INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Shu-Li Wei,Ying Yang,Cong-Cong Wang,Xue-Min Li,Yuan-Wei Li,Xiao-Li Li,Yang Zhou,Tong Du,Ru-Tao Liu,Ying Liu,Bing Yang,Rui-Sheng Duan,Peng Zhang,Chun-Lin Yang
MCT1 is highly expressed by activated and germinal center B cells. • Targeting MCT1 suppressed humoral response and autoimmunity. • Targeting MCT1 inhibited B cell survival by modulating NAD(H) redox state. Immunometabolism has garnered significant attention due to its essential roles in regulating B cell activation, proliferation and differentiation. Monocarboxylate transporters (MCTs), a family of solute carrier transporters responsible for lactate transport across biological membranes, have been shown to play a pivotal role in immune responses across various immune cell types. However, the expression and functional significance of MCTs in B cells remain poorly understood. In this study, we demonstrated that germinal center B cells and activated B cells exhibit elevated levels of MCT1 expression. Pharmacologically blocking MCT1 with AZD3965 inhibited both T-cell dependent and independent humoral response and ameliorated autoimmunity in the experimental autoimmune myasthenia gravis. Mechanically, MCT1 blockade led to the accumulation of intracellular lactate, which in turn suppressed NAD + regeneration, thereby inhibiting B cell activation and survival. Taken together, these findings suggest that MCT1 might be a potential therapeutical target in antibody-mediate autoimmune disease. Download: Download high-res image (95KB) Download: Download full-size image
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高影响因子
Materials Today Bio
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2026
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IF 11
Huaze Ding,Xinhui Huang,Peng Hu,Xiaoyan Zhang,Yulin Wang,Baiwei Mao,Jianxin Ye,Dianwen Song,Chong Zhang,Changping Wang
Acute kidney injury (AKI) represents a critical medical condition with high mortality and no effective pharmacotherapy. Mitochondrial dysfunction in proximal tubular epithelial cells (PTECs), characterized by NAD + depletion, CoQ oxidation, and reactive oxygen species (ROS) overproduction, is a central driver of tubular damage and maladaptive repair. As central metabolic molecules, NAD + and CoQ can effectively ameliorate acute kidney injury by alleviating mitochondrial oxidative stress. However, the bioavailability of NAD + is limited by its short half-life, instability, and poor membrane permeability, whereas CoQ, despite being lipophilic, lacks specific mitochondrial targeting, preventing maximal therapeutic efficacy. Here, we report carrier-free NAD + /MitoQH 2 nanoparticles (NM NPs) with ultrasmall size and ROS-responsive properties. NM NPs are designed to pass through the glomerular filtration barrier and preferentially accumulate in injured renal tubules, where they may replenish the NAD + pool and provide a pre-reduced, mitochondria-targeted ubiquinol to support the CoQ axis under oxidative stress. Through renal accumulation and ROS-responsive release, NM NPs showed therapeutic efficacy in hypoxia/reoxygenation- and cisplatin-induced AKI models, as evidenced by reduced ROS accumulation, improved mitochondrial oxidative phosphorylation, enhanced autophagy, and attenuated ferroptosis. This work presents a metabolic nanomedicine strategy based on the co-assembly of bioactive molecules to modulate the mitochondrial NAD + –CoQ axis, providing a promising platform for AKI therapy and potentially other mitochondria-associated diseases.
