MATERIALS & DESIGN
·
2022
·
IF 9.417
Lingling Pan,Dawei Jiang,Luqi Pan,Zhizhen Meng,Yangyang Zhuang,Yueyue Huang,Fanrong Ye,Changcan Shi,Jie Chen,Jingye Pan
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and causes high ratios of morbidity and mortality worldwide. Although many potential therapeutic targets have been reported, the therapeutic effect needs to be further improved. Herein, we report a strategy to specifically target inflammation site via anti-ICAM-1 antibody bonded antibacterial peptides polymeric nanoparticle. Antibacterial peptide (KR-12) grafted amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 block copolymer and PCL- b -P(OEGMA- co -AMA)- g -biotin block copolymer were synthesized by ring-opening polymerization and click chemistry. Then, antibacterial peptides polymeric nanoparticles (AMPNP) were prepared by co-assembly of amphipathic PCL- b -P(OEGMA- co -AMA)- g -Cys-KR-12 and PCL- b -P(OEGMA- co -AMA)- g -biotin in aqueous solution. Intercellular adhesion molecule-1 (ICAM-1) is highly expressed on the surface of inflammatory endothelial cells, and the anti-ICAM-1 antibody can specifically bind to it. To obtain the anti-ICAM-1-AMPNP nanoparticles, biotinylated anti-ICAM-1 antibodies were bonded on the surface of AMPNP nanoparticles through the biotin-avidin system. The anti-ICAM-1-AMPNP nanoparticles had low systemic toxicity and exhibited ideal antibacterial property against drug-resistant bacteria, Gram-negative bacteria and Gram-positive bacteria. The anti-ICAM-1-AMPNP nanoparticles exhibited favorable targeting capabilities to inflammation endothelial cells in vitro and significantly reduced the inflammatory response of CLP mice in vivo . The present investigation might provide a specific strategy for targeting combating sepsis with anti-ICAM-1-AMPNP nanoparticles.
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Advanced Healthcare Materials
·
2023
·
IF 10
Jian Tang,Yang Liu,Mingxi Li,Xiao Wang,Anning Du,Ning Gu,Fang Yang
Vascular inflammation is an early manifestation and common pathophysiological basis of numerous cardiovascular and cerebrovascular diseases. However, effective surveillance methods are lacking. In this study, sulfur hexafluoride (SF 6 )-loaded polylactic acid- co -glycolic acid (PLGA) nanobubbles (NBs) with a surface assembly of cyclodextrin (CD) and sphingosine-1-phosphate (S1P) (S1P@CD-PLGA NBs) are designed. The characterization results show that S1P@CD-PLGA NBs with diameters of ≈200 nm have good stability, biosafety, and ultrasound imaging-enhancement effects. When interacting with inflammatory vascular endothelial cells, S1P molecules encapsulated in cyclodextrin cavities exhibit a rapid, excellent, and stable targeting effect owing to their specific interaction with the highly expressed S1P receptor 1 (S1PR1) on the inflammatory vascular endothelial cells. Particularly, the S1P–S1PR1 interaction further activates the downstream signaling pathway of S1PR1 to reduce the expression of tumor necrosis factor-α (TNF-α) to protect endothelial cells. Furthermore, mouse models of carotid endothelial injuries and mesenteric thrombosis demonstrate that S1P@CD-PLGA NBs have excellent capabilities for in vivo targeting imaging. In summary, this study proposes a new strategy of using S1P to target inflammatory vascular endothelial cells while reducing the expression of TNF-α, which has the potential to be utilized in the targeted surveillance and treatment of vascular inflammatory diseases.
