Scientific Reports
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2017
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IF 4.259
Cong Xie,Tong-Meng Yan,Jia-Mei Chen,Xiao-Yan Li,Juan Zou,Li-Jun Zhu,Lin-Lin Lu,Ying Wang,Fu-Yuan Zhou,Zhong-Qiu Liu,Ming Hu
This study aims to determine whether enzyme activities are correlated with protein amounts and mRNA expression levels of five major human sulfotransferase (SULT) enzymes in 10 matched pericarcinomatous and hepatocellular carcinoma liver samples. The MRM UHPLC-MS/MS method, Western blot and RT-PCR were used along with SULT activity measurement using probe substrates. The LC-MS/MS method was specific for all five tested SULTs, whereas Western blot was specific for only two isoforms. The activities of SULT1A1, SULT1B1, SULT1E1 and SULT2A1 in 9 of 10 samples showed a significant decrease in tumor tissues relative to matched pericarcinomatous tissues, whereas the activities of SULT1A3 in 7 of 10 samples increased. The turnover numbers of SULTs did not change, except for SULT1A1. A generally high degree of correlations was observed between SULT activities and protein amounts (r 2 ≥ 0.59 except one), whereas a low degree of correlations was observed between SULT activities and mRNA expression levels (r 2 ≤ 0.48 except one). HCC reduced the SULT activities via impaired protein amounts. LC-MS/MS quantification of SULTs is highly reliable measurement of SULT activities, and may be adopted for implementing precision medicine with respect to drugs mainly metabolized by SULTs in healthy and HCC patients.
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Scientific Reports
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2017
·Vol. 7
·期 1
·1-8
·
IF 4.259
Guo Dongsheng,Liu Haikun,Ruzi Aynisahan,Gao Ge,Nasir Abbas,Liu Yanli,Yang Fan,Wu Feima,Xu Guosheng,Li Yin-xiong
Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8 -deficient stem cells generated by the CRISPR/Cas9 system. ABCC8- deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8- deficient cells recapitulated the CHI disease phenotype in vitro , which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-15
·
IF 9.429
Jiang Zengxin,Wang Hao,Zhang Zeng,Pan Jianfeng,Yuan Hengfeng
Targeting cartilage is a promising strategy for the treatment of osteoarthritis, and various delivery vehicles were developed to assist the therapeutic agents into cartilage. However, the underlying biomechanisms and potential bioactivities remain oversimplified. Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β. Then a functional reactive oxygen species (ROS) responsive nanocarrier, mesoporous silica nanoparticles (MSN) modified with methoxy polyethylene glycol-thioketal, was constructed. In vitro biomolecular results showed that compared with OL alone, MSN-OL could significantly activate Nrf2/HO-1 signaling pathway, which exhibited better ROS-scavenging proficiency and greater anti-apoptotic ability to protect mitochondrial membrane potential of chondrocytes. Further bioinformatics analysis revealed that MSN-OL suppressed clusters of genes associated with extracellular matrix organization, cell apoptosis and cellular response to oxidative stress. Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.
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Communications Biology
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2025
·
IF 5.1
Wang Shanshan,Wu Zankai,Song Wenqin,Zhang Hui,Bu Xueshan,Gao Wenwei,Wu Kefan,Xia Zhongyuan,Zhao Bo,Wang Wei
Activation of the cGAS-STING pathway has been proposed as a potential pathogenic mechanism underlying postoperative cognitive dysfuncton (POCD). Analysis of public transcriptomic data from the hippocampus of male mice suggests upregulation of Rbm47 in an experimental POCD model. In vitro, knockdown (KD) of Rbm47 in BV2 cells reduces levels of cGAS, STING, TNF-α, IL-6, and IFN-β under isoflurane and lipopolysaccharide (Iso + LPS) conditions. HT22 cells exposed to culture medium from Rbm47 -KD BV2 cells treated with Iso + LPS show increased levels of MEF2C, GPX4, GSH, and SOD, and reduced levels of MDA and iron. Microglial Rbm47 overexpression amplifies cGAS-STING signaling and aggravates neuronal ferroptosis, which is reversed by the cGAS inhibitor RU.521. Rbm47 KD combined with RU.521 treatment synergistically ameliorates POCD in male mice. Mechanistically, the RRM2 domain of RBM47 interacts with the 3’UTR of cGAS mRNA, enhancing its stability. RUNX1 directly binds to the Rbm47 promoter and facilitates its transcription. RUNX1 overexpression activates the RBM47-cGAS-STING axis and exacerbates neuronal ferroptosis. Conversely, RUNX1 ablation ameliorates POCD, dampens the cGAS-STING signaling, and inhibits ferroptosis, which is abolished by RBM47 depletion. Our findings suggest that repression of RUNX1/RBM47 may represent a promising therapeutic strategy for POCD.
