Neural Regeneration Research
·
2020
·
IF 3.171
Jian-Zhu Bo,Ling Xue,Shuang Li,Jing-Wen Yin,Zheng-Yao Li,Xi Wang,Jun-Feng Wang,Yan-Shu Zhang
Although exogenous D-serine has been applied as a neural regulatory intervention in many studies, the role played by D-serine in hippocampal injuries caused by lead exposure remains poorly understood. Rat models of chronic lead exposure were established through the administration of 0.05% lead acetate for 8 weeks. Simultaneously, rats were administered 30 or 60 mg/kg D-serine, intraperitoneally, twice a day. Our results showed that D-serine treatment shortened the escape latency from the Morris water maze, increased the number of times that mice crossed the original platform location, and alleviated the pathological damage experienced by hippocampal neurons in response to lead exposure. Although D-serine administration did not increase the expression levels of the N-methyl-D-aspartate receptor subtype 2B (NR2B) in the hippocampi of lead-exposed rats, 60 mg/kg D-serine treatment restored the expression levels of NR2A, which are reduced by lead exposure. These findings suggested that D-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of NR2A in the hippocampus. This study was approved by the Animal Ethics Committee of North China University of Science and Technology, China (approval No. LX2018155) on December 21, 2018.
研究领域:
神经科学
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毒理学
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药理学
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NEURON
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2024
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IF 14.7
Xinyi Zhou,Qian Xiao,Yaohui Liu,Shuai Chen,Xirong Xu,Zhigang Zhang,Yuchuan Hong,Jie Shao,Yuewen Chen,Yu Chen,Liping Wang,Fan Yang,Jie Tu
Assessing and responding to threats is vital in everyday life. Unfortunately, many mental illnesses involve impaired risk assessment, affecting patients, families, and society. The brain processes behind these behaviors are not well understood. We developed a transgenic mouse model (disrupted-in-schizophrenia 1 [DISC1]-N) with a disrupted avoidance response in risky settings. Our study utilized single-nucleus RNA sequencing and path-clamp coupling with real-time RT-PCR to uncover a previously undescribed group of glutamatergic neurons in the basolateral amygdala (BLA) marked by Wolfram syndrome 1 (WFS1) expression, whose activity is modulated by adjacent astrocytes. These neurons in DISC1-N mice exhibited diminished firing ability and impaired communication with the astrocytes. Remarkably, optogenetic activation of these astrocytes reinstated neuronal excitability via D-serine acting on BLA WFS1 neurons’ NMDA receptors, leading to improved risk-assessment behavior in the DISC1-N mice. Our findings point to BLA astrocytes as a promising target for treating risk-assessment dysfunctions in mental disorders.
研究领域:
神经科学
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分子生物学
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行为科学
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精神病学
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NEUROBIOLOGY OF DISEASE
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2025
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IF 5.6
Teng Teng,Shaofan Yang,Jin Li,Haoyu Wang,Fengjuan Wu,Yong He,Jihua Fan,Hongwei Shi,Mingzhu Huang,Xiang Zhou,Ying Liu,Mingyue Gong,Chuanyan Yang,Huiquan Wang,Zhenlu Cai,Hongli Li,Kuan Zhang
The astrocyte–neuron network in the primary somatosensory cortex (S1) responds dynamically to pain stimuli and plays a pivotal role in pain processing. These stimuli activate astrocytic α7-nicotinic acetylcholine receptors (α7-nAChRs), yet their contribution to pain perception remains largely unclear. This study investigates the role of astrocytic α7-nAChRs in pain information processing and perception. Astrocytic α7-nAChRs were selectively deleted by injecting rAAV5-GfaABC 1 D-NLS-Cre-P2A-mCherry into the S1 region of LoxP-Chrna7 transgenic mice or by tamoxifen administration in ALDH1-CreERT2:Chrna7 loxP/loxP mice. Immunohistochemistry was used to assess the expression of α7-nAChR and gliotransmitter d -serine. Astrocytic Ca 2+ transients were monitored in vivo using