Bioactive Materials
·
2023
·
IF 18.9
Zhiguo Lu,Ruichen Zhao,Yi Li,Jianze Wang,Jing Guo,Chaobo Bai,Jing Chen,Jun Yang,Yiwan Geng,Tianlu Zhang,Yanyue Wu,Xiyue Jiao,Yining Wang,Junliang Yuan,Xin Zhang
Reactive oxygen species (ROS)-mediated oxidative stress exacerbates chronic diseases such as organ damage and neurodegenerative disorders. The Keap1-Nrf2-ARE pathway is a widely distributed endogenous antioxidant system. However, ROS under redox homeostasis regulates a wide range of life activities. Therefore, smart scavenging of excess ROS under pathological conditions is essential to treat chronic diseases safely. This study reports a smart antioxidant function enhancement (SAFE) strategy. On-demand release of nucleic acid drugs in a pathological ROS environment smartly activates the endogenous antioxidant system, thereby smartly alleviating oxidative stress in an exogenous antioxidant-independent manner. Through structural modulation and ligand modification, we develop SAFE nanoparticles based on nanohybrid complexes (SAFE-complex) adapted to brain delivery of nucleic acid drugs. SAFE-complex with homogeneous monodisperse structure efficiently treat ROS-related neurodegenerative diseases while protecting the major organ from oxidative stress damage. Moreover, SAFE-complex can stabilize storage in the form of freeze-dried powder. These data indicate that SAFE nanoparticles hold promise for treating ROS-related chronic diseases and comorbidities through rational transformation.
研究领域:
药理学
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纳米技术
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神经科学
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分子生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Jingjing Yao,Yajuan Guo,Ting Wan,Shaofang Yu,Qinghong Shen,Min Huang,Yu Li,Fuping Xu,Huiyan Zeng,Zhongqiu Liu,Linlin Lu
Ethnopharmacological relevance Aconitum carmichaelii Debx. exhibits overwhelming efficacy against heart failure, inflammation and pain, but its clinical application is limited by concomitant cardiotoxicity and neurotoxicity. Aconitine (AC), the most abundant bioactive alkaloid, has narrow therapeutic window, with well-defined toxic and therapeutic thresholds. However, the overlapping molecular targets mediating dual toxicity and efficacy of AC remain poorly characterized. Aims of the study This study aimed to evaluate dual pharmacological and toxicological roles of AC through integrative pharmacology and transgenic mouse models. Materials and methods The overlapping targets of AC-related toxicity/efficacy were identified based on integrative pharmacology. By generating Cyp3a −/− transgenic mice expressing human CYP3A4 (hCYP3A4), Ugt1, P-gp, Mrp2, BCRP, and Nrf2 knockout mice, the effects of AC on toxicity, pain, inflammation, and heart failure were assessed. Results We identified 143 overlapping targets predominantly enriched in metabolic pathways. Symptom-based toxicity scores were strikingly elevated in AC-exposed hCYP3A4, Mrp2 −/− , P-gp −/− , BCRP −/− , and Nrf2 −/− mice compared to WT mice. Additionally, AC prolonged the latency of response by approximately 18s, 15s, 14s, and 5s, respectively, in hCYP3A4, Mrp2 −/− , P-gp −/− , and Nrf2 −/− mice by hot plate assay. Interestingly, both toxicity score and analgesic latency initially increased and subsequently decreased, peaking at 60 min. AC obviously decreased the acetic acid-induced writhing and permeability by 45.7% and 22.2% in hCYP3A4 mice, whereas these changes were amplified in Mrp2 −/− mice compared to WT mice. Furthermore, AC attenuated DOX induced heart failure in hCYP3A4 mice, with an effective rate of 20.9%, with Septin4 implicated in AC-related metabolism. Conclusions Metabolic targets may elucidate the mechanistic overlap between the toxicity and efficacy of AC. Notably, hCYP3A4 exhibited heightened toxicity, alongside enhanced analgesic, anti-inflammatory, and cardioprotective effects. Our findings position metabolic pathways as critical nodes for AC-related dual effect, and establish Septin4 as a candidate mediator of its metabolic regulation.
