DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2025
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IF 2.4
Hao Wang,Junfu Guo,Xuanyi Chen,Siqi Liu,Wenna Li,Lu Yang,Jianmiao Wang,Yinglun Han
The regulation of inflammatory balance is central to immune homeostasis, with disruptions contributing to autoimmune diseases. As representatives of early vertebrates, lampreys offer a valuable model for investigating the evolutionary foundations of immune regulation. This study examines the dual role of L-TGF-β2 in modulating inflammation in lampreys, providing insights into the evolutionary origins of immune homeostasis mechanisms. Using lipopolysaccharide (LPS)-induced inflammation models, recombinant L-TGF-β2 was found to enhance leukocyte chemotaxis in quiescent states while inhibiting excessive migration during activation. Quantitative PCR revealed that L-TGF-β2 stimulates pro-inflammatory cytokine expression during early inflammatory phases and attenuates it during resolution. Tissue-specific expression patterns of TGF-β receptors indicated their potential role in mediating the distinct regulatory effects of L-TGF-β2 across diverse immune environments. These findings align with the biphasic functions of TGF-β observed in higher vertebrates, underscoring the evolutionary conservation of this signaling pathway. This research enhances understanding the functional versatility of TGF-β signaling and its pivotal role in vertebrate immune evolution, providing insights into ancient mechanisms of immune homeostasis and their modern implications for inflammatory disease research.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Sai Fang,Zhe Wang,Lanxin Xiao,Yan Meng,Yixuan Lei,Tianxin Liang,Yuhuan Chen,Xiaoshu Zhou,Gang Xu,Lirong Yang,Wenlong Zheng,Jianping Wu
l -threonine aldolase (LTA) catalyzes the synthesis of β -hydroxy- α -amino acids, which are important chiral intermediates widely used in the fields of pharmaceuticals and pesticides. However, the limited thermostability of LTA hinders its industrial application. Furthermore, the trade-off between thermostability and activity presents a challenge in the thermostability engineering of this enzyme. This study proposes a strategy to regulate the rigidity of LTA's V-shaped subunit by modifying its opening and hinge regions, distant from the active center, aiming to mitigate the trade-off. With LTA from Bacillus nealsonii as targeted enzyme, a total of 25 residues in these two regions were investigated by directed evolution. Finally, mutant G85A/M207L/A12C was obtained, showing significantly enhanced thermostability with a 20 °C increase in T 50 60 to 66 °C, and specific activity elevated by 34 % at the optimum temperature. Molecular dynamics simulations showed that the newly formed hydrophobicity and hydrogen bonds improved the thermostability and boosted proton transfer efficiency. This work enhances the thermostability of LTA while preventing the loss of activity. It opens new avenues for the thermostability engineering of other industrially relevant enzymes with active center located at the interface of subunits or domains.
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PEST MANAGEMENT SCIENCE
·
2020
·Vol. 76
·期 12
·4036-4045
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IF 3.75
Yifan Li,Hong Sun,Zhen Tian,Xinxin Su,Yue Li,Xuan Ye,Yifei Zhou,Shengli Zheng,Jiyuan Liu,Yalin Zhang
BACKGROUND Insect glutathione S-transferases (GSTs) play a crucial role in insecticide detoxification. However, there remains a distinct lack of information regarding the role of GSTs in the detoxification of Tolfenpyrad (TFP) in insects. RESULTS Real-time quantitative PCR showed significant upregulation of PxGSTs after exposure to TFP for 6 h. An in vitro inhibition assay showed that TFP could inhibit PxGSTδ, PxGSTε and PxGSTσ, and the most pronounced inhibitory effect was on PxGSTσ. Metabolism assays displayed that PxGSTσ was superior to other test PxGSTs in metabolizing TFP. The molecular docking of TFP and PxGSTσ revealed that the H-bond provided by the sidechains of Tyr107 and Tyr162 were key to the detoxification of TFP by PxGSTσ. Further tests using mutant PxGSTσ proteins at the sites of Tyr107 (PxGSTσY107A) and Tyr162 (PxGSTσY162A) corroborated that the individual replacement of Tyr107 and Tyr162 could greatly weaken the binding and metabolic abilities to TFP. CONCLUSION Metabolic interactions between the Plutella xylostella (L.) GSTs (PxGSTs) and TFP were deciphered. This study illustrates the molecular metabolism mechanism of PxGSTσ towards TFP and provides theoretical underpinnings for the design and optimization of novel TFP-like insecticides. © 2020 Society of Chemical Industry
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TALANTA
·
2025
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IF 6.1
Xuemei Pi,Rong Wang,Yiyu Guo,Xianwen Kan
