MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Xudong Xie,Tiantian Sun,Heyu Pan,Dongliang Ji,Zhongyuan Xu,Ge Gao,Jiefei Miao,Lei Wang,Yanan Zhang,Ji Liu,Yong Ling,Xing Su
Chemo-photodynamic therapy is a treatment method that combines chemotherapy and photodynamic therapy and has demonstrated significant potential in cancer treatment. However, the development of chemo-photodynamic therapeutic agents with fewer side effects still poses a challenge. Herein, we designed and synthesized a novel series of β-carboline/furylmalononitrile hybrids 10a–i and evaluated their chemo-photodynamic therapeutic effects. Most of the compounds were photodynamically active and exhibited cytotoxic effects in four cancer cells. In particular, 10f possessed type-I/II photodynamic characteristics, and its 1O2 quantum yield increased by 3-fold from pH 7.4 to 4.5. Most interestingly, 10f exhibited robust antiproliferative effects by tumor-selective cytotoxicities and hypoxic-overcoming phototoxicities. In addition, 10f generated intracellular ROS and induced hepatocellular apoptosis, mitochondrial damage, and autophagy. Finally, 10f demonstrated extremely low acute toxicity (LD50 = 1415 mg/kg) and a high tumor-inhibitory rate of 80.5% through chemo-photodynamic dual therapy. Our findings may provide a promising framework for the design of new photosensitizers for chemo-photodynamic therapy.
研究领域:
药理学
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肿瘤学
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生物化学
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IEEE SENSORS JOURNAL
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2026
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IF 4.5
Chengzhang Han,Jinli Li,Zhenyu Wang,He Lv,Yusuf Suleiman Dambatta,Jingjie Dai
Cardiovascular diseases remain a leading cause of death worldwide, with acute myocardial infarction (AMI) accounting for a significant proportion of fatalities. The rapid and accurate detection of cardiac troponin I (cTnI) is critical for early diagnosis of AMI. We report an innovative, highly sensitive, solidly mounted resonator (SMR) biosensor based on a c-axis-tilted scandium-doped aluminum nitride (Sc0.1Al0.9N) film for label-free cTnI detection. The SMR device, fabricated by magnetron sputtering and incorporating an acoustic Bragg reflector, is designed to operate in the shear acoustic mode. The sensor demonstrates a quality factor of 2030 and an effective electromechanical coupling coefficient of 2.6%. Functionalized with a self-assembled monolayer and monoclonal antibodies, the sensor achieves a detection limit of 3 pg/mL for cTnI in serum, with a rapid response time of 100 s and high selectivity against common interferents. The device also exhibits significant potential for integration with CMOS electronics, supporting the development of miniaturized, point-of-care (POC) diagnostic systems for cardiovascular diseases.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Jinying Shi,Zhendong He,Yifan Xu,Wen Chen
Ethylene is a crucial gaseous phytohormone that regulates diverse aspects of plant growth and development. In Arabidopsis thaliana , perception of ethylene is mediated primarily by ETHYLENE RESPONSE 1 (ETR1), a prototypic membrane protein that couples ligand sensing to signal transduction through a transmembrane copper cofactor-dependent ethylene-binding site and a cytoplasmic histidine kinase domain. Previous work established that ETR1 binds copper and forms covalent homodimers, but the functional significance of its dimeric architecture in signal transduction has remained elusive. In this study, we expressed and purified full-length ETR1 from Pichia pastoris, enabling the systematic dissection of its oligomeric state, copper redox chemistry, and ligand binding effects. Using an in vitro luminescent kinase assay, we demonstrate that the Cu(I)-ethylene complex strongly suppresses ETR1 autophosphorylation, but only when the receptor is in its disulfide-linked dimer form. Monomeric ETR1 generated by reductive cleavage retained basal kinase activity yet was insensitive to ethylene. Furthermore, the ethylene antagonists Ag + and 1-MCP reversed the ligand-induced suppression. Mutational analysis revealed that the H353Q variant lacked kinase activity, while the C65S/H69A double mutant retained basal activity but was resistant to ethylene-induced inhibition, implicating both the catalytic histidine residue and the copper-binding site in the regulatory mechanism. Together, these findings establish that ETR1 functions as a dimer-dependent ethylene sensor, in which covalent dimerization is essential for allosteric coupling between the ligand-binding and kinase domains. This work thus provides a definitive biochemical model for ethylene perception and offers a robust platform for future structural and mechanistic studies of plant membrane-receptor signaling.
