Antioxidants
·
2025
·Vol. 14
·期 10
·1222
·
IF 6.6
Hanziyi Zhou,Shibo Sun,Haowen Liu,Tong Li,Yiran Xu,Rui Yang,Haiyan Liu,Leiyu He,Weiping Xu,Shui Guan,Jianqiang Xu
Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys497-Sec498) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition.
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高影响因子
Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-14
·
IF 9.6
Zhang Pengchao,Cheng Jian,Liu Zhao,Adeshakin Funmilayo O.,Dai Liujiang,Niu Xiangyun,Zhang Ziyang,Peng Xixia,Li Long,Liu Maoxuan,Yan Dehong,Yang Xiaolu,Wan Xiaochun,Zhang Guizhong
Anoikis resistance, an essential prerequisite for tumor metastasis, is now recognized as a promising target in the fight against tumor progression. However, the detailed mechanisms of anoikis resistance are not fully understood, and drugs targeting anoikis resistance are not currently available. Here we report that NY-ESO-1, a well-known cancer-testis antigen, is linked to a poor prognosis in tumor patients and that it is crucial for anoikis resistance and tumor metastasis. Overexpression of NY-ESO-1 in cancer cells enhanced ERK1/2 activation, which in turn promoted resistance to anoikis, increased colony formation in soft agar, and facilitated lung metastasis in mice. Conversely, NY-ESO-1 knockdown significantly reduced ERK1/2 activity, leading to enhanced anoikis, diminished colony formation, and impaired metastatic potential. Mechanistically, NY-ESO-1 acts as a scaffold protein to recruit the deubiquitinase OTUB1 to PP1α, forming a ternary complex that prevents PP1α from being ubiquitinated. The OTUB1’s deubiquitinase activity, not its ability to suppress E2 enzymes, is necessary for reducing polyubiquitination and improving PP1α stability. Finally, accumulated PP1α proteins significantly activate downstream ERK1/2. Blockade of ERK1/2 or knocking down PP1α antagonized NY-ESO-1-mediated anoikis resistance. These results not only reveal a previously unrecognized mode for deubiquitinase substrate expansion but also highlight the function of NY-ESO-1 in anoikis resistance and suggest NY-ESO-1 as a novel attractive target for preventing tumor metastasis.
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JOURNAL OF ELECTRONIC MATERIALS
·
2024
·Vol. 53
·期 10
·6553-6562
·
IF 2.2
Zhang Yu,Ma Jianli,Chen Chen,She Yubin
In this work, non-stoichiometric Li 2(1+ x ) Mg 3 Ti 4 O 12 (L x MTO, x = 0.00–0.05) ceramics with excess lithium were prepared through a simple reaction sintering route to suppress lithium volatilization. According to the characterization of the phase composition and microscopic morphology of the pellets, single-phase L x MTO ceramics with a good microstructure were obtained. Excess lithium effectively inhibited the volatilization and optimized the morphology of the ceramics. A trend in relative density with an initial increase followed by a steep decrease was a predominant observation with the change in dielectric properties. The permittivity of the samples was dominated by the relative density and distortion of the [TiO 6 ] octahedron structure caused by Li + . The dielectric loss primarily originated from the refraction loss and scattering generated by pores, and the grain boundaries also contributed to the loss in the quality factor. Ultimately, at 1220°C, the Li 2.08 Mg 3 Ti 4 O 12 ceramics exhibited excellent microwave dielectric properties: ε r = 17.83, Q × f = 69,823 GHz and τ f = −18.19 ppm/°C.
研究领域:
材料科学
·
无机非金属材料
·
介电材料
·
陶瓷学
·
固态化学
·
电子材料
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JOURNAL OF ALLOYS AND COMPOUNDS
·
2016
·
IF 3.014
Qiuyan Hao,Yixia Chu,Xuerong Zheng,Zhenya Liu,Liming Liang,Jiakun Qi,Xin Zhang,Gang Liu,Hui Liu,Hongjian Chen,Caichi Liu
Recently, planar perovskite solar cells based on CH 3 NH 3 PbI 3 have attracted many researcher's interest due to their unique advantages such as simple cell architecture, easy fabrication and potential multijunction construction comparing to the initial mesoporous structure. However, the preparation of planar perovskite films with high quality is still in challenge. In this paper, we developed a vapor-assisted solution process using a novel and green solvent of 1-Ethyl-2-pyrrolidone (NEP) instead of the traditional N, N-dimethylformamide (DMF) to construct a high-quality perovskite CH 3 NH 3 PbI 3 thin film with pure phase, high compactness, small surface roughness and controlled size. The phase evolution and growth mechanism of the perovskite films are also discussed. Utilizing the NEP of low volatility and moderate boiling point as solvent, we dried the PbI 2 -NEP precursor films at different temperature under vacuum and then obtained PbI 2 thin films with different crystalline degree from amorphous to highly crystalline. The perovskite films with crystal size ranged from hundreds of nanometers to several micrometers can be prepared by reacting the PbI 2 films of different crystalline degree with CH 3 NH 3 I vapor. Moreover, planar-structured solar cells combining the perovskite film with TiO 2 and spiro-OMeTAD as the electron and holes transporting layer achieves a power conversion efficiency of 10.2%.
