MOLECULAR NEUROBIOLOGY
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2025
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IF 4.3
Li Xinying,Li Weiran,Xie Xinying,Fang Ting,Yang Jingwen,Shen Yue,Wang Yicheng,Wang Hongyan,Tao Liqing,Zhang Heng
Rotenone, a plant-derived natural insecticide, is widely used to induce Parkinson’s disease (PD) models. However, the mechanisms of rotenone-induced cell death remain unclear. Here, we found that rotenone (0.01, 0.1, or 1 μmol/L) suppressed SH-SY5Y dopamine neuron viability and led to PD-like pathological changes, such as reduced tyrosine hydroxylase (TH) but increased α-synuclein. Rotenone increased the levels of intracellular reactive oxygen species (ROS) and mitochondrial ROS, as well as the levels of the antioxidants nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), ultimately resulting in oxidative stress. Moreover, rotenone significantly downregulated the expression of GPX4 and xCT but upregulated the expression of COX2 and NCOA4, which are markers of ferroptosis. Furthermore, rotenone decreased phosphorylated mTOR level but increased Beclin-1, ATG5, LC3 and p62 expression, suggesting that rotenone enhances autophagy and reduces autophagy flux. Additionally, rotenone reduced Bcl-2 levels and the mitochondrial membrane potential (MMP) while promoting BAX and Caspase-3 expression, thus initiating cell apoptosis. N-acetylcysteine (NAC), a ROS scavenger, and ferrostatin-1 (Fer-1) and deferoxamine (DFO), two ferroptosis inhibitors, significantly eliminated rotenone-induced autophagy and apoptosis. Moreover, ML385, a specific inhibitor of Nrf2, suppressed rotenone-induced ferroptosis. Our results demonstrated that ROS might mediate rotenone-induced PD-like pathological changes by regulating iron death, autophagy, and apoptosis. Inhibiting ferroptosis blocked the rotenone-induced increase in autophagy and apoptosis. Thus, the ability of ROS to regulate rotenone-induced death through autophagy and apoptosis is dependent on ferroptosis. The findings require validation in multiple neuronal cell lines and in vivo.
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Nano Research
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2024
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IF 9.5
Wang Ding,Jiang Qi,Shen Ruoyu,Peng Lijun,Zhou Wentao,Meng Tingting,Hu Fuqiang,Wang Jianwei,Yuan Hong
The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological damage. Numerous studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease (IBD). Oral administration is the most common route for intestinal diseases. In this study, a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment, which can interrupt the pathological process of IBD, resulting in the significantly improved efficacy of existing treatments. Based on the specific pH values and high reactive oxygen species (ROS) levels in inflammatory sites of IBD, an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed, and confirmed in vitro and in vivo . The antiinflammatory drug dexamethasone acetate (Dex) and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions (TJs). The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with colitis. In brief, a drug delivery system and a therapeutic strategy for IBD are successfully developed.
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Nature Communications
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2024
·Vol. 15
·期 1
·1-12
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IF 14.7
Guo Kexin,Yang Xuehan,Zhou Chao,Li Chuang
Environmentally adaptive hydrogels that are capable of reconfiguration in response to external stimuli have shown great potential toward bioinspired actuation and soft robotics. Previous efforts have focused mainly on either the sophisticated design of heterogeneously structured hydrogels or the complex manipulation of external stimuli, and achieving self-regulated reversal shape deformation in homogenous hydrogels under a constant stimulus has been challenging. Here, we report the molecular design of structurally homogenous hydrogels containing simultaneously two spiropyrans that exhibit self-regulated transient deformation reversal when subjected to constant illumination. The deformation reversal mechanism originates from the molecular sequential descending-ascending charge variation of two coexisting spiropyrans upon irradiation, resulting in a macroscale volumetric contraction-expansion of the hydrogels. Hydrogel film actuators were developed to display complex temporary bidirectional shape transformations and self-regulated reversal rolling under constant illumination. Our work represents an innovative strategy for programming complex shape transformations of homogeneous hydrogels using a single constant stimulus.
