Arabian Journal of Chemistry
·
2024
·
IF 5.3
Ping Cheng,Botao Wang,Shuying Liang,Yuqi Yang,Shixin Gui,Kai Zhang,Yingying Sun,Shaoqi Qu,Lin Li
Colistin used to be regarded as the last-resort treatment for the infection caused by multidrug-resistant gram-negative bacteria. However, the emergence and widespread of mcr-1 seriously reduce the clinical effectiveness of colistin, constituting a serious threat to global public health. Due to the difficulties in the development of new antibiotics, restoring antibiotic susceptibility with adjuvants is undoubtedly a rational option. As naturally occurring compounds, resveratrol and capsaicin could be extracted from many natural plants, due to various antimicrobial properties, they have received significant attention. Herein, the synergistic activity of colistin combined with resveratrol and capsaicin against mcr-1 -positive Escherichia coli were investigated by checkerboard method and time-killing assays. The in-depth molecular mechanisms were elucidated by scanning electron microscopy, fluorescent probe experiments, transcriptome and metabolome analysis. Molecular docking assay was taken to analyse potential interactions between resveratrol/capsaicin and MCR-1. Finally, the in vivo efficacy of combined therapy against mcr-1- positive Escherichia coli was assessed. Our results demonstrated that colistin combined with resveratrol and capsaicin acted synergistic activity against mcr-1- positive Escherichia coli both in vivo and in vitro . Further mechanistic studies showed that the combined therapy could exacerbate cell membrane damage, increase membrane permeability, disrupt the homeostasis of PMF, inhibit ATP synthesis, and efflux pump activity. In addition, the combined therapy could inhibit central carbon metabolism, and reduce tricarboxylic acid cycle and oxidative phosphorylation. Moreover, molecular docking assay revealed resveratrol/capsaicin could bind to MCR-1 stably. Our study indicated that colistin in combination with resveratrol and capsaicin as a novel therapy could provide a trustworthy foundation to establish the treatment plan for mcr-1- positive Escherichia coli.
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Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-16
·
IF 9.6
Yang Mengxue,Wang Ting,Shao Jingrong,Ran Xinna,Xiao Rui,Zhao Rui,Wu Chunyan,Ji Ming,Tian Weiping,Sun Huabing,Liu Jiao,Zuo Shengkai
Myocardial infarction (MI) remains one of the leading causes of mortality worldwide, and cardiomyocyte death plays a critical role in cardiac remodeling after MI. Ferroptosis is a recently identified form of iron-dependent programmed cell death that has been shown to be involved in the progression of various cardiovascular diseases, including MI. Bromodomain-containing protein 4 (BRD4) is an epigenetic reader and a key regulator of cell survival. In this study, we screened an epigenetic target library containing 773 small-molecule compounds and found that (+)-JQ-1(hereafter abbreviated as JQ-1), a BRD4-specific inhibitor, markedly attenuated ferroptosis induced by erastin (a ferroptosis inducer) in cardiomyocytes. Both prophylactic and therapeutic JQ-1 administration significantly improved cardiac remodeling and reduced cardiomyocyte ferroptosis in mice with MI. Mechanistically, JQ-1 protected cardiomyocytes from erastin-induced ferroptosis by downregulating the expression of nicotinate phosphoribosyltransferase (NAPRT) and upregulating the expression of nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin1 (SIRT1). Inhibition of NAMPT or SIRT1 abrogated the protection conferred by JQ-1 in erastin-treated H9C2 cardiomyocytes. The combination of proteolysis-targeting chimeras (PROTACs) with JQ-1 (JQ-1-PROTAC) promoted BRD4 protein degradation and rescued erastin-induced ferroptosis in H9C2 cardiomyocytes, and prevented erastin-induced ferroptosis in human cardiomyocytes. Thus, JQ-1 can protect cardiomyocytes from ferroptosis through the NAMPT-SIRT1 pathway, and JQ-1-based therapy may serve as a novel promising strategy to improve cardiac remodeling after MI.
