Exploration
·
2025
·
IF 22.5
Tongyao Zhao,Yao Chen,Haimeng Yuan,Shuqian Yang,Hongyuan Zhang,Yuequan Wang,Shenwu Zhang,Qin Chen,Jin Sun,Zhonggui He,Cong Luo
Cancer stem cells (CSCs) are widely recognized as the culprits of chemoresistance, tumor metastasis, and relapse. Moreover, most chemotherapeutic drugs not only fail to eliminate CSCs effectively, but also induce the acquisition of stemness characteristics in non-stem cancer cells. Herein, we propose a cancer cells/CSCs double-killing modality for breast cancer treatment. Specifically, a carrier-free nano-cocktail is developed through the precise co-assembly of a redox-responsive docetaxel (DTX) dimeric prodrug and salinomycin (SAL, an anti-CSCs drug). Precision combination of DTX and SAL not only shows synergistic tumor-killing activity, but also sharply reduces the proportion of CSCs in tumors. More importantly, tumor-specific prodrug activation-initiated drug release from the nano-cocktail confers high drug co-delivery efficiency and low off-target toxicity risk. As expected, such a one-stone-two-birds nanomedicine presents satisfactory performance on tumor stemness eradication, antitumor responses, and safety in both xenograft and orthotopic 4T1 breast cancer mouse models. This study advances cancer cells/CSCs double-killing nanotherapeutics towards clinical breast cancer therapy.
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Nano Today
·
2023
·
IF 17.4
Honglei Zhu,Huayan Li,Kunjie Gao,Yi Huang,Yuru Liao,Weichu Hu,Feng Chen,Haoyuan Jiang,Xiaomei Liang,Haonan Song,Yuxin Wang,Hanrong Huang,Yifan Wang,Fan Liu,Hao Huang,Qian Wang,Xiao Yi
Intrauterine adhesion (IUA) is one of the main causes of female infertility. Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs), are consisted of a complete lipid bilayer structure, rich in multiple factors and miRNAs related to tissue regeneration , which are the main effective paracrine components of MSCs to treat IUA. However, the poor secretion and bioactivity of EVs leading to the unexpected therapeutic efficacy of MSC-EVs, have been obstacles to their widespread use in clinical practice. Here, we developed human chorionic villi (CV)-derived nanofibers that mimic the tissue-specific ECM microenvironment of CV-derived MSCs, maintain the stemness of MSCs for a long time, and are rich in apolipoproteins , HSP90 , ANXA1-A6, etc., which can enhance EV secretion and bioactivity. Then, the CV-nanofiber bionic culture system for mesenchymal stem cells was constructed to achieve large-scale cultivation of MSCs for continuous collection of high-concentration EVs enrichment supernatant. Additionally, EVs obtained by this system were encapsulated with CV-nanofibers to form EVs-ECM aggregate, which can effectively promote endometrium regeneration toward supporting fetal development and live births. Our study provides a new idea for enhancing EV secretion and bioactivity, and a cell-free therapy for treating IUA by EVs, thus promoting the potential of clinical application.
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MEDICAL ENGINEERING & PHYSICS
·
2025
·
IF 2.3
SHENGJIE WANG,WEI LIU,CHAO YANG,XIANLONG ZHANG,CHUNMING LYU
Prosthetic loosening represents a catastrophic postoperative complication in artificial joint replacement, resulting in severe patient morbidity and substantial healthcare costs. This investigation aimed to develop a novel strategy for preventing prosthetic loosening. Two-dimensional MXene V 2 C nanosheets were synthesized and subsequently immobilized onto three-dimensional porous sulfonated polyetheretherketone (SPEEK) surfaces with polydopamine (PDA) to form V 2 C-PDA@SPEEK (Abbrev. V 2 C-PS). The biocompatibility was systematically evaluated using rat bone marrow mesenchymal stem cells (rBMSCs) and murine models. The osteogenic differentiation potential of V 2 C-PS was assessed through real-time PCR analysis, Alkaline phosphatase (ALP) staining, and Alizarin Red staining. The in vivo osteogenic capacity of V 2 C-PS surrounding the implant material was evaluated in rat femoral models using micro-CT analysis, biomechanical pull-out testing, sequential fluorescent labeling of newly formed bone, and Van Gieson staining. The molecular mechanisms underlying V 2 C-PS -mediated osteogenic differentiation of rBMSCs were investigated both in vitro and in vivo using chemical inhibitors, β-catenin shRNA lentiviral silencing, and β-catenin mRNA lentiviral overexpression. The results demonstrated that V 2 C-PS exhibited excellent biocompatibility. Quantitative analysis revealed substantial upregulation (p<0.05) of critical osteogenic markers, including RUNX2 (4.4-fold), COL-1 (5.7-fold), OCN (3.3-fold), BMP-2 (4.4-fold), OPN (3.1-fold), BSP (3.3-fold), ON (4.3-fold), and OSX (2.83-fold), in the 25V 2 C-PS treatment group compared to PS group. The bone parameters were also remarkably enhanced in the 25V 2 C-PS group (BMD increased by 241 %, bone-implant contact by 159 %, BV/TV by 225 %, Tb.N by 281 %, Tb.Th by 214 %, maximum pull-out force by 250 %, and Tp.Sp decreased by 33 %). Furthermore, V 2 C-PS were found to enhance rBMSC osteogenic differentiation through activation of the Wnt/β-catenin signaling pathway. This study presents a promising approach for preventing orthopedic prosthetic loosening and demonstrates significant potential for clinical translation.
