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Prostate cancer (PCa) is the second leading cause of cancer-related death among men in western countries. Evidence has indicated the significant role of the androgen receptor (AR) as the main driving factor in controlling the development of PCa, making androgen receptor inhibition (ARI) therapy a pivotal management approach. In addition, AR independent signaling pathways also contribute to PCa progression. One such signaling pathway that has garnered our attention is N6-Methyladenosine (m6A) signaling, which refers to a chemical modification on RNA with crucial roles in RNA metabolism and disease progression, including PCa. It is important to comprehensively summarize the role of each individual m6A regulator in PCa development and understand its interaction with AR signaling. This review aims to provide a thorough summary of the involvement of m6A regulators in PCa development, shedding light on their upstream and downstream signaling pathways. This summary sets the stage for a comprehensive review that would benefit the scientific community and clinical practice by enhancing our understanding of the biology of m6A regulators in the context of PCa.

Abstract Integrable systems constitute an essential part of modern physics. Traditionally, to approve a model is integrable one has to find its infinitely many symmetries or conserved quantities. In this letter, taking the well known Korteweg-de Vries and Boussinesq equations as examples, we show that it is enough to find only one nonlocal key-symmetry to guarantee the integrability. Starting from the nonlocal key-symmetry, recursion operator(s) and then infinitely many symmetries and Lax pairs can be successfully found.

Abstract Metastatic clear cell renal cell carcinoma (ccRCC) is a lethal sub-type of kidney cancer. Vascular mimicry (VM) has been postulated as an alternative route to supply tumors with nutrients, playing key role in tumor development. Whether VM development is linked to pazopanib efficacy, however, remains unclear. Here, our in vitro and in vivo models identified that VM development was profoundly increased in pazopanib resistant ccRCC as compared to the sensitive controls, which was due to the activation of IGFL2-AS1/AR/TWIST1 signaling. IGFL2-AS1, a m6A modified long coding RNA, was demethylated by METTL3/METTL14 complex and stabilized owing to its failing recognition by YTHDF2 upon chronic pazopanib treatment. Further mechanistic dissection illustrated that IGFL2-AS1 physically interacted with the 5’-UTR AR mRNA and neutralized the negative regulation of 5’-uORF (upstream open reading frame) on AR translation. Indeed, IGFL2-AS1 short of AR binding region failed to promote AR expression, VM formation and pazopanib resistance. In vivo xenografted mouse model also elucidated that inhibition of AR activity with enzalutamide or silence of IGFL2-AS1 with siRNAs all led to retarded growth of pazopanib resistant ccRCC tumors. Together, these results suggest that IGFL2-AS1 may represent a key player to mediate pazopanib-induced VM formation of ccRCC cells via regulating AR expression and targeting this newly identified IGFL2-AS1/AR signaling may help us to better suppress ccRCC VM formation and to increase the therapeutic efficacy of pazopanib.

Abstract Utilizing some conservation laws of (1+1)-dimensional integrable local evolution systems, it is conjectured that higher dimensional integrable equations may be regularly constructed by a deformation algorithm. The algorithm can be applied to Lax pairs and higher order flows. In other words, if the original lower dimensional model is Lax integrable (possesses Lax pairs) and symmetry integrable (possesses infinitely many higher order symmetries and/or infinitely many conservation laws), then the deformed higher order systems are also Lax integrable and symmetry integrable. For concreteness, the deformation algorithm is applied to the usual (1 + 1)-dimensional Korteweg-de Vries (KdV) equation and the (1 + 1)-dimensional Ablowitz-Kaup-Newell-Segur (AKNS) system (including nonlinear Schrödinger (NLS) equation as a special example). It is interesting that the deformed (3+1)-dimensional KdV equation is also an extension of the (1 + 1)-dimensional Harry-Dym (HD) type equations which are reciprocal links of the (1+1)-dimensional KdV equation. The Lax pairs of the (3 + 1)-dimensional KdV-HD system and the (2 + 1)-dimensional AKNS system are explicitly given. The higher order symmetries, i.e., the whole (3 + 1)-dimensional KdV-HD hierarchy, are also explicitly obtained via the deformation algorithm. The single soliton solution of the (3 + 1)-dimensional KdV-HD equation is implicitly given. Because of the effects of the deformation, the symmetric soliton shape of the usual KdV equation is no longer conserved and deformed to be asymmetric and/or multi-valued. The deformation conjecture holds for all the known (1 +1)-dimensional integrable local evolution systems that have been checked, and we have not yet found any counter-example so far. The introduction of a large number of (D + 1)-dimensional integrable systems of this paper explores a serious challenge to all mathematicians and theoretical physicists because the traditional methods are no longer directly valid to solve these integrable equations.

