CLINICA CHIMICA ACTA
·
2023
·
IF 5
Yueyuan Zhang,Sha Xu,Jianxin Xu,Fuchao Xu,Geng Lu,Jiawei Zhou,Shuangshuang Gu,Jun Wang
Background Early evaluation of the severity of sepsis and estimation of its prognosis remains one of the main challenges in current therapeutic strategies. This study aimed to evaluate the prognostic value of plasma 7-ketocholesterol (7-KC) in sepsis. Methods We retrospectively measured by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) the plasma 7-KC concentration in 176 patients with sepsis and 90 healthy volunteers. A multivariate Cox proportional hazard model was introduced to identify independent factors, including plasma 7-KC and clinical features, for the 28-day mortality of sepsis, and a nomogram for predicting the 28-day mortality of sepsis was established. Decision curve analysis (DCA) was performed to assess the prediction model of death risk of sepsis. Results The area under the curve (AUC) of plasma 7-KC in diagnosing sepsis was 0.899 (95% CI = 0.862–0.935, P < 0.001), while it was 0.830 (95% CI = 0.764–0.894, P < 0.001) in diagnosing septic shock. The AUCs of plasma 7-KC in predicting the survival of sepsis patients in the training cohort and the test cohort were 0.770 (95% CI = 0.692–0.848, P < 0.05) and 0.869 (95% CI = 0.763–0.974, P < 0.05), respectively. In addition, high plasma 7-KC expression predicts poor prognosis in sepsis. Then, 7-KC and platelet count were identified as the two factors with significant differences by a multivariate Cox proportional hazard model, and the 28-day mortality probability ranged from 0.002 to 0.985 and was assessed using a nomogram. DCA results revealed that the combination of plasma 7-KC and platelet count showed the best prognostic efficiency of the risk threshold compared to a single factor in both the training cohort and test cohort. Conclusions Collectively, the elevated plasma 7-KC level is an indicator of sepsis and was identified as a prognostic indicator for sepsis patients, providing a landscape for predicting survival in early sepsis with potential clinical utility.
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高影响因子
Biotechnology Journal
·
2023
·
IF 4.7
Xia Ke,Zi-Hao Pan,Hong-Fei Du,Yi Shen,Ji-Dong Shen,Zhi-Qiang Liu,Yu-Guo Zheng
Background 7-dehydrocholesterol (7-DHC) can be directly converted to vitamin D 3 by UV irradiation and d e novo synthesis of 7-DHC in engineered Saccharomyces cerevisiae has been recognized as an attractive substitution to traditional chemical synthesis. Introduction of sterol extracellular transport pathway for the secretory production of 7-DHC is a promising approach to achieve higher titer and simplify the downstream purification processing. Methods and results A series of genes involved in ergosterol pathway were combined reinforced and reengineered in S. cerevisiae . A Biphasic fermentation system was introduced and 7-DHC was found to be enriched in oil-phase with an increased titer by 1.5-folds. Quantitative PCR revealed that say1, atf2, pdr5, pry1-3 involved in sterol storage and transport were all significantly induced in sterol overproduced strain. To enhance the secretion capacity, lipid transporters of Pry (Pathogen-related yeast proteins), NPC2(Niemann-Pick disease type C2), ABC(ATP-binding cassette)-family and their homologues were screened. Both individual and synergetic overexpression of Pr-1 (Plant pathogenesis Related protein-1) and St1 (Sterol transport1) largely increased the de novo biosynthesis and secretory productivity of 7-DHC, and the final titer reached 28.2 mg/g with a secretion ratio of 41.4%, which was 26.5-folds higher than the original strain. In addition, the cooperation between Pr-1 and St1 in sterol transport was further confirmed by confocal microscopy, molecular docking and directed site-mutation. Conclusion Selective secretion of different sterol intermediates was characterized in sterol over-produced strain and the extracellular export of 7-DHC developed in present study significantly improved the cell biosynthetic capacity, which offered a novel modification idea for 7-DHC de novo biosynthesis by S. cerevisiae cell factory. This article is protected by copyright. All rights reserved