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INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
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2025
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IF 8.3
Mingxin Cai,Qinghua Ye,Ziru Wang,Peilei He
Electrochemical water splitting for hydrogen production is currently constrained by the sluggish kinetics of the anodic oxygen evolution reaction (OER). NiFe-based catalysts have emerged as promising alternatives to precious metal OER catalysts due to their low cost and relatively high electrocatalytic activity. However, NiFe-based catalysts prepared by conventional synthesis methods suffer from a low density of exposed active sites and ambiguous structures. Herein, we report a straightforward solution-thermal strategy for constructing two-dimensional sub-1 nm nanosheets (SNSs) through the self-assembly of an iron-substituted polyoxometalate (FeMo 6 ) cluster with Ni 3 S 2 . The Ni 3 S 2 –FeMo 6 SNSs exhibit excellent electrocatalytic performance in 1 M KOH, achieving an overpotential of only 342 mV at a current density of 100 mA cm −2 and maintaining stability for 100 h at 10 mA cm −2 . The synergistic effect between Fe and Ni 3 S 2 effectively modulates the electronic structure of the catalyst, accelerating the formation of the active NiOOH phase. Furthermore, Fe incorporation actively enhances hydroxyl groups adsorption on the catalyst surface and facilitates lattice oxygen participation in the reaction. This work clarifies the role of Fe in NiFe-based electrocatalysts, providing new perspectives for developing facile-to-synthesize and high-performance electrocatalysts.
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ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jia Yao,Pengtao Chen,Dingqi Xie,Jianqingchen Chen,Xiao Lin,Yujin Xu
Radiotherapy (RT) is a widely used clinical treatment for cancer, leveraging ionizing radiation; however, some patients exhibit resistance to radiation due to insufficient reactive oxygen species (ROS) production. Copper-based nanomaterials represent a promising class of antitumor agents capable of generating abundant ROS. In this study, R837 and Cu2–xSe were incorporated into PLGA (50:50)20k-PEG2k-iRGD to develop a targeted nanomaterial for tumor therapy. These nanoparticles effectively induced cuproptosis, inhibited tumor cell proliferation, remodeled the tumor immune microenvironment (TME), and promoted immunogenic cell death (ICD), thereby enhancing the efficacy of PD-1 checkpoint blockade therapy (αPD-1). Furthermore, our results demonstrated that the Cu2–xSe(R837)-iRGD nanoformulations, in combination with radiotherapy, promoted the infiltration of CD8+ T cells and activated antitumor immune responses in vivo. In conclusion, our study confirmed that Cu2–xSe(R837)-iRGD nanoformulations combined with radiotherapy yielded promising therapeutic outcomes and held potential for clinical application in osteosarcoma (OS) treatment.
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Translational Neurodegeneration
·
2025
·Vol. 14
·期 1
·1-27
·
IF 15.2
Wang Jie,Ni Hong,Wang Yu,Wei Luyao,Ding Hanqing,Guo Zhongzhao,Pan Hao,Yu Ying,Luo Jia,Pan Weidong,Wang Deheng,Ke Zun-Ji
Background Alzheimer's disease (AD) is a neurodegenerative disease with major symptoms including memory and learning deficits. Neuroinflammation associated with reactive microglia promotes AD progression. These reactive microglia secrete prostaglandins, which are synthesized through the enzymatic activity of cyclooxygenase (COX)-1 and COX-2. Here, we aimed to elucidate the specific mechanisms of COX1 in AD pathogenesis and its interactions with neuroinflammatory processes.Methods We conducted backcrossing between COX-1 knockout (KO) and 5 × FAD mice to evaluate the effect of COX-1 deficiency on neuroinflammation. In addition, single-cell sequencing and microarray datasets from public databases and ingenuity pathway analysis in vitro were employed to explore gene expression profiles in the brains of AD mice.Results We identified a significant upregulation of COX-1 in 5 × FAD mice, with expression specifically localized to microglia in an age-dependent manner. Additionally, COX-1 KO alleviated neuroinflammation and accumulation of Aβ plaques, subsequently improving cognitive behavior in 5 × FAD mice. Moreover, microglia exhibited an amoeboid morphology in 5 × FAD mice, whereas in age-matched 5 × FAD/COX-1 KO mice, microglia had a ramified appearance. Additionally, our study demonstrated a pharmacological approach that inhibits the prostaglandin E2 (PGE2)/EP2 receptors via inhibition of the cAMP-PKA-NFκB-p65 pathway and NLRP3 inflammasome activation, producing similar beneficial effects as observed in COX-1 KO mice.Conclusion Our findings indicate that targeting the COX-1/PGE2/EP2 signaling pathway may alleviate neuroinflammation and impede AD progression. Moreover, the EP2 receptor presents a promising pharmacological target for mitigating the pathological effects associated with COX-1 activity in AD patients.
