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Advanced Healthcare Materials · 2023 · IF 10

Hollow Microfiber Assembly-Based Endocrine Pancreas-on-a-Chip for Sugar Substitute Evaluation

Lingling Tian,Jingyan Shi,Wei Li,Yuan Zhang,Xinghua Gao

With the increasing demand for low-sugar, low-calorie healthy diets, artificial sweeteners are widely used as substitutes for sugar in the food industry. Therefore, developing models that can better predict the effects of sugar substitutes on the human body is necessary. Here, a new type of endocrine pancreas-on-a-chip is developed based on a microfiber assembly and its stimulation of pancreatic secretion by glucose or sugar substitutes is evaluated. This new endocrine pancreas-on-a-chip is assembled using two components: (1) a cell-loaded hollow methacrylate gelatin (GelMA)/calcium alginate (CaA) composite microfiber prepared by microfluidic spinning to achieve vascular simulation and material transport, and (2) a 3D pancreatic islet culture layer, which also serves as a fiber assembly microchip. Using this established organ chip, the effects of five sweeteners (glucose, erythritol, xylitol, sodium cyclamate, and sucralose) were investigated on pancreatic islet cell viability and insulin and glucagon secretion. The constructed endocrine pancreas-on-a-chip has potential for the safety evaluation of sugar-substituted food additives, which can expand the application of organ chips in the field of food safety and provide a new platform for evaluating various food additives.

研究领域: 生物医学工程 · 组织工程 · 食品科学 · 内分泌学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CELLULAR PHYSIOLOGY · 2024 · IF 4.5

Regulation of spermatogonial stem cell differentiation by Sertoli cells-derived exosomes through paracrine and autocrine signaling

Hairui Tian,Xingju Wang,Xiaoxiao Li,Weixiang Song,Jiaqi Mi,Kang Zou

In the orchestrated environment of the testicular niche, the equilibrium between self-renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC-derived exosomes (SC-EXOs) in the SSC-testicular niche. Our investigation hinged on the hypothesis that SC-EXOs, secreted by SCs from the testes of 5-day-old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC-EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC-SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC-EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR-493-5p within SC-EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC-EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations.

研究领域: 生殖生物学 · 干细胞生物学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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RSC Advances · 2022 ·Vol. 12 ·期 15 ·9435-9444 · IF 4.036

Effects of rice root exudates on aggregation, dissolution and bioaccumulation of differently-charged Ag nanoparticles

Jiajia Yang,Hongyu Duan,Xiya Wang,Huan Zhang,Zhifeng Zhang

The biological toxicity and eco-environmental risk of metal nanoparticles (MNPs) is closely related to their stability. The stability of MNPs not only depends on their own properties but also on the effects of biological and environmental factors. To better understand the interaction between biological factors and MNPs in aquatic environments, the effects of total rice root exudates (T-RRE) on the aggregation, dissolution and bioaccumulation of Ag nanoparticles (AgNPs) with different surface charges were investigated in detail. Results indicated that T-RRE can induce the aggregation and sedimentation, and hinder the dissolution of polyethyleneimine-coated AgNPs (AgNPs@PEI) with positive surface charges as well as reducing the bioaccumulation of Ag in rice roots. T-RRE had no obvious effect on the dispersion stability of AgNPs@Cit (negatively charged citrate-coated AgNPs) and AgNPs@PVP (near electrically neutral polyvinylpyrrolidone-coated AgNPs), although T-RRE could induce the dissolution of AgNPs@Cit and AgNPs@PVP. In the molecular fractions of T-RRE, high-molecular-weight root exudates (H-RRE) play a key role in inducing the aggregation of AgNPs@PEI and hindering the bioaccumulation of Ag in rice roots. Compared with H-RRE, low-molecular-weight root exudates (L-RRE) can promote the dissolution of AgNPs@Cit and AgNPs@PVP, but it can obviously promote silver accumulation in rice roots. The difference in charge intensity between L-RRE and T-RRE plays a key role in inducing the aggregation and dissolution of AgNPs with different charges. These findings provide a foundation for investigation of the interactions between rice root exudates and nanoparticles with different surface charges in complex environmental systems.