Background: Bortezomib (BTZ) is a powerful proteasome inhibitor that has been approved for the treatment of haematologic malignancies. Its effectiveness has been assessed against different types of solid tumours. BTZ is ineffective in most solid tumours because of drug resistance, including cholangiocarcinoma, which is associated with a proteasome bounce-back effect. However, the mechanism through which proteasome inhibitors induce the proteasome bounce-back effect remains largely unknown. Methods: Cholangiocarcinoma cells were treated with BTZ, cisplatin, or a combination of both. The mRNA levels of Nfe2l1 and proteasome subunit genes (PSMA1, PSMB7, PSMD1, PSMD11, PSMD14, and PSME4) were determined using quantitative real time polymerase chain reaction (qPCR). The protein levels of nuclear factor-erythroid 2-related factor 1 (Nfe2l1) and proteasome enzyme activity were evaluated using western blotting and proteasome activity assays, respectively. Transcriptome sequencing was performed to screen for potential transcription factors that regulate Nfe2l1 expression. The effect of zinc finger E-box-binding homeobox 1 (ZEB1) on the expression of Nfe2l1 and proteasome subunit genes, as well as proteasome enzyme activity, was evaluated after the knockdown of ZEB1 expression with siRNA before treatment with BTZ. The transcriptional activity of ZEB1 on the Nfe2l1 promoter was detected using dual-luciferase reporter gene and chromatin immunoprecipitation assays. Cell viability was measured using the cell counting kit-8 (CCK-8) assay and cell apoptosis was assessed using western blotting and flow cytometry. Results: Cisplatin treatment of BTZ-treated human cholangiocarcinoma cell line (RBE) suppressed proteasome subunit gene expression (proteasome bounce-back) and proteasomal enzyme activity. This effect was achieved by reducing the levels of Nfe2l1 mRNA and protein. Our study utilised transcriptome sequencing to identify ZEB1 as an upstream transcription factor of Nfe2l1, which was confirmed using dual-luciferase reporter gene and chromatin immunoprecipitation assays. Notably, ZEB1 knockdown using siRNA (si-ZEB1) hindered the expression of proteasome subunit genes under both basal and BTZ-induced conditions, leading to the inhibition of proteasomal enzyme activity. Furthermore, the combination treatment with BTZ, cisplatin, and si-ZEB1 significantly reduced the viability of RBE cells. Conclusions: Our study uncovered a novel mechanism through which cisplatin disrupts the BTZ-induced proteasome bounce-back effect by suppressing the ZEB1/Nfe2l1 axis in cholangiocarcinoma. This finding provides a theoretical basis for developing proteasome inhibitor-based strategies for the clinical treatment of cholangiocarcinoma and other tumours.

Fluorescence images enhancement is important as it can provide more information for medical diagnosis. In this work, we design three simple yet useful filters based on the combinations of mathematical functions, which are proved to be effective in strengthening the images acquired from the fluorescence microscope. Using these filters, detailed objects can be found in the dark sections of the fluorescence images. In addition, these filters can be used to enhance the low-light image, which provide satisfactory visual information and marginal profile for the blurred objects in the image. Moreover, these filters have been used to enhance the image with high degradation by the Gaussian noise, where clear edge profile can be extracted. Finally, we have shown that these filters can be utilized for the image compression. Compression ratio can be obtained to be 0.9688. This study shows the making of the filters with dual functions for the image enhancement and the image compression. Our designed filters are showing the potentials in the field of biomedical imaging and pattern identification.

As a new data acquisition technology, network telemetry has greatly enriched the diversity of data acquisition and expanded the range of traditional OAM data acquisition, whose goal is to realize real-time global network state visibility and traffic visibility.By combining with big data and AI technology, it can reduce human intervention and improve the operation and maintenance level of network automation.Firstly, the problems and challenges faced by the current IP network operation and maintenance were analyzed, and then it was elaborated that the network telemetry technology was the key enabler to realize the automatous network operation and maintenance.On this basis, the application of network telemetry technology in the IP network automatic operation and maintenance was investigated and discussed, and the reference and guidance for the automatic operation and maintenance of large-scale IP network were provided.

The accurate tooth surface modeling of the helical-face gear pair with linear contact cross axis is given. Based on the meshing theory, the mathematical model of the tooth surface of the helical-face gear with cross axis is established, and the discrete data points of the tooth surface are calculated. According to the tooth surface uniform discrete point output data, the tooth surface is reconstructed, the precise solid modeling of the face gear is realized and the meshing simulation is carried out. By using the tooth surface deviation method, accuracy of the model is evaluated, the model can be used for the digital design and manufacture of face gear.