研究领域:
药理学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 186
·期 1
·1-6
·
IF 5.705
Liu Jinshui,Bao Huijuan,Ma Dik-Lung,Leung Chung-Hang
The authors show that silver nanoclusters functionalized with Ce(III) ions are a viable fluorescent probe for selective and sensitive detection of sulfide at pH 7.0. The blue fluorescence of silver nanoclusters (with excitation/emission peaks at 358/426 nm) is enhanced on the addition of Ce(III) ions but is quenched in the presence of a trace concentrations of sulfide. A fluorometric assay was worked out using the Ce(III)/AgNCs as the probe. Sulfide can be detected in concentrations up to 2.0 μM, and the detection limit is 15 nM. The method was successfully applied to the determination of sulfide in spiked real samples.
Silver nanoclusters functionalized with Ce(III) ions are a viable “turn-on-off” fluorescent probe for selective and sensitive detection of sulfide at pH 7.0.
研究领域:
分析化学
·
生物化学
✓ 已验证
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Xinyi Zhou,Qian Xiao,Jie Tu
It is very important to maintain normal levels of risk avoidance in daily life. We found that DISC1-N TM mice, which are a model for mental disorders, had a phenotype marked by a risk-avoidance impairment as measured in an open-field test (OFT). We used optogenetic methods to modulate glutamatergic neurons in the basolateral amygdala (BLA) in an attempt to rescue this risk-avoidance impairment. We found that photostimulation of BLA neurons at 20 Hz modified DISC1-N TM mouse behavior from low risk avoidance to high risk avoidance. We observed following photostimulation that, compared to controls, the number of entries to the center of the open field was lower and less time was spent in the central area. We also found that the time spent immobile was higher during photostimulation compared with WT mice. We also used a lower photostimulation frequency of 5 Hz, which activated BLA glutamatergic neurons and rescued the risk-avoidance impairment in DISC1-N TM mice. Our findings confirm that the BLA participates in diverse risk-avoidance behavior. Our results are also a reminder that differences in neuronal firing patterns within the same pathway may lead to different physiological functions.
研究领域:
神经科学
·
行为科学
·
心理健康
✓ 已验证
DOI
PubMed
高影响因子
Cell Death & Disease
·
2019
·Vol. 10
·期 10
·1-17
·
IF 5.959
Zhang Yue,He Wenhua,He Cong,Wan Jianhua,Lin Xiao,Zheng Xi,Li Lei,Li Xueyang,Yang Xiaoyu,Yu Bingjun,Xian Xunde,Zhu Yin,Wang Yuhui,Liu George,Lu Nonghua
Hypertriglyceridemia severity is linked to acute pancreatitis prognosis, but it remains unknown why a portion of severe hypertriglyceridemia patients do not develop severe acute pancreatitis. To investigate whether hypertriglyceridemia subtypes affect acute pancreatitis progression, we analyzed two genetically modified hypertriglyceridemia mouse models—namely, glycosylphosphatidylinositol high-density lipoprotein binding protein 1 knockout (Gpihbp1−/−) and apolipoprotein C3 transgenic (ApoC3-tg) mice. Acute pancreatitis was induced by 10 intraperitoneal caerulein injections. Biochemical assays and pathological analysis were performed for the severity evaluation of acute pancreatitis. Plasma triglyceride-rich lipoproteins (TRLs), including chylomicrons and very low-density lipoprotein (VLDL), were collected via ultracentrifugation to evaluate their cytotoxic effects on primary pancreatic acinar cells (PACs). We found that the particle sizes of Gpihbp1−/− TRLs were larger than ApoC3-tg TRLs. Severe pancreatic injury with large areas of pancreatic necrosis in the entire lobule was induced in Gpihbp1−/− mice when plasma triglyceride levels were greater than 2000 mg/dL. However, ApoC3-tg mice with the same triglyceride levels did not develop large areas of pancreatic necrosis, even upon the administration of poloxamer 407 to further increase triglyceride levels. Meanwhile, in the acute pancreatitis model, free fatty acids (FFAs) in the pancreas of Gpihbp1−/− mice were greater than in ApoC3-tg mice. TRLs from Gpihbp1−/− mice released more FFAs and were more toxic to PACs than those from ApoC3-tg mice. Chylomicrons from patients showed the same effects on PACs as TRLs from Gpihbp1−/− mice. Gpihbp1−/− mice with triglyceride levels below 2000 mg/dL had milder pancreatic injury and less incidence of pancreatic necrosis than those with triglyceride levels above 2000 mg/dL, similar to Gpihbp1−/−mice with triglyceride levels above 2000 mg/dL but with fenofibrate administration. These findings demonstrated that hypertriglyceridemia subtypes with large TRL particles could affect acute pancreatitis progression and that chylomicrons showed more cytotoxicity than VLDL by releasing more FFAs.
