ONCOGENE
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2024
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IF 6.9
Du Kaixuan,Luo Yongbo,Zhang Lei,Zeng Youmiao,Dai Yiheng,Ren Mengda,Pan Wenbang,Liu Yuanhao,Tian Fengyan,Zhou Lijie,Gu Chaohui
Cuproptosis, a cell death process caused by copper ions, is mediated by protein lipidation related to lipoic acid metabolism. There is a close connection between cuproptosis and the progression and prognosis of various tumors. Here, we identified lipoyltransferase 1 (LIPT1), a key gene related to cuproptosis, was downregulated in bladder cancer (BLCA) and was associated with unfavorable patient prognosis. Restoring the LIPT1 expression in BLCA cells suppressed the proliferation and promoted cuproptosis. Moreover, the consequences of RNA sequencing and Bodipy staining showed that the metabolic pathway mediated by LIPT1 inhibited the accumulation of lipid droplets in cells, disrupted endoplasmic reticulum (ER) homeostasis, and promoted cell apoptosis. Additionally, overexpression of LIPT1 not only repressed the proliferation rate of BLCA cells in vitro but also in vivo. Mechanistically, YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) promoted the degradation of LIPT1 mRNA in a m 6 A-dependent manner. In summary, these conclusions reveal that LIPT1 promotes cuprotosis and ER stress to inhibit the progression of BLCA, indicating that LIPT1 will provide a powerful treatment direction and drug target for treating BLCA.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2024
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IF 7.1
Yiming Zhou,Mengting Zhang,Siyu Lu,Li Liu,Zhigui Duan,Fang Wei,Guolin Li
Purpose While reactive oxygen species (ROS) have been identified as key redox signaling agents contributing to aging process, which and how specific oxidants trigger healthy longevity remain unclear. This paper aimed to explore the precise role and signaling mechanism of superoxide (O 2 •− ) in health and longevity. Methods A tool for precise regulation of O 2 •− levels in vivo was developed based on the inhibition of superoxide dismutase 1 (SOD1) by tetrathiomolybdate (TM) in Caenorhabditis elegans ( C. elegans ). Then, we examined the effects of TM on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the signaling mechanism for longevity induced by TM-O 2 •− was screened by transcriptome analysis and tested in sod-1 and argk-1 RNAi strains, sod-2 , sod-3 , and daf-16 mutants. Results TM promoted longevity in C. elegans with a concomitant extension of healthy lifespan as indicated by increasing fertility and mobility and reducing lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanically, TM could precisely regulate O 2 •− levels in nematodes via modulating SOD1 activity. An O 2 •− scavenger Mn(III)TBAP abolished TM-induced lifespan extension, while an O 2 •− generator paraquat at low concentration mimicked the life prolongation effects. The longevity in TM-treated worms was abolished by sod-1 RNAi but was not affected in sod-2 or sod-3 mutants. Further transcriptome analysis revealed arginine kinase ARGK-1 and its downstream insulin/insulin-like growth factor 1 signaling (IIS) as potential effectors for TM-O 2 •‾ -induced longevity, and argk-1 RNAi or daf-16 mutant nullified the longevity. Conclusions These findings indicate that it is feasible to precisely control specific oxidant in vivo and O 2 •− orchestrates TM-induced health and longevity in C. elegans via ARGK-1-IIS axis.
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ENVIRONMENTAL RESEARCH
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2025
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IF 7.7
Kai Wu,Wenlong Wang,Shubing Yang,Xu Zhang,Peizeng Yang,Yuefei Ji,Jing Chen,Junhe Lu
As global warming intensifies freeze-thaw cycles, the understanding of environmental chemistry processes in ice and their potential impact on global water quality becomes increasingly important. This study investigated the transformation of 1-naphthol in the presence of nitrite (NO 2 - ) under slightly acidic conditions in ice, focusing on the formation of nitro-naphthol. Results demonstrated that increasing NO 2 - concentration enhanced the conversion of 1-naphthol and the formation of nitrated products. This transformation of 1-naphthol was attributed to the freeze-concentration effect, which led to the accumulation of H + , NO 2 - , and 1-naphthol in the liquid-like grain boundary layer amid ice crystals. In this brine, NO 2 - underwent protonation to form reactive nitrous acid (HNO 2 ) and nitrosonium ions (NO + ), which facilitated the nitration, nitrosation, and oxidative coupling reactions, respectively. The pH was shown to influence nitro products formation by altering the HNO 2 to NO + ratio. Toxicity assessment revealed increased toxicity of the NO 2 - /1-naphthol solution after freezing treatment, likely due to the formation of nitrated products, whereas natural organic matter (NOM) reduced this toxicity by suppressing the generation of nitrated products. The findings of this study advance the understanding of NO 2 - chemistry and the behavior of hydroxylated polycyclic aromatic hydrocarbons in cold environments.
