The Nanomaterial Metabolite Corona Determined Using a Quantitative Metabolomics Approach: A Pilot Study

Nanomaterials (NMs) are promptly coated with biomolecules in biological systems leading to the formation of the so‐called corona. To date, research has predominantly focused on the protein corona and how it affects NM uptake, distribution, and bioactivity by conferring a biological identity to NMs enabling interactions with receptors to mediate cellular responses. Thus, protein corona studies are now integral to nanosafety assessment. However, a larger class of molecules, the metabolites, which are orders of magnitude smaller than proteins (<1000 Da) and regulate metabolic pathways, has been largely overlooked. This hampers the understanding of the bio–nano interface, development of computational predictions of corona formation, and investigations into uptake or toxicity at the cellular level, including identification of molecular initiating events triggering adverse outcome pathways. Here, a capillary electrophoresis–mass spectrometry based metabolomics approach reveals that pure polar ionogenic metabolite standards differentially adsorb to a range of 6 NMs (SiO₂, 3 TiO₂ with different surface chemistries, and naïve and carboxylated polystyrene NMs). The metabolite corona composition is quantitatively compared using protein‐free and complete plasma samples, revealing that proteins in samples significantly change the composition of the metabolite corona. This key finding provides the basis to include the metabolite corona in future nanosafety endeavors.     

Nano or Not Nano? A Structured Approach for Identifying Nanomaterials According to the European Commission’s Definition

Identifying nanomaterials (NMs) according to European Union legislation is challenging, as there is an enormous variety of materials, with different physico‐chemical properties. The NanoDefiner Framework and its Decision Support Flow Scheme (DSFS) allow choosing the optimal method to measure the particle size distribution by matching the material properties and the performance of the particular measurement techniques. The DSFS leads to a reliable and economic decision whether a material is an NM or not based on scientific criteria and respecting regulatory requirements. The DSFS starts beyond regulatory requirements by identifying non‐NMs by a proxy approach based on their volume‐specific surface area. In a second step, it identifies NMs. The DSFS is tested on real‐world materials and is implemented in an e‐tool. The DSFS is compared with a decision flowchart of the European Commission’s (EC) Joint Research Centre (JRC), which rigorously follows the explicit criteria of the EC NM definition with the focus on identifying NMs, and non‐NMs are identified by exclusion. The two approaches build on the same scientific basis and measurement methods, but start from opposite ends: the JRC Flowchart starts by identifying NMs, whereas the NanoDefiner Framework first identifies non‐NMs.     

高质量发展导向的文博文创设计治理体系研究

为满足国家治理现代化建设、解决文博文创产业实际问题、顺应博物馆学与设计学发展等多方面的需要,从设计学视角对治理研究理论进行了审视,搭建了数条有助于治理研究与设计学理论交流的通道,并将设计治理分为对设计活动的治理、通过设计活动来治理两种,整合了国内外设计治理的不同含义。通过对文化治理内核的分析,分解了文博文创设计治理的目标,再结合对博物馆高质量发展的国家任务和文博文创产业实际问题的深入剖析,进一步明确了文博文创的设计治理对象,通过对设计治理工具的补充优化,为文博文创设计治理的下一步工作提供了治理工具包的选择建议。明确了文博文创设计治理的内涵与外延,研究了面向高质量发展的文博文创产业设计治理体系,为该领域研究奠定了前期基础,对未来研究也具有启发价值。     

Owl meets beehive: how impact assessment and governance relate

This article analyses the complex relationship between impact assessments (IAs) of all types (such as comprehensive, regulatory, economic, social or environmental IAs) and their governance environment, using an analytical framework based on the concepts of governance styles and metagovernance. It is argued that each governance system builds on specific values, traditions and history and produces specific mixtures of hierarchical, network and market styles of governance (with or without an explicit metagovernance approach). Although governance can be considered as a non-normative perspective on polity and politics, the normative dimension of governance practice results in, for example, conflicting convictions about which type of knowledge or ‘evidence’ is valid for IA processes. This is particularly relevant because IAs have an important role in improving the knowledge base of governance. The concrete governance system in a specific country or other administrative entity influences the design and governance of IA systems positively or negatively, which leads to a variety of challenges. The conclusion is drawn that understanding the governance context and its dynamics can help improving IA governance.     

