SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Dandan Hu,Tianyu Zhan,Zhiyong Guo,Sui Wang,Yufang Hu
A novel dual-modality readout biosensing method is developed for Cu(II), coenzyme (CoA) and histone acetyltransferase (HAT) analysis based on an electrosynthesized tris(bipyridine)ruthenium(II)-functionalized metal-organic framework (Ru-MOF). In this protocol, the Ru-MOF with a delicate structure serves as both an electrochemiluminescent (ECL) and fluorescent (FL) probe. Interestingly, Cu(II) can hinder the two distinct processes favorably, thus realizing bidirectional detection of Cu(II) via an “on-off” method. Simultaneously, CoA, which contains a sulfhydryl group, can ignite a reverse “off-on” process due to the polymeric interaction of CoA and Cu(II) (2: 1). Similarly, abundant CoA molecules could also be generated regularly by a typical HAT p300-driven acetylation reaction, hence accomplishing HAT p300 activity analysis. Subsequently, an ingenious “on-off” route is exhibited again by the introduction of some small molecules (including anacardic acid and C646), which present an inhibiting effect on HAT p300 activity. Furthermore, quantitative analysis of Cu(II), CoA and HAT p300 (ECL/FL) is achieved brightly with detection limits of 0.19/0.76 nM, 1.3/6.5 nM and 1.5/8.8 nM, respectively. Ultimately, this two-channel biosensor with excellent analytical performance is applied successfully in real samples, demonstrating its potential use in bioanalysis.
研究领域:
分析化学
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生物化学
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分子生物学
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DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2025
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IF 4.2
Xiaoqi Wang,Shuang Liu,Di Su,Jiayu Sui,Xiangyu Yan,Jia Yang,Ziqi Zheng,Penghe Wang,Weijun Song,Zexi Jin,Mingyan E,Maomao Zhang,Bo Yu
Background and aims Viral myocarditis is an inflammatory pathology of the myocardium that involves innate immune responses, especially those involving neutrophils. However, strategies targeting neutrophils to alleviate inflammation have not achieved complete success. Alpha lipoic acid (ALA), a natural organosulfur compound, has the capacity to modulate immune cell behavior. This study aimed to investigate whether ALAs can regulate innate immunity to provide protection against coxsackievirus B3 (CVB3)-induced myocarditis. Methods and results Abdominal administration of ALA improved cardiac dysfunction and reduced mortality in a CVB3-induced mouse model of myocarditis (VM). ALA treatment induced neutrophils and inhibited Ly6C hi pro-inflammatory macrophages, favoring a reparatory environment in the myocardium. However, depleting neutrophils with anti-Ly6G antibodies increased Ly6C hi pro-inflammatory macrophage recruitment in blood and heart in ALA-treated VM mice. Further flow cytometry analysis indicated that ALA promoted Ym-1 expression of neutrophils. Blocking Ym-1 significantly reversed ALA-mediated cardiac reparative macrophages infiltration and cardiac function improvement post-VM. Recombinant Ym-1 drives macrophages toward a reparative phenotype and attenuates CVB3-induced viral myocarditis. Mechanistically, ALA reprogrammed neutrophil metabolic patterns, leading to increased production of the metabolite acetyl-CoA, thereby increasing the transcription of Ym-1 by promoting STAT6 acetylation. Conclusions ALA protects against VM by activating metabolic reprogramming/STAT6 acetylation/Ym-1 axis in neutrophils. These results highlight the heterogeneity of neutrophils and suggest that ALA might represent a feasible strategy to improve the prognosis of VM patients.
