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Deoxynivalenol (DON) is a prevalent toxin causing severe liver damage through hepatocellular oxidative stress. However, the underlying mechanisms and effective therapeutic approaches remain unknown. Here, the unique role of the xenobiotic metabolism factor pregnane X receptor (PXR) in mediating DON‐induced hepatocellular oxidative stress is investigated. Treatment with the PXR agonist 3‐indole‐propionic acid (IPA) alleviates DON‐induced oxidative stress and liver injury both in vitro and in vivo. Mechanistically, it is discovered for the first time that PXR agonist IPA directly transactivates the m6A demethylase FTO expression, leading to site‐specific demethylation and decreased abundance of YTHDC1‐bound Malat1 lncRNA at single‐nucleotide resolution. The diminished m6A modification of Malat1 lncRNA reduces its stability and augments antioxidant pathways governed by NRF2, consequently mitigating DON‐induced liver injury. Furthermore, Malat1 knockout mice exhibit decreased DON‐induced liver injury, emphasizing the role of Malat1 lncRNA in oxidative stress. Collectively, the findings establish that PXR‐mediated m6A‐dependent Malat1 lncRNA expression determines hepatocyte oxidative stress via m6A demethylase FTO, providing valuable insights into the potential mechanisms underlying DON‐induced liver injury and offers potential therapeutic strategies for its treatment. [ABSTRACT FROM AUTHOR]

Using the enactment of Document No. 18 as a quasi-natural event, we take a sample of Chinese A-share listed companies from 2010 to 2017 to test the impact of depoliticization on stock price crash risk based on the difference-in-differences (DID) model. Our results show that depoliticization reduces future stock price crash risk more significantly among non-state-owned enterprises. Furthermore, depoliticization can mitigate stock price crash risk through the effects of financing needs, censorship risk and agency cost. [ABSTRACT FROM AUTHOR]

(1) Objective: The objective of this study was to experimentally obtain the ideal pressure distribution model of buttock and thigh support for office workers in forward-leaning and upright sitting postures, reproduce the support provided by mesh materials with elastic materials, and propose an effective seat design scheme to improve the comfort of office workers. (2) Method: Based on the seven most popular mesh chairs on the market, pressure distribution experiments, and the fuzzy clustering algorithm, the relatively ideal body pressure distribution matrices were generated for office workers under two common sitting postures, and the corresponding partitioned sitting support surfaces were obtained. A prototype chair was created and validated by combining the ergonomics node coordinates and the physical properties of the materials. (3) Result: An ideal support model of four zones was constructed, and prototype pads were designed and produced according to this model. Subjects were recruited to test the ability of the prototypes to reproduce the ideal pressure distribution maps. (4) Conclusion: The four-zone ideal support model is capable of effectively representing the buttock and thigh support requirements in forward-leaning and upright sitting postures, and it is useful for the development of related products. Studying sitting postures and pressure values generated by different activities of office workers will help to refine the needs of office personnel and provide new ideas for the design of office chairs. [ABSTRACT FROM AUTHOR]

Aims: Our purpose was to clarify the effect of sulfamethoxazole (SMX) on the start‐up period, particle formation, and treatment efficiency of an aerobic granular sludge system. Methods and Results: We compared an R1 granular sequencing batch reactor (GSBR) started with 5 μg L−1 SMX and an R2 GSBR started without SMX, as a control, to investigate the impact of a trace amount of SMX (5 μg L−1) on aerobic granular sludge (AGS) characteristics and the removal of conventional contaminants. AGS granulation in the R1 system was not inhibited by SMX, but the granule particle size was smaller than that in the R2 system. Both systems had good performance removing conventional pollutants. Extracellular polymeric substance secretion in the R1 system was lower than that in the R2 system. After stabilizing reactor operations, the SMX removal efficiency in the R1 system (~73.93%) was higher than that in the R2 system (~70.66%). The start‐up modes also determined the differences in the microbial community structure of the AGS systems. Conclusions: SMX‐activated AGS performed better than AGS without SMX. Significance and Impact of Study: The study can help engineers determine start‐up modes with varieties of antibiotics in AGS processes and provide references for the optimization of water treatment processes. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hypoxia‐induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord‐derived MSC‐conditioned medium (hu‐MSC‐CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia. Methods: Neonatal porcine islet cell clusters were cultured with hu‐MSC‐CM, with or without exosomes, and native medium RPMI‐1640 (Control) under hypoxic conditions (1% O2). The effects of exosomes on NICCs viability and function in vitro were examined by FACS, the Loops system, and the Extracellular Flux assay, respectively. Results: Compared with NICCs cultured in RPMI‐1640 medium and hu‐MSC‐CM without exosomes, the survival ratio, viability, and function increased in NICCs cultured in hu‐MSC‐CM with exosomes. Conclusions: This study found that hu‐MSC‐CM could protect NICCs from hypoxia‐induced dysfunction, and exosomes played an important role in hypoxic resistance, suggesting a potential strategy to improve islet transplantation outcomes. [ABSTRACT FROM AUTHOR]