Corporate governance impact on banking risk

This study aims to determine the relationship between several factors of governance and the level of risk in 10 Tunisian banks during an analysis period of eight years. We propose an important empirical question and examine the internal mechanisms of governance aimed at reducing financial risks. This estimation is based on a model with a single equation that examines variables relative to governance and credit risk to determine their impact on banking financials. Results demonstrate that the internal mechanisms of governance present diverging effects on the financial risk of the Tunisian banks in our case study (i.e., credit risk). Moreover, making applications work by putting together a process and model for banking risk is important. This model can be applied in any bank, and the results can be used to make decisions in real time.     

15 Years of Small: Research Trends in Nanosafety

In the field of nano‐ and microscale science and technology, Small has become one of the worldwide leading journals since its initiation 15 years ago. Among all the topics covered in Small, “nanosafety” has received growing interest over the years, which accounts for a large proportion of the total publications of Small. Herein, inspired by its coming Special Issue “Rethinking Nanosafety,” a general bibliometric overview of the nanosafety studies that have been published in Small is presented. Using the data derived from the Web of Science Core Collection, the annual publication growth, most influential countries/institutions as well as the visualized collaborations between different countries and institutions based on CiteSpace software are presented. A special emphasis on the impact of the previous Special Issue from Small that is related to nanosafety research is given and the research trend from the most highly cited papers during last 15 years is analyzed. Lastly, future research directions are also proposed.     

Engineering Biomimetic Nanofiber Microspheres with Tailored Size,Predesigned Structure,and Desired Composition via Gas Bubble–Mediated Coaxial Electrospray

Minimally invasive therapies avoiding surgical complexities evoke great interest in developing injectable biomedical devices. Herein, a versatile approach is reported for engineering injectable and biomimetic nanofiber microspheres (NMs) with tunable sizes, predesigned structures, and desired compositions via gas bubble–mediated coaxial electrospraying. The sizes and structures of NMs are controlled by adjusting processing parameters including air flow rate, applied voltage, distance, and spinneret configuration in the coaxial setup. Importantly, unlike the self‐assembly method, this technique can be used to fabricate NMs from any material feasible for electrospinning or other nanofiber fabrication techniques. To demonstrate the versatility, open porous NMs are successfully fabricated that consist of various short nanofibers made of poly(ε‐caprolactone), poly(lactic‐co‐glycolic acid), gelatin, methacrylated gelatin, bioglass, and magneto‐responsive polymer composites. Open porous NMs support human neural progenitor cell growth in 3D with a larger number and more neurites than nonporous NMs. Additionally, highly open porous NMs show faster cell infiltration and host tissue integration than nonporous NMs after subcutaneous injection to rats. Such a novel class of NMs holds great potential for many biomedical applications such as tissue filling, cell and drug delivery, and minimally invasive tissue regeneration.     

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging‐guided surgery (IGS) as well as surgery‐assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS‐assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS‐assisted precision synergistic cancer therapy.     

肇庆市营商环境优化与标准化治理研究

作为政府治理的手段、科技创新的刚需和产业发展的标配,标准化在优化区域营商环境中的作用重大。本文以肇庆为例,从标准化治理逻辑出发,探讨标准化治理与营商环境优化间的内在逻辑,以此梳理肇庆市营商环境优化中标准化治理的显著成效。并以新发展理念为脉络,提出肇庆营商环境优化中标准化治理的发展路径。     

Pathways of nanotoxicity: Modes of detection,impact, and challenges

Nanotoxicology has become the subject of intense research for more than two decades. Thousands of articles have been published but the space in understanding the nanotoxicity mechanism and the assessment is still unclear. Recent researches clearly show potential benefits of nanomaterials (NMs) in diagnostics and treatment, targeted drug delivery, and tissue engineering owing to their excellent physicochemical properties. However, these NMs display hazardous health effect then to the greater part of the materials because of small size, large surface area-to-volume ratio, quantum size effects, and environmental factors. Nowadays, a large number of NMs are used in industrial products including several medical applications, consumer, and healthcare products. However, they came into the environment without any safety test. The measurement of toxicity level has become important because of increasing toxic effects on living organisms. New realistic mechanism-based strategies are still needed to determine the toxic effects of NMs. For the assessment of NMs toxicity, reliable and standardized procedures are necessary. This review article provides systematic studies on toxicity of NMs involving manufacturing, environmental factors, eco-toxic and genotoxic effects, some parameters which have been ignored of NMs versus their biological counterparts, cell heterogeneity, and their current challenges and future perspectives.     