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高影响因子
Small
·
2026
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IF 11.8
Le Jing,Yexin Pan,Yangyi Huang,Nan Xu,Siyu Chen,Haosong Zhong,Yi Chen,Yee Him Timothy Chan,Mitch Guijun Li
Nicotinamide adenine dinucleotide ( NAD + ${\rm NAD}^+$ ) is a core redox cofactor, and its concentration reflects age and metabolic state, which has driven the development of NAD + ${\rm NAD}^+$ biochemical analytical techniques. Although electrochemical techniques can rapidly and directly detect NAD + ${\rm NAD}^+$ levels, the translation of laboratory sensors into deployable solutions is often limited by the complexity of electrode interface preparation and batch-to-batch variability. Especially among enzyme-assisted methods, the multi-step biochemical immobilization and activity preservation processes are required. Therefore, developing enzyme-free and scalable NAD + ${\rm NAD}^+$ electroanalytical manufacturing strategies remains important. Here, a rapid two-step laser-induced transfer strategy is proposed to fabricate flexible silver nanoparticle–decorated carbon cloth electrodes (AgNPs@CC) for enzyme-free NAD + ${\rm NAD}^+$ sensing. This strategy reduced interfacial impedance and established a robust cathodic window for enzyme-free NAD + ${\rm NAD}^+$ detection. The electrodes exhibit a linear operating range of 10–300 , an excellent sensitivity (S = −3.16 ) at the low concentration range(10–100 ), and outstanding tolerance to typical interferents (LA, UA, AA, glucose, and NADH) and robust storage stability. This method eliminates the wet-chemical nanoparticle synthesis step and simplifies the production workflow, offering potential for applications like integration into portable sensing platforms.
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高影响因子
Nanomaterials
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2018
·Vol. 8
·期 2
·127
·
IF 3.504
Sen Lin,Shiyong Sun,Ke Wang,Kexuan Shen,Biaobiao Ma,Yuquan Ren,Xiaoyu Fan
The bioinspired design and construction of enzyme@capsule microreactors with specific cell-like functionality has generated tremendous interest in recent years. Inspired by their fascinating complexity, scientists have endeavored to understand the essential aspects of a natural cell and create biomimicking microreactors so as to immobilize enzymes within the hierarchical structure of a microcapsule. In this study, simultaneous encapsulation of alcohol dehydrogenase (ADH) was achieved during the preparation of microcapsules by the Pickering emulsion method using amphiphilic modified TiO2nanoparticles (NPs) as building blocks for assembling the photocatalytic microcapsule membrane. The ADH@TiO2NP microreactors exhibited dual catalytic functions, i.e., spatially confined enzymatic catalysis and the membrane-associated photocatalytic oxidation under visible light. The sustainable cycling of nicotinamide adenine dinucleotide (NAD) coenzyme between NADH and NAD+was realized by enzymatic regeneration of NADH from NAD+reduction, and was provided in a form that enabled further photocatalytic oxidation to NAD+under visible light. This bioinspired ADH@TiO2NP microreactor allowed the linking of a semiconductor mineral-based inorganic photosystem to enzymatic reactions. This is a first step toward the realization of sustainable biological cycling of NAD+/NADH coenzyme in synthetic functional microsystems operating under visible light irradiation.Keywords:enzyme encapsulation;bioinspired microreactors;nicotinamide coenzymes cycling;alcohol dehydrogenase;TiO2nanoparticles
研究领域:
生物化学
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材料科学
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光催化
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高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
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2023
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IF 4.3
Yuan-Yang Guo,Ze-Hua Tian,Yu-Chen Han,Dandan Ma,Tianju Shao,Zhiyong Jiang
Graphical Chemically stable Hantzsch ester is discovered to be an efficient and economical NAD(P)H mimic as sacrificial electron source in in vitro bioconversions. Biocatalysis has emerged as a valuable and reliable tool for industrial and academic societies, particularly in fields related to bioredox reactions. The cost of cofactors, especially those needed to be replenished at stoichiometric amounts or more, is the chief economic concern for bioredox reactions. In this study, a readily accessible, inexpensive, and bench-stable Hantzsch ester is verified as the viable and efficient NAD(P)H mimic by four enzymatic redox transformations, including two non-heme diiron N -oxygenases and two flavin-dependent reductases. This finding provides the potential to significantly reduce the costs of NAD(P)H-relying bioredox reactions.
