Biofilm Homeostasis Interference Therapy via 1O2-Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination

The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel “interference-regulation strategy” based on bovine serum albumin–iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (¹O₂)-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H₂O₂ inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O₂), which can efficiently enhance the generation of ¹O₂ under near-infrared irradiation. The ¹O₂-induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and ¹O₂ penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this ¹O₂-sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy.     

融合双注意力机制3D U-Net的肺肿瘤分割

目的 精确的肺肿瘤分割对肺癌诊断、手术规划以及放疗具有重要意义。计算机断层扫描（computed tomography,CT）是肺癌诊疗中最重要的辅助手段,但阅片是一项依靠医生主观经验、劳动密集型的工作,容易造成诊断结果的不稳定,实现快速、稳定和准确的肺肿瘤自动分割方法是当前研究的热点。随着深度学习的发展,使用卷积神经网络进行肺肿瘤的自动分割成为了主流。本文针对3D U-Net准确度不足,容易出现假阳性的问题,设计并实现了3维卷积神经网络DAU-Net（dual attention U-Net）。方法 首先对数据进行预处理,调整CT图像切片内的像素间距,设置窗宽、窗位,并通过裁剪去除CT图像中的冗余信息。DAU-Net以3D U-Net为基础结构,将每两个相邻的卷积层替换为残差结构,并在收缩路径和扩张路径中间加入并联在一起的位置注意力模块和通道注意力模块。预测时,采用连通域分析对网络输出的二值图像进行后处理,通过判断每个像素与周围26个像素的连通关系获取所有的连通域,并清除最大连通域外的其他区域,进一步提升分割精度。结果 实验数据来自上海胸科医院,总共1 010例肺癌患者,每例数据只包含一个病灶,专业的放射科医师提供了金标准,实验采用十折交叉验证。结果表明,本文提出的肺肿瘤分割算法与3D U-Net相比,Dice系数和哈斯多夫距离分别提升了2.5%和9.7%,假阳性率减少了13.6%。结论 本文算法能够有效提升肺肿瘤的分割精度,有助于实现肺癌的快速、稳定和准确分割。     

Elastic Janus film for Wound Dressings: Unidirectional Biofluid Transport and Effectively Promoting Wound Healing

The intrinsic hydrophilicity of conventional dressings cannot achieve effective management of excessive biofluid around the wound bed, which inevitably causes infection and hinders wound healing. In addition, present dressings such as medical gauze or band aids have a limited stretching capability, which does not comply well with the skin deformation during muscle movement, thus impacting patient comfort. Herein, a Janus wound dressing is reported by assembling an external hydrophobic (HP) adhesive tape, a filter paper, and a polydimethylsiloxane (PDMS) Janus film. The PDMS Janus film as the primary dressing can unidirectionally remove biofluid away from the wound bed. The mechanism of the unidirectional biofluid transport is investigated, demonstrating that the stretching or bending of the Janus dressing is beneficial for unidirectional biofluid draining. It indicates that the Janus PDMS film has potential for practical applications on stretched or bended skin surface. In addition, in order to prevent bacterial infection, amoxicillin powder is uniformly encapsulated on the HP layer of Janus film, resulting in faster wound healing. This study is valuable for designing and fabricating next-generation dressings with high performance for clinical applications.     

An end-connected dual bus topology for metropolitan area networks

We propose a new topology and the associated medium access protocol for Metropolitan Area Networks (MAN's). The network uses a dual bus with connected ends as the topology. The protocol uses a token passing scheme with destination stripping as the access mechanism. Additional transmissions, referred here as restricted transmissions are also included in the protocol. These transmissions are made possible by the end-connected topology. Using this scheme, a station can make use of even a reserved slot for transmission up to the reserving station on the bus. This mechanism considerably improves the network utilization over those of the conventional Distributed Queue Dual Bus (DQDB) and the Destination Stripping Dual Ring (DSDR) protocols. We carried out simulations to study the utilization and the delay characteristics of the proposed protocol under various network conditions. We demonstrate that the performance of the proposed protocol is much better than that of the DQDB with slot reuse.     

