Frontiers in Chemistry
·
2024
·
IF 3.8
Zhenghua Zhang,Yang Tian,Wenjun Gao,Yubin Hu,Liangping Luo,Lichang Lei,Shasha Shen,Dan Han
Objectives: Immune checkpoint inhibitors (ICIs) have demonstrated potential in inhibiting the growth of malignant pleural mesothelioma (MPM), and their efficacy is associated with the expression of programmed death-ligand 1(PD-L1). This study evaluated a PD-L1-targeted nanoprobe for detecting PD-L1 expression in a nude mouse model of malignant pleural mesothelioma (MPM).Methods: A PD-L1-binding peptide (WL-12) was conjugated with superparamagnetic iron oxide nanoparticles (SPIONs) to create the nanoprobe WL-12@Fe₃O₄. The nanoprobe’s stability, biotoxicity, targeting ability, and in vivo magnetic resonance (MR) imaging effects were assessed and compared to non-targeted Fe₃O₄ nanoparticles. ΔT2 values and PD-L1 expression were measured in H226 and MSTO-211H tumor tissues over 4 weeks to analyze correlations.Results: The WL-12@Fe₃O₄ nanoprobe demonstrated uniform distribution and a spherical shape, with a larger size (43.82 nm) and lower surface potential (−9.34 ± 0.54 mV) compared to Fe₃O₄ (32.67 nm, −20.20 ± 0.88 mV, P < 0.05). The XPS and FT-IR analysis results indicate the successful coupling of WL-12 with Fe3O4. It was well dispersed in serum and saline and showed no cytotoxicity or organ damage in vivo. The probe selectively accumulated in PD-L1-expressing MPM cells, especially MSTO-211H, and exhibited significantly higher uptake in high PD-L1-expressing H460 cells (930.22 ± 11.75 ng/mL) compared to low PD-L1-expressing A549 cells (254.89 ± 17.33 ng/mL, P < 0.05). Tumor iron levels in the WL-12@Fe₃O₄ group were significantly elevated (141.02 ± 17.33 μg/g) compared to controls (36.43 ± 3.56 μg/g, P < 0.05), with no significant differences in other organs (P > 0.05). The T2 values of H226 and MSTO-211H tumors decreased after probe injection, with ΔT2 values significantly higher in the targeted group than the nontargeted group (P < 0.05). ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05).Conclusion: The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.
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Arabian Journal of Chemistry
·
2024
·
IF 5.3
Xiaohai Chen,Fengsheng Hong,Hualu Wu,Yuxin Shen,Hailun Xia,Ren-ai Xu,Lu Shi
The primary objective of this study was to investigate the effects of baicalein and fangchinoline on the metabolism of abemaciclib. We hypothesized that these two natural compounds could significantly affect the metabolism of abemaciclib by inhibiting the activity of the CYP3A4 enzyme, thus potentially increasing its concentration in the body. In vitro , rat liver microsomes (RLM) and human liver microsomes (HLM) were employed to explore the inhibitory effects and mechanisms of baicalein and fangchinoline on abemaciclib. In vivo , twelve healthy male Sprague-Dawley (SD) rats were randomly assigned to three groups: Group A (control group), Group B (baicalein), and Group C (fangchinoline). The concentrations of abemaciclib and its metabolite N-desethylabemaciclib (M2) were evaluated using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Finally, molecular docking method was employed to understand the interaction between abemaciclib and baicalein. It was indicated by the in vitro findings that both baicalein and fangchinoline inhibited abemaciclib metabolism in RLM through a mixed mechanism of competitive and non-competitive inhibition pathway. In HLM, baicalein inhibited abemaciclib metabolism by employing a hybrid mechanism of uncompetitive and non-competitive inhibition, while fangchinoline exhibited its inhibition in a competitive manner. In vivo , pharmacokinetic experiments revealed significant increases for AUC (0-t) and AUC (0-∞) of abemaciclib in Group B and Group C when compared to Group A, while the plasma clearance (CLz/F) of abemaciclib exhibited significant reductions. Moreover, molecular docking studies showed that both abemaciclib and baicalein docked to the active pocket of CYP3A4. This study demonstrated that the co-administration of baicalein or fangchinoline significantly affected the metabolism of abemaciclib, providing valuable insights for its clinical application.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2024
·
IF 4.5
Jinxue Cao,Yaping Xiu,Siqi Wang,Fangling Wu,Ji Li,Dongkai Wang
Andrographolide (AG) is known as a "natural antibiotic". It has been clinically developed into capsules, dropping pills, disperse tablets, etc., for the treatment of viral and bacterial upper respiratory tract infections. It has poor water solubility, obvious P-glycoprotein efflux, and low bioavailability, so its wide application in clinical practice is limited. In this work, a novel AG dry powder inhaler (AG-DPI) was developed using experimental design to optimize the prescription and spray-drying process to obtain higher local concentrations in the lungs while lowering the administered dose; avoiding hepatic first-pass effects and gastrointestinal p-glycoprotein efflux. The short-term local anti-inflammatory effects in the lungs were evaluated using a rat model of acute pneumonia compared with oral administration. The prepared AG-DPI showed that (1) it had good aerosolization properties and was suitable for pulmonary administration, with emitted doses >90%, and fine particle fractions >60%; (2) it was superior to oral administration in the assessment of local anti-inflammatory effects in the lungs by acting on acute pneumonia. This study provides some theoretical value and reference for the inhalable dry powder of AG as a potential targeted treatment modality for lung diseases and infections.
