Human dermal fibroblast activation under pulsed electrical stimulation via conductive fabrics : signalling pathways and potential benefit for wound healing

Lors de la cicatrisation, plusieurs types cellulaires dont les kératinocytes et les fibroblastes ainsi que plusieurs facteurs de croissance jouent d’importants rôles. La cicatrisation cutanée peut aussi être activée par des facteurs exogènes, dont la stimulation électrique (SE). La SE peut moduler les fonctions fibroblastiques durant la cicatrisation. Le fibroblaste contribue de façon active à la cicatrisation en sécrétant différentes protéines (collagène, fibronectine, élastine) pour favoriser le comblement tissulaire. Les fibroblastes adoptent aussi un phénotype contractile en exprimant l’α-actine contribuant à la fermeture de la plaie. Notre hypothèse est que certaines de ces fonctions fibroblastiques pourraient être modulées par une stimulation électrique. Pour vérifier cette hypothèse nous avons utilisé une membrane biocompatible et conductrice à base de polyethylene terephthalate (PET) recouvert de polypyrrole (PPy). Les fibroblastes dermiques humains ont été cultivés sur ces membranes conducteurs, puis exposés ou non à un courant pulsé (PES) selon deux régimes : soit 10s PES suivi de 1200s de repos, ou 300s PES suivi de 600s de repos, durant 24 h. Deux intensités électriques ont été étudiées, 50 et 100 mV/mm. Nos travaux démontrent que la SE favorise l’adhésion, la prolifération et la migration des fibroblastes dermiques. Ces activités cellulaires sont consolidées par une sécrétion importante de FGF2 et d’α-SMA. Il est important de noter que l’effet de la SE favorise le changement phénotypique des fibroblastes en myo-fibroblastes grâce à la voie des Smad et de TGFβ/ERK. Nous avons aussi démontré que l’effet de la SE est maintenue à long terme et est transférable de la cellule mère vers les cellules filles. En effet après sous-culture les cellules expriment toujours de façon importante l’α-SMA. En conclusion, nous avons démontré que la stimulation électrique pulsée module positivement les fonctions cicatricielles des fibroblastes humains. Ces travaux démontrent pour la première fois les voies de signalisation (Smad et TGFβ/ERK) sollicitées par la SE pour activer les fibroblastes lors de la cicatrisation. Ces travaux suggèrent l’utilisation de la SE pour favoriser la guérison/cicatrisation des plaies.During skin wound healing, cutaneous cells particularly fibroblasts and keratinocytes as well as several growth factors play important roles. Wound healing can be activated by exogenous factors, including electrical stimulation (ES). ES can also modulate fibroblast functions. Fibroblasts contribute to healing by secreting structural proteins (collagen, fibronectin, elastin) to repair the wound area. Fibroblasts also adopt a contractile phenotype expressing α-actin contributing to wound closure. The hypothesis of the thesis is that fibroblasts proliferate and transdifferentiate into myofibroblasts by sensing pulsed electrical signals and adjusting relevant signalling pathways. To test this hypothesis we used biocompatible polyethylene terephthalate (PET) fabrics coated with electrically conductive polypyrrole (PPy). Human dermal fibroblasts were cultured on these conductive fabrics and exposed to the optimized pulsed ES: either 10s PES in a period of 1200s, or 300s PES in 600s period, for a total of 24 hours. Two electric intensities were studied, 50 and 100 mV/ mm. Our work showed that the PES promoted the adhesion, proliferation and migration of dermal fibroblasts. These cellular activities were consolidated by an elevated level of fibroblast growth factor 2 (FGF2) and the high expression of α-smooth muscle actin (α-SMA). Important findings were that PES promoted the phenotypic change of fibroblasts to myofibroblasts, and such change was coordinated through the Smad and TGFβ/ERK pathways. It also demonstrated that the effect of PES was able to maintain for a long period of time after the end of stimulation, and was transferable from the mother cells to the daughter cells. Following subculture, the electrically stimulated fibroblasts still expressed significant amount of α-SMA. In conclusion, this thesis demonstrates that PES through conductive fabrics can activate the wound healing functions in human dermal fibroblasts. This work revealed for the first time that Smad and TGFβ/ERK pathways are required by the PES-induced fibroblasts-to-myofibroblasts differentiation. This work also demonstrated that the PES activated cells can survive in vivo. These studies suggest the application of the PES in promoting tissue regeneration and wound healing