Almond allergens: update and perspective on identification and characterization

Almond (Prunus dulcis) is not only widely used as a human food as a result of its flavor, nutrients, and health benefits, but it is also one of the most likely tree nuts to trigger allergies. Almond allergens, however, have not been studied as extensively as those of peanuts and other selected tree nuts. This review provides an update of the molecular properties of almond allergens to clarify some confusion about the identities of almond allergens and our perspective on characterizing putative almond allergens. At present, the following almond allergens have been designated by the World Health Organization/International Union of Immunological Societies Allergen Nomenclature Sub-Committee: Pru du 3 (a non-specific lipid transfer protein 1, nsLTP1), Pru du 4 (a profilin), Pru du 5 (60S acidic ribosomal protein 2), Pru du 6 (an 11S legumin known as prunin) and Pru du 8 (an antimicrobial protein with cC3C repeats). Besides, almond vicilin and almond γ-conglutin have been identified as food allergens, although further characterization of these allergens is still of interest. In addition, almond 2S albumin was reported as a food allergen as a result of the misidentification of Pru du 8. Two more almond proteins have been called allergens based on their sequence homology with known food allergens and their ‘membership’ in relevant protein families that contain allergens in many species. These include the pathogenesis related-10 protein (referred to as Pru du 1) and the thaumatin-like protein (referred to as Pru du 2). Almonds thus have five known food allergens and five more likely ones that need to be investigated further. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.     

A DES-based group decision model for group decision making with large-scale alternatives

To solve group decision making problems with large-scale alternatives, this paper proposes a dynamic ensemble selection (DES) based group decision model by using historical decision data. The historical decision data of a group of experts are collected from the same multi-criteria decision framework and are mixed to train a set of base classifiers (BCs) to learn group preferences. For each new alternative, the predictions derived from BCs are used to determine its similar historical alternatives from historical data, and the BC with the highest accuracy in predicting the similar historical alternatives is identified as the best individual BC for the new alternative. By iteratively comparing the accuracy of an ensemble of randomly selected BCs and the best individual BC in predicting the similar historical alternatives of the new alternative, a novel DES method is developed to select a competent subset of BCs for the new alternative. The developed DES method effectively avoids the error-independence assumption to a certain extent. Based on the similar historical alternatives determined by the ensemble of selected BCs, a group decision optimization model is developed to learn criterion weights from their assessments on criteria and ensemble predictions derived from the selected BCs. With the learned criterion weights, the understandable group decision result is generated for the new alternative. Case study validates the superiority of the proposed model in diagnosing thyroid nodules using group capabilities. Empirical comparisons on thirty real datasets examine the competence of the proposed DES method against five representative DES methods.

     

Reversing Immunosuppression in Hypoxic and Immune-Cold Tumors with Ultrathin Oxygen Self-Supplementing Polymer Nanosheets under Near Infrared Light Irradiation

Solid tumors are characterized by a hypoxic and immunologically “cold” microenvironment that dramatically limits the therapeutic outcomes of immunotherapy. Thus, strategies and materials that are capable of reversing immunosuppression in immune-cold tumors are highly desired. Herein, it is reported that oxygen (O₂) self-supplementing conjugated microporous polymer nanosheets can be utilized to elicit a robust antitumor T cell immune response in the hypoxic and immunosuppressive tumor microenvironment. The ultrathin nanosheets can generate O₂ through the water splitting reaction and produce massive reactive oxygen species (ROS) under near infrared light irradiation. Meanwhile, the unique photothermal property of the conjugated polymer nanosheets generates hyperthermia under irradiation. Consequently, they are able to maximize the immunogenic cell death (ICD) performance by inducing adequate damage-related molecular patterns in hypoxic tumors. Other than fostering T cell infiltration by the elicited ICD, the loaded indoleamine 2,3-dioxygenase in nanosheets can reverse the immunosuppression and empower ICD effect for efficient T cells priming. In vivo experiments conclusively prove that the designed polymer nanosheets exhibit great potential for tumor eradication, metastasis prevention, as well as long-term survival. Such a photocatalytic platform opens up new paths for reversing immunosuppression in immune-cold tumors and broadens the application of polymer-based nanosheets for cancer therapy.     

