查找使用阿拉丁产品的科研文献

The Gut Microbiota-Produced Indole-3-Propionic Acid Confers the Antihyperlipidemic Effect of Mulberry-Derived 1-Deoxynojirimycin

Yougui Li,Wenyi Xu,Fang Zhang,Shi Zhong,Yuqing Sun,Jinxi Huo,Jianxun Zhu,Chongming Wu

Hyperlipidemia is a worldwide epidemic with an obvious gender disparity in incidence. Modulations on gut microbiota by traditional Chinese medicines (TCM) are emerging as a potential rationale governing the profitable effects of drugs on hyperlipidemia. However, it is unclear how gut microbes regulate the progression of hyperlipidemia. Here, we found that mulberry leaf extract (MLE) and its active component 1-deoxynojirimycin (DNJ) diminished hyperglycemia and hypertriglyceridemia with similar efficacy in male and female mice but preferentially alleviated hypercholesterolemia in female mice. Further investigations showed that DNJ sex-specifically downregulated the expression of lipogenic genes, especially cholesterol-biosynthetic genes. Oral administration of DNJ imposed more profound modulation on gut microbiota in female mice than in male ones, as estimated by 16S rRNA metatranscriptomic analysis. DNJ markedly enriched Akkermansia and Clostridium group XIVa and promoted the production of indole-3-propionic acid (IPA) in a sexually dimorphic way. Importantly, IPA tightly associates with the antihyperlipidemic effect of DNJ and exhibited a potent lipid-lowering effect both in vitro and in vivo. Together, our results have established a regulatory mechanism by which DNJ sex-specifically improves hyperlipidemia, offering an in-depth theoretical basis for therapeutic exploitation of DNJ as a sex-specific intervention against hyperlipidemia.IMPORTANCE Hyperlipidemia has been intensively focused on by researchers around the world owing to its major contribution to cardiovascular diseases. Various evidence reveals that women are more susceptible than male counterparts to dyslipidemia, making sex-dependent therapeutic strategies and drugs urgently needed. In the present work, we demonstrate that DNJ, the main active component of mulberry leaves, exerts an obvious female-preferential antihyperlipidemic effect through specifically enriching Akkermansia and Clostridium XIVa and elevating an active microbial metabolite, indole-3-propionic acid (IPA), in female mice. Moreover, we have corroborated the potent lipid-lowering efficacy of IPA both in vitro and in vivo. These findings not only indicate a potential mechanism by which gut microbes and their metabolites confer the beneficial role of DNJ in ameliorating hyperlipidemia but also provide an in-depth theoretical basis for therapeutic exploitation of DNJ as a female-specific intervention against hyperlipidemia.

Pharmacokinetics and pharmacodynamics of bioactive compounds in Penyanqing preparation in THP-1 inflammatory cells induced by Lipopolysaccharide

Gong Linna,Miao Zhishuo,Zhang Li,Shi Birui,Xiao Zuoqi,Qiu Panzi,Liu Menghua,Zou Wei

Background Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.Methods The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC–MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).Results The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9—-0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.Conclusion The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.

4-Amino-1-(3-mercapto-propyl)-pyridine Hexafluorophosphate Ionic Liquid Functionalized Gold Nanoparticles for IgG Immunosensing Enhancement

Rui Li,Kangbing Wu,Changxian Liu,Yin Huang,Yanying Wang,Huaifang Fang,Huijuan Zhang,Chunya Li

