CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 6
·1667-1677
·
IF 5.5
Yuhua Chen,Wei He,Hong Wei,Cuicui Chang,Lingjian Yang,Jiao Meng,Tianlin Long,Quanhua Xu,Chi Zhang
Aim Ferroptosis is increasingly becoming to be considered as an important mechanism of pathological cell death during stroke, and specific exogenous ferroptosis inhibitors have the ability to reverse cerebral ischemia/reperfusion injury. However, research on Srs11-92 (AA9), a ferrostatin-1 (Fer-1) analog, in preclinical studies is limited. Methods In the middle cerebral artery occlusion-reperfusion (MCAO/R) mice model or oxygen–glucose deprivation/reperfusion (OGD/R) cell model, Fer-1, AA9, and/or ML385 were administered, and brain infarct size, neurological deficits, neuronal damage, oxidative stress, and neuroinflammation were determined after the damage, in vitro and in vivo. Results Fer-1 and AA9 improved brain infarct size, neuronal damage, and neurological deficits in mice model of MCAO/R, and inhibited the overloaded iron deposition, ROS accumulation, and neuroinflammation response: it also increased the expression of GPx4, Nrf2, and HO-1 and suppressed the expression of HMGB1 and NF-κB p65 in the epicenter of injured hippocampal formation. However, Nrf2 inhibitor ML385 reversed the neuroprotective effect of AA9, including the oxidative stress and neuroinflammation. In vitro studies showed that AA9 relieved OGD/R-induced neuronal oxidative stress and neuroinflammation via the Nrf2 pathway, which was impaired by ML385 in primary neurons. Conclusion The findings imply that Fer-1 analog AA9 may be suitable for further translational studies for the protection of neuronal damage via Nrf2 signal pathway-mediated oxidative stress and neuroinflammation in stroke and others neurological diseases.
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
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神经病学
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DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2021
·
IF 1.571
Fang Chen,Shi-Yun Huang,Shu-Qing Xiang,Xiao-Xu Qiao,Guo-Chao Liao,Zhong-Qiu Liu,Hua Zhou,Peng Wu
Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.
研究领域:
天然产物化学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Catalysis
·
2025
·
IF 4.9
Shuo Wang,Binhao Wang,Guochao Xu,Ye Ni
Chiral lactones are valuable aroma compounds which have wide applications in food and fragrance industries. However, the synthesis of chiral lactones often faces challenges such as low yield, poor stereoselectivity, high production costs and harsh reaction conditions. To overcome these issues, a novel multi-enzyme cascade reaction was designed to achieve dynamic resolution of decalactones through stereoconvergent preparation of hydroxydecanoic acids. Utilizing lactonase Rpa 3624 for hydrolysis, Hb KR for stereoselective oxidation, and Sm CR V4 for stereoselective reduction, 50 mM racemic γ -decalactone was stereoselectively converted into ( R )- γ -decalactone with 96.5 % ee and 89.2 % yield in 1 h. By replacing Sm CR V4 with Sm CR M5 , 50 mM racemic δ -decalactone was also efficiently converted into ( R )- δ -decalactone with excellent stereoselectivity of 95.5 % and 84.9 % yield. The one-pot process could be operated under mild conditions, enhanced atom economy and reduced production costs, and provides a sustainable approach for the synthesis of chiral decalactones. This work demonstrates the potential of multi-enzyme systems in synthesis of chiral lactones for industrial application.
研究领域:
生物化学
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工业生物技术
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香料化学
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产品关联
DOI
高影响因子
Journal of Cleaner Production
·
2024
·
IF 9.7
Xin Li,Xifan Li,Guijing Chen,Di Zhang,Lun Tian,Jun Chen,Changhui Liu,Bo Li,Alberto Tiraferri,Baicang Liu
To minimize manganese loss during acid leaching and to enhance the lithium adsorption capacity from shale gas wastewater of H 1.33 Mn 1.67 O 4 , this adsorbent material was doped with metallic elements in this study. Doping was achieved using solid-phase synthesis, resulting first in a Li 1.33 R X Mn 1.67−X O 4 (R = Fe, Ni, Al) precursor powder through high-temperature calcination. Then, lithium was leached out under acidic environment to obtain the desired H 1.33 R X Mn 1.67−X O 4 (HMO-R) adsorbents. The equilibrium adsorption capacities of HMO-R powders were measured as 20.7 mg/g, 20.7 mg/g, and 29.0 mg/g, for Fe, Ni, and Al dopants, respectively, surpassing that of the former H 1.33 Mn 1.67 O 4 (13.7 mg/L). Moreover, an average reduction of manganese loss by 30% for HMO-R was observed during lithium recovery/extraction cycles by acid leaching compared to undoped Li 1.33 Mn 1.67 O 4 . Overall, the doped adsorbent exhibited a stable crystal structure and high adsorption capacity, enhanced stability, performance, and efficiency in cycling experiments with respect to the undoped material.