研究领域: 环境科学 · 纳米技术 · 植物生物学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2009 · IF 2.562

Calcium Leads to Further Increase in Glycine-Enhanced Extracellular Secretion of Recombinant α-Cyclodextrin Glycosyltransferase in Escherichia coli

Zhao-Feng Li,Bin Li,Zhi-Guo Liu,Miao Wang,Zheng-Biao Gu,Guo-Cheng Du,Jing Wu,Jian Chen

Overexpression of recombinant genes in Escherichia coli and targeting recombinant proteins to the culture medium are highly desirable for the production of industrial enzymes. However, a major barrier is inadequate secretion of recombinant protein across the two membranes of E. coli cells. In the present study, we have attempted to circumvent this secretion problem of the recombinant α-cyclodextrin glycosyltransferase (α-CGTase) from Paenibacillus macerans strain JFB05-01. It was found that glycine, as a medium supplement, could enhance the extracellular secretion of recombinant α-CGTase in E. coli. In the culture with glycine at the optimal concentration of 150 mM, the α-CGTase activity in the culture medium reached 23.5 U/mL at 40 h of culture, which was 11-fold higher than that of the culture in regular TB medium. A 2.3-fold increase in the maximum extracellular productivity of recombinant α-CGTase was also observed. However, further analysis indicated that glycine supplementation exerted impaired cell growth as demonstrated by reduced cell number and viability, increased cell lysis, and damaged cell morphology, which prevented further improvement in overall enzyme productivity. Significantly, Ca2+ could remedy cell growth inhibition induced by glycine, thereby leading to further increase in the glycine-enhanced extracellular secretion of recombinant α-CGTase. In the culture with 150 mM glycine and 20 mM Ca2+, both extracellular activity and maximum productivity of recombinant enzyme were 1.5-fold higher than those in the culture with glycine alone. To the best of our knowledge, this is the first article about the synergistic promoting effects of glycine and Ca2+ on the extracellular secretion of a recombinant protein in E. coli.

CAS / MDL: 90-30-2
研究领域: 微生物学 · 生物技术 · 分子生物学 · 酶学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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APPLIED AND ENVIRONMENTAL MICROBIOLOGY · 2018 ·Vol. 84 ·期 20 · IF 3.633

Boosting Secretion of Extracellular Protein by Escherichia coli via Cell Wall Perturbation

Haiquan Yang,Xiao Lu,Jinyuan Hu,Yuan Chen,Wei Shen,Long Liu

Escherichia coli is one of the most widely used host microorganisms for recombinant protein expression and metabolic engineering, but it cannot efficiently secrete recombinant proteins to extracellular space. Here, extracellular protein secretion was enhanced in E. coli by deleting two d,d-carboxypeptidase genes (dacA and dacB, single and double deletions) to perturb the cell wall peptidoglycan network. Deletion of dacA and dacB enhanced the accumulation of intracellular soluble peptidoglycan in E. coli and affected cell morphology, resulting in a more irregular cell shape and the appearance of transparent bulges. Deletion of dacA and dacB appears to disrupt the normal rigid structure, presumably due to perturbation and destruction of the cell wall peptidoglycan network. The extracellular green fluorescent protein (GFP) fluorescence intensity of deletion mutants was increased by >2.0-fold compared with that of control cells, and that of the double deletion mutant was increased by 2.7-fold. Extracellular recombinant fibroblast growth factor receptor 2 (FGFR2) and collagen E4 secretion in deletion mutants was also enhanced compared with that in the control cells. Additionally, the extracellular recombinant amylase activity of single-deletion mutants BL21 ΔdacA pETDuet-amyk and BL21 ΔdacB pETDuet-amyk was increased 2.5- and 3.1-fold, respectively. The extracellular distribution of α-galactosidase by deletion mutants was also increased by >2.0-fold. Deletion of dacA and dacB increased outer membrane permeability, which could explain the enhanced extracellular protein secretion.IMPORTANCE Cell surface structure stabilization is important for extracellular secretion of proteins in Escherichia coli. As the main constituent of the cell wall, peptidoglycan contributes to cell structure robustness and stability. Here, we perturbed the peptidoglycan network by deleting dacA and dacB genes encoding d,d-carboxypeptidase enzymes to improve extracellular protein secretion. This new strategy could enhance the capacity of E. coli as a microbial cell factory for extracellular secretion of proteins and chemicals.

