SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Han Fu,Maogang Li,Mengjun Guo,Hongsheng Tang,Tianlong Zhang,Hua Li
The precise and accurate synthesis mechanism of typical energetic materials (EMs) intermediate is extremely important for the optimization of synthesis technology of EMs. In this research, on-line Raman spectroscopy technique combined with multivariate curve resolution-alternating least squares(MCR-ALS) method was proposed and used to investigate the synthesis mechanism of EMs intermediate (3,5-diamino-1,2,4-triazole, DAT). Initially, on-line Raman spectroscopy was applied to collect the Raman spectral data of DAT synthesis process. Secondly, principal component analysis (PCA), coupled with singular value decomposition (SVD) were used to determine the number of component of the reaction system and the components was 5. Thirdly, MCR-ALS was used to extract the pure Raman spectra and concentration curves of each substance of DAT synthesis process. During the MCR-ALS operation, evolving factor analysis (EFA) was choose to acquire the initial concentration estimation for MCR-ALS. Several constraints were selected to apply to ALS optimization including non-negative, closure, equality and correlation constraint. And the correlation coefficient between the Raman spectra and the actual Raman spectra of the hydrazine hydrochloride, dicyandiamide and DAT was calculated, their correlation coefficient R 2 were 0.9522, 0.9446, 0.9908 respectively which showed a good data fit of MCR-ALS method. Finally, according to the results of MCR-ALS analysis, the structure of the synthetic intermediates was successfully deduced and the mechanism of DAT synthesis was proposed. Hence, a precise and comprehensive method for analyzing the DAT synthesis reaction mechanism is proposed, which is helpful to provide a new idea for the analysis of the synthesis reaction mechanism of energetic materials.
研究领域:
化学
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含能材料
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分析化学
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过程分析技术
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光谱学
✓ 已验证
DOI
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2024
·
IF 13.7
Wu Yachen,Zheng Wenzhong,Xu Guofeng,Zhu Lijun,Li Zhiqiang,Chen Jincao,Wang Lianrong,Chen Shi
Sterol regulatory element binding transcription factors (SREBPs) play a crucial role in lipid homeostasis. They are processed and transported to the nucleus via COPII, where they induce the expression of lipogenic genes. COPII maintains the homeostasis of organelles and plays an essential role in the protein secretion pathways in eukaryotes. The formation of COPII begins at endoplasmic reticulum exit sites (ERES), and is regulated by SEC16A, which provides a platform for the assembly of COPII. However, there have been few studies on the changes in SEC16A protein levels. The repetitive expansion of the hexanucleotide sequence GGGGCC within the chromosome 9 open reading frame 72 (C9orf72) gene is a prevalent factor in the development of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here, we found that the absence of C9orf72 leads to a decrease in SEC16A protein levels, resulting in reduced localization of the guanine nucleotide exchange factor SEC12 at the ERES. Consequently, the small GTP binding protein SAR1 is unable to bind the endoplasmic reticulum normally, impairing the assembly of COPII. Ultimately, the disruption of SREBPs transport decreases de novo lipogenesis. These results suggest that C9orf72 acts as a novel role in regulating lipid homeostasis and may serve as a potential therapeutic target for obesity.
研究领域:
分子生物学
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脂质代谢
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 16
·6358-6368
·
IF 1.938
Chao Kang,Hai-Long Wu,Shou-Xia Xiang,Li-Xia Xie,Ya-Juan Liu,Yong-Jie Yu,Jing-Jing Sun,Ru-Qin Yu
A practical analytical method based on intrinsic fluorescence is proposed for simultaneous determination of L-phenylalanine, L-tyrosine, and L-tryptophan in cell culture and human plasma. By using a three-way calibration method coupled with excitation–emission matrix fluorescence, the proposed method successfully achieved quantitative analysis of the three aromatic amino acids in the two different complex systems simultaneously, even in the presence of three unknown, uncalibrated serious interferents. The method needs little preparation by using “mathematical separation” instead of chemical or physical separation, which makes it efficient and environmentally friendly. Satisfactory results have been achieved for calibration, validation, and prediction sets. For phenylalanine, tyrosine, and tryptophan, the calibration ranges are 6.00 to 60.00, 0.40 to 4.00, and 0.10 to 1.00 μg mL−1 respectively. The average spike recoveries (mean ± standard deviation) are 98.5 ± 7.8%, 103.7 ± 6.9%, and 102.3 ± 7.9% respectively. The relative errors are −4.2%, 6.3%, and −0.8% for predicting real contents of phenylalanine, tyrosine, and tryptophan in cell culture respectively. Additionally, we discussed the potential of the three-way calibration method for determining analytes of interest in different systems simultaneously, to further explore the second-order advantages. The paired t-test results indicate that the predicted results between prediction in two systems simultaneously and prediction in a single system individually have no significant difference. The satisfactory results obtained in this work indicate that the use of the three-way calibration method coupled with the EEM array is a promising tool for multi-component simultaneous determination in multiple complex systems containing uncalibrated spectral interferents.