研究领域:
医学
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生物化学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Xin Zhao,Ting Hao,Jianmin Sang,Miaomiao Xia,Linxi Li,Ren-shan Ge,Congde Chen
Dithiocarbamates have been widely used in various industrial applications, such as insecticides (ferbam) or drug (disulfiram). This study explored the inhibitory effects of dithiocarbamates on human and rat gonadal 3β-hydroxysteroid dehydrogenases (3β-HSD) and investigated the structure-activity relationship and mechanistic insights. The inhibitory activity of six dithiocarbamates and thiourea on the conversion of pregnenolone to progesterone was evaluated using human KGN cell and rat testicular microsomes, with subsequent progesterone measurement using HPLC-MS/MS. The study found that among the tested compounds disulfiram, ferbam, and thiram exhibited significant inhibitory activity against human 3β-HSD2 and rat 3β-HSD1, with ferbam demonstrating the highest potency. The mode of action for these compounds was characterized, showing mixed inhibition for human 3β-HSD2 and mixed/noncompetitive inhibition for rat 3β-HSD1. Additionally, it was observed that dithiothreitol dose-dependently reversed the inhibitory effects of dithiocarbamates on both human and rat gonadal 3β-HSD enzymes. The study also delved into the penetration of these dithiocarbamates through the human KGN cell membrane and their impact on progesterone production, highlighting their potency in inhibiting human 3β-HSD2. Furthermore, bivariate correlation analysis revealed a positive correlation of LogP (lipophilicity) with IC 50 values for both enzymes. Docking analysis indicated that dithiocarbamates bind to NAD + and steroid-binding sites, with some interactions with cysteine residues. In conclusion, this study provides valuable insights into the structure-activity relationship and mechanistic aspects of dithiocarbamates as inhibitors of human and rat gonadal 3β-HSDs, suggesting that these compounds likely exert their inhibitory effects through binding to cysteine residues.
研究领域:
药理学
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毒理学
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内分泌学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Haohao Zhang,Xiaoran Gong,Jiachen Ye,Xue Li
The triboelectric charge of the triboelectric nanogenerator (TENG) will decrease due to the interfacial electric field. This work prepared PVDF/BaTiO 3 /MXene nanocomposite films as the intermediate layer between the negative friction material and the bottom electrode. The output voltage is about 450 % higher than that without the intermediate layer. Adding PVDF/BaTiO 3 enhanced the polarization effect, and adding MXene material provided abundant electron capture sites. Under the synergistic impact of electron storage and polarization effect, the triboelectric output of HOT-TENG is enhanced. Based on a single-electrode model, the e-skin patch collaboratively utilizes electrical stimulation and the photothermal effects of MXene to promote the proliferation and migration of fibroblasts over a short period (about 24 hours) without significant effects on cell survival. These findings support the development of TENG for wound healing and highlight the potential for developing portable enhanced electrical stimulation and photothermal patch devices.
