Advances in the regulatory mechanisms of mTOR in necroptosis

The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis

Role of dimensional crossover on spin-orbit torque efficiency in magnetic insulator thin films

Magnetic insulators (MIs) attract tremendous interest for spintronic applications due to low Gilbert damping and absence of Ohmic loss. Magnetic order of MIs can be manipulated and even switched by spin-orbit torques (SOTs) generated through spin Hall effect and Rashba-Edelstein effect in heavy metal/MI bilayers. SOTs on MIs are more intriguing than magnetic metals since SOTs cannot be transferred to MIs through direct injection of electron spins. Understanding of SOTs on MIs remains elusive, especially how SOTs scale with the film thickness. Here, we observe the critical role of dimensionality on the SOT efficiency by systematically studying the MI layer thickness dependent SOT efficiency in tungsten/thulium iron garnet (W/TmIG) bilayers. We first show that the TmIG thin film evolves from two-dimensional to three-dimensional magnetic phase transitions as the thickness increases, due to the suppression of long-wavelength thermal fluctuation. Then, we report the significant enhancement of the measured SOT efficiency as the thickness increases. We attribute this effect to the increase of the magnetic moment density in concert with the suppression of thermal fluctuations. At last, we demonstrate the current-induced SOT switching in the W/TmIG bilayers with a TmIG thickness up to 15 nm. The switching current density is comparable with those of heavy metal/ferromagnetic metal cases. Our findings shed light on the understanding of SOTs in MIs, which is important for the future development of ultrathin MI-based low-power spintronics

Changes in the MicroRNA Profile of the Mandible of Ovariectomized Mice

Background/Aims: In postmenopausal women, a decrease in bone mineral density (BMD) at the hip and spine is associated with an increased risk of tooth loss, possibly caused by the loss of the alveolar bone. The present study explored the effect of the ovariectomy (OVX) of mice on the miRNA expression profile of their bones. Methods: Micro-CT and histological analysis were performed on mice following OVX or sham-operation using the right mandibles. The left mandibles were used for microarray and quantitative RT-PCR to explore the change in their miRNA expression profile. The differentially expressed miRNAs (DEmiRs) of the OVX and sham-operated mice were analyzed by constructing the miRNA-mRNA-function complex network. We then also analyzed the different roles of the regulation of miRNAs in the mandible and femur by combining public data from GEO. Results: OVX could lead to a significant decrease in the BMD in the mandible. A total of 53 DEmiRs including, 18 up-regulated and 35 down-regulated miRNAs, were identified. The analysis of the miRNA-mRNA-pathway complex network suggested that miR-17-5p and miRNA-297a-5p were potential biomarkers in the development of mandibles of OVX mice. A comparison of the analysis data on the mandible and femur showed that the transforming growth factor-β signaling pathway was specifically regulated in the mandible, whereas the Wnt signaling pathway was specifically regulated in the femur. Moreover, miR-17-5p and miR-133a-3p showed different expression tendencies in the mandible and in the femur after OVX. Conclusion: This study provides an integrated function analysis of miRNA in mandibles after OVX and of miR-17-5p and miR-133a-3p as potential biomarkers. Moreover, the mechanism in mandibles may not be comparable with that in femurs with estrogen deficiency

Effect of Precursors and Their Regulators on the Biosynthesis of Antibiotics in <i>Actinomycetes</i>

During the life activities of microorganisms, a variety of secondary metabolites are produced, including antimicrobials and antitumor drugs, which are widely used in clinical practice. In addition to exploring new antibiotics, this makes it one of the research priorities of Actinomycetes to effectively increase the yield of antibiotics in production strains by various means. Most antibiotic-producing strains have a variety of functional regulatory factors that regulate their growth, development, and secondary metabolite biosynthesis processes. Through the study of precursor substances in antibiotic biosynthesis, researchers have revealed the precursor biosynthesis process and the mechanism by which precursor synthesis regulators affect the biosynthesis of secondary metabolites, which can be used to obtain engineered strains with high antibiotic production. This paper summarizes the supply of antibiotic biosynthesis precursors and the progress of research on the role of regulators in the process of precursors in biosynthesis. This lays the foundation for the establishment of effective breeding methods to improve antibiotic yields through the manipulation of precursor synthesis genes and related regulators

Interprovincial Metal and GHG Transfers Embodied in Electricity Transmission across China: Trends and Driving Factors

With the increasing proportion of low-carbon power in electricity generation mix, power generation will be transformed from carbon-intensive to metal-intensive. In this context, metal and GHG transfers embodied in electricity transmission of China from 2015 to 2019 are quantified by the Quasi-Input-Output model. Combined with complex network theory, we have distinguished whether metal and GHG transfers show different trends as electricity trade changes. Driving factors contributing to forming the metal and GHG transfers are also explored based on the Quadratic Assignment Procedure. The results show that the electricity trade change has strengthened the metal transfer network significantly, while several key links in the GHG transfer network have weakened. Moreover, we find provincial differences in low-carbon electricity investment contributing to the metal transfer while affecting the GHG transfer little. The above facts imply an expanding embodied metal transfer in the future and shed light on policy making for power system decarbonization