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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Point-of-need quantitation of 2,4-dichlorophenoxyacetic acid using a ratiometric fluorescent nanoprobe and a smartphone-based sensing system

Yun Liu,Meng Xiao,Ningxia Xu,Mengsu Yang,Changqing Yi

This study reports a new ratiometric fluorescence probe (referred to as [email protected] @bCDs) and a smartphone-based sensing system for on-site quantitation of Fe 3+ , ascorbic acid (AA), alkaline phosphatase (ALP) and 2,4-dichlorophenoxyacetic acid (2,4-D). [email protected] @bCDs with well-resolved dual emissions is facilely synthesized by covalent conjugation of red-emissive quantum dots (rQDs), the internal standard, with blue-emissive carbon dots (bCDs), the Fe 3+ -specific fluorescent indicator . 2,4-D can specifically inhibit the enzymatic activity of ALP, leading to suppress the production of AA which can reduce Fe 3+ to Fe 2+ and thereafter trigger the fluorescence response of [email protected] @bCDs. Taking advantages of these highly specific cascade catalytic reactions , ratiometric fluorescence schemes are established for sensing Fe 3+ , AA, ALP and 2,4-D both in aqueous solution and on paper-based microarray . The smartphone-based fluorescence detector integrated with the [email protected] @bCDs-based microarray demonstrated good sensing performance with a wide linear range and low detection limit, and is successfully applied to quantitate 2,4-D in cabbage and tap water samples. The reported method which enables point-of-need quantitation in a sample-in-result-out manner and highlights its features of cost-effectiveness and ease-of-use, is ideally for food safety inspection, environment surveillance, health monitoring at point-of-need, especially in low resource settings.

研究领域: 分析化学 · 环境科学 · 食品安全 · 生物技术
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2021 · IF 5.268

Three-dimensional porous reduced graphene oxide/hydroxyapatite membrane for guided bone regeneration

Wei Liu,Xingtong Dong,Han Qin,Lei Sui,Jian Wang

The guided bone regeneration (GBR) membrane is intended to provide sufficient space for alveolar bone regeneration and meanwhile prevent the invasion of gingival epithelium. In this study, three-dimensional porous reduced graphene oxide/hydroxyapatite (3D rGO/HA) membrane with two different sides was prepared using a two-step electrochemical method. One side of this composite membrane facing the bone defect was formed by 3D porous rGO with HA deposited on the frame of the 3D structure, and the other side of the membrane presented a dense 2D rGO surface to prevent the invasion of the gingival epithelium. The morphology, phase composition, and physical properties of the 3D rGO/HA composite membrane were characterized. Then the cell morphology, viability, and proliferation of pre-osteoblasts (MC3T3-E1 cells) on the 3D porous structure surface of membranes were evaluated and alkaline phosphatase (ALP) secretion as an indication of osteogenic differentiation was also investigated. Meanwhile, cell morphology, viability, and proliferation of HUVEC and L929 cells on the dense structure surface were examined. Finally, a cranial defect model of rat was employed to evaluate the effect of 3D rGO/HA as a GBR membrane in vivo. The results revealed the 3D rGO/HA membrane had good biocompatibility for MC3T3-E1 and HUVEC cells and could significantly enhance ALP secretion. Furthermore, this membrane also promoted the repair of calvarial defects in vivo . These results demonstrated that 3D porous rGO/HA composite membrane with a porous side and another dense side represents great application potential as an ideal GBR membrane.

