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Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulated in HCC tissues and inversely correlated with miR-124 expression. The overexpression of miR-124 decreased AQP3 expression. Indeed, AQP3 overexpression promoted cell proliferation and migration, whereas miR-124 knockdown suppressed cell proliferation and migration. Furthermore, we found that circular RNA HIPK3 (circHIPK3) acted as a miR-124 sponge and regulated the expression of the miR-124 target gene AQP3. circHIPK3 was upregulated in HCC tissues and positively correlated with AQP3 expression. Thus, silencing circHIPK3 inhibited cell proliferation and migration by downregulating AQP3 expression. Moreover, miR-124 inhibition rescued circHIPK3 knockdown induced reduction in cell proliferation and migration, as well as AQP3 expression. In vivo experiments also confirmed that circHIPK3 regulated xenograft tumor growth via the miR-124-AQP3 axis. These observations indicate a possible novel therapeutic strategy involving circular RNAs in HCC.

In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant immune cells, which act as a key regulator in tumorigenesis and progression. Increasing evidence have demonstrated that the TME alters the nature of macrophages to maintain dynamic tissue homeostasis, allowing TAMs to acquire the ability to stimulate angiogenesis, promote tumor metastasis and recurrence, and suppress anti-tumor immune responses. Furthermore, tumors with high TAM infiltration have poor prognoses and are resistant to treatment. In the field of solid tumor, the exploration of tumor-promoting mechanisms of TAMs has attracted much attention and targeting TAMs has emerged as a promising immunotherapeutic strategy. Currently, the most common therapeutic options for targeting TAMs are as follows: the deletion of TAMs, the inhibition of TAMs recruitment, the release of phagocytosis by TAMs, and the reprogramming of macrophages to remodel their anti-tumor capacity. Promisingly, the study of chimeric antigen receptor macrophages (CAR-Ms) may provide even greater benefit for patients with solid tumors. In this review, we discuss how TAMs promote the progression of solid tumors as well as summarize emerging immunotherapeutic strategies that targeting macrophages.

Cancer metastasis is responsible for the vast majority of cancer‐related deaths worldwide. In contrast to numerous discoveries that reveal the detailed mechanisms leading to the formation of the primary tumor, the biological underpinnings of the metastatic disease remain poorly understood. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle, and grow at other parts of the body. Epithelial‐mesenchymal transition and anoikis resistance of tumor cells are the main forces to promote metastasis, and multiple components in the tumor microenvironment and their complicated crosstalk with cancer cells are closely involved in distant metastasis. In addition to the three cornerstones of tumor treatment, surgery, chemotherapy, and radiotherapy, novel treatment approaches including targeted therapy and immunotherapy have been established in patients with metastatic cancer. Although the cancer survival rate has been greatly improved over the years, it is still far from satisfactory. In this review, we provided an overview of the metastasis process, summarized the cellular and molecular mechanisms involved in the dissemination and distant metastasis of cancer cells, and reviewed the important advances in interventions for cancer metastasis. Cancer metastasis is a complex process in which cancer cells escape from the primary tumor, settle and grow at other parts of the body. A variety of stromal cells, immune cells and other molecular components surrounding the tumor provide signals that enhance the metastatic potential of cancer cells. With the deepening understanding of mechanisms of tumorigenesis and metastasis in recent years, a plethora of treatment approaches have been established in patients with metastatic cancer.

BMP signaling plays an important role in dentin development. BMPs and antagonists regulate odontoblast differentiation and downstream gene expression via canonical Smad and non-canonical Smad signaling pathways. The interaction of BMPs with their receptors leads to the formation of complexes and the transduction of signals to the canonical Smad signaling pathway (for example, BMP ligands, receptors, and Smads) and the non-canonical Smad signaling pathway (for example, MAPKs, p38, Erk, JNK, and PI3K/Akt) to regulate dental mesenchymal stem cell/progenitor proliferation and differentiation during dentin development and homeostasis. Both the canonical Smad and non-canonical Smad signaling pathways converge at transcription factors, such as Dlx3, Osx, Runx2, and others, to promote the differentiation of dental pulp mesenchymal cells into odontoblasts and downregulated gene expressions, such as those of DSPP and DMP1. Dysregulated BMP signaling causes a number of tooth disorders in humans. Mutation or knockout of BMP signaling-associated genes in mice results in dentin defects which enable a better understanding of the BMP signaling networks underlying odontoblast differentiation and dentin formation. This review summarizes the recent advances in our understanding of BMP signaling in odontoblast differentiation and dentin formation. It includes discussion of the expression of BMPs, their receptors, and the implicated downstream genes during dentinogenesis. In addition, the structures of BMPs, BMP receptors, antagonists, and dysregulation of BMP signaling pathways associated with dentin defects are described.

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells 1 – 4 . The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses 5 , 6 . Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor 7 , 8 . It catalyses the synthesis of cyclic GMP-AMP (cGAMP) 9 – 12 , which stimulates the induction of type I interferons through the STING–TBK1–IRF-3 signalling axis 13 – 15 . STING oligomerizes after binding of cGAMP, leading to the recruitment and activation of the TBK1 kinase 8 , 16 . The IRF-3 transcription factor is then recruited to the signalling complex and activated by TBK1 8 , 17 – 20 . Phosphorylated IRF-3 translocates to the nucleus and initiates the expression of type I interferons 21 . However, the precise mechanisms that govern activation of STING by cGAMP and subsequent activation of TBK1 by STING remain unclear. Here we show that a conserved PLPLRT/SD motif within the C-terminal tail of STING mediates the recruitment and activation of TBK1. Crystal structures of TBK1 bound to STING reveal that the PLPLRT/SD motif binds to the dimer interface of TBK1. Cell-based studies confirm that the direct interaction between TBK1 and STING is essential for induction of IFNβ after cGAMP stimulation. Moreover, we show that full-length STING oligomerizes after it binds cGAMP, and highlight this as an essential step in the activation of STING-mediated signalling. These findings provide a structural basis for the development of STING agonists and antagonists for the treatment of cancer and autoimmune disorders. A molecular model of STING-mediated signalling is proposed, as structural analysis identifies a crucial motif for the binding of TBK1 to STING, and a separate model involved in IRF-3 binding.