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高影响因子
DEVELOPMENTAL CELL
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2020
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IF 10.092
Yejun Zou,Aoxue Wang,Li Huang,Xudong Zhu,Qingxun Hu,Yinan Zhang,Xianjun Chen,Fengwen Li,Qiaohui Wang,Hu Wang,Renmei Liu,Fangting Zuo,Ting Li,Jing Yao,Yajie Qian,Mei Shi,Xiao Yue,Weicai Chen,Zhuo Zhang,Congrong Wang,Yong Zhou,Linyong Zhu,Zhenyu Ju,Joseph Loscalzo,Yi Yang,Yuzheng Zhao
Summary Understanding of NAD + metabolism provides many critical insights into health and diseases, yet highly sensitive and specific detection of NAD + metabolism in live cells and in vivo remains difficult. Here, we present ratiometric, highly responsive genetically encoded fluorescent indicators, FiNad, for monitoring NAD + dynamics in living cells and animals. FiNad sensors cover physiologically relevant NAD + concentrations and sensitively respond to increases and decreases in NAD + . Utilizing FiNad, we performed a head-to-head comparison study of common NAD + precursors in various organisms and mapped their biochemical roles in enhancing NAD + levels. Moreover, we showed that increased NAD + synthesis controls morphofunctional changes of activated macrophages, and directly imaged NAD + declines during aging in situ . The broad utility of the FiNad sensors will expand our mechanistic understanding of numerous NAD + -associated physiological and pathological processes and facilitate screening for drug or gene candidates that affect uptake, efflux, and metabolism of this important cofactor.
研究领域:
分子生物学
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细胞生物学
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生物化学
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衰老研究
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成像技术
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2025
·
IF 5.6
Heng Tang,Ke Ning,Boji Wu,Xuhong Wang,Jingyu He,Pingping Li,Lina Pan,Jiawen Zhang,Yi He,Shizhu Bian,Xingyu Ma,Jihang Zhang,Chuan Liu,Zhexue Qin,Houyuan Hu
Scutellarein (Sc), a natural flavonoid, holds potential for treating pulmonary arterial hypertension (PAH), yet its mechanisms remain unexplored. This study investigated Sc’s therapeutic effects and underlying pathways in PAH. In vivo experiments demonstrated that Sc significantly attenuated right ventricular hypertension, pulmonary arterial remodeling, αSMA expression, and vascular inflammation in PAH models. In vitro, Sc suppressed hypoxia-induced proliferation, migration, inflammation, and pyroptosis in human pulmonary artery smooth muscle cells (HPASMCs). Mechanistically, Sc activated the SIRT1/NAD + axis to restore mitochondrial homeostasis: it upregulated SIRT1 expression and elevated NAD + levels by promoting SIRT1-mediated deacetylation of nicotinamide nucleotide transhydrogenase (NNT), thereby enhancing NNT activity. Elevated NAD + further activated SIRT1, forming a self-reinforcing SIRT1/NNT/NAD + feedback loop that mitigated hypoxia-induced mitochondrial dysfunction. This study identifies Sc as a novel regulator of the SIRT1-dependent NNT deacetylation pathway, which stabilizes NAD + homeostasis to counteract HPASMCs dysregulation in PAH. These findings highlight Sc’s potential as a therapeutic candidate for PAH, offering insights into targeting mitochondrial-metabolic pathways for vascular remodeling diseases.
研究领域:
药理学
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心血管疾病
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分子生物学
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Song Lin,Zhengyu Tao,Zhenhui Li,Shangsong Li,Xiaoliang Wang,Xiaoman Liu,Xin Huang
The development of biotic-abiotic photosynthetic systems is becoming one of the most promising strategies towards the thirsty demand for sustainable energy production. However, considerable efforts are still required to further optimize the design and avoid the utilization of high-value substances while achieving highly efficient hydrogen production. Here we show a way to construct an Escherichia coli ( E. coli )-quantum dots hybrid system by expressing ferredoxin (Fd), Fd-NAD(P) + reductase (FNR), and [FeFe]-hydrogenase ([FeFe]H 2 ase) as a potential biocatalyst. We reveal that electrons originating from the quantum dots could be redirected through the newly established electron transport chain NADH/NAD + -FNR-Fd to [FeFe]H 2 ase, which contributes a key mechanism to boost the highest H 2 production activity (3149.5 μmol g dcw −1 h −1 ) by only using glycerol as the carbon source. Our work sheds light on the advantages of an intracellular biological hybrid system by combining the photocatalytic capacity with the optimized metabolic power to produce biofuels.