The energy-intensive industrial sector (EIIS) occupies a majority of global CO2 emissions, but spatially monitoring the spatiotemporal dynamics of these emissions remains challenging. In this study, we used the Chinese province with the largest carbon emissions, Shandong Province, as an example to investigate the capacity of remotely sensed thermal anomaly products to identify annual industrial heat source (IHS) patterns at a 1 km resolution and estimated the carbon emissions of these sources using auxiliary datasets and the boosting regression tree (BRT) model. The IHS identification accuracy was evaluated based on two IHS references and further attributed according to corporate inventory data. We followed a bottom-up approach to estimate carbon emissions for each IHS object and conducted model fitting using the explanatory strength of the annual population density, nighttime light (NTL), and relevant thermal characteristic information derived from the Visible Infrared Imaging Radiometer Suite (VIIRS). We generated a time series of IHS distributions from 2012 to 2020 containing a total of over 3700 IHS pixels exhibiting better alignment with the reference data than that obtained in previous work. The results indicated that the identified IHSs mostly belonged to the EIIS, such as energy-related industries (e.g., thermal power plants) and heavy manufacturing industries (e.g., chemistry and cement plants), that primarily use coal and coke as fuel sources. The BRT model exhibited a good performance, explaining 61.9% of the variance in the inventory-based carbon emissions and possessing an index of agreement (IOA) of 0.83, suggesting a feasible goodness of fit of the model when simulating carbon emissions. Explanatory variables such as the population density, thermal power radiation, NTL, and remotely sensed thermal anomaly durations were found to be important factors for improving carbon emissions modeling. The method proposed in this study is useful to aid management agencies and policymakers in tracking the carbon footprint of the EIIS and regulating high-emission corporations to achieve carbon neutrality.

An AB modified KdV (AB-mKdV) system which can be used to describe two-place event is studied in this manuscript. Because the AB-mKdV system is considered as a special reduction of the famous AKNS system, the properties of the AKNS system are first revealed by using symmetry analysis. The nonlocal symmetries related to truncated Painlevé expansion, the finite transformation, and the symmetry reduction solutions of the AKNS system are presented. The corresponding Bäcklund transformations and the interaction solutions of the AB-mKdV system are constructed based on the special reduction. The results demonstrate that the AB-mKdV system possesses many kinds of interaction solutions, such as the interactions between kink and soliton and kink and cnoidal waves. The soliton can be changed from bright to dark during propagation.

Influence of the always-on service of 1ittle traffic on Ev-Do network was analyzed. Optimization solutions especia11y for the always-on service of 1ittle traffic were given. Also，the coping strategies such as wireless operation index forecast and traffic guidance were put forward.

A rotational fluid model which can be used to describe broad vortical flows ranging from large scale to the atmospheric mesoscale and the oceanic submesoscale is studied by the symmetry group theory. After introducing one scalar-, two vector-, and two tensor potentials, we find that the Lie symmetries of the extended system include many arbitrary functions of z and {z,t}. The obtained Lie symmetries are used to find some types of exact solutions. One of exact solutions can be used to qualitatively describe the three-dimensional structure of hurricanes.

Prostate cancer (PCa) is the second leading cause of cancer-related death among men in western countries. Evidence has indicated the significant role of the androgen receptor (AR) as the main driving factor in controlling the development of PCa, making androgen receptor inhibition (ARI) therapy a pivotal management approach. In addition, AR independent signaling pathways also contribute to PCa progression. One such signaling pathway that has garnered our attention is N6- Methyladenosine (m6A) signaling, which refers to a chemical modification on RNA with crucial roles in RNA metabolism and disease progression, including PCa. It is important to comprehensively summarize the role of each individual m6A regulator in PCa development and understand its interaction with AR signaling. This review aims to provide a thorough summary of the involvement of m6A regulators in PCa development, shedding light on their upstream and downstream signaling pathways. This summary sets the stage for a comprehensive review that would benefit the scientific community and clinical practice by enhancing our understanding of the biology of m6A regulators in the context of PCa. [ABSTRACT FROM AUTHOR]

This study investigated the corrosion and tribocorrosion behavior of CrN and CrAlN coatings deposited on steel through direct current magnetron sputtering. Additionally, the effects of Al addition on the microstructure, corrosion inhibition, and tribocorrosion behavior of CrN coatings were evaluated. Compared with the CrN coating, the CrAlN coating exhibited a denser columnar crystal structure and a higher hardness of 23.8 GPa. The CrAlN coating reacted with water to form Al2O3 and Cr2O3 films, which enhanced its corrosion resistance. Moreover, the addition of Al enhanced the wear resistance of the CrN coating and reduced the material loss due to corrosion, wear, and their synergistic effects. The CrAlN coating exhibited a low corrosion current density of 1.14 × 10−8 A/cm2, indicating a 92% reduction compared with the CrN coating. Furthermore, under either open circuit potential or anodic accelerated tribocorrosion conditions, the CrAlN coating featured significantly lower total material loss and synergistic material loss than the CrN coating, demonstrating higher corrosion and tribocorrosion protection. [ABSTRACT FROM AUTHOR]