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PurposeThis study examines the customer strategies for small- and medium-sized manufacturing suppliers (SMMSs) in customer dominance markets, particularly regarding power asymmetry. It has two key objectives: (1) to identify factors impacting SMMSs' customer strategies, including technological and marketing capabilities and the importance of the main customer and (2) to examine the impact of these strategies on firm growth.Design/methodology/approachUsing the survey data on 279 Korean manufacturing suppliers in B2B markets, nine hypotheses were verified through a structural equation model (SEM). It involved capturing the varied influence of organizational capabilities on the two types of customer strategies and the link between customer strategy and firm growth.FindingsTechnology and marketing capabilities affect new customer acquisition directly, while in the case of main customer retention, marketing capability affects main customer retention through the overall satisfaction about the existing relationship. Although the importance of the main customer suppresses new customer acquisition strategies, SMMSs should actively pursue both customer acquisition and retention to promote firm growth.Originality/valueThe findings reveal how SMMSs, leveraging technological and marketing capabilities, can concurrently pursue new customer acquisition and main customer retention. Additionally, it empirically demonstrates the impact of the main customer’s importance on these customer strategies and underscores the positive impact of both strategies on firm growth. This provides a blueprint for a value-creation process linking capabilities, customer strategies and firm performance.

Hippo signaling controls the expression of genes regulating cell proliferation and survival and organ size. The regulation of core components in the Hippo pathway by phosphorylation has been extensively investigated, but the roles of ubiquitination–deubiquitination processes are largely unknown. To identify deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA screening and found that YOD1 controls biological responses mediated by YAP/TAZ. Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP/TAZ level. Furthermore, we show that the miR-21-mediated regulation of YOD1 is responsible for the cell-density-dependent changes in YAP/TAZ levels. Using a transgenic mouse model, we demonstrate that the inducible expression of YOD1 enhances the proliferation of hepatocytes and leads to hepatomegaly in a YAP/TAZ-activity-dependent manner. Moreover, we find a strong correlation between YOD1 and YAP expression in liver cancer patients. Overall, our data strongly suggest that YOD1 is a regulator of the Hippo pathway and would be a therapeutic target to treat liver cancer.

Aloe-emodin, an anthraquinone compound naturally derived from Rheum undulatum L., has gained extensive research attention owing to its various pharmacological effects, including its potential as an anticancer, antivirus, anti-inflammatory, antibacterial, and anti-parasitic agent. It has demonstrated notable inhibitory effects against various types of cancer and cancer cells. Prostate cancer is among the most commonly identified cancers globally and remains a leading cause of cancer-associated deaths in men, often presenting challenges in early detection due to its asymptomatic nature during initial stages. The aim of present study was to determine the biological activity of aloe-emodin obtained from Rheum undulatum L. involving activation of the p53-dependent pathway in certain human prostate cancer cell lines. We explored the mechanisms underlying the anticancer effects of aloe-emodin using LNCaP cells, which include p53-wild type and phosphatase and tensin homolog-deficient mutated genes, a widely studied model in genomic research. Aloe-emodin induced apoptosis in LNCaP cells through several mechanisms, including upregulation of the cleavage of caspase-8 (a cross-linked promoter of cell death signals), phosphorylation of p53 at serine 15, DNA fragmentation, cleavage of poly [ADP-ribose] polymerase, and promotion of cell death. These findings strongly indicated that aloe-emodin's anticancer properties in human prostate cancer involve the activation of p53-induced cellular senescence. Conclusively, the findings of this study imply that aloe-emodin extracted from Rheum undulatum L. is a potential therapeutic compound for adjuvant chemotherapy that induces apoptosis and pyroptosis, an innate immune response, in preventing the progression of precancerous lesions in patients with prostate cancer.

