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Selenium-rich foods serve the dual-function of providing nutrients and organic selenium. In the situation of selenium deficiency in the entire population, it is crucial to understand the sources of selenium and its circulation in the natural environment and biological systems. Current research on selenium-rich foods focuses mostly on chemical synthesis and bio-organic conversion, which is highly specialized and not suitable for horizontal comparison of different selenium-rich foods. There are few studies on the circulation of selenium and the selenium contents and health benefits of different selenium-rich foods. This article summarizes the sources, circulation and metabolism of selenium, the sources and forms of natural selenium in selenium-rich foods, and the selenium absorption and metabolism pathways in plants, animals, and microorganisms. Next, it reviews the current status of research on selenium-rich foods from various sources, and gives an outlook on the future of selenium-rich foods. This review may serve as a foundation for in-depth comparison of selenium-rich foods from various sources, and provide scientific guidance for the research and development of novel healthy selenium-rich foods.

Aiming at the challenges to the accurate and stable heading control of underactuated unmanned surface vehicles arising from the nonlinear interference caused by the overlay and the interaction of multi interference, and also the uncertainties of model parameters, a heading control algorithm for an underactuated unmanned surface vehicle based on an improved backpropagation neural network is proposed. Based on applying optimization theory to realize that the underactuated unmanned surface vehicle tracks the desired yaw angle and maintains it, the improved momentum of weight is combined with an improved tracking differentiator to improve the robustness of the system and the dynamic property of the control. A hyperbolic tangent function is used to establish the nonlinear mappings an approximate method is adopted to summarize the general mathematical expressions, and the gradient descent method is applied to ensure the convergence. The simulation results show that the proposed algorithm has the advantages of strong robustness, strong anti-interference and high control accuracy. Compared with two commonly used heading control algorithms, the accuracy of the heading control in the complex environment of the proposed algorithm is improved by more than 50%.

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that of highly recurrent missense mutations in the GTPase RHOA. The function of these mutations has remained unresolved. We demonstrate that RHOAY42C, the most common RHOA mutation in DGC, is a gain-of-function oncogenic mutant, and that expression of RHOAY42C with inactivation of the canonical tumor suppressor Cdh1 induces metastatic DGC in a mouse model. Biochemically, RHOAY42C exhibits impaired GTP hydrolysis and enhances interaction with its effector ROCK. RHOA Y42C mutation and Cdh1 loss induce actin/cytoskeletal rearrangements and activity of focal adhesion kinase (FAK), which activates YAP-TAZ, PI3K-AKT, and β-catenin. RHOAY42C murine models were sensitive to FAK inhibition and to combined YAP and PI3K pathway blockade. These results, coupled with sensitivity to FAK inhibition in patient-derived DGC cell lines, nominate FAK as a novel target for these cancers. SIGNIFICANCE: The functional significance of recurrent RHOA mutations in DGC has remained unresolved. Through biochemical studies and mouse modeling of the hotspot RHOAY42C mutation, we establish that these mutations are activating, detail their effects upon cell signaling, and define how RHOA-mediated FAK activation imparts sensitivity to pharmacologic FAK inhibitors.See related commentary by Benton and Chernoff, p. 182.This article is highlighted in the In This Issue feature, p. 161.

In this paper, a novel dynamic surface sliding mode control (DSSMC) method, combined with a lateral velocity tracking differentiator (LVTD), is proposed for the cooperative formation control of underactuated unmanned surface vehicles (USVs) exposed to complex marine environment disturbances. Firstly, in view of the kinematic and dynamic models of USVs and the design idea of a virtual control law in a backstepping approach, the trajectory tracking control problem of USVs’ cooperative formation is transformed into a stabilisation problem of the virtual control law of longitudinal and lateral velocities. Then, aiming at the problem of differential explosion caused by repeated derivation in the process of backstepping design, the first-order low-pass filter about the virtual longitudinal velocity and intermediate state quantity of position is constructed to replace differential calculations during the design of the control law, respectively. In order to reduce the steady-state error when stabilising the virtual lateral velocity control law, the integral term is introduced into the design of the sliding mode surface with a lateral velocity error, and then the second-order sliding mode surface with an integral is structured. In addition, due to the problem of controller oscillation and the role of the tracking differentiator (TD) in active disturbance rejection control (ADRC), the LVTD is designed to smooth the state quantity of lateral velocity. Subsequently, based on the dynamic model of USV under complex marine environment disturbances, the nonlinear disturbance observer is designed to observe the disturbances and compensate the control law. Finally, the whole cooperative formation system is proved to be uniformly and ultimately bounded, according to the Lyapunov stability theory, and the stability and validity of the method is also verified by the simulation results.