研究领域:
材料科学
·
光伏器件
·
纳米科技
·
无机非金属材料
·
能源化学
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CELLULOSE
·
2014
·Vol. 21
·期 5
·3311-3322
·
IF 3.033
Zhang Min,Ding Cuicui,Huang Liulian,Chen Lihui,Yang Haiyang
Collagen/cellulose blended solutions with collagen/cellulose mass ratio (Col/Cel) of 0, 1/40, 1/20, 1/10 and 1/5 were prepared using [Emim]Ac as solvent. The interactions between the two polymers before and after regeneration were investigated. In steady shear flow, all of the experimental viscosity values were greater than those of the estimated values calculated from the log-additivity rule for each sample, suggesting interactions between the two polymers in solutions. All solutions exhibited shear thinning behavior and the flow curves could be described by Cross model. Zero shear viscosity ( η
0 ) versus Col/Cel was examined and a linear increase (from 8.73 to 16.39 Pa·s) can be observed for η
0 as Col/Cel ≤ 1/10, while there was only a slight increase (from 16.39 to 18.42 Pa·s) in η
0 as Col/Cel increased to 1/5. Dynamic rheology results suggested the existence of aggregates in solution with Col/Cel = 1/10. Furthermore, the activation energy of solution was 84.5 kJ mol −1 as Col/Cel = 1/10, higher than that of cellulose solution (44.2 kJ mol −1 ). Regenerated films were prepared and characterized to trace back the interactions between the two polymers in [Emim]Ac. Fourier transform infrared spectroscopy indicated the hydrogen-bond interaction between collagen and cellulose in films. The denaturation temperature of collagen in films with Col/Cel ≤ 1/10 could be improved, but it was decreased with the increase of collagen content, and finally was reduced to be close to that of collagen as Col/Cel = 1/5. The features of dynamic mechanical analysis for films were indicative of the lack of homogeneity between collagen and cellulose as Col/Cel = 1/5. Atomic force microscopy images further confirmed the phase-separation when Col/Cel = 1/5.
研究领域:
高分子科学
·
材料化学
·
流变学
·
生物材料
·
可持续材料
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Molecular Catalysis
·
2023
·
IF 4.6
Yuqing Wang,Miao Jiang,Li Yan,Cunyao Li,Guoqing Wang,Wenxiu He,Yunjie Ding
A series of porous organic polymer with different concentrations of tri(4-vinylphenyl)phosphite (P(OPh) 3 ) moieties were synthesized through the solvothermal synthesis technique. Their performance were investigated in 1-butene hydroformylation after metalation with metal species. The effect of the concentration of P(OPh) 3 moieties and pore structure of the polymers on catalytic efficiency were investigated in detail. The polymer-based Rh catalysts demonstrated a decrease in catalytic activity and inverse trends in selectivity with the increasing concentration of P(OPh) 3 . More importantly, Rh/POP-PhPh 3 -BP-P(OPh) 3 -x catalysts containing biphephos moieties exhibited more excellent catalytic performance than the corresponding Rh/POP-PhPh 3 -P(OPh) 3 -x catalysts. And the optimal catalytic performance, a valeraldehyde n/i ratio of 60.4, a valeraldehyde TOF of 9589.9 h −1 , and good catalytic stability were acquired for Rh/POP-PhPh 3 -BP-P(OPh) 3 –0.9 catalyst. The extraordinary catalytic properties are attributed to the formation of abundant active pentacoordinated hydridorhodium complexes, as demonstrated by in situ FT-IR experiments.
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MATERIALS CHEMISTRY AND PHYSICS
·
2023
·
IF 4.6
Yatao Pan,Guangjing Hou,Xiaojuan Wang,Xia Ran,Pingan Liu,Lijun Guo
Developing novel inhibitors for the fibrillization of amyloid peptides and understanding the relevant assembly processes are essential for biomedical and biomaterial sciences. Herein, we have synthesized and characterized the nitrogen and fluorine co-doped graphene quantum dots (N, F-GQDs), and investigated their inhibition of the fibrillization of Amyloid-beta peptide (1–42) (Aβ 42 ) by monitoring the assembly morphologies in the Aβ 42 /N, F-GQDs systems. Our results indicate that the N, F-GQDs functionalized with multiple surface groups effectively inhibits the fibrillization of amyloid Aβ 42 . The strong adsorption of Aβ 42 on N, F-GQDs significantly reduces the generation of β-sheet structures and the cytotoxicity of Aβ 42 /N, F-GQDs aggregates. Accordingly, a morphological evolution from the long fibrils of Aβ 42 to the spherical particles and unique closed-loop structures of Aβ 42 /N, F-GQDs have been captured. A possible interpretation for the observed phenomena in the presence of N, F-GQDs has been proposed by combining the different inhibition effects of other GQDs on the fibrillization of Aβ 42 and the results from various control experiments. Moreover, the inhibition activity of N, F-GQDs demonstrates good adaptability to resist the fluctuation of pH value and the interference of divalent metal ions , facilitating their practical applications in the future.
