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Zinc oxide nanoparticles (ZnONPs) are widely utilized across various industries, raising concerns about their potential toxicity, especially in the respiratory system. This study explores the role of autophagy, regulated by microtubule-associated protein 1A/1B-light chain 3B (LC3B), in ZnONPs-induced toxicity using both in vivo (LC3B knockout mice) and in vitro (BEAS-2B cells) models. Our findings demonstrate that LC3B-regulated autophagy mitigates ZnONPs-induced epithelial cell dysfunction and acute lung injury. In the absence of LC3B, oxidative stress, inflammation, and intracellular zinc accumulation are exacerbated, resulting in mitochondrial dysfunction and epithelial cell death. In vitro, LC3B knockdown disrupted zinc ion transporter expression and impaired mitophagic flux in BEAS-2B cells. Treatment with zinc ion chelators alleviated these toxic effects, confirming that free zinc ions play a critical role in driving ZnONPs toxicity. These findings highlight that targeting autophagy and maintaining zinc homeostasis could offer therapeutic strategies to reduce ZnONPs-induced lung damage. [ABSTRACT FROM AUTHOR]

Based on our previously proposed three-phase solidification model, a comprehensive analysis on the impact of the only electromagnetic stirring (EMS) and combined EMS on the microscopic structure evolution and solute segregation behavior in a 500 mm diameter 42CrMo steel of continuously cast round bloom. The results indicate that M-EMS has a notable impact on expediting the dissipation of superheat, enhancing the initiation of grain formation, and enlarging the equiaxed region. The percentage of equiaxed grains increased from 59.26 to 63.37% with the increment in current intensities of M-EMS from 250 to 350 A. However, higher M-EMS current intensities were found to enhance local positive segregation in the transition zone between columnar and equiaxed grains. The impact of M-EMS on improving center positive segregation was minimal, as the ratio of center positive segregation remained consistently around 1.17. Furthermore, the implementation of F-EMS demonstrated its effectiveness in reducing center positive segregation. The ratio of center positive segregation decreased from 1.14 to 1.10, when the current intensity increases from 150 to 250 A. However, it should be noted that F-EMS alone did not contribute to the expansion of the equiaxed zone. On the other hand, when M-EMS was combined with F-EMS (referred to as combined EMS), it showed potential in mitigating center segregation during continuous casting round blooms. The benefits observed with M-EMS in terms of promoting grain nucleation and expanding the equiaxed grain zone were also evident in this combined EMS process. Furthermore, a notable enhancement in the equiaxed grain ratio up to 60.13% was observed combined EMS models were simultaneously employed during continuous casting of round blooms. And, there was a reduction in center segregation ratio for round blooms to as low as 1.09. [ABSTRACT FROM AUTHOR]

The inhibition of Nav1.7 is a promising strategy for the development of analgesic treatments. Spider venom‐derived peptide toxins are recognized as significant sources of Nav1.7 inhibitors. However, their development has been impeded by limited selectivity. In this study, eight peptide toxins from three distinct spider venom Nav channel families demonstrated robust inhibition of hNav1.7, rKv4.2, and rKv4.3 (rKv4.2/4.3) currents, exhibiting a similar mode of action. The analysis of structure and function relationship revealed a significant overlap in the pharmacophore responsible for inhibiting hNav1.7 and rKv4.2 by HNTX‐III, although Lys25 seems to play a more pivotal role in the inhibition of rKv4.2/4.3. Pharmacophore‐guided rational design is employed for the development of an mGpTx1 analogue, mGpTx1‐SA, which retains its inhibition of hNav1.7 while significantly reducing its inhibition of rKv4.2/4.3 and eliminating cardiotoxicity. Moreover, mGpTx1‐SA demonstrates potent analgesic effects in both inflammatory and neuropathic pain models, accompanied by an improved in vivo safety profile. The results suggest that off‐target inhibition of rKv4.2/4.3 by specific spider peptide toxins targeting hNav1.7 may arise from a conserved binding motif. This insight promises to facilitate the design of hNav1.7‐specific analgesics, aimed at minimizing rKv4.2/4.3 inhibition and associated toxicity, thereby enhancing their suitability for therapeutic applications. [ABSTRACT FROM AUTHOR]

The instantaneous abnormal mold level fluctuation (IAMLF) has significant harmful effects on slab quality. This article proposes a prediction and control method for IAMLF. First, the data processed by difference method is used for the IAMLF prediction and stopper‐rod position prediction. Then, the bidirectional long short‐term memory (BI‐LSTM) is introduced to predict the IAMLF; the corresponding stopper‐rod position is predicted according to the mold level prediction result. BI‐LSTM can predict the IAMLF with the mean absolute error of 1.52 mm and the false alarm rate of 1.8%, and also performs well in predicting the stopper‐rod position with a mean absolute error of only 1.92 mm. Furthermore, the two prediction models are combined to form a closed loop, where the mold level fluctuation is predicted according to the industrial data processed by data difference method, and the stopper‐rod position is adjusted in advance to eliminate IAMLF. Finally, the fuzzy proportional‐integral‐derivative (PID) controller is used to control mold level based on the mold level and stopper‐rod position prediction results. The prediction accuracy of IAMLF reaches 98.4%, and the present proposed fuzzy PID controller can effectively prevent the occurrence of IAMLF with a success rate of 95.6%. [ABSTRACT FROM AUTHOR]

A graphics‐processing‐unit (GPU)‐accelerated 3D heat‐transfer and solidification model is proposed to predict the temperature field and solidification field for continuously cast slab. The fully 3D model is developed based on the finite difference method and implemented on the compute unified device architecture (CUDA)/C++ platform. The model is verified by solving the 1D Stefan problem and validated by surface temperature measurements. The model is proven to be 18.91 times faster for the coarsest mesh of 35 million nodes and 22.92 times faster for the finest mesh of 50 million nodes than a central‐processing‐unit (CPU)‐based parallel version with 28 threads. The corresponding relative calculational times are 0.19 and 0.32, which indicate that the model has great computation efficiency. The model is proven to be robust enough for the dynamic continuous casting (CC) process via a test of dynamic casting speed. Further analysis of the nonuniform heat transfer and solidification shows that the model is able to predict the nonuniform heat transfer efficiently. In the studied cases, a higher casting speed will lead to a remarkable enhancement of the unevenness of heat transfer and solidification in general. [ABSTRACT FROM AUTHOR]

Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity. [ABSTRACT FROM AUTHOR]