A novel ionic liquid, 4-amino-1-(3-mercapto-propyl)-pyridine hexafluorophosphate (AMPPH), was successfully synthesized and characterized. Subsequently, AMPPH was used as a functional monomer to fabricate AMPPH-modified gold nanoparticles (AMPPH–AuNPs) via a one-pot synthesis method. The as-prepared AMPPH–AuNPs were confirmed with transmission electron microscopy and X-ray photoelectron spectroscopy. AMPPH–AuNPs were used to construct a biocompatible interface to immobilize rabbit anti-human IgG (anti-HIgG) onto a glassy carbon electrode (GCE) surface, followed by a cross-linking step with glutaraldehyde to fabricate an anti-HIgG–AMPPH–AuNPs/GCE. The nonspecific binding sites were enclosed with bovine serum albumin (BSA) to develop an immunosensor for human IgG. Electrochemical impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry were used to investigate the electrochemical properties of the developed immunosensor. The results indicate that AMPPH–AuNPs can improve the immunosensing performance. The current response of the immunosensor was found linearly related to human IgG concentration in the range of 0.1–5.0 ng mL–1 and 5.0–100.0 ng mL–1. The detection limit is estimated to be 0.08 ng mL–1 (S/N = 3). The obtained immunosensor was successfully applied to the analysis human IgG immunoglobulin in human serum, and the results were well consistent with ELISA method.

Study on the structure and properties of (1-x) BiYbO3-xBaTiO3 ceramics synthesized by sol–gel method

Gang Chen,Chunlin Deng,Xiaodong Peng,Chunlin Fu,Wei Cai,Rongli Gao,Xiaoling Deng

Glypican-1-antibody-conjugated Gd–Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer

Xin Huang,Chengqi Fan,Huanhuan Zhu,Wenjun Le,Shaobin Cui,Xin Chen,Wei Li,Fulei Zhang,Yong Huang,Donglu Sh,Zheng Cui,Chengwei Shao,Bingdi Chen

Modified polybutene-1 film with high dielectric constant based on low doping amount of fluorine-based compound

Yantong Long,Yongcheng Pan,Yongjun Xu,Yibin Yan

In this paper, a C8 perfluoroacrylate/polybutene-1 composite film was prepared by solution casting method. Analysis by FTIR, XRD and SEM shows that C8 perfluoroacrylate has been successfully and uniformly integrated into the matrix polybutene-1, and the crystal structure of the matrix polybutene-1 remains intact without any change. When the content of the filler is very low, local structural changes can occur, resulting in an increase in dielectric constant and breakdown field strength , and can reduce conduction losses at high frequencies. Therefore, at room temperature, when f = 1kHz and the filler content is 0.2wt%, the dielectric constant of the composite film ε = 12.81, which is nearly 620 % higher than that of the pure PB-1 film ( ε = 1.78), and the dielectric loss still remains in tan σ = 0.011, and the composite film storage performance as well as the most excellent U e = 8.65 J/cm 3 , which is 8.5 times the energy storage density of the pure PB-1 material ( U e = 1.02 J/cm 3 ). The composite materials in this work show excellent properties such as high dielectric constant, low dielectric loss, and high breakdown field strength, which are prospective in the application of capacitors.

Synthesis of low-symmetry 2D Ge(1−x)SnxSe2 alloy flakes with anisotropic optical response and birefringence

Yijun Liu,Minghui Wu,Zhaoyang Sun,Shengxue Yang,Chunguang Hu,Li Huang,Wanfu Shen,Bin Wei,Zhongchang Wang,Shiqi Yang,Yu Ye,Yan Li,Chengbao Jiang

Low-symmetry two-dimensional (2D) materials with unique in-plane anisotropy can promote both fundamental science and practical applications in optics, optoelectronics, electronics, and polarization detection. As a member of 2D materials, doping/alloying material systems have gained great attention owing to the tunable bandgap and special properties. However, the in-plane anisotropic optical and electrical properties of these 2D alloy materials have rarely been reported. In this work, low-symmetry 2D Ge(1−x)SnxSe2 (x = 0–1.0) alloy flakes have been synthesized by chemical vapor deposition (CVD) with a bandgap varying from 1.55 eV (GeSe2, x = 0) to 1.90 eV (SnSe2, x = 1.0). Angle-resolved polarized Raman spectroscopy (ARPRS) is used to confirm the in-plane vibrational anisotropy, and azimuth-dependent reflectance difference microscopy (ADRDM) is applied to visualize the in-plane optical anisotropy. Polarization-dependent transmission spectroscopy (PDTS) is carried out to reflect the in-plane absorptional anisotropy and linear dichroism, and birefringence characteristics are also found in the subsequent studies. All of the results indicate the unique in-plane optical anisotropy and birefringence characteristics of the 2D Ge(1−x)SnxSe2 alloy flakes, providing new opportunities for polarization-controlled devices, optical wave plates, and polarizers.

