MicroRNA-205 promotes hair regeneration by modulating mechanical properties of hair follicle stem cells.

Stiffness and actomyosin contractility are intrinsic mechanical properties of animal cells required for the shaping of tissues. However, whether tissue stem cells (SCs) and progenitors located within SC niche have different mechanical properties that modulate their size and function remains unclear. Here, we show that hair follicle SCs in the bulge are stiff with high actomyosin contractility and resistant to size change, whereas hair germ (HG) progenitors are soft and periodically enlarge and contract during quiescence. During activation of hair follicle growth, HGs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation, and cell cycle reentry. Induction of miR-205, a novel regulator of the actomyosin cytoskeleton, reduces actomyosin contractility and activates hair regeneration in young and old mice. This study reveals the control of tissue SC size and activities by spatiotemporally compartmentalized mechanical properties and demonstrates the possibility to stimulate tissue regeneration by fine-tuning cell mechanics.

Study on the mechanism of action of Wu Mei Pill in inhibiting rheumatoid arthritis through TLR4-NF-κB pathway.

BACKGROUND: Wu Mei Pills (WMP) is a traditional Chinese medication that exhibits considerable anti-inflammatory effects. While WMP has been documented for its efficacy in treating RA, its mechanism of action on the condition remains unestablished. METHODS: The chemical composition of WMP was analyzed through UPLC-MS. Next, the enzyme-linked immunosorbent assay, cell scratch, Transwell, and Western blotting techniques were used to investigate its intrinsic mechanism. Lastly, the effect of WMP in inhibiting RA was explored by applying it to CIA rats. RESULT: UPLC-MS analysis detected 181 compounds in WMP. RA-FLS migration and invasion mechanisms were significantly hindered by serum containing WMP (2%, 8%). Moreover, WMP (0.5 g/kg, 2 g/kg) restricted arthritis and immune organ indices in CIA rats with type II collagen-induced rheumatoid arthritis by blocking TLR4-NF-κB inflammatory pathway activation. CONCLUSIONS: WMP is valuable in mitigating the course of RA through inhibiting the classical TLR4-NF-κB inflammatory pathway and reducing the secretion of inflammatory factors in the serum of RA-FLS and CIA rats. Moreover, it regulates the dynamic balance of MMP-2/TIMP-2, MMP-9/TIMP-1, modulates the mechanism of RA-FLS invasion, and safeguards articular cartilage tissues in RA.

scHolography: a computational method for single-cell spatial neighborhood reconstruction and analysis.

Spatial transcriptomics has transformed our ability to study tissue complexity. However, it remains challenging to accurately dissect tissue organization at single-cell resolution. Here we introduce scHolography, a machine learning-based method designed to reconstruct single-cell spatial neighborhoods and facilitate 3D tissue visualization using spatial and single-cell RNA sequencing data. scHolography employs a high-dimensional transcriptome-to-space projection that infers spatial relationships among cells, defining spatial neighborhoods and enhancing analyses of cell-cell communication. When applied to both human and mouse datasets, scHolography enables quantitative assessments of spatial cell neighborhoods, cell-cell interactions, and tumor-immune microenvironment. Together, scHolography offers a robust computational framework for elucidating 3D tissue organization and analyzing spatial dynamics at the cellular level.

Reconstruction of 3-dimensional tissue organization at the single-cell resolution.

Recent advances in spatial transcriptomics (ST) have allowed for the mapping of tissue heterogeneity, but this technique lacks the resolution to investigate gene expression patterns, cell-cell communications and tissue organization at the single-cell resolution. ST data contains a mixed transcriptome from multiple heterogeneous cells, and current methods predict two-dimensional (2D) coordinates for individual cells within a predetermined space, making it difficult to reconstruct and study three-dimensional (3D) tissue organization. Here we present a new computational method called scHolography that uses deep learning to map single-cell transcriptome data to 3D space. Unlike existing methods, which generate a projection between transcriptome data and 2D spatial coordinates, scHolography uses neural networks to create a high-dimensional transcriptome-to-space map that preserves the distance information between cells, allowing for the construction of a cell-cell proximity matrix beyond the 2D ST scaffold. Furthermore, the neighboring cell profile of a given cell type can be extracted to study spatial cell heterogeneity. We apply scHolography to human skin, human skin cancer and mouse brain datasets, providing new insights into gene expression patterns, cell-cell interactions and spatial microenvironment. Together, scHolography offers a computational solution for digitizing transcriptome and spatial information into high-dimensional data for neural network-based mapping and the reconstruction of 3D tissue organization at the single-cell resolution.

