Microenvironments to regulate cellular behavior for neural development and regeneration

Strategies for regeneration after injury or during aging require the development of biomaterials able to reconstruct the essential components and properties of natural extracellular microenvironment. A particular feature in neural regeneration is the oriented disposition of neurons within nerves and cortex. In this thesis, through the spatiotemporal control of the availability of adhesive ligands at the surface of a biomaterial, these biomaterials allow directing the migration of neuron. This Thesis is structured in four parts. The first part presents microcontact printed patterns with adhesive compositions and geometries to allow directional migration and, uniquely, in vitro reconstruction of the somal translocation events occurring during cortical layering. In part 2 in situ directed neurites extension in defined directions is demonstrated using biomaterials functionalized with photo-activatable peptidomimetics of the laminin. In part 3 spatiotemporal and reversible regulations of actin dynamics in living cells is demonstrated using light-dosed delivery of Cytochalasin D. In the last part, the first demonstration of a light-regulated adhesive interaction between mammalian cells and a bacterial biointerface is provided.Strategien zur Regeneration nach Verletzungen oder während des Alterns benötigen die Entwicklung von Biomaterialien, die essentielle Komponenten und Eigenschaften der nativen extrazellulären Mikroumgebung rekonstruieren können. Eine besondere Eigenschaft in der Regeneration von Nervengewebe ist die elongierte Morphologie und gerichtete Disposition von Neuronen in Nerven und Kortex. Die räumlich-zeitliche Kontrolle der Verfügbarkeit von Zell-adhesiven Liganden auf der Oberfläche des Biomaterials, wie in dieser These beschrieben,erlaubt es hierbei die Migration von Neuronen steuern. Diese These ist in vier Abschnitte gegliedert. Der erste Teil präsentiert Mikrokontakt gedruckte Muster mit optimisierten, adhesiven Komponenten und Geometrien, um eine gerichtete Migration und in vitro erstmalig die Rekonstruktion der somalen Translokation zu gewährleisten, welche während der embryonalen Entwicklung des zerebralen Kortex stattfindet. In Teil 2 wird in situ der gerichtete Neuritenauswuchs in definierter Richtung gezeigt. Hierbei werden Biomaterialien verwendet, die mit Photo-aktivierbaren Peptidomimetika des Matrixproteins Laminin funktionalisiert sind. Im Teil 3 wird die räumlich-zeitliche und reversible Regulation der Dynamik des Actinzytoskellettes unter Zugabe von Licht-dosiertem Cytochalasin D gezeigt. Im letzten Teil, wird erstmalig die Licht-regulierte Interaktion zwischen Säugetierzellen und einer bakteriellen Biogrenzfläche demonstriert

Microenvironments Designed to Support Growth and Function of Neuronal Cells

Strategies for neural tissue repair heavily depend on our ability to temporally reconstruct the natural cellular microenvironment of neural cells. Biomaterials play a fundamental role in this context, as they provide the mechanical support for cells to attach and migrate to the injury site, as well as fundamental signals for differentiation. This review describes how different cellular processes (attachment, proliferation, and (directional) migration and differentiation) have been supported by different material parameters, in vitro and in vivo. Although incipient guidelines for biomaterial design become visible, literature in the field remains rather phenomenological. As in other fields of tissue regeneration, progress will depend on more systematic studies on cell-materials response, better understanding on how cells behave and understand signals in their natural milieu from neurobiology studies, and the translation of this knowledge into engineered microenvironments for clinical use

Numerical Schemes for Stochastic Differential Equations with Variable and Distributed Delays: The Interpolation Approach

A kind of the Euler-Maruyama schemes in discrete forms for stochastic differential equations with variable and distributed delays is proposed. The linear interpolation method is applied to deal with the values of the solutions at the delayed instants. The assumptions of this paper on the coefficients and related parameters are somehow weaker than those imposed by the related past literature. The error estimations for the Euler-Maruyama schemes are given, which are proved to be the same as those for the fundamental EulerMaruyama schemes

Mechanically reinforced catechol-containing hydrogels with improved tissue gluing performance