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DIGESTIVE DISEASES AND SCIENCES
·
2023
·Vol. 68
·期 6
·2414-2426
·
IF 3.1
Lin Mengjuan,Hu Guiying,Wang Zhengqiang,Yu Baoping,Tan Wei
Background The mechanism underlying irritable bowel syndrome (IBS), a common disease with hyperalgesia, remains elusive. The spinal cholinergic system is involved in pain modulation, but its role in IBS is unknown. Aims To determine whether high-affinity choline transporter 1 (CHT1, a major determinant of the cholinergic signaling capacity), is implicated in spinal modulation of stress-induced hyperalgesia. Methods A rat IBS model was established by water avoidance stress (WAS). Visceral sensations were detected by abdominal withdrawal reflex (AWR) and visceromotor response (VMR) to colorectal distension (CRD). Abdominal mechanical sensitivity was determined by von Frey filaments (VFFs) test. RT-PCR, Western blot, and immunostaining were performed for spinal CHT1 expression. Spinal acetylcholine (ACh) was measured by ELISA; the influence of spinal CHT1 on hyperalgesia were evaluated by intrathecal administration of MKC-231 (a choline uptake enhancer) and hemicholinium-3 (HC-3, a specific inhibitor of CHT1). Minocycline treatment was used to explore the role of spinal microglia in hyperalgesia. Results After 10 days of WAS, AWR scores and VMR magnitude to CRD, and the number of withdrawal events in VFF test were increased. Double-labeling showed that CHT1 in the dorsal horn was expressed in most of the neurons and almost all the microglia. The CHT1 expression and ACh levels in the spinal cord and the density of CHT1-positive cell in the spinal dorsal horn were enhanced in WAS-exposed rats. HC-3 enhanced pain responses in WAS rats; MKC-231 alleviated pain in WAS rats by upregulating CHT1 expression and increasing ACh production in the spinal cord. Furthermore, microglial activation in the spinal dorsal horn promoted the stress-induced hyperalgesia, and MKC-231 achieved analgesic effects by inhibiting the spinal microglial activation. Conclusions CHT1 exerts antinociceptive effects in spinal modulation of chronic stress-induced hyperalgesia by increasing ACh synthesis and suppressing microglial activation. MKC-231 has potential for treating disorders accompanied by hyperalgesia.
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TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Yufen Liao,Xin Wang,Guangyun Ran,Shiyu Zhang,Chutian Wu,Rong Tan,Ying Liu,Yan He,Ting Liu,Zhongxiu Wu,Ying Peng,Weiwei Li,Jiang Zheng
Columbin (CLB) is the most abundant (>1.0%) furan-containing diterpenoid lactone in herbal medicine Tinospora sagittate (Oliv.) Gagnep. The furano-terpenoid was found to be hepatotoxic, but the exact mechanisms remain unknown. The present study demonstrated that administration of CLB at 50 mg/kg induced hepatotoxicity, DNA damage and up-regulation of PARP-1 in vivo . Exposure to CLB (10 μM) induced GSH depletion, over-production of ROS , DNA damage, up-regulation of PARP-1 and cell death in cultured mouse primary hepatocytes in vitro . Co-treatment of mouse primary hepatocytes with ketoconazole (10 μM) or glutathione ethyl ester (200 μM) attenuated the GSH depletion, over-production of ROS, DNA damage, up-regulation of PARP-1, and cell death induced by CLB, while co-exposure to L -buthionine sulfoximine (BSO, 1000 μM) intensified such adverse effects resulting from CLB exposure. These results suggest that the metabolic activation of CLB by CYP3A resulted in the depletion of GSH and increase of ROS formation. The resultant over-production of ROS subsequently disrupted the DNA integrity and up-regulated the expression of PARP-1 in response to DNA damage, and ROS-induced DNA damage was involved in the hepatotoxicity of CLB.