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Nature Communications
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2025
·
IF 15.7
Liu Tao,Sun Youlong,Wang Yantao,Zhang Shu,Zhang Yuchen,Dong Shanmu,Wang Jinzhi,Li Chuanchuan,Hu Lei,Xue Weijiang,Ju Jiangwei,Ma Jun,Tang Bo,Cui Guanglei
All-solid-state lithium batteries for electric vehicles require high specific power, challenged in thick negative electrodes by fragile conducting networks during volume changes and dendrite growth at high currents. We propose an In 0.38 Sn 0.33 Bi 0.29 ternary alloy negative electrode creating a mixed ionic-electronic conducting continuum that overcomes these limitations. The stepwise formation of multiple phases with sufficient mechanical robustness during Li-alloying effectively stabilizes the ionic and electronic conducting percolation by relieving stress concentration and minimizing crack propagation. The unique reversibility of the multiple phase changes during lithiation/delithiation ensures stable cycling performance. The In 0.38 Sn 0.33 Bi 0.29 negative electrode exhibits a high capacity of ~ 724 mAh g −1 and a critical current density of 150 mA cm −2 at 5.0 mAh cm –2 . The In 0.38 Sn 0.33 Bi 0.29 | |LiCoO 2 full cell with industry-level mass loading (6.49 mAh cm –2 ) can retain 87.5% capacity over 1300 cycles at 4.0 C, delivering a jellyroll specific energy of 203.1 Wh kg −1 and 670.6 Wh L −1 at 5.0 C. The fast-charging capability is further validated by large-format pouch cells. The design principles can be extended to other negative electrode designs for solid-state batteries.
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Scientific Reports
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2025
·
IF 3.9
Xu Qiuling,Liu Zhuoxi,Wang Liyuan,Liu Guoyang,Zhao Long,Yue Hui,Liu Yong
Diabetic cardiomyopathy (DCM) requires a systematic approach for effective management. Focusing on key signaling pathways in myocardial fibrosis could offer novel therapeutic approaches for DCM. The objective of this research is to investigate new biomarker and the underlying mechanisms by which baicalin intervenes in the progression of DCM. Swiss Target Prediction databases and weighted correlation network analysis (WGCNA) were employed to collect and analyze targets of baicalin and DCM. Intersection targets were obtained through venn online website, network visualization was conducted through STRING database and Cytoscape 3.7.2 software. Molecular docking validation was completed via AutoDock Vina software. Western blotting, RT-qPCR and histology were carried out to validate the direct targets of baicalin and explore the molecular mechanism during DCM progression. In mice induced to DCM, we observed that disruptor of telomeric silencing 1-like (DOT1L) was upregulated. Baicalin (BC) reduced myocardial fibrosis in mice as indicated by the reduced expression levels of fibrosis markers COL-1 and TGF-β. The inhibitory effect of BC was reversed by overexpressed DOT1L and further enhanced by silenced DOT1L. Our results indicate that cardiomyocyte DOT1L exerts a pathogenic role in DCM and BC specifically targets DOT1L/COL-1 signaling to reduce myocardial fibrosis in DCM.
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POLYMER BULLETIN
·
2021
·Vol. 79
·期 8
·6409-6429
·
IF 2.87
Ding Guanjun,Wang Ao,Shi Xinming,Li Jumei,You Lijun,Wang Shaoyun
Polyphosphazene microspheres (PZS) multispectral encoded by fluorescence and surface enhanced Raman spectra (SERS) were prepared and used as solid phase carrier of capture antibody for antibody detection. A variety of fluorescent encoded polyphosphazene microspheres (FPZS) incorporating single and multiple fluorescent molecules were prepared. Multiple SERS encoded polyphosphazene microspheres (SPZS) were obtained by modification of different Raman reporters on the surface of PZS@Ag, which were fabricated with rough morphology through in situ deposition of Ag nanoparticles. Fluorescence and SERS spectral combined encoded polyphosphazene microspheres (FSPZS) were prepared by encoding of fluorescent molecules and SERS reporters. The optical signals in the two independent detection channels were separable and ensured the accuracy for the encoding method. Immunoassays of goat IgG, rabbit IgG and mouse IgG were performed by the as-prepared FPZS, SPZS and FSPZS as solid phase carrier of capture antibody and fluorescent labeled second antibody, using sandwich immunoassay method. The immunoassay results showed that the multiple-spectra encoded microspheres have stable and distinguishable encoding signals, large encoding volume and multiplexed analytical capability in sandwich immunoassays.