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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2025
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IF 5.4
Chunying Jiang,Shudan Yang,Yuting Wang,Liyuan Du,Miao-Miao Niu,Dongli Zhang
Poly (ADP-ribose) polymerase 1 (PARP-1) exhibits high expression levels in colorectal cancer (CRC) patients and participates in multiple DNA damage repair pathways, thereby emerging as an attractive target. Herein, we identified a series of PARP-1 inhibitors (termed as compounds 1-6) by pharmacophore modelling, virtual screening and biological evaluation. Enzyme inhibition assays demonstrated that compound-5 significantly inhibited PARP-1 activity (IC50 = 0.07 ± 0.01 nM) and exhibited high selectivity for PARP-1 among 63 different kinases. Molecular dynamic simulations indicated that compound-5 stably bound to the catalytic domain of PARP-1. Cellular assays demonstrated that compound-5 significantly inhibited the proliferation of a panel of human CRC cell lines (HCT116, SNU-1, Caco-2, HT-29). The data suggest that compound-5 may be a highly potent and selective PARP-1 inhibitor for CRC therapy.
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Toxics
·
2025
·Vol. 13
·期 8
·662
·
IF 4.1
Jiahong Jiang,Qi Liu,Boxiang Zhang,Lei Zhao,Dan Xu
Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS inCaenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulatedpmk-1andskn-1, modulating oxidative stress and neuronal function.pmk-1mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS inCaenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative.
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BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2025
·
IF 3.6
Xiong Neng,Chen Jia-Yu,Lei Pei-Qi,Fu Teng-Teng,Xu Rui,Xue Ya-Ping,Zheng Yu-Guo
Immobilized enzyme bioreactors provide a controlled reaction environment and integrated reaction-separation processes for biocatalysis. In this study, a biocatalytic process based on resin-immobilized nitrilase and a partial-mixed recirculating bed bioreactor was developed for the synthesis of 1-cyanocyclohexaneacetic acid, a gabapentin intermediate. The resin catalyst prepared by immobilizing the regioselective nitrilase AcN-S on the activated amino resin LX-1000EPHA achieved 99.12% immobilization yield, 73.40 U/g specific activity, and 95.42% activity recovery when loaded with 10 mg/g crude enzyme. The resin catalyst (100 g/L) could convert 1 M (148.2 g/L) substrate 1-cyanocyclohexaneacetonitrile to 1-cyanocyclohexaneacetic acid within 18 h, achieving a conversion of 95.40%. At a substrate concentration of 0.5 M, > 85% conversion could still be achieved after 15 batches. In a partial-mixed recirculating bed reactor, the resin catalyst (100 g/L) could completely convert 500 mM substrate within 10 h, and achieve > 90% conversion after 20 batches, with residual activity of 93.23%. Resin activation and cross-linking treatment after immobilization were found to improve operational stability, reduce protein leakage, and ensure high immobilization yield and activity recovery. The reactor provided a low-shear environment and recirculating flow, which together improve catalyst reusability and reduce product inhibition. The constructed reaction system provides a solution for the efficient conversion of slightly soluble/insoluble substrates and the integration of reaction and separation.
