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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY · 2025 · IF 4

CYP321F3 mediates metabolic resistance to methoxyfenozide in rice stem borer, Chilo suppressalis

Fang-Rui Guo,Shu-Chao Wang,Yan Liu,Shuai Wang,Jing-Mei Huang,Hao Sun,Lin-Feng He,Yuan Xie,Song-Tao Qiao,Feng-Xia Yang,Chris Bass,Cong-Fen Gao,Shun-Fan Wu

The development of insecticide resistance in insect populations is a major challenge to sustainable agriculture and food security worldwide. Methoxyfenozide, an insect growth regulator that acts as an agonist of 20-hydroxyecdysone (20E), has severely declined in its efficacy against the rice stem borer ( Chilo suppressalis ), a notorious pest of rice crops in East and Southeast Asia. To date, however, the genes involved in methoxyfenozide resistance in target pests remain unclear. We conducted a long-term (seven years from 2017 to 2023) and large geographical scale (8 provinces and 45 cities in China) resistance monitoring program for methoxyfenozide in C. suppressalis . Resistance was seen to arise rapidly in this species, with >100-fold resistance being detected in nearly all the field populations after 2018 . Piperonyl butoxide (PBO), an inhibitor of cytochrome P450 enzymes (P450s), significantly increased the sensitivity of resistant strains of C. suppressalis to methoxyfenozide, implicating P450s in resistance. Six P450 genes: CYP321F3, CYP6CV5, CYP9A68 , CYP6AB45, CYP324A12 and CYP6SN2 were identified as highly expressed in resistant C. suppressalis by transcriptome profiling. Of these, ectopic expression of CYP321F3 in Drosophila melanogaster resulted in a 7.0-fold increase in resistance to methoxyfenozide demonstrating its causal role in resistance. Collectively, these findings provide insight into the mechanisms mediating resistance to insect growth regulators and will inform the development of future pest and resistance management strategies.

CAS / MDL: 141-05-9 51-03-6
研究领域: 昆虫学 · 分子生物学 · 农业科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Animal Models and Experimental Medicine · 2024 · IF 3.8

Adipose-derived mesenchymal stem cell-incorporated PLLA porous microspheres for cartilage regeneration

Chang Gao,Wenlong Yuan,Dongcheng Wang,Xin Zhang,Tong Zhang,Zhimin Zhou

Background In facial plastic surgery, patients with nasal deformity are often treated by rib cartilage transplantation. In recent years, cartilage tissue engineering has developed as an alternative to complex surgery for patients with minor nasal defects via injection of nasal filler material. In this study, we prepared an injectable nasal filler material containing poly-L-lactic acid (PLLA) porous microspheres (PMs), hyaluronic acid (HA) and adipose-derived mesenchymal stem cells (ADMSCs). Methods We seeded ADMSCs into as-prepared PLLA PMs using our newly invented centrifugation perfusion technique. Then, HA was mixed with ADMSC-incorporated PLLA PMs to form a hydrophilic and injectable cell delivery system (ADMSC-incorporated PMH). Results We evaluated the biocompatibility of PMH in vitro and in vivo. PMH has good injectability and provides a favorable environment for the proliferation and chondrogenic differentiation of ADMSCs. In vivo experiments, we observed that PMH has good biocompatibility and cartilage regeneration ability. Conclusion In this study, a injectable cell delivery system was successfully constructed. We believe that PMH has potential application in cartilage tissue engineering, especially in nasal cartilage regeneration.

CAS / MDL: 1066-33-7
研究领域: 组织工程 · 生物医用材料 · 再生医学 · 整形外科
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2024 · IF 6.2

Benzalkonium chloride induces hematopoietic stem cell reduction and immunotoxicity in zebrafish larvae

Junquan Zeng,Si Dong,Chao Chen,Yongliang Zheng,Yuhua Zuo,Yuxin Liu,Ting Ding,Fasheng Liu,Qinyuan Shen,Yunyun Du,Xiaoping Wang,Wenguo Xie,Chenjun Zhou,Huiqiang Lu

Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c , il-8 , tir4 and inf-γ , but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC.

