Carbon Nanotubes and Graphene Materials as Xenobiotics in Living Systems: Is There a Consensus on Their Safety?

Carbon nanotubes and graphene are two types of nanomaterials that have unique properties and potential applications in various fields, including biomedicine, energy storage, and gas sensing. However, there is still a debate about the safety of these materials, and there is yet to be a complete consensus on their potential risks to human health and the environment. While some studies have provided recommendations for occupational exposure limits, more research is needed to fully understand the potential risks of these materials to human health and the environment. In this review, we will try to summarize the advantages and disadvantages of using carbon nanotubes and graphene as well as composites containing them in the context of their biocompatibility and toxicity to living systems. In addition, we overview current policy guidelines and technical regulations regarding the safety of carbon-based nanomaterials.

Vanillin: A Promising Biosourced Building Block for the Preparation of Various Heterocycles.

The preparation of heterocyclic compounds often involves the use of petroleum-based or non-renewable sources. Considering the actual societal and environmental awareness towards sustainable chemistry, new and green sources of organic carbon are sought. In this regard, vanillin is a molecular building block that can be obtained from the depolymerization of lignin. Due to its different functional groups (hydroxyl, aldehyde, and methoxy) vanillin can undergo a variety of reactions leading to various heterocycles such as pyrimidines, quinoxalines, imidazoles or thiazoles to name a few. This mini-review will focus on the preparation of accessible heterocycles building blocks from the vanillin moiety in regard to the medicinal, pharmaceutical, and material fields.

Physical Activity Interventions in Rehabilitation Programs for Outpatients With Mild Traumatic Brain Injury.

Introduction: There is limited scientific evidence about the optimal content and parameters of physical activity (PA) interventions for rehabilitation outpatients with persisting symptoms of a mild traumatic brain injury (mTBI). Clinicians have thus had to develop services based on their expertise, feasibility and patient needs. Objectives: This study aimed to document PA interventions delivered in specialized programs of a Canadian province offering outpatient rehabilitation services for individuals with persisting symptoms of mTBI to inform clinical intervention development and future research. Materials and methods: Cross-sectional study using an online survey containing 32 multiple choice and short open-ended questions to be answered by program administrators, with their clinical team's input. Content analysis and descriptive statistics were used. Results: Data from 94% of rehabilitation sites (n = 17) revealed that PA interventions are delivered to children (n = 4), adults (n = 15) and older adults (n = 5) with mTBI symptoms lasting ≥1 month to ≥1 year post injury. PA interventions aim to increase participation (n = 14), improve body functions (n = 9), manage persisting mTBI symptoms (n = 5) and improve self-management skills (n = 5) and knowledge (n = 4). Interventions include individual (n = 15) or group-based (n = 12) format, home-programs (n = 7), and teaching/education (n = 6). Most PA interventions include aerobic and resistance exercises. PA dosage parameters vary greatly. Conclusion: Clinical experts use multimodal interventions for rehabilitation program users that target improvement in body functions, participation and symptoms. The results can inform the development, enhancement and evaluation of PA interventions. Studies evaluating the effectiveness of these interventions for this clientele are warranted.

Biosourced Vanillin-Based Building Blocks for Organic Electronic Materials.

Forest biomass is viewed as a significant source of organic carbon and thus the ideal replacement of petroleum products. From the resources derived from biomass, lignocellulose is the most abundant biobased material on earth. One of the aromatic added value compounds obtained from the depolymerization of lignin is vanillin. Here, we report the preparation of new compounds having benzothiophene, indole, isatin, benzofuroxan, benzofurazan, benzothiadiazole, and phthalimide heteroaromatic ring structures. More precisely, our results show that vanillin can be used as a biosourced starting material for the preparation of a variety of aromatic dibrominated monomers. X-ray crystallography on single crystals was also performed to obtain meaningful information on their solid-state ordering. This work opens the way to new, sustainable, biosourced aromatic materials (small molecules or polymers) for organic electronics.

CD34 Differentially Regulates Contractile and Noncontractile Elements of Airway Reactivity.