研究领域: 生物材料 · 组织工程 · 生物医学工程 · 骨科 · 牙科材料
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Biomaterials Advances · 2022 · IF 0

Mechanically enhanced composite hydrogel scaffold for in situ bone repairs

Yiwen Zhang,Zhixiang Li,Ziqi Wang,Bomin Yan,Ao Shi,Jinnuo Xu,Jianzhong Guan,Li Zhang,Pinghui Zhou,Yingji Mao

High-efficiency repair of critical bone defects is a pressing problem in clinical practice. However, most biological replacement materials do not simultaneously satisfy the dual requirements of mechanical strength and cell compatibility. In this study, chitosan methacryloyl (CSMA) and β-tricalcium phosphate (β-TCP) were subjected to photo-crosslinking to form the CSMA/β-TCP composite hydrogel, which has strong mechanical properties contributing to bone regeneration. In addition, its scaffold can alter the morphology of bone marrow mesenchymal stem cells (BMSCs), promote their proliferation, enhance the expression of alkaline phosphatase (ALP), and augment the nodular deposition of calcium. Meanwhile, the expressions of osteogenic proteins (ALP, osteocalcin, and osteopontin) were upregulated and the regulatory mechanism of the Hippo signaling pathway was verified. Moreover, animal experiments have confirmed that CSMA/β-TCP has adequate biocompatibility and bone regeneration. These results demonstrate the immense potential of the CSMA/β-TCP composite hydrogel in bone regeneration therapy.

CAS / MDL: 7758-87-4 9012-76-4
研究领域: 组织工程 · 生物材料 · 再生医学 · 骨科
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SCIENCE OF THE TOTAL ENVIRONMENT · 2024 · IF 8.2

Bioenzyme–nanoenzyme–chromogen all-in-one test strip for convenient and sensitive detection of malathion in water environment

Hanwen Zhang,Jiabin Jin,Xini Wang,Wei Han,Lei Qin,Lin Chen,Xiaoyan Mao,Zhenjiang Liu,Xingwei Xiang

The presence of pesticide residues in aquatic environments poses a significant threat to both aquatic ecosystems and human health. The presence of these residues can result in significant harm to aquatic ecosystems and can negatively impact the health of aquatic organisms. Consequently, this issue requires urgent attention and effective measures to mitigate its impact. However, developing sensitive and rapid detection methods remains a challenge. In this study, an all-in-one test strip, which integrated bioenzymes, nanoenzymes, and a chromogen, was developed in combination with an enzyme labeling instrument for a highly sensitive and convenient sensing of malathion residues. The oxidase activity of heme chloride (Hemin) in the strip can catalyze the oxidation of H 2 O 2 and 3,3′,5,5′-tetramethylbenzidine (TMB) to produce a blue-colored oxide. Simultaneously, the alkaline phosphatase (ALP) present in the strip can break down l -ascorbic acid-2-phosphate to produce ascorbic acid (AA). This AA then acts to reduce the oxidized form of TMB, turning it into a colorless substance and leading to the disappearance of its fluorescent signal. In the presence of a pesticide, the activity of ALP is inhibited and formation of AA is blocked, thereby preventing the reduction of oxidized TMB and producing a colored signal. According to this principle, the integrated test strip detected the target pesticide with high performance as per the optical density value determined via an enzyme marker. The detection limit of the test strip was 0.209 ng/mL with good sensitivity. The method was used for detecting malathion in actual river water samples, and the recoveries were in the range of 93.53 %–96.87 %. The newly devised technique effectively identified malathion in samples of natural water. This research has introduced a novel approach for the precise and convenient surveillance of pesticide remnants. Additionally, these discoveries could inspire the advancement of proficient multi-enzyme detection systems.

研究领域: 环境科学 · 分析化学 · 生物技术 · 水质监测
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JOURNAL OF ETHNOPHARMACOLOGY · 2024 · IF 4.8

Desmodium styracifolium (Osb.) Merr. extracts alleviate cholestatic liver disease by FXR pathway

Zhiyuan Zhang,Guoqiang Guan,Zixuan Tang,Weimin Wan,Zhipeng Huang,Yuefeng Wang,Jianzhao Wu,Bo Li,Mingli Zhong,Kefeng Zhang,Lixian Nong,Ya Gao,Houkang Cao