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Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-11
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IF 4.8
Huang Ni,Yang Yi-Na,Huang Jia,Shao Hui-Yan,Li Yan-Lang,Qin Shi-Hui,Li Han-Fen,Shen Xiao-Jiang,Yang Liu,Hu Jiang-Miao
Dictyophora rubrovalvata is a valuable fungus homologous to food and medicine, and its polysaccharide have been gaining increasing attention because of its plentiful activity. However, the structure and activity of its homogeneous polysaccharide have not been studied enough. In this study, two polysaccharides DRP-I and DRP-II were purified from D. rubrovalvata . Their structures were characterized by chemical composition, monosaccharide composition analysis, methylation analysis and nuclear magnetic resonance spectroscopy. The results showed that DRP-I and DRP-II were neutral heteropolysaccharides with molecular weights of 5.79 × 10 3 and 1.25 × 10 4 Da, respectively, which were composed of mannose, galactose, glucose, xylose and fucose. The main chains were → 6)- α -D-Gal p -(1 → 6)- α -D-Gal p -(2,1 → 6)- α -D-Man p -(2,1 → 6)- α -D-Gal p -(1, and branch chains were β -D-Xyl p -(1 → 3)- α -L-Fuc p -(1 → 4)- α -D-Man p -(1 → and α -D-Gal p -(1 → 3)- α -D-Gal p -(1 → . The in vitro immunoactivity assays on dendritic cells showed that DRP-I and DRP-II could up-regulate the expression of IL-10 and IL-6 and inhibit the expression of TNF-α in a concentration-dependent manner. This research indicated that DRP-I and DRP-II possessed immunoactivity by balancing the excessive inflammation, and molecular weight is an important factor affecting immunoactivity. Graphical Abstract
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Nature Communications
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2024
·Vol. 15
·期 1
·1-15
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IF 14.7
Jiang Peng,Zhang Ludan,Liu Xiaolong,Ye Chenliang,Zhu Peng,Tan Ting,Wang Dingsheng,Wang Yuguang
The reaction system of hydrogen peroxide (H 2 O 2 ) catalyzed by nanozyme has a broad prospect in antibacterial treatment. However, the complex catalytic activities of nanozymes lead to multiple pathways reacting in parallel, causing uncertain antibacterial results. New approach to effectively regulate the multiple catalytic activities of nanozyme is in urgent need. Herein, Cu single site is modified on nanoceria with various catalytic activities, such as peroxidase-like activity (POD) and hydroxyl radical antioxidant capacity (HORAC). Benefiting from the interaction between coordinated Cu and CeO 2 substrate, POD is enhanced while HORAC is inhibited, which is further confirmed by density functional theory (DFT) calculations. Cu-CeO 2 + H 2 O 2 system shows good antibacterial properties both in vitro and in vivo. In this work, the strategy based on the interaction between coordinated metal and carrier provides a general clue for optimizing the complex activities of nanozymes.
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Nature Communications
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2024
·Vol. 15
·期 1
·1-11
·
IF 14.7
Zhang Yue,Mu Xueqin,Liu Zhengyang,Zhao Hongyu,Zhuang Zechao,Zhang Yifan,Mu Shichun,Liu Suli,Wang Dingsheng,Dai Zhuhui
The development of efficient and robust catalysts for hydrogen evolution reaction is crucial for advancing the hydrogen economy. In this study, we demonstrate that ultra-low coordinated hollow PtRuNi-O x nanocages exhibit superior catalytic activity and stability across varied conditions, notably surpassing commercial Pt/C catalysts. Notably, the PtRuNi-O x catalysts achieve current densities of 10 mA cm −2 at only 19.6 ± 0.1, 20.9 ± 0.1, and 21.0 ± 0.1 mV in alkaline freshwater, chemical wastewater, and seawater, respectively, while maintaining satisfied stability with minimal activity loss after 40,000 cycles. In situ experiments and theoretical calculations reveal that the ultra-low coordination of Pt, Ru, and Ni atoms creates numerous dangling bonds, which lower the water dissociation barrier and optimizing hydrogen adsorption. This research marks a notable advancement in the precise engineering of atomically dispersed multi-metallic centers in catalysts for energy-related applications.
