Considerable evidence indicates that autophagy plays a vital role in the biological processes of various cancers. The aim of this study is to evaluate the prognostic value of autophagy-related genes in patients with head and neck squamous cell carcinoma (HNSCC). Transcriptome expression profiles and clinical data acquired from The Cancer Genome Atlas (TCGA) database were analyzed by Cox proportional hazards model and Kaplan–Meier survival analysis to screen autophagy-related prognostic genes that were significantly correlated with HNSCC patients’ overall survival. Functional enrichment analyses were performed to explore biological functions of differentially expressed autophagy-related genes (ARGs) identified in HNSCC patients. Six ARGs (EGFR, HSPB8, PRKN, CDKN2A, FADD, and ITGA3) identified with significantly prognostic values for HNSCC were used to construct a risk signature that could stratify patients into the high-risk and low-risk groups. This signature demonstrated great value in predicting prognosis for HNSCC patients and was indicated as an independent prognostic factor in terms of clinicopathological characteristics (sex, age, clinical stage, histological grade, anatomic subdivision, alcohol history, smoking status, HPV status, and mutational status of the samples). The prognostic signature was also validated by data from the Gene Expression Omnibus (GEO) database and International Cancer Genome Consortium (ICGC). In conclusion, this study provides a novel autophagy-related gene signature for predicting prognosis of HNSCC patients and gives molecular insights of autophagy in HNSCC.

Bone tissue is remodeled through the catabolic function of the osteoclasts and the anabolic function of the osteoblasts. The process of bone homeostasis and metabolism has been identified to be co‐ordinated with several local and systemic factors, of which mechanical stimulation acts as an important regulator. Very recent studies have shown a mutual effect between bone and other organs, which means bone influences the activity of other organs and is also influenced by other organs and systems of the body, especially the nervous system. With the discovery of neuropeptide (calcitonin gene‐related peptide, vasoactive intestinal peptide, substance P, and neuropeptide Y) and neurotransmitter in bone and the adrenergic receptor observed in osteoclasts and osteoblasts, the function of peripheral nervous system including sympathetic and sensor nerves in bone resorption and its reaction to on osteoclasts and osteoblasts under mechanical stimulus cannot be ignored. Taken together, bone tissue is not only the mechanical transmitter, but as well the receptor of neural system under mechanical loading. This review aims to summarize the relationship among bone, nervous system, and mechanotransduction.

Tissue engineering has the potential to overcome the limitations of tracheal reconstruction. To tissue-engineer a tracheal cartilage, auricular chondrocytes were encapsulated in a photocurable poly(ethylene glycol)/poly(ε-caprolactone) (PEG/PCL) hydrogel. Chondrogenic genes, including Sox9, Acan and Col2a1, were up-regulated in auricular chondrocytes after 2 weeks of in vitro cultivation in the PEG/PCL hydrogel. Co-cultivation of 70 % auricular chondrocytes and 30 % bone marrow mesenchymal stem cells (BMSCs) accelerated the chondrogenic genes' expression in the PEG/PCL hydrogel. Cartilaginous matrix markers, including proteoglycans and collagen type II, were detected in the chondrocytes-encapsulated PEG/PCL hydrogel after 4 weeks of in vitro cultivation. The higher expression level of cartilaginous matrix markers was observed in the PEG/PCL hydrogel with co-cultivation of 70 % chondrocytes and 30 % BMSCs. After 4 weeks of ectopic cultivation in rabbits, the cylindrical PEG/PCL structure was sustained with the use of a luminal silicon stent. However, without the stent, the construct collapsed under a compression force. No fibrosis or vessel ingrowth were found in the PEG/PCL hydrogel after 4 weeks of ectopic cultivation, whereas the auricular chondrocytes showed proteoglycans' accumulation and collagen type II production. Rabbit auricular chondrocytes could survive and retain chondrogenic ability in the PEG/PCL hydrogel under both in vitro and in vivo conditions. While the PEG/PCL hydrogel did not show sufficient mechanical properties for supporting the cylindrical shape of the construct, the high chondrogenesis level of chondrocytes in the PEG/PCL hydrogel displayed the potential of this material for tracheal tissue engineering.