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MICROPOROUS AND MESOPOROUS MATERIALS
·
2023
·
IF 5.2
Dingmei Han,Meiyu Liu,Chengming Huang,Xinyu Sun,Linjie Guan,Binbin He,Yi Mei,Yun Zu
Co-based catalysts are promising alternatives to replace expensive Pt- and toxic Cr-based catalysts for propane dehydrogenation (PDH), while the catalytic stability and propylene selectivity have been subjected to the diversity of Co speciations. Given the situation, uniformly stable hydroxylated Co 2+ silicate sites (depicted as {OH–Si–(OH)–Co–O–Si-(OH) 3 }) are successfully embedded into the silicalite-1 zeolite framework located in the straight and intersection channels (Co@S-1) with the assistance of Co precursors and geminal silanols via a facile hydrothermal synthesis , as revealed by detail characterizations. Under comparable conditions, a superior catalytic PDH performance with attractive propylene formation rate of 14.6 mmol·g cat −1 ·h −1 , propylene selectivity higher than 93% and very low deactivation rate of 0.0206 h −1 after 7 h is achieved over the Co@S-1(EDA) catalyst. Furthermore, the catalytic performance can be restored to the same as that of the fresh catalyst after 3 successive regenerations. In situ FTIR spectra analysis further reveals the dynamic changes in the characteristic absorption bands associated with the hydroxylated Co 2+ silicate sites and the intermediate product (2-propyl) during the PDH reaction and a reaction mechanism is proposed accordingly. This work provides a new insight for designing high-efficiency nonprecious metal PDH catalysts.
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Microbiology Spectrum
·
2023
·Vol. 11
·期 3
·
IF 3.7
Jinchao Xing,Chen Hu,Siqi Che,Yixin Lan,Lihong Huang,Lele Liu,Youqin Yin,Huanan Li,Ming Liao,Wenbao Qi
Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus that can cause central nervous system diseases in humans and animals. Host factors attempt to limit virus replication when the viruses invade the host by using various strategies for replication. It is essential to clarify the host factors that affect the life cycle of JEV and explore its underlying mechanism. Here, we found that USP1-associated factor 1 (UAF1; also known as WD repeat-containing protein 48) modulated JEV replication. We found that JEV propagation significantly increased in UAF1-depleted Huh7 cells. Moreover, we found that knockdown of UAF1 activated cell autophagic flux in further functional analysis. Subsequently, we demonstrated that autophagy can be induced by JEV, which promotes viral replication by inhibiting interferon-stimulated gene (ISG) expression in Huh7 cells. The knockdown of UAF1 reduced ISG expression during JEV infection. To explore the possible roles of autophagy in UAF1-mediated inhibition of JEV propagation, we knocked out ATG7 to generate autophagy-deficient cells and found that depletion of UAF1 failed to promote JEV replication in ATG7 knockout cells. Moreover, in ATG7-deficient Huh7 cells, interference with UAF1 expression did not lead to the induction of autophagy. Taken together, these findings indicate that UAF1 is a critical regulator of autophagy and reveal a mechanism by which UAF1 knockdown activates autophagy to promote JEV replication.IMPORTANCE Host factors play an essential role in virus replication and pathogenesis. Although UAF1 is well known to form complexes with ubiquitin-specific proteases, little is known about the function of the UAF1 protein itself. In this study, we confirmed that UAF1 is involved in JEV replication. Notably, we discovered a novel function for UAF1 in regulating autophagy. Furthermore, we demonstrated that UAF1 modulated JEV replication through its autophagy regulation. This study is the first description of the novel function of UAF1 in regulating autophagy, and it clarifies the underlying mechanism of the antiviral effect of UAF1 against JEV. These results provide a new mechanistic insight into the functional annotation of UAF1 and provide a potential target for increasing virus production during vaccine production.
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Small
·
2023
·Vol. 19
·期 28
·2301162
·
IF 13.3
Zewei Lian,Tingqing Wu,Huadong Wang,Jimei Chi,Lijun Cheng,Daixi Xie,Xiangyu Pan,Yuming Hu,Zhiyu Tan,Sisi Chen,Xu Yang,Yang Yun,Wei Wu,Chunbao Li,Meng Su,Yanlin Song
Rapid and ultra-sensitive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for early screening and management of COVID-19. Currently, the real-time reverse transcription polymerase chain reaction (rRT-PCR) is the primary laboratory method for diagnosing SARS-CoV-2. It is not suitable for at-home COVID-19 diagnostic test due to the long operating time, specific equipment, and professional procedures. Here an all-printed photonic crystal (PC) microarray with portable device for at-home COVID-19 rapid antigen test is reported. The fluorescence-enhanced effect of PC amplifies the fluorescence intensity of the labeled probe, achieving detection of nucleocapsid (N-) protein down to 0.03 pg mL −1 . A portable fluorescence intensity measurement instrument gives the result (negative or positive) by the color of the indicator within 5 s after inserting the reacted PC microarray test card. The N protein in inactivated virus samples (with cycle threshold values of 26.6–40.0) can be detected. The PC microarray provides a general and easy-to-use method for the timely monitoring and eventual control of the global coronavirus pandemic.
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