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Journal of Flow Chemistry
·
2023
·Vol. 13
·期 4
·375-383
·
IF 2.7
Lai Liangchuan,Gao Liang,Liu Minjie,Guo Yongxing,Cheng Dang,Jiang Meifen,Chen Fener
Continuous flow technology has been widely adopted in manufacturing active pharmaceutical ingredients (APIs). Herein, we report an expeditious multi-step continuous-flow strategy for an efficient and highly productive flow synthesis of 7-methoxy-1-tetralone, which is an essential intermediate for the opioid analgesic drug (-)-dezocine. Compared with the traditional batch operation, this work presents significant advantages of continuous-flow chemistry with dramatically reduced reaction time, highly improved reaction efficiency, good controls over reaction optimizing conditions, etc. The flow protocol in this work provided the desired product in an overall yield of up to 76.6% with 99% purity, much higher than those from batch process (i.e., 50% yield, 92% purity). Moreover, reaction efficiency is highly improved with a throughput of 0.49 g/h, the total reaction time is markedly reduced from hours in batch to minutes in flow process. Graphical abstract
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Yingli Han,Yuehua Wang,Fangyu Zhou,Yuyang Jiang,Feng Liu
Human apurine/apyrimidine endonuclease (APE) is a multifunctional enzyme that affects the occurrence and development of cancer through DNA repair and redox regulation. It has been identified as a tumor marker for detection and prognosis and drug target due to its overexpression in a variety of cancers. However, the accurate detection of APE 1 activity is still a huge challenge. Traditional approaches exist some disadvantages, including low sensitivity, complex operation and professional equipment requirements. Therefore, it is necessary to develop a fast, sensitive and simple biosensor to detect APE 1 activity in vivo and in vitro. In this report, a new tetrahedral molecular beacon (TMB) probe is designed for the detection of APE 1 activity. This probe not only has the advantage that the tetrahedron can enter the cells without a transfection agent, but also has the advantages of simple operation and low cost. The extracellular detection limit of TMB is as low as 0.0026 U/mL, and this program has successfully achieved APE 1 intracellular imaging to distinguish cancer cells overexpressing APE 1 from normal cells. In addition, the probe which is an effective mean for screening APE 1 inhibitor can also monitor the response of APE 1 to different drugs. All in all, our probe can be successfully applied to detect APE 1 activity in vivo and vitro, and can achieve living cells drug screening. And this probe also provides a general method for the detection of other endogenous biological targets in living cells.
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APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
·
2021
·Vol. 127
·期 12
·1-13
·
IF 2.584
Li Wenchuan,Wu Heng,Ao Hong,Zeng Zhixin,Gao Rongli,Cai Wei,Fu Chunlin,Deng Xiaoling,Chen Gang,Wang Zhenhua,Lei Xiang
Multiferroic composite ceramics x Ni 0.15 Cu 0.25 Zn 0.6 Fe 2 O 4 -(1- x ) Ba 0.85 Ca 0.15 Zr 0.1 Ti 0.9 O 3 ( x = 0, 0.2, 0.3, 0.4, 0.5, 0.6, 0.9 and 1) were prepared by combining chemical co-precipitation method with sol–gel method; the microstructure, dielectric, ferroelectric, magnetic and multiferroic properties were comparatively investigated. XRD results show that all the specimens have obvious bi-phases structure. The grains with larger size are magnetic phase Ni 0.15 Cu 0.25 Zn 0.6 Fe 2 O 4 (NCZF), while that of smaller size can be attributed to ferroelectric phase Ba 0.85 Ca 0.15 Zr 0.1 Ti 0.9 O 3 (BCZT). The dielectric constant of the sample with x = 0.6 is the largest at low frequency but the specimen x = 0.2 has the highest value of dielectric constant in high-frequency region. When x = 0.9, the ceramic has the largest loss, while it presents the lowest loss value when x = 0.3. The height of the peak decreases with increase in the frequency, and the position of the peak moves to higher temperature range with the decrease in x . The dielectric loss increases sharply with temperature, especially when x = 0.9, when the temperature is higher than 300 °C, the dielectric loss reaches hundreds of times under low frequency. Al samples present apparent ferroelectric hysteresis loops, but further characterization shows that the hysteresis may be attributed to leakage current. The remnant polarization( P r ) and coercive field( E c ) do not monotonically change with x , P r is 0.1576 μC/cm 2 at 2 kHz when x = 0.6. The magnetization monotonically changes with the x , indicating that there is a strong interfacial interaction between the two phases. Under the action of an external magnetic field of 1 mT, the magnetoelectric (ME) coupling is the strongest (relative polarization change 37%) when x = 0.2.
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MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 12
·1-8
·
IF 5.479
Meng Xiangying,Chen Xiao,Wu Weihua,Zheng Wei,Deng Haohua,Xu Luyao,Chen Wei,Li Zhulai,Peng Huaping
Molybdenum oxide quantum dots (MoO x QDs) were synthesized by a one-pot method and used as a versatile probe in an electrochemiluminescent (ECL) immunoassay of the non-small cell lung cancer biomarker cytokeratin 19 fragment 21–1 (CYFRA21-1) as a model analyte. The MoO x QDs exhibited stable and strong cathodic green ECL, with an emission peak at 535 nm, in the presence of K 2 S 2 O 8 within the potential range of −2.0 to 0 V. On exposure to CYFRA21-1, the ECL decreases because of the immunoreaction between CYFRA21-1 and its antibody which generates a barrier for electron transfer. The determination of CYFRA21-1 with favorable analytical performances was successfully realized under the optimal conditions. ECL decreases linearly in the 1 pg mL −1 to 350 ng mL −1 CYFRA21-1 concentration range, and the detection is as low as 0.3 pg mL −1 . Excellent recoveries from CYFRA21-1-spiked human serum indicate that the assay can be operated under physiological conditions.
