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BACKGROUND: Cadmium (Cd) is a highly toxic and widespread environmental oxidative stressor that causes a myriad of health problems, including osteoporosis and bone damage. Although nuclear factor erythroid 2-related factor 2 (NRF2) and its Cap 'n' Collar and basic region Leucine Zipper (CNC-bZIP) family member nuclear factor erythroid 2-related factor 1 (NRF1) coordinate various stress responses by regulating the transcription of a variety of antioxidant and cytoprotective genes, they play distinct roles in bone metabolism and remodeling. However, the precise roles of both transcription factors in bone loss induced by prolonged Cd exposure remain unclear. OBJECTIVES: We aimed to understand the molecular mechanisms underlying Cd-induced bone loss, focusing mainly on the roles of NRF2 and NRF1 in osteoclastogenesis provoked by Cd. METHODS: Male wild-type (WT), global Nrf2-knockout (Nrf[2.sup.-/-]) and myeloid-specific Nrf2 knockout [Nrf2(M)-KO] mice were administered Cd (50 or 100 ppm) via drinking water for 8 or 16 wk, followed by micro-computed tomography, histological analyses, and plasma biochemical testing. Osteoclastogenesis was evaluated using bone marrow-derived osteoclast progenitor cells (BM-OPCs) and RAW 264.7 cells in the presence of Cd (10 or 20 nM) with a combination of genetic and chemical modulations targeting NRF2 and NRF1. RESULTS: Compared with relevant control mice, global Nrf[2.sup.-/-] or Nrf2(M)-KO mice showed exacerbated bone loss and augmented osteoclast activity following exposure to 100ppm Cd in drinking water for up to 16 wk. In vitro osteoclastogenic analyses suggested that Nrf2-deficient BM-OPCs and RAW 264.7 cells responded more robustly to low levels of Cd (up to 20 nM) with regard to osteoclast differentiation compared with WT cells. Further mechanistic studies supported a compensatory up-regulation of long isoform of NRF1 (L-NRF1) and subsequent induction of nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (NFATc1) as the key molecular events in the Nrf2 deficiency-worsened and Cd-provoked osteoclastogenesis. L-Nrf1 silenced (via lentiviral means) Nrf2-knockdown (KD) RAW cells exposed to Cd showed dramatically different NFATc1 and subsequent osteoclastogenesis outcomes compared with the cells of Nrf2-KD alone exposed to Cd, suggesting a mitigating effect of the Nrf1 silencing. In addition, suppression of reactive oxygen species by exogenous antioxidants N-acetyl-L-cysteine (2mM) and mitoquinone mesylate (MitoQ; 0.2 [micro]M) mitigated the L-NRF1-associated effects on NFATc1-driven osteoclastogenesis outcomes in Cd-exposed Nrf2-KD cells. CONCLUSIONS: This in vivo and in vitro study supported the authors' hypothesis that Cd exposure caused bone loss, in which NRF2 and L-NRF1 responded to Cd and osteoclastogenic stimuli in a cooperative, but contradictive, manner to coordinate Nfatc1 expression, osteoclastogenesis and thus bone homeostasis. Our study suggests a novel strategy targeting NRF2 and L-NRF1 to prevent and treat the bone toxicity of Cd. https://doi.org/10.1289/EHP13849, Introduction Cadmium (Cd), a nonessential heavy metal, is considered as one of the most toxic environmental and occupational hazards. (1) Human long-term exposure to Cd, which occurs mainly from consumption [...]

Cis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets. [ABSTRACT FROM AUTHOR]

