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Tissue fibrosis is a pathological condition that is associated with impaired epithelial repair and excessive deposition of extracellular matrix (ECM). Fibrotic lesions increase the risk of cancer in various tissues, but the mechanism linking fibrosis and cancer is unclear. Yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are core components of the Hippo pathway, which have multiple biological functions in the development, homeostasis, and regeneration of tissues and organs. YAP/TAZ act as sensors of the structural and mechanical features of the cell microenvironment. Recent studies have shown aberrant YAP/TAZ activation in both fibrosis and cancer in animal models and human tissues. In fibroblasts, ECM stiffness mechanoactivates YAP/TAZ, which promote the production of profibrotic mediators and ECM proteins. This results in tissue stiffness, thus establishing a feed-forward loop of fibroblast activation and tissue fibrosis. In contrast, in epithelial cells, YAP/TAZ are activated by the disruption of cell polarity and increased ECM stiffness in fibrotic tissues, which promotes the proliferation and survival of epithelial cells. YAP/TAZ are also involved in the epithelial–mesenchymal transition (EMT), which contributes to tumor progression and cancer stemness. Importantly, the crosstalk with transforming growth factor (TGF)-β signaling and Wnt signaling is essential for the profibrotic and tumorigenic roles of YAP/TAZ. In this article, we review the latest advances in the pathobiological roles of YAP/TAZ signaling and their function as a molecular link between fibrosis and cancer.

Generation of structural color is one of the essential functions realized by living organisms, and its industrial reproduction can result in numerous applications. From this viewpoint, the mechanisms, materials, analytical methods and fabrication technologies of the structural color are reviewed in this paper. In particular, the basic principles of natural photonic materials, the ideas developed from these principles, the directions of applications and practical industrial realizations are presented by summarizing the recent research results.

Fibroblasts constitute a ubiquitous mesenchymal cell type and produce the extracellular matrix (ECM) of connective tissue, thereby providing the structural basis of various organs. Fibroblasts display differential transcriptional patterns unique to the organ of their origin and they can be activated by common stimuli such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF) signaling. Cancer-associated fibroblasts (CAFs) reside in the cancer tissue and contribute to cancer progression by influencing cancer cell growth, invasion, angiogenesis and tumor immunity. CAFs impact on the tumor microenvironment by remodeling the ECM and secreting soluble factors such as chemokines and growth factors. Differential expression patterns of molecular markers suggest heterogeneous features of CAFs in terms of their function, pathogenic role and cellular origin. Recent studies elucidated the bimodal action of CAFs on cancer progression and suggest a subgroup of CAFs with tumor-suppressive effects. This review attempts to describe cellular features of colorectal CAFs with an emphasis on their heterogeneity and functional diversity.

Small cell lung cancer (SCLC) is a highly aggressive and metastatic malignancy that shows rapid development of chemoresistance and a high rate of recurrence. Recent genome and transcriptome studies have provided the whole landscape of genomic alterations and gene expression changes in SCLC. In light of the inter‐individual heterogeneity of SCLC, subtyping of SCLC might be helpful for prediction of therapeutic response and prognosis. Based on the transcriptome data of SCLC cell lines, we undertook transcriptional network‐defined SCLC classification and identified a unique SCLC subgroup characterized by relatively high expression of Hippo pathway regulators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) (YAP/TAZ subgroup). The YAP/TAZ subgroup displayed adherent cell morphology, lower expression of achaete‐scute complex homolog 1 (ASCL1) and neuroendocrine markers, and higher expression of laminin and integrin. YAP knockdown caused cell morphological alteration reminiscent of floating growth pattern in many SCLC cell lines, and microarray analyses revealed a subset of genes regulated by YAP, including Ajuba LIM protein (AJUBA). AJUBA also contributed to cell morphology regulation. Of clinical importance, SCLC cell lines of the YAP/TAZ subgroup showed unique patterns of drug sensitivity. Our findings shed light on a subtype of SCLC with YAP and TAZ expression, and delineate molecular networks underlying the heterogeneity of SCLC. Subtypes of SCLC cell lines defined by expression patterns of transcription factors. Two‐dimensional hierarchical clustering of expression levels of 1520 transcription factors in SCLC cell lines.