l -Cysteine (L-Cys), one kind of aminothiol, ubiquitously exists in proteins and plays important roles in the food industry and biological processes. Herein, an electrochemiluminescence (ECL) sensor was constructed for the sensitive detection of L-Cys. As an ECL emitter, europium-porphyrin coordination polymer (Eu-PCP) was synthesized and subsequently modified with copper benzene-1,4-dicarboxylate (CuBDC) as a coreaction accelerator, which achieved high self-enhanced ECL responses. CuBDC on Eu-PCP was decomposed by the introduced L-Cys due to the coordination between Cu 2+ and L-Cys, resulting in the decrease of ECL signal. Besides, L-Cys could consume the co-reactant of K 2 S 2 O 8 to reduce the production of free radical SO 4 •– , further decrease ECL signal. Thus, this L-Cys coordination-driven decomposition of coreaction accelerator and consumption of co-reactant strategy was employed to doubly suppress the ECL signal for detecting L-Cys without additional recognition and amplification elements. The constructed ECL sensor exhibited a linear range of 1.0 × 10 −10 –5.0 × 10 −5 mol/L with a limit of detection of 2.0 × 10 −11 mol/L. This work has opened up new prospects for developing novel ECL sensing strategies in food safety monitoring and disease diagnosis.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Lishan Lin,Danhui Huang,Haohua Huang,Lingyan Xie,Yi Huang,Cuiping Ye,Lanhe Chu,Yujie Qiao,Xiaojing Meng,Shaoxi Cai,Hangming Dong
Inhaled environmental allergens, such as house dust mites (HDM), have been shown to induce an inflammatory reaction, tissue injury, and increased airway sensitivity in the lungs, ultimately leading to the development of allergic asthma. The imbalance of respiratory microbiota and metabolites plays a crucial role in the progression of allergic asthma. However, there is limited knowledge available regarding the alterations in respiratory microbiota and metabolites and their impact on the host in the context of asthma. The aim of this study was to investigate the potential pathways involved in the development of asthma through the analysis of lung flora and metabolites. A mouse model of house dust mite (HDM)-induced asthma was established, and alveolar lavage samples were collected for microbiome 16S rRNA sequencing and untargeted metabolic analysis. Microbiological analyses indicated a significant alteration in the microbiota after 4 and 6 weeks of HDM nebulisation stimulation. This was characterized by a decrease in microbial diversity, as well as reductions in the relative proportion of Gallionella and Lactobacillus . Conversely, the abundance of Flavobacterium and Ralstonia increased in the HDM4W and HDM6W groups, respectively. Metabolomic analyses revealed seven distinct metabolites, among them L-malic acid, which were linked to signaling pathways in a mouse model of HDM-induced asthma. The correlation analysis demonstrated a positive association between L-malic acid and Rhodanobacter and Nocardioides . L-malic acid was discovered to be efficacious in reducing airway inflammation in mice with house dust mite-induced asthma. Further analysis revealed that this change was linked to lipid peroxidation and changes in ferroptosis markers, namely GPX4 and FTH. These findings suggest that L-malate inhibits ferroptosis. However, the introduction of ferroptosis inducers, such as Erastin, was observed to negate the beneficial effect of butyrate. In summary, this research implies that the respiratory microbiota metabolite L-malic acid lessens airway inflammation in asthma by inhibiting ferroptosis, offering a potential approach for managing asthma.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Qianqian Jiang,Qi Chu,Qi Zhang,Chaoqiang Wu,Tongqing Tang,Xin Wang,Feifei Chen,Alei Zhang,Kequan Chen
Adol condensation mediated by L-threonine aldolase (LTA) is a promising route to synthesize β-hydroxy-α-amino acids, such as the anti-Parkinson's disease drug L- threo -3,4-dihydroxyphenylserine (L- threo -DOPS; droxidopa). However, the biocatalytic approach generally suffered from poor stereoselectivity at the C β chiral center. Herein, several LTAs from diverse microorganisms were examined for the stereoselective synthesis of L- threo -DOPS, and an LTA from Firmicutes bacterium ( Fb LTA) was identified with relatively high stereoselectivity. A semi-rational design was then employed to further enhance the stereoselectivity, resulting in the identification of beneficial mutations and the generation of beneficial mutants with markedly elevated stereoselectivity (up to 80 % de) over the wild-type (23 % de). Molecular dynamics (MD) simulation revealed that the significant improvement of stereoselectivity could be attributed to the structural reconstitution of substrate tunnels. Finally, the best mutant was applied to a scaled-up reaction, affording 1.3 g/L yield of L- threo -DOPS with 80 % de. This study provides new insights into the stereoselectivity control of LTAs and potential engineered LTAs for the manufacture of L- threo -DOPS.