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MACROMOLECULES
·
2024
·
IF 5.1
Xinru Guo,Fei Gao,Fengbiao Chen,Yujun Cheng,Wang Li,Liang Shen,Yinjun Chen
An effective and accurate strategy for tailoring the dynamic properties of covalent adaptable networks (CANs), which relies on the capability to trigger bond rearrangements within the polymer network, involves the precise control of the material’s microstructure through molecular-scale structural design. Herein, we propose a novel approach to modulate the dynamics of vinylogous bonds by changing the adjacent chemical moieties of the functional monomers, thereby enabling reversible exchange reactions with alcoholic hydroxyl groups. Vinylogous bonds-modified carbonyl group (vinylogous ester bond) revealed dynamic behavior at a lower temperature than vinylogous bonds attaching to ester motif (vinylogous carbonate bond). It was attributed to the extended conjugated region in vinylogous ester moieties. Meanwhile, the dynamic vinylogous ester bonds exhibited a dissociative mechanism, and an association mechanism was offered by vinylogous carbonate motifs. Additionally, CANs composed of a vinylogous ester bond (BPAP–OH) displayed a rapid dynamic feature and a lower activated energy, compared with that of CANs consisting of vinylogous carbonate motifs. Similarly, the shape fixation ratio also indicates comparable dynamic properties. It is noteworthy that BPAP–OH enables degradation in DMSO and recyclability by hot press. This approach offers a versatile tool for tuning the dynamic characteristics of CANs and exploring their potential in various applications.
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MATERIALS & DESIGN
·
2024
·
IF 7.6
Rui Ruan,Behzad Shiroud Heidari,Peilin Chen,Junjie Gao,Ziming Chen,Lianzhi Chen,Euphemie Landao-Bassonga,Yongquan Wang,Lingqiang Chen,Bing Wang,Minghao Zheng
Nacre of Pinctada maxima is a natural biomineralized matrix, appeared 7 million years before hominins. In this study, we converted nacre into a self-setting particle bound with multiple calcium orthophosphates that reassemble mammals’ bone mineral matrices for induction of bone regeneration. The nacre-based calcium orthophosphates composite (NCOC) exhibited a compression strength of 10 MPa, which is superior to human trabecular bone. In vitro bioactivity tests revealed the formation of apatite with nano-porous flake-like crystals on the composite surface that mimic HA structure of a human bone matrix. NCOC demonstrated efficient attachment and proliferation of osteoblast cells, promoting osteogenic differentiation by increasing expressions of RUNX2 and OPN . In vivo studies using rabbit back fascia demonstrated that NCOC displays better bone healing and biocompatibility than conventional bone substitute apatite in critical bone defect models. The degradation of calcium carbonate crystal in vivo does not compromise structural integrity of NCOC. Overall, our data showed that NCOC produced through self-setting reactions, presents advantages such as accelerated biodegradation and osteostimulative properties, making it a promising bone substitute for effective bone regeneration.
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FUEL
·
2024
·
IF 6.7
Shutian Chen,Yating Jian,Yaowei Liu,Zhanying Zhang,Xinlong Li,Qiang Yu
A deep eutectic solvent (DES) system of ChCl-MeOH-AlCl 3 ·6H 2 O was developed for simultaneous dissolution of lignin from Evodia lepta residue and in-situ hydrogenolysis of lignin to aromatic phenol ketones using a Ru-C catalyst. The use of this DES led to a delignification of reached 93.1 % and cellulose and hemicellulose retentions of 95.3 % and 47.8 % respectively at the molar ratio of 1:12:0.2. While the total aromatic phenol ketones yield reached 92.4 % under 130 °C for 3 h with 17.2 % yields of vanillyl methyl ketone, 9.1 % syringylacetone, 25.4 % dihydroeugenol, and 40.7 % 4-propyl-2,6-dimethoxyphenol. The improved Ru-C properties in the DES system like thermal stability, the specific surface area and reduction potential contributed on the exceptional high product yields. The aromatic phenol ketones were 312.5 % higher than the reported yields of hydrogenolysis of aromatic monomers by ethanol/1,4-dioxane/formic acid under 300 °C–2 h conditions.
