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Advanced Science · 2025 · IF 14.1

ADA2 Forms Nuclear Condensates with GCN5 and ATP-Citrate Lyase (ACL) to Modulate H3K9 Acetylation at Genes Functioning in Rice Meristems

Yaping Yue,Tingting Lu,Xiaoyuan Guo,Biao Liu,Shiteng Lv,Heba A. M. Abdalla,Xuelei Lai,Ruihui Zhang,Jianpin Guo,Yu Zhao,Dao-Xiu Zhou,Shaoli Zhou

SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved histone acetyltransferase (HAT) complex in eukaryotes, playing a crucial role in regulating gene transcription during development. The complex consists of two core components: GCN5, the HAT subunit, and ADA2, which primarily functions as an adaptor and enhances the complex HAT activity. Beyond its well-established roles, it is discovered in this work that ADA2 in rice possesses a broadly existing intrinsically disordered region (IDR) that directs the formation of nuclear condensates. Moreover, ADA2 is found to interact with a subunit of ATP-citrate lyase (ACL), an enzyme that produces acetyl-CoA, leading to the formation of a GCN5-ADA2-ACL (GAA) complex. ADA2 promotes the condensation of both GCN5 and ACL in vivo. Within these condensates, ACL contributes to the production and enrichment of acetyl-CoA, thereby promoting histone acetylation. Genetic evidence showed that knock-out or suppression of these genes led to similarly diminished root meristem zone sizes and reduced branch primordia numbers, accompanied by significant reductions in genomic H3K9 acetylation and transcriptional attenuation of essential genes for meristem function. In summary, the findings unveil a novel mechanism of HAT action by forming phase separation to enrich acetyl-CoA within nuclear puncta, facilitating histone acetylation at target genes essential for meristem development.

CAS / MDL: 28631-66-5
研究领域: 植物生物学 · 分子遗传学 · 表观遗传学 · 发育生物学 · 生物化学
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PHARMACEUTICAL BIOLOGY · 2021 · IF 3.503

Hypouricaemic and nephroprotective effects of Poria cocos in hyperuricemic mice by up-regulating ATP-binding cassette super-family G member 2

Danling Liang,Tianqiao Yong,Xue Diao,Shaodan Chen,Diling Chen,Chun Xiao,Dan Zuo,Yizhen Xie,Xinxin Zhou,Huiping Hu

Context Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action.Objective To examine hypouricaemic action of Poria coco.Materials and methods Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed.Results P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 μmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 μmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 μmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate.Discussion and conclusions This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2020 · IF 7.1

Four-stage signal amplification for trace ATP detection using allosteric probe-conjugated strand displacement and CRISPR/Cpf1 trans-cleavage (ASD-Cpf1)

Xianfeng Wang,Xiaolong Chen,Chengxiang Chu,Yuanyi Deng,Mei Yang,Zhong Ji,Faliang Xu,Danqun Huo,Yang Luo,Changjun Hou

High-performance detection of adenosine triphosphate (ATP) is of great importance due to its irreplaceable roles in various physiological processes. In this work, a four-stage signal amplification was established for ATP detection based on an allosteric probe-conjugated strand displacement amplification (SDA) integrated with CRISPR/Cpf1 system (ASD-Cpf1). An allosteric probe (AH) with a hairpin structure was designed to reduce background interference from self-extension and non-specific amplification during the SDA reaction. ATP bound with the aptamer segment at 5′-terminal of AH probe and subsequently opened the AH probe to activate the SDA reaction. The amplification products were recognized by CRISPR/Cpf1 system and triggered the ssDNase activity of Cpf1, resulting in robust cleavage of surrounding DNA FQ-reporter (fluorophore-quencher labeled short single-stranded DNA sequence). With the four-step amplification, ATP was measured with high sensitivity and low background interference. Under the optimal conditions, a linear relationship was obtained between the fluorescence response and ATP concentrations ranging from 2 pM to 10 μM with a limit of detection (LOD) as low as 1.8 pM. Successful detection of ATP in diluted human serum samples further indicated that ASD-Cpf1 system provided a potential platform for detection of small molecules.