Deriving Analytical Expression of Current-Voltage Characteristics of dc-SQUID with Frequency-Phase-Locking Model

The direct-current Superconducting Quantum Interference Device (dc-SQUID) is hybrid circuit with Josephson junctions and normal circuit elements considering the parasitic capacitors and inductors introduced by tightly coupled input coils. Its equivalent circuit is becoming more and more complicated with the development of practical SQUID integrated circuits. It is difficult to derive the analytical expression of current-voltage characteristics directly from the nonlinear circuit equations. This article introduces a frequency domain analysis method to derive the analytical current-voltage expression using four network impedances instead of the nonlinear circuit equations. A frequency-phase-locking model is derived to depict the working principle inside the dc-SQUID. In this model, two Josephson junctions and the linear network form two cross-linked lock-in amplifiers, where the Josephson junction functions as both the voltage-controlled oscillator (VCO) and the mixer; the current-voltage characteristics of the dc-SQUID are the projections of the network impedances. The application of the model is demonstrated in the analysis of a typical dc SQUID magnetometer; the current-voltage characteristics predicted by the analytical expression agree well with the results through the numerical simulation. This frequency-phase-locking model improves our understanding of the working mechanism inside the dc-SQUID circuit.Comment: 7 pages, 11 figure

An Electromagnetic-Flux-Distribution Model for the Analyses of Superconducting Josephson Junction Circuits and Quantum Phase-Slip Junction Circuits

Josephson junctions and the quantum phase-slip (QPS) junctions are two quantum circuit elements introduced by superconducting electronics to create various hybrid circuits. Josephson junctions bring the developments of superconducting quantum interference devices (SQUIDs) and single-flux quantum (SFQ) digital circuits; as the dual element of Josephson junctions, QPS junctions are used to design the new devices dual to Josephson junction circuits. In order to bridge the gap between superconducting and non-superconducting circuits, this article presents an electromagnetic-flux-distribution model to unify the superconducting and non-superconducting circuit analyses. This model redefines the circuit laws and functions of circuit elements using the conventional electric variables; it provides the unified circuit equations to depict the working principles of circuits viewed from electric and magnetic fields; it also derives the mathematical expression of duality principles between Josephson junction and QPS Junction circuits. The application of this electromagnetic-flux-distribution model is demonstrated in the analyses of a Josephson junction circuit and its dual QPS junction circuit. It shows that Josephson junction circuits are the magnetic-flux-distribution systems, while QPS junction circuits are the electric-flux-distribution systems, they are modulated by the Josephson effect and the phase-slip effect.Comment: 8 pages, 13 figure

Exploración de las percepciones de los profesores en formación chinos sobre el desarrollo profesional autodirigido: Beneficios y retos revelados

