TGF-ß specifies TFH versus TH17 cell fates in murine CD4+ T cells through c-Maf.

T follicular helper (TFH) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse TFH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor-ß (TGF-ß) induces robust expression of TFH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4+ T cells in vitro. TGF-ß-induced mouse CXCR5+ TFH cells are phenotypically, transcriptionally, and functionally similar to in vivo-generated TFH cells and provide critical help to B cells. The study further reveals that TGF-ß-induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-ß-containing T helper 17 (TH17)-inducing conditions also yield separate CXCR5+ and IL-17A-producing cells, highlighting shared and distinct cell fate trajectories of TFH and TH17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-ß-induced TFH cell program, that TFH and TH17 cells share a common developmental stage, and that c-Maf acts as a switch factor for TFH versus TH17 cell fates in TGF-ß-rich environments in vitro and in vivo.

A bistable cholesteric liquid crystal film stabilized by a liquid-crystalline epoxy/thiol compound-based polymer.

Bistable cholesteric liquid crystals have promising application prospects in various fields, such as smart windows and displays. However, the long-term stability of two individual states is not easy to achieve, hindering their practical use. In this research, the bistable feature was enhanced by constructing a microsphere-type polymer with a liquid-crystalline epoxy/thiol monomer in negative dielectric anisotropic cholesteric liquid crystals. Spectroscopic and optical examinations revealed that either the transparent planar state or the opaque focal conic state can be maintained without the aid of an external field. Moreover, they can be switched to each other by applying a high- or low-frequency electric field. Further, factors such as the chemical structure of thiol compounds, curing temperature and curing time were investigated to explore their influences on the micro morphology of the polymer and thereby the electro-optical properties. In addition, the frequency-dependent driving scheme was analysed. Finally, bistable switching was demonstrated using an optimized sample. This energy-efficient bistable film shines light on future applications in smart windows, photonic paper and other electro-optical devices.

Effects of noninvasive brain stimulation on dual-task performance in different populations: A systematic review.

Background: Increasing research has investigated the use of noninvasive brain stimulation (NIBS) on augmenting dual-task (DT) performance. Objective: To investigate the effects of NIBS on DT performance in different populations. Methods: Extensive electronic database search (from inception to November 20, 2022) was conducted in PubMed, Medline, Cochrane Library, Web of Science and CINAHL to identify randomized controlled trials (RCTs) that investigated the effects of NIBS on DT performance. Main outcomes were balance/mobility and cognitive function under both single-task (ST) and DT conditions. Results: Fifteen RCTs were included, involving two types of intervention techniques: transcranial direct current stimulation (tDCS) (twelve RCTs) and repetitive transcranial magnetic stimulation (rTMS) (three RCTs); and four different population groups: healthy young adults, older adults, Parkinson's disease (PD), and stroke. For tDCS, under DT condition, significant improvement in speed was only observed in one PD and one stroke RCT, and stride time variability in one older adults RCT. Reduction in DTC in some gait parameters was demonstrated in one RCT. Only one RCT showed significant reduction in postural sway speed and area during standing under DT condition in young adults. For rTMS, significant improvements in fastest walking speed and time taken to Timed-up-and-go test under both ST and DT conditions were observed at follow-up in one PD RCT only. No significant effect on cognitive function in any RCT was observed. Conclusion: Both tDCS and rTMS showed promising effects in improving DT walking and balance performance in different populations, however, due to the large heterogeneity of included studies and insufficient data, any firm conclusion cannot be drawn at present.

In Vivo and In Vitro Assay to Address Dendritic Cell Antigen Cross-Presenting Capacity.

Antigen cross-presentation by dendritic cells is an important pathway to prime CD8+ T cells in infections, cancer, and other immune-mediated pathologies. Particularly in cancer, cross-presentation of tumor-associated antigens is crucial for an effective antitumor CTL response. The mostly accepted cross-presentation assay is to use chicken ovalbumin (OVA) as a model antigen and then utilize OVA-specific TCR transgenic CD8+ T (OT-I) cells to measure the cross-presenting capacity. Here we describe in vivo and in vitro assays to measure the function of antigen cross-presentation using cell-associated OVA.