CAS / MDL: 100-02-7 90-30-2
研究领域: 生物工程 · 微生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Communications Biology · 2025 ·Vol. 8 ·期 1 ·1-13 · IF 5.1

The secretion of Pseudomonas unconventional peroxidase facilitates extracellular carbon acquisition from heterogeneous lignin

Liang Congying,Lin Lu,Wang Xiaoyan,Zhu Wenping

The secretion of ligninolytic enzyme provides a competitive advantage for microbial survival. These enzymes are commonly transported to the extracellular milieu via signal peptides for the catabolism of lignin, which cannot be translocated through the cell membrane. However, some bacterial ligninolytic enzymes lack signal peptides, yet they can still be secreted. It remains unclear how these unconventional proteins cross the cell membrane. Here, we reveal a secretion mechanism for the unconventional B-type dye-decolorizing peroxidase (DypB) in Pseudomonas putida A514. Type VI secretion system (T6SS) mediates the inner membrane channel, where interaction of DypB with the T6SS components VgrG and Hcp accounts for periplasmic delivery. Once in the periplasm, DypB is allocated into outer membrane vesicles (OMVs) and released to the extracellular space. The crosslinked translocation model for DypB delivery represents an ingenious mechanism by which bacteria harness extant systems to thrive in a nutrient-poor environment. Moreover, we develop an OMV-surface display platform to improve DypB secretion and further enhance lignin utilization, exemplifying the applicability of OMVs as a lignin biocatalytic nanoreactor. Our study demonstrates the previously unrecognized crosslinking of T6SS and OMVs for the secretion of unconventional ligninolytic peroxidase and provides new perspectives on its biotechnological applications.

CAS / MDL: 30931-67-0
研究领域: 微生物学 · 生物化学 · 生物技术 · 环境微生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL GEOCHEMISTRY AND HEALTH · 2024 ·Vol. 46 ·期 9 ·1-11 · IF 3.2

Phenolic endocrine-disrupting compounds in the Xiangjiang River: occurrence and risk assessment

Yang Yu,Li Jing,Xu Jie

The levels of three phenolic endocrine-disrupting compounds (EDCs), NP, BPA and 4-t-OP were determined in water and sediment collected from sites along the Xiangjiang River, Zunyi, China. The NP, BPA and 4-t-OP concentrations ranged from 18.02 to 311.79 ng/L in the surface water, 16.04–408.12 ng/L in the submerged water, and 21.13–892.37 μg/kg dw in the sediment. NP contamination was most severe in both the river water and sediment. The ranges of the three phenolic EDCs were slightly greater in the submerged water than in the surface water ( p  > 0.05). The concentrations in the middle reaches were greater than those in the upstream and downstream reaches in both the water and sediment, and significant differences in content were detected in some reaches. The levels of three phenolic EDCs in the water and sediment had a positive correlation. In addition, the distribution coefficient (K d ) indicated that NP was more likely to adsorb to the sediment, and BPA and 4-t-OP were more likely to adsorb to river water. Moreover, the risk quotient (RQ) and hazard quotients (HQ) were used to reveal the environmental and health risks caused by coexposure to the three phenolic pollutants. The results showed that the current pollution is a threat to the environment of the study area and not a threat to the health of the local population.

研究领域: 环境科学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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GREEN CHEMISTRY · 2021 ·Vol. 23 ·期 5 ·2079-2094 · IF 10.182

Efficient extracellular laccase secretion via bio-designed secretory apparatuses to enhance bacterial utilization of recalcitrant lignin