CAS / MDL: 67-68-5 8001-54-5
研究领域: 水生毒理学 · 免疫学 · 发育生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioactive Materials · 2025 · IF 20.3

Topological cues of microparticles train stem cells for tissue repair via mechanotransduction

Jiannan Mao,Yichang Xu,Wenbo Wang,Xiongwei Deng,Yujian Hui,Min Rui,Jincheng Tang,Wei Wang,Yiyang Huang,Liang Wu,Kun Xi,Yunrong Zhu,Yong Gu,Liang Chen

Microspheres (MPs) and porous microspheres (PMPs) are the two most widely used microparticles in tissue engineering and stem cell therapy. However, how stem cells perceive the topological differences between them to regulate cell function remains to be unclear. Here, we systematically studied the changes in stem cell function under the action of MPs and PMPs and elucidated the related mechanisms. Our findings show that the porous structure of PMPs can be sensed by focal adhesions (FAs), which triggers the synthesis of F-actin to inhibit the phosphorylation and degradation of Yes-associated protein (YAP), while also transmitting stress to the nucleus through the contraction of F-actin, thereby enhancing the nuclear translocation of YAP protein. The activation of YAP significantly enhances the proliferation, osteogenesis, paracrine and glucose metabolism of BMSCs, making them exhibit stronger bone repair ability in both in vivo and in vitro experiments. In summary, this study provides a comprehensive and reliable understanding of the behavior of BMSCs in response to MPs and PMPs. It also deepens our understanding of the association between microparticles’ topological cues and biological functions, which will provide valuable guidance for the construction of bone tissue engineering (BTE) scaffolds.

研究领域: 组织工程学 · 细胞生物学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Mesenchymal Stem Cell-Based Biomimetic Liposome for Targeted Treatment of Rheumatoid Arthritis

Lan Ma,Honghui Wu,Jian Cao,Nan Zhang,Yaosheng Li,Juanjuan Zheng,Xinchi Jiang,Jianqing Gao

Rheumatoid arthritis (RA) is a systemic autoimmune disorder that severely compromises joint health. The primary therapeutic strategy for advanced RA aims to inhibit joint inflammation. However, the nonspecific distribution of pharmacological agents has limited therapeutic efficacy and heightens the risks associated with RA treatment. To address this issue, we developed mesenchymal stem cell (MSC)-based biomimetic liposomes, termed MSCsome, which were composed of a fusion between MSC membranes and liposomes. MSC some with relatively simple preparation method effectively enhanced the targeting efficiency of drug to diseased joints. Interaction between lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 enhanced the affinity of the MSCsome for polarized macrophages, thereby improving its targeting capability to affected joints. The effective targeted delivery facilitated drug accumulation in joints, resulting in the significant inhibition of the inflammation, as well as protection and repair of the cartilage. In conclusion, this study introduced MSCsome as a promising approach for the effective treatment of advanced RA, providing a novel perspective on targeted drug delivery therapy for inflammatory diseases.

CAS / MDL: 97281-47-5
研究领域: 药理学 · 免疫学 · 生物技术 · 干细胞研究 · 药物递送系统
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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Polarization of Stem Cells Directed by Magnetic Field-Manipulated Supramolecular Polymeric Nanofibers

Bing Zhang,Qilin Yu,Yu Liu

Precise assembly of the cytoskeleton (e.g., actin, tubulin, and intermediate filaments) is of great importance for stem cell polarization and tissue regeneration. Recently, artificial manipulation of cytoskeleton assembly for remodeling stem cell polarization and ultimate cell fates attracts more and more interest of both chemists and biologists. Herein, we report the magnetic field-directed formation of biocompatible supramolecular polymeric nanofibers composed of two subunits: a β-cyclodextrin-bearing hyaluronic acid host polymer (HACD) and magnetic nanoparticles modified with actin-binding peptide and adamantane (MS-ABPAda). Transmission electron microscopy indicated that when HACD and MS-ABPAda were exposed to a magnetic field, they self-assembled into long nanofibers along the direction of the magnetic field, and the rate of nanofiber formation was linearly correlated with the strength of the magnetic field. Interestingly, when incubated with dental pulp stem cells, the nanofibers specifically drove tip extension and polarization of the cells, a phenomenon that can be attributed to targeting of actin-binding peptide to the actin cytoskeleton and subsequent polarization of the nanofibers. The successful application of these magnetic field-responsive supramolecular polymers on accurately driving polarization of mammalian cells is expected to be of great value for artificially manipulating cell fate and developing intelligent responsive materials in regenerative medicine.