two-photon Ca 2+ imaging following AAV5-GfaABC 1 D-cytoGCaMP6f-SV40 labeling. Neuronal Ca 2+ transients in S1 evoked by plantar electric shock were recorded via fiber photometry in freely moving mice. Nociceptive and sensory behaviors were evaluated using hot plate and von Frey tests. Statistical analyses included Welch's t -tests for normally distributed data, Mann–Whitney U tests for non-normal data, and two-way ANOVA. Results showed that conditional deletion of α7-nAChRs in astrocytes markedly reduced d -serine levels within astrocytic territories. Two-photon Ca 2+ imaging and fiber photometry revealed that α7-nAChR deletion attenuated both astrocytic Ca 2+ transients and footshock-evoked neuronal Ca 2+ activity in S1. Behaviorally, thermal pain responses were significantly impaired, whereas tactile thresholds and open-field behaviors were unaffected. These findings identify astrocytic α7-nAChRs in S1 facilitate d -serine levels and enhance astrocytic activity. Their physiological function is essential for pain-related information processing within astrocyte–neuron networks and plays a critical role in regulating pain perception.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-11
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IF 14.7
Chen Chao,Ma Yinglin,Yao Kunda,Ji Qingmin,Liu Wei
Chiral metal surfaces provide an environment for enantioselective adsorption in various processes such as asymmetric catalysis, chiral recognition, and separation. However, they often suffer from limitations such as reduced enantioselectivity caused by kink coalescence and atomic roughness. Here, we present an approach using medium-entropy ceramic (MEC), specifically (CrMoTa)Si 2 with a C40 hexagonal crystal structure, which overcomes the trade-off between thermal stability and enantioselectivity. Experimental confirmation is provided by employing quartz crystal microbalance (QCM), where the electrode is coated with MEC films using non-reactive magnetron sputtering technology. The chiral nature is verified through transmission electron microscopy and circular dichroism. Density-functional theory (DFT) calculations show that the stability of MEC films is significantly higher than that of high-index Cu surfaces. Through a combination of high-throughput DFT calculations and theoretical modeling, we demonstrate the high enantioselectivity (42% e.e.) of the chiral MEC for serine, a prototype molecule for studying enantioselective adsorption. The QCM results show that the adsorption amount of L-serine is 1.58 times higher than that of D-serine within a concentration range of 0-60 mM. These findings demonstrate the potential application of MECs in chiral recognition.
研究领域:
材料科学
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表面化学
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催化
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手性
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SEPARATION AND PURIFICATION TECHNOLOGY
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2024
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IF 8.1
Dongbo Wang,Jingting Sang,Mingyang Wang,Dawei Luo,Dandan Han,Bowen Zhang,Jingtao Wang,Junbo Gong
Stereoselective recognition using “tailor-made” chiral ionic liquids (CILs) is an effective approach to obtaining enantiopure compounds through crystallization resolution. In this study, CILs were used as additives to stereoselectively inhibit the nucleation and growth of unwanted enantiomers via a conformational matching mechanism. Interestingly, a cosolvency phenomenon was found in the threonine-CILs-ethanol solvent system. Based on this, an enhanced stereoselective crystallization resolution strategy that combines ultrasound and cosolvency was proposed. The goal of this strategy was to improve the crystallization yield and enantiomeric purity. The results showed that the crystallization resolution yield of the cosolvency system was 33.43%, higher than that of the pure water system (13.56%). More importantly, the introduction of ultrasonic enhancement further increased the crystallization resolution yield to 39.45%. This work will facilitate the exploration of the unlimited potential of utilizing the cosolvency phenomenon and ultrasonic enhancement for crystallization resolution.