研究领域:
分析化学
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生物化学
✓ 已验证
产品关联
DOI
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Bochui Zhao,Xian Xu,Binghua Li,Zhizun Qi,Jinan Huang,Ali Hu,Guiqi Wang,Xiaomin Liu
Digitaria sanguinalis is a competitive and annual grass weed that commonly infests crops across the world. In recent years, the control of D. sanguinalis by nicosulfuron has declined in Hebei Province, China. To determine the resistance mechanisms of D. sanguinalis to nicosulfuron, a population of D. sanguinalis where nicosulfuron had failed was collected from a maize field of Hebei Province, China. Whole-plant dose–response experiments demonstrated that the resistant population (HBMT-15) displayed 6.9-fold resistance to nicosulfuron compared with the susceptible population (HBMT-5). Addition of the glutathione S-transferase (GSTs) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBD-Cl) significantly reduced the resistance level of the HBMT-15 population to nicosulfuron, and the GSTs activity of the HBMT-15 population was higher than the HBMT-5 population after nicosulfuron treatment. In vitro acetolactate synthase (ALS) enzyme experiments revealed that the nicosulfuron I 50 value for the HBMT-15 population was 41 times higher than that of the HBMT-5 population. An Asp 376 to Glu substitution in the ALS gene was identified in the HBMT-15 population. The HBMT-15 population had a moderate (2- to 4-fold) level of cross-resistance to three other ALS inhibitors (imazethapyr, pyroxsulam, and flucarbazone‑sodium), but was susceptible to pyrithiobac‑sodium. This study demonstrated that both an Asp 376 to Glu substitution in the ALS gene and GSTs-involved metabolic resistance to ALS inhibitors coexisted in a D. sanguinalis population .
研究领域:
植物学
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杂草科学
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植物生理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Anand Babu Perumal,Reshma B Nambiar,Xuelun Luo,Zhenzhu Su,Xiaoli Li,Yong He
Recently, essential oils (EO) have gained a lot of interest for use as antifungal agent in food and agricultural industry and extensive research is ongoing to understand their mode of action. However, the exact mechanism is not yet elucidated. Here, we integrated spectral unmixing and Raman microspectroscopy imaging to unveil the antifungal mechanism of green tea EO based nanoemulsion (NE) against Magnaporthe oryzae . The dramatic change in protein, lipid, adenine , and guanine bands indicate that NE has a significant impact on the protein, lipid and metabolic processes of purine . The results also demonstrated that the NE treatment caused damage to fungal hyphae by inducing a physical injury leading to cell wall damage and loss of integrity. Our study shows that MCR−ALS (Multivariate Curve Resolution-Alternating Least Squares) and N-FINDR (N-finder algorithm) Raman imaging could serve as a suitable complementary package to the traditional methods, for revealing the antifungal mechanism of action of EO/NE.