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Biotechnology Journal · 2025 ·Vol. 20 ·期 2 ·e202400707 · IF 3.1

Efficient Conversion of Nicotinamide Mononucleotide Based on Elucidation of the Limitations in Multienzyme Cascade Reactions

Fengrui Yu,Hongwen Li,Xianglong Li,Jianping Shi,Yanbin Feng,Song Xue

Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD), provides a direct method for maintaining NAD levels, which may alleviate aging and metabolic disorders. However, the enzymatic conversion of NMN in cascade reactions is limited by intermediate product inhibition, and quantitative insights into these limitations remain scarce. Here, an efficient multienzyme cascade system was developed by quantifying intermediate inhibition, which synthesizes NMN from D-ribose in three tandem reactions with an Adenosine Triphosphate (ATP) regeneration system and pyrophosphatase (PPase). A critical Adenosine Diphosphate (ADP) concentration of 0.5 mM was determined, which inhibits phosphoribosyl pyrophosphate synthetase (Prs) at 0.08 µM. The incorporation of an ATP regeneration system and PPase markedly increased the NMN yield to 81.3%. The intermediate phosphoribosyl pyrophosphate (PRPP) hydrolysis rate was measured at 3 µM/min. The highly active nicotinamide phosphoribosyltransferase (Nampt) could compete with PRPP hydrolysis, thereby increasing the yield of NMN. This research facilitates large-scale, efficient NMN manufacturing.

CAS / MDL: 1094-61-7
研究领域: 生物化学 · 代谢工程 · 合成生物学
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Autophagy · 2016 · IF 9.108

PRKAA/AMPK restricts HBV replication through promotion of autophagic degradation

Na Xie,Kefei Yuan,Li Zhou,Kui Wang,Hai-Ning Chen,Yunlong Lei,Jiang Lan,Qinqin Pu,Wei Gao,Lu Zhang,Guobo Shen,Qifu Li,Hengyi Xiao,Hong Tang,Rong Xiang,Mingliang He,Pinghui Feng,Edouard C. Nice,Yuquan Wei,Haiyuan Zhang,Jiayin Yang,Canhua Huang

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial energy sensor that maintains cellular energy homeostasis. AMPK plays a critical role in macroautophagy/autophagy, and autophagy facilitates hepatitis B virus (HBV) replication. To date, the intrinsic link among AMPK, autophagy and HBV production remains to be elucidated. Here, we demonstrate that PRKAA (a catalytic subunit of AMPK) is activated in response to HBV-induced oxidative stress, which in turn decreases the production of HBV. Mechanistic studies reveal that the autophagy machinery is associated with the inhibitory effect of PRKAA/AMPK on HBV production. Activation of PRKAA/AMPK promotes autolysosome-dependent degradation through stimulation of cellular ATP levels, which then leads to the depletion of autophagic vacuoles. Taken together, our data suggest that the activation of AMPK might be a stress response of host cells to restrict virus production through promotion of autophagic degradation. These findings therefore indicate that AMPK could provide a potential therapeutic target for HBV infection.

CAS / MDL: 99126-64-4
研究领域: 病毒学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2024 · IF 4.4

Analysis of microRNAs and the microRNA-messengerRNA regulatory network in chronic alcohol exposure

Du Ailin,Chen Yingying,Qiao Siyu,Dong Jiaxing,Li Yulin,Cao Bokai,Zhao Rongyu,Zhang Ruiling