Capybara: A computational tool to measure cell identity and fate transitions.

Measuring cell identity in development, disease, and reprogramming is challenging as cell types and states are in continual transition. Here, we present Capybara, a computational tool to classify discrete cell identity and intermediate "hybrid" cell states, supporting a metric to quantify cell fate transition dynamics. We validate hybrid cells using experimental lineage tracing data to demonstrate the multi-lineage potential of these intermediate cell states. We apply Capybara to diagnose shortcomings in several cell engineering protocols, identifying hybrid states in cardiac reprogramming and off-target identities in motor neuron programming, which we alleviate by adding exogenous signaling factors. Further, we establish a putative in vivo correlate for induced endoderm progenitors. Together, these results showcase the utility of Capybara to dissect cell identity and fate transitions, prioritizing interventions to enhance the efficiency and fidelity of stem cell engineering.

Solid-state cooling by elastocaloric polymer with uniform chain-lengths.

Although the elastocaloric effect was found in natural rubber as early as 160 years ago, commercial elastocaloric refrigeration based on polymer elastomers has stagnated owing to their deficient elastocaloric effects and large extension ratios. Herein, we demonstrate that polymer elastomers with uniform molecular chain-lengths exhibit enormous elastocaloric effects through reversible conformational changes. An adiabatic temperature change of -15.3 K and an isothermal entropy change of 145 J kg-1 K-1, obtained from poly(styrene-b-ethylene-co-butylene-b-styrene) near room temperature, exceed those of previously reported elastocaloric polymers. A rotary-motion cooling device is tailored to high-strains characteristics of rubbers, which effectively discharges the cooling energy of polymer elastomers. Our work provides a strategy for the enhancement of elastocaloric effects and could promote the commercialization of solid-state cooling devices based on polymer elastomers.

Effect of Stretching on Crystalline Structure, Ferroelectric and Piezoelectric Properties of Solution-Cast Nylon-11 Films.

Compared to polyvinylidene fluoride (PVDF) and its copolymers, castor-oil-derived nylon-11 has been less explored over the past decades, despite its excellent piezoelectric properties at elevated temperatures. To utilize nylon-11 for future sensor or vibrational energy harvesting devices, it is important to control the formation of the electroactive δ' crystal phase. In this work, nylon-11 films were first fabricated by solution-casting and were then uniaxially stretched at different stretching ratios (SR) and temperatures (Ts) to obtain a series of stretched films. The combination of two-dimensional wide-angle X-ray diffraction (2D-WAXD) and differential scanning calorimetry (DSC) techniques showed that the fraction of the δ' crystal phase increased with the stretching ratio and acquired a maximum at a Ts of 80 °C. Further, it was found that the ferroelectric and piezoelectric properties of the fabricated nylon-11 films could be correlated well with their crystalline structure. Consequently, the stretched nylon-11 film stretched at an SR of 300% and a Ts of 80 °C showed maximum remanent polarization and a remarkable piezoelectric coefficient of 7.2 pC/N. A simple piezoelectric device with such a nylon-11 film was made into a simple piezoelectric device, which could generate an output voltage of 1.5 V and a current of 11 nA, respectively.

High-resolution transcriptional and morphogenetic profiling of cells from micropatterned human ESC gastruloid cultures.

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell types. Ectodermal cells segregated from endodermal and extraembryonic but mixed with mesodermal cells. Our work demonstrates that the gastruloid system models primate-specific features of embryogenesis, and that gastruloid cells exhibit evolutionarily conserved sorting behaviors. This work generates a resource for transcriptomes of human extraembryonic and embryonic germ layers differentiated in a stereotyped arrangement.