研究领域:
化学
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材料科学
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ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Lilan Tan,Wenrong Cai,Fangqin Wang,Junyao Li,Datong Wu,Yong Kong
Electrochemiluminescence (ECL), integrating the characteristics of electrochemistry and fluorescence, has the advantages of high sensitivity and low background. However, only a few studies have been reported for enantioselective sensing based on the ECL-active platform because of the huge challenges in constructing tunable chiral ECL luminophores. Here, we developed a facile strategy to design and prepare ECL-active chiral covalent organic frameworks (COFs) Ph-triPy+-(R)-Ru(II) for enantioselective sensing. In such an artificial structure, the ionic skeleton of COFs was beneficial to the electron transfer on the working electrode surface and the chiral Ru-ligand was used as the chiral ECL-active luminophore. It was found that Ph-triPy+-(R)-Ru(II) coupled with sodium persulfate (Na2S2O8) as the coreactant exhibited obvious ECL signals. More importantly, a clear difference toward l- and d-enantiomers was observed in the response of the ECL intensity, resulting in a uniform recognition law. That is, for amino alcohols, d-enantiomers (1 mM) measured by Ph-triPy+-(R)-Ru(II) showed a higher ECL intensity compared with l-enantiomers. Differently, amino acids (1 mM) gave an inverse recognition phenomenon. The ECL intensity ratios between l- and d-enantiomers (1 mM) are in the range of 1.25–1.94 for serine, aspartic acid, glutamic acid, valine, leucine, leucinol, and valinol. What is more interesting is that the ECL intensity was closely related to the concentration of l-amino alcohols and d-amino acids, whereas their inverse configurations remained unchanged. In a word, the present concept demonstrates a feasible direction toward chiral ECL-active COFs and their potential for efficient enantioselective sensing.
研究领域:
材料科学
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分析化学
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CHEMICAL ENGINEERING JOURNAL
·
2026
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IF 12.5
Yixuan Jiang,Yanlin Zhao,Fan Zhao,Xiaowei Cao,Dingding Jing,Haifeng Huang,Qinglei Hang
Chiral D Au NCs capillary SERS for label-free non-invasive saliva D-Glc assay. • Sensor achieves 0.30 nM LOD, covering clinical saliva glucose ranges. • Assay finishes in 10 min with 50 μL sample, high accuracy and anti-interference. • Assay shows correlation with GOD-POD gold std. (R 2 = 0.9313) and 0.947 AUC. • It offers a promising tool for early diabetes screening and clinical translation. Early, non-invasive screening and risk prediction of diabetes are crucial for effective prevention and control, as well as for delaying the onset and progression of complications. In this study, we developed a capillary surface-enhanced Raman scattering (SERS) sensor based on chiral gold nanocubes (D Au NCs) for the non-invasive, label-free, and rapid detection of d -glucose (D-Glc) in saliva. By leveraging the chiral recognition capability and strong SERS activity of D Au NCs, the sensor specifically identifies D-Glc and significantly amplifies its characteristic Raman signals, enabling quantitative analysis in complex saliva matrices without labeling. The sensor demonstrates outstanding analytical performance, covering the clinically relevant range of salivary glucose concentrations with a detection limit as low as 0.30 nM. Based on a capillary detection platform, the assay is simple and rapid, completed within 10 min using only a 50 μL micro-sample, while demonstrating strong anti-interference capability and high detection accuracy. Clinical saliva testing showed strong correlation with the glucose oxidase-peroxidase (GOD-POD) gold standard (R 2 = 0.9313), enabling reliable discrimination between healthy individuals and diabetic patients. Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.947, confirming its high efficacy in diabetes risk screening and strong diagnostic performance. Consequently, the D Au NCs-based capillary SERS sensor provides a promising strategy for early, non-invasive diabetes screening and prevention, possessing broad potential for clinical translation and application.