Battery performance is highly related to the intrinsic properties of battery materials. To develop commercial anode electrode materials for advanced sodium‐based batteries, it is crucial to understand whose fundamental issues including compositions and structure of the bulk and interface, dynamics and electrochemical reactions during cycling. The key for present and ongoing success of carbon‐based and sodium metal anode is to overcome an intrinsic challenge associated with transport and storage of ions and complicated interface activities, especially for the sodiation process with associated risk of dendrite. Advanced Nuclear Magnetic Resonance (NMR) technique has unique advantages in characterizing the local or microstructure of anode electrode materials and their interfacial evolutions down to the atomic level by a noninvasive and nondestructive manner. In this review, an overview is provided of the recent advances in understanding the fundamental issues of carbon based and sodium metal anode materials using advanced NMR approaches. Here, latest advancements of NMR are presented for applications in characterizing structures and dynamics of anode electrode material as well as their interfacial evolutions. Finally, the prospect and limitation of NMR techniques in batteries research will be highlighted, thereby paving the way for accelerating the development of next generation sodium batteries. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the critical role of MDSCs in CRC immune suppression, focusing on the CSF1R and JAK/STAT3 signaling axis. Additionally, it assessed the therapeutic efficacy of LNCs@CSF1R siRNA and anti-PD-1 in combination. Methods: Single-cell transcriptome sequencing data from CRC and adjacent normal tissues identified MDSC-related differentially expressed genes. RNA-seq analysis comprehensively profiled MDSC gene expression in murine CRC tumors. LNCs@CSF1R siRNA nanocarriers effectively targeted and inhibited CSF1R. Flow cytometry quantified changes in MDSC surface markers post-CSF1R inhibition. RNA-seq and pathway enrichment analyses revealed the impact of CSF1R on MDSC metabolism and signaling. The effect of CSF1R inhibition on the JAK/STAT3 signaling axis was validated using Colivelin and metabolic assessments. Glucose and fatty acid uptake were measured via fluorescence-based flow cytometry. The efficacy of LNCs@CSF1R siRNA and anti-PD-1, alone and in combination, was evaluated in a murine CRC model with extensive tumor section analyses. Results: CSF1R played a significant role in MDSC-mediated immune suppression. LNCs@CSF1R siRNA nanocarriers effectively targeted MDSCs and inhibited CSF1R. CSF1R regulated MDSC fatty acid metabolism and immune suppression through the JAK/STAT3 signaling axis. Inhibition of CSF1R reduced STAT3 activation and target gene expression, which was rescued by Colivelin. Combined treatment with LNCs@CSF1R siRNA and anti-PD-1 significantly slowed tumor growth and reduced MDSC abundance within CRC tumors. Conclusion: CSF1R via the JAK/STAT3 axis critically regulates MDSCs, particularly in fatty acid metabolism and immune suppression. Combined therapy with LNCs@CSF1R siRNA and anti-PD-1 enhances therapeutic efficacy in a murine CRC model, providing a strong foundation for future clinical applications. [ABSTRACT FROM AUTHOR]

This paper proposes a solution for the cooperative obstacle avoidance path planning problem in dual manipulator arms using an improved Rapidly Exploring Random Tree (RRT) algorithm. The dual manipulator arms are categorized into a main arm and a secondary arm. Initially, the obstacle avoidance path for the master arm is planned in the presence of static obstacles. Subsequently, the poses of the master arm during its movement are treated as dynamic obstacles for planning the obstacle avoidance path for the slave arm. A cost function incorporating a fast convergence policy is introduced. Additionally, adaptive weights between distance cost and variation cost are innovatively integrated into the cost function, along with increased weights for each joint, enhancing the algorithm's effectiveness and feasibility in practical scenarios. The smoothness of the planned paths is improved through the introduction of interpolation functions. The improved algorithm is numerically modeled and simulated in MATLAB. The verification results demonstrate that the improved RRT algorithm proposed in this paper is both feasible and more efficient. [ABSTRACT FROM AUTHOR]

Hydraulic fracturing technology is a crucial technique for effectively developing shale oil reservoirs. In field fracturing treatment operations, these reservoirs are often consisting of a combination of various rock types that making them complex. Therefore, this study specially focuses on the sandstone–shale layers in the G zone of the Daqingzi Well G Area in the southern part of the Songliao Basin. It aims to provide essential parameter support for subsequent theoretical and numerical research through laboratory mechanical experiments. Using the finite discrete element method, we have established four different numerical models for the hydraulic fracturing of shale oil with varying geological conditions, (including transition zones). The study reveals that when the vertical stress difference is 6 MPa, the crack height increases, and the offset distance decreases. At 8 and 10 MPa, crack propagation exhibits a "forking" phenomenon. A decrease in rock cohesion leads to increased offset distances in the transition zone, along with an increase in crack height. For type a and b transition zones, it is recommended to use a fracturing fluid with a viscosity of approximately 10 mPa s and a flow rate of 12 m3/min for fracturing. For type c transition zones, it is advisable to select fracturing fluid with a viscosity in the range of 10–30 mPa s and use a flow rate of 12 m3/min for fracturing. For the type d transition zones in the fracturing reservoir, it is recommended to use fracturing fluid with a viscosity of around 10 mPa s and a flow rate of 15 m3/min for optimal field fracturing operations. [ABSTRACT FROM AUTHOR]