研究领域:
生物技术
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生物能源
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光合作用
·
催化
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Bin Liu,Xiaoyang Zhang,Xia Xue,Fazhan Li,Feifei Ren,Ihtisham Bukhari,Baitong Hu,Xiangdong Sun,Bo Zhang,Yong Yu,Quan Zheng,Wanqiang Wu,Yuming Fu,Junwei Bai,Haipeng Liu,Alfred Tay,Thomas F. Meyer,Barry J. Marshall,Pengyuan Zheng,Yang Mi
Gastric intestinal metaplasia (GIM) is a progressive lineage reprogramming process characterized by loss of gastric identity and acquisition of intestinal features. Although disruption of NAD + (nicotinamide adenine dinucleotide) homeostasis is closely linked to chronic inflammation, its role in gastric metaplastic conversion remains unclear. Here, we establish the first human-derived organoid model of type III incomplete GIM recapitulating goblet cell differentiation, alongside four complementary mouse models representing distinct etiologies of metaplasia. Across human tissues, organoids, and in vivo models, we identify consistent upregulation of the NAD + -consuming enzyme CD38, resulting in chronic NAD + depletion. We also confirm NAD + loss reduces SIRT1 activity and increases acetylation of the gastric lineage regulator SOX2 at lysine 73, promoting its nuclear export and functional inactivation. The acute NAD + depletion disrupts gastric lineage maintenance programs without immediately inducing CDX2, while sustained metabolic erosion permits stable intestinal commitment, defining a hierarchical model of lineage conversion. In parallel, the supplementation with nicotinamide mononucleotide (NMN) restores NAD + pools, rescues SIRT1 activity, reduces SOX2 acetylation, and reverses metaplastic phenotypes in both human-derived organoids and mouse models. Our findings reveal a CD38–NAD + –SIRT1–SOX2 axis that metabolically drives gastric epithelial identity and position NAD + homeostasis as a potential strategy for intercepting early gastric tumorigenesis.
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高影响因子
ACS Sustainable Chemistry & Engineering
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2025
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IF 7.3
Weiwei Liu,Zichen Yu,Zhichao Chen,Ling Ma,Yanghao Liu,Zhen Zhang,Qingyang Xu
5-Hydroxytryptamine (5-HT), also known as serotonin, plays a critical role in mood regulation, insomnia treatment, and free radical scavenging. Currently, 5-HT production primarily relies on plant extraction, which is challenged by limited raw materials and environmental concerns, emphasizing the need for innovative green production strategies. In this study, we explored a high-performance producer for biosynthesizing 5-HT in Escherichia coli. First, we constructed and optimized the 5-HT biosynthetic pathway to convert L-tryptophan (l-Trp) to 5-HT, avoiding the accumulation of tryptamine and 5-hydroxytryptophan. Moreover, precursor enrichment eliminated the need for l-Trp supplementation and dynamic downregulation of pyruvate kinase balanced growth and production. Further, the metabolic flux between the tetrahydrobiopterin (BH4) module and the hydroxylation-decarboxylation module was optimized, reducing l-Trp accumulation. A novel “GXAA” system was implemented to enhance intracellular NAD(P)H supply, including (1) expression of gdhbsu (glucose dehydrogenase) from Bacillus subtilis, gapXfbr (mutated glyceraldehyde-3-phosphate dehydrogenase) from Corynebacterium glutamicum, and pntAB (pyridine nucleotide transhydrogenase); (2) knockout of ldhA (lactate dehydrogenase). Finally, transcriptomic analysis under high-5-HT stress revealed a potential 5-HT transporter, YhjX. The resulting strain WW15 produced 15.5 g/L 5-HT and a yield of 0.063 g/g glucose through a two-stage fed-batch fermentation, representing the highest titer and yield reported to date.