研究领域:
食品科学
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农业科学
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微生物学
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光谱学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
·
2018
·
IF 3.44
Tianhang Wang,Jiling Cheng,Shuyu Wang,Xudong Wang,Hongquan Jiang,Yueqing Yang,Ying Wang,Chunting Zhang,Weiwei Liang,Honglin Feng
Amyotrophic lateral sclerosis (ALS) is a degenerative disease with a progressive loss of motor neurons in the central nervous system (CNS). However, there are unsolved problems with the therapies for this disease. α-Lipoic acid (LA) is a natural, universal antioxidant capable of scavenging hydroxyl radicals as well as regenerating a series of antioxidant enzymes that has been widely used in clinical settings. This study aimed to evaluate the antioxidant and neuroprotective effects of LA in ALS cell and Drosophila models with mutant G85R and G93A hSOD1 genes. The biological effects of LA and the protein levels of several antioxidant factors were examined, as were those of phospho-Akt and phospho-ERK. Furthermore, specific inhibitors of the PI3K/Akt and MEK/ERK signaling pathways were used to analyze their effects on LA-induced antioxidant expression in vivo and in vitro . Evidences showed that the mutant hSOD1 resulted in the increased oxidative stress, abnormal antioxidant signaling and pathological behaviors in motor performance and survival compared with non-mutant hSOD1 models, treatment with LA improved motor activity and survival in transgenic flies, prevented NSC34 cells from mutant hSOD1 or H 2 O 2 induced decreased antioxidant enzymes as well as increased ROS levels. In addition, LA regulated the expression levels of antioxidant proteins in a dose- and periodical time-dependent manner, which might be mediated by ERK/Akt pathway activation and independent from the mutant hSOD1 gene. Our observations suggest that LA exerts strong and positive antioxidant and neuroprotective effects through the activation of the ERK-Akt pathway in hSOD1 ALS models.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Discovery
·
2023
·Vol. 9
·期 1
·1-18
·
IF 33.5
Gao Xiu Kui,Sheng Zu Kang,Lu Ye Hong,Sun Yu Ting,Rao Xi Sheng,Shi Lin Jing,Cong Xiao Xia,Chen Xiao,Wu Hao Bo,Huang Man,Zheng Qiang,Guo Jian-sheng,Jiang Liang Jun,Zheng Li Ling,Zhou Yi Ting
The scaffold protein IRS-1 is an essential node in insulin/IGF signaling. It has long been recognized that the stability of IRS-1 is dependent on its endomembrane targeting. However, how IRS-1 targets the intracellular membrane, and what type of intracellular membrane is actually targeted, remains poorly understood. Here, we found that the phase separation-mediated IRS-1 puncta attached to endoplasmic reticulum (ER). VAPB, an ER-anchored protein that mediates tethers between ER and membranes of other organelles, was identified as a direct interacting partner of IRS-1. VAPB mainly binds active IRS-1 because IGF-1 enhanced the VAPB-IRS-1 association and replacing of the nine tyrosine residues of YXXM motifs disrupted the VAPB-IRS-1 association. We further delineated that the Y745 and Y746 residues in the FFAT-like motif of IRS-1 mediated the association with VAPB. Notably, VAPB targeted IRS-1 to the ER and subsequently maintained its stability. Consistently, ablation of VAPB in mice led to downregulation of IRS-1, suppression of insulin signaling, and glucose intolerance. The amyotrophic lateral sclerosis (ALS)-derived VAPB P56S mutant also impaired IRS-1 stability by interfering with the ER-tethering of IRS-1. Our findings thus revealed a previously unappreciated condensate-membrane contact (CMC), by which VAPB stabilizes the membraneless IRS-1 signalosome through targeting it to ER membrane.
研究领域:
细胞生物学
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分子生物学
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内分泌学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemMedChem
·
2024
·
IF 3.6
Yifeng Pei,Sentao Liu,Lixun Wang,Chao Chen,Mengqiu Hu,Yi Xue,Dezhong Guan,Lingfeng Xie,Hong Liao,Jinpei Zhou,Huibin Zhang
The eukaryotic initiation factor 2B (eIF2B) is a key regulator in protein-regulated signaling pathways and is closely related to the function of the central nervous system. Modulating eIF2B could retard the process of neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and vanishing white matter disease (VWM) et al. Here, we designed and synthesized a series of novel eIF2B activators containing oxadiazole fragments. The activating effects of compounds on eIF2B were investigated through testing the inhibition of ATF4 expression. Of all the targeted compounds, compounds 21 and 29 exhibited potent inhibition on ATF4 expression with IC50 values of 32.43 nM and 47.71 nM, respectively, which were stronger than that of ISRIB (IC50 = 67.90 nM). ATF4 mRNA assay showed that these two compounds could restore ATF4 mRNA to normal levels in thapsigargin-stimulated HeLa cells. Protein Translation assay showed that both compounds were effective in restoring protein synthesis. Compound potency assay showed that both compounds had similar potency to ISRIB with EC50 values of 5.844 and 37.70 nM. Cytotoxicity assay revealed that compounds 21 and 29 had low toxicity and were worth further investigation.