研究领域:
材料科学
·
环境工程
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Heyong Wang,Meiluan Wang,Guixiang Huang,Mingye Zhao,Yongzhen Peng,Ning Zhu,Zheng Fang,Yujing Hu,Kai Guo
Optically active ethyl ( R )-2-hydroxy-4-phenylbutanoate (( R )-HPBE), is a key component in the production of angiotensin-converting enzyme (ACE) inhibitors, which are essential for treating hypertension. However, the high cost of starting materials has been a barrier to the industrial synthesis of ( R )-HPBE. Herein, we have established for the first time a four-step enzymatic reaction in continuous flow for the efficient synthesis of ( R )-HPBE from inexpensive benzaldehyde and pyruvic acid. This route also overcomes the issues of chemical disequilibrium and incompatibility of reaction conditions that are common in multi-enzyme cascades. The immobilization methods for aldolase/ene-reductase/keto-reductase were developed, and the immobilized enzymes were initially used in three individual flow modules to produce ( R )-2-hydroxy-4-phenylbutanoic acid (( R )-HPB), achieving high space–time yields of 3103 g (OPBEA) L −1 d −1 , 1685 g (OPBE) L −1 d −1 and 1709 g ( R )-HPB L −1 d −1 respectively. Moreover, integrating three modules in continuous flow achieved a space–time yield of about 350 g ( R )-HPB L −1 d −1 after 108 h, and maintained high operational stability with a conversion of >99 % and a product ee of >99.9 % after 192 h. Subsequently, the ethyl esterification of ( R )-HPB as the fourth module for producing ( R )-HPBE obtained a high space–time yield of 2117 g ( R )-HPBE L −1 d −1 , marking a substantial 74.5-fold increase over the batch system.
研究领域:
生物化学
·
制药工程
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酶工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 3
·2126
·
IF 5.6
Shouchao Xu,Jiehong Yang,Haitong Wan,Li Yu,Yu He
Promotion of angiogenesis and restoration of the blood flow in the ischemic penumbra is an effective treatment for patients with ischemic stroke (IS). Radix astragali-safflower (AS), a classic herbal pair for accelerating blood circulation and dispersing blood stasis, has been used for thousands of years to treat patients with IS in China. Even so, the mechanism of the treatment of IS by AS is still undecipherable. In the current study, network pharmacology was firstly employed to unveil the mechanism of AS in treating IS, which showed that AS might promote angiogenesis associated with PTGS2 silence. Middle cerebral artery occlusion/reperfusion (MCAO/R) model rats were then used as the experimental animals to verify the prediction result. The experimental results revealed that treatment with AS improved the cerebral infarct volume, neurological damage, and cerebral histopathological damage; inhibited cell apoptosis; increased the contents of PDGF-BB, EPO, and TGF-β1; and reduced the levels of PF4, Ang-2, and TIMP-1 in serum. Immunohistochemical staining demonstrated that the expression of PTGS2 was dramatically increased in the hippocampus and cerebral cortex of rats with MCAO/R, and this trend was reversed by the treatment of AS. Immunofluorescent staining expressed that AS reversed the down-regulation of VEGF and further promoted the expression of CD31, which indicated that AS promoted angiogenesis in MCAO/R rats. The abnormal protein or mRNA expression of PTGS2, PGI2, bFGF, TSP-1, and VEGF in the penumbra were transposed by AS or Celecoxib (an inhibitor of PTGS2). In conclusion, the protective mechanism of AS for IS promoted angiogenesis and was involved with PTGS2 silence.Keywords:Radix astragali and safflower;angiogenesis;ischemic stroke;ischemic penumbra;PTGS2
研究领域:
药理学
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神经科学
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中医药学
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产品关联
DOI
PubMed
高影响因子
LETTERS IN APPLIED MICROBIOLOGY
·
2023
·Vol. 76
·期 8
·
IF 2.4
Wang Nengqiang,Li Xiaojun
(R)-1-(4-methoxyphenyl) ethanol [(R)-1b] is an essential precursor for the synthesis of aryl propanoic acids’ anti-inflammatatory drugs. Biocatalysts for (R)-1b preparation are limited and reductase has problems of low substrate concentration and low conversion rate. As a result, there is a constant need for discovering novel biocatalysts with excellent catalytic performances. In this study, a novel reductase LpSDR from Lacisediminihabitans profunda for the biocatalytic reduction of p-methoxyacetophenone (1a) to (R)-1b was obtained based on gene-mining technology, and some key reaction parameters were also investigated to improve the conversion rate of 1a using whole cells of recombinant Escherichia coli expressing reductase LpSDR as biocatalysts. It was found that the optimal concentration of isopropanol, ZnSO4·7H2O solution, 1a, and recombinant E. coli resting cells, the optimal reaction temperature, buffer pH, and reaction time were 1.95 mol l−1, 0.75 mmol l−1, 75 mmol l−1, 250 g (wet weight) l−1, 28°C, 7.0, and 21 h, respectively. Under the above conditions, a conversion rate of 99.5% and an enantiomeric excess of 99.6% were obtained, which were superior to the corresponding values previously reported. This study provides a novel reductase LpSDR, which is helpful in reducing 1a to (R)-1b.
