INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Wencheng Zhao,Hengzheng Yang,Huizi Cui,Wannan Li,Shu Xing,Weiwei Han
Vitamin B 12 is a group of biologically active cobalamin compounds. In this study, we investigated the inhibitory effects of methylcobalamin (MeCbl) and hydroxocobalamin acetate (OHCbl Acetate) on protein tyrosine phosphatase 1B (PTP1B). MeCbl and OHCbl Acetate exhibited an IC 50 of approximately 58.390 ± 2.811 μM and 8.998 ± 0.587 μM, respectively. The K i values of MeCbl and OHCbl Acetate were 25.01 μM and 4.04 μM respectively. To elucidate the inhibition mechanism, we conducted a 500 ns Gaussian accelerated molecular dynamics (GaMD) simulation. Utilizing PCA and tICA, we constructed Markov state models (MSM) to examine secondary structure changes during motion. Our findings revealed that the α-helix at residues 37–42 remained the most stable in the PTP1B-OHCbl Acetate system. Furthermore, upon binding of OHCbl Acetate or MeCbl, the WPD loop of PTP1B moved inward to the active pocket, forming a closed conformation and potentially obstructs substrate entry. Protein-ligand interaction analysis and MM-PBSA showed that OHCbl Acetate exhibited lower binding free energy and engaged in more residue interactions with PTP1B. In summary, our study confirmed the substantial inhibitory activity of OHCbl Acetate against PTP1B, with its inhibitory potency notably surpassing that of MeCbl. We demonstrated potential molecular mechanisms of OHCbl Acetate inhibiting PTP1B.
研究领域:
生物化学
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药物化学
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计算生物学
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产品关联
DOI
PubMed
高影响因子
WATER RESEARCH
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2024
·
IF 11.4
Meng Liu,Xin Su,Jing Yuan,Xueling Yang,Yuxuan Chen,Qianru Xu,Xiaowei Huang,Jianming Xu,Yan He
Hundreds of studies have demonstrated the bioremediation of chlorinated organic pollutants (COPs) in flooded environments. However, the role of specific functional strains in degrading COPs under complex media such as wetlands is still unclear. Here, we focused on the microbial characteristics of COP-polluted sediments, identified the bacteria responsible for degradation and conducted a genomic analysis of these bacteria. Four strains were obtained and identified as Petrimonas sulfuriphila PET, Robertmurraya sp. CYTO, Hungatella sp. CloS1 and Enterococcus avium PseS3, respectively. They were capable of degrading a typical COP, γ-hexachlorocyclohexane (γ-HCH). The residual γ-HCH concentrations were 58.8 % (PET), 45.6 % (CYTO), 60.2 % (CloS1), and 69.3 % (PseS3) of its initial value, respectively. Strain PET, CYTO and CloS1 could degrade γ-HCH to its dehalogenation product chlorobenzene. Each strain harbors genes annotated to the pathway of halogenated organic matter degradation (e.g. 2-haloacid dehalogenase) and cobalamin biosynthesis, which are involved in the degradation of COPs. Comparative genomic analysis of the four strains and other classical organohalide-respiring bacteria (e.g. Dehalococcoides mccartyi and Sulfurospirillum multivorans DSM 12446) showed that they share orthologous clusters related to the cobalamin biosynthetic process (GO:0009236). VB 12 was also detected in the culture systems of the four strains, further highlighting the importance of cobalamin in COPs degradation. In the genome of the four strains, some genes were annotated to the halogenated organic matter degradation and cobalamin biosynthesis pathway within horizontal gene transfer (HGT) regions. This further indicated that microorganisms carrying these genes can adapt faster to pollution stress through HGT. Together, these findings revealed the co-evolution mechanism of functional strains and may provide novel insights into improved bioremediation strategies for COP-polluted complex media based on generalist organochlorine-degrading bacteria.
研究领域:
环境科学
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微生物学
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基因组学
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DOI
PubMed
高影响因子
LAB ON A CHIP
·
2022
·Vol. 23
·期 2
·341-348
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IF 7.517
Haiying Shen,Qiliang Li,Wenqi Song,Xingyu Jiang
On-chip valves can simplify a microfluidic chip and make it easy to operate. However, most on-chip valves already reported still need complicated manufacture and sophisticated supporting devices. In this work, we present a straightforward on-chip valve, which can be serially connected, to form an on-chip pump. The liquid can horizontally flow one way by the regular deformations of flexure strips in the two valves at both sides of the chamber under pressure changes in microchannels generated by repeated vertical movements of linear actuators. The volume of this system including the chip and the supporting device is 0.65 cubic decimeters, which is much smaller than that of reported systems with a volume of at least 12 cubic decimeters, and the weight of this system is only 0.56 kg, making it possible for point-of-care testing. We carry out an immunoassay of folic acid on chip, and the results show satisfactory reproducibility with acceptable coefficients of variation. We determine 163 clinical human serum samples for folic acid. Furthermore, we detect transferrin, cobalamin and folic acid simultaneously on one chip with both sandwich and competitive binding immunoassay methods. We anticipate that this on-chip valve and pump can be applied in immunoassays and other biosensing applications.
