BACKGROUND: Periodontal ligament stem cells (PDLSCs) are important seed cells in tissue engineering and clinical applications. They are the priority receptor cells for sensing various mechanical stresses. Yes-associated protein (YAP) is a recognized mechanically sensitive transcription factor. However, the role of YAP in regulating the fate of PDLSCs under tension stress (TS) and its underlying mechanism is still unclear.
METHODS: The effects of TS on the morphology and fate of PDLSCs were investigated using fluorescence staining, transmission electron microscopy, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). Then qRT-PCR, western blotting, immunofluorescence staining and gene knockdown experiments were performed to investigate the expression and distribution of YAP and its correlation with PDLSCs proliferation. The effects of cytoskeleton dynamics on YAP nuclear translocation were subsequently explored by adding cytoskeleton inhibitors. The effect of cytoskeleton dynamics on the expression of the LINC complex was proved through qRT-PCR and western blotting. After destroying the LINC complex by adenovirus, the effects of the LINC complex on YAP nuclear translocation and PDLSCs proliferation were investigated. Mitochondria-related detections were then performed to explore the role of mitochondria in YAP nuclear translocation. Finally, the in vitro results were verified by constructing orthodontic tooth movement models in Sprague-Dawley rats.
RESULTS: TS enhanced the polymerization and stretching of F-actin, which upregulated the expression of the LINC complex. This further strengthened the pull on the nuclear envelope, enlarged the nuclear pore, and facilitated YAP\'s nuclear entry, thus enhancing the expression of proliferation-related genes. In this process, mitochondria were transported to the periphery of the nucleus along the reconstructed microtubules. They generated ATP to aid YAP\'s nuclear translocation and drove F-actin polymerization to a certain degree. When the LINC complex was destroyed, the nuclear translocation of YAP was inhibited, which limited PDLSCs proliferation, impeded periodontal tissue remodeling, and hindered tooth movement.
CONCLUSIONS: Our study confirmed that appropriate TS could promote PDLSCs proliferation and periodontal tissue remodeling through the mechanically driven F-actin/LINC complex/YAP axis, which could provide theoretical guidance for seed cell expansion and for promoting healthy and effective tooth movement in clinical practice.

OBJECTIVE: To investigate whether a labially inclined implant axis compromises the clinical outcomes of immediate implant placement and provisionalization (IIPP) in the anterior maxilla.
METHODS: Patients with unsalvageable central or lateral maxillary incisors were enrolled. IIPP with simultaneous connective tissue graft (CTG) was performed in all participants. In the control group, the alveolar ridge had a long axis aligned with the tooth, which ensured that the immediate implant was aimed at the incisor edge or the cingulum of future restoration. The test group had a large angle between the axes of the ridge and tooth. To avoid bone fenestration, the implants were placed labially inclined and emerged from the labial side of future restoration. Intra-oral scanning and cone-beam computed tomography were performed to record soft and hard tissue profiles at baseline and 1 year later. Soft tissue stability, bone remodeling, and pink esthetic score (PES) were evaluated and compared between two groups.
RESULTS: Thirty-nine participants (19 tests and 20 controls) completed the study. At 1-year post-surgery, the mid-facial gingival margin migrations were 0.85 ± 0.37 mm (test) and 0.81 ± 0.33 mm (control), without significant differences. No differences were identified in buccal profile alteration, linear ridge reduction, buccal bone thickness, or PES scores. The test group demonstrated thinner buccal soft tissue at the crestal level than the control group.
CONCLUSIONS: When large tooth-ridge angulation presented, labially inclined implant, avoiding buccal ridge fenestration in IIPP with CTG, did not compromise the clinical outcome in short term.

Insulin-like Growth Factor-Binding Protein 7 (IGFBP7) is an extracellular matrix (ECM) glycoprotein, highly enriched in activated vasculature during development, physiological and pathological tissue remodeling. Despite decades of research, its role in tissue (re-)vascularization is highly ambiguous, exhibiting pro- and anti-angiogenic properties in different tissue remodeling states. IGFBP7 has multiple binding partners, including structural ECM components, cytokines, chemokines, as well as several receptors. Based on current evidence, it is suggested that IGFBP7\'s bioactivity is strongly dependent on the microenvironment it is embedded in. Current studies indicate that during physiological angiogenesis, IGFBP7 promotes endothelial cell attachment, luminogenesis, vessel stabilization and maturation. Its effects on other stages of angiogenesis and vessel function remain to be determined. IGFBP7 also modulates the pro-angiogenic properties of other signaling factors, such as VEGF-A and IGF, and potentially acts as a growth factor reservoir, while its actual effects on the factors\' signaling may depend on the environment IGFBP7 is embedded in. Besides (re-)vascularization, IGFBP7 clearly promotes progenitor and stem cell commitment and may exhibit anti-inflammatory and anti-fibrotic properties. Nonetheless, its role in inflammation, immunomodulation, fibrosis and cellular senescence is again likely to be context-dependent. Future studies are required to shed more light on the intricate functioning of IGFBP7.

Macrophages play crucial and versatile roles in regulating tissue repair and regeneration upon injury. However, due to their complex compositional heterogeneity and functional plasticity, deciphering the nature of different macrophage subpopulations and unraveling their dynamics and precise roles during the repair process have been challenging. With its distinct advantages, zebrafish (Danio rerio) has emerged as an invaluable model for studying macrophage development and functions, especially in tissue repair and regeneration, providing valuable insights into our understanding of macrophage biology in health and diseases. In this review, we present the current knowledge and challenges associated with the role of macrophages in tissue repair and regeneration, highlighting the significant contributions made by zebrafish studies. We discuss the unique advantages of the zebrafish model, including its genetic tools, imaging techniques, and regenerative capacities, which have greatly facilitated the investigation of macrophages in these processes. Additionally, we outline the potential of zebrafish research in addressing the remaining challenges and advancing our understanding of the intricate interplay between macrophages and tissue repair and regeneration.