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PLANT SCIENCE
·
2025
·
IF 4.1
Yang Yang,Mengting Zhu,Yijia Jin,Hui Cai,Yiran Huang,Yingling Wan,Yan Liu
Paeonia lactiflora is an important garden ornamental flower and has become a new cut flower in the international market in recent years. Stem mechanical strength is an important index of cut flower quality. P. lactiflora cultivars possess varying stem mechanical strength, which directly result in different cut P. lactiflora quality. In our previous study, a significant difference in phloem callose deposition was detected between two P. lactiflora cultivars with varying stem mechanical strength. However, the relationship and interaction mechanism between the phloem callose and mechanical strength in P. lactiflora stems are still unclear. This study aimed to analyze the effects of reduced phloem callose on the mechanical strength in P. lactiflora stems. The results revealed a negative correlation between the callose content and mechanical strength in P. lactiflora stems during early developmental stages. Exogenous 2DDG treatment led to a 13.6% reduction in the callose content, concomitantly enhancing the stem mechanical strength by 14.2% via facilitating the formation and secondary cell wall (SCW) thickening of xylem fiber cells. Further investigations showed that exogenous 2DDG treatment promoted carbon transport in P. lactiflora stems, thereby increasing the carbon content. Additionally, it induced alterations in the metabolism of lipids, amino acids, and organic acids in the stems and spurred the diffusion of lipids from the pith to the xylem. Consequently, reducing the content of callose improved the formation and SCW thickening of xylem fiber cells by modifying material transport and metabolism, thereby enhancing the stem mechanical strength of P. lactiflora . This study offers novel perspectives regarding the regulatory mechanism of P. lactiflora stem mechanical strength.
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JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2025
·Vol. 172
·期 4
·045502
·
IF 3.3
Lingling Zhang,Shuangru Yang,Yuge Liu,Yongmei Jia,Zhiguo Li
Understanding the electron transfer performance of DNA self-assembled monolayers (SAMs) on a transducer substrate was important for constructing DNA electrochemical sensors with high sensitivity. Here we immersed the gold electrodes in mixed solutions comprising thiol-modified stem-loop DNA (SL-DNA) or linear DNA (L-DNA) terminally bound with methylene blue (MB), and aliphatic thiols (HOC6SH, C6SH, HOOCC5SH, H2NC6SH, HOC11SH, C12SH, or HOOCC10SH) to obtain DNA/thiols mixed self-assembled monolayers (SAMs). MB electron transfer performances through SL-DNA/thiols and L-DNA/thiols mixed SAMs were investigated by cyclic voltammetry (CV). Our results showed that the mixed assembly of thiols with DNA was conducive to MB electron transfer. The electron transfer rate (ks) values of MB through L-DNA SAMs were bigger than those through SL-DNA SAMs, indicating that the flexibility of DNA chains was important to MB electron transfer. Thiols chain length or terminal groups influenced ks of MB significantly, that increasing NaCl or MgCl2 concentrations in solution around DNA availed MB electron transfer, and Mg2+ advanced MB electron transfer more than Na+, and that the stability of L-DNA/thiols SAMs was much better than SL-DNA/thiols SAMs. These conclusions might provide a reference for studying DNA electron transfer mechanisms or designing DNA or RNA electrochemical sensors with optimal performance.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Xinlei Yuan,Fang Wu,Le Cheng,Tengteng Ji,Chenyan Zheng,Yumeng Ma,Yutong Jin,Jianguo Dong,Yan Jin,Bing Fang