研究领域:
免疫学
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病毒学
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心脏病学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Metabolism
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2025
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IF 30.9
Yu Cao,Yang Zhao,Tan Deng,Qigang Zhou,Gang Hu,Zhuang-Li Hu,Yan-Yi Jiang,Xiao-Han Yang,Fang Wang,Peng-Fei Wu,Jian-Guo Chen
Extensive research highlights impaired brain energy metabolism in neuropsychiatric disorders, whereas much less is known about the role of the peripheral metabolic state. The liver is the metabolic hub, and herein we demonstrate that hepatic hydrolysis of acetyl-coenzyme A, a central metabolic intermediate, signals the brain and helps buffer stress. Using a chronic social defeat stress paradigm in male mice, we observed a hepatic glucose-to-acetate metabolic switch, followed by a glucocorticoid-repressed transcription of the acetyl-coenzyme A hydrolase, acetyl-coenzyme A thioesterase 12, to confer stress vulnerability. Hepatic overexpression of acetyl-coenzyme A thioesterase 12 alleviated depression-like phenotypes via increasing acetate output to promote histone acetylation in the ventral hippocampus, which bolstered the expression of programmed cell death ligand 1 in astrocytes, limiting neuroinflammation and rescuing inhibitory synaptic transmission dysfunction. Our findings demonstrate that hepatic acetyl-coenzyme A hydrolysis serves as a key liver-brain axis component that regulates depression susceptibility.
研究领域:
神经生物学
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代谢学
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精神病学
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分子生物学
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免疫神经学
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表观遗传学
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肝脏病学
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转化医学
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产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
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2025
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IF 16.6
Guo Xiaoyu,Zhong Jinjing,Qian Jingyu,Pan Xiuyi,Zhang Xinyue,Chen Xueqin,Zeng Hao,Chen Ni,Nie Ling,Yu Ting,Zhou Qiao
Transfer RNA (tRNA)-derived fragments (tRFs) are a class of small non-coding RNAs that have recently been implicated in various physiological and pathological processes, including tumor development and progression. Identification of the roles of tRFs in cancer could provide insights into tumor biology and treatment strategies. Here, we found that tRF-21LeuTAA supported progression of prostate cancer by regulating glutathione metabolic enzymes and promoting reactive oxygen species (ROS) accumulation. Nuclear tRF-21LeuTAA upregulated leucyl aminopeptidase 3 (LAP3) by binding to its promoter and recruiting H3K27ac acetyltransferase P300 and transcription factor STAT1. The increased cystine-glycine dipeptidase activity of LAP3 led to increased degradation of the antioxidant glutathione. Alternatively, cytoplasmic tRF-21LeuTAA suppressed glutathione-S-transferase mu 3 (GSTM3) by repressing its mRNA post-transcriptionally, which further elevated ROS by decreasing scavenger glutathione S-transferase activity. The accumulation of intracellular ROS downstream of tRF-21LeuTAA-mediated alterations in LAP3 and GSTM3 resulted in AKT activation. Overexpression of tRF-21 promoted proliferation and migration of prostate cancer cells, formation of spheroids, and initiation and growth of tumors in a xenograft model. In patients, elevated tRF-21 and LAP3 levels were associated with unfavorable survival outcomes. The regulatory circuitry revealed in the present study may represent potential therapeutic targets for prostate cancer as well as various malignancies with tRF-21 overexpression.
研究领域:
分子生物学
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癌症研究
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生物化学
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遗传学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEURON
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2026
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IF 16.9
Ming-Yue Bao,Xiu-Qing Li,Qing-Qing Sun,Yan He,Yu-Jing Yin,Si-Han Li,Ruo-Yan Du,Gai-Xin Ma,Chen-Yu Feng,Bing Han,Rui Jia,Xuan Wang,Li-Bin Wang,Ya-Ping Yan,Xing Li,Yuan Zhang
Myelin injury, a hallmark of several neurological diseases, is highly sensitive to glucose metabolism disruptions. Here, we reveal that oligodendrocytes (OLs) within demyelinating lesions exhibit reduced glycolytic efficiency and lactate production compared with mature OLs. Administration of lactate, the product of glycolysis, or specific overexpression of lactate dehydrogenase A (LDHA), the enzyme in lactate production, in Olig1 + OLs significantly enhances remyelination. In contrast, conditional knockout of LDHA in the Olig1 + lineage or CNPase + premyelinating OLs leads to severe neuropathy with dysmyelination in a development-dependent and cell-specific manner. Mechanistic insights show that OLs within demyelinating lesions undergo lactylation silencing, a lactate-induced epigenetic modification that impedes myelin restoration. Furthermore, lactylation of LDHA and carbonic anhydrase II (CAII) couples glycolysis with OL maturation. Our findings elucidate the metabolic interplay among glycolysis, lactylation, and OL maturation and provide novel enzymatic therapeutic perspectives for demyelinating disorders, for which effective therapies are currently lacking.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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