A B S T R A C T Ethnopharmacological relevance Cholestatic liver disease (CLD) is a disease characterized by cholestasis. Farnesoid X receptor (FXR) is a nuclear receptor that maintains homeostasis in bile acid metabolism. Studies have shown that gut microbiota interfered with the FXR pathway. Modulation of FXR to inhibit cholestasis has become a key measure in the treatment of CLD. In traditional folk medicine, Desmodium styracifolium (Osb.) Merr. was used as a primary treatment for gallstones, gonorrhea, jaundice, cholecystitis and other diseases. Modern pharmacological studies had also found that the herb has anti-calculus, anti-inflammatory, antioxidant, diuretic and liver damage. Therefore, we speculated that Desmodium styracifolium (Osb.) Merr. extracts (DME) could alleviate CLD through the FXR pathway and might be associated with the gut microbiota. However, studies of DME alleviating CLD through the FXR pathway have not been reported. Aim of study To study the effect and mechanism of DME in relieving CLD through in vivo and in vitro experiments. Materials and methods First, mice were administrated with alpha-naphthyl isothiocyanate (ANIT) to establish a CLD model in vivo . Meanwhile, HepG2 cells were induced by lithocholic acid (LCA) to establish the CLD model in vitro . To evaluate the therapeutic effect of DME on CLD mice, hematoxylin-eosin (HE) staining, and biochemical indicators were performed. The prototype of the blood components in mice serum was detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 16S rDNA sequencing was used to analyze the gut microbiota. Finally, the protein and mRNA expression of the FXR pathway in mice liver tissues or HepG2 cells were detected by Western blot, qRT-PCR, or immunofluorescence. Results Pathological testing and biochemical indexes showed that DME significantly reduced serum ALT, AST, ALP, TBIL, DBIL, TBA and liver TBA levels, and attenuated liver tissue injury, necrosis and jaundice in CLD mice. In addition, MetagenomeSeq analysis of gut microbiota showed that DME significantly up-regulated the abundance of Parvibacter , down-regulated the abundance of Paenalcaligenes , and regulated bile acid homeostasis. In terms of mRNA expression, DME significantly upregulated the mRNA levels of Nr1h4, Abcb11, Cyp7a1 and Slc10a1. Meanwhile, in terms of protein expression, DME significantly up-regulated the protein expression levels of FXR, BSEP, CYP7A1 and NTCP, which regulated bile acid homeostasis. Finally, the molecular docking results showed that the components of DME, such as Lumichrome, Daidzein and Folic acid, all had good binding ability with FXR, and the surface plasmon resonance (SPR) results also showed that both Lumichrome and Daidzein had a relatively high affinity with FXR. Conclusion DME alleviated CLD through the FXR pathway, and the mechanisms might be associated with the gut microbiota.

研究领域: 药理学 · 肝病学 · 分子生物学 · 微生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Increased physiological osteochondral repair via space-specific sequestrating endogenous BMP-2 founctional hydrogel

Yuping Wang,Yiting Lei,Nan Wang,Jun Zhang,Wenguo Cui,Xiaoji Luo

The challenge of achieving graded regeneration of adjacent tissues remains significant in tissue repair and regeneration. For instance, the disruption of the microenvironment caused by “osteogenesis mobilization” often results in fibrosis of the regenerated cartilage, ultimately leading to osteoarthritis. Inspired by the utilization of activated carbon for adsorbing and filtering small particles in air purification and water treatment, we have designed an integrated hydrogel scaffold capable of absorbing the endogenous BMP-2 produced by “osteogenesis mobilization”, confining it to the bone defect area, and preventing its diffusion into the cartilage region, thereby facilitating physiological osteochondral gradient regeneration. The osteogenic layer of this integrated scaffold is NHAP-AHAMA-B2A, which captures the BMP-2 produced by “osteogenesis mobilization” and amplifies its osteogenic effect through the grafted peptide B2A. This upregulation enhances the expression of ALP, OCN, and OPN in MSCs within the osteogenic layer, promoting osteogenic differentiation. The chondrogenic layer, HAMA-B2A, utilizes the peptide B2A to upregulate the expression of COL II and ACAN in MSCs, fostering chondrogenic differentiation. This integrated HAMA-B2A/NHAP-AHAMA-B2A hydrogel scaffold confines the BMP-2 produced by “osteogenesis mobilization” to the bone defect area, prevents its diffusion into the cartilage defect area, and effectively utilizes it to induce stem cell osteogenic differentiation. Simultaneously, it induces stem cell chondrogenic differentiation in the cartilage defect area, achieving transparent cartilage regeneration. In summary, the osteogenic and chondrogenic layers of this integrated scaffold collaborate to achieve a physicochemical gradient regeneration of bone-cartilage.