Teaching has long been regarded as a demanding and complicated job, in which teachers play a vital role. To be effective and successful in this profession, they need to constantly engage in professional development programs. However, such programs are mostly externally driven with teachers playing passive roles. Against this pitfall, self-directed professional development (SDPD) has recently captured the attention of educational researchers. Yet, the benefits and challenges of SDPD in pre-service programs are unknown in EFL contexts. To fill this gap, this study used a semi-structured interview with 50 Chinese pre-service teachers regarding their perceptions of this mode of professional development. The findings of thematic analysis obtained by MAXQDA software (v. 2022) revealed that the most frequent benefits of SDPD were being “needs-based” and “self-directed”, which, in turn, produce “flexibility”, “autonomy”, and “professional knowledge development” in teachers. Concerning the challenges in implementing SDPD, “lack of professional interaction/assistance” from external forces and being “labor-intensive” for teachers were posed most frequently by the participants. Despite these complexities, most of the Chinese pre-service teachers (82%) preferred self-directed and self-initiated PD given their potential and effectiveness. The study encourages EFL educators to revisit their perspectives, plans, and strategies regarding professionalism and professional development. FUNDING INFORMATION. This study is a part of a research project on ‘The Training Mode of the Five-Year Bilingual International Talents under the Background of New Liberal Arts Construction’ supported by Nanjing Normal University’s New Liberal Arts Research and Reform Project in 2021.La enseñanza se ha considerado como un trabajo exigente y complicado en que los docentes desempeñan un papel vital. Para ser efectivos y exitosos, los maestros deben participar en programas de desarrollo profesional (DP). Sin embargo, tales programas son principalmente impulsados con roles pasivos. El desarrollo profesional autodirigido (SDPD) ha llamado la atención de los investigadores. Los beneficios y desafíos del SDPD en programas de pre-servicio se desconocen en el contexto chino de EFL. Este estudio adoptó una entrevista semiestructurada con 50 futuros maestros chinos sobre el SDPD. Los hallazgos obtenidos por MAXQDA (Versión 2022) revelaron que los beneficios más frecuentes del SDPD eran ser “basado en necesidades” y “autodirigido”, lo que produce “flexibilidad”, “autonomía” y “desarrollo del conocimiento profesional” en los docentes. Con respecto a los desafíos en implementar SDPD, los participantes plantearon con mayor frecuencia la “falta de interacción/ asistencia profesional” de fuerzas externas y el hecho de que sean “intensivos en labor”. A pesar de estas complejidades, el 82% de los entrevistados preferían el DP autodirigido y autoiniciado debido a su potencial y eficacia. El estudio alienta a los educadores de EFL a revisar sus perspectivas, planes y estrategias con respecto al profesionalismo y el DP

Aprecio y cuidado del profesor en deseos comunicativos en clase de alumnos chinos e iraníes

This mixed-methods cross-cultural study examined the role of instructor confirmation and care in EFL students’ willingness to attend classes (WTAC). For the quantitative phase, 1006 and 605 EFL university students were chosen respectively from Chinese and Iranian universities, and for the qualitative phase, sub-groups of 43 Chinese and 34 Iranian participants were selected. Three close-ended scales and semi-structured interviews were used to collect data. Results of confirmatory factor analysis approved the factor structure and validity of the three scales. Results of correlation and Structural Equation Modeling (SEM) analyses indicated the positive associative/predictive role of perceived teacher caring and confirmation in Chinese and Iranian students’ WTAC. The independent samples t-tests results showed significant differences in perceptions of caring, confirmation, and WTAC, with Chinese participants significantly outperforming Iranians. Frequency counts of qualitative data revealed that both Chinese and Iranian students believed in the facilitative role of confirmation and caring in WTAC. Further content analysis of the data through MAXQDA presented four themes of teacher-, student-, context, and task-related factors, among which the teacher-related factors theme and its teacher interpersonal factors sub-theme were deemed very influential by Chinese and Iranian students in predicting WTAC.El presente estudio mediante métodos mixtos investigó el papel del aprecio y cuidado del profesor en la voluntad comunicativa de los alumnos en clases de inglés como lengua extranjera. Para la fase cuantitativa, se eligieron 1006 y 605 alumnos universitarios chinos e iraníes respectivamente para el muestreo, y para la cualitativa, 43 chinos y 34 iraníes. Se utilizaron tres escalas y entrevistas semiestructuradas para recopilar datos. Los resultados aprobaron la estructura factorial y la validez de las tres escalas e indicaron el papel asociativo y predictivo positivo del aprecio y cuidado del profesor en el WTAC de los alumnos chinos e iraníes. Mientras tanto, mostraron diferencias significativas en las percepciones de cuidado, aprecio y WTAC, en que los participantes chinos superaron notablemente a los iraníes. El análisis también reveló que tanto los alumnos chinos como los iraníes creían en el papel facilitador del aprecio y del cuidado en WTAC. El análisis de los datos mediante MAXQDA presentó cuatro temas de factores relacionados con el profesor, el alumno, el contexto y la tarea, entre los cuales el tema del profesor y su subtema de factores interpersonales fueron considerados muy influyentes por los alumnos chinos e iraníes en la predicción de WTAC.&nbsp