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Nature Communications
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2025
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IF 15.7
Qian Zhengyi,Han Guokang,Tan Yingjun,Ye Na,Wang Shuguang,Lin Zheng,Huang Qizheng,Gu Yu,Guo Hongyu,Liu Fei,Wang Kai,Li Lu,Shang Changshuai,Luo Mingchuan,Guo Shaojun
Copper-based catalysts are the premier choice for electrochemical reduction of CO 2 (CO 2 RR) into hydrocarbons or oxygenates. However, the facilely structural reconstruction of copper sites during electrolysis poses significant challenges to the long-life electrolytic efficiency. Herein, we leverage the strong σ-π dative bonding between Cu δ+ and alkyne-based ligands to stabilize copper sites for the prolonged CO 2 RR. We demonstrate the feasibility of taming the electronic structures of copper sites through the tug of war between σ and π backbonding interactions. The optimal copper organic polymer with methoxy group functionalization (OMe-PhCu) exhibits a moderate charge density of copper sites and an intensified local asymmetric charge distribution of coordinative carbon, enhancing the selectivity of methane with a Faradaic efficiency of 68.8% and a partial current density of 324.5 mA cm −2 in acidic electrolyte. In situ spectra and density functional theory calculations reveal enhanced *CO adsorption and lowered energy barrier for CO 2 RR into methane over OMe-PhCu. Building upon such stable Cu δ+ sites, we further construct Cu δ+ /Cu 0 catalytic interfaces for the generally enhanced electrosynthesis of multi-carbons and ammonias. This synthetic chemistry paves the pathway for the design of stable catalytic active sites for renewable conversions.
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npj Science of Food
·
2025
·
IF 7.8
Zheng Anru,Dong Minghua,Zhang Zhendong,Fang Jiaxin,Pan Yu,Jiang Lele,Tian Caiyun,Tan Jiayao,Deng Siwei,Zhang Cheng,Wang Zhong,Zhou Chengzhe,Guo Yuqiong
Oolong tea flavor is shaped by metabolite variations induced by season, processing, and cultivar. This study investigated the metabolic basis of sensory characteristics in Yongchun Foshou (YCFS) tea by integrating HS-SPME/GC-MS, HPLC, quantitative descriptive analysis (QDA), and chemometrics. Orthogonal partial least squares discriminant analysis (OPLS-DA) pinpointed key differential compounds between spring (YCFS-S) and autumn (YCFS-A) teas. Two-way ANOVA with effect size analysis confirmed that season was the dominant factor influencing most metabolites, although grade was the primary driver for free amino acids. YCFS-S contained significantly higher levels of taste-related phytochemical compounds, whereas YCFS-A exhibited elevated tea polyphenols. Statistical sensory analysis further identified a subset of key aroma compounds as drivers of seasonal and grade-based aroma differences. Correlation network analysis pinpointed 27 key sensory drivers: 12 aroma compounds defining a complex aroma profile dominated by floral and herbal notes, and 15 phytochemical compounds responsible for the umami, overall richness, and balanced bitterness. These findings were synthesized to construct the first dedicated flavor wheel for YCFS, elucidating how seasonality and grade collectively shape its flavor profile and providing a scientific basis for quality control and standardized production.
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DIABETOLOGIA
·
2025
·
IF 10.2
Yun Yue,Liu Yu-Dan,Yang Ze-Mian,Wang Yi-Qiao,Zhang Nan,Li Wen-Jing,Gao Di,Sha Lei
Aims/hypothesis While Roux-en-Y gastric bypass (RYGB) effectively treats diabetes, its underlying mechanisms remain unclear, highlighting the need to develop less-invasive alternatives. Emerging evidence suggests duodenal involvement in metabolic homeostasis and type 2 diabetes pathophysiology, yet the role of duodenal myoelectrical activity in diabetes and RYGB is poorly understood. This study aims to characterise duodenal myoelectrical changes in diabetes and RYGB, and evaluate their therapeutic potential. Methods Duodenal myoelectrical activity was recorded in male Sprague Dawley rats and high-fat diet/streptozocin (HFD/STZ)-induced diabetic rats, with or without RYGB. An antro-duodenum electrical stimulation (ADES) system was developed to mimic RYGB-associated myoelectrical hyperactivity. Its effects were examined by reducing stimulating power or chemically ablating duodenal myoelectrical activity with benzalkonium chloride, alongside pancreatic morphometric analyses. ADES was further validated in male Zucker diabetic fatty (ZDF) rats. Results RYGB induced duodenal