This study aimed to identify muscle synergies of the lower limb during treadmill running on level and inclined ground. Eight subjects ran on a treadmill at three speeds (2.5, 3.3, and 4.1 m/s) and two grades (level and 10% grade). Surface electromyographic (EMG) signals were recorded from 10 muscles of the lower limb, including deeper muscles such as vastus intermedius, adductor magnus, and adductor longus. Muscle synergies were extracted applying a non-negative matrix factorization algorithm, and relative co-activations across muscles and the temporal recruitment pattern were identified by muscle synergy vector and synergy activation coefficient, respectively. The scalar product between pairs of synergy vectors and synergy activation coefficients during level and uphill running conditions were analyzed as a similarity index, with values above 0.8 recognized as similar. Approximately 4 muscle synergies controlled the majority of variability in 10 EMGs during running, and were common between level and uphill conditions. At each running speed, inter-condition similarity was observed in synergy vector ( r  > 0.83) and synergy activation coefficients ( r  > 0.84) at each type of synergy. These results suggest that types of synergy are consistent between level and uphill running.

The recent emergence of antibiotic-resistant bacteria requires the development of new antibiotics or new agents capable of enhancing antibiotic activity. This study evaluated the antibacterial activity of lysozyme-chitosan oligosaccharide conjugates (LYZOX) against Pseudomonas aeruginosa, Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA), which should resolve the problem of antibiotic-resistant bacteria. Bactericidal tests showed that LYZOX killed 50% more P. aeruginosa (NBRC 13275), A. baumannii and MRSA than the control treatment after 60 min. In addition, LYZOX was shown to inhibit the growth of P. aeruginosa (NBRC 13275 and PAO1), A. baumannii and MRSA better than its components. To elucidate the antibacterial mechanism of LYZOX, we performed cell membrane integrity assays, N-phenyl-1-naphthylamine assays, 2-nitrophenyl β-D-galactopyranoside assays and confocal laser scanning microscopy. These results showed that LYZOX affected bacterial cell walls and increased the permeability of the outer membrane and the plasma membrane. Furthermore, each type of bacteria treated with LYZOX was observed by electron microscopy. Electron micrographs revealed that these bacteria had the morphological features of both lysozyme-treated and chitosan oligosaccharide-treated bacteria and that LYZOX destroyed bacterial cell walls, which caused the release of intracellular contents from cells. An acquired drug resistance test revealed that these bacteria were not able to acquire resistance to LYZOX. The hemolytic toxicity test demonstrated the low hemolytic activity of LYZOX. In conclusion, LYZOX exhibited antibacterial activity and low drug resistance in the presence of P. aeruginosa, A. baumannii and MRSA and showed low hemolytic toxicity. LYZOX affected bacterial membranes, leading to membrane disruption and the release of intracellular contents and consequent bacterial cell death. LYZOX may serve as a novel candidate drug that could be used for the control of refractory infections.

Static stretching and proprioceptive neuromuscular facilitation stretching techniques can modulate specific neural mechanisms to improve the range of motion. However, the effects of modulation of these neural pathways on changes in the range of motion with static stretching remain unclear. Patterned electrical stimulation of the sensory nerve induces plastic changes in reciprocal Ia inhibition. The present study examined the effects of patterned electrical stimulation and static stretching on a range of motion and passive torque in plantarflexion muscles. The subjects were 14 young men (age 20.8 ± 1.3 years). The effects of patterned electrical stimulation (10 pulses at 100 Hz every 1.5 s) or uniform electrical stimulation (one pulse every 150 ms) to the common peroneal nerve for 20 min on reciprocal Ia inhibition of the Hoffman reflex (H-reflex) were examined. Reciprocal Ia inhibition was evaluated as short-latency suppression of the soleus H-reflex by conditioning stimulation of the common peroneal nerve. Then, the effects of transcutaneous electrical nerve stimulation (patterned electrical stimulation or uniform electrical stimulation) or prolonged resting (without electrical stimulation) and static 3-min stretching on the maximal dorsiflexion angle and passive torque were investigated. The passive ankle dorsiflexion test was performed on an isokinetic dynamometer. Stretch tolerance and stiffness of the muscle-tendon unit were evaluated by the peak and slope of passive torques, respectively. Patterned electrical stimulation significantly increased reciprocal Ia inhibition of soleus H-reflex amplitude (9.7 ± 6.1%), but uniform electrical stimulation decreased it significantly (19.5 ± 8.8%). The maximal dorsiflexion angle was significantly changed by patterned electrical stimulation (4.0 ± 1.4°), uniform electrical stimulation (3.8 ± 2.3°), and stretching without electrical stimulation (2.1 ± 3.3°). The increase in stretch tolerance was significantly greater after patterned electrical stimulation and uniform electrical stimulation than after stretching without electrical stimulation. Stiffness of the muscle-tendon unit was significantly decreased by patterned electrical stimulation, uniform electrical stimulation, and stretching without electrical stimulation. Transcutaneous electrical nerve stimulation and static stretching improve stretch tolerance regardless of the degree of reciprocal Ia inhibition.