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PubMed
高影响因子
Cells
·
2023
·Vol. 12
·期 6
·831
·
IF 6
Xuehui Wang,Jiaying Wang,Zihui An,Aifen Yang,Mengsheng Qiu,Zhou Tan
Mounting evidence suggests that circular RNAs play important roles in the development and progression of cancers. However, their function in glioblastomas (GBM) is still unclear. By circRNA array analysis, we found that circXPO1 (hsa_circ_102737) was significantly upregulated in GBM, and qPCR analysis verified that the circXPO1 expression level was increased in both GBM tissues and cell lines. Functional studies demonstrated that the knockdown of circXPO1 in GBM cell lines repressed cell proliferation and migration; conversely, the overexpression of circXPO1 promoted the malignancy of GBM cells. In line with these findings, circXPO1 inhibition effectively suppressed gliomagenesis in the in situ transplantation model of nude mice. Through bioinformatic analyses and dual-luciferase reporter assays, we showed that circXPO1 directly bound to miR-7-5p, which acted as a tumor suppressor through the negative regulation ofRAF1. In conclusion, our studies suggest that the circXPO1/miR-7-5p/RAF1axis promotes brain tumor formation and may be a potential therapeutic target for GBM treatment.Keywords:circXPO1;glioblastomas;ceRNA;miR-7-5p;RAF1
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高影响因子
Food Frontiers
·
2025
·
IF 6.9
Peng Han,Bo Wang,Luyang Han,Yanbo Zhu,Jiawei Dong,Yuekang Xu,Xiaoying Liu,Jinyao Li
Zanthoxylum ailanthoides , a medicinal and edible plant, was mostly used as medicinal materials or spices, in which 7-demethylsuberosin (7-Dem) was identified as active component, but its function and mechanism on dendritic cells (DCs) are not clear. The objective of this study was to explore the effect and mechanism of 7-Dem on the maturation and function of DCs in the treatment of rheumatoid arthritis. The impact of 7-Dem on DCs was assessed using flow cytometry and ELISA. Agonists of the Toll-like receptor pathway and cytochalasin D were employed to validate the pathway affected by 7-Dem. Furthermore, molecular docking, network pharmacology, Western blotting, and CETSA were used to explore the targets of 7-Dem. The immunomodulatory effects of 7-Dem were examined using the adjuvant-induced arthritis (AIA) mouse model. The results showed that 7-Dem did not damage the viability of DCs at doses below 10 µM but suppressed the maturation of DCs induced by lipopolysaccharide in vitro and in vivo , enhanced phagocytosis, and restrained migration. DCs exhibited an impaired stimulation of CD4 + T cell proliferation and restored the imbalance of CD4 + T cell subtypes after treatment with 7-Dem. At molecular levels, 7-Dem inhibited the maturation of DCs induced by agonists and decreased the expression of TRAF6, not TRAF3. Furthermore, 7-Dem improved the thermal stability and reduced the phosphorylation of MAPK14. In vivo , 7-Dem alleviated joint inflammation with restored imbalance of T cell subtypes. In conclusion, 7-Dem inhibits the maturation and function of DCs by targeting MAPK14 and inhibiting the phosphorylation of MAPK14, which thereby restores immune tolerance and alleviates inflammation in the AIA joints.