Schematic representation of the fabrication of molybdenum oxide quantum dots (MoO x QDs) and the electrochemiluminescent (ECL) immunoassay based on the use of the MoO x QDs ECL probe for cytokeratin 19 fragment 21–1 (CYFRA21-1).
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2023
·
IF 1.7
Jin-Bu Xu,Shi-Xing Miao,Feng Gao,Lin-Xi Wan
A series of arylated huperzine A (HPA) derivatives (1–24) were efficiently synthesized in good yields (45–88% yields) through the late-stage modification of structurally complex natural anti-Alzheimer’s disease (AD) drug huperzine A (HPA), using the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. The acetylcholinesterase (AChE) inhibitory activity of all synthesized compounds was evaluated to screen the potential anti-AD bioactive molecules. The results showed that introducing the aryl groups to C-1 position of HPA resulted in the unsatisfactory AChE inhibitory activity. The present study demonstrably verifies pyridone carbonyl group could be the necessary and unchangeable pharmacophore for maintaining HPA's anti-AChE potency, and provides the helpful information on the further research for developing anti-AD HPA analogues.
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Biomedical Optics Express
·
2023
·Vol. 14
·期 11
·5921-5931
·
IF 3.4
Hang Qu,Linyao Tan,Fang-Cai Wu,Weiyuan Huang,Kaiwei Li,Xiaoyong Chen,Xiaoyong Chen,Yi-Wei Xu,Yi-Wei Xu,Xuehao Hu
Autoantibodies against New York esophageal squamous cell cancer 1 (NY-ESO-1) play a crucial role in the diagnosis of esophageal cancer. In this work, a surface plasmonic tilted fiber Bragg grating (TFBG) biosensor is proposed for the detection of NY-ESO-1 antibody, as well as the investigation of the hook effect (which refers to the false negative result in some immunoassays when the concentration of antibodies in the sample is very high) during biomolecular binding between NY-ESO-1 antigen and antibody. The biosensor is made by an 18° TFBG coated with a 50-nm-thick gold film over the fiber surface together with NY-ESO-1 antigens attached to the metallic surface serving as bio-receptors. This biosensor can provide a limit of detection at a concentration of 2 × 10−7 µg/ml with a good linearity in the range from 2 × 10−7 to 2 × 10−5 µg/ml. For a concentration higher than 2 × 10−3 µg/ml, the performance of the sensor probe is reduced owing to the hook effect. Furthermore, experimental results have also demonstrated the repeatability of the proposed biosensor. This proposed biosensor features label-free, compactness, and fast response, which could be potentially applied in the diagnosis of esophageal cancer.
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JOURNAL OF CHROMATOGRAPHY A
·
2021
·
IF 4.759
Tao Bao,Sicen Wang,Nan Zhang,Juan Zhang
Inspired by the outstanding functions of 3-aminopropyltriethoxysilane (APTES), which can be used for functionalization of both covalent organic frameworks (COFs) and substrate surfaces, herein, a proof-of-concept demonstration was carried out by one-step synthesis and immobilization of COF-1 in capillary. COF-1 was grown on the inner wall of capillary using APTES, which played a triple role of catalyst, stabilizer, and connecting arm during the process. The immobilization of COF-1 on silicon surface was confirmed by scanning electron microscopy. Moreover, COF-1 modified capillary (COF-1@capillary) column exhibited excellent performance in the electrochromatographic separation of amino acids . High resolution and separation efficiency (225,378 plates/m for 4-methylbiphenyl) were successfully achieved. Separation of methylbenzene , styrene , ethylbenzene , chlorobenzene , 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, 4-methylbiphenyl, naphthalene , and 4-vinylbipheny in the electro-driven mode confirmed the successful growth of COF-1 on the inner wall of capillary. The developed facile method for the immobilization of COF-1 may pave the way for further application prospects of boron-based COFs.