Metabolomics-based mechanism of colour change in Cuibi No.1 flue-cured tobacco leaves during early aging

Qishan Xie,Jiawei Yang,Jianwei Wang,Lufan Yang,Bingye Yang,Han Yan,Aiguo Wang,Xiang Zhang,Ying Cui,Shengfeng Wang,Xuan Chen,Xinyi Zhang,Penghui Lyu,Yanling Zhang

Early aging is critical for colour formation in tobacco leaves, yet the underlying metabolic mechanisms remain elusive. This study integrated image processing with untargeted and targeted LC-MS to construct a metabolic network characterising colour evolution in flue-cured tobacco (cv. Cuibi-1, CB-1 ) during early aging (0–120 days). Results indicated that leaf colour significantly brightened during the first 30 days, followed by deepening and reddening. Specifically, L* and b* values showed an initial increase followed by a decrease, whereas the a* value exhibited a sustained upward trend. The constructed metabolic network was anchored in saccharide metabolism, connecting downstream phenolic, flavonoid, sphingolipid, and terpenoid pathways. Sixteen differentially accumulated metabolites (DAMs) were identified across categories including alcohols, flavonoids, lignans, nucleotides, phenolic acids, saccharides, and xanthophylls. These DAMs exhibited distinct change patterns and significant correlations with colour parameters (L* and a*, r ranging from −0.88 to −0.58 and 0.56–0.74, respectively; P  < 0.05). For the first time, this study elucidated the metabolic mechanisms governing colour changes in CB-1 tobacco leaves during early aging for the first time, providing novel insights for assessing aging progression and maintaining high-value raw material quality.

CARD9 Conveys Pancreatic Islet Sympathetic Nervous β2 Signals to Reshape Macrophage Creatine Metabolism in Type 1 Diabetes

Huimin Yuan,Senlin Li,Shuai Liu,Hong Zhou,Yue Xu,Wenhui Li,Mengxuan Wang,Mengheng Wang,Mengzhu Zheng,Wenxi Shi,Xin Li,Yiting Feng,Ming Xiang

Type 1 diabetes (T1D) is an autoimmune disorder marked by the injury of pancreatic β cells, during which sympathetic neurons in the endocrine region of pancreas are lost, whereas those in the exocrine regions surrounding islets remain intact. This abnormal sympathetic nervous signaling may disrupt the balance of the neuroendocrine-immune network and contribute to the development of T1D, although its underlying molecular mechanisms are still elusive. Here, single-cell omics and whole-tissue immunostaining reveal a decrease in pancreatic sympathetic nerve density in T1D patients and T1D mouse models. Surgical and chemical desensitization of the sympathetic nervous system exacerbates T1D, while macrophage depletion mitigates this effect. Mechanistically, diminished norepinephrine (NE) release impairs β2-adrenergic receptor (β2-AR)-PKA-CREB1 signaling in islet macrophages, leading to downregulation of the adaptor caspase recruitment domain family member 9 (CARD9). Loss of CARD9 decreases SLC6A8-mediated creatine uptake, shifts macrophages toward a pro-inflammatory phenotype, and promotes sympathetic axon ferroptosis driven by decreased neurotrophic factor and anti-inflammatory factor release. Conversely, β2-AR agonist formoterol restores PKA-CREB1-CARD9 activation, preserves creatine metabolism, and maintains anti-inflammatory macrophage polarization. These findings define a novel sympathetic-macrophage-creatine metabolic axis governed by CARD9 that links neural signals to immune and metabolic regulation in T1D, highlighting neuroimmune interactions as targets for therapies.

