Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.

CTGF/CCN2 promotes the proliferation of human osteosarcoma cells via cross-talking with the stromal CXCL12/CXCR4-AKT-αvβ3 signaling axis in tumor microenvironment

Osteosarcoma (OS) is the most common histological form of primary bone cancer in childhood cancer and young adults. At present, OS is widely investigated because of the interaction between the tumor and bone microenvironment and the effect of such interaction on OS progression and metastasis.1 The connective tissue growth factor (CTGF), also known as cellular communication network factor 2 (CCN2), is a secreted extracellular matrix-associated protein. CTGF is as active as the regulators of signaling activities of several different pathways and an orchestrator of their cross-talk.2 Therefore, we conducted experiments to investigate the effects of CTGF on OS tumor progress and the cross-talk with stromal cells in the tumor microenvironment.

Anthropogenic pressures increase extinction risk of an isolated Asian elephant(Elephas maximus)population in southwestern China,as revealed by a combination of molecular-and landscape-scale approaches

Identification of the effect of anthropogenic threats on ecosystem is crucial.We used molecular tools and remote sensing to evaluate the population status of an isolated Asian elephant population in southwestern China in response to changes in habitat suitability between 1989 and 2019.A total of 22 unique genotypes were identified from 117 dung samples collected between March and June 2018 using microsatellite DNA analysis,including 13 males and 9 females.Based on the size of fecal boli,1 animal was a juvenile,9 were subadults,and 12 were adults,indicating that recruitment was limited.The effective population size was small(15.3)but there was no signature of a recent population bottleneck.We observed a low genetic diversity(He=0.46±0.05)and a high level of inbreeding(Fis of 0.43±0.11),suggesting low population viability and high risk of extinction.In total,these elephants lost nearly two thirds(62%)of their habitat in 3 decades.The expansion of agriculture and rubber plantations followed by an increase in human settlements after 1989 increased the isolation of this population.We recommend that resettlement of 800 inhabitants of 2 villages and the abandonment of associated farmland and rubber plantations would make an additional 20 km2 of suitable habitat available.This could allow a population increase of 14 elephants,possibly by translocating individuals from elsewhere in China.Ourfindings can be applied to the management and conservation of other fragmented populations in China or in other range countries of Asian elephants.

二值图像超分辨率重建网络

近年来,深层卷积神经网络在图像超分辨率重建任务中取得了巨大成功,然而复杂的深度神经网络会消耗大量存储空间以及计算资源,严重限制了其在资源有限的移动端设备上的部署.因此降低模型的资源消耗将有助于扩展深度超分辨率网络的实际应用范围.二值神经网络占用存储空间小、计算效率高,激励我们将二值化算法应用于目前的深度超分辨率重建领域,满足现有移动设备对于超分辨率的实际应用需求.因此,本文关注于二值图像超分辨率重建网络的研究.为此,我们首先总结了现有二值化方法,并针对其技术细节和算法特点进行了详细介绍.随后,我们探索了目前二值化方法在超分辨率领域的实际应用效果,并面向图像超分辨率重建任务提出一种新的二值化算法,主要通过提高网络前向过程表达能力和减少网络反向过程训练损失提升二值超分辨率网络的性能.实验表明,无论对比现有基于分类任务的二值化算法还是对比基于超分辨率任务的二值化算法,我们的方法均可以取得最优的性能.