Introduction: Chronic alcoholism is one of the most common neurological diseases in modern society. However, the key mechanisms underlying learning and memory impairments caused by chronic alcohol exposure remain unclear. In this study, a microRNA-messenger RNA (miRNA-mRNA) network was constructed to explore the potential function of key genes in chronic alcohol exposure, their effects on the hippocampus, and their mechanisms which facilitate brain injury in mice.Methods: The Morris water maze test was used to assess the learning ability of mice in each group. Mitochondrial ATPase activity and H2S levels in the hippocampi of mice were determined. Differentially expressed miRNAs and mRNAs in the mouse hippocampus were identified using second-generation sequencing. Using the TargetScan, miRTarBase, and miRDB databases, we predicted miRNA target genes and constructed a miRNA-mRNA regulatory network. Furthermore, using the Gene Ontology and KEGG databases we performed functional enrichment and protein-protein interaction analyses. Real-time quantitative polymerase chain reaction (qPCR) and other methods were employed to verify the mRNA expression of related genes.Results: The Morris water maze test revealed that mice exposed to chronic alcohol exhibited a significantly reduced learning ability compared to the control group (p < 0.05). Compared with the control group, the activity of mitochondrial ATPase in the hippocampal tissue of alcohol-treated mice was significantly decreased (p < 0.01), suggesting brain injury. In the model group, H2S significantly increased in the mice hippocampi (p < 0.01), indicating that chronic alcohol exposure could activate cystathionineβ-synthase (CBS) and catalyze the mass formation of H2S, suggesting brain injury. A total of 208 differentially expressed miRNAs and 377 differentially expressed mRNAs were screened through bioinformatic analysis. Enrichment analysis indicated that the main pathways were involved in neurodegeneration and regulation of the Wnt signaling pathway. The PCR detected a significant downregulation in the expressions of FOS and EGR1 genes.Discussion: Consequently, chronic alcohol exposure may regulate the expression of FOS and EGR1 in the hippocampus through miR-222-3p, miR-132-3p, miR-212-3p, and miR-191-5p, reduce the activity of hippocampal mitochondrial ATPase, activate CBS, catalyze the large amount of H2S formation, and destroy the mitochondrial structure, resulting in decreased learning ability. Our findings revealed valuable genes and miRNAs for the study of chronic alcohol exposure.

CAS / MDL: 64-17-5
研究领域: 神经生物学 · 分子生物学 · 生物信息学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC PLANT BIOLOGY · 2022 ·Vol. 22 ·期 1 ·1-12 · IF 5.26

Functional analysis revealed the involvement of ZmABCB15 in resistance to rice black-streaked dwarf virus infection

Yue Runqing,Sun Qi,Ding Jianguo,Li Wenlan,Li Wencai,Zhao Meng,Lu Shouping,Zeng Tingru,Zhang Hua,Zhao Suxian,Tie Shuanggui,Meng Zhaodong

Background Maize rough dwarf disease (MRDD), caused by rice black-streaked dwarf virus (RBSDV) belonging to the Fijivirus genus, seriously threatens maize production worldwide. Three susceptible varieties (Ye478, Zheng 58, and Zhengdan 958) and two resistant varieties (P138 and Chang7–2) were used in our study. Results A set of ATP-binding cassette subfamily B (ABCB) transporter genes were screened to evaluate their possible involvements in RBSDV resistance. In the present study, ZmABCB15 , an ABCB transporter family member, was cloned and functionally identified. Expression analysis showed that ZmABCB15 was significantly induced in the resistant varieties, not in the susceptible varieties, suggesting its involvement in resistance to the RBSDV infection. ZmABCB15 gene encodes a putative polar auxin transporter containing two trans-membrane domains and two P-loop nucleotide-binding domains. Transient expression analysis indicated that ZmABCB15 is a cell membrance localized protein. Over-expression of ZmABCB15 enhanced the resistance by repressing the RBSDV replication ratio. ZmABCB15 might participate in the RBSDV resistance by affecting the homeostasis of active and inactive auxins in RBSDV infected seedlings. Conclusions Polar auxin transport might participate in the RBSDV resistance by affecting the distribution of endogenous auxin among tissues. Our data showed the involvement of polar auxin transport in RBSDV resistance and provided novel mechanism underlying the auxin-mediated disease control technology.

研究领域: 植物病理学 · 分子生物学 · 功能基因组学
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ENVIRONMENTAL POLLUTION · 2017 · IF 5.099

The cardiovascular toxicity of triadimefon in early life stage of zebrafish and potential implications to human health