Polymorphism in F pocket affects peptide selection and stability of type 1 diabetes-associated HLA-B39 allotypes

A. W. Peshala Amarajeewa,Aslihan Özcan,Alveena Mukhtiar,Xu Ren,Qianyu Wang,Pemra Ozbek,Malgorzata A. Garstka,Onur Serçinoğlu

HLA-B*39:06, HLA-B*39:01, and HLA-B*38:01 are closely related HLA allotypes differentially associated with type 1 diabetes (T1D) risk and progression. B*39:06 is highly predisposing, while B*39:01 and B*38:01 are weakly predisposing and protective allotypes, respectively. Here, we aimed to decipher molecular mechanisms underlying the differential association of these allotypes with T1D pathogenesis. We addressed peptide binding and conformational stability of HLA-B allotypes using computational and experimental approaches. Computationally, we found that B*39:06 and B*39:01 allotypes had more rigid peptide-binding grooves and were more promiscuous in binding peptides than B*38:01. Peptidomes of B*39:06 and B*39:01 contained fewer strong binders and were of lower affinity than that of B*38:01. Experimentally, we demonstrated that B*39:06 and B*39:01 had a higher capacity to bind peptides and exit to the cell surface but lower surface levels and were degraded faster than B*38:01. In summary, we propose that promiscuous B*39:06 and B*39:01 may bind suboptimal peptides and transport them the cell surface, where such unstable complexes may contribute to the pathogenesis of T1D.

Insights into the hepatotoxicity of pyrene and 1-chloropyrene using an integrated approach of metabolomics and transcriptomics

Yun Luo,Baoqin Zhang,Ningbo Geng,Shuai Sun,Xiaoyao Song,Jiping Chen,Haijun Zhang

The toxicity of pyrene (Pyr) and its chlorinated species have not be comprehensively and clearly elucidated. In this study, an integrated approach of metabolomics and transcriptomics were applied to evaluate the hepatotoxicity of Pyr and 1-chloropyrene (1-Cl-Pyr) at human exposure level, using human L02 hepatocytes. After 24 h exposure to Pyr and 1-Cl-Pyr at 5–500 nM, cell viability was not significantly changed. Transcriptomics results showed that exposure to Pyr and 1-Cl-Pyr at 5 and 50 nM obviously altered the gene expression profiles, but did not significantly induce the expression of genes strongly related to the activation of aryl hydrocarbon receptor (AhR), such as CYP1A1 , CYP1B1, AHR, ARNT . Pyr and 1-Cl-Pyr both induced a notable metabolic perturbation to L02 cells. Glycerophospholipid metabolism was found to be the most significantly perturbed pathway after exposure to Pyr and 1-Cl-Pyr, indicating their potential damage to the cell membrane. The other significantly perturbed pathways were identified to be oxidative phosphorylation (OXPHOS), glycolysis, and fatty acid β oxidation, all of which are related to energy production. Exposure to Pyr at 5 and 50 nM induced the up-regulation of fatty acid β oxidation and OXPHOS. The similar result was observed after exposure to 5 nM 1-Cl-Pyr. In contrast, exposure to 50 nM 1-Cl-Pyr induced the down-regulation of OXPHOS by inhibiting the activity of complex I. The obtained results suggested that the modes of action of Pyr and 1-Cl-Pyr on energy production remarkably varied not only with molecular structure change but also with exposure concentration.

Nickel-catalyzed cross-coupling of sterically hindered 1-bromomethyl-o-carborane with alkyl and aryl Grignard reagents

Juyou Lu,Hong Wan,Yunna Xue,Yongmei Du,Jian Lu

A convenient and efficient Ni-catalyzed reaction has been developed for synthesis of mono-substituted o -carboranes, involving cross-coupling of readily available and sterically hindered 1-bromomethyl- o -carborane with various alkyl and aryl Grignard reagents under mild conditions, and the corresponding o -carborane derivatives were obtained in good to excellent yields. This method should provide a new strategy for construction of diverse and useful functionalized boron cluster compounds for medicinal chemistry and material chemistry.