A framework to integrate software behavior into dynamic probabilistic risk assessment

Software plays an increasingly important role in modern safety-critical systems. Although, research has been done to integrate software into the classical probabilistic risk assessment (PRA) framework, current PRA practice overwhelmingly neglects the contribution of software to system risk. Dynamic probabilistic risk assessment (DPRA) is considered to be the next generation of PRA techniques. DPRA is a set of methods and techniques in which simulation models that represent the behavior of the elements of a system are exercised in order to identify risks and vulnerabilities of the system. The fact remains, however, that modeling software for use in the DPRA framework is also quite complex and very little has been done to address the question directly and comprehensively. This paper develops a methodology to integrate software contributions in the DPRA environment. The framework includes a software representation, and an approach to incorporate the software representation into the DPRA environment SimPRA. The software representation is based on multi-level objects and the paper also proposes a framework to simulate the multi-level objects in the simulation-based DPRA environment. This is a new methodology to address the state explosion problem in the DPRA environment. This study is the first systematic effort to integrate software risk contributions into DPRA environments.     

Rethinking the tendering frameworks of construction contractors in the context of a soft systems methodology approach

Limited research has been conducted on the internal tendering procedures (ITP) of construction contractors because of the commercially sensitive and confidential nature of the subject matter. This limitation explains the reluctance of contractors to undergo interviews. Existing research (outside bid/no-bid and margin decision factor identification and subsequent decision modeling development) only begins to provide insights into key tendering stages, particularly around risk assessments and corporate review processes. Early research suggested one to three review stages. However, when considering the whole work procurement process from prospect identification to contract execution, five to seven series of reviews can be arguably applied by some contractors, wherein some reviews stepped through several layers of internal senior management. Tendering processes were presented as flowchart models that traditionally follow “hard” system (rectangular shapes and straight line arrows) steps, which suggest that a precise process also leads to precise results. However, given that contractors do not win every tender they submit, the process is less precise than that suggested in rigidly structured flowcharts. Twenty-five detailed semi-structured interviews were held with purposely selected high-profile publicly and privately owned construction companies in Australia with significantly varied turnovers. Analyses show that contractors are concerned about the negative effects of increasing corporate governance demands, with many stating that people involved are the most critical element to tendering success. A new way of presenting the ITP of contractors is assessed using a soft systems methodology (SSM) approach. SSM offers an alternative way of considering human interaction challenges within the ITP of contractors, which needs to be tested with the industry. The format graphics of SSM guidelines are presented as a way of offering contractors a different approach, which may assist individuals who are looking to re-structure their tendering activities in a more humanistic and less rigid procedural approach.     

When Would Immunologists Consider a Nanomaterial to be Safe? Recommendations for Planning Studies on Nanosafety

The immune system is professional in recognizing and responding to non‐self, including nanomaterials. Immune responses by professional and nonprofessional immune cells are thus nearly inevitable upon exposure of cells and organisms to such materials. The state of research into taking the immune system into account in nanosafety studies is reviewed and three aspects in which further improvements are desirable are identified: 1) Due to technical limitations, more stringent testing for endotoxin contamination should be made. 2) Since under overdose conditions immunity shows unphysiological responses, all doses used should be justified by being equivalent to tissue‐delivered doses. 3) When markers of acute inflammation or cell stress are observed, functional assays are necessary to distinguish between homeostatic fluctuation and genuine defensive or tolerogenic responses. Since immune activation can also indicate that the immune system considers a stimulus to be harmless and induces tolerance, activation markers by themselves do not necessarily imply a danger to the body. Guidelines such as these are necessary to approach the point where specific nanomaterials are classified as safe based on reliable testing strategies.     

Is the Feminist Ethics of Care framework a useful lens for GM crop risk appraisal in the global south?

The risk assessment of genetically modified (GM) crops is assumed to be a benign regulatory tool due to its perceived objectivity and freedom from the morals and values that pervade society. Yet, against the current backdrop of ecological, social and political volatility, issues that cannot be resolved using the existing framework in South Africa are consistently emerging. This paper calls for a reformation of regulatory procedures by exploring the potential of Feminist Care Ethics to illuminate an alternative approach to the assessment of GM crops. While fresh thinking is welcome into the entangled field of biotechnology governance, there remains little understanding of how to accommodate such approaches in the context of the Global South. Twenty three interviews with participants from governmental, non-governmental and academic bodies were carried out in order to explore the potential of a Feminist Ethic of Care as an alternative framework. By examining the current appraisal procedures and tracing their evolution, problems with the current system were illuminated. To assess the suitability of the care ethic framework and ensure reflexivity, a hybrid approach to thematic analysis was applied. Using themes derived from feminist literature such as relationships, context, power, narrative and emotion, new ‘ways of seeing’ risk emerged and illuminated salient issues that are habitually ignored by the current science-based risk approach to assessment. The current approach was found to be flawed, stemming from a neoliberal, productivist perception of our socio-ecological environment. Feminist perspectives instead ask us to broaden the framing of risk, to consider different knowledges, to re-imagine ourselves as social, rather than economic beings, to tap into the capacity of socio-ecological relations and to recognize and dismantle power structures. The research concludes that although the care ethics themes offer a new approach to GM crop regulation, meaningful change will not arise from simply adding these elements to the current system. Rather, a call must be made for a re-imagining, and redesigning, both institutionally and politically-economically.     