In situ forming hydrogels with catechol groups as tissue reactive functionalities are interesting bioinspired materials for tissue adhesion. Poly(ethylene glycol) (PEG)–catechol tissue glues have been intensively investigated for this purpose. Different cross-linking mechanisms (oxidative or metal complexation) and cross-linking conditions (pH, oxidant concentration, etc.) have been studied in order to optimize the curing kinetics and final cross-linking degree of the system. However, reported systems still show limited mechanical stability, as expected from a PEG network, and this fact limits their potential application to load bearing tissues. Here, we describe mechanically reinforced PEG–catechol adhesives showing excellent and tunable cohesive properties and adhesive performance to tissue in the presence of blood. We used collagen/PEG mixtures, eventually filled with hydroxyapatite nanoparticles. The composite hydrogels show far better mechanical performance than the individual components. It is noteworthy that the adhesion strength measured on skin covered with blood was >40 kPa, largely surpassing (>6 fold) the performance of cyanoacrylate, fibrin, and PEG–catechol systems. Moreover, the mechanical and interfacial properties could be easily tuned by slight changes in the composition of the glue to adapt them to the particular properties of the tissue. The reported adhesive compositions can tune and improve cohesive and adhesive properties of PEG–catechol-based tissue glues for load-bearing surgery applications

The Chinese Translation Study of the Cognitive Reserve Index Questionnaire

PurposeThe purpose of this study was to perform the translation and adaption of the Cognitive Reserve Index questionnaire into Chinese and assess the reliability of the Chinese version.Materials and MethodsThe Chinese version of the Cognitive Reserve Index questionnaire was created from a standard forward-backward translation. A total of 371 volunteers, aged between 20 and 89 years, participated in this survey. Participants were divided into three age-groups (Young, Middle-aged, and Elderly), and subgroup differences were examined by independent samples t-tests, ANOVA analysis as well as post-hoc analysis. Pearson correlation analysis was applied to test the association between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime). The internal consistency and test-retest reliability of the Cognitive Reserve Index questionnaire were assessed. The test-retest reliability was measured among 40 participants with a 2-week interval using intraclass correlation coefficient.ResultsStrong correlations were observed between the total scores and each subscore (CRI-Education, CRI-WorkingActivity, and CRI-LeisureTime: r = 0.65, 0.79, and 0.70, respectively). In contrast, it was found low to moderate correlations among three subscores. The internal consistency was acceptable (Cronbach's alpha coefficient = 0.68). The intraclass correlation coefficient for total scores of the Chinese version of the Cognitive Reserve Index questionnaire was 0.87 (95% CI 0.74–0.93).ConclusionThe Chinese version of the Cognitive Reserve Index questionnaire was a potentially reliable and practical tool for evaluating cognitive reserve accumulated through a person's life span

Integrated glycomic analysis of ovarian cancer side population cells

Additional file 2. The category of representative lectins for glycan profiling

The association between ambient temperature and antimicrobial resistance of Klebsiella pneumoniae in China: a difference-in-differences analysis

IntroductionAntimicrobial resistance (AMR) of Klebsiella pneumoniae (K. pneumoniae) poses a significant global public health threat and is responsible for a high prevalence of infections and mortality. However, knowledge about how ambient temperature influences the AMR of K. pneumoniae is limited in the context of global warming.MethodsAMR data of 31 Chinese provinces was collected from the China Antimicrobial Resistance Surveillance System (CARSS) between 2014 and 2020. Socioeconomic and meteorological data were collected from the China Statistical Yearbook during the same period. A modified difference-in-differences (DID) approach was applied to estimate the association between ambient temperature and third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and carbapenem-resistant K. pneumoniae (CRKP). Furthermore, moderating effects of socioeconomic factors were also evaluated.ResultsEvery 1°C increase in annual average temperature was associated with a 4.7% (relative risk (RR):1.047, 95% confidence intervals (CI): 1.031–1.082) increase in the detection rate of 3GCRKP, and a 10.7% (RR:1.107, 95% CI: 1.011–1.211) increase in the detection rate of CRKP. The relationships between ambient temperature and 3GCRKP and CRKP were found to be moderated by socioeconomic status (GDP per capita, income per capita, and consumption per capita; the interaction p-values <0.05), where higher economic status was found to strengthen the effects of temperature on the detection rate of 3GCRKP and weaken the effects on the detection rate of CRKP.DiscussionAmbient temperature was found to be positively associated with AMR of K. pneumoniae, and this association was moderated by socioeconomic status. Policymakers should consider the impact of global warming and high temperatures on the spread of 3GCRKP and CRKP when developing strategies for the containment of AMR

Numerical Schemes for Stochastic Differential Equations with Variable and Distributed Delays: The Interpolation Approach

A kind of the Euler-Maruyama schemes in discrete forms for stochastic differential equations with variable and distributed delays is proposed. The linear interpolation method is applied to deal with the values of the solutions at the delayed instants. The assumptions of this paper on the coefficients and related parameters are somehow weaker than those imposed by the related past literature. The error estimations for the Euler-Maruyama schemes are given, which are proved to be the same as those for the fundamental Euler-Maruyama schemes