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NATURE
·
2025
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IF 48.5
Huang He,Hu Yitao,Hou Yajun,Wang Xingkai,Dong Qiujiang,Zhao Zhixin,Ji Mingfang,Zhang Wanxing,Li Jinyang,Xie Jianping,Guo Hao,Han Xiaopeng,Ouyang Xiaoping,Hu Wenbin
The development of high-energy lithium metal batteries (LMBs) is essential for advances in next-generation energy storage and electric vehicle technologies 1 , 2 , 3 . Nevertheless, the practical applications of LMBs are constrained by current electrolyte designs that inherently rely on dominant solvation structures, preventing transformative progress in performance optimization 4 , 5 . Here, we address this limitation through a delocalized electrolyte design that fosters a more disordered solvation microenvironment, thereby mitigating dynamic barriers and stabilizing interphases. The resulting delocalized electrolyte delivers notable energy densities of 604.2 Wh kg −1 in a 5.5-Ah LiNi 0.9 Co 0.05 Mn 0.05 O 2 (Ni90)||Li pouch cell with a lean electrolyte design (1.0 g Ah −1 ) and 618.2 Wh kg −1 in a 5.2-Ah Ni90||Li pouch cell with an ultralean electrolyte design (0.9 g Ah −1 ), maintaining significant cycle stability over 100 and 90 cycles, respectively. In addition, the 70–104 V NCM811||Li battery pack (3,904 Wh) exhibits a high energy density of 480.9 Wh kg −1 and stable cycling over 25 cycles. These results demonstrate the need to circumvent inherent reliance on dominant solvation structures in electrolyte design to achieve the high-energy Battery600 and scalable Pack480 targets.
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npj Precision Oncology
·
2025
·Vol. 9
·期 1
·1-15
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IF 8
Huo Ran,Xu Quan-guo,You Yi-qing,Chen Yan-lin,Su Guang-jian,Yang Kun-rong,Xiao Yan-ping,Xue Zhong,Li Yang-jin,Sun Pei,Cui Zhao-lei,Lin Ying-ying,Guo Jun-ying,Xu Hai-yan,Chen Zhao-shuo,Xie Wen-ting,Xu Shao-hua,Chen Min-yong,Wu Jing,He Shi-jie,Xiao Zhen-zhou,Chen Yan
Hepatocellular carcinoma (HCC) is a prevalent and deadly cancer. Gut microbiota affect tumor immunity and immunotherapy efficacy, but the exact mechanisms are unclear. A study compared gut microbiota in HCC patients and healthy controls (HC) using 16S rDNA analysis and metabolomics. It found higher levels of Bifidobacterium and a positive correlation between Bifidobacterium and isobutyric acid in HC group. Animal models showed that the combination of HC fecal matter and αPD-1 treatment reduced tumor volume more effectively than the combination of HCC fecal matter and αPD-1. The combination of Bifidobacterium or isobutyrate with αPD-1 also decreased tumor size. In vitro, isobutyrate-stimulated CD8 + T cells increased IFN-γ secretion, suppressed liver cancer cells, and downregulated the JAK/STAT3 pathway. Combined treatments increased CD8 + T cells and IFN-γ levels and reduced JAK/STAT3 signaling in the tumor microenvironment. This suggests that Bifidobacterium and isobutyrate can inhibit tumor growth, offering insights into gut microbiota-host interactions and potential strategies to overcome HCC immunotherapy resistance.