Simple Summary: Foot-and-mouth disease (FMD) inactivated vaccines play a crucial role in curbing the spread of FMDV. The 50% protective dose (PD50) is considered the "gold standard" to assess the efficacy of FMD inactivated vaccines. It is a highly important metric to evaluate vaccine quality. However, assessing PD50 requires antibody-negative pigs or cattle, and so it is time-consuming and costly and requires high-level biosafety facilities. The 146S component, which represents intact virus particles containing all the neutralizing epitopes of FMDV, can effectively stimulate the production of protective antibodies in animals. We found that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. The determination of 146S contents could serve as a new method for potency testing, offering an alternative to animal challenge tests. This approach would not only significantly reduce the cost and duration of vaccine production testing but also minimize the need for animal challenge tests, thereby enhancing animal welfare. To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests. [ABSTRACT FROM AUTHOR]

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer (CRC) cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione (GSH) via the upregulation of RRM2B—a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3′UTR of RRM2B increased its mRNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence (CDS) of OPA1—an essential GTPase protein for mitochondrial inner membrane fusion—also increased mRNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development. [ABSTRACT FROM AUTHOR]

Cancer-associated mutations in the guanosine triphosphatase (GTPase) RHOA are found at different locations from the mutational hotspots in the structurally and biochemically related RAS. Tyr42-to-Cys (Y42C) and Leu57-to-Val (L57V) substitutions are the two most prevalent RHOA mutations in diffuse gastric cancer (DGC). RHOAY42C exhibits a gain-of-function phenotype and is an oncogenic driver in DGC. Here, we determined how RHOAL57V promotes DGC growth. In mouse gastric organoids with deletion of Cdh1, which encodes the cell adhesion protein E-cadherin, the expression of RHOAL57V, but not of wild-type RHOA, induced an abnormal morphology similar to that of patient-derived DGC organoids. RHOAL57V also exhibited a gain-of-function phenotype and promoted F-actin stress fiber formation and cell migration. RHOAL57V retained interaction with effectors but exhibited impaired RHOA-intrinsic and GAP-catalyzed GTP hydrolysis, which favored formation of the active GTP-bound state. Introduction of missense mutations at KRAS residues analogous to Tyr42 and Leu57 in RHOA did not activate KRAS oncogenic potential, indicating distinct functional effects in otherwise highly related GTPases. Both RHOA mutants stimulated the transcriptional co-activator YAP1 through actin dynamics to promote DGC progression; however, RHOAL57V additionally did so by activating the kinases IGF1R and PAK1, distinct from the FAK-mediated mechanism induced by RHOAY42C. Our results reveal that RHOAL57V and RHOAY42C drive the development of DGC through distinct biochemical and signaling mechanisms. Editor's summary: Mutations in the GTPase RHOA are common in a type of aggressive, hereditary gastric cancer caused by loss of CDH1, which encodes a cell adhesion receptor. Schaefer et al. found that the two most common RHOA mutations drive the development and progression of this cancer in distinct ways (see also the Focus by Benton and Chernoff). Both the Y42C and L57V mutations conferred a similar gain-of-function phenotype that promoted the interaction of RHOA with the actin cytoskeleton and activation of the transcriptional coactivator YAP1 to promote malignant transformation, growth, and cell motility in Cdh1-deficient mouse-derived gastric organoids. However, distinct from Y42C, L57V engaged the kinases PAK1 and IGF1R, and inhibition of either kinase suppressed the growth of organoids. These results reveal potential drug targets in the treatment of gastric cancer. —Leslie K. Ferrarelli [ABSTRACT FROM AUTHOR]