研究领域:
生物化学
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合成生物学
·
微生物学
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高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2025
·
IF 3.9
Zhaoyuan Zhang,Jiehu Liu,Meng Wang,Yang Li,Minglei Hou,Jiaren Cao,Jing Wu,Lingqia Su
Nicotinamide mononucleotide (NMN) serves as a crucial precursor in the biosynthesis of NAD + and has garnered significant attention in the food, dietary supplement, and cosmetic industries. This study engineered an Escherichia coli strain capable of high NMN production. Firstly, the strain with reduced NMN degradation and the ability to transport NMN extracellularly was constructed. Meanwhile, the gene encoding nicotinamide phosphoribosyltransferase ( pncA ) was disrupted to minimize substrate nicotinamide (NAM) degradation. Then, the induction starting point was optimized to alleviate the metabolic burden on the engineered strain. Subsequently, systematic remodeling of E. coli 's glucose metabolism was conducted to enhance its suitability for NMN production by overexpressing key enzymes of the pentose phosphate pathway (Zwf and Gnd), knocking out genes related to the Entner-Doudoroff pathway ( gntR and edd ), and further attenuating the glycolytic pathway. Then, we concentrated on optimizing the cellular metabolic state, meticulously balancing intracellular redox homeostasis. Finally, using glucose and 2 g/L of NAM as substrates, the extracellular NMN yield reached 4.96 g/L, which is the highest yield reported so far in similar research. These findings contribute to the commercial production of NMN and offer valuable insights for constructing efficient cell factories for other nucleotide compounds.
研究领域:
生物工程
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合成生物学
·
微生物学
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2026
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IF 5.4
Zhi Jia,Liqiang Wang,YongLan Yang,Yuezhao Zhou,Chunfeng Zhang,Yujia Liu,Jie Liu
Modulating mitochondrial dysfunction by alleviating oxidative stress has recently emerged as a promising therapeutic strategy for Alzheimer’s disease (AD), but it ignores the fact of ROS regeneration caused by dysfunctional mitochondria. Herein, we developed a mitochondria-targeted ruthenium nanozyme, Ru@CP5-TPP, to enhance mitochondrial function by simultaneously scavenging reactive oxygen species (ROS) and eliminating damaged mitochondria. Ru@CP5-TPP was fabricated by modifying ultrasmall ruthenium nanoparticles (Ru NPs) with cationic pillar[5]arene (CP5), followed by the conjugation of the mitochondria-targeting molecule triphenylphosphine (TPP) through host-guest recognition. Under NIR-I laser irradiation, Ru@CP5-TPP can bypass the blood-brain barrier (BBB), target microglial mitochondria, and scavenge existing ROS through its intrinsic CAT-like and SOD-like activities. Moreover, by mimicking NADH oxidase (NOX), Ru@CP5-TPP catalyzes the conversion of NADH into NAD + , thereby inducing mitophagy and ultimately preventing ROS regeneration. As a result, Ru@CP5-TPP effectively alleviates mitochondrial dysfunction, inhibits Aβ deposition, relieves neuroinflammation, and ameliorates memory defects in an AD mouse model. This study provides a novel approach for the multi-target treatment of AD by leveraging the multi-enzyme activity of nanozymes. Download: Download high-res image (195KB) Download: Download full-size image Ru@CP5-TPP was constructed by modifying cationic pillar[5]arene (CP5)-capped Ru nanoparticles (Ru@CP5) with the mitochondria-targeting ligand TPP. Under NIR-I light irradiation, Ru@CP5-TPP can cross the blood-brain barrier (BBB), target microglial mitochondria, scavenge ROS, and promote mitophagy, thereby preventing ROS regeneration and ultimately alleviating Alzheimer's disease.
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