研究领域:
生物医学工程
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材料科学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Chem
·
2020
·
IF 19.735
Fenglei Shi,Wenpei Gao,Hao Shan,Fan Li,Yalin Xiong,Jiaheng Peng,Qian Xiang,Wenlong Chen,Peng Tao,Chengyi Song,Wen Shang,Tao Deng,Hong Zhu,Hui Zhang,Deren Yang,Xiaoqing Pan,Jianbo Wu
Summary Corrosion of nanoparticles during electrocatalysis, such as oxygen reduction reaction (ORR), occurs at the nanoscale and is vital for catalyst stability. Here, using liquid cell (LC) transmission electron microscopy (TEM), we study the corrosion process of palladium@platinum (Pd@Pt) core-shell octahedra in real time and reveal that both the static local strain and the evolving curvature synergistically control the nanoscale corrosion kinetics. Specifically, in locations with tensile strain and high local curvature, the etching process is much faster. Density functional theory (DFT) calculation suggests that the dissolution potential of the Pd nanocrystal decreases as the strain increases; meanwhile, Pd atoms tend to be corroded more easily on a surface under tensile strain than on one under compressive strain. With these insights on the corrosion mechanism at the nanoscale, we subsequently designed and synthesized nanoparticles with smaller strain, and these showed higher durability in both an in situ LC study and an ex situ ORR stability test.
研究领域:
材料科学
·
化学
✓ 已验证
DOI
高影响因子
Virulence
·
2026
·
IF 6.8
Xiuwen Bao,Ruiqi Wang,Xiaolin Qian,Yapei Wang,Ting Li,Qinghe Wang,Sijing Liu,Shuqi Niu,Jinlin Guo
Chinese cordyceps consists of fruiting body and sclerotia (larvae part) formed through the parasitism of the insect Hepialidae by the fungus Ophiocordyceps sinensis, but artificial cultivation is hindered by fruiting body abortion, severely impacting yield and quality. The interactions between the fungus, its host insects, and soil are critical for its development. Multi-omics analyses were conducted to compare normally and abnormally developing samples, examining microbial communities and metabolites in fungus-colonized host larvae and the mycosphere soil. Abnormal fruiting body development was associated with profound shifts in microbial ecology: fungal diversity increased significantly in both endophytic larvae and mycosphere soil, whereas bacterial diversity decreased within host larvae. The microbial composition in and around abnormal samples was markedly altered, characterized by a high enrichment of Penicillium fungi and a depletion of Bacillus bacteria. Cross-kingdom microbial network analysis showed fewer connections and lower stability in abnormally developing samples. Untargeted metabolomic profiling revealed significant accumulation of the antibiotics N1-hydroxy-roquefortine C and glandicoline A, both roquefortine C derivatives characteristic of Penicillium metabolism, along with enriched pathways involved in antibiotic biosynthesis. Exploratory Partial Least Squares Structural Equation Modeling (PLS-SEM) analysis supported an associative pathway in which Penicillium-mediated toxicity is correlated with microbial dysbiosis, which in turn is associated with fruiting body abortion. Conversely, Bacillus may play a critical role in suppressing Penicillium overgrowth and maintaining microbial homeostasis, representing a promising target for biocontrol strategies. This study is the first to reveal potential links between Penicillium‑mediated toxicity, microbial imbalance, and developmental disorders of Chinese cordyceps.
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Saifei Liu,Muye Xiao,Anfei Fang,Binnian Tian,Yang Yu,Chaowei Bi,Dongfang Ma,Yuheng Yang
Plant lysin motif (LysM) ectodomain receptors interact with pathogen-associated molecular patterns (PAMPs) and have critical functions in plant–microbe interactions. In this study, 65 LysM family genes were identified using the recent version of the reference sequence of bread wheat (Triticum aestivum), in which 23, 16, 20, and 6 members belonged to LysM-containing receptor-like kinases (LYKs), LysM-containing receptor-like proteins (LYPs), extracellular LysM proteins (LysMes), and intracellular nonsecretory LysM proteins (LysMns), respectively. The study found that TaCEBiP, TaLYK5, and TaCERK1 were highly responsive to PAMP elicitors and phytopathogens, with TaCEBiP and TaLYK5 binding directly to chitin. TaCERK1 acted as a coreceptor with TaCEBiP and TaLYK5 at the plasma membrane. Overexpression of TaCEBiP, TaLYK5, and TaCERK1 in Nicotiana benthamiana leaves exhibited enhanced resistance to Sclerotinia sclerotiorum. Subsequently, knocking down TaCEBiP, TaLYK5, and TaCERK1 genes with barley stripe mosaic virus–VIGS compromised the wheat defense response to an avirulent strain of Puccinia striiformis. The study concluded that wheat has two synergistic chitin perception systems for detecting pathogen elicitors, with the activated CERK1 intracellular kinase domain leading to signaling transduction. This research provides valuable insights into the functional roles and regulatory mechanisms of wheat LysM members under biotic stress.
