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Despite widespread utilization of immunotherapy, treating immune-cold tumors remains a challenge. Multiomic analyses and experimental validation identified the OTUD4/CD73 proteolytic axis as a promising target in treating immune-suppressive triple negative breast cancer (TNBC). Mechanistically, deubiquitylation of CD73 by OTUD4 counteracted its ubiquitylation by TRIM21, resulting in CD73 stabilization inhibiting tumor immune responses. We further demonstrated the importance of TGF-[beta] signaling for orchestrating the OTUD4/CD73 proteolytic axis within tumor cells. Spatial transcriptomics profiling discovered spatially resolved features of interacting malignant and immune cells pertaining to expression levels of OTUD4 and CD73. In addition, ST80, a newly developed inhibitor, specifically disrupted proteolytic interaction between CD73 and OTUD4, leading to reinvigoration of cytotoxic [CD8.sup.+] T cell activities. In preclinical models of TNBC, ST80 treatment sensitized refractory tumors to anti-PD-LI therapy. Collectively, our findings uncover what we believe to be a novel strategy for targeting the immunosuppressive OTUD4/CD73 proteolytic axis in treating immune-suppressive breast cancers with the inhibitor ST80., Introduction Despite the widespread utilization of immunotherapy, the poor clinical response by immune-suppressive tumors is an emerging challenge in use of current immune checkpoint inhibitors. Triple negative breast cancers (TNBCs) [...]

Tuning immune‐cold tumor hot has largely attracted attention to improve cancer treatment, including immunotherapy and antibody‐drug conjugates (ADCs). Utilizing multiomic analyses and experimental validation, this work identifies a pivotal role for the USP10/B7‐H4 proteolytic axis in mediating the interplay between tumor immune responses and ADC efficacy, particularly for sacituzumab govitecan (SG) in treating triple negative breast cancers (TNBCs). Mechanistically, the inhibition of autocrine motility factor receptor (AMFR)‐mediated ubiquitylation of B7‐H4 by the deubiquitinase USP10 leads to the stabilization of B7‐H4, which suppresses tumor immune activity and reduces SG treatment effectiveness. Pharmacological inhibition of USP10 promotes the degradation of B7‐H4, enhancing tumor immunogenicity and consequently improving the tumor‐killing efficacy of SG. In preclinical TNBC models, suppression of USP10/B7‐H4 proteolytic axis is effective in increasing SG killing efficacy and reducing tumor growth, especially for the tumors with the USP10high/B7‐H7high signature. Collectively, these findings uncover a novel strategy for targeting the immunosuppressive molecule B7‐H4 for cancer therapy. [ABSTRACT FROM AUTHOR]

This study selected two sweet potato varieties as research subjects and conducted a field experiment using a two-factor design with two potassium (K) levels (K0 and K1) and five nitrogen (N) levels (N0–N4). The physiological changes in sweet potato leaves under different N and K treatments were measured, and nutrients such as the soluble sugar, protein, and starch content of sweet potato roots were analyzed. The results indicate that the activity of glutamine synthetase (GS) and the soluble protein content in sweet potato leaves increase first and then decrease with increasing N application, while K application can significantly increase the activity of GS and the soluble protein content. The N metabolic capacity of leaves is strongest when the fertilizer ratio is K1N2. The SPAD value of sweet potato leaves increases with increasing N application. The net photosynthetic rate, stomatal conductance, and intercellular CO2 concentration first increase and then decrease with increasing N application. K fertilizer has a significant effect on these parameters. As the N application rate increases, the starch and protein content in the tubers increase, while the soluble sugar content decreases. However, the number of tubers per plant, fresh weight of the tubers, and dry weight of the tubers increase initially and then decrease, while the vine length continuously increases. The application of K fertilizer can significantly increase the number of tubers per plant and stem thickness of sweet potato. In conclusion, the appropriate N–K combined application can promote N metabolism, enhance the photosynthetic capacity of sweet potato, increase yield, and improve quality. [ABSTRACT FROM AUTHOR]