The acceptable daily intake (ADI) and maximum residue limits in food for chlorpyrifos (CPF), a widely used organophosphorus pesticide, may damage the intestine. Here, we evaluated damage to the intestine by CPF at the ADI (0.01 mg/kg bodyweight/day) and at 10 times the ADI (10ADI; 0.1 mg/kg bodyweight/day) in mice after 8 weeks of exposure and evaluated the resulting immune response to an enterotoxigenic Escherichia coli (ETEC) infection. CPF at the ADI dose significantly disrupted the intestinal integrity and intestinal stem cell functionality, which may be associated with reduced indole-3-propionic acid levels. However, mice in the 10ADI group exhibited only elevated pro-inflammatory cell and cytokine levels. During ETEC infection, intestinal mucosal immunity was activated by the 10ADI dose, as indicated by increased regulatory T cells and IL-10 levels, which were associated with decreased fecal butyric acid content. Our study demonstrated that the effects of pesticide residues appear to be dose-specific, bringing attention to the health risk at the ADI level.
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International Journal of Surgery
·
2025
·
IF 10.1
Wang Xuesheng,Zhang Fan,Zhou Zhonghan,Fu Qiang,Liao Limin
Background: Bladder augmentation with gastrointestinal segments is a widely used surgical procedure for neurogenic bladder, but it carries a risk of many side effects. However, there have been no systematic studies on which biomaterials are suitable for bladder augmentation and reconstruction. The aim of this study was to compare the safety and applicability of small intestinal submucosa (SIS), poly(l-lactic) acid (PLLA) nanofibrous scaffold, and PLLA/gelatin composite nanofibrous scaffold as a potential bladder wall substitute material in tissue-engineered bladder augmentation and reconstruction. The results provide a scientific basis for selecting appropriate materials in clinical applications. Materials and Methods: The microstructure, cytocompatibility, cell adhesion, and histocompatibility of scaffolds including SIS, PLLA nanofiber scaffold, and PLLA/Gelatin were observed. Furthermore, bladder augmentation rabbit models were constructed using scaffolds with and without adipose-derived stem cells (ASCs) implantation. Cystography and urodynamic examination were performed to evaluate the morphology and function of the reconstructed bladder. Histologic and immunofluorescence were used to assess the regeneration status of the reconstructed bladder. Results: Compared to SIS and PLLA/Gelatin scaffolds, the PLLA scaffold possessed appropriate mechanical properties, pore size and porosity, which could facilitate suturing, maintain bladder form, and promote the adhesion and proliferation of seeded ASCs. All animals survived in the experiment with no complications, and the structural integrity of the implantation site was demonstrated using cystography and urodynamics. Histological and immunohistochemical analyses indicated that the three kinds of scaffold could regenerate the bladder wall structure at 6 and 12 weeks. Bladder reconstructed with the ASCs-PLLA scaffold showed superior structural and functional properties, with no significant differences in the regenerated urothelium, smooth muscle, or vessels of the ASCs-PLLA and control groups. Conclusion: The ASCs-PLLA scaffold—composed of PLLA with favorable biological properties and ASCs with facilitating regeneration—presents a promising candidate as an ideal scaffold for bladder augmentation and reconstruction.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kuangpin Liu,Hailei Wang,Le Wang,Wei Ma,Jinwei Yang,Chunyan Li,Jinhua Liu,Wenli Bao,Liyan Li,Yan Du,Hongqiang Gao
Peripheral nerve injuries (PNI) remain challenging to treat due to limited regeneration capacity and the lack of effective therapeutic scaffolds to support nerve repair. This study aims to develop and evaluate a 3-aminophenylboronic acid-modified hyaluronic acid (HAB) hydrogel as a 3D scaffold to enhance Dorsal root ganglion-derived stem cells (DRGSCs) attachment, migration, and neuronal differentiation for peripheral nerve regeneration. The HAB hydrogel was synthesized through an amidation reaction and characterized using Fourier transform infrared spectroscopy (FTIR) and 1 H nuclear magnetic resonance ( 1 H NMR). DRGSCs were cultured in HAB hydrogel, and neuronal differentiation was assessed through immunofluorescence staining, PCR, and multi-electrode array (MEA) recordings. Cytotoxicity, proliferation, and in vivo biocompatibility were evaluated through live/dead staining, CCK-8 assays, and subcutaneous implantation in rats. Transcriptomic analysis was performed to explore gene expression profiles. Our results shown that DRGSCs cultured in HAB hydrogel exhibited