研究领域:
神经科学
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药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2018
·
IF 3.382
T.H. Wang,S.Y. Wang,X.D. Wang,H.Q. Jiang,Y.Q. Yang,Y. Wang,J.L. Cheng,C.T. Zhang,W.W. Liang,H.L. Feng
Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro , as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Jie Li,Yufeng Gu,Wenwen Sun,Baoyu Wen,Bin Li,Jie Liu,Zhihong Sun,Qi Zhao,Chengming Sun
Triple-negative breast cancer (TNBC) poses a significant challenge owing to its complex pathological features and treatment resistance. In recent years, immune checkpoint blockade (ICB) therapy has shown satisfactory results in the treatment of TNBC. ICB therapy targeting T cells’ inhibitory receptors and innate immune checkpoints has gradually become a research hotspot. However, a study has found that compared with single immune checkpoint inhibition, dual ICB has a more significant therapeutic effect. This study aimed to develop an engineered nanocarrier, aLS@VpNPs, loaded with the photosensitizer verteporfin and coated with TNBC cell membranes loaded with antilymphocyte activation gene-3 (anti-LAG3) and sialic acid binding immunoglobulin-like lectin 10 (Siglec10) proteins for delivering combination therapies. The biomimetic vector can mimic the surface characteristics of tumor cells, showing better biocompatibility and efficient tumor-targeting ability. Under photodynamic therapy (PDT), reactive oxygen species (ROS) are generated at the tumor site to directly kill cancer cells and induce immunogenic cell death, transforming “cold tumors” into “hot tumors” and further enhancing the efficacy of dual ICB targeting T cells and macrophages. In summary, this approach improves drug delivery efficiency and therapeutic precision and activates the host immune system through the synergistic mechanisms of PDT and ICB. In addition, the study reveals potential mechanisms for the combined therapy in modulating the tumor microenvironment, offering effective strategies and directions for TNBC treatment.
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
癌症研究
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2020
·
IF 6.306
Tian-Qin Peng,Xiao-Li Yin,Hui-Wen Gu,Weiqing Sun,Baomiao Ding,Xian-Chun Hu,Li-An Ma,Shu-Dong Wei,Zhi Liu,Shi-Yi Ye
Laoshan green teas plucked in summer and autumn were measured by high performance liquid chromatography-diode array detector (HPLC-DAD). After baseline correction, the fingerprints data were resolved by multivariate curve resolution-alternating least squares (MCR-ALS) and a total of 57 components were acquired. Relative concentrations of these components were afterwards applied to distinguish plucking seasons using principal component analysis (PCA), support vector machines (SVM) and partial least squares-discriminant analysis (PLS-DA). For both SVM and PLS-DA models, the total recognition rates of training set, cross-validation and testing set were 100%, 91.3% and 100%, respectively. Besides, three variable selection methods were employed to determine characteristic components for the authentication of summer and autumn teas. Results showed that PLS-DA model based on three characteristic components selected by VIP possesses identical predictive ability as the original model. This study demonstrated that our proposed strategy is competent for the authentication of plucking seasons of Laoshan green tea.
研究领域:
分析化学
·
食品科学
·
化学计量学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ULTRASONICS
·
2024
·
IF 3.8
Ji Zhang,Kaili Chen,Yizhe Chen,Lingchen Hua,Siping Chen,Xin Chen,Liangyu Zou,Shupeng Li,Xifei Yang,Yuanyuan Shen
Background Amyotrophic lateral sclerosis (ALS) is marked by the deterioration of both cortical and spinal cord motor neurons. Despite the underlying causes of the disease remain elusive, there has been a growing attention on the well-being of cortical motor neurons in recent times. Focused ultrasound combined with microbubbles (FUS/MB) for opening the blood–brain barrier (BBB) provides a means for drug delivery to specific brain regions, holding significant promise for the treatment of neurological disorders. Objectives We aim to explore the outcomes of FUS/MB-mediated delivery of arctiin (Arc), a natural compound with anti-inflammatory activities, to the cerebral motor cortex area by using a transgenic ALS mouse model. Methods The ALS mouse model with the SOD1 G93A mutation was used and subjected to daily Arc administration with FUS/MB treatment twice a week. After six-week treatments, the motor performance was assessed by grip strength, wire hanging, and climbing-pole tests. Mouse brains, spinal cords and gastrocnemius muscle were harvested for histological staining. Results Compared with the mice given Arc administration only, the combined treatments of FUS/MB with Arc induced further mitigation of the motor function decline, accompanied by improved health of the gastrocnemius muscle. Furthermore, notable neuroprotective effect was evidenced by the amelioration of motor neuron failure in the cortex and lumbar spinal cord. Conclusion These preliminary results indicated that the combined treatment of FUS/MB and arctiin exerted a potentially beneficial effect on neuromuscular function in the ALS disease.
研究领域:
神经学
·
药理学
·
生物医学工程
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）