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ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Fangqin Wang,Wenrong Cai,Lilan Tan,Junyao Li,Datong Wu,Yong Kong
Although electroactive chiral covalent–organic frameworks (CCOFs) are considered an ideal platform for chiral electroanalysis, they are rarely reported due to the difficult selection of suitable precursors. Here, a facile strategy of liquid–liquid interfacial polymerization was carried out to synthesize the target electroactive CCOFs Ph-Py+-(S,S)-DPEA·PF6– and Ph-Py+-(R,R)-DPEA·PF6–. That is, a trivalent Zincke salt (4,4′,4″-(benzene-1,3,5-triyl)tris(1-(2,4-dinitrophenyl)pyridin-1-ium)) trichloride (Ph-Py+-NO2) and enantiopure 1,2-diphenylethylenediamine (DPEA) were dissolved in water and chloroform, respectively. The Zincke reaction occurs at the interface, resulting in uniform porosity. As expected, the cyclic voltammetry and differential pulse voltammetry measurements showed that the tripyridinium units of the CCOFs afforded obvious electrochemical responses. When Ph-Py+-(S,S)-DPEA·PF6– was modified onto the surface of a glassy carbon electrode as a chiral sensor, the molecules, which included tryptophan, aspartic acid, serine, tyrosine, glutamic acid, mandelic acid, and malic acid, were enantioselectively recognized in the response of the peak current. Very importantly, the discriminative electrochemical signals were derived from Ph-Py+-(S,S)-DPEA·PF6–. The best peak current ratios between l- and d-enantiomers were in the range of 1.31–2.68. Besides, a good linear relationship between peak currents and enantiomeric excess (ee) values was established, which was successfully harnessed to determine the ee values for unknown samples. In a word, the current work provides new insight and potential of electroactive CCOFs for enantioselective sensing in a broad range.
研究领域:
材料科学
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分析化学
·
电化学
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ANALYTICAL CHEMISTRY
·
2020
·
IF 6.785
Chengyi Xie,Liancheng Gu,Qidi Wu,Lei Li,Chenlu Wang,Jiancheng Yu,Keqi Tang
Chiral analysis is critical to many research fields due to different biological functions of enantiomers in living systems. Although the use of ion mobility spectrometry (IMS) has become an alternative technology in the area of chiral measurements, there is still a lack of a general chiral selector for IMS-based chiral recognition, especially for small chiral molecules. Here, a new method using oligosaccharides as the chiral selector has been developed to discriminate chiral amino acids (AAs) by trapped ion mobility spectrometry-mass spectrometry (TIMS-MS). We analyzed 21 chiral amino acids, including small molecules (e.g., alanine and cysteine). Our data showed that the use of nonreducing tetrasaccharides was effective for the separation of chiral AAs, which differentiated 21 chiral AAs without using metal ions. By further incorporating a copper ion, the separation resolution could be improved to 1.64 on average, which accounts for an additional 52% improvement on top of the already achieved separation in metal-free analysis. These results indicate that the use of tetrasaccharides is an effective strategy for the separation of AA enantiomers by TIMS. The method developed in this study may open up a new strategy for effective IMS-based chiral analysis.
研究领域:
分析化学
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质谱
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手性
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生物化学
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2024
·
IF 2.8
Wenchan Deng,Chundan Ye,Wei Wang,Rongrong Huang,Cheng Guo,Yuanjiang Pan,Cuirong Sun
Colorectal cancer (CRC) is a common malignant tumor in the gastrointestinal tract. Changes in amino acid metabolites have been implicated in tumorigenesis and disease progression. Biomarkers on the basis of chiral amino acids, especially D-amino acids, have not been established for early diagnosis of CRC. Quantification of chiral amino acids, especially very low concentrations of endogenous D-amino acids, is technically challenging. We report here the quantification of L- and D-amino acids in urine samples collected from 115 CRC patients and 155 healthy volunteers, using an improved method. The method of chiral labeling, liquid chromatography, and tandem mass spectrometry enabled separation and detection of 28 amino acids (14 L-amino acids, 13 D-amino acids and Gly). Orthogonal partial least squares discriminant analysis identified 14 targeted variables among these chiral amino acids that distinguished the CRC from the healthy controls. Binary logistic regression analysis revealed that D-α-aminobutyric acid (D-AABA), L-alanine (L-Ala), D-alanine (D-Ala), D-glutamine (D-Gln) and D-serine (D-Ser) could be potential biomarkers for CRC. A receiver operating characteristic curve analysis of combined multi-variables contributed to an area under the curve (AUC) of 0.995 with 98.3 % sensitivity and 96.8 % specificity. A model constructed with D-AABA, D-Ala, D-Gln, and D-Ser achieved an AUC of 0.988, indicating important contributions of D-amino acids to the association with CRC. Further analysis also demonstrated that the metabolic aberration was associated with age and the development of CRC, D-methionine (D-Met) was decreased in CRC patients with age over 50, and D/L-Gln in patients at stage IV was higher than patients at stage I. This study provides the signature of D-amino acids in urine samples and offers a promising strategy for developing non-invasive diagnosis of CRC.