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Lipids in Health and Disease
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2025
·Vol. 24
·期 1
·1-15
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IF 4.2
An He,Cheng Dong-liang,Xia Xian-ru,Li Xian-dong,Ruan Zhi-hua,Peng Chun-yan
Background Dyslipidemia has been extensively documented as a key driver of cardiovascular pathology. Regulating lipid homeostasis holds promise for treating atherosclerosis (AS). Although the protein phosphatase 2 catalytic subunit beta (PPP2CB) is involved in post-transcriptional gene regulation, its role in AS-associated dyslipidemia is not well understood. Methods The study included both human participants and animal models. The following techniques were employed: cell culture, extraction of exosomes, preparation of pooled hyperlipidemic serum (HS), transfection, western blotting, immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), co-immunoprecipitation, low-density lipoprotein cholesterol (LDL-C) uptake assay, biochemical assays, assessment of aortic atherosclerotic lesions, as well as statistical analysis. Results This study identified a marked upregulation of PPP2CB expression in peripheral blood leukocytes of AS patients, artery plaque of ApoE −/− mice given a high-fat diet, and hepatic cells exposed to hyperlipidemic stimuli. Overexpression of PPP2CB in hepatic cells exacerbated lipid accumulation and low-density lipoprotein uptake, whereas silencing PPP2CB mitigated this effect. Immunofluorescence co-localization and co-immunoprecipitation analysis confirmed a direct interaction between PPP2CB and lectin-like oxidized LDL receptor-1 (LOX-1). Notably, PPP2CB manipulation disrupted hyperlipidemia-induced LOX-1 expression. Additionally, PPP2CB-mediated lipid dysregulation was linked to the activation of the LOX-1/ mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling cascade. Conclusions These results unveil PPP2CB as a novel lipid regulator in the progression of pathological AS and highlight its involvement in signaling regulation during abnormal lipid metabolism. PPP2CB could be considered a promising candidate for biomarker development and therapeutic intervention in AS.
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ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Xuecheng Yang,Xiaoyu Zhang,Ge Yu,Yubin Ma,Xin Li,Yiyang Guo,Shuping Wang,Dan Ge,Changying Xue,Kun Jin,Bingbing Sun
Amyloid-β (Aβ) fibrillation is a spontaneous, thermodynamic process governed by nucleation and elongation. While many studies have explored the ability of engineered nanomaterials (ENMs) to modulate Aβ fibrillation, such as inhibitors, promoters, and dual-modulators, the key physicochemical property of ENMs that determines this behavior remains unclear. In this study, we developed a comprehensive library of ENMs with well-controlled physicochemical properties, including surface charges, morphologies, and hydrophilicity, to systematically investigate their effects on Aβ40 fibrillation. We identified hydrophilicity as the primary determinant of ENM-mediated modulation, rather than surface charge or morphology. Thioflavin T (ThT) kinetics assays indicated that hydrophilic ENMs exhibited bidirectional modulation, both promoting and inhibiting fibrillation depending on concentration. This bidirectional effect results from a competition between accelerated nucleation and decelerated elongation. While hydrophobic ENMs exhibited only unidirectional inhibition from the initial nucleation phase, two-dimensional-NMR (2D-NMR) mechanism studies indicated that this difference resulted from specific interactions with Aβ40 residues. Hydrophilic ENMs targeted hydrophilic residues involved in elongation, including Arginine R5, Glycine G9, G25, G33, G37, and G38, Lysine K28, and Alanine A30, while hydrophobic ENMs bound to hydrophobic residues critical for nucleation, such as I31. These findings provide mechanistic insight into NP–peptide interactions and lay a foundation for the rational design of nanomaterials to modulate amyloid fibrillation.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2025
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IF 8.2
Xiaomeng Ji,Jingquan Dong,Wenting Zhu,Shasha Zhang,Yaru Chen,Xiao Liu,Yan Cao,Panpan Zhao,Zibo Dong