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Cartilage
·
2021
·
IF 4.634
Yunliang Lei,Jiabin Peng,Zhu Dai,Ying Liao,Quanhui Liu,Jian Li,Yonghui Jiang
ObjectiveThis study was undertaken to elucidate the mechanism of improved chondrocyte migration after juvenile articular cartilage fragmentation.DesignIn vitro organ culture with rabbit cartilage fragments and cell culture with rabbit chondrocytes were performed. In part A, minced juvenile cartilage fragments (~0.5 × 0.5 × 0.5 mm) from rabbits, planted in gelatin sponge and fibrin glue, were cultured for 2, 4, or 6 weeks in vitro and compared with the cartilage chunks (~4 × 4 × 1 mm) and membrane type 1 matrix metalloprotease (MT1-MMP) inhibitor groups. Chondrocyte outgrowth was evaluated on histology and confocal laser scanning microscopy. MT1-MMP expression was compared between the cartilage fragment group and the cartilage chunks group. In part B, articular chondrocytes were harvested from juvenile rabbits, MT1-MMP was transfected into the cells, and cell migration was evaluated using the Transwell and wound healing tests.ResultsThe histology and confocal microscopy results revealed that cell accumulation occurred at the edge of cartilage fragments, and outgrowth was better in the cartilage fragment group than those in the cartilage chunks group. Similar results were observed for MT1-MMP expression. After MT1-MMP inhibition, cells did not accumulate at the edge of the cartilage fragments, and chondrocyte outgrowth did not occur. Furthermore, overexpression of MT1-MMP enhanced the migration of articular chondrocytes.ConclusionsJuvenile articular cartilage fragmentation improved chondrocyte migration by upregulating MT1-MMP.
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INTERNATIONAL JOURNAL OF CHEMICAL KINETICS
·
2021
·Vol. 54
·期 2
·71-80
·
IF 1.462
Yufei Yang,Yadong Zhang
In this work, a HPW/ZSM-5 catalyst was prepared by impregnating phosphotungstic acid (HPW) with carrier ZSM-5 zeolite and characterized by XRD, SEM, N 2 adsorption/desorption isotherm, NH 3 -TPD, and FT-IR techniques. The catalytic performance of HPW/ZSM-5 was investigated by using the decomposition reaction of cyclohexylbenzene-1-hydroperoxide (CHBHP) to phenol and cyclohexanone. The conversion rate of CHBHP was up to 97.28%. In addition, the reusability test exhibited that the high durability HPW/ZSM-5 as the conversion rate of CHBHP only decreased by 3.11% after five runs. The kinetic study of the decomposition reaction indicated it was a primary reaction. The apparent activation energy of the decomposition reaction was 102.39 kJ·mol –1 in the temperature range of 45–60℃. All results indicate that the HPW/ZSM-5 catalyst has good performance and promising applications in acid catalyzed organic chemistry.
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JOURNAL OF CONTROLLED RELEASE
·
2021
·
IF 9.776
Mengshi Jiang,Bing Qin,Lihua Luo,Xiang Li,Yingying Shi,Junlei Zhang,Zhenyu Luo,Chunqi Zhu,Guannan Guan,Yongzhong Du,Jian You
The hypoxic tumor microenvironment (TME) hinders the effectiveness of immunotherapy . Alleviating tumor hypoxia to improve the efficacy of immune checkpoint inhibitors (ICIs) represented by programmed cell death protein 1 (PD-1) antibody has become a meaningful strategy. In this study, we adopted three methods to alleviate hypoxia, including direct oxygen delivery using two different carriers and an indirect way involving HIF-1α inhibition. Both in vivo and in vitro experiments showed that liposomes modified with perfluorocarbon or hemoglobin ( [email protected] or [email protected] ) were able to efficiently load and release oxygen, relieving tumor hypoxia. However, the gas release behavior of [email protected] was uncontrollable, which might induce acute hyperoxia side effects during intravenous injection and reduce its biosafety. In contrast, whether administered locally or systemically, [email protected] revealed high animal tolerance, and was much safer than commercial HIF-1α inhibitor (PX-478), displaying prospects as a promising oxygen carrier for clinical practice. Pharmacodynamic experiments suggested that [email protected] helped PD-1 antibody break the therapeutic bottleneck and significantly inhibited the progression of 4 T1 breast cancer. But in CT26 colon cancer , the combination therapy failed to suppress tumor growth. After in-depth analysis and comparison, we found that the ratio of M1/M2 tumor associated macrophages (TAMs) between these two tumor models were dramatically different. And the lower M1/M2 ratio in CT26 tumors limited the anti-tumor effect of combination therapy. In this study, three methods for alleviating tumor hypoxia were compared from the perspectives of biosafety, efficacy and clinical applicability. Among them, [email protected] stood out, and its combined use with PD-1 antibody exhibit a distinct synergistic suppression effect on tumors with more M1 macrophages presented in the microenvironment. Our work provided a good reference for improving the efficacy of PD-1 antibody by alleviating tumor hypoxia.
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