For chronic kidney disease, regeneration of lost nephrons with human kidney organoids derived from induced pluripotent stem (iPS) cells is proposed to be an attractive potential therapeutic option. It remains unclear, however, whether organoids transplanted into kidneys in vivo would be safe or functional. Here, we purified kidney organoids and transplanted them beneath the kidney capsules of immunodeficient mice to test their safety and maturity. Kidney organoid grafts survived for months after transplantation and became vascularized from host mouse endothelial cells. Nephron-like structures in grafts appeared more mature than kidney organoids in vitro, but remained immature compared with the neighboring mouse kidney tissue. Ultrastructural analysis revealed filtration barrier-like structures, capillary lumens, and tubules with brush border in the transplanted kidney organoids, which were more mature than those of the kidney organoids in vitro but not as organized as adult mammalian kidneys. Immaturity was a common feature of three separate differentiation protocols by immunofluorescence analysis and single cell RNA sequencing. Stroma of transplanted kidney organoid grafts were filled with vimentin-positive mesenchymal cells, and chondrogenesis, cystogenesis, and stromal expansion were observed in the long term. Transcription profiles showed that long-term maintenance after kidney organoid transplantation induced transcriptomic reprogramming with prominent suppression of cell-cycle-related genes and upregulation of extracellular matrix organization. Our data suggest that kidney organoids derived from iPS cells may be transplantable but strategies to improve nephron differentiation and purity are required before they can be applied in humans as a therapeutic option. Kidney disease: “Mini-organ” transplantation needs more work The safety and effectiveness of treating kidney disease by transplanting cultured clumps of kidney structures grown from stem cells and known as organoids need further investigation. Sun Ah Nam at The Catholic University of Korea in Seoul, with colleagues elsewhere in South Korea and the USA investigated the potential of the procedure by transplanting organoids made from human stem cells into mice. The animals were immunodeficient, thus avoiding rejection problems. The grafts generated resembled the blood-filtering structures of the kidney called nephrons, but remained insufficiently developed. Analyzing gene activity also suggested that the organoids were not adequately differentiating into the cells needed to treat disease effectively. The researchers conclude that methods to improve development and maturity of the organoids are required before organoid transplantation becomes a safe and viable treatment option in humans.

Angiogenesis is essential for successful tissue regeneration, particularly in clinical contexts such as ischemic injury, wound healing, and reconstructive therapies. However, the establishment of functional vasculature remains a major limitation in organoid-based systems. In this study, we developed vascularized organoid tissue modules (Angio-TMs) by incorporating human umbilical vein endothelial cells (HUVECs) into scaffold-free, self-organized constructs. Remarkably, the inclusion of HUVECs at 1% of the total cell population was sufficient to generate highly reproducible and structurally stable Angio-TMs, which exhibited clear endothelial differentiation and vascular functionality both in vitro and in vivo. Furthermore, inhibition of transforming growth factor (TGF)-β signaling in Angio-TMs led to a 2.5-fold increase in vessel length density, demonstrating a substantial enhancement in angiogenic potential. These findings highlight Angio-TMs as a robust and modular platform for engineering vascularized tissues and underscore their translational relevance in regenerative medicine and tissue transplantation.

Renal tubulointerstitial fibrosis (TIF) is the final pathway of various renal injuries that result in chronic kidney disease. The mammalian Hippo-Salvador signaling pathway has been implicated in the regulation of cell proliferation, cell death, tissue regeneration, and tumorigenesis. Here, we report that the Hippo-Salvador pathway plays a role in disease development in patients with TIF and in a mouse model of TIF. Mice with tubular epithelial cell (TEC)-specific deletions of Sav1 (Salvador homolog 1) exhibited aggravated renal TIF, enhanced epithelial-mesenchymal transition-like phenotypic changes, apoptosis, and proliferation after unilateral ureteral obstruction (UUO). Moreover, Sav1 depletion in TECs increased transforming growth factor (TGF)-β and activated β-catenin expression after UUO, which likely accounts for the abovementioned enhanced TEC fibrotic phenotype. In addition, TAZ (transcriptional coactivator with PDZ-binding motif), a major downstream effector of the Hippo pathway, was significantly activated in Sav1 -knockout mice in vivo . An in vitro study showed that TAZ directly regulates TGF-β and TGF-β receptor II expression. Collectively, our data indicate that the Hippo-Salvador pathway plays a role in the pathogenesis of TIF and that regulating this pathway may be a therapeutic strategy for reducing TIF.