Background Sepsis-associated encephalopathy (SAE) represents one of the most common neurological complications observed in sepsis patients, contributing to both increased mortality and long-term cognitive impairment. Microglial mitochondrial reactive oxygen species (mtROS) overproduction and NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation were key pathological drivers of SAE. Although PIM-1, a serine/threonine kinase, was known to regulate both mtROS generation and NLRP3 signaling, its specific contribution to SAE remained poorly defined. Methods This study established a SAE mouse model using cecal ligation and puncture (CLP) surgery, and screened the differentially expressed gene PIM-1 through immunohistochemistry, GEO database analysis, and etc. An in vitro model was established using Lipopolysaccharide + Adenosine(LPS + ATP) Triphosphate stimulated Mouse Microglia (BV-2), and the regulation mechanism of PIM-1 was analyzed through siRNA interference, RNA-seq, and etc. Potential drug Urolithin B (UB) targeting PIM-1 inhibition was screened through molecular docking, and its inhibitory effect on PIM-1 and therapeutic potential in SAE were evaluated through thermal stability experiments, behavioral experiments, etc. Results PIM-1 was upregulated in SAE, which was associated with brain damage. PIM-1 knockdown suppressed microglial activation and reduced inflammatory cytokines release. Further investigation indicated that PIM-1 modulated mtROS generation and facilitated NLRP3 inflammasome activation. Notably, pharmacological inhibition of PIM-1 by UB alleviated SAE both in vivo and in vitro , resulting in improved neuronal damage and cognitive impairment. Conclusion PIM-1 played a critical role in SAE progression, potentially through its mediation of microglial activation and neuroinflammation via the mtROS/NLRP3 axis. Notably, pharmacological inhibition of PIM-1 with urolithin B significantly alleviated SAE.
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MICROPOROUS AND MESOPOROUS MATERIALS
·
2024
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IF 4.8
Ying Zhang,Qinqin Wang,Mingyuan Zhu,Bin Dai
The prevailing Zn/AC catalysts was plagued by limited lifetime and difficulties in regeneration for acetylene acetoxylation. In order to exploring renewable catalyst for acetylene acetoxylation, Zn/S-1 catalyst was synthesized using Silicalite-1(S-1) as support. The catalytic performance of Zn/S-1 was compared with Zn/AC catalyst using active carbon as support. The CH 3 COOH conversion of Zn/S-1 catalyst only decreased 15 % after running 225 h, much better than the 66 % of Zn/AC after 154 h. TG analysis revealed that the improved stability of Zn/S-1 catalyst was attributed to its better resistance for carbon deposition with the presence of S-1 support. A series of characterizations and DFT results elucidated that the Lewis acid sites of S-1 support and Zn component serve as dual active sites, which enhanced the adsorption of CH 3 COOH and inhibited the carbon deposition. In addition, the deactivated Zn/S-1 catalyst could be regenerated by calcination in air atmosphere due to the thermal stability of S-1, and the regenerated Zn/S-1 catalyst showed similar catalytic activity with the fresh catalyst.
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Analytical Methods
·
2017
·Vol. 9
·期 37
·5502-5508
·
IF 1.9
Yanmei Zhang,Feng Li,Jingwu Kang
A method for the screening of histone deacetylase 1 (HDAC1) inhibitors in natural products by using capillary electrophoresis (CE) coupled with laser induced fluorescence (LIF) detection was developed. The method was developed by employing a 5-carboxyfluorescein labelled peptide with an acetylated lysine residue as the substrate of HDAC1 and a small chemical library composed of 38 purified natural products. The biochemical assay was performed by means of CE separation, i.e. the deacetylated product in the enzymatic reaction solution was separated from the substrate peptide; therefore, the enzyme activity can be accurately calculated through the measurement of the peak area of the deacetylated product. For inhibitor screening, the tested samples were spiked in the substrate solution and the resulting solution mixtures were then incubated with the enzyme solution for proceeding the deacetylation reaction for a short period of time at 30 °C. After quenching the reaction by putting the reaction vial in boiling water, the resulting solution was injected for CE separation with 100 mM Tris–H3PO4 buffer (pH 8.0) containing 30 mM NaCl and 0.05% (m/v) hexadimethrine bromide (HDB). The inhibitor could be readily identified as long as the peak area of the deacetylated product is reduced in comparison with that of the negative control in the absence of any inhibitor. Dynamically coating the capillary wall with positively charged HDB is very necessary to diminish the serious adsorption of the substrate and product peptides onto the capillary wall. A rapid, cost-effective method for HDAC1 inhibitor screening is proposed.