Stretching‐induced impairments of muscle performance are attributed to neural adaptations and mechanical changes. Inhibition of muscle spindle sensitivity appears to have long‐lasting effects after stretching. However, whether a dose–response relationship exists between stretching duration and muscle spindle sensitivity remains unclear. The present study aimed to reveal the effect of static stretching duration on modulation of muscle spindle sensitivity in the soleus muscle. The present study used data obtained from 19 young men. Static stretching intervention involved five 1‐min stretches with 1‐min intervals between stretches under maximal dorsiflexion. The Hoffmann‐reflex (H‐reflex) and tendon‐reflex (T‐reflex) were recorded from the soleus before and during stretching, at intervals between stretching. Time‐course changes in H‐reflex and T‐reflex amplitudes from baseline (i.e., before stretching) were calculated. The H‐reflex amplitude depressed 51.5%–55.2% during static stretching, and these H‐reflex depressions recovered in the interval following each stretch. T‐reflex amplitudes depressed 71.2%–73.5% during static stretching, and these T‐reflex depressions remained following each interval. Inhibitions of the T‐reflex amplitude after the second to fifth stretches were not significantly stronger than that after the first static stretch. These results suggest that 1‐min static stretching under maximal dorsiflexion achieves sufficient modulation of muscle spindle sensitivity of the soleus.

Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS‐NEC) and unraveled its unique and organ‐specific genomic drivers. However, the epigenomic features of GIS‐NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS‐NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase‐accessible chromatin sequencing (ATAC‐seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super‐enhancer–related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss‐of‐function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS‐NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor‐promoting pathways were activated in the ELF3 signature–high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor‐promoting properties in NEC. Multiorgan comprehensive epigenomic analysis identified ELF3 as a super‐enhancer–associated transcription factor and revealed its oncogenic properties in neuroendocrine carcinoma.

This study sought to determine whether lower extremity muscle size, power and strength could be a determinant of whole-body maximal aerobic performance in athletes. 20 male and 19 female young athletes (18 ± 4 years) from various sporting disciplines participated in this study. All athletes performed a continuous ramp-incremental cycling to exhaustion for the determination of peak oxygen uptake ( V ˙ O 2 p e a k : the highest V ˙ O 2 over a 15-s period) and maximal power output (MPO: power output corresponding to V ˙ O 2 p e a k ). Axial scanning of the right leg was performed with magnetic resonance imaging, and anatomical cross-sectional areas (CSAs) of quadriceps femoris (QF) and hamstring muscles at 50% of thigh length were measured. Moreover, bilateral leg extension power and unilateral isometric knee extension and flexion torque were determined. All variables were normalised to body mass, and six independent variables ( V ˙ O 2 p e a k , CSAs of thigh muscles, leg extension power and knee extension and flexion torque) were entered into a forward stepwise multiple regression model with MPO being dependent variable for males and females separately. In the males, V ˙ O 2 p e a k was chosen as the single predictor of MPO explaining 78% of the variance. In the females, MPO was attributed to, in the order of importance, V ˙ O 2 p e a k (p < 0.001) and the CSA of QF (p = 0.011) accounting for 84% of the variance. This study suggests that while oxygen transport capacity is the main determinant of MPO regardless of sex, thigh muscle size also has a role in whole-body maximal aerobic performance in female athletes.