Wastewater management is of considerable economic and environmental importance for the dyeing industry. Digital textile printing (DTP), which is based on sublimation transfer and does not generate wastewater, is currently being explored as an inkjet-based method of printing colorants onto fabric. It finds wide industrial applications with most poly(ethylene terephthalate) (PET) and nylon fibers. However, for additional industrial applications, it is necessary to use natural fibers, such as cotton. Therefore, to expand the applicability of DTP, it is essential to develop a novel reactive disperse dye that can interact with the fabric. In this study, we introduced a blocked isocyanate functional group into the dye to enhance binding to the fabric. The effect of sublimation transfer on fabrics as a function of temperature was compared using the newly synthesized reactive disperse dyes with different blocking groups based on pyrazole derivatives, such as pyrazole (Py), di-methylpyrazole (DMPy), and di-tert-butylpyrazole (DtBPy). Fabrics coated with the new reactive disperse dyes, including PET, nylon, and cotton, were printed at 190 °C, 200 °C, and 210 °C using thermal transfer equipment. In the case of the synthesized DHP-A dye on cotton at 210 °C, the color strength was 2.1, which was higher than that of commercial dyes and other synthesized dyes, such as DMP-A and DTP-A. The fastness values of the synthesized DHP-A were measured on cotton, and it was found that the washing and light fastness values on cotton are higher than those of commercial dyes. This study confirmed the possibility of introducing isocyanate groups into reactive disperse dyes.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by aberrant fibroblast activation, lysosomal dysfunction, and cellular senescence. Transcriptomic analyses have identified ependymin-related 1 (EPDR1) as a fibroblast-enriched gene in IPF, but its biological function remains unclear. EPDR1 expression was assessed in lung fibroblasts, lung tissues, bronchoalveolar lavage fluid (BALF), and serum from IPF patients and controls using qPCR, Western blotting, ELISA, and immunohistochemistry. Lysosomal function, autophagic flux, and senescence markers were analyzed in primary fibroblasts following siRNA-mediated EPDR1 knockdown. EPDR1 was significantly upregulated in IPF-derived fibroblasts and localized to fibrotic regions enriched with α-SMA+, COL1A1+, and FN1+ myofibroblasts of IPF-derived lung tissues. EPDR1 levels were markedly elevated in the BALF and serum of IPF patients and correlated with increased mortality. IPF fibroblasts exhibited reduced lysosomal acidification and impaired autophagic flux, indicated by p62 and LC3B accumulation. EPDR1 knockdown restored lysosomal function; enhanced autophagic degradation; and reduced senescence markers, including p21, p16, and SA-β-gal activity. EPDR1 drives lysosomal dysfunction and fibroblast senescence in IPF. Its elevated expression in lung tissue and biological fluids, together with its association with prognosis, highlights EPDR1 as a potential biomarker and therapeutic target in IPF.

Purpose The extent of honeycombing and reticulation predict the clinical prognosis of IPF. Emphysema, consolidation, and ground glass opacity are visible in HRCT scans. To date, there have been few comprehensive studies that have used these parameters. We conducted automated quantitative analysis to identify predictive parameters for clinical outcomes and then grouped the subjects accordingly. Methods CT images were obtained while patients held their breath at full inspiration. Parameters were analyzed using an automated lung texture quantification system. Cluster analysis was conducted on 159 IPF patients and clinical profiles were compared between clusters in terms of survival. Results Kaplan-Meier analysis revealed that survival rates declined as fibrosis, reticulation, honeycombing, consolidation, and emphysema scores increased. Cox regression analysis revealed that reticulation had the most significant impact on survival rate, followed by honeycombing, consolidation, and emphysema scores. Hierarchical and K-means cluster analyses revealed 3 clusters. Cluster 1 ( n  = 126) with the lowest values for all parameters had the longest survival duration, and relatively-well preserved FVC and DLCO. Cluster 2 ( n  = 15) with high reticulation and consolidation scores had the lowest FVC and DLCO values with a predominance of female, while cluster 3 ( n  = 18) with high honeycombing and emphysema scores predominantly consisted of male smokers. Kaplan-Meier analysis revealed that cluster 2 had the lowest survival rate, followed by cluster 3 and cluster 1. Conclusion Automated quantitative CT analysis provides valuable information for predicting clinical outcomes, and clustering based on these parameters may help identify the high-risk group for management.

Respiratory distress syndrome (RDS), which is induced by insufficient production of surfactant, is the leading cause of mortality in preterm babies. Although several transcription factors are known to be involved in surfactant protein expression, the molecular mechanisms and signaling pathways upstream of these transcription factors have remained elusive. Here, using mammalian Hippo kinases (Mst1/2, mammalian sterile 20-like kinase 1/2) conditional knockout mice, we demonstrate that Mst1/2 kinases are critical for orchestration of transcription factors involved in surfactant protein homeostasis and prevention of RDS. Mice lacking Mst1/2 in the respiratory epithelium exhibited perinatal mortality with respiratory failure and their lungs contained fewer type I pneumocytes and more immature type II pneumocytes lacking microvilli, lamellar bodies, and surfactant protein expression, pointing to peripheral lung immaturity and RDS. In contrast to previous findings of YAP (Yes-associated protein)-mediated canonical Hippo signaling in the liver and intestine, loss of Mst1/2 kinases induced the defects in pneumocyte differentiation independently of YAP hyperactivity. We instead found that Mst1/2 kinases stabilized and phosphorylated the transcription factor Foxa2 (forkhead box A2), which regulates pneumocyte maturation and surfactant protein expression. Taken together, our results suggest that the mammalian Hippo kinases play crucial roles in surfactant homeostasis and coordination of peripheral lung differentiation through regulation of Foxa2 rather than of YAP.