CAS / MDL: 106797-53-9 760-93-0
研究领域: 组织工程 · 再生医学 · 生物材料科学 · 骨科
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Journal of Materials Chemistry B · 2018 ·Vol. 6 ·期 37 ·6008-6015 · IF 4.776

Fluorescence assay for alkaline phosphatase activity based on energy transfer from terbium to europium in lanthanide coordination polymer nanoparticles

Fengyi Wang,Xuan Hu,Jing Hu,Qianqian Peng,Baozhan Zheng,Juan Du,Dan Xiao

In this study, bimetallic lanthanide coordination polymer nanoparticles (Tb-GMP-Eu CPNs) were developed for sensing alkaline phosphatase (ALP) by utilizing guanine monophosphate (GMP) as the bridge ligand to self-assemble with Tb3+ and Eu3+ in Tris–HCl buffer solution. In this polymer framework, an efficient energy transfer from Tb3+ to Eu3+ occurred because the emission energy of Tb3+ matched well with the absorption energy of Eu3+. As a result, the synthesized Tb-GMP-Eu CPNs exhibited the characteristic red emission of Eu3+ when excited at 290 nm. When ALP was introduced into the Tb-GMP-Eu CPNs system, it would destruct the combination between Tb and GMP by a dephosphorylation process, resulting in interruption of energy transfer from Tb3+ to Eu3+ and therefore the fluorescence quenching of Eu3+. Based on these facts, a fluorescence assay based on bimetallic lanthanide coordination polymer nanoparticles for ALP detection was developed. Such a Tb-GMP-Eu CPNs sensor exhibited sensitive response to ALP with a detection limit down to 0.004 U L−1. Moreover, the successful application of ALP inhibitor evaluation and determination of ALP in serum samples have been demonstrated. Therefore, the proposed method has great potential application for ALP detection in biological and clinical diagnosis.

CAS / MDL: 57584-27-7
研究领域: 分析化学 · 生物化学 · 纳米技术 · 生物医学工程 · 临床诊断
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Nanoscale · 2019 ·Vol. 11 ·期 48 ·23423-23437 · IF 6.97

Synergistic osteogenesis promoted by magnetically actuated nano-mechanical stimuli

Lili Hao,Linlong Li,Peng Wang,Zongliang Wang,Xincui Shi,Min Guo,Peibiao Zhang

Functional biomaterials with magnetic properties are considerably useful for regulating cell behavior and promoting bone regeneration. And the combination of such biomaterials with physical environmental cues (such as magnetic fields and mechanical stress) might be more favorable for the regulation of cell function. This study is aimed at investigating the combined effects of magnetically responsive materials and a static magnetic field (SMF) on the osteogenic differentiation of osteoblasts and the potential mechanism involved. In this study, oleic acid modified iron oxide nanoparticles (IO-OA NPs) were utilized to generate homogeneous magnetic nanocomposites with poly(lactide-co-glycolide) (PLGA) used as the base and to enhance the mechanical properties of the composites. In vitro experimental results show that in the presence of an external SMF, cell attachment and osteogenic differentiation were significantly improved using the IO-OA/PLGA composites, as indicated by enhanced alkaline phosphatase (ALP) activity, increased mineralized nodule formation, and upregulated bone-associated gene expression (ALP, OCN, and BMP2), in a dose- and time-dependent manner. Furthermore, the upregulated expression levels of piezo-type mechanosensitive ion channel component 1 (Piezo1), a key receptor for sensing mechanical stimuli, implied that the synergistically enhanced osteogenic differentiation was mainly caused as a result of the mechanical stimuli. Such magnetically actuated mechanical stimuli were induced through the nano-deformation of the magnetic substrate under a SMF, which was directly characterized via in situ scanning using atomic force microscopy (AFM). This study demonstrates that magnetically actuated nano-mechanical stimuli may underpin the synergistic effects of magnetic composites and magnetic stimuli to enhance osteogenic differentiation, and they could form the basis of a potential strategy to accelerate bone formation for bone tissue engineering and regenerative medicine applications.