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JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Yanming Xia,Lixin Hu,Yuhan Hu,Shihao Wang,Qingqing Xiong,Xiaohu Wang,Yiqun Li,Lifang Yin,Jian Wang,Suxin Li
The stimulator of interferon genes (STING) has emerged as a promising target for cancer immunotherapy. However, STING agonists alone have demonstrated limited clinical success. Indoleamine 2,3-dioxygenase 1 (IDO1) has been implicated as a key resistance mechanism that undermines the antitumor effects of STING activation, yet the cell-type-specific roles and the combined impact of STING and IDO1 on tumor immune orchestration remain poorly understood. In this study, we report that a co-delivery nanosystem of STING agonists and IDO1 inhibitors, rather than their simple combination, yields synergistic antitumor responses. This nanomedicine exhibits tropism toward myeloid cell populations in vivo , particularly dendritic cells (DCs), and facilitates pH-responsive cytosolic delivery of both agents. As a result, it enhances antigen cross-presentation, DC maturation, and cytokine secretion, driving effective priming of cytotoxic T lymphocytes. Compared to monotherapies or physical nanoparticle combinations of STING agonists and IDO1 inhibitors, this two-in-one nanomedicine significantly suppresses tumor growth and confers a survival benefit. Depletion of STING in the host ( Tmem173 −/− mice) or deficiency in type I conventional DCs (cDC1s, Batf3 −/− mice) abolishes therapeutic efficacy, whereas depletion of STING in tumor cells exerts minimal impact. A bone marrow chimera experiment further supports the STING-cDC1 dependence. Its capability to overcome tumor resistance and the underlying mechanism were further investigated in a well-established tumor model. Our findings highlight the cooperative role of STING activation and IDO1 blockade within cDC1s and introduce an integrated drug delivery system to combat immune tolerance in cancer therapy.
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CHEMISTRY OF MATERIALS
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2022
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IF 10.508
Wen Ma,Jinlin Yin,Xinfeng Chen,Chen Sun,Xueling Song,Honghan Fei
Organometal halide hybrids are an emerging class of single-component white-light emitters originating from self-trapped excitons (STEs), showing many promising attributes such as intrinsic nature and a high color-rendering index (CRI). However, one challenge is to develop rational synthetic strategies to tune the photoluminescence properties on a molecular level. Herein, for the first time, we report the isostructural postsynthetic incorporation of NH3 into organometal halide crystalline materials to enhance the STE-based warm white-light emission, affording substantially increased photoluminescence quantum yields (PLQYs) from 5–5.5 to 60–75%. The NH3-incorporated CuI–halide hybrids are rare examples of lead-free single-component yellowish white-light emitters with high PLQYs and a high CRI of 64–72. The single-crystal-to-single-crystal transformation is monitored by X-ray crystallography and density functional theory calculations, suggesting that the incoming NH3 molecules serve as spacers to isolate linear CuI–halide species at the excited state to facilitate the exciton confinement. Moreover, the precise modification process is highly reversible and selective over many common gaseous molecules or other amines. The organocopper(I) halide hybrids also feature high structural and emissive stabilities for at least 18 months in air at room temperature, affording a high potential for commercial uses in solid-state lighting. This study demonstrates a potentially general strategy to enhance the STE emission on the molecular level.