研究领域:
肿瘤学
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代谢组学
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医学诊断
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JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
·
2017
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IF 0.697
Yanni Miao,Qi Liu,Wei Wang,Li Liu,Li Wang
A new chiral capillary electrophoresis (CE) analytical method for the determination of six pairs of amino acid enantiomer-derivatized precapillary with 9-fluorenylmethoxycarbonyl chloride (FMOC) was developed. CE separation parameters such as the pH of background electrolyte, the boric acid concentration, the addition of D-fructose and isopropanol, and the effect of new binary chiral selectors on the electropherograms were investigated. Precapillary and in-capillary derivatization was compared as well. The results showed that enantiomeric separations were obtained with enantio-resolution (Rs) ranged from 2.61 to 9.99 for the FMOC-derivatized amino acid enantiomers except alanine with Rs 1.06. Precapillary derivatization method provides overall better Rs for nearly all the targets except FMOC-aspartate with efficiency up to 1.309 × 106 plates and limit of detection (LOD) down to 2.5 μM. This method was successfully applied to analyze the concentration of the D/L-glutamic acid and D/L-aspartate in seven rice wine samples.
研究领域:
分析化学
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食品科学
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TALANTA
·
2022
·
IF 6.556
Shutong Yang,Liancheng Gu,Fangling Wu,Xinhua Dai,Fuxing Xu,Qiaoyu Li,Xiang Fang,Shaoning Yu,Chuan-Fan Ding
Chiral recognition is of highly interest in the areas of chemistry , pharmaceuticals, and bioscience. An effective strategy of enantiomeric determination of amino acids (AAs) was developed in this work. All 19 natural AAs enantiomers can be easily distinguished by ion mobility-mass spectrometry of the non-covalent complexes of AAs with cyclodextrins (α-CD, β-CD and γ-CD) and Mg 2+ without any chemical derivatization . Differences of the mobilities between the enantiomers’ complexes is from 0.006 to 0.058 V s/cm 2 . In addition, the complex of [β-CD + Phe + Mg] 2+ was selected as an example to study the relative quantification by measuring L/D-Phe at different molar ratio of 10:1 to 1:10 in the μM range, resulting in a good linearity (R 2 > 0.99) and high sensitivity at 2 μM. A DFT calculation was also performed to illustrate the detailed molecular structure of the complexes of CDs , Mg 2+ and D- or L-Phe. Both experiment and theoretical calculation showed that Mg 2+ plays an important role in host/guest interactions, which changed the molecular conformations by non-covalent interaction between Mg 2+ and CDs, and resulted in the different collision cross-sections of the complex ions of CDs, Mg 2+ and D- or L-AAs in the gas phase. This effective and convenient strategy could potentially be utilized in scientific research and industry for routine enantiomeric determination of natural AAs, peptides and some other small chiral biomolecules such as non-natural AAs and carboxylic acid-containing drugs.
研究领域:
化学
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生物科学
·
制药科学
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