myoelectrical hyperactivity in HFD/STZ rats, characterised by shortened migrating myoelectric complex cycles, a nearly doubled phase III duration, and a 50.9% increase in fed-state spike frequency. By replicating these specific patterns, ADES achieved glucose-lowering effects comparable with those of RYGB, decreasing fasting glucose levels, reducing the OGTT AUC by approximately 40%, and enhancing insulin secretion by 71.7% at the 30 min time point. These glycaemic improvements were attenuated by either reducing the stimulating power or through benzalkonium chloride-mediated ablation of myoelectrical activity. Furthermore, ADES promoted pancreatic beta cell recovery, increasing beta cell mass by 1.5-fold through a 65.3% enhancement in proliferation and a 39.0% reduction in apoptosis. It also preserved beta cell identity, as evidenced by upregulated expression and promoted nuclear localisation of the key transcription factors pancreatic and duodenal homeobox factor-1 (PDX1) and MAF bZIP transcription factor A (MAFA). In ZDF rats, ADES similarly improved glucose homeostasis, significantly lowering 120 min OGTT glucose, and ameliorated hyperinsulinaemia, reducing plasma insulin levels by 35.1%. Conclusions/interpretation ADES mimics RYGB-induced duodenal hyperactivity, offering comparable glucose-lowering effects. Targeting duodenal myoelectrical activity may provide a minimally invasive alternative to RYGB for diabetes treatment. Graphical
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JOURNAL OF ELECTRONIC MATERIALS
·
2025
·Vol. 54
·期 10
·8561-8569
·
IF 2.5
Dong Tianhao,Cui Yongpeng,Wei Lianghuan,Zhu Shengjie,Si Jianxiao
CaM(M = Cu, Ag)Sb Zintl-phase compounds have ignited tremendous research activities due to their promising thermoelectric properties. In this work, a series of CaCu 1− x Ag x Sb (x = 0, 0.2, 0.4, 0.6, 0.7, 0.8, 0.9, 1) samples have been synthesized and investigated. The continuous structure transition from the hexagonal CaCuSb to the orthorhombic CaAgSb is characterized as the composition regulation on Cu/Ag ratios. Lattice bonding hardens and the electrical band structure changes as a result of this transition. The lattice thermal conductivity of CaCu 0.2 Ag 0.8 Sb, which benefitted from the structure transition, showed a minimum value of 1.05 W m −1 K −1 at 323 K. At the same time, the Seebeck coefficient was improved as a result of the rise in effective mass. The findings show that the CaMSb compounds have flexible structural tunability for thermoelectric applications if the hole concentration can be further optimized. Graphical
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Acta Geochimica
·
2025
·Vol. 44
·期 5
·931-944
·
IF 1.3
Gong Huan,Yang Jing,Du Wei
The size of basalt fragments in Chang’E-5 (CE-5) regolith are small (< 6 mm 2 ), resulting in large variation on the estimated bulk composition of CE-5 basalt. For example, the estimated TiO 2 content of CE-5 basalt ranges from 3.7 wt% to 12.7 wt% and the Mg# (molar percentage of Mg/[Mg + Fe]) also shows a wide range (26.2 − 42.4). Preliminary experimental studies have shown that these geochemical characteristics of CE-5 basalt are critical for investigating the crystallization sequence and formation mechanism of its parent magma. This study presents new experimental data on the distribution coefficient of titanium between pyroxene and lunar basaltic magma \(\left( {{\text{D}}_{{{\text{Ti}}}}^{{\text{Px/melt}}} } \right)\) . Combining with available literature data, we confirm that \({\text{D}}_{{{\text{Ti}}}}^{{\text{Px/melt}}}\) is affected by crystallization conditions such as pressure and temperature, but it is mainly controlled by the CaO content of pyroxene. Comparing with previous experimental results under similar conditions, we parameterized the effect as \({\text{D}}_{{{\text{Ti}}}}^{{\text{Px/Melt}}} {\text{ = D}}_{{{\text{Ti}}}}^{{\text{Px/Melt}}} { \;= - 0}{\text{.0005X}}_{{{\text{Cao}}}}^{{2}} { \;+\; 0}{\text{.0218X}}_{{{\text{CaO}}}} { \;+\; 0}{\text{.0425} ({\text{R}}^{2} = 0}{.82)}\) \(\text{,}\) where X CaO is the CaO content in pyroxene in weight percentage. The new experimental results suggest that pyroxene with high TiO 2 content (> 2.5 wt%) in CE-5 basalt is not a product of equilibrium crystallization, and the CaO content in pyroxene is also affected by cooling rate of its parent magma. The TiO 2 content in the CE-5 parent magma is estimated to be about 5 wt% based on the Mg# of pyroxene and its calculated CaO content, which is consistent with those estimated from olivine grains.
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