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Environmental Science-Nano
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2022
·Vol. 9
·期 9
·3385-3396
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IF 9.473
Yu Luo,Zonglin Weng,Yuanfang Lin,Bin Han,Xinwen Ou,Yang Zhou,Jin Jiang
Thallium (Tl) is an extremely toxic trace element with high bioaccumulation. Selective and ultrafast Tl+ removal from water is critical to the safety of water resources but remains a grand challenge. Here, by intercalating KOH into multilayered Ti3C2Tx MXene, an efficient adsorbent with coordination/cation exchangeable sites (KOH@Ti3C2Tx) has been developed for Tl+ removal. Almost 99.6% of Tl+ could be removed over optimal KOH@Ti3C2Tx in just 10 s, and the maximal uptake capacity was up to 238.1 mg g−1, which is 3.8-fold larger than that of the pristine Ti3C2Tx (61.4 mg g−1). Moreover, benefitting from a wider working pH window and excellent selectivity, KOH@Ti3C2Tx could quickly remove almost all Tl+ from actual wastewater, demonstrating great potential for water purification. Control experiments and calculations jointly demonstrated that the boosted performance can be attributed to the synergistic effect of the abundant hydroxyl groups and exchangeable K+ sites, in which the hydroxyl groups can capture Tl+via coordination while the K+/Tl+ cation exchange contributes to selectivity and fast uptake kinetics. This work highlights the interaction mechanism of active sites and metal ions, providing fundamental guidance to the selective and rapid removal of heavy metals from water, especially in emergency disposal of heavy metal pollution accidents.
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Acta Biomaterialia
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2022
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IF 10.633
Liyue Zhou,Qiangwei Liang,Yifan Li,Yongjing Cao,Juan Li,Jiayu Yang,Jinxia Liu,Jiawei Bi,Yanhua Liu
Liver fibrosis is a pathological process of multiple chronic liver diseases progressing to cirrhosis for which there are currently no effective treatment options. During fibrosis progression, the overproduction of extracellular matrix (ECM) collagen secreted by hepatic stellate cells (HSCs) greatly impedes drug delivery and reduces drug therapeutic effects. In this study, a glycyrrhetinic acid (GA)-conjugated prodrug micellar system with collagenase I (COL) decoration (COL-HA-GA, abbreviated as CHG) was designed to codelivery sorafenib (Sora/CHG, abbreviated as S/CHG) for potentiating ECM degradation and HSCs targeting on liver fibrosis therapy. In ECM barrier models established in vitro or in vivo , CHG micelles efficiently degraded pericellular collagen and demonstrated enormous ECM penetration abilities as well as superior HSCs internalization . Moreover, CHG micelles exhibited more Sora & GA accumulations and activated HSCs targeting efficiencies in the fibrotic livers than those in the normal livers. More importantly, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating the fibrosis-related factors, leading to reverse the fibrotic liver to normal liver through the multi-mechanisms including angiogenesis reduction, liver fibrosis microenvironment regulation, and epithelial-mesenchymal transition inhibition. In conclusion, the developed COL decorated nano-codelivery system with fibrotic ECM collagen degradation and activated HSCs targeting dual-functions exhibited great potential for liver fibrosis therapy. Statement of significance A glycyrrhetinic acid (GA)-conjugated prodrug with collagenase I (COL) decoration (CHG) was designed for codelivery with sorafenib (S/CHG), potentiating extracellular matrix (ECM) degradation-penetration and hepatic stellate cells (HSCs) targeting on liver fibrosis therapy. In ECM barrier models, CHG micelles efficiently degraded pericellular collagen and demonstrated ECM penetration abilities, as well as displayed superior HSCs internalization. Moreover, S/CHG micelles were more effective in anti-liver fibrosis by lowering the collagen content, inhibiting the HSCs activation, as well as down-regulating cytokines, reversing the fibrotic liver to normal through various mechanisms. In conclusion, the developed fibrotic ECM degradation and HSCs targeting dual-functional nano-codelivery system provided a prospective potentiality in liver fibrosis therapy.