研究领域:
微流控
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生物传感
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即时诊断
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分析化学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Materials
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2022
·Vol. 15
·期 24
·9057
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IF 3.748
Guang Yu,Yujia Cheng,Zhuohua Duan
As novel fluorescent nanomaterials, carbon dots have attracted increasing research attention because of their simple synthesis, robust fluorescence, low toxicity, and easy functionalisation. Previous research was focused on preparing carbon dots from biomass and chemical materials; however, most of these carbon dots exhibited blue fluorescence. Moreover, the fluorescence quantum yield was generally low, significantly limiting their application in biological imaging. To broaden the application scope of carbon dots, this study prepared long-wavelength emitting nano-carbon dots that exhibited increased quantum yield. Novel N-doped yellow fluorescent nano-carbon dots (Y-CDs) were synthesised via a hydrothermal method using L-tartaric acid and urea as the precursors. The Y-CDs had a high quantum yield (15.9%) and demonstrated photostability at various pHs, temperatures, and ionic strengths. The Y-CDs could detect cobalamin effectively and selectively, showing a linear relationship between fluorescence intensity and cobalamin concentration. The related coefficient was 0.997, and the detection limit was 2.101 μmol/L. In addition, the Y-CDs were successfully used as an imaging probe for MDA-MB-231 cells. Therefore, the Y-CDs developed in this study can be used for cobalamin detection and cell imaging.Keywords:fluorescent nanomaterials;carbon dots;Y-CDs;cell imaging probe
研究领域:
纳米技术
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生物医学工程
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分析化学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2021
·
IF 5.64
Law Kai P.,He Wei,Tao Jianchang,Zhang Chuanlun
Marine Thaumarchaeota (formerly known as the marine group I archaea) have received much research interest in recent years since these chemolithoautotrophic organisms are abundant in the subsurface ocean and oxidize ammonium to nitrite, which makes them a major contributor to the marine carbon and nitrogen cycles. However, few studies have investigated the chemical composition of their exometabolome and their contributions to the pool of dissolved organic matter (DOM) in seawater. This study exploits the recent advances in ion mobility mass spectrometry (IM-MS) and integrates this instrumental capability with bioinformatics to reassess the exometabolome of a model ammonia-oxidizing archaeon, Nitrosopumilus maritimus strain SCM1. Our method has several advantages over the conventional approach using an Orbitrap or ion cyclotron resonance mass analyzer and allows assignments or annotations of spectral features to known metabolites confidently and indiscriminately, as well as distinction of biological molecules from background organics. Consistent with the results of a previous report, the SPE-extracted exometabolome of N. maritimus is dominated by biologically active nitrogen-containing metabolites, in addition to peptides secreted extracellularly. Cobalamin and associated intermediates, including α-ribazole and α-ribazole 5′-phosphate, are major components of the SPE-extracted exometabolome of N. maritimus. This supports the proposition that Thaumarchaeota have the capacity of de novo biosynthesizing cobalamin. Other biologically significant metabolites, such as agmatidine and medicagenate, predicted by genome screening are also detected, which indicates that Thaumarchaeota have remarkable metabolic potentials, underlining their importance in driving elemental cycles critical to biological processes in the ocean.
研究领域:
微生物学
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海洋生物学
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分析化学
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环境科学
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DOI
PubMed
高影响因子
Animal Nutrition
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2025
·
IF 7.5
Jing Zhang,Jiaojiao Lang,Changjian Xue,Qiang Liu,Caixia Pei
Cobalamin (vitamin B 12 , VB 12 ) has the potential to enhance the digestion of dietary nutrients, optimize energy distribution, and stimulate the proliferation of mammary epithelial cells (MECs), which in turn can promote milk production performance. The influence of VB 12 on nutrient digestion and energy distribution has been studied; however, its effects on MEC proliferation and the underlying mechanism remain unclear. This study investigated the influence of coated VB 12 (CVB 12 ) on milk production, nutrient digestion, MECs proliferation and milk fatty acid synthesis in dairy cows. This in vivo study involved 88 multiparous Holstein cows with similar body weight (BW; 633 ± 16.2 kg), previous 305-d milk production (9035 ± 186.2 kg), parity (3.1 ± 0.28), and age (5.6 ± 0.31 years). These cows were selected from 6 weeks preparturition to 9 weeks postparturition. They were blocked by parity, previous milk yield, and expected calving date and divided into four treatment groups of 22 cows per group: control, low CVB 12 (LCVB 12 ), medium CVB 12 (MCVB 12 ), and high CVB 12 (HCVB 12 ), receiving 0, 6, 12, and 18 mg of VB 12 per cow per day, respectively. Although dry matter intake was unaffected, yields of actual milk, 4% fat-corrected milk, energy-corrected milk, and milk components (fat, true protein, and lactose) increased quadratically ( P < 0.05). Milk fat content increased linearly ( P = 0.021) with no significant changes in milk true protein and lactose contents after CVB12 supplementation. The apparent nutrient digestibility of dry matter, organic matter, crude protein, ether extract, neutral detergent fiber, and acid detergent fiber increased linearly ( P < 0.05) following the provision of CVB 12 . Serum contents of VB 12 , glucose, and total protein linearly increased ( P < 0.05), while those of methylmalonic acid, nonesterified fatty acid, and β-hydroxybutyric acid linearly decreased ( P < 0.05) following CVB 12 provision. Supplementing 12 mg/d of CVB 12 promoted MECs proliferation and fatty acid synthesis, as indicated by the upregulated expression of proliferation-related proteins, the suppression of apoptosis-related proteins, the phosphorylation of protein kinase B (Akt) and rapamycin target protein (mTOR), and the increased expression of fatty acid synthesis-related proteins. The in vitro study verified the promoting effect of VB 12 on MECs proliferation and further elucidated that VB 12 regulates MECs proliferation in dairy cows through the AKT/mTOR signalling pathway. In conclusion, CVB 12 increases milk and milk component production by promoting nutrient digestion, energy distribution, and MECs proliferation through the AKT/mTOR signalling pathway, and fatty acid synthesis-related proteins expression. These findings offer a robust theoretical foundation for future strategies aimed at enhancing milk performance in dairy cows through CVB 12 nutrition.
研究领域:
动物营养
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乳品科学
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分子生物学
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生物化学
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动物生理学
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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）