scale silicon ultrafast laser lays a foundation for a new class of nonlinear devices,in which a combination with multiple functional silicon photonic circuits enables efficient nonlinear interaction at the micrometer scale and less than 1 W of power consumption.

复分解电渗析清洁制备碘化锂实验研究

碘化锂广泛应用在燃料电池的合成中,目前碘化锂的生产方式主要有联氨法和硫化氢还原法,制备过程中需使用联胺或硫化氢,这些均属于危险化学品,存在较大安全风险,制约它的工业化生产。本工作以初级锂盐硫酸锂为原料,采用复分解电渗析清洁制备碘化锂,研究了操作电压、产品液与原料液初始体积比和原料液初始浓度对制备过程的影响,并对碘化锂产品与制备过程进行评价与经济性分析。实验结果表明,提高操作电压可以缩短反应时间;降低产品液与原料液初始体积比可以明显提升碘化锂产品浓度,但电流效率会下降;增加初始原料液浓度可以显著提升碘化锂产品的浓度,提升系统的产能。在操作电压为25 V,初始碘化钾浓度为0.2 mol/L,初始硫酸锂浓度为0.1 mol/L,产品液与原料液初始体积比为1:1的条件下,制备的碘化锂产品纯度可达98.8%,工艺过程成本约为3.6¥/kg LiI。复分解电渗析制备碘化锂具有工艺流程简单、能耗低、环境友好等明显优势,这对电驱动膜分离在锂盐清洁生产的应用具有重要参考意义。