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ENVIRONMENTAL ENTOMOLOGY
·
2025
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IF 1.5
Yang Jie,Wen Xi,Huang Xingrui,Zou Jie,Lu Yun,Yuan Fang,Xiao Sijie,Tang Xiaochao,Liu Zhixiao,Wu Zhengwei,Huang Xinglong
Pesticides released into the environment are increasingly recognized as a global threat to freshwater ecosystems because of their adverse effects on non-target organisms, particularly aquatic insects and other arthropods. Superoxide dismutases (SODs) are important antioxidant enzymes that play a crucial role in protecting organisms from oxidative stress induced by harmful materials. In this study, we identified 2 cellular SODs (PxSOD1 and PxSOD2) in Protohermes xanthodes Navás (Megaloptera: Corydalidae), an freshwater predatory insect, and determined the oxidative stress induced in P. xanthodes larvae by sublethal exposure to chlorpyrifos (CPF). PxSOD1 and PxSOD2 are members of the cytoplasmic Cu/ZnSODs and mitochondrial MnSODs, respectively, and differ substantially in protein structure. Both PxSOD1 and PxSOD2 recombinant proteins demonstrated catalytic activity toward O2•− in the activity assays. After exposure to sublethal concentrations of CPF, malondialdehyde (MDA) content and SOD activities were increased in P. xanthodes larvae in a dose-dependent manner. PxSOD1 expression was decreased in the 0.42 and 4.2 μg/L CPF groups and increased in the 4.2 μg/L CPF group. PxSOD2 was upregulated by 0.42, 4.2, and 8.4 μg/L CPF treatments and the expression levels in the 4.2 and 8.4 μg/L CPF groups were significantly higher than that in the no CPF control. Our results suggest that sublethal concentrations of CPF can induce oxidative stress in P. xanthodes larvae, and the cellular SODs in P. xanthodes larvae may contribute to the protection against CPF-induced oxidative stress.
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Journal of Physical Chemistry C
·
2024
·
IF 3.3
Zhi-Qiang Wang,Wanjun Guo,Shengchao Jia,Yaxuan Jing,Shiting Li,Yong Guo,Xiaohui Liu,Xue-Qing Gong,Yanqin Wang
The selective production of primary amines through reductive amination has received increasing attention due to their extensive applications, while efficient reductive amination is still challenging. Herein, a novel strategy was developed to realize the efficient reductive amination of carbonyl compounds with NH3 via d–d orbital coupling strategies in RuCo alloys. The designed series of RuCo alloy catalysts not only exhibited excellent performance in conversion of various substrates but also demonstrated universal applicability across different supports. The key role of RuCo alloy is its unique ability to effectively catalyze the ammonolysis of a Schiff base, the rate-determining step in reductive amination. Theoretical studies reveal that the d–d orbital coupling strategies break the five d orbital equivalent contributions of metal (Co or Ru) atoms, and the d orbitals primarily contribute through the dz2 and dx2-y2 orbitals of Ru and the dz2 orbital of Co on the RuCo(001) surface, which significantly driving the homolytic NH3 dissociation during the ammonolysis of the Schiff base. Furthermore, stable Co–H covalent bond species and RuCo-NH2 half-ionic and half-covalent bond species on the RuCo(001) surface were generated with lower energy levels. This work not only achieves efficient reductive amination but also provides an atomic orbital-level understanding of the d–d orbital coupling strategies for heterogeneous catalysis.
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JOURNAL OF HAZARDOUS MATERIALS
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2017
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IF 6.065
Mingming Sun,Mao Ye,Wentao Jiao,Yanfang Feng,Pingfeng Yu,Manqiang Liu,Jiaguo Jiao,Xiaojia He,Kuan Liu,Yuanchao Zhao,Jun Wu,Xin Jiang,Feng Hu
The emerging mixed contamination of antibiotics and microplastics in greenhouse soil has made the control of antibiotic resistant gene (ARG) transmission a novel challenge. In this work, surfactant sophorolipid was applied to enhance the dissipation of tetracycline (TC) and tet genes in the presence of microplastics in greenhouse soil. During 49 days of incubation, soil bacteria and phages were both found to be the crucial reservoirs of ARGs. Meanwhile, microplastic’s presence significantly inhibited the dissipation of TC and ARGs in the soil. However, sophorolipid application was proved to outweigh the negative impact caused by microplastic existence, and lead to the highest dissipation of soil TC and ARGs. Significant positive correlation was detected between the dissipation rate of water-soluble and exchangeable TC content and bacteria/phage co-mediated ARG levels. This also held true between the two fractions of soil TC and the ratio of ARG level in the bacteria to that in the phages (B ARGs /P ARGs ). The opposite impacts of microplastic presence and sophorolipid amendment on the TC/ARG dissipation found in this work provides new information for understanding ARG transmission between bacteria and phages in the mixed contaminated greenhouse soil.