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FISH & SHELLFISH IMMUNOLOGY
·
2022
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IF 4.622
Xiaoyu Yang,Ying Wu,Panpan Zhang,Guisen Chen,Zhenjie Cao,Jingqun Ao,Yun Sun,Yongcan Zhou
Chemokines are a family of small signaling proteins that are secreted by various cells. In addition to their roles in immune surveillance , localization of antigen, and lymphocyte trafficking for the maintenance of homeostasis , chemokines also function in induce immune cell migration under pathological conditions. In the present study, a novel CC chemokine gene ( CaCC1 ) from humpback grouper ( Cromileptes altivelis ) was cloned and characterized. CaCC1 comprised a 435 bp open reading frame encoding 144 amino acid residues. The putative molecular weight of CaCC1 protein was 15 kDa CaCC1 contains four characteristic cysteines that are conserved in other known CC chemokines. CaCC1 also shares 11.64%–90.28% identity with other teleost and mammal CC chemokines. Phylogenetic analysis revealed that CaCC1 is most closely related to Epinephelus coioides EcCC1, both of which are in a fish-specific CC chemokine clade. CaCC1 was constitutively expressed in all examined C. altivelis tissues, with high expression levels in skin, heart, liver, and intestine. Vibrio harveyi stimulation up-regulated CaCC1 expression levels in liver, spleen , and head-kidney. Functional analyses revealed that the recombinant protein (rCaCC1) could induce the migration of head-kidney lymphocytes from C. altivelis . Moreover, rCaCC1 significantly enhanced phagocytosis in head-kidney macrophages from C. altivelis . In addition, rCaCC1 exhibited antimicrobial activities against Staphylococcus aureus , Edwardsiella tarda , and V. harveyi . In vivo , CaCC1 overexpression improved bacterial clearance in V. harveyi infected fish. Conversely, CaCC1 knockdown resulted in a significant decrease of bacterial clearance. These results demonstrate the important roles that CaCC1 plays in homeostasis and in inflammatory response to bacterial infection.
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JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Mengshi Jiang,Wei Li,Chunqi Zhu,Xiang Li,Junlei Zhang,Zhenyu Luo,Bing Qin,Yongzhong Du,Lihua Luo,Jian You
The application of nanocarriers as drug delivery system for chemotherapeutic drugs has become a research hotspot in cancer treatment. Chemotherapy with high tumor-targeting accuracy and drug release specificity is the key to improve the efficacy of tumor chemotherapy and reduce the side effects caused by repeated doses drugs. Here, we synthesized a redox-sensitive nano-micelle formed by hyaluronic acid (HA) conjugated with d -α-tocopherol succinate (TOS) using a disulfide bond as the linker (HA-SS-TOS, HSST), which could actively accumulate to the tumor sites and metastasis cancer cells with high expression of CD44. The micelles could dissociate under the high GSH level in cancer cells, triggering a release of paclitaxel (PTX). Surprisingly, the precise chemotherapy instead induced a suppressive tendency of immune system, manifested by a significant increase in TGF-β, which weakened the therapeutic effect of micelles. Moreover, the high levels of TGF-β might be related to the increased drug-resistance of cancer cells. Research has shown that PD-1 pathway blockade can result in reduction in TGF-β expression, thus, a PLGA microsphere encapsulating PD-1 antagonist peptides A12 ( [email protected] ) was further prepared to activate the host immune response. Our data indicated that PTX-loaded HSST could accurately “find” the tumors as well as metastasis cancer cells, and efficiently kill most of them. The joining of a durable PD-1 blockage significantly boosted the efficacy of [email protected] on multiple tumor models, including lung metastatic tumors and even multidrug-resistant tumors. Thus, our work presented an optimal chemo-immunotherapy combined system, which shows profound significance for future cancer therapy in clinic.
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