Airway hyperresponsiveness (AHR), a major hallmark of asthma, results from alterations of contractile and noncontractile elements of airway reactivity. CD34 is a sialomucin that is expressed on various cells involved in asthma, such as eosinophils and airway smooth muscle precursors, highlighting its potential influence in AHR. To study the role of CD34 in regulating the contractile and noncontractile elements of AHR, AHR was induced by chronic exposure to house dust mite (HDM) antigen. To assess the role of CD34 on the contractile elements of AHR, airway reactivity and airway smooth muscle contractility in response to methacholine were measured. To assess CD34's role in regulating the noncontractile elements of AHR, a chimeric mouse model was used to determine the impact of CD34 expression on inflammatory versus microenvironmental cells in AHR development. Extracellular matrix production, mucus production, and mast cell degranulation were also measured. Whereas wild-type mice developed AHR in response to HDM, a loss of airway reactivity was observed in Cd34-/- mice 24 hours after the last exposure to HDM compared with naive controls. This was reversed when airway reactivity was measured 1 week after the last HDM exposure. Additionally, mast cell degranulation and mucus production were altered in the absence of CD34 expression. Importantly, simultaneous expression of CD34 on cells originating from the hematopoietic compartment and the microenvironment was needed for expression of this phenotype. These results provide evidence that CD34 is required for AHR and airway reactivity maintenance in the early days after an inflammatory episode in asthma.

A Phosphorylatable Sphingosine Analog Induces Airway Smooth Muscle Cytostasis and Reverses Airway Hyperresponsiveness in Experimental Asthma.

In asthma, excessive bronchial narrowing associated with thickening of the airway smooth muscle (ASM) causes respiratory distress. Numerous pharmacological agents prevent experimental airway hyperresponsiveness (AHR) when delivered prophylactically. However, most fail to resolve this feature after disease is instated. Although sphingosine analogs are primarily perceived as immune modulators with the ability to prevent experimental asthma, they also influence processes associated with tissue atrophy, supporting the hypothesis that they could interfere with mechanisms sustaining pre-established AHR. We thus assessed the ability of a sphingosine analog (AAL-R) to reverse AHR in a chronic model of asthma. We dissected the pharmacological mechanism of this class of agents using the non-phosphorylatable chiral isomer AAL-S and the pre-phosphorylated form of AAL-R (AFD-R) in vivo and in human ASM cells. We found that a therapeutic course of AAL-R reversed experimental AHR in the methacholine challenge test, which was not replicated by dexamethasone or the non-phosphorylatable isomer AAL-S. AAL-R efficiently interfered with ASM cell proliferation in vitro, supporting the concept that immunomodulation is not necessary to interfere with cellular mechanisms sustaining AHR. Moreover, the sphingosine-1-phosphate lyase inhibitor SM4 and the sphingosine-1-phosphate receptor antagonist VPC23019 failed to inhibit proliferation, indicating that intracellular accumulation of sphingosine-1-phosphate or interference with cell surface S1P1/S1P3 activation, are not sufficient to induce cytostasis. Potent AAL-R-induced cytostasis specifically related to its ability to induce intracellular AFD-R accumulation. Thus, a sphingosine analog that possesses the ability to be phosphorylated in situ interferes with cellular mechanisms that beget AHR.

FTY720 promotes pulmonary fibrosis when administered during the remodelling phase following a bleomycin-induced lung injury.

Fibrosis complicates numerous pathologies including interstitial lung diseases. Sphingosine analogs such as FTY720 can alleviate lung injury-induced fibrosis in murine models. Contradictorily, FTY720 also promotes in vitro processes normally leading to fibrosis and high doses in vivo foster lung fibrosis by enhancing vascular leakage into the lung. The goal of this study was to determine the effect of low doses of FTY720 on lung fibrosis triggered by an acute injury in mice. We first defined the time-boundaries delimiting the inflammatory and remodelling phases of an injury elicited by bleomycin based on neutrophil counts, total lung capacity and lung stiffness. Thereafter, FTY720 (0.1 mg/kg) was delivered during either the inflammatory or the remodelling phases of bleomycin-induced injury. While FTY720 decreased fibrosis by 60% and lung stiffness by 28% when administered during the inflammatory phase, it increased fibrosis (2.1-fold) and lung stiffness (1.7-fold) when administered during the remodelling phase. FTY720-induced worsening of fibrosis was associated with an increased expression of connective tissue growth factor, but not with vascular leakage into the lung. Thus, the timing of FTY720 delivery following a bleomycin-induced lung injury determines pro-vs anti-fibrotic outcomes.