研究领域:
植物学
·
分子生物学
·
植物病理学
✓ 已验证
DOI
高影响因子
GENOME BIOLOGY
·
2024
·Vol. 25
·期 1
·1-26
·
IF 10.1
Sun Daming,Bian Gaorui,Zhang Kai,Liu Ning,Yin Yuyang,Hou Yuanlong,Xie Fei,Zhu Weiyun,Mao Shengyong,Liu Junhua
Background The function of diverse ruminal microbes is tightly linked to rumen development and host physiology. The system of ruminal microbes is an excellent model to clarify the fundamental ecological relationships among complex nutrient–microbiome–host interactions. Here, neonatal lambs are introduced to different dietary regimes to investigate the influences of early-life crosstalk between nutrients and microbiome on rumen development. Results We find starchy corn-soybean starter-fed lambs exhibit the thickest ruminal epithelia and fiber-rich alfalfa hay-fed lambs have the thickest rumen muscle. Metabolome and metagenome data reveal that indole-3-carboxaldehyde (3-IAld) and prostaglandin D2 (PGD2) are the top characteristic ruminal metabolites associated with ruminal epithelial and muscular development, which depend on the enhanced ruminal microbial synthesis potential of 3-IAld and PGD2. Moreover, microbial culture experiment first demonstrates that Bifidobacterium pseudolongum is able to convert tryptophan into 3-IAld and Candida albicans is a key producer for PGD2. Transcriptome sequencing of the ruminal epithelia and smooth muscle shows that ruminal epithelial and muscular development is accompanied by Wnt and Ca 2+ signaling pathway activation. Primary cell cultures further confirm that 3-IAld promotes ruminal epithelial cell proliferation depending on AhR-wnt/β-catenin signaling pathway and PGD2 accelerates ruminal smooth muscle cell proliferation via Ca 2+ signaling pathway. Furthermore, we find that 3-IAld and PGD2 infusion promote ruminal epithelial and musculature development in lambs. Conclusions This study demonstrates that early-life ruminal microbiome-derived 3-IAld and PGD2 are effective promoters of rumen development, which enhances our understanding of nutrient–microbiome–host interactions in early life.
研究领域:
动物科学
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Lei Xu,Yuting Wang,Erqun Song,Yang Song
Polybrominated diphenyl ethers (PBDEs) are a category of brominated flame retardants , which were widely used in industrial products since the 1970 s. Our previous studies indicated quinone-type metabolites of PBDEs (PBDE-Qs) cause neurotoxicity, however, their inherent toxicological mechanism remains unclear. Here, we first synthesized PBDE-Qs and corresponding reduced hydroquinone homologous (PBDE-HQs) with different pattern of bromine substitution. Their nucleophilic and redox properties were investigated. PBDE-Qs react with reduced glutathione (GSH) via Michael addition and bromine displacement reaction, whilst PBDE-HQs lack the ability of reacting with GSH. Of note, the displacement reaction only occurs with bromine on the quinone ring of PBDE-Qs but not phenyl ring. Next, electron paramagnetic resonance (EPR) analysis revealed the generation of SQ •− , along with their downstream hydroxyl radical (HO ) and methyl radical ( CH 3 ) through a PBDE quinone/semiquinone/hydroquinone (Q/SQ •− /HQ) futile cycle. In addition, a structure-dependent cytotoxicity pattern was found, the exposure of PBDE-Q/HQ with bromine substitution on the quinone ring resulted in higher level of apoptosis and autophagy in BV2 cells. In conclusion, this work clearly demonstrated that the nucleophilic and redox properties of PBDE-Qs/HQs are responsible for their neurotoxicity, and this finding provide better understanding of neurotoxicity of PBDEs.
研究领域:
环境科学
·
毒理学
·
神经科学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）