研究领域:
生药学
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免疫学
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天然产物研究
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分子生物学
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风湿病学
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功能食品
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民族药理学
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2024
·
IF 8.1
Qiyu Duan,Shao-Lu Li,Youcai Chen,Mengfan Wang,Dandan Cheng,Genghao Gong,Yunxia Hu
In recent years, OSN technology has gained great attention for its environmental friendly nature, energy efficiency, and small carbon footprint. Herein, we prepared TFC OSN membranes BINOL-TPC and BINOL-IPC with higher selectivity by employing a contorted molecule 7,7′-dihydroxy-2,2′-binaphthol (7,7′-OH-BINOL) with four functional groups and diacyl chloride (TPC/IPC) via interfacial polymerization (IP) method compared to with trimesoyl chloride (TMC). The use of monomer 7,7′-OH-BINOL with rigid, twisted and multiple reaction sites endow the resulted polyarylate layer with high microporosity and cross-linking density. Notably, the BINOL-TPC and BINOL-IPC membranes exhibited good performance in retaining small molecular solutes, with MWCO values of 288 and 344 Da, respectively. Meanwhile, the methanol permeance of the two composite membranes reach 5.81 and 7.06 LMH/bar, respectively. In addition, the membrane BINOL-TPC could achieve precise separation of mixed dyes with similar molecular weight but opposite charge. As can be seen, by designing and utilizing IP monomers with different structures and functionalities, it is possible to fabricate membranes with diverse microstructures and properties, ultimately leading to varied separation performances. This research offers some new insights in the view of molecular-level tailoring for the fabrication of high performance OSN membranes.
研究领域:
材料科学
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化学工程
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环境科学
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MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 10
·1-9
·
IF 6.232
Huang Lingting,Wang Jun,Wang Qingshui,Tang Dianping,Lin Yao
A paper-based visual fluorescence immunoassay is presented for the detection of matrix metalloproteinase-7 (MMP7) that is related to renal cancer. The method is based on the distance-dependent fluorescence quenching of CdTe quantum dots (QDs) on a nitrocellulose membrane by Ag + following a sandwich-type immunoreaction on microtiter wells using silver nanoparticle (AgNP)–labeled secondary antibody– and primary antibody–coated microtiter wells. The silver nanoparticles captured in the well are dissolved with HNO 3 , while the quenching effect of QDs is based on silver ion-exchange reaction under 365-nm excitation light irradiation. Increasing concentration of released Ag + , thus higher concentration of the protein, leads to an increased distance of quenching on the nitrocellulose membrane. The paper-based immunoassay by combination of AgNP-assisted ion-exchange reaction with QD gives good distance-dependent responses and allows the detection of MMP7 at a concentration as low as 7.3 pg mL −1 . The coefficients of variation are less than 6.9% and 12.4% for intra-assay and inter-assay, respectively. High specificity and long-term stability are achieved during the assay. Importantly, the testing of human serum samples using our strategy shows well-matched results with commercial human MMP7 ELISA kits.
A distance-dependent visual immunoassay is developed for the determination of serum matrix metalloproteinase-7 on CdTe quantum dot–impregnated paper with silver ion-exchange reaction.
研究领域:
分析化学
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生物化学
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医学诊断
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纳米技术
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PubMed
高影响因子
Journal of Diabetes and Metabolic Disorders
·
2022
·Vol. 21
·期 2
·1731-1741
·
IF 0
Wu Tongyu,Li Chun,Zhou Jing,Han Liang,Qiang Shaojia,Hu Zhuozhou,Liu Jingjing,Li Xiangxiang,Zhao Wenyang,Chen Xinping
Background The global prevalence of type 2 diabetes mellitus (T2DM) raises the rates of its complications, such as diabetic nephropathy and cardiovascular diseases. To conquer the complications, new strategies to reverse the deterioration of T2DM are urgently needed. In this project, we aimed to examine the hypoglycemic effect of primaquine and explore its specific target. Methods In vitro T2DM insulin resistance model was built in HepG2 cells to screen the potential anti-diabetic chemicals. On the other hand, the potential protein targets were explored by molecular docking. Accordingly, we chose C57BL/6 N mice to establish T2DM model to verify the effect of the chemicals on anti-hyperglycemia and diabetic complications. Results By targeting the Keratin 7 (K7) to activate EGFR/Akt glucose metabolism signaling pathway, primaquine poses a potent hypoglycemic effect. The level of acetyl-CoA is enhanced markedly, supporting that primaquine upregulates the aerobic glycolysis. Moreover, primaquine ameliorates kidney function by reducing the secretion of urinary proteins and creatinine, especially for the urea nitrogen which is significantly decreased compared to no-treatment T2DM mice. Notably, primaquine restores the level of plasma low-density lipoprotein cholesterol (LDL-C) nearly to normal, minimizing the incidence of cardiovascular diseases. Conclusions We find that primaquine may reverse the dysregulated metabolism to prevent diabetic complications by stimulating EGFR/Akt signaling axis, shedding new light on the therapy of T2DM. Graphical abstract
Insulin resistance is characterized by reduced p-Akt and glucose metabolism, dominated by anaerobic glycolysis. Primaquine activates the complex made of K7 and EGFR, further stimulating Akt phosphorylation. Then, p-Akt promotes the aerobic glucose metabolism and upregulates Ac-CoA to mobilize TCA cycle, improving insulin sensitivity.