Hong-cui Liu,Tian-yi Chu,Li-li Chen,Wen-jun Gui,Guo-nian Zhu

The health risk of triadimefon (TF) to cardiovascular system of human is still unclear, especially to pesticide suicides population, occupational population (farmers, retailers and pharmaceutical workers), and special population (young children and infants, pregnant women, older people, and those with compromised immune systems) who are at a greater risk. Therefore, firstly we explored the toxic effects and possible mechanism of cardiovascular toxicity induced by TF using zebrafish model. Zebrafish at stage of 48 h post fertilization (hpf) exposed to TF for 24 h exhibited morphological malformations which were further confirmed by histopathologic examination, including pericardial edema, circulation abnormalities, serious venous thrombosis and increased distance between the sinus venosus (SV) and bulbus arteriosus (BA) regions of the heart. In addition to morphological changes, TF induced functional deficits in the heart of zebrafish, including bradycardia and a significant reduced cardiac output that became more serious at higher concentrations. To better understand the possible molecular mechanisms underlying cardiovascular toxicity in zebrafish, we investigated the transcriptional level of genes related to calcium signaling pathway and cardiac muscle contraction . Q-PCR (quantitative real-time polymerase chain reaction) results demonstrated that the expression level of genes related to ATPase ( atp2a1l , atp1b2b , atp1a3b ), calcium channel ( cacna1ab , cacna1da ) and cardiac troponin C ( tnnc1a ) were significantly decreased after TF exposure. For the first time, the present study revealed that TF exposure had observable morphological and functional negative impacts on cardiovascular system of zebrafish. Mechanistically, this toxicity might result from the pressure of down-regulation of genes associated with calcium signaling pathway and cardiac muscle contraction following TF exposure. These findings generated here can provide information for better pesticide poisoning treatments, occupational disease prevention, and providing theoretical foundation for risk management measures.

CAS / MDL: 30525-89-4
研究领域: 毒理学 · 环境健康 · 分子生物学 · 药理学
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Materials Today Bio · 2022 · IF 10.761

A multifunctional ATP-generating system by reduced graphene oxide-based scaffold repairs neuronal injury by improving mitochondrial function and restoring bioelectricity conduction

Huiquan Jiang,Xu Wang,Xiao Li,Yi Jin,Zhiwen Yan,Xiangyun Yao,Wei-En Yuan,Yun Qian,Yuanming Ouyang

Peripheral nerve injury usually impairs neurological functions. The excessive oxidative stress and disrupted bioelectrical conduction gives rise to a hostile microenvironment and impedes nerve regeneration. Therefore, it is of urgent need to develop tissue engineering products which help alleviate the oxidative insults and restore bioelectrical signals. Melatonin (MLT) is an important endogenous hormone that diminishes the accumulation of reactive oxygen species. Reduced graphene oxide (RGO) possesses the excellent electrical conductivity and biocompatibility. In this study, a multilayered MLT/RGO/Polycaprolactone (PCL) composite scaffold was fabricated with beaded nanostructures to improve cell attachment and proliferation. It also exhibited stable mechanical properties by high elastic modulus and guaranteed structural integrity for nerve regeneration. The live/dead cell staining and cell counting kit assay were performed to evaluate the toxicity of the scaffold. JC-1 staining was carried out to assess the mitochondrial potential. The composite scaffold provided a biocompatible interface for cell viability and improved ATP production for energy supply. The scaffold improved the sensory and locomotor function recovery by walking track analysis and electrophysiological evaluation, reduced Schwann cell apoptosis and increased its proliferation. It further stimulated myelination and axonal outgrowth by enhancing S100β, myelin basic protein, β3-tubulin, and GAP43 levels. The findings demonstrated functional and morphological recovery by this biomimetic scaffold and indicated its potential for translational application.

研究领域: 生物医学工程 · 神经科学 · 组织工程 · 材料科学
✓ 已验证 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2024 · IF 4.9

In situ complexation of bio-based ATP with copper and cobalt on graphene surfaces to improve the fire resistance of epoxy coatings

Mingwu Wang,Fei Zhong,Chunyan Chen,Xubin Yang,Chunlin Chen,Bin Wang,Hong Xia,Jiaming Song

Adenosine triphosphate (ATP), consisting of ribose, adenine and phosphate groups, can be used as a carbon, acid and gas source, respectively, in the combustion process, thereby being known as an ‘all-in-one’ intumescent flame retardant. Here, we prepared a new type of ATP-Cu/Co nanoparticles through the strong interaction between active N,O groups in the ATP structure and metal ions (Cu 2 + , Co 2+ ), and combined them with reduced graphene oxide (RGO) with high barrier ability to obtain a composite flame retardant (RGO@ATP-Cu/Co). The data showed that RGO/ACC 2.0 % /EP displayed the lowest backside temperature value (164.6 °C) during flame impingement. In comparison, RGO/ACC 2.0 % /EP displayed a significantly highest expansion height and expansion rate (25.4 mm, 16.96) during the calcination process. The RGO/ACC 2.0 % /EP ultimately reached the highest limiting oxygen index (LOI, 31.7 %), residual carbon content (31.4 %), and achieved a V 0 rating for the UL-94 test. Furthermore, the peak heat release rate (PHRR), total heat release rate (THR), peak smoke production rate (PSPR), total smoke production (TSP), and peak CO production rate (PCOPR) of RGO/ACC 2.0 % /EP were reduced by 38.4 %, 45.9 %, 46.6 %, 41.3 %, and 57.5 %, respectively, compared to pure EP, which proves its excellent flame retardant properties. In addition, signal markers specific to metal oxides were identified in the RGO/ACC 2.0 % /EP residual char structure, which significantly enhanced the oxidation resistance and thermal isolation efficacy of the residual carbon.