Introduction: 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) is a novel synthetic bipolar photosensitizer with many promising applications. This study investigated the impact of EtNBSe-mediated photodynamic therapy (EtNBSe-PDT) on the autophagy and endoplasmic reticulum (ER) stress of squamous carcinoma cells (A-431 cells), as well as the related molecular mechanisms. Methods: The potency of EtNBSe-PDT against squamous cell carcinoma was evaluated in BALB/c nude mice. Cell viability was evaluated using MTT. Western blotting and immunofluorescence were used to determine the expression levels of ER stress- and autophagy-related proteins. Results: Both morphological and microscopic findings showed that the tumor on the xenograft mice exhibited an apparent reduction in volume and was replaced with fibrosis 20 days after EtNBSe-PDT. Additionally, in an in vitro study using A-431 cells, EtNBSe-PDT was found to inhibit A-431 cell survival in an EtNBSe concentration- and light dose- dependent manner, and to induce ER stress via the PERK-eIF2α signaling pathway. Additionally, EtNBSe-PDT could also induce autophagy of A-431 cells. Furthermore, the ER stress inhibitor 4-PBA and the eIF2αinhibitor salubrinal were found to inhibit the autophagy induced by EtNBSe-PDT. Conclusion: This study demonstrated that the PERK-eIF2α signaling pathway was involved in the ER stress induced by EtNBSe-PDT. Meanwhile, the ER stress via the PERK-eIF2α pathway promoted the occurrence of autophagy in A-431 cells. [ABSTRACT FROM AUTHOR]

To solve the problem of satellite communication signal modulation mode recognition, a novel method based on the cyclic spectrum and high-order cumulants is proposed. In this method, the cyclic spectrum feature is added in the high-order cumulants method and many feature parameter dicisions are combined to construct identifier, cyclic spectrum is used to solve the classification problem of ASK, FSK, PSK and {2ASK, 4ASK}modulation recognition firstly, then, higher-order cumulants method is adopted to realize class recognition of FSK, PSK modulation signal. Simulation results show that the algorithm can recognize the main modulations {ASK, 2ASK, 2FSK, 4FSK, BPSK, QPSK} used by satellite communication and the average recognition rate is more than 88% when the signal-to-noise ratio(SNR)⩾5 dB. [ABSTRACT FROM AUTHOR]

Background: The dysfunction of islet grafts is generally attributed to hypoxia‐induced damage. Mesenchymal stem cells (MSCs) are currently thought to effectively protect cells from various risk factors via regulating autophagy. In our study, we investigated if human umbilical cord‐derived MSCs could ameliorate hypoxia‐induced apoptosis in porcine islets by modulating autophagy, and we explored the underlying mechanisms. Methods: Neonatal porcine islet cell clusters (NICCs) were cultured with human umbilical cord‐derived MSC conditioned medium (huc‐MSC‐CM) and RPMI‐1640 medium (control) under hypoxic conditions (1% O2) in vitro. NICCs were treated with 3‐methyladenine (3‐MA) and chloroquine (CQ) to examine the role of huc‐MSC‐CM in regulating autophagy. Finally, the levels of several cytokines secreted by huc‐MSCs were detected by ELISAs, and the corresponding inhibitors were applied to investigate which cytokine mediates the protective effects of huc‐MSC‐CM. The effects of huc‐MSC‐CM on NICCs viability and autophagy were examined using AO/PI staining, flow cytometry analysis, transmission electron microscopy (TEM) and confocal fluorescence microscopy analysis. The insulin secretion of NICCs was tested with an insulin immunoradiometric assay kit. Results: Compared to the control, the huc‐MSC‐CM treatment improved the viability of NICCs, inhibited apoptosis, increased autophagic activity and the levels of PI3K class III and phosphorylated Akt, while the ratio of phosphorylated mTOR/mTOR was reduced. These changes were reversed by CQ and 3‐MA treatments. High concentrations of IL‐6 were detected in hu‐MSC‐CM. Furthermore, recombinant IL‐6 pre‐treatment exerted similar effects as huc‐MSC‐CM, and these effects were reversed by a specific inhibitor of IL‐6 (Sarilumab). Conclusions: Our results demonstrated that huc‐MSC‐CM improved islet viability and function by increasing autophagy through the PI3K/Akt/mTOR pathway under hypoxic conditions. Additionally, IL‐6 plays an important role in the function of huc‐MSC‐CM. [ABSTRACT FROM AUTHOR]