Topological Distribution of Wound Stiffness Modulates Wound-Induced Hair Follicle Neogenesis.

In the large full-thickness mouse skin regeneration model, wound-induced hair neogenesis (WIHN) occurs in the wound center. This implies a spatial regulation of hair regeneration. The role of mechanotransduction during tissue regeneration is poorly understood. Here, we created wounds with equal area but different shapes to understand if perturbing mechanical forces change the area and quantity of de novo hair regeneration. Atomic force microscopy of wound stiffness demonstrated a stiffness gradient across the wound with the wound center softer than the margin. Reducing mechanotransduction signals using FAK or myosin II inhibitors significantly increased WIHN and, conversely, enhancing these signals with an actin stabilizer reduced WIHN. Here, α-SMA was downregulated in FAK inhibitor-treated wounds and lowered wound stiffness. Wound center epithelial cells exhibited a spherical morphology relative to wound margin cells. Differential gene expression analysis of FAK inhibitor-treated wound RNAseq data showed that cytoskeleton-, integrin-, and matrix-associated genes were downregulated, while hair follicular neogenesis, cell proliferation, and cell signaling genes were upregulated. Immunohistochemistry staining showed that FAK inhibition increased pSTAT3 nuclear staining in the regenerative wound center, implying enhanced signaling for hair follicular neogenesis. These findings suggest that controlling wound stiffness modulates tissue regeneration encompassing epithelial competence, tissue patterning, and regeneration during wound healing.

Room-Temperature Negative Differential Resistance and High Tunneling Current Density in GeSn Esaki Diodes.

Tunnel field-effect transistors (TFETs) are a promising candidate for low-power applications owing to their steep subthreshold swing of sub-60 mV per decade. For silicon- or germanium-based TFETs, the drive current is low due to the indirect band-to-band tunneling (BTBT) process. Direct-bandgap germanium-tin (GeSn) can boost the TFET performance since phonon participation is not required during the tunneling process. Esaki diodes with negative differential resistance (NDR) are used to characterize the BTBT properties and calibrate the tunneling rates for TFET applications. This work demonstrates high-performance GeSn Esaki diodes with clear NDR at room temperature with very high peak-to-valley current ratios of 15-53 from 300 K to 4 K. A record-high peak current density of 545 kA cm-2 at 4 K is also reported for the tensile-strained Ge0.925 Sn0.075 device (strain ≈0.6 %). By applying tensile stresses to n-GeSn epitaxial films, the direct BTBT process dominates, leading to high tunneling rates. Hall measurements further confirm that more electrons populate in the direct Γ valley in the tensile-strained n-GeSn epitaxial films.

Strain Effects on Rashba Spin-Orbit Coupling of 2D Hole Gases in GeSn/Ge Heterostructures.

A demonstration of 2D hole gases in GeSn/Ge heterostructures with a mobility as high as 20 000 cm2 V-1 s-1 is given. Both the Shubnikov-de Haas oscillations and integer quantum Hall effect are observed, indicating high sample quality. The Rashba spin-orbit coupling (SOC) is investigated via magneto-transport. Further, a transition from weak localization to weak anti-localization is observed, which shows the tunability of the SOC strength by gating. The magneto-transport data are fitted to the Hikami-Larkin-Nagaoka formula. The phase-coherence and spin-relaxation times, as well as spin-splitting energy and Rashba coefficient of the k-cubic term, are extracted. The analysis reveals that the effects of strain and confinement potential at a high fraction of Sn suppress the Rashba SOC caused by the GeSn/Ge heterostructures.

TREM-1-dependent M1 macrophage polarization restores intestinal epithelium damaged by DSS-induced colitis by activating IL-22-producing innate lymphoid cells.

BACKGROUND: Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed on macrophages in inflamed intestines and reportedly promotes inflammatory bowel disease (IBD) by augmenting pro-inflammatory responses. To study the mechanism mediated by TREM-1 on macrophages, we generated an independent TREM-1 deficient mouse. METHODS: Acute colitis was induced in C57BL/6 and TREM-1-deficient mice by the administration of dextran sodium sulfate (DSS). Colonic lamina propria immune cell composition and cytokines were analyzed. An innate lymphoid cell (ILC) co-culture experiment with macrophages was used to analyze IL-22 levels. Exogenous IL-22 and TREM-1-expressing macrophages were supplied to TREM-1-deficient mice for examining their effects on intestinal barrier integrity. RESULTS: In inflamed colons, TREM-1 loss compromised the activation of ILC3 and their production of IL-22, which is required for intestinal barrier integrity. ILC3-mediated IL-22 production depends on IL-1ß secreted by M1-polarized macrophages, and we found that TREM-1 deficiency results in a decreased number of IL-1ß producing-M1 macrophages in colons exposed to DSS. Accordingly, DSS-mediated damage was ameliorated by supplying exogenous IL-22 and TREM-1-expressing macrophages to TREM-1-deficient mice. CONCLUSIONS: TREM-1 plays a crucial role in regulating IL-22 production by ILC3 through modulating M1-macrophage polarization during DSS-induced acute colitis.

Regeneration of rete ridges in Lanyu pig (Sus scrofa): Insights for human skin wound healing.

Rete ridges are important to the mechanical function of skin in animals with minimal hair, including humans. As mice do not exhibit rete ridges, the need for a quality animal model is pertinent. Here, we develop a Lanyu pig (Sus scrofa) full-thickness wound model to explore tissue regeneration because the architecture and function are similar to humans and inbred genetic variants are available. Full- and partial-thickness wounds were generated on the dorsum. Full-thickness wounds at post-wound day 57 exhibit severe scar with no signs of wound-induced hair follicle neogenesis. Wound contraction is greater in the anterior/posterior relative to the medial/lateral axis. In wound beds, K14+ cells increased while K10+ , p63+ and PCNA+ cells decreased compared to unwounded tissue. Epithelial ß-catenin is unchanged. The wound bed expresses more ColI, less ColIII and no elastin. Rete ridges do not form after full-thickness wounding, but incompletely regenerate after partial-thickness wounding. An alkaline phosphatase (ALP)+ cell population, not associated with hair follicles, is present at the bottom of the rete ridge basal layer in pig and human unwounded skin. These K5+ /K10- /PCNA- /ALP+ epithelial cells are absent after full-thickness wounding but reappear after partial-thickness wounding, before invagination of new rete ridges. In summary, full-thickness wounding on the dorsum of Lanyu pigs results in scar formation and perturbed molecular expression while partial-thickness wounding permits limited rete ridge and papillary dermis regeneration. Future functional studies and further characterization will help contribute knowledge for the regenerative medicine field.