Tuning the Photoinduced Electron Transfer in a Zr‐MOF: Toward Solid‐State Fluorescent Molecular Switch and Turn‐On Sensor

The immobilization of fluorescent photoinduced electron transfer (PET) switches/sensors into solid state, which usually cannot maintain their identical properties in solution, has remained a big challenge. Herein, a water‐stable anthracene and maleimide appended zirconium‐based‐metal–organic framework (Zr‐MOF; UiO‐68‐An/Ma) is reported. Unlike the regular intramolecular “fluorophore–spacer–receptor” format, the separated immobilization of fluorescent (anthracene) and acceptor (maleimide) groups into the framework of a multivariate MOF can also favor a pseudo‐intramolecular fluorescent PET process, resulting in UiO‐68‐An/Ma with very weak fluorescence. Interestingly, after Diels–Alder reaction or thiol‐ene reaction of maleimide groups, the pseudo‐intramolecular fluorescent PET process in UiO‐68‐An/Ma fails and the solid‐state fluorescence of the crystals is recovered. In addition, UiO‐68‐An/Ma shows an interesting application as solid‐state fluorescent turn‐on sensor for biothiols, with the naked eye response at a low concentration of 50 µmol L^?1 within 5 min. This study represents a general strategy to enable the efficient tuning of fluorescent PET switches/sensors in solid state, and considering the fluorescence of the PET‐based MOFs can be restored after addition of analyte/target species, this research will definitely inspire to construct stimuli‐responsive fluorescent MOFs for interesting applications (e.g., logic gate) in future.     

Role of Artificial Intelligence and Machine Learning in Nanosafety

Robotics and automation provide potentially paradigm shifting improvements in the way materials are synthesized and characterized, generating large, complex data sets that are ideal for modeling and analysis by modern machine learning (ML) methods. Nanomaterials have not yet fully captured the benefits of automation, so lag behind in the application of ML methods of data analysis. Here, some key developments in, and roadblocks to the application of ML methods are reviewed to model and predict potentially adverse biological and environmental effects of nanomaterials. This work focuses on the diverse ways a range of ML algorithms are applied to understand and predict nanomaterials properties, provides examples of the application of traditional ML and deep learning methods to nanosafety, and provides context and future perspectives on developments that are likely to occur, or need to occur in the near future that allow artificial intelligence to make a deeper contribution to nanosafety.     

Large-scale App privacy governance

Recently, the problem of mobile applications (Apps) leaking users’ private information has aroused wide concern. As the number of Apps continuously increases, effective large-scale App governance is a major challenge. Currently, the government mainly filters out Apps with potential privacy problems manually. Such approach is inefficient with limited searching scope. In this regard, we propose a quantitative method to filter out problematic Apps on a large scale. We introduce Privacy Level (P-Level) to measure an App’s probability of leaking privacy. P-Level is calculated on the basis of Permission-based Privacy Value (P-Privacy) and Usage-based Privacy Value (U-Privacy). The former considers App permission setting, whereas the latter considers App usage. We first illustrate the privacy value model and computation results of both values based on real-world dataset. Subsequently, we introduce the P-Level computing model. We also define the P-Level computed on our dataset as the PL standard. We analyze the distribution of average usage and number of Apps under the levels given in the PL standard, which may provoke insights into the large-scale App governance. Through P-Privacy, U-Privacy, and P-Level, potentially problematic Apps can be filtered out efficiently, thereby making up for the shortcoming of being manual.     

Inhibiting Solid Tumor Growth In Vivo by Non‐Tumor‐Penetrating Nanomedicine

Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor‐penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual‐functional, nontumor‐penetrating NM is demonstrated. The intended NM contains 5,6‐dimethylxanthenone‐4‐acetic acid (DMXAA), a vascular‐disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual‐functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.