Functional exercise on patients after sports meniscus injury / Exercício funcional em pacientes após lesão esportiva de menisco / Ejercicio funcional en pacientes tras lesión deportiva de menisco

ABSTRACT Introduction Knee meniscus injury is a common sports injury, and minimally invasive surgery under knee arthroscopy has become an ideal method to treat meniscus injuries. This surgery rehabilitation has been improved, and several studies on the effects of functional exercise in the range of treatment are still inconclusive. Objective Study the functional exercise rehabilitation effects in patients after sports meniscus injury. Methods Twenty patients with meniscus-medial injury being operated on were selected, including eight men and 12 women. They were randomly divided into neuromuscular and strength training groups (11). Signs and symptoms were assessed before and eight weeks after treatment. JOA score indices and gait tests were compared. The impact of rehabilitation differences was evaluated in each group. Results Eight weeks after rehabilitation in both groups, the scores of the strength training group were higher than the neuromuscular group; the difference between the groups was statistically significant (P<0.05). Conclusion Functional exercise accelerates joint recovery, reflected in increased strength of adjacent muscles. The muscle and joint training effects on postoperative meniscus injury are worthy of recognition. The baropodometry revealed distinctions in walking patterns between different rehabilitation methods. From the perspective of this research, rehabilitation methods combined with proprioceptive exercises are complementary. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução Lesão no menisco do joelho é uma lesão esportiva comum e a cirurgia minimamente invasiva sob artroscopia no joelho tornou-se um método ideal para tratar lesões no menisco. A reabilitação dessa cirurgia vem sendo aprimorada e vários estudos sobre os efeitos do exercício funcional no leque de tratamento ainda são inconclusivos. Objetivo Estudar os efeitos da reabilitação com exercício funcional em pacientes após a lesão esportiva do menisco. Métodos Foram selecionados 20 pacientes com lesão menisco-medial a serem operados, incluindo 8 homens e 12 mulheres. Divididos aleatoriamente em 2 grupos: grupo de treinamento neuromuscular e grupo de treinamento força (11). Sinais e sintomas foram avaliados antes do tratamento e 8 semanas após o tratamento, índices de score JOA e teste de marcha foram comparados, as diferenças do impacto da reabilitação em cada grupo foram avaliadas. Resultados Oito semanas após a reabilitação dos dois grupos, os escores do grupo de treinamento de força foram superiores aos do grupo neuromuscular, a diferença entre os grupos foi estatisticamente significante (P<0,05). Conclusão O exercício funcional acelera a recuperação das articulações, refletida no aumento da força dos músculos adjacentes. O efeito do treinamento muscular e articular na lesão do menisco pós-operatório é digno de reconhecimento. A baropodometria revelou distinções no padrão de marcha entre os diferentes métodos de reabilitação. Na perspectiva desta pesquisa, métodos de reabilitação combinados com exercícios proprioceptivos são complementares. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción La lesión de menisco de la rodilla es una lesión deportiva común y la cirugía mínimamente invasiva por artroscopia de rodilla se ha convertido en un método ideal para tratar las lesiones de menisco. La rehabilitación de esta cirugía ha sido mejorada y varios estudios sobre los efectos del ejercicio funcional en el rango de tratamiento aún no son concluyentes. Objetivo Estudiar los efectos de la rehabilitación con ejercicio funcional en pacientes tras una lesión de menisco deportiva. Métodos Se seleccionaron 20 pacientes con lesión de menisco-medial para ser operados, incluyendo 8 hombres y 12 mujeres. Se dividieron aleatoriamente en 2 grupos: grupo de entrenamiento neuromuscular y grupo de entrenamiento de fuerza (11). Se evaluaron los signos y síntomas antes del tratamiento y 8 semanas después del mismo, se compararon los índices de puntuación JOA y la prueba de marcha, y se evaluaron las diferencias del impacto de la rehabilitación en cada grupo. Resultados Ocho semanas después de la rehabilitación para ambos grupos, las puntuaciones del grupo de entrenamiento de fuerza fueron mayores que las del grupo neuromuscular, la diferencia entre los grupos fue estadísticamente significativa (P<0,05). Conclusión El ejercicio funcional acelera la recuperación de la articulación, lo que se refleja en el aumento de la fuerza de los músculos adyacentes. El efecto del entrenamiento muscular y articular en la lesión postoperatoria del menisco es digno de reconocimiento. La baropodometría reveló diferencias en el patrón de la marcha entre los diferentes métodos de rehabilitación. Desde la perspectiva de esta investigación, los métodos de rehabilitación combinados con los ejercicios propioceptivos son complementarios. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells.

Conventional type 1 dendritic cells (cDC1s) are inherently resistant to many viruses but, paradoxically, possess fewer acidic phagosomes that enable antigen retention and cross-presentation. We report that palmitoyl-protein thioesterase 1 (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to VSV. Conversely, PPT1-deficient cDC1s enhance the priming of naive CD8+ T cells into tissue-resident KLRG1+ effectors and memory T cells, resulting in rapid clearance of tumors and Listeria monocytogenes Mechanistically, PPT1 protects steady state DCs from viruses by promoting antigen degradation and endosomal acidification via V-ATPase recruitment. After DC activation, immediate down-regulation of PPT1 is likely to facilitate efficient cross-presentation, production of costimulatory molecules and inflammatory cytokines. Thus, PPT1 acts as a molecular rheostat that allows cDC1s to crossprime efficiently without compromising viral resistance. These results suggest potential therapeutics to enhance cDC1-dependent crosspriming.