研究领域: 生物材料 · 组织工程 · 再生医学 · 细胞生物学
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Advanced Healthcare Materials · 2023 · IF 10

In Situ Enzymatic Reaction Generates Magnesium-Based Mineralized Microspheres with Superior Bioactivity for Enhanced Bone Regeneration

Zhuyun Cai,Xiaohao Liu,Miao Hu,Yichen Meng,Jianquan Zhao,Yixuan Tan,Xiong Luo,Ce Wang,Jun Ma,Zhongyi Sun,Yingying Jiang,Bingqiang Lu,Rui Gao,Feng Chen,Xuhui Zhou

Bone is a naturally mineralized tissue with a remarkable hierarchical structure, and the treatment of bone defects remains challenging. Microspheres with facile features of controllable size, diverse morphologies, and specific functions display amazing potentials for bone regeneration. Herein, inspired by natural biomineralization, a novel enzyme-catalyzed reaction is reported to prepare magnesium-based mineralized microspheres. First, silk fibroin methacryloyl (SilMA) microspheres are prepared using a combination of microfluidics and photo-crosslinking. Then, the alkaline phosphatase (ALP)-catalyzed hydrolysis of adenosine triphosphate (ATP) is successfully used to induce the formation of spherical magnesium phosphate (MgP) in the SilMA microspheres. These SilMA@MgP microspheres display uniform size, rough surface structure, good degradability, and sustained Mg 2+ release properties. Moreover, the in vitro studies demonstrate the high bioactivities of SilMA@MgP microspehres in promoting the proliferation, migration, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis shows that the osteoinductivity of SilMA@MgP microspheres may be related to the activation of the PI3K/Akt signaling pathway. Finally, the bone regeneration enhancement units (BREUs) are designed and constructed by inoculating BMSCs onto SilMA@MgP microspheres. In summary, this study demonstrates a new biomineralization strategy for designing biomimetic bone repair materials with defined structures and combination functions.

研究领域: 生物医学工程 · 组织工程 · 材料科学 · 细胞生物学 · 再生医学
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ANALYTICAL CHEMISTRY · 2024 · IF 6.7

Enzymatically Mediated In Situ Generation of Z-Scheme Bi2S3/Bi2MoO6 Heterojunction-Based Organic Photoelectrochemical Transistor for METTL3/METTL14 Detection

Miao Zhang,Haowei Zhang,Yunlei Zhou,Huanshun Yin,Zhengkun Yu,Xinyue Zhang,Shiyun Ai,Minghui Wang