Lanfang Cao,Lu Lin,Haiyan Sui,Heng Wang,Zhichao Zhang,Nianzhi Jiao,Jizhong Zhou

Microbial-driven lignin conversion has a significant impact on the biogeochemistry of global ecosystems and biomass utilization. During this process, secretion of extracellular ligninolytic enzymes is the first, essential step, yet there is a significant challenge to the secretion of these high-redox potential enzymes in bacteria, especially in Gram-negative bacteria. In this study, genome and proteome analyses enabled us to bio-design two types of extracellular secretory apparatus, both of which effectively secreted a heterologous laccase in Pseudomonas putida, up to ∼300 U mL−1. Importantly, a strong cooperation between P. putida A514 cells and the extracellular laccase, which was either released to the medium or displayed on the cell surface, was observed to significantly promote cell growth (9 × 1010 CFUs mL−1) and lignin consumption (12.5%). Chemical analyses of lignin further confirmed the effect on lignin utilization. Moreover, we demonstrated that a free laccase-A514 cell system exhibited greater effect on lignin utilization than that of a cell-immobilized laccase complex, which challenges the current view of bacterial polymer catabolism, and suggests the importance of secretory pathways and sufficient reaction surface for lignin biocatalysis. Our study advances the knowledge of secretion mechanisms in Gram-negative bacteria and provides novel insights into the lignin utilization by extracellular lignolytic enzyme-bacterial cell systems.

CAS / MDL: 30931-67-0 28752-68-3
研究领域: 微生物学 · 生物技术 · 环境科学 · 生物化学
✓ 已验证 产品关联 DOI 高影响因子
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Frontiers in Microbiology · 2021 · IF 5.64

Antifungal Effect of Antimicrobial Photodynamic Therapy Mediated by Haematoporphyrin Monomethyl Ether and Aloe Emodin on Malassezia furfur

Cui Zixin,Zhang Miaomiao,Geng Songmei,Niu Xinwu,Wang Xiaopeng,Zhu Yanyan,Ye Feng,Liu Chengcheng

Infectious dermatological diseases caused by Malassezia furfur are often chronic, recurrent, and recalcitrant. Current therapeutic options are usually tedious, repetitive, and associated with adverse effects. Alternatives that broaden the treatment options and reduce side effects for patients are needed. Antimicrobial photodynamic therapy (aPDT) is an emerging approach that is quite suitable for superficial infections. The aim of this study is to investigate the antimicrobial efficacy and effect of aPDT mediated by haematoporphyrin monomethyl ether (HMME) and aloe emodin (AE) on clinical isolates of M. furfur in vitro. The photodynamic antimicrobial efficacy of HMME and AE against M. furfur was assessed by colony forming unit (CFU) assay. The uptake of HMME and AE by M. furfur cells was investigated by fluorescence microscopy. Reactive oxygen species (ROS) probe and flow cytometry were employed to evaluate the intracellular ROS level. The effect of HMME and AE-mediated aPDT on secreted protease and lipase activity of M. furfur was also investigated. The results showed that HMME and AE in the presence of light effectively inactivated M. furfur cells in a photosensitizer (PS) concentration and light energy dose-dependent manner. AE exhibited higher antimicrobial efficacy against M. furfur than HMME under the same irradiation condition. HMME and AE-mediated aPDT disturbed the fungal cell envelop, significantly increased the intracellular ROS level, and effectively inhibited the activity of secreted protease and lipase of M. furfur cells. The results suggest that HMME and AE have potential to serve as PSs in the photodynamic treatment of dermatological diseases caused by M. furfur, but further ex vivo or in vivo experiments are needed to verify that they can meet the requirements for clinical practice.

CAS / MDL: 23491-52-3 4091-99-0
研究领域: 皮肤科 · 光生物学 · 微生物学 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomed Research International · 2018 · IF 2.583

Characteristics of Organic Acid Secretion Associated with the Interaction between Burkholderia multivorans WS-FJ9 and Poplar Root System