How to improve the success of new project development through the collection of resources in the preliminary stages of new project development is a new area of research. Given the speed and magnitude of changes in the folk sports market environment, this study analyses the impact of tapping folk tourism resources on sports projects at the project development stage. Through stratified regression analyses of 600 Chinese firms engaged in folk sports project development, this paper finds that tapping internal tourism resources positively affects the Fuzzy Front-End Performance of incremental innovative project development. In contrast, tapping external tourism resources positively affects the Fuzzy Front-End Performance of breakthrough innovation projects. The study also indicates that the speed of environmental change (SEC) positively moderates the relationship between exploring external tourism resources (ERS) and Fuzzy Front-End Performance of incremental innovation projects. In contrast, the magnitude of environmental change (MEC) negatively moderated the relationship between internal tourism resource exploration (IRS) and the FFE-P of similar projects.

The scouring and sedimentation of wharf bank slopes significantly impact port safety and efficiency. To overcome the limitations of existing monitoring technologies in real-time capability, adaptability, and precision, this study introduces an innovative device based on distributed fiber optic sensing technology. By analyzing changes in the temperature gradient at the water–soil interface, the device enables dynamic monitoring of the results of scouring and sedimentation processes. It employs a modular design, integrating a linear heat source with fiber optic temperature sensing to capture high-resolution changes. Laboratory experiments evaluated variables such as heating duration, pipe material, pipe diameter, and fiber winding pitch. Results show optimal performance with a 20-min heating duration, with PVC sensors offering higher sensitivity and steel sensors providing greater stability. This study presents a high-precision, real-time solution for monitoring wharf bank slopes, offering insights for equipment optimization and engineering applications.

Cellular senescence occurs in proliferating cells as a consequence of various triggers including telomere shortening, DNA damage, and inappropriate expression of oncogenes. The senescent state is accompanied by failure to reenter the cell cycle under mitotic stimulation, resistance to cell death and enhanced secretory phenotype. A growing number of studies have convincingly demonstrated a paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. Cellular senescence was initially described as a physiological suppressor mechanism of tumor cells, because cancer development requires cell proliferation. However, there is growing evidence that senescent cells may contribute to oncogenesis, partly in a senescence-associated secretory phenotype (SASP)-dependent manner. On the one hand, SASP prevents cell division and promotes immune clearance of damaged cells, thereby avoiding tumor development. On the other hand, SASP contributes to tumor progression and relapse through creating an immunosuppressive environment. In this review, we performed a review to summarize both bright and dark sides of senescence in cancer, and the strategies to handle senescence in cancer therapy were also discussed.

This article investigates the finite‐time tracking control problem for disturbed non‐holonomic systems with input saturation and state constraints. Input saturation is ensured by utilizing saturated state feedback and designing auxiliary variables. A rigorous design procedure, which combines barrier Lyapunov function‐based backstepping and neural networks, is introduced to satisfy state constraints and overcome the influence of lumped disturbances. A finite‐time filter is developed to address the explosion of complexity problem. Together with relay switching, the designed saturated controller guarantees that the tracking errors converge to arbitrarily small neighbourhoods around zero within a finite time. Stability analysis indicates that all closed‐loop system signals maintain bounded, and the desired input and state constraints are not violated throughout the control process. To demonstrate the effectiveness of the proposed approach, simulation and experimental results on a wheeled mobile robot are presented. This article presents a systematic NN‐based finite‐time practical tracking control for disturbed non‐holonomic systems subject to input saturation and state constraints. By dexterously using relay switching, dynamic surface control and finite‐time filters, it leads to a control process that is computationally simple.

The polycyclic aromatic hydrocarbon (PAH) concentrations in total suspended particulate matter (TSP) samples collected from October, 2021 to September, 2022 were analyzed to clarify the pollution characteristics and sources of 16 PAHs in the atmospheric TSP in Bengbu City. The ρ(PAHs) concentrations ranged from 1.71 to 43.85 ng/m 3 and higher concentrations were detected in winter, followed by spring, autumn, and summer. The positive matrix factorization analysis revealed that, in spring and summer, PAH pollution was caused mainly by industrial emissions, gasoline and diesel fuel combustion, whereas in autumn and winter, it was coal, biomass and natural gas combustion. The cluster and potential source factor analyses showed that long-range transport was a significant factor. During spring, autumn, and winter, the northern and northwestern regions had a significant impact, whereas the coastal area south of Bengbu had the greatest influence in summer. The health risk assessment revealed that the annual total carcinogenic equivalent concentration values for PAHs varied from 0.0159 to 7.437 ng/m 3 , which was classified as moderate. Furthermore, the annual incremental lifetime cancer risk values ranged from 1.431 × 10 −4 to 3.671 × 10 −3 for adults and from 6.823 × 10 −5 to 1.749 × 10 −3 for children, which were higher than the standard.