研究领域:
药理学
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内分泌学
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分子生物学
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糖尿病研究
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细胞信号传导
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DOI
PubMed
Advanced Healthcare Materials
·
2022
·Vol. 11
·期 12
·2102739
·
IF 11.092
Yanyun Hao,Hui Li,Huajun Zhao,Yutong Liu,Xiaoyan Ge,Xia Li,Hongfei Chen,Ailu Yang,Jing Zou,Xue Li,Xuechun Sun,Xinke Zhang,Xiao Wang,Zepeng Li,Qilu Zhang,Hao Wu,Guan Wang,Jian Zhang,Bruno G. De Geest,Zhiyue Zhang
Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (folic acid (FA)/1-(4-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (IMDQ)-oxaliplatin (F/IMO)@CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared-responsive inorganic CuS nanoparticles, acting as a photosensitizer and carrier of the chemotherapeutic agent oxaliplatin, and enters tumor cells owing to the presence of folic acid on the surface of CuS upon intratumoral injection. Furthermore, a toll-like receptor (TLR) 7/8 agonist-conjugated polymer, anchored on the surface of CuS, is modified with mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing oxaliplatin, to ablate tumor cells and amplify immunogenic cell death in combination with photothermal therapy. Mannose-modified polymer-TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long-term immune protection to prevent tumor recurrence.
研究领域:
肿瘤学
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免疫学
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纳米技术
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药学
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PubMed
高影响因子
Foods
·
2021
·Vol. 10
·期 10
·2453
·
IF 4.35
Jingfei Hu,Xueqing Tian,Tong Wei,Hangjie Wu,Jing Lu,Mingsheng Lyu,Shujun Wang
Helicobacter pyloriis a cause of gastric cancer. We extracted the exopolysaccharide (EPS) ofLactobacillus plajomiPW-7 for antibacterial activity versusH. pylori, elucidating its biological activity and structural characteristics. The minimum inhibitory concentration (MIC) of EPS againstH. pyloriwas 50 mg/mL. Disruption of the cell membranes of pathogenic bacteria by EPS was indicated via the antibacterial mechanism test and confirmed through electron microscopy. EPS also has antioxidant capacity. The IC50of EPS for 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide anions, and hydroxyl radicals were 300 μg/mL, 180 μg/mL, and 10 mg/mL, respectively. The reducing power of EPS was 2 mg/mL, equivalent to 20 μg/mL of ascorbic acid. EPS is a heteropolysaccharide comprising six monosaccharides, with an approximate molecular weight of 2.33 × 104Da. Xylose had a significant effect onH. pylori. EPS fromL. plajomiPW-7 showed potential as an antibacterial compound and antioxidant, laying a foundation for the development of EPS-based foods.Keywords:Helicobacter pylori;Lactobacillus plajomi;exopolysaccharide;antibacterial activity;antioxidant activity
研究领域:
微生物学
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食品科学
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医学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2024
·
IF 8.1
Chengguo Yan,Jiaguang Zheng,Ao Xia,Qingbo Zhang,Meiling Lv,Zhenxuan Ma,Chao Su,Zhendong Yao
Among conventional hydrogen storage materials , LiBH 4 has been regarded as one of the best hydrogen transporters due to its relatively large hydrogen capacities. However, because of its extraordinarily high dehydrogenation temperatures, LiBH 4 was not suitable for hydrogen storage due to its stable thermodynamic features. Herein, we present a novel approach to LiBH 4 that uses solid-state multi-hydroxyl mannitol as a reactant, regulating hydrogen release below 69.9 °C. More than 7 wt% H 2 could be released with ultra-fast rates at 140 °C from the LiBH 4 -mannitol composite. XRD , FTIR , and SEM tests revealed that the reaction between mannitol (H δ+ ) and LiBH 4 (H δ− ) to produce hydrogen was accompanied by the generation of large amounts of heat in situ, which further promoted the decomposition of LiBH 4 for hydrogen production , exceeding the theoretical dehydrogenation amount of H δ+ - H δ− reaction. This work indicates possibilities for the development of fast and easy high-capacity hydrogen generation systems based on complex hydrides.