As a critical component in mechanical systems, the operational status of rolling bearings plays a pivotal role in ensuring the stability and safety of the entire system. However, in practical applications, the fault diagnosis of rolling bearings often encounters limitations due to the constraint of sample size, leading to suboptimal diagnostic accuracy. This article proposes a rolling bearing fault diagnosis method based on an improved denoising diffusion probability model (DDPM) to address this issue. The practical value of this research lies in its ability to address the limitation of small sample sizes in rolling bearing fault diagnosis. By leveraging DDPM to generate one-dimensional vibration data, the proposed method significantly enriches the datasets and consequently enhances the generalization capability of the diagnostic model. During the model training process, we innovatively introduce the feature differences between the original vibration data and the predicted vibration data generated based on prediction noise into the loss function, making the generated data more directional and targeted. In addition, this article adopts a one-dimensional convolutional neural network (1D-CNN) to construct a fault diagnosis model to more accurately extract and focus on key feature information related to faults. The experimental results show that this method can effectively improve the accuracy and reliability of rolling bearing fault diagnosis, providing new ideas and methods for fault detection and prevention in industrial applications. This advancement in diagnostic technology has the potential to significantly reduce the risk of system failures, enhance operational efficiency, and lower maintenance costs, thus contributing significantly to the safety and efficiency of mechanical systems. [ABSTRACT FROM AUTHOR]

Dissimilar metal welds (DMWs), widely used in many components of nuclear power plants, may cause catastrophic failures because of damages (such as corrosion). Pulsed eddy current testing (PECT) could be used for DMW detection for its advantages of broadband property and high lift-off immunity. However, the research on PECT for DMW detection has seldom been studied because its structure and material are complicated. In this paper, the detection and evaluation of flaws in DMWs are studied based on the transmitter-receiver (Tx-Rx) PECT probe. Simulation and experiment studies show that, for better detection accuracy, the Tx coil of the probe should be located above the pressure vessel, the Rx coil should be located above the weld, and the minimum distance between the Tx and Rx coils is suggested. Moreover, the peak value of the differential signal and the coefficient a1 of the fitted differential signals with a second-order Gaussian function can be used for defect evaluation. The research in this paper is beneficial for DMW detection by using PECT Tx-Rx probes. [ABSTRACT FROM AUTHOR]

Phosphorus (P) availability in soil is often limited, posing a challenge for sustainable agricultural production. Phosphate solubilizing microorganisms (PSMs) have emerged as a promising biological approach to enhance soil P availability while minimize negative environmental impacts. Exploring the impact of PSMs on increasing soil available P is crucial for optimizing the utilization of insoluble P in soil and promoting sustainable agricultural practices. In this article, we provide a comprehensive review on the dynamics of soil available P, including its input, loss and transformation processes. Additionally, we draw a conclusion about how PSMs increase the availability of P in soil, including solubilizing inorganic P (Pi) and organic P (Po) by secreting substances such as protons, organic acids, inorganic acids, exopolysaccharides, hydrogen sulfide, siderophores and phosphatases. Notably, the factors influencing the P solubilizing activity of PSMs in soil are thoroughly discussed. Moreover, practical applications of PSMs for increasing soil P availability are summarized. Future research should focus on exploring novel PSM isolates, conducting long-term field experiments to assess the effects and potential risk of PSMs under diverse conditions, and investigating synergistic approaches with other P activators or beneficial microorganisms. This review will advance our understanding of PSMs and their practical application, enabling their widespread adoption in agricultural systems. [ABSTRACT FROM AUTHOR]

Mammalian cells use a complex network of redox-dependent processes necessary to maintain cellular integrity during oxidative metabolism, as well as to protect against and/or adapt to stress. The disruption of these redox-dependent processes, including those in the mitochondria, creates a cellular environment permissive for progression to a malignant phenotype and the development of resistance to commonly used anticancer agents. An extension of this paradigm is that when these mitochondrial functions are altered by the events leading to transformation and ensuing downstream metabolic processes, they can be used as molecular biomarkers or targets in the development of new therapeutic interventions to selectively kill and/or sensitize cancer versus normal cells. In this Review we propose that mitochondrial oxidative metabolism is altered in tumor cells, and the central theme of this dysregulation is electron transport chain activity, folate metabolism, NADH/NADPH metabolism, thiol-mediated detoxification pathways, and redox-active metal ion metabolism. It is proposed that specific subgroups of human malignancies display distinct mitochondrial transformative and/or tumor signatures that may benefit from agents that target these pathways., Introduction Mitochondria contain the oxidation/reduction (redox) [O.sub.2]-consuming metabolic pathways necessary for cellular and organismal survival. The functions of these pathways include energy production and the removal and/or detoxification of damaging [...]