研究领域:
生物化学
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药物合成
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酶工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2022
·
IF 3.119
Yanjuan Peng,Ziteng Wang,Wenhao Jiao,Xinxin Cheng,Jingjing Yang,Yonghong Hu,Li Mi
This article deals with the saturated solubility and solvation behavior of 2-bromo-9-fluorenone in 10 industrial common solvents and three binary mixed solvents by means of experimental and mathematical correlations. Solubility experiments were investigated using the static equilibrium method combined with high-performance liquid chromatography (HPLC) from 278.15 to 323.15 K at atmospheric pressure. The results showed that the maximum and minimum solubility of 2-bromo-9-fluorenone was 0.0526 (mole fraction) in 1,4-dioxane at 323.15 K and 0.0002 (mole fraction) in methanol at 278.15 K, respectively, and the solubility increased with the increase in temperature in all solvents. Furthermore, the solubility data of 2-bromo-9-fluorenone was analyzed using the Apelblat model, the Buchowski–Ksiazaczak λh model in pure solvents, CNIBS/R-K model, and the Jouyban–Acree model in binary solvent mixtures. By error comparison, the Apelblat model and the CNIBS/R-K model can better predict the solubility of 2-bromo-9-fluorenone. In addition, the solvation behavior was illustrated by the KAT-LSER model in pure solvents, and the result shows that the cohesive energy density in the solution is the main factor affecting 2-bromo-9-fluorenone. Therefore, the solubility data is very important for optimizing the extraction process and recrystallizing 2-bromo-9-fluorenone to obtain a higher yield in industry production.
研究领域:
化学工程
·
物理化学
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产品关联
DOI
高影响因子
NEUROCHEMISTRY INTERNATIONAL
·
2024
·
IF 4.4
Hong Guo,Yuanwei Dong,Danqing Luo,Meng Gong,Jianfeng Sun,Zhipeng Wu,Zhixiang Liu,Lei Zhong,Song Jin
Neuronal death is the key cause of ischemic stroke. Acupuncture (Acu) is a recognized method for the treatment and amelioration of cerebral ischemia. However, the molecular mechanism of Acu for treating ischemic stroke has not yet been detailedly elucidated. Based our microarray analysis results, mitochondrial ribosomal protein L41 (MRPL41), which is related to apoptosis, was identified as the target of Acu. MRPL41 expression was increased in middle cerebral artery occlusion/reperfusion (MCAO/R) model and reduced after Acu treatment. Following, MCAO/R model and oxygen and glucose deprivation/reoxygenation (OGD/R) model were established to explore the effect of MRPL41. Knockdown of MRPL41 increased cell viability and ani-apoptotic protein (Bcl-2) expression, and reduced apoptosis intensity and pro-apoptotic protein (Bax and Cleaved caspase-3) of OGD/R neurons. In vivo , MRPL41 silencing decreased neurological severity score, shrank infarct area, reduced encephaledema and neuron apoptosis. In addition, reduction of MRPL41 caused loss of p53. Our data uncover that Acu targets MRPL41, following with inhibiting neuron apoptosis via p53 pathway, thereby ameliorating ischemic stroke.