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Current Research in Food Science
·
2025
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IF 7
Le Cheng,Haoyue Bai,Mingfang Zhang,Fengping Yang,Difeng Ren,Yunpeng Du
The emerging technology of inhibiting polyphenol oxidase (PPO) is crucial for preventing enzymatic browning in food. This study aimed to investigate the effects of 4.5 kJ/m 2 ultraviolet (UV)-C radiation and 0.02 mg/mL L-cysteine (L-cys) treatment on the enzyme activity, physico-chemical properties, thermal properties, structure, and molecular microstructure of PPO. UV-C/L-cys decreased PPO activity and had the highest aggregation index and turbidity of PPO. UV-C/L-cys further reduced the denaturation temperature point and increased the denaturation enthalpy of PPO. UV-C/L-cys turned the α-helix to random coil of PPO and destroyed the tertiary structure. This combined treatment aggregated the microstructure of PPO, which led to covering the active center of the enzyme, leading to its inactivation. Molecular docking simulation confirmed that L-cys bound to PPO through hydrogen bonding and ionic contact. This study established a foundation for the application of UV-C radiation and L-cys treatment to control food browning.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 21
·11436
·
IF 5.924
Zhiyuan Chen,Bin Wang,Jiali Dong,Yuan Li,Shuqin Zhang,Xiaozhou Zeng,Huiwen Xiao,Saijun Fan,Ming Cui
Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derivedl-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level ofl-Histidine in fecal pellets, which was increased following fecal microbiota transplantation.l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure.l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite ofl-Histidine, accumulated in peripheral blood and lung tissues followingl-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-producedl-Histidine and ImP are promising radioprotective agents.Keywords:radiation-induced cardiopulmonary injury;gut microbiota metabolites;imidazole propionate;pyroptosis;l-histidine
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CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Chen Shen,Teng Wang,Feng Guo,Kunlai Sun,Bin Wang,Jie Wang,Zefeng Zhang,Xing Zhang,Yuqin Zhao,Yin Chen
The sea buckthorn ( Hippophae rhamnoides L.) berries are rich in various bioactive components and widely used as fruit and traditional medicine. In this study, a novel heteropolysaccharide fraction (SP0.1-1) was isolated from Sea buckthorn berries. SP0.1-1 is composed of mannose , glucose, galactose , and arabinose in the molar ratio of 1:2.3:1.9:11.2 with a core structure containing 1,4-linked-α- d -Glc p , 1,4,6-linked-α- d -Glc p and 1,4-linked-α- d -Man p residues as the backbone. And the side-chains comprised of 1,3,5-linked-α- l -Ara f , 1,5-linked-α- l -Ara f , terminal α-Ara f and 1,4-linked-β- d -Gal p . Furthermore, a diet supplemented with SP0.1-1 extended the mean lifespan, enhanced antioxidant enzyme (superoxide dismutase, SOD; glutathione peroxidase , GSH-Px; and catalase , CAT) activities, and decreased the malondialdehyde (MDA) level and hydrogen peroxide (H 2 O 2 )-induced mortality rate in fruit flies ( Drosophila melanogaster ). To summarize, the study's findings will provide evidence for the development of sea buckthorn polysaccharide products.