CAS / MDL: 10031-43-3
研究领域: 材料科学 · 化学工程
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JOURNAL OF HAZARDOUS MATERIALS · 2025 · IF 11.3

A zeolitic imidazolate framework-90 enhanced ultrasensitive ATP sensing platform with HCR and CRISPR-Cas12a dual signal amplification for live bacteria detection

Haoran Zheng,Jiayu Guo,Han Wang,Yurou Wang,Wenxiang Zhou,Ke Liu,Qiang Ma,Yanfei Qi

Bacteria are prevalent environmental pollutants. Live bacteria can proliferate and spread under appropriate conditions, presenting higher risks compared to non-viable counterparts. However, detecting live bacteria remains a challenge. Adenosine triphosphate (ATP), an energy currency in organisms, offers a reliable biomarker for the live bacteria sensing. Herein, we developed a zeolitic imidazolate framework-90 (ZIF-90) enhanced ATP sensing platform to detect live bacteria. The nanosystem which based on ZIF-90, encapsulating the DNA decorated magnetic beads (MB@S1) through self-assembly. When the S. aureus aptamers on ZIF-90 bonded to bacteria, the skeleton structure of ZIF-90 was disrupted by ATP leakage from live bacteria, leading to the release of MB@S1. Then, the MB@S1 initiated the hybridization chain reaction (HCR) and they were transduced by CRISPR-Cas12a to amplify the signal twice. The proposed ZIF-90 blocking sensing strategy (ZIF-90 strategy) exhibited remarkable sensitivity with the limit of detection (LOD) down to 0.223 pM for ATP detection, about 500 folds lower than the traditional ATP aptamer blocking sensing strategy (aptamer strategy). Furthermore, we used a smartphone for on-site analysis, realizing the quantification of live S. aureus with the LOD of 2.0 CFU/mL. Therefore, the approach possessed great application potential for public health, environment monitoring, bioanalysis and food safety.

研究领域: 生物化学 · 分子生物学 · 纳米医学 · 环境科学 · 食品安全
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2026 · IF 8.7

ATP-responsive injectable DNA hybrid hydrogels for regulating the “on-demand release” of fibroblast growth factor 21 cytokines to facilitate muscle regeneration

Ping-Ping He,Xinyu Wang,Zhaosheng Fan,Kunpeng Ma,Zhaoyan Tian,Zhe Wang,Enxiang Zhang

Effective regeneration of injured skeletal muscle remains a major challenge in clinical medicine. There is an urgent demand for therapeutic strategies capable of achieving precise spatiotemporal control over the muscle repair process. To address this clinical challenge, we propose an ATP-responsive injectable DNA hybrid hydrogel, specifically designed to enable “on-demand release” of cytokines, thereby enhancing muscle regeneration. Through the implementation of rational DNA sequence design and optimized cross-linking methodologies, the three-dimensional network of the hydrogel, which is capable of efficiently encapsulating a diverse range of cytokines known to promote tissue repair and remodeling, was constructed. This hydrogel can respond to the characteristic increases in ATP concentration fluctuations within the local tissue microenvironment, enabling precise control over cytokine release and thereby promoting the proliferation and differentiation of muscle cells. This DNA hydrogel, exhibiting excellent biocompatibility, creates a more favorable and functionally optimized microenvironment that supports and promotes muscle regeneration. This “on-demand release” capability not only enhances therapeutic efficacy but also prevents premature drug release prior to reaching the target site and minimizes off-target drug distribution to non-target tissues, thereby improving both the safety and controllability of regenerative treatments.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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