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Toxins
·
2017
·Vol. 9
·期 8
·249
·
IF 3.03
Kai Wang,Dongju Lin,Xiucai Guo,Wenlin Huang,Jiang Zheng,Ying Peng
Diosbulbin B (DIOB), a hepatotoxic furan-containing compound, is a primary ingredient inDioscorea bulbiferaL., a common herbal medicine. Metabolic activation is required for DIOB-induced liver injury. Protein covalent binding of an electrophilic reactive intermediate of DIOB is considered to be one of the key mechanisms of cytotoxicity. A bromine-based analytical technique was developed to characterize the chemical identity of interaction of protein with reactive intermediate of DIOB. Cysteine (Cys) and lysine (Lys) residues were found to react with the reactive intermediate to form three types of protein modification, including Cys adduction, Schiff’s base, and Cys/Lys crosslink. The crosslink showed time- and dose-dependence in animals given DIOB. Ketoconazole pretreatment decreased the formation of the crosslink derived from DIOB, whereas pretreatment with dexamethasone or buthionine sulfoximine increased such protein modification. These data revealed that the levels of hepatic protein adductions were proportional to the severity of hepatotoxicity of DIOB.Keywords:diosbulbin B;hepatotoxicity;protein covalent binding;metabolic activation;bromine-based analytical technique
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Environmental Technology & Innovation
·
2024
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IF 6.7
Di Ju,Chao Hu,Yuntong Lv,Yuting Li,Ping Gao,Xueqing Yang
The insecticide resistance development poses challenges to the pest control effectiveness. As phase III detoxification enzyme, ATP-binding cassette (ABC) transporters play a crucial role in conferring resistance by facilitating the elimination of insecticides. However, the precise involvement of ABCs in insecticides metabolism remains unclear. In this study, a competitive assay utilizing microinjection of the ABC substrate Texas Red (TR) was established in Lepidoptera for the first time to investigate the contribution of ABCs to the detoxification process of Cydia pomonella towards lambda -cyhalothrin (LCT) and abamectin (ABM). Results revealed that the elimination of TR was hindered by ABC inhibitor verapamil, LCT, or a combination of both, implying a shared subsets of ABCs involved in the transportation of TR and LCT. Moreover, the application of ABM alone led to marked inhibition of TR elimination, with verapamil not further exacerbating this inhibitory effect, indicating that ABM exhibited a highly competitive ABC substrate characteristic and has a strong interaction with them. Furthermore, silencing key resistance associated ABC genes through RNAi resulted in increased mortality of larvae under LCT or ABM exposure, affecting TR elimination and ATP hydrolysis. These findings imply that ABC genes are critical for the active transport function of ABCs energized by ATP, ultimately reducing larvae tolerance to insecticides. In conclusion, our findings not only validated the feasibility of a competitive bioassay using fluorescent ABC substrate in lepidopteran larvae but also highlighted that ABCs in enhancing the efflux capacity of C. pomonella larvae, facilitating the binding and transportation of insecticides and their metabolites.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
·
IF 4.9
Dongxu Zhang,Xin Wang,Cheng Liu,Lechun Song,Huiyuan Li,Qiyu Huang,Jianfeng Zhang
Hydrate formation is one of the major flow assurance issues for the subsea multiphase pipelines. The effects of the interaction between heavy fractions of crude oil components on hydrate behaviors are still not well understood. In this study, the effects of resins on hydrate formation behaviors in asphaltene-containing emulsions were investigated using a high-pressure reactor apparatus. The results indicated that both resins and asphaltenes inhibited hydrate nucleation and increased the induction time. Furthermore, considerable synergistic effects of asphaltenes and resins on the hydrate formation behaviors were discovered in the water-in-oil emulsions, depending on the aggregation state of asphaltenes. The addition of resins was observed to disperse the asphaltene aggregates significantly and enhance the inhibitory effect of asphaltenes on hydrate nucleation. Additionally, the calculated results of gas consumption showed that the presence of resins can decrease the growth rate of hydrates in the asphaltene-containing emulsions. A potential mechanism was presented to illustrate how resins affect hydrate formation in an emulsion with varying asphaltene aggregation states. These findings offer a better knowledge of the synergistic effects between the heavy components of resins and asphaltenes and have potential application in the hydrate management of crude oil pipelines.
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