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Natural Products and Bioprospecting
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2024
·Vol. 14
·期 1
·1-17
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IF 4.8
Yang Suqin,Huang Jingtao,Tan Wenjing,Xia Xiankun,Gan Dali,Ren Yalei,Su Hanwen,Xiang Meixian
Xiaoyankangjun tablet (XYKJP) is a traditional Chinese medicine formulation used to treat intestinal disorders in clinical practice. However, the specific therapeutic mechanism of action of XYKJP in colitis has not yet been elucidated. This study aimed to reveal the multifaceted mechanisms of action of XYKJP in treating colitis. The model established based on DSS-induced colitis in C57BL/6 mice was employed to estimate the effect of XYKJP on colitis, which was then followed by histological assessment, 16S rRNA sequencing, RT-qPCR, ELISA, and Western blot. XYKJP alleviated the symptoms of DSS-induced colitis mainly by reducing oxidative stress, inflammatory responses, and intestinal mucosal repair in colitis tissues. In addition, XYKJP regulated the intestinal flora by increasing the relative abundance of Akkermansia and Bifidobacterium and reducing the relative abundance of Coriobacteriaceae_UCG-002 . Mechanistically, XYKJP increased the content of short-chain fatty acids (SCFAs) in the feces, particularly propanoic acid and butyric acid, activated their specific receptor GPR43/41, furthermore activated the Nrf2/HO-1 pathway, and suppressed the JAK2/STAT3 pathway. XYKJP significantly alleviated the symptoms of experimental colitis and functioned synergistically by regulating the intestinal flora, increasing the production of SCFAs, and activating their specific receptors, thereby repressing oxidative stress and inflammation. Graphical Abstract
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RARE METALS
·
2025
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IF 11
Zhang Qi,Zhang Zhiqiang,Zeng Fangyuan,Li Wenjie,Liu Jinhao,Ai Shubo,Zheng Yun,Li Zhe,Shao Huaiyu,Liu Zhi-Quan
Kirkendall voids (KVs) at the Cu/Sn interface are a typical failure in integrated circuits, leading to solder joint cracking and electrical disconnection. Although the formation of KVs has been attributed to the difference in atomic diffusion rates at the Cu/Sn interface, the role of Cu intrinsic "quality" parameters (crystal defects) in this process remains unclear. This work systematically investigated the effects of Cu crystal defects on KVs: Cu substrates with different lattice defects and grain boundaries were prepared using proprietary electrodeposition additives, and the number of defects was quantitatively characterized by micro-strain, geometric dislocation density, and geometric phase analysis. The thermal aging experiments further showed that the formation of intermetallic compounds and KVs was related to crystal defect energy. When the grain boundary energy was higher than the lattice energy, the additional driving force resulted in short-circuit diffusion, causing local Cu depletion and voids. The low-crystal-defect samples maintained the local Cu/Sn interdiffusion equilibrium, resulting in fewer voids after 1000 h. This study emphasizes that regulating the crystal defects can reduce KVs and provides a new insight for improving the integrated solder joint’s reliability.
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Microsystems & Nanoengineering
·
2025
·Vol. 11
·期 1
·1-10
·
IF 9.9
Ma Yanmei,Li Xinhao,Hu Weikang,Ruan Muyang,Yang Ming,Chang Lingqian,Gu Hongri,Hu Chengzhi
Ferroptosis is an iron-dependent form of regulated cell death driven by phospholipid peroxidation and the accumulation of reactive oxygen species (ROS), holding significant importance for therapeutic applications via its induction or inhibition. Accurate detection of intracellular Fe 2+ and ROS is essential, as these molecules play essential roles in initiating and propagating ferroptosis. In this study, we present a novel electrochemical nanoprobe for real-time, highly selective detection of intracellular Fe 2+ . The nanoprobes are prepared by coating gold nanoparticles (AuNPs) and poly(3,4-ethylenedioxythiophene) (PEDOT) onto silicon carbide nanowires (SiC NWs), which are subsequently functionalized with ferrocenyl endoperoxide carboxylic acid (FDCA) and integrated with a liquid metal-filled glass nanopipette. FDCA is specifically synthesized to enable precise electrochemical detection of Fe 2+ with high selectivity (0.1 nM to 1 µM) and exceptional specificity. PEDOT and AuNPs can improve electrical conductivity and provide a versatile interface for further FDCA decoration. We use the nanoprobes to evaluate the intracellular change of Fe 2+ in MCF-7 breast cancer cells during erastin-induced ferroptosis. We observe a significant increase in intracellular Fe 2+ levels in MCF-7 cells undergoing ferroptosis, accompanied by a notable rise in ROS levels. These findings underscore the potential of this nanoprobe to enhance our understanding of the mechanism of ferroptosis in tumor development and as a potential treatment target.