The OPECT biosensing platform, which connects optoelectronics and biological systems, offers significant amplification and more possibilities for research in biological applications. In this work, a homogeneous organic photoelectrochemical transistor (OPECT) biosensor based on a Bi2S3/Bi2MoO6 heterojunction was constructed to detect METTL3/METTL14 protein activity. The METTL3/METTL14 complex enzyme was used to catalyze adenine (A) on an RNA strand to m6A, protecting m6A-RNA from being cleaved by an E. coli toxin (MazF). Alkaline phosphatase (ALP) catalyzed the conversion of Na3SPO3 to H2S through an enzymatic reaction. Due to the adoption of the strategy of no fixation on the electrode, the generated H2S was easy to diffuse to the surface of the ITO electrode. The Bi2S3/Bi2MoO6 heterojunction was formed in situ through a chemical replacement reaction with Bi2MoO6, improving photoelectric conversion efficiency and realizing signal amplification. Based on this “signal on” mode, METTL3/METTL14 exhibited a wide linear range (0.00001–25 ng/μL) between protein concentration and photocurrent intensity with a limit of detection (LOD) of 7.8 fg/μL under optimal experimental conditions. The applicability of the developed method was evaluated by investigating the effect of four plasticizers on the activity of the METTL3/METTL14 protein, and the molecular modeling technique was employed to investigate the interaction between plasticizers and the protein.

研究领域: 生物化学 · 生物传感器 · 光电化学 · 蛋白质活性检测
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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-26 · IF 10.6

Enhanced osteogenic differentiation in 3D hydrogel scaffold via macrophage mitochondrial transfer

Qiu Shui,Cao Lili,Xiang Dingding,Wang Shu,Wang Di,Qian Yiyi,Li Xiaohua,Zhou Xiaoshu

To assess the efficacy of a novel 3D biomimetic hydrogel scaffold with immunomodulatory properties in promoting fracture healing. Immunomodulatory scaffolds were used in cell experiments, osteotomy mice treatment, and single-cell transcriptomic sequencing. In vitro, fluorescence tracing examined macrophage mitochondrial transfer and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Scaffold efficacy was assessed through alkaline phosphatase (ALP), Alizarin Red S (ARS) staining, and in vivo experiments. The scaffold demonstrated excellent biocompatibility and antioxidant-immune regulation. Single-cell sequencing revealed a shift in macrophage distribution towards the M2 phenotype. In vitro experiments showed that macrophage mitochondria promoted BMSCs’ osteogenic differentiation. In vivo experiments confirmed accelerated fracture healing. The GAD/Ag-pIO scaffold enhances osteogenic differentiation and fracture healing through immunomodulation and promotion of macrophage mitochondrial transfer.

研究领域: 生物材料 · 组织工程 · 再生医学 · 免疫学 · 干细胞生物学
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Biomaterials Science · 2024 · IF 5.8

Fast bone regeneration using injectable fully biomimetic organoids with biomineralized and organic microenvironments

Runquan Zheng,Ning Zhang,Songbo Mao,Jiawei Li,Xuesong Yan,Guichun Zhang,Yongxian Zhang,Xianhu Yue

Bone defects and congenital bone deficiencies are common clinical conditions. However, conventional non-degradable artificial materials often lead to serious complications, such as severe infections and material displacement. The emergence of tissue engineering and the organoids concept presents a promising approach for the repair of bone defects, facilitating physiological reconstruction while minimizing complications. Nevertheless, previous studies have not developed injectable organoids that incorporates fully mineralized and organic microenvironments to achieve rapid osteogenesis and convenient application in bone regeneration. Therefore, it is imperative to devise an effective strategy to address these challenges. This study first prepared injectable GL scaffolds with varying concentrations and identified the optimal GL concentration for osteogenesis through systematic evaluation of osteogenic efficiency. Subsequently, inorganic salts of native bone (NBIS) and extracellular matrix from the periosteum (pECM) were integrated into the optimal GL scaffold to create an injectable scaffold featuring biomimetic mineralized and organic microenvironments. This scaffold was further utilized for in vitro analysis of osteogenic mechanisms and injected subcutaneously into rabbits for only four weeks to assess its osteogenic efficacy in vivo. The results indicated that the incorporation of NBIS and pECM significantly enhanced osteogenic efficacy by actively regulating ossification and ECM-receptor interaction signaling pathways, as well as upregulating RUNX2, ALP, COL1, and LAMA. This study introduces a promising injectable strategy for rapid osteogenesis using fully mineralized and organic biomimetic organoids.

研究领域: 组织工程 · 骨再生 · 生物材料 · 医学生物技术
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