Parylene-coated ionic liquid-carbon nanotube actuators for user-safe haptic devices.

Simple fabrication, high power-to-weight and power-to-volume ratios, and the ability to operate in open air at low voltage make the ionic electroactive polymer actuators highly attractive for haptic applications. Whenever a direct tactile stimulation of the skin is involved, electrical and chemical insulation as well as a long-term stability of the actuator are required. Because of its inherent physicochemical properties such as high dielectric strength, resistance to solvents, and biological inactivity, Parylene C meets the requirements for making biocompatible actuators. We have studied the displacement and the generated force of Parylene-coated carbon nanotube actuators as well as the encapsulation quality. A 2 µm coating creates an effective electrical insulation of the actuators without altering the blocking force at frequencies from 50 mHz to 1 Hz. Moreover, the generated strain is preserved at higher frequencies (from 0.5 to 5 Hz). We employed a simple mechanical model to explain the relation between the key parameters-flexural stiffness, displacement, and force-for uncoated and coated actuators. In addition, we demonstrated that our Parylene-coated actuators are not damaged by rinsing in liquid media such as 2-propanol or water. In conclusion, our results indicate that Parylene C encapsulated actuators are safe to touch and can be used in contact with human skin and in biomedical applications in direct contact with tissues and physiological fluids.

Treatment with a sphingosine analog after the inception of house dust mite-induced airway inflammation alleviates key features of experimental asthma.

BACKGROUND: In vivo phosphorylation of sphingosine analogs with their ensuing binding and activation of their cell-surface sphingosine-1-phosphate receptors is regarded as the main immunomodulatory mechanism of this new class of drugs. Prophylactic treatment with sphingosine analogs interferes with experimental asthma by impeding the migration of dendritic cells to draining lymph nodes. However, whether these drugs can also alleviate allergic airway inflammation after its onset remains to be determined. Herein, we investigated to which extent and by which mechanisms the sphingosine analog AAL-R interferes with key features of asthma in a murine model during ongoing allergic inflammation induced by Dermatophagoides pteronyssinus. METHODS: BALB/c mice were exposed to either D. pteronyssinus or saline, intranasally, once-daily for 10 consecutive days. Mice were treated intratracheally with either AAL-R, its pre-phosphorylated form AFD-R, or the vehicle before every allergen challenge over the last four days, i.e. after the onset of allergic airway inflammation. On day 11, airway responsiveness to methacholine was measured; inflammatory cells and cytokines were quantified in the airways; and the numbers and/or viability of T cells, B cells and dendritic cells were assessed in the lungs and draining lymph nodes. RESULTS: AAL-R decreased airway hyperresponsiveness induced by D. pteronyssinus by nearly 70%. This was associated with a strong reduction of IL-5 and IL-13 levels in the airways and with a decreased eosinophilic response. Notably, the lung CD4(+) T cells were almost entirely eliminated by AAL-R, which concurred with enhanced apoptosis/necrosis in that cell population. This inhibition occurred in the absence of dendritic cell number modulation in draining lymph nodes. On the other hand, the pre-phosphorylated form AFD-R, which preferentially acts on cell-surface sphingosine-1-phosphate receptors, was relatively impotent at enhancing cell death, which led to a less efficient control of T cell and eosinophil responses in the lungs. CONCLUSION: Airway delivery of the non-phosphorylated sphingosine analog, but not its pre-phosphorylated counterpart, is highly efficient at controlling the local T cell response after the onset of allergic airway inflammation. The mechanism appears to involve local induction of lymphocyte apoptosis/necrosis, while mildly affecting dendritic cell and T cell accumulation in draining lymph nodes.