研究领域: 生物材料 · 细胞生物学 · 纳米技术 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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ADVANCED FUNCTIONAL MATERIALS · 2019 ·Vol. 29 ·期 30 ·1807860 · IF 15.621

Biomimetic Composite Scaffolds to Manipulate Stem Cells for Aiding Rheumatoid Arthritis Management

Yue Zhao,Zhonghan Wang,Yingnan Jiang,Hou Liu,Shanliang Song,Chenyu Wang,Zuhao Li,Zhe Yang,He Liu,Jincheng Wang,Bai Yang,Quan Lin

Stem cell transplantation is a promising alternative therapy for rheumatoid arthritis (RA) patients, with the potential to suppress autoimmune inflammation and prevent joint damage. However, widespread application of RA therapy based on stem cell transplantation is limited due to poor migration, local retention, and uncontrolled differentiation of stem cells. Here, inspired by the dynamic construction of bone matrix, a structurally and functionally optimized scaffold for loading bone marrow stem cells (BMSCs) is designed to aid RA management. The composite scaffolds consist of stiff 3D printing porous metal scaffolds (3DPMS) and soft multifunctional polysaccharide hydrogels, wherein 3DPMS meet the requirements for large-scale bone defects caused by RA. Attractively, the fabricated hydrogels on the composite scaffold are self-healable, injectable, biocompatible, and biodegradable, which endow the resultant scaffold many aspects mimicking the extracellular matrix (ECM). After encapsulation of BMSCs, hydrogels are administered into the inner pores of 3DPMS, abbreviated as BMSCs@3DPMS/hydrogels. In this study, BMSCs@3DPMS/hydrogels have a good effect on improving RA, such as remodeling of knee joint articular cartilage, inhibition of inflammatory cytokines, and promotion of subchondral bone regeneration. Besides RA, the innovative scaffolds may also serve as an ideal biomaterial for other bone regenerative therapies in various orthopedic diseases.

研究领域: 组织工程 · 再生医学 · 生物医学工程 · 骨科
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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Designer Hydrogel with Intelligently Switchable Stem-Cell Contact for Incubating Cartilaginous Microtissues

Zijie Xiahou,Yunlang She,Jiahui Zhang,Yechi Qin,Guifei Li,Lili Zhang,Haowei Fang,Kunxi Zhang,Chang Chen,Jingbo Yin

Stem-cell-derived organoid can resemble in vivo tissue counterpart and mimic at least one function of tissue or organ, possessing great potential for biomedical application. The present study develops a hydrogel with cell-responsive switch to guide spontaneous and sequential proliferation and aggregation of adipose-derived stem cells (ASCs) without inputting artificial stimulus for in vitro constructing cartilaginous microtissues with enhanced retention of cell–matrix and cell–cell interactions. Polylactic acid (PLA) rods are surface-aminolyzed by cystamine, followed by being involved in the amidation of poly(( l-glutamic acid) and adipic acid dihydrazide (ADH) to form a hydrogel. Along with tubular pore formation in hydrogel after dissolution of PLA rods, aminolyzed PLA molecules with disulfide bonds on rod surfaces are covalently transferred to the tubular pore surfaces of poly(l-glutamic acid)/ADH hydrogel. Because PLA attaches cells, while poly(l-glutamic acid)/ADH hydrogel repels cells, ASCs are found to adhere and proliferate on the tubular pore surfaces of hydrogel first and then cleave disulfide bonds by secreting molecules containing thiol, thus inducing desorption of PLA molecules and leading to their spontaneous detachment and aggregation. Associated with chondrogenic induction by TGF-β1 and IGF-1 in vitro for 28 days, the hydrogel as an all-in-one incubator produces well-engineered columnar cartilage microtissues from ASCs, with the glycosaminoglycans (GAGs) and collagen type II (COL II) deposition achieving 64 and 69% of those in chondrocytes pellet, respectively. The cartilage microtissues further matured in vivo for 8 weeks to exhibit extremely similar histological features and biomechanical performance to native hyaline cartilage. The GAGs and COL II content, as well as compressive modulus of the matured tissue show no significant difference with native cartilage. The designer hydrogel may hold a promise for long-term culture of other types of stem cells and organoids.