研究领域:
神经科学
·
分子生物学
·
针灸
·
中风研究
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产品关联
DOI
PubMed
高影响因子
BIOTECHNOLOGY LETTERS
·
2025
·Vol. 48
·期 1
·2
·
IF 2.1
Yang Xiaole,Tian Xia,Zhu Hai,Jia Weiwei,Li Jiahuan,Tang Ruizhou,Zhang Chuanzhi,Cao Yang,Li Tingting
Chiral amines, as essential chiral building blocks in drug synthesis, present a considerable challenge in biomanufacturing due to the requirement for highly efficient stereoselective synthesis. In this study, we successfully cloned and heterologously expressed a novel ( R )-amine transaminase, MagAT, from Mycolicibacterium agri . Systematic analysis showed optimal activity at pH 7.0, with the highest reaction rate occurring within 30 min at 50 ℃. However, considering overall thermal stability, 40℃ was selected as the operating temperature for subsequent experiments. Furthermore, the enzyme retained nearly 100% catalytic activity in the presence of 10% methanol, DMSO, and chloroform. Kinetic analysis demonstrated that MagAT possessed high substrate affinity, with Michaelis constants (K m ) of 5.13 ± 0.45 mM for ( R )-1-phenylethan-1-amine and 3.73 ± 0.34 mM for pyruvate. Substrate specificity studies indicated that MagAT efficiently catalyzed the conversion of C3-C8 aliphatic amines (e.g., ( R )-2-aminooctane) and monocyclic aromatic amines (e.g., ( R )-1-phenylethan-1-amine), whereas its catalytic activity significantly declined for sterically hindered substrates such as naphthylamine. 3D structural modeling with AlphaFold3 and molecular docking showed that steric hindrance from key residues in the O-pocket critically influences substrate specificity. This study not only provides an efficient biocatalyst for the biosynthesis of chiral amines but also establishes a theoretical basis for the rational design of transaminases with broader substrate adaptability.
研究领域:
生物催化
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酶工程
·
应用微生物学
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分子生物学
·
结构生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HEAT AND MASS TRANSFER
·
2025
·
IF 5.8
Junjie He,Xingang Wang,Xiangyang Xu,Xin Zhou,Wenxiao Chu,Qiuwang Wang
To ensure the stable operation of high-power transmitter and receiver (T/R) module in the complex aerospace environment, this study presents an integrated thermal buffer combing a vapor chamber (VC) with trapezoidal microgroove wick structure and heat storage container filled by phase change materials (PCMs). A common surface between the two components is manufactured by 3D printer without thermal contact resistance. The effects of gravity and vibration conditions on the thermal management performance are considered. Results show that the sustained operation significantly depends on the heat dissipation efficiency at the VC condensing surface while the tested integrated thermal buffer is capable to guarantee the continuous operation of the simulated T/R module for at least 5 cycles. However, when operating under a higher thermal power, the safely operating cycle drops to three dues to the not fully exploited PCM during fast charging process. Meanwhile, it is found that the high-frequency vibration can maintain the thermal resistance of vapor chamber below 0.15 K/W and suppress the temperature rise rate of simulated T/R module by 1.65 °C/min. Based on the standardized multiple linear regression, the deviation of the PCM's temperature from its melting point might lead to adverse effect on heat transfer performance. Provided that the heat dissipation performance at the condensing surface is maintained, increasing the heat flux or vibration frequency can reduce the average thermal resistance of VC. Among these, the variation in heat flux yields the most significant amelioration.
研究领域:
热科学与工程
·
航空航天工程
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电子封装
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相变材料
·
传热学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Yuncheng Mu,Chengzhi Li,Shu Zhou,Fuhao Xue,Chao Yun,Rui Wu,Xiangguo Li,Yanglong Hou
The integration of magnetism and semiconductivity in a single material remains a central challenge in condensed matter physics, as conventional approaches struggle to reconcile the competing requirements of a finite bandgap and robust magnetic ordering. Here, we report a complementary strategy that inverts the traditional design logic: starting from a magnetic metal, we induce a controlled metal-to-insulator transition (MIT) through dimensionality reduction in two-dimensional (2D) layers. Using rhombohedral (r-)Cr 2 Se 3 as a model system, we show that thinning from bulk to atomically thin nanosheets progressively opens a bandgap while preserving antiferromagnetic ordering. Transport measurements reveal a pronounced thickness-dependent crossover from metallic to semiconducting behavior, driven primarily by quantum confinement under dimensional reduction, while the effects of external magnetic and electric fields remain minor. Supported by first-principles calculations, our results establish r-Cr 2 Se 3 as a rare non-van der Waals 2D antiferromagnetic semiconductor and illustrate that dimensionality-driven MIT offers a viable pathway for engineering robust 2D magnetic semiconductors, providing a new platform for spintronic and multifunctional device applications.
研究领域:
凝聚态物理
·
材料科学
·
自旋电子学
·
纳米电子学
✓ 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）