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JOURNAL OF LIGHTWAVE TECHNOLOGY
·
2025
·
IF 4.8
Hongrong Zheng,Xin Kang,Qihao Yang,Haider Syed Irshad,Dingyi Feng,Fu Liu,Xuetao Gan,Biqiang Jiang
Recent increased attention to environmental and health monitoring demands faster response and reliable gas concentration measurement technology. Herein, we propose an optical fiber-based strategy for fast ethanol gas concentration sensing using a tilted fiber grating (TFG) assisted with a nanolayer of HKUST-1. The TFG excites unique cladding mode resonances and strong evanescent field that interact with the in-situ grown HKUST-1 nanolayer that provides a path for the penetration and absorption of ethanol gas. The TFG, functionalized with 281 nm thick HKUST-1 nanolayer, exhibits a sensitivity of 7.7 nm/% over an ethanol gas concentration range of 0∼0.14% and a limit of detection of 35 ppm at room temperature, by tracking the resonance wavelength shift of a cladding mode. Time-domain experiments reveal the response and recovery times of 26.7 s and 10.3 s, respectively, attributed to the high surface area and porosity of the HKUST-1 nanolayer. The proposed fiberoptic ethanol gas sensor offers ease of integration, rapid response, and high repeatability and reliability, making it suitable for applications such as chemical plant leakage monitoring and medical breath analysis.
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BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Chunxia Chen,Shujie Duan,Jianing Ji,Mengli Wu,Zhan Yang,Mengyang Cai,Menghan Xue,Lanju Wang,Rui Chen,Sima Yaron,Keying Guo,Sergio Benardini,Zhizeng Wang,Yang Luo
Conventional point-of-care lateral flow immunoassays are characterized by an antibody-tagged probe irregular coupling that can limit sensitivity and require a long assay’s time. We synthesized polyethylene glycol-modified selenium nanoparticles (PEG-SeNPs) by template method and developed a strategy to set antibody probes targeted and orderly by using PEG-SeNPs. Synthesized PEG-SeNPs with high stability could immobilize antibodies in the “stand-up” orientation, resulting in a faster detection time of less than 1 min by direct observer visualization without instruments or equipment. Results showed that SARS-CoV-2 antibody could be systematically structured on the chip, resulting in a detection limit of 10 pg/mL, significantly higher than conventional chips. The new device has been validated on 192 clinical samples and we found 100% negative coincidence, 93.94% positive coincidence, and 95.83% overall coincidence with reverse transcriptional PCR test. The orderly arrayed probe’s stability allowed to detect throat swabs, saliva, serum, fingertip blood samples, and mutant strains without cross-reactivity with common respiratory viruses or pathogenic strains, demonstrating promising potential for a universal colorimetric platform for ultrafast field-deployable diagnostics.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
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.
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Nature Energy
·
2022
·Vol. 7
·期 6
·511-519
·
IF 67.439
Li Yuqi,Zhou Quan,Weng Suting,Ding Feixiang,Qi Xingguo,Lu Jiaze,Li Yu,Zhang Xiao,Rong Xiaohui,Lu Yaxiang,Wang Xuefeng,Xiao Ruijuan,Li Hong,Huang Xuejie,Chen Liquan,Hu Yong-Sheng
Sodium-based batteries have attracted wide interests in the academic and industrial fields. However, their energy density is still lower than that of Li-based batteries. Here we report an initial anode-free Na battery with an energy density of over 200 Wh kg −1 , which is even higher than that of the commercial LiFePO 4 ||graphite battery. Through introducing graphitic carbon coating on the Al current collector and boron-containing electrolytes in the battery, we show that uniform nucleation and robust interphases enable reversible and crack-free Na deposition. Benefitting from the synergetic effects derived from the built cooperative interfaces, the cycling lifetime of the Na battery without applying additional pressure reaches 260 cycles, which is the longest life for large-size cells with zero excess Na. The insights gained from the Na plating/stripping behaviour and interfacial chemistry in this work pave the way for further development of Na batteries with even higher performance.
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