研究领域: 生物材料 · 组织工程 · 干细胞生物学 · 再生医学
✓ 已验证 DOI PubMed 高影响因子
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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Zhewei Gu,Zhiyu Yin,Pengbo Song,Ying Wu,Ying He,Maoshu Zhu,Zhengxin Wu,Sicheng Zhao,Hongri Huang,Huihuang Wang,Cailing Tong,Zhongquan Qi

As a new cell-free therapy, exosomes have provided new ideas for the treatment of various diseases. Human induced pluripotent stem cells (hiPSCs) cannot be used in clinical trials because of tumorigenicity, but the exosomes derived from hiPSCs may combine the advantages of iPSC pluripotency and the nanoscale size of exosomes while avoiding tumorigenicity. Currently, the safety and biodistribution of hiPSC-exosomes in vivo are unclear. Here, we investigated the effects of hiPSC-exosomes on hemolysis, DNA damage, and cytotoxicity through cell experiments. We also explored the safety of vein injection of hiPSC-exosomes in rabbits and rats. Differences in organ distribution after nasal administration were compared in normal and Parkinson’s disease model mice. This study may provide support for clinical therapy and research of intravenous and nasal administration of hiPSC-exosomes.

研究领域: 干细胞研究 · 药学 · 神经科学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF SURGICAL RESEARCH · 2021 · IF 2.192

IGF-1-Expressing Placenta-Derived Mesenchymal Stem Cells Promote Scalding Wound Healing

Shaohang Cheng,Runxiao Lv,Jing Xu,Abdul Razaq Hirman,Lili Du

ABSTRACT Background Stem cell-based regenerative therapy is a novel approach to severe damaged skin. Perinatal tissues such as placenta are considered as promising alternatives. The present study aimed to investigate the effect of insulin-like growth factor-1 (IGF-1)-expressing placenta-derived mesenchymal stem cells (hPMSCs) on healing of burn wounds. Materials and methods hPMSCs were isolated from human placenta, and IGF-1 was transducted into hPMSCs via lentivirus . Flow cytometry and MTT assay were performed to assess cell apoptosis and viability, respectively. Immunostaining of CK19 and ki67 was for evaluating epithelial differentiation ability and cell proliferation . For in vivo studies, we established a mouse model of scalding and performed local administration of IGF-1-expressing hPMSCs via subcutaneous injection . Wound histology was analyzed with H&E staining. The expression of fibrogenic cytokines was detected by western blot. The production of pro-inflammatory factors was measured by ELISA. Results Overexpression of IGF-1 promoted cell proliferation and epithelial differentiation of hPMSCs in vitro and in vivo . Mice with burn injury displayed increased wound contraction and healing rates following treatment with IGF-1-expressing hPMSCs. There was less inflammatory infiltration and reduced collagen disposition in the presence of IGF-1 at the wound site. Administration of IGF-1-expressing hPMSCs suppressed inflammation by decreasing the levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Besides, IGF-1 increased VEGF expression, and decreased TGF-β1, collagen I and collagen III expressions in vivo . Conclusions IGF-1-expressing PMSCs promotes cell proliferation and epithelial differentiation, inhibits inflammation and collagen deposition, and thus contributes to wound healing.

研究领域: 干细胞生物学 · 再生医学 · 伤口愈合 · 免疫学
✓ 已验证 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2020 ·Vol. 31 ·期 30 ·305707 · IF 3.551

CD271 antibody-functionalized HGNs for targeted photothermal therapy of osteosarcoma stem cells