研究领域:
材料科学
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无机化学
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能源化学
·
氢能源存储
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DOI
高影响因子
BIOORGANIC CHEMISTRY
·
2026
·
IF 5.1
Yun Bin Han,Li Sha Lin,Nanxi Wang,Ren Xiang Tan
Carthamidin and isocarthamidin as well as their 7-O-glucuronides are abundant tetrahydroxyflavanones in Scutellaria barbata , but their biosynthesis remains poorly defined. Here, we combined metabolite profiling, transcriptome-guided gene discovery, heterologous expression, enzymatic assays, virus-induced gene silencing (VIGS), and transient pathway reconstruction to elucidate their biosynthetic pathway. SbarCHS1 and SbarCHI form the naringenin-producing module. Three CYP82D enzymes then catalyze regioselective A-ring hydroxylation: SbarCYP82D1 and SbarCYP82D8 function as naringenin 6-hydroxylases to generate carthamidin, whereas SbarCYP82D5 acts as an efficient naringenin 8-hydroxylase to produce isocarthamidin. A UGT88-family enzyme, SbarUGAT, catalyzes 7-O-glucuronidation of both hydroxylated flavanones. Non-enzymatic interconversion observed between carthamidin and isocarthamidin and between their corresponding 7-O-glucuronides further suggests that chemical equilibration contributes to this branched biosynthetic pathway. VIGS confirmed the in planta roles of SbarCHS1, SbarCYP82D8, and SbarUGAT, identifying SbarCYP82D8 as the dominant hydroxylation enzyme in leaves. Reconstitution in Nicotiana benthamiana enabled de novo production of both glucuronides, and co-expression of SbarUGDH further enhanced glucuronide accumulation. These findings define the S. barbata biosynthesis of bioactive flavanone glucuronides and provide enzymes for future metabolic engineering of such specialized flavonoids.
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Yaqiang Li,Xuesong Peng,Ruopeng Li,Jie Jiang,Meng Fan,Youzheng Wu,Changsheng Cao,Guangzhao Wang,Penghui Ren,Hao Xu,Maozhong An
Achieving metal interconnect for printed circuit boards (PCBs) is pivotal for electronics industry. Through electrochemical analysis for Basic Blue 7 (BB7), excellent suppressing effect was analyzed. Chronopotentiometry was used to study the possible concentration range for microvias filling and 50-150 mg·L-1 was selected to achieve superfilling electrodeposition. Difunctional mechanism of coordination and adsorption of BB7 during electrodeposition is proposed by density functional theory (DFT) calculation and in situ Raman spectroscopy analysis. The interaction among BB7, copper substrate and Cu2+ leads to the suppression for copper growth. Superfilling electroplating process is optimized and high filling performance can be achieved at 100 mg·L-1 with filling percentage (FP) values of 80.19%, 84.70% and 87.90% for microvias with diameters of 100 μm, 125 μm and 150 μm, respectively. Besides, Differential Diffusion Filling Mechanism was proposed to illustrate the blind microvias filling process of newly proposed electroplating system based on interaction analysis among additives and diffusion kinetics. What’s more, the performance of copper interconnect layer, including surface morphology, phase structure and signal transmittance, was evaluated.
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高影响因子