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ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Wenwu Xiao,Qingtao Li,Huimin He,Wenxiu Li,Xiaodong Cao,Hua Dong
Precise manipulation of biomolecule distribution and functions via biomolecule–matrix interaction is very important and challenging for tissue engineering and regenerative medicine. As a well-known biomimetic matrix, electrospun fibers often lack the unique spatial complexity compared to their natural counterparts in vivo and thus cannot deliver fully the regulatory cues to biomolecules. In this paper, we report a facile and reliable method to fabricate micro- and nanostructured poly(l-lactic acid) (PLLA) fibrous matrices with spatial complexity by a combination of advanced electrospinning and agarose hydrogel stamp-based micropatterning. Specifically, advanced electrospinning is used to construct multi-nanostructures of fibrous matrices while solvent-loaded agarose hydrogel stamps are used to create microstructures. Compared with other methods, our method shows extreme simplicity and flexibility originated from the mono-/multi-spinneret conversion and limitless micropatterns of agarose hydrogel stamps. Three types of PLLA fibrous matrices including patterned nano-Ag/PLLA hybrid fibers, patterned bicompartment polyethylene terephthalate/PLLA fibers, and patterned hollow PLLA fibers are fabricated and their capability to manipulate biomolecule distribution and functions, that is, bacterial distribution and antibacterial performance, cell patterning and adhesion/spreading behaviors, and protein adsorption and delivery, is demonstrated in detail. The method described in our paper provides a powerful tool to restore spatial complexity in biomimetic matrices and would have promising applications in the field of biomedical engineering.
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NEW JOURNAL OF CHEMISTRY
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2022
·Vol. 46
·期 22
·10637-10643
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IF 3.925
Juan-Juan Hu,Zhong-Ying Ma,Xin-Rui He,Yi-Gang Wu,Qian Chen,Xue-Qing Song,Guan-Yuan Wang,Yi-Han Li,Jing-Yuan Xu
Gastric adenocarcinomas present elevated cyclooxygenase-2 (COX-2) expression compared to non-neoplastic mucosa. Four oxaliplatin (L-OHP)-based Pt(IV) complexes, CP-L-OHP (1), ED-L-OHP (2), KP-L-OHP (3), and SL-L-OHP (4), were synthesized with the non-steroidal anti-inflammatory drugs (COX inhibitors) carprofen, etodolac, ketoprofen and sulindac, respectively, as axial ligands to inhibit BGC-823 gastric cancer cells. Complexes 1–4 displayed comparable cytotoxicity to L-OHP, of which 1 displayed the lowest IC50 value and best selectivity in BGC-823 cells compared to normal liver cells (LO2). Complex 1 significantly enhanced Pt accumulation, DNA damage and apoptosis in BGC-823 cells. Overexpression of COX-2 can lead to a more aggressive behavior in gastric cancer, inducing metastatic and invasive processes. The wound-healing assay displayed that 1 could significantly delay BGC-823 cell metastasis with the lowest wound-healing rate compared to L-OHP and carprofen after treatment for 24 h. Interestingly, few 1-treated cells were observed to adhere to Matrigel, while the cell adhesion was hardly affected by the other treatment groups such as carprofen in cell adhesion experiments. Immunofluorescence studies indicated that 1 exhibited a longer-acting COX-2 response than carprofen alone. Carprofen (20 μM) effectively inhibited COX-2 at 1 and 5 h of treatment in BGC-823 cells, but did not work at 24 h. In contrast, 1 could retain the high inhibitory activity against COX-2 up to 24 h at least.
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Catalysts
·
2022
·Vol. 12
·期 6
·587
·
IF 4.501
Guosi Li,Fucheng Zhu,Fangli Gu,Xinjian Yin,Qilin Xu,Menghua Ma,Li Zhu,Baowei Lu,Naidong Chen
Reaction coupling separation systems using calcium fumarate as a substrate can break the reaction equilibrium and promote the production ofl-malate. However, the low reusability and stability of fumarase limit its further application. In this study, partially purified fumarase ofThermus thermophilus(87.0 U mg−1) was immobilized within konjac-κ-carrageenan beads. An amalgamation of konjac and carrageenan gum (2%) was used to form the beads, and polyethylene polyamine (0.2%) and glutaraldehyde (0.1%) were used as the cross-linking agents. The pH and temperature profiles of free and immobilized fumarases were remarkably similar. The diffusion limit of immobilized fumarase caused a decline in the maximal velocity (Vmax), whereas the kinetic constant (Km) value increased. Optimization of the parameters for biotransformation by immobilized fumarase showed that 88.3% conversion of 200 mM calcium fumarate could be achieved at 55 °C within 8 h. The beads were stored for 30 days at 4 °C with minimal loss in activity and were reusable for up to 20 cycles with 78.1% relative activity. By recycling the reaction supernatant, a total amount of 3.98 M calcium fumarate was obtained with a conversion of 99.5%, which is the highest value ever reported.Keywords:l-malate;fumarase;immobilization;konjac-κ-carrageenan beads
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