2D级联CNN模型的放疗危及器官自动分割

目的 精准的危及器官（organs at risk,OARs）勾画是肿瘤放射治疗过程中的关键步骤。依赖人工的勾画方式不仅耗费时力,且勾画精度容易受图像质量及医生主观经验等因素的影响。本文提出了一种2D级联卷积神经网络（convolutional neural network,CNN）模型,用于放疗危及器官的自动分割。方法 模型主要包含分类器和分割网络两部分。分类器以VGG（visual geometry group）16为骨干结构,通过减少卷积层以及加入全局池化极大地降低了参数量和计算复杂度;分割网络则是以U-Net为基础,用双线性插值代替反卷积对特征图进行上采样,并引入Dropout层来缓解过拟合问题。在预测阶段,先利用分类器从输入图像中筛选出包含指定器官的切片,然后使用分割网络对选定切片进行分割,最后使用移除小连通域等方法对分割结果进一步优化。结果 本文所用数据集共包含89例宫颈癌患者的腹盆腔CT（computed tomography）图像,并以中国科学技术大学附属第一医院多位放射医师提供的手工勾画结果作为评估的金标准。在实验部分,本文提出的分类器在6种危及器官（左右股骨、左右股骨头、膀胱和直肠）上的平均分类精度、查准率、召回率和F1-Score分别为98.36%、96.64%、94.1%和95.34%。基于上述分类性能,本文分割方法在测试集上的平均Dice系数为92.94%。结论 与已有的CNN分割模型相比,本文方法获得了最佳的分割性能,先分类再分割的策略能够有效地避免标注稀疏问题并减少假阳性分割结果。此外,本文方法与专业放射医师在分割结果上具有良好的一致性,有助于在临床中实现更准确、快速的危及器官分割。     

A549/DDP derived exosomes can affect cisplatin chemosensitivity via transporting CXCR4 to A549 cells

The resistance of cancer cells to the anti-cancer drugs is the most important reason that affecting the efficacy of the non-small cell lung cancer (NSCLC) chemotherapy; thus, to explore the underlying mechanism of drug resistance of NSCLC medications is urgently needed for improving the therapeutic efficacy of current anti-NSCLC chemotherapies. The aim of the present study is to explore the roles of exosomes in the chemosensitivity of A549 cells and the related mechanism. A549 cells and cisplatin resistant cell line A549/DDP derived exosomes were isolated, and the expressions of CXCR4 were compared. Then, after cisplatin treatment, A549 cells were treated with exosomes, and the proliferation, apoptosis, migration, and invasion of the cells were examined. Finally, the tumorigenic effect of A549/DDP derived exosomes were also evaluated by cisplatin treated xenograft tumor mice models in vivo. We found that A549/DDP derived exosomes increased the proliferation, migration, and invasion, and inhibited the apoptosis and cisplatin sensitivity of A549 cells. CXCR4 was also significantly increased in cells treated with A549/DDP derived exosomes. Furthermore, A549/DDP derived exosomes may also decrease the chemosensitivity of NSCLC cells to cisplatin in vivo. Our data suggested that A549/DDP derived exosomes can affect the chemosensitivity of A549 cells to cisplatin, possibly by transporting CXCR4 to A549 cells. Our data may provide novel evidence for the investigation of drug resistance of NSCLC.     

Using asynchronous AV communication tools to increase academic self-efficacy

Technology-enhanced learning environments (TELEs) deliver instructional content and provide an array of scaffolding features designed to support independent student learning. TELEs also support teacher efforts to guide student inquiry within these sometimes complex environments. Self-efficacy, defined by Bandura [Bandura, A. (1994). Self-efficacy. In V. S. Ramachaudran (Ed.), Encyclopedia of human behavior (Vol. 4, pp. 71–81). New York: Academic Press] as a person’s beliefs about his capabilities is also known to influence student academic performance in a learning environment. This paper discusses the potential importance of designing scaffolds in TELEs that intentionally promote academic self-efficacy. We advocate for designing asynchronous Audio/Visual tools into TELEs to promote student self-efficacy and ultimately performance.