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BIOCHEMICAL PHARMACOLOGY
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2022
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IF 6.1
Xin Xie,Ting-ting Shen,Hai-lian Bi,Zhuo-lin Su,Zi-qi Liao,Ying Zhang,Lei Shi,Yun-long Xia
Angiotensin II (Ang II) induced Atrial fibrillation (AF) often accompanied with reduced ATRAP which is a negative modulator of Ang II type 1 receptor (AT1R). Melatonin can protect against AF, but the underlying molecular mechanism remains poorly understood. In this study, Ang II was used to induce AF, and AF inducibility and duration were documented telemetrically. Ang II-infused mice had a higher AF incidence, which was associated with atrial fibrosis, inflammation, and oxidative stress. Melatonin partially inhibited these effects, and enforced expression of siRNA-ATRAP in atria counteracted the beneficial role of melatonin. Specifically, melatonin inhibited expression of Ang II-induced proteasome and immunoproteasome subunits β2, β2i, β5, and β5i as well as their corresponding trypsin-like and chymotrypsin-like activities and blocked ATRAP degradation. In turn, this inhibited AT1R-mediated NF-κB signaling, transforming growth factor (TGF)-β1/Smad signaling in the atria, and thereby affected atrial remodeling and AF. Melatonin receptor inhibition by the chemical inhibitor luzindole partially inhibited the inhibitory effects of melatonin on proteasome activity and also Ang II-induced pathological changes in the atria. Overall, our study demonstrates that melatonin protects against Ang II-induced AF by inhibiting proteasome activity and stabilizing ATRAP expression, and these effects are partially dependent on melatonin receptor activation.
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CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
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2022
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IF 4.175
Qing Liu,Xin Fang,Zeng-Ping Chen,Cai-Xia Shi,Ru-Qin Yu
Herein, the hydrolysis patterns of DNase I against a DNA probe in both single-strand form and DNA/miRNA heteroduplex were experimentally investigated in detail by mass spectrometric technique. Based on the knowledge obtained in the experiments, DNase I-assisted signal amplification strategy was proposed and used to design a mass spectrometric platform for miRNA detection. As a proof of concept, the performance of the proposed platform was evaluated for the detection of miRNA-122 in cell lysate samples. An advanced calibration model was explicitly derived to model the relationships between the concentration of miRNA-122 and the mass spectral signals of mass spectrometrically detected fragments of the DNA probe produced in the DNase I-assisted signal amplification process. With the aid of the advanced calibration model, the proposed mass spectrometric platform achieved quite accurate quantification results for miRNA-122 in cell lysate samples of Huh-7 and HepG-2 cell lines with recovery rates ranging from 98% to 104%. It is noteworthy that the proposed mass spectrometric platform can differentiate the target miRNA from other non-target ones based on their mass spectral response patterns instead of mass spectral intensities, and hence possesses high specificity for the target miRNA. It is reasonable to expect that the combination of mass spectrometry based on DNase I-assisted signal amplification with the advanced chemometric model provides a competitive alternative for designing cost-effective and label-free miRNA detection methods.
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CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Meng-yuan Zhang,Jun Cai
Red dragon fruit peel is a pectin-rich fruit waste that is a potential source of prebiotics and whose different sources and structures will influence its prebiotic function. Thus, we compared the effects of three extraction methods on the structure and prebiotic function of red dragon fruit pectin, the results showed that the citric acid extracted pectin produced a high Rhamnogalacturonan-I (RG-I) region (66.59 mol%) and more side-chains of Rhamnogalacturonan-I ((Ara + Gal)/Rha = 1.25), which can promote bacterial proliferation significantly. The side-chains of Rhamnogalacturonan-I may be an important factor in that pectin can promote the proliferation of B. animalis. Our results provide a theoretical basis for the prebiotic application of red dragon fruit peel.
