IGF2BP3 prevent HMGB1 mRNA decay in bladder cancer and development.

BACKGROUND: IGF2BP3 functions as an RNA-binding protein (RBP) and plays a role in the posttranscriptional control of mRNA localization, stability, and translation. Its dysregulation is frequently associated with tumorigenesis across various cancer types. Nonetheless, our understanding of how the expression of the IGF2BP3 gene is regulated remains limited. The specific functions and underlying mechanisms of IGF2BP3, as well as the potential benefits of targeting it for therapeutic purposes in bladder cancer, are not yet well comprehended. METHODS: The mRNA and protein expression were examined by RT-qPCR and western blotting, respectively. The methylation level of CpG sites was detected by Bisulfite sequencing PCR (BSP). The regulation of IGF2BP3 expression by miR-320a-3p was analyzed by luciferase reporter assay. The functional role of IGF2BP3 was determined through proliferation, colony formation, wound healing, invasion assays, and xenograft mouse model. The regulation of HMGB1 by IGF2BP3 was investigated by RNA immunoprecipitation (RIP) and mRNA stability assays. RESULTS: We observed a significant elevation in IGF2BP3 levels within bladder cancer samples, correlating with more advanced stages and grades, as well as an unfavorable prognosis. Subsequent investigations revealed that the upregulation of IGF2BP3 expression is triggered by copy number gain/amplification and promoter hypomethylation in various tumor types, including bladder cancer. Furthermore, miR-320a-3p was identified as another negative regulator in bladder cancer. Functionally, the upregulation of IGF2BP3 expression exacerbated bladder cancer progression, including the proliferation, migration, and invasion of bladder cancer. Conversely, IGF2BP3 silencing produced the opposite effects. Moreover, IGF2BP3 expression positively correlated with inflammation and immune infiltration in bladder cancer. Mechanistically, IGF2BP3 enhanced mRNA stability and promoted the expression of HMGB1 by binding to its mRNA, which is a factor that promotes inflammation and orchestrates tumorigenesis in many cancers. Importantly, pharmacological inhibition of HMGB1 with glycyrrhizin, a specific HMGB1 inhibitor, effectively reversed the cancer-promoting effects of IGF2BP3 overexpression in bladder cancer. Furthermore, the relationship between HMGB1 mRNA and IGF2PB3 is also observed in mammalian embryonic development, with the expression of both genes gradually decreasing as embryonic development progresses. CONCLUSIONS: Our present study sheds light on the genetic and epigenetic mechanisms governing IGF2BP3 expression, underscoring the critical involvement of the IGF2BP3-HMGB1 axis in driving bladder cancer progression. Additionally, it advocates for the investigation of inhibiting IGF2BP3-HMGB1 as a viable therapeutic approach for treating bladder cancer.

Tungsten oxide polymorphs and their multifunctional applications.

Owing to the natural abundance, easy availability, high stability, non-stoichiometry, and chemical diversity, considerable interest has been devoted to tungsten oxide (WO3-x) nanomaterials, and many advances have been achieved ranging from traditional catalysts and electronics to emerging artificial intelligence. This review focuses on recent progress of WO3-x polymorphs and their multifunctional applications. The structural diversity and crystal phase transitions of WO3-x and recent advances on the general synthesis of various WO3-x nanostructures are first summarized, since the crystal structure and morphology adjustment obviously affect the physiochemical merits of WO3-x materials. Then, their applications and related mechanisms in different fields are demonstrated, such as gas sensing, chromogenic (electro-, photo-, gaso-, and thermochromic), photocatalytic (pollutant degradation and water splitting), and emerging applications (biomedical, antibiotic, and artificial intelligence). With the advances highlighted here and the ongoing research efforts, the continuous breakthrough in functionalized WO3-x nanostructure and their attractive applications is foreseeable in the future.

Evolution of Welding Residual Stresses within Cladding and Substrate during Electroslag Strip Cladding.

Hydrogenation reactors are important oil-refining equipment that operate in high-temperature and high-pressure hydrogen environments and are commonly composed of 2.25Cr-1Mo-0.25V steel. For a hydrogenation reactor with a plate-welding structure, the processes and effects of welding residual stress (WRS) are very complicated due to the complexity of the welding structure. These complex welding residual stress distributions affect the service life of the equipment. This study investigates the evolution of welding residual stress during weld-overlay cladding for hydrogenation reactors using the finite element method (FEM). A blind hole method is applied to verify the proposed model. Unlike the classical model, WRS distribution in a cladding/substrate system in this study was found to be divided into three regions: the cladding layer, the stress-affected layer (SAL), and the substrate in this study. The SAL is defined as region coupling affected by the stresses of the cladding layer and substrate at the same time. The evolution of residual stress in these three regions was thoroughly analyzed in three steps with respect to the plastic-strain state of the SAL. Residual stress was rapidly generated in Stage 1, reaching about -440 MPa compression stress in the SAL region at the end of this stage after 2.5 s. After cooling for 154 s, at the end of Stage 2, the WRS distribution was fundamentally shaped except for in the cladding layer. The interface between the cladding layer and substrate is the most heavily damaged region due to the severe stress gradient and drastic change in WRS during the welding process. The effects of substrate thickness and preheat temperature were evaluated. The final WRS in the cladding layer first increased with the increase in substrate thickness, and then started to decline when substrate thickness reached a large-enough value. WRS magnitudes in the substrate and SAL decreased with the increase in preheat temperature and substrate thickness. Compressive WRS in the cladding layer, on the other hand, increased with the increase in preheat temperature.

Concurrence of quantum anomalous Hall and topological Hall effects in magnetic topological insulator sandwich heterostructures.

The quantum anomalous Hall (QAH) effect is a consequence of non-zero Berry curvature in momentum space. The QAH insulator harbours dissipation-free chiral edge states in the absence of an external magnetic field. However, the topological Hall (TH) effect, a hallmark of chiral spin textures, is a consequence of real-space Berry curvature. Here, by inserting a topological insulator (TI) layer between two magnetic TI layers, we realized the concurrence of the TH effect and the QAH effect through electric-field gating. The TH effect is probed by bulk carriers, whereas the QAH effect is characterized by chiral edge states. The appearance of the TH effect in the QAH insulating regime is a consequence of chiral magnetic domain walls that result from the gate-induced Dzyaloshinskii-Moriya interaction and occurs during the magnetization reversal process in the magnetic TI sandwich samples. The coexistence of chiral edge states and chiral spin textures provides a platform for proof-of-concept dissipationless spin-textured spintronic applications.

A valley valve and electron beam splitter.

Developing alternative paradigms of electronics beyond silicon technology requires the exploration of fundamentally new physical mechanisms, such as the valley-specific phenomena in hexagonal two-dimensional materials. We realize ballistic valley Hall kink states in bilayer graphene and demonstrate gate-controlled current transmission in a four-kink router device. The operations of a waveguide, a valve, and a tunable electron beam splitter are demonstrated. The valley valve exploits the valley-momentum locking of the kink states and reaches an on/off ratio of 8 at zero magnetic field. A magnetic field enables a full-range tunable coherent beam splitter. These results pave a path to building a scalable, coherent quantum transportation network based on the kink states.