For stem cell research, three‐dimensional (3D) hydrogels are increasingly recognized as more physiological systems than two‐dimensional culture plates due to bidirectional and 3D interaction of stem cells and surrounding matrix. Among various stem cells, mesenchymal stem cells (MSCs) are one of the most widely applied from bench to bedside. In 3D hydrogels, MSCs are allowed to actively remodel the surrounding matrix through proteolytic degradation and cell‐exerted force, which highly resembles in vivo situation. Notably, factors affecting hydrogel modifiability including matrix viscoelasticity and matrix degradability have been found to regulate adhesion, morphology, and fate decision of MSCs. In addition, MSCs within 3D hydrogels have been found to employ multiple mechanotransduction mechanisms including not only the classic integrin–actomyosin cytoskeleton system but also ion channels, microtubule cytoskeleton, and self‐secreted proteinaceous matrix. This review summarizes the effects of biophysical cues on MSCs differentiation in 3D hydrogels and underlying mechanobiology in a hope to update our readers' understanding of stem cell biology and guide tissue engineering.

Backgrounds: Both matrix stiffness and cell morphology have been found as important factors directing MSCs (mesenchymal stem cells) differentiation, but cells also spontaneously adapt their morphology under matrix stiffness stimulation. This study aimed to investigate the interplay of cell morphology and matrix stiffness on osteogenesis and adipogenesis of rBMSCs(rat bone BMSCs) on 2D substrates.Methods and Results: First, we modulated MSCs morphology through different bronectin (FN) concentrations on tissue culture plates (TCPs). We found FN promoted and osteogenesis of BMSCs while suppressing adipogenesis, mediated by FN-induced F-actin polymerization and cell spreading. Based on these ndings, we modulated BMSCs morphology on 0.5 kPa and 32 kPa CytoSoft ® plates through FN concentrations. We found BMSCs on 0.5 kPa substrates coated with 300μg/ml of FN manifested similarly spreading morphology with cells on 32 kPa substrates coated with 100 μg/ml of FN, and cells in both groups dominantly commit osteogenesis. On the other hand, BMSCs on 32 kPa substrates coated with 30μg/ml of FN manifested similarly restricted morphology with cells in on 0.5 kPa substrates with 100μg/ml of FN, and in both groups cells mainly commit adipogenesis. Immuno uorescence staining indicated YAP/TAZ mainly located in cytoplasm when cells exhibited restricted morphology on stiff matrices, while exhibiting signi cant nuclear translocation when cells spread on soft matrices.Conclusions: Cell morphology overrode effects of matrix stiffness on BMSCs differentiation through more robust regulation of YAP/TAZ. Matrix stiffness depended on cell morphology to regulate osteogenesis and adipogenesis of BMSCs.

Objectives: Cephalometric analysis is essential for diagnosis, treatment planning and outcome assessment of orthodontics and orthognathic surgery. Utilizing artificial intelligence (AI) to achieve automated landmark localization has proved feasible and convenient. However, current systems remain insufficient for clinical application, as patients exhibit various malocclusions in cephalograms produced by different manufacturers while limited cephalograms were applied to train AI in these systems. Methods: A robust and clinically applicable artificial intelligence system was proposed for automatic cephalometric analysis. First, 9870 cephalograms taken by different radiography machines with various malocclusions of patients were collected from 20 medical institutions. Then 30 landmarks of all these cephalogram samples were manually annotated to train an artificial intelligence system, composed of a two-stage convolutional neural network (CNN) and a software-as-a-service (SaaS) system. Further, more than 100 orthodontists participated to refine the AI-output landmark localizations and re-train this system. Results: The average landmark prediction error of this system was as low as 0.94 ± 0.74 mm and the system achieved an average classification accuracy of 89.33%. Conclusions: An automatic cephalometric analysis system based on CNN was proposed, which can realize automatic landmark location and cephalometric measurements classification. This system showed promise in improving diagnostic efficiency in clinical circumstances.

Stem cells are promising candidates for cell-based therapies in diverse conditions including regenerating damaged tissues, treating inflammation in virtue of sepsis, acute renal failure, and cardiovascular disease. Advancement of these therapies relies on the ability to guide stem cells to migrate directly and differentiate towards specific cell phenotypes. During the past decade, many researchers have demonstrated that exogenous applied forces could significantly affect the migration and lineage differentiation of stem cells. Besides, recent advances have highlighted the critical role of internal forces due to cellmatrix interaction in the function of stem cells. Stem cells can generate contractile forces to sense the mechanical properties of cell-generated force microenvironment, and thereby perceive mechanical information that directs broad aspects of stem cell functions, including migration and lineage commitment. In the review, we recount the cell-generated force microenvironment of stem cells and discuss the interactions between cell-generated forces with migration and differentiation of stem cells. We also summarize key experimental evidence of a tight linkage between migration and lineage differentiation of stem cells and pose important unanswered questions in this field.

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