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2024
·Vol. 108
·期 1
·1-12
·
IF 3.9
Lin Yilin,Fang Meimei,Liu Jun,Zhang Yehui,Yu Yigang
Abstract Phenyllactic acid (PLA) generally recognized as a natural organic acid shows against Vibrio parahaemolyticus activity. In this study, V. parahaemolyticus ATCC17802 ( Vp 17802) was cultured under the stress of 1/2MIC PLA, and then the antibacterial mechanisms were explored via transcriptomics. The minimum inhibitory concentration (MIC) of PLA against Vp 17802 was 3.2 mg/mL, and the time-kill analysis resulted that Vp 17802 was inhibited. PLA was able to destroy the bacterial membrane, leading to the leakage of intracellular substances and decline of ATP levels. The RNA-sequencing analysis results indicated that 1616 significantly differentially expressed genes were identified, among which 190 were up-regulated and 1426 were down-regulated. Down-regulation of the icd2 gene in the TCA cycle mediates blockage of tyrosine metabolic, arginine biosynthesis, and oxidative phosphorylation, causing insufficient energy supply of Vp 17802. Moreover, PLA could cause amino acids, metal ions, and phosphate transporters to be blocked, affecting the acquisition of nutrients. The treatment by PLA altered the expression of genes encoding functions involved in quorum sensing, flagellar assembly, and cell chemotaxis pathway, which may be interfering with the biofilm formation in Vp 17802, reducing cell motility. Overall, 1.6 mg/mL PLA inhibited the growth of Vp 17802 by disrupting to uptake of nutrients, cell metabolism, and the formation of biofilms. The results suggested a new direction for exploring the activity of PLA against Vp 17802 and provided a theoretical basis for bacterial pathogen control in the food industry. Key points •RNA sequencing was carried out to indicate the antibacterial mechanism of Vp17802. •The icd2 gene in the TCA cycle mediates blockage of metabolic of Vp17802. •The biofilm formation has interfered with 1.6 mg/mL PLA, which could reduce cell motility and virulence. Graphical Abstract
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Hepatology International
·
2025
·
IF 6.1
Yang Yanfang,Wang Tao,Fu Yuyin,Li Xukui,Yu Fuxun
Background Hepatitis B virus (HBV) is a pathogen that poses a serious threat to human health. The interaction between HBV and host has made great progress in recent years. SUMOylation is involved in virus-related cancer progression, but there are fewer studies on the mechanism of SUMOylation on HBV replication and antiviral defense. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a critical adaptor of the NF-κB pathways. Here, we focus on the roles of TRIM28 in regulating TRAF6 SUMOylation in HBV-replicating cells. Methods The SUMO1-modified TRAF6 proteins were enriched from total cellular proteins by immunoprecipitation with anti-SUMO1 antibody, then the SUMOylated TRAF6 was detected by western blot using an anti-TRAF6 antibody. The interaction between TRAF6 and TRIM28 was identified by immunoprecipitation and LC–MS/MS. The modification sites of TRAF6 SUMOylation were identified by amino acid site mutation. Expression and localization of TRAF6 and TRIM28 were assessed by immunohistochemistry and immunofluorescence. The hydrodynamic injection HBV mouse model was used to determine the function of TRIM28-mediated TRAF6 SUMOylation in vivo. Results The results show that the levels of SUMO1-modified TRAF6 are elevated in HBV-replicating cells. Lys453 is a major SUMO1 modification site of TRAF6. There is an antagonistic interaction between SUMOylation and ubiquitination of TRAF6 protein. The SUMO ligase TRIM28 is responsible for catalyzing TRAF6 SUMOylation. Compared to the wild-type TRAF6, its SUMO site mutant TRAF6 K453R promotes NF-κB activation. Moreover, TRIM28 overexpression attenuates TRAF6-mediated NF-κB activation, thereby inhibiting HBV replication in vivo. Conclusions Our findings demonstrate that SUMO ligase TRIM28 affects the ability of TRAF6 on NF-κB activation, nucleocytoplasmic shuttling and HBV replication-related indicators. Our data reveal that TRIM28-mediated SUMOylation of TRAF6 is a novel mechanism to regulate the inflammatory response, which may pave the way for new strategies to control anti-HBV.
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ARCHIVES OF VIROLOGY
·
2024
·Vol. 169
·期 4
·1-10
·
IF 2.5
Yuan Juan,Pan Jianli,Zhang Xiaofang,Gao Rui
Triple motif protein 21 (TRIM21) has an antiviral function that inhibits various viral infections. However, its role in the progress of influenza A virus (IAV) infection is unclear. In this study, we investigated the role and molecular mechanism of TRIM21 in IAV infection. RT-qPCR was used to determine the level of TRIM21 mRNA, and ELISA was used to measure the levels of IFN-α, IFN-β, IL-6, and TNF-α. The levels of the TRIM21, NP, TBK1, IRF3, p-TBK1, and p-IRF3 proteins were estimated by Western blot. The results showed that, after IAV infection, TRIM21 was upregulated in clinical patient serum and A549 cells, and this was correlated with the IFN response. Overexpression of TRIM21 reduced IAV replication and transcription in in vitro cell experiments. TRIM21 also increased IFN-α and IFN-β levels and decreased IL-6 and TNF-α levels in A549 cells. In addition, overexpression of TRIM21 inhibited IAV-induced apoptosis. Further experiments demonstrated that TBK1-IRF3 signaling was activated by TRIM21 and was involved in the inhibitory effect of TRIM21 on virus replication. In summary, our study suggests that TRIM21 inhibits viral replication by activating the TBK1-IRF3 signaling pathway, further inhibiting the infection process of IAV.
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