significantly improved attachment (78.5 % ± 3.2 % vs. 45.3 % ± 2.8 %, p < 0.05) and migration speeds (21.4 μm/h vs. 12.9 μm/h, p < 0.05) compared to 2D cultures. Neuronal differentiation efficiency, as indicated by Tuj1-positive cells, was also higher (72.6 % ± 4.1 % vs. 42.8 % ± 3.9 %, p < 0.01). RNA sequencing identified 990 differentially expressed genes (627 upregulated, 363 downregulated), with pathways involved in synaptic vesicle cycling, glutamatergic and GABAergic synapses significantly enriched ( p < 0.05). Validation revealed that the expression trends of Gnao1 and Grm7 in the plastic petri dish and HAB hydrogel groups were consistent with the RNA sequencing results. In vivo, the hydrogel showed excellent biocompatibility, with reduced TNF-α and IL-1β expression over a 28-day degradation cycle ( p < 0.01). The HAB hydrogel provides a supportive 3D microenvironment that enhances DRGSCs differentiation and electrophysiological activity, highlighting its potential as a promising scaffold for peripheral nerve regeneration and neuroregenerative medicine.
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Advanced Science
·
2025
·
IF 14.1
Jiaojiao Li,Maoxiang Xu,Boyu Cai,Xiangyu Li,Zhanping Liang,Xiaohuan Xia,Haitao Zhang,Zhiwen Zhang,Fei Tan,Jialin Charlie Zheng
Traumatic brain injury (TBI) poses serious physical, psychosocial, and economic threats to millions of patients globally each year. While current treatment options, primarily surgery and medication, vary with TBI severity, there is no universal therapeutic agent applicable in both surgical and medical contexts. In the present study, exosomes derived from induced neural stem cells (iNSC-Exo) as a versatile therapeutic agent for TBI are investigated using a preclinical murine model. The iNSC-Exo treatment is found to exert therapeutic effects by mediating anti-neuroinflammation and neuroprotection, thereby promoting functional and cognitive recovery in TBI mice. Besides, two clinically inspired administration modalities are established for iNSC-Exo: local delivery and systemic delivery. Their efficacy is enhanced via a novel injectable hydrogel and RVG targeting for systemic delivery, respectively. Finally, the unprecedented single-cell characterization of mouse brain tissue, both pre- and post-iNSC-Exo treatment, confirms that microglia represent the predominant type of cells affected. Two microglial subpopulations (i.e., Microglia_Nrg3 and Microglia_Rarb) are identified with a reduced state of differentiation, and their connectivity with neurons is predicted through activation of the NRXN signaling pathway. Overall, these findings demonstrated that iNSC-Exo offers a versatile and potent treatment platform with clinical potential for TBI management.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2025
·
IF 9
Xuanjia Yu,Tianyuan Xiao,Lu Wu,Lingzhi Huang,Wenchao Jia,Mizhao Song,Bing Wang,Xueru Sheng,Pedram Fatehi,Ying Sun,Haiqiang Shi
Hemp straw bark, a high-yield renewable resource, faces sustainable development challenges due to underutilized lignin in traditional fractionation processes, often discarded as low-value waste. Herein, a one-pot strategy using choline chloride/lactic acid (ChCl/LA, 1:5) deep eutectic solvent (DES) enables controllable depolymerization and nanoscale self-assembly of lignin from it. Optimal conditions (solid-liquid ratio 1:80, 6 h) achieve a 98.6 % lignin yield relative to the initial lignin content in the raw material. FTIR and HSQC NMR confirm a selective β-O-4 ether bond cleavage with preserved aliphatic hydroxyls; 31 P NMR shows 3.1 mmol/g phenolic hydroxy and 1.28 mmol/g carboxy, enhancing interfacial activity. GPC reveals regulated molecular weights (M n 2160, M w 3632 g/mol, PDI = 1.68). Depolymerized lignin (L33) self-assembles into 190.1–220.2 nm nanoparticles (−32.5 mV zeta potential, good stability) with high thermostability (40 % char at 800 °C) and antioxidant activity (DPPH scavenging 73.9 % ± 1.1). LNPs (0.1 mg/mL) show potential as Pickering emulsion stabilizers, valorizing lignin into high-value materials. This study realized the effective and efficient separation of lignin from hemp straw bark, thereby offering a promising method for the industrial application of this lignin.