Jiguang Tian,Ying Gu,Yonggang Li,Ting Liu

Cancer stem cells (CSCs) are considered to maintain the vitality of tumor cell populations through self-renewal and infinite proliferation, but their accessibility is still under investigation. In addition, CSCs are more resistant to chemotherapy and radiotherapy compared with common tumor cells. This study aimed to develop a kind of novel and feasible nanomaterial for targeted photothermal ablation of osteosarcoma stem cells, which could be a promising anticancer strategy. The osteosarcoma stem cells were extracted by serum-free culture and we further verified the stem cell properties. We evaluated the expression of CD271 by flow cytometry. PEGylated multifunctional hollow gold nanospheres (HGNs) were prepared based on CD271 monoclonal antibody. Bifunctional SH-PEG-COOH was used to facilitate the covalent linkage between HGNs and antibody. The efficient uptake and distribution of the functionalized HGNs were investigated using ICP-MS and TEM. Morphological studies and quantitative apoptosis evaluation were performed to detect the effect of photothermal therapy (PTT). Afterwards, we explored the possible mechanism by which PTT induced targeted killing of cancer stem cells. Osteosarcoma cells isolated from serum-free culture were detected to show stem cell properties. CD271 was found to be a potential novel surface marker for osteosarcoma stem cells. By conjugating with CD271 monoclonal antibody, these biomimetic nanoparticles can be targeted and absorbed by osteosarcoma stem cells. HGNs-PEG-CD271 achieved excellent cell viability inhibition compared with non-targeted PEGylated HGNs upon near-infrared (NIR) laser irradiation. The mechanism of targeted killing may be related to the apoptosis pathway and DNA double-strand injuries. CD271 was considered to be a surface biomarker for osteosarcoma stem cells. Functionalized HGNs based on CD271 antibody exhibited excellent potential for targeted PTT, which may be a promising strategy for osteosarcoma treatment.

研究领域: 肿瘤学 · 纳米技术 · 生物医学工程 · 癌症干细胞 · 光热治疗
✓ 已验证 DOI PubMed 高影响因子
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Biomaterials Advances · 2026 · IF 6.7

Dynamic stiffening hydrogels orchestrate macrophage- mesenchymal stem cells interactions for bone regeneration

Wenkai Li,Shuo Feng,Zhenyin Chen,Yang Zou,Yonggang Lv

Slow stiffening hydrogel was achieved via gradual low-dose Ca 2+ crosslinking. • The hydrogel replicates early bone repair's dynamic mechanical niche. • Dynamic stiffness fosters a pro-osteogenic immune microenvironment. • Dynamic stiffness-driven macrophage-MSCs interaction promotes osteogenesis. During bone defect repair, the phenotypes, differentiation, and paracrine functions of both macrophages (Mφ) and mesenchymal stem cells (MSCs) are critically regulated by matrix stiffness. These two cell types interact via paracrine signaling, forming a bidirectional “immune-osteogenic” regulatory axis that jointly drives bone regeneration. Based on this, the present study employed a dynamically stiffening hydrogel system based on calcium ion-crosslinked gelatin/sodium alginate (Gel/SA), combined with a conditioned medium (CM)-based coculture model, to investigate the interaction between Mφ and MSCs under conditions of dynamic matrix stiffness evolution. Experimental results demonstrated that dynamic stiffness, together with inflammatory factors secreted by stiffness-modulated Mφ, synergistically enhanced the osteogenic differentiation of MSCs, leading to significantly higher differentiation levels in the dynamic stiffness group compared to other groups. Meanwhile, dynamic stiffness, along with prostaglandin E2 (PGE2) secreted by stiffness-modulated MSCs, collectively influenced Mφ, resulting in an inflammatory factor expression profile intermediate between those in the high- and low-stiffness groups. The data demonstrated that dynamic rigidity steers Mφ polarization and MSCs immunomodulation, and that dynamic stiffness-mediated Mφ-MSCs crosstalk tailors the injury microenvironment to accelerate early osteogenic commitment. These findings reveal the mechanism by which dynamic matrix mechanics guide bone regeneration through modulation of the early inflammatory microenvironment. Low-stiffness static hydrogels (Low-stiffness group) were prepared using gelatin (Gel) and sodium alginate (SA), while high-stiffness static hydrogels (High-stiffness group) were fabricated by adding a high concentration of CaCl₂ to the Gel/SA mixture. Hydrogels with dynamically increasing stiffness (Dynamic group) were achieved through daily supplementation of a low concentration of CaCl₂. All hydrogels were crosslinked via ethyldimethylaminopropyl carbodiimide/N-hydroxysuccinimide (EDC/NHS) for 24 h. Furthermore, by integrating the dynamic-stiffness hydrogel system with a conditioned medium-based coculture model, this work systematically investigated the effects of the dynamic mechanical microenvironment on macrophage phenotype polarization and the intercellular crosstalk between macrophages and mesenchymal stem cells (MSCs), thereby elucidating its role in modulating the immune microenvironment and directing osteogenic differentiation. Download: Download high-res image (302KB) Download: Download full-size image

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