Contamination tolerance and long-term mechanical support are the two critical properties of meshes for contaminated abdominal wall defect repair. However, biological meshes with excellent pollution tolerance fail to provide bio-adaptive long-term mechanical support due to their rapid degradation. Here, a novel double-layer asymmetric porous mesh (SIS/PVA-EXO) is designed by simple and efficient in situ freeze-thaw of sticky polyvinyl alcohol (PVA) solution on the loosely porous surface of small intestinal submucosal decellularized matrix (SIS), which can successfully repair the contaminated abdominal wall defect with bio-adaptive dynamic mechanical support through only single-stage surgery. The exosome-loaded degradable loosely porous SIS layer accelerates the tissue healing; meanwhile, the exosome-loaded densely porous PVA layer can maintain long-term mechanical support without any abdominal adhesion. In addition, the tensile strength and strain at break of SIS/PVA-EXO mesh change gradually from 0.37 MPa and 210% to 0.10 MPa and 385% with the degradation of SIS layer. This unique performance can dynamically adapt to the variable mechanical demands during different periods of contaminated abdominal wall reconstruction. As a result, this SIS/PVA-EXO mesh shows an attractive prospect in the treatment of contaminated abdominal wall defect without recurrence by integrating local immune regulation, tissue remodeling, and dynamic mechanical supporting.

Orthodontic tooth movement (OTM) involves mechanical-biochemical signal transduction, which results in tissue remodeling of the tooth-periodontium complex and the movement of orthodontic teeth. The dynamic regulation of osteogenesis and osteoclastogenesis serves as the biological basis for remodeling of the periodontium, and more importantly, the prerequisite for establishing periodontal homeostasis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key effectors of the Hippo signaling pathway, which actively respond to mechanical stimuli during tooth movement. Specifically, they participate in translating mechanical into biochemical signals, thereby regulating periodontal homeostasis, periodontal remodeling, and tooth development. YAP and TAZ have widely been considered as key factors to prevent dental dysplasia, accelerate orthodontic tooth movement, and shorten treatment time. In this review, we summarize the functions of YAP and TAZ in regulating tooth development and periodontal remodeling, with the aim to gain a better understanding of their mechanisms of action and provide insights into maintaining proper tooth development and establishing a healthy periodontal and alveolar bone environment. Our findings offer novel perspectives and directions for targeted clinical treatments. Moreover, considering the similarities and differences in the development, structure, and physiology between YAP and TAZ, these molecules may exhibit functional variations in specific regulatory processes. Hence, we pay special attention to their distinct roles in specific regulatory functions to gain a comprehensive and profound understanding of their contributions.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a vast stromal reaction that arises mainly from cancer-associated fibroblasts (CAFs) and promotes both immune escape and tumor growth. Here, we used a mouse model with deletion of the activin A receptor ALK4 in the context of the KrasG12D mutation, which strongly drives collagen deposition that leads to tissue stiffness. By ligand-receptor analysis of single-cell RNA-sequencing data, we identified that, in stiff conditions, neoplastic ductal cells instructed CAFs through sustained platelet-derived growth factor (PDGF) signaling. Tumor-associated tissue rigidity resulted in the emergence of stiffness-induced CAFs (siCAFs) in vitro and in vivo. Similar results were confirmed in human data. siCAFs were able to strongly inhibit CD8+ T-cell responses in vitro and in vivo, promoting local immunosuppression. More importantly, targeting PDGF signaling led to diminished siCAF and reduced tumor growth. Our data show for the first time that early paracrine signaling leads to profound changes in tissue mechanics, impacting immune responses and tumor progression. Our study highlights that PDGF ligand neutralization can normalize the tissue architecture independent of the genetic background, indicating that finely tuned stromal therapy may open new therapeutic avenues in pancreatic cancer.

BACKGROUND: The excellent efficacy is mitigated by the limited safety profile of microfocused ultrasound procedures.
OBJECTIVE: We sought to assess the safety and tightening efficacy of a novel microfocused ultrasound.
METHODS: The randomized middle and lower face and submental region of the participants were treated with the novel device using the following transducers: M4.5, D4.5, M3.0, and D3.0. Improvement in paired comparison of pretreatment and posttreatment photographs, three-dimensional (3D) volumetric assessments, skin thickness measured by B-ultrasonography, and skin photoaging parameters were evaluated. Adverse events and patient satisfaction were also recorded.
RESULTS: A total of 20 participants (20 female) were enrolled. Fourteen of 20 participants (70%) were judged to show clinically significant facial tightening during 3-month follow-up (P < 0.05). The mean volumetric change in the lower face, as quantitatively assessed after 3 months was -0.29 mL compared with +0.42 mL on the control side (P < 0.05). The VAS pain score was 3.00 ± 1.19 without any oral or intramuscular anesthesia.
CONCLUSIONS: A small sample size, lack of clinical scales, and impersonalized treatment parameters. The novel microfocused ultrasound appears to be a safe and effective modality for lower-face tightening.
BACKGROUND: ChiCTR 2200064666.

The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues. The T and B cell receptor repertoires were skewed in NP. This study highlights the deviated immune response and remodeling mechanisms that contribute to the pathogenesis of uncontrolled severe CRSwNP. CLINICAL IMPLICATIONS: We identified differences in the cellular compositions, transcriptomes, proteomes, and deviations in the immune profiles of T cell and B cell receptors as well as alterations in the intercellular communications in uncontrolled severe CRSwNP patients versus healthy controls, which might help to define potential therapeutic targets in the future.