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ACS Nano
·
2025
·
IF 16
Yi Li,Jian Cao,Chengzhen Liang,Yuang Zhang,Kesi Shi,Haibin Xu,Kaishun Xia,Xianpeng Huang,Chao Yu,Jiangjie Chen,Feng Cheng,Jinyang Chen,Ronghao Wang,Kanbin Wang,Fangcai Li,Qixin Chen,Jianqing Gao,Xiaopeng Zhou
Stem cells hold great promise for repairing degenerated nucleus pulposus (NP) in intervertebral disc degeneration (IVDD) via differentiating into NP-like cells and replenishing the extracellular matrix (ECM). However, the harsh environment in degenerated NP contributes to poor survival, low differentiation efficiency, and matrix catabolism, hampering stem cells’ long-term transplantation and efficacy. Herein, a hyaluronic acid (HA)-based hydrogel (Pep-aGel) functionalized with collagen mimetic peptide and amination is fabricated to deliver glycoengineered stem cells for NP repair. The peptide (GFOGER), which contains the integrin recognition sequence of collagen, is selectively bound to the upregulated integrin-β1 of glycoengineered stem cells, thereby promoting their NP-like differentiation. The amination introduced amino groups in hydrogel and further enhanced the integration of cell-secreted glycosaminoglycans (GAGs) on the HA chains, which mimicked the biosynthesis of Aggrecan, creating an NP-like nanostructure in the hydrogel. Pep-aGel loading with glycoengineered cells showed injectable properties and significantly improved disc height, extracellular matrix content, and GAG deposition in rat degenerated discs. This approach established a self-sufficient system that consists of NP cell replenishment, in situ ECM supply, and GAG anchoring, which may offer a concise, yet synergistic, strategy for the regeneration of IVDD.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xinyu Liu,Xiaofan Liu,Yuping Zhao,Yang Liu,Huimin Wang,Yi Li,Nan Ma,Hongchen Sun,Fermín E. González,Youliang Zhu,Junfeng Zhou,Yuewei Zhang,Ding Zhou,Xiaowei Xu
Insufficient nutrient and oxygen supply remains a critical barrier to cell survival and tissue regeneration in three-dimensional scaffolds. Here, we developed a self-supplying glucose/oxygen hydrogel (SGO-Gel) that intrinsically provides sustained metabolic support for dental pulp stem cells (DPSCs). The hydrogel was constructed by crosslinking oxidized dextran with phenylboronic acid-grafted carboxymethyl chitosan through dynamic Schiff-base and phenylboronic ester bonds, yielding an injectable, self-healing network capable of releasing glucose upon dextranase degradation. Polydopamine-coated calcium peroxide nanoparticles were incorporated to achieve controlled oxygen release while maintaining structural stability. SGO-Gel exhibited a uniform porous architecture that facilitated nutrient diffusion, as confirmed by molecular dynamics simulations. In vitro , the hydrogel significantly enhanced DPSCs survival under combined glucose starvation and hypoxia, maintaining viability above 70 % after 7 days compared to less than 30 % in control gels. Transcriptomic analysis revealed activation of the MAPK/Erk1/2 pathway and upregulation of VEGF, which was consistent with functional assays showing enhanced endothelial migration and tube formation. In an ectopic transplantation model, SGO-Gel promoted the formation of vascularized pulp-like tissue with abundant collagen deposition and odontoblast differentiation. Overall, SGO-Gel shifts the paradigm from passive scaffolds to metabolically active matrices, offering a promising strategy for dental pulp regeneration and broader tissue engineering applications where ischemia and limited vascularization remain key challenges.
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危险品化学品经营许可证（带存储）