Guan-Xi Li,Xiao-Qin Wu,Jian-Ren Ye,He-Chuan Yang

The objective of this study was to investigate whether plant-bacteria interaction affects the secretion of organic acids by both organisms and to assess whether the production of IAA by the bacterium increases the secretion of organic acids by root exudates, and if the stress produced by low available phosphorus (P) affects the production of organic acids by bacteria, by roots, or by root exudates in presence of bacterial cultures. With this purpose, we used as a biological model poplar plants and one strain of Burkholderia multivorans able to solubilize P. High performance liquid chromatography was utilized to measure organic acids. The tests, the inductive effects of exogenous indole-3-acetic acid (IAA) on secretion of organic acids, the 2 × 4 × 2 factorial design experiment, and the ability of organic acids to solubilize tricalcium phosphate were performed to investigate the interactive effects. The results showed that, after B. multivorans WS-FJ9 interacted with the poplar root system, the key phosphate-solubilizing driving force was gluconic acid (GA) which was produced in three ways: (1) secreted by the root system in the presence of IAA produced by B. multivorans WS-FJ9; (2) secreted by B. multivorans WS-FJ9; and (3) secreted by the poplar root system in the presence of phosphorus stress. When phosphorus stress was absent, the GA was produced as outlined in (1) and (2) above. These results demonstrated that inoculating B. multivorans WS-FJ9 into the poplar root system could increase the amount of GA secretion and implied that the interaction between B. multivorans WS-FJ9 and the poplar root system could contribute to the increase of P available fraction for poplar plants.

研究领域: 植物学 · 微生物学 · 土壤科学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE · 2025 ·Vol. 29 ·期 9 ·e70416 · IF 4.2

Disruption of PPARG Activity and CPT1A Regulation by Bisphenol A: Implications for Hepatic Lipid Metabolism

Xiliang Zhu,Qi Liu,Zhaoyun Cheng,Yi Luo

Bisphenol A (BPA) is a widely used industrial chemical with potential endocrine-disrupting effects on metabolic processes. This study investigates the impact of BPA on hepatic function and transcriptional regulation in mouse livers and AML12 cells. Male mice were exposed to low (5 g/kg) and high (50 g/kg) doses of BPA for six weeks. Transcriptomic analysis was performed on liver tissues, and histological examinations were conducted. AML12 cells were treated with varying BPA concentrations, and PPARG transcriptional activity was assessed using a luciferase reporter assay. Additionally, molecular docking, molecular dynamics (MD) simulations, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), MM-PBSA calculations, and multi-species protein structure comparative analysis were employed to analyse the interaction between BPA and PPARG. Transcriptomic analysis revealed a decrease in differentially expressed genes with higher BPA doses, with low-dose exposure significantly downregulating hepatic Cpt1a mRNA levels. Histological examination indicated lipid vacuole formation at high doses without collagen deposition. BPA consistently inhibited PPARG activity in both MCF7 cells and mouse livers. BPA exposure disrupts hepatic lipid metabolism and PPARG activity, highlighting its role as an endocrine disruptor. Further research is needed to elucidate the long-term effects of BPA on liver health.

CAS / MDL: 80-05-7
研究领域: 毒理学 · 分子生物学 · 代谢研究
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Environmental Science-Processes & Impacts · 2024 · IF 4.3

New insight into the spatiotemporal distribution and ecological risk assessment of endocrine-disrupting chemicals in the Minjiang and Tuojiang rivers: perspective of watershed landscape patterns

Weike Zhao,Peilin Li,Bo Yang

This study evaluated the pollution characteristics, spatiotemporal distribution, and ecological risks of eight endocrine-disrupting chemicals (EDCs) in the Minjiang and Tuojiang rivers. Utilizing 3S technology (ArcGIS, remote sensing, GPS) and Fragstats, the research calculated eight landscape pattern indices related to land use types along the Minjiang river and established correlations between landscape factors and EDC distribution through stepwise multiple regression. The results indicated that bisphenol A (BPA) and nonylphenol (NP) were the most concerning EDCs, with detection frequencies of 97–100% and peak concentrations up to 63.35 ng L−1, primarily located in the middle and lower reaches of the Minjiang river and the upper reaches of the Tuojiang river. There was a significant correlation between the spatial distribution of pollutants and landscape patterns, where increased fragmentation, a higher number of patches, and complex patch shapes within a 10-kilometer buffer zone were associated with elevated levels of river pollution. By integrating four classical mathematical models to fit curves for acute and chronic toxicity data of BPA and NP, the findings suggested that BPA posed a higher ecological risk. This interdisciplinary research provided essential theoretical insights for investigating river pollution and its influencing factors, offering a new perspective on simultaneous river pollution control, urban functional zoning, and adjustment of watershed landscape spatial patterns from an urban planning standpoint.

研究领域: 环境科学 · 生态学 · 地理信息系统
✓ 已验证 DOI PubMed 高影响因子
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