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PHARMACEUTICAL BIOLOGY
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2022
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IF 3.889
Bo Lu,Jianhua Li,MingTai Gui,Lei Yao,Mingsong Fan,Xunjie Zhou,Deyu Fu
Context Salvianolic acid B (SalB) can attenuate myocardial ischemia/reperfusion (I/R) injury, but the mechanisms are not entirely known.Objective Our study investigates if SalB protects cardiomyocytes against I/R injury by regulating Tripartite motif (TRIM) protein.Materials and methods AC16 cardiomyocytes were treated with I/R, and then with SalB (10, 25 and 50 μM) for 24 h, while control cells were cultured under normal conditions. Female Sprague-Dawley rats were subjected to I/R injury, and then intravenously injected with 20, 40, or 60 mg/kg SalB or saline, as a control, rats received sham operation and saline injection.Results Upon treatment, apoptotic rate, reactive oxygen species (ROS), and malondialdehyde (MDA) were increased 10-, 3.8-, and 1.3-fold, respectively, while superoxide dismutase (SOD) activity was reduced by 62.1% compared to control cells. I/R treatment elevated the mRNA and protein expression of TRIM8. SalB treatment remarkably abolished the above-mentioned effects of I/R treatment. TRIM8 knock-down could partially alleviate I/R-induced myocardial injury. TRIM8 overexpression promoted cardiomyocyte injury, which was alleviated by SalB. Moreover, TRIM8 negatively regulated protein expression of antioxidant enzyme glutathione peroxidase 1 (GPX1). TRIM8 protein interacted with GPX1 and TRIM8 overexpression promoted GPX1 ubiquitnation. GPX1 knock-down abolished the protective effects of SalB on I/R-injured cardiomyocytes. Our in vivo experiments confirmed the effects of SalB on I/R-induced myocardial injury.Discussion and conclusions SalB protected cardiomyocytes from I/R-induced apoptosis and oxidative stress in vitro and in vivo, which was partly mediated by the TRIM8/GPX1 axis. This suggests that down-regulation of TRIM8 expression may ameliorate I/R-induced myocardial injury.
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JOURNAL OF LUMINESCENCE
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2022
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IF 4.171
Xiaobo Hu,Yanqiao Xu,Jiancheng Wang,Jiaxin Ma,Lianjun Wang,Wan Jiang
All-inorganic CsPbX 3 (X=Cl, Br, I) perovskite nanocrystals (NCs) exhibit attractive optoelectronic properties for lighting and displays application but suffer from the lack of profound insights into their reaction kinetics. Herein, a modified ligand-assisted reprecipitation (LARP) method was developed to synthesize high-quality CsPbBr 3 NCs by utilizing oleic acid (OA) and n-octylamine (OTAm) as surface ligands, and the effect of Cs/Pb ratio, precursors and ligands concentration on the structure, morphology and fluorescence properties was systematically investigated. The monodisperse CsPbBr 3 NCs with cubic shape and average particle size of 13.7 nm are obtained by optimizing the reaction parameters. Appropriately increasing the Cs/Pb ratio and precursors concentration to 0.5 and 1.0 mM are favorable for forming a more complete crystal structure with lower defect states density, which can significantly enhance the PL intensity. Notably, the surface defect states of CsPbBr 3 NCs are effectively passivated by the coordinated OA and OTAm ligands, and the maximum photoluminescence quantum yield (PLQY) can reach to 85.2%. Importantly, the effective synthesis of high-quality CsPbBr 3 NCs can be amplified up to 50 times of reaction volume after finely optimizing the reaction parameters. Based on a facile anion exchange process, the CsPbX 3 NCs with variable halogen composition exhibit tunable emission of 443.3∼649.1 nm and a wide color gamut of 117% NTSC standard. This work provides profound sights on the reaction kinetics of perovskite NCs, and further promotes its practical application in optoelectronic field.
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