The gain of smooth muscle's contractile capacity induced by tone on in vivo airway responsiveness in mice.

Airway hyperresponsiveness to a spasmogenic challenge such as methacholine, and an increased baseline tone measured by the reversibility of airway obstruction with a bronchodilator, are two common features of asthma. However, whether the increased tone influences the degree of airway responsiveness to a spasmogen is unclear. Herein, we hypothesized that increased tone augments airway responsiveness in vivo by increasing the contractile capacity of airway smooth muscle (ASM). Anesthetized, tracheotomized, paralyzed, and mechanically ventilated mice were either exposed (experimental group) or not (control group) to tone for 20 min, which was elicited by nebulizing serial small doses of methacholine. Respiratory system resistance was monitored during this period and the peak response to a large cumulative dose of methacholine was then measured at the end of 20 min to assess and compare the level of airway responsiveness between groups. To confirm direct ASM involvement, the contractile capacity of excised murine tracheas was measured with and without preexposure to tone elicited by either methacholine or a thromboxane A2 mimetic (U46619). Distinct spasmogens were tested because the spasmogens liable for increased tone in asthma are likely to differ. The results indicate that preexposure to tone increases airway responsiveness in vivo by 126 ± 37% and increases the contractile capacity of excised tracheas ex vivo by 23 ± 4% for methacholine and 160 ± 63% for U46619. We conclude that an increased tone, regardless of whether it is elicited by a muscarinic agonist or a thromboxane A2 mimetic, may contribute to airway hyperresponsiveness by increasing the contractile capacity of ASM.

Synthesis of new pyridazine-based monomers and related polymers for photovoltaic applications.

New aromatic compounds with a pyridazine core have been synthesized. Four electron-withdrawing monomers have been easily prepared from simple condensation reactions and ring closure procedures. Optimized HOMO, LUMO, and bandgap energy levels have been obtained. The resulting conjugated polymers have been tested in organic solar cells. First studies have revealed power conversion efficiencies up to 0.5% for an active area of 1.0 cm(2) .

Toward a rational design of poly(2,7-carbazole) derivatives for solar cells.

On the basis of theoretical models and calculations, several alternating polymeric structures have been investigated to develop optimized poly(2,7-carbazole) derivatives for solar cell applications. Selected low band gap alternating copolymers have been obtained via a Suzuki coupling reaction. A good correlation between DFT theoretical calculations performed on model compounds and the experimental HOMO, LUMO, and band gap energies of the corresponding polymers has been obtained. This study reveals that the alternating copolymer HOMO energy level is mainly fixed by the carbazole moiety, whereas the LUMO energy level is mainly related to the nature of the electron-withdrawing comonomer. However, solar cell performances are not solely driven by the energy levels of the materials. Clearly, the molecular weight and the overall organization of the polymers are other important key parameters to consider when developing new polymers for solar cells. Preliminary measurements have revealed hole mobilities of about 1 x 10(-3) cm2 x V(-1) x s(-1) and a power conversion efficiency (PCE) up to 3.6%. Further improvements are anticipated through a rational design of new symmetric low band gap poly(2,7-carbazole) derivatives.

Reconstruction of real tomographic data using algebraic methods.

We propose an algebraic image reconstruction method that can cope with the size and features of datasets produced by actual scanners, such as angular flying focal spot and detector offset. Image reconstruction is performed by minimizing a penalized least squares objective function by means of a preconditioned conjugate gradient (PCG) algorithm. Efficient implementation of the matrix-vector products that represent projection and backprojection operations is crucial to reconstruction speed, as such operations are performed at least once per iteration. For this purpose, we developed an efficient storage scheme for the projection matrix that allowed fast matrix-vector products. These features, along with an appropriate choice of the preconditioning matrix, yielded a numerically efficient method which produces results with better quality than those provided by usual filtered backprojection techniques.