BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Fengxin Zheng,Jiale Ke,Shiqin Lin,Wenjie Ye,Zhenkun Wu,Yuexin Xu,Suiqing Mai,Yishuang Chen,Zitao Guo,Huazhong Hu,Shuqin Zhang,Jianxin Pang,Qun Zhang,Zean Zhao
Inhibition of human concentrative nucleoside transporter 2 (CNT2) could suppress increases in serum urate levels derived from dietary purines. However, the structural basis for substrate recognition of CNT2 is still unknown and only a few inhibitors have been reported. In this study, a homology model of CNT2 was constructed and residues T315, E316, N426, N491, E492, F536 and N538 were identified as binding sites for adenosine through site-directed mutagenesis and a 3 H-adenosine uptake assay. To explore potential CNT2 inhibitors, a database containing 4704 saccharides and glycosides was constructed, followed by high-throughput virtual screening. The top 20 compounds with the highest docking scores were then evaluated their in vitro activity. Among them, cyanidin-3-O-galactoside (Cy3Gal) demonstrated the most potent inhibitory activity against CNT2, exhibiting an IC 50 value of 9.40 μM. Docking analysis revealed that residues M314, T315, T347, N422, F536 and S541 contributed to a strong binding affinity with Cy3Gal. In addition, Cy3Gal exhibited minimal inhibitory effects on CNT3 and equilibrative nucleoside transporters (ENTs) in vitro . At doses of 5–20 mg/kg, Cy3Gal effectively reduced serum and urine levels of uric acid and adenosine in vivo . The CCK-8 assay revealed that Cy3Gal displayed minimal cytotoxicity to mTEC and hIEC cells at a concentration of 100 μM. The serum CR and BUN levels indicate that Cy3Gal does not exhibit any apparent renal toxicity compared to lesinurad and allopurinol. HE examination showed no noticeable pathological changes in the kidneys or colons after treatment with Cy3Gal. In summary, Cy3Gal could be a CNT2 inhibitor with favorable drugability for the treatment of hyperuricemia.
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Wei Zhu,Pei Zhao,Tingting Liu,Feng Gao,Qi Li,Xin Cai,Man Zhang,Alex Aliper,Feng Ren,Alex Zhavoronkov,Xiao Ding
The dual inhibition of SIK2/3 has been considered as a potential treatment approach for MEF2C-high acute myeloid leukemia (AML). Although diverse scaffolds of pan-SIK or SIK2/3 inhibitors have been reported, few of them showed sufficient in vitro or in vivo antitumor activity. Based on the proposed binding mode of the hit molecule (7), chemical space in the solvent/P-loop region was explored via fragment growing/replacement, supported by the generative chemistry platform. Further SAR exploration and ADME optimization led to the discovery of 7s, which exhibited excellent potency and strong selectivity in MEF2C high-expression cell lines over MEF2C-low cell lines. Moreover, oral administration of 7s was found to demonstrate significant tumor growth inhibition in a MV4-11 AML mice CDX model without any body weight loss. This work highlights the potential of targeting MEF2C-dependent AML by selective oral SIK2/3 inhibitors, which was supported by the generative models.
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高影响因子
CARBON
·
2025
·
IF 11.6
Jin Chen,Pei Liu,Kai Xu,Zhilei Hao,Guohui Tang,Changtian Zhu,Zixuan Ding,Shuai Yin,Zhiqiang Li,Zhen Ding,Yi Wang,Zhanpeng Liu,Siwen Yu,Xing Xin,Fenghua Liu
Na 3 V 2 (PO 4 ) 3 (NVP) material has evolved as a significant candidate for electrode materials in the development of sodium-ion batteries. However, the low conductivity of NVP material leads to low cycling performance, limiting their application in high-efficiency battery materials. To address this issue, this work proposes a novel strategy for materials design through constructing 3D network carbon-coatings on the surface of NVP materials. The carbon-coatings are achieved via a combination of sol-gel technique and heat treatment using pyrolytic carbon (C), carbon nanotubes (CNTs) and graphene (GN). In comparison to NVP@C, the electrochemical properties of NVP@C/GN, NVP@C/CNTs, and NVP@C/GN/CNTs have shown improvements. Among these, NVP@C/GN/CNTs exhibit the most outstanding electrochemical performance in the half-cell test. Specifically, this material demonstrates exceptional cycling stability, with a capacity of 92 mAh g −1 that can be maintained even after 800 cycles at a high-rate performance of 10C, with an attenuation of 10.6 %. The enhanced electrochemical performance is attributed to the specific ternary carbon-coating conductive structure, which significantly shortens the diffusion paths of Na + ions and electrons within NVP, resulting in improved Na + ion and electron transport kinetics. This study provides a new design paradigm for improving the conductivity of cathode material for sodium-ion batteries.
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高影响因子
ACS Applied Polymer Materials
·
2024
·
IF 4.4
Xiaoxu Wang,Longyi Nan,Haoyuan Song,Jiaqi Wang,Shuai Zhang,Yu Cai,Jie Liu,Jianpeng Guo,Liang Fang
In transdermal patches, pressure-sensitive adhesives (PSAs) are considered the most critical excipients due to their ability to provide adhesion and act as a drug reservoir. However, the loaded drugs plasticize the patches, resulting in a cold flow phenomenon, which poses a product safety risk and reduces treatment efficacy. Herein, 3-methacryloxypropyltrimethoxysilane (KH-570)-modified hydroxyl acrylate PSA (AAOK) was proposed. Diclofenac, ketoprofen, tulobuterol, and oxybutynin were selected as model drugs. The results showed that when not loaded with drugs, the performance of AAOK was not significantly different from that of hydroxyl acrylate PSA (AAOH). Interestingly, when loaded with drugs, AAOK automatically forms a cross-linked system through drug catalysis, which exerts a strong antiplasticity without reducing the ability of AAOK to load and deliver the drug. Specifically, the shear strength of drug-loaded AAOK increased by more than 10-fold compared to AAOH. The cold flow area of drug-loaded AAOK was reduced by more than 15-fold compared to commercial DURO-TAK 87-2287. In addition, the “dark ring” phenomenon was not observed with AAOK compared to that with DURO-TAK 87-2287 on the human forearm after drug loading. After loading four model drugs into AAOK, a high drug loading and efficient drug delivery were endowed for AAOK in vitro and in vivo. The molecular mechanism for the improved antiplasticity of the drug-loaded AAOK was that the drug molecules had a catalyzing effect on the self-condensation reactions of KH-570. This study opens up ideas for the investigation of transdermal patches with high antiplasticity and efficient transdermal application.
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高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2024
·
IF 4.1
Lei Wu,Menghan Liu,Yuting Chen,Ming Li,Tingting Yin,Cong Ma,Wei Fan
UF is widely used as a wastewater treatment and recycling technology. However, membrane fouling is still an important factor affecting the wide application. In this study, APIm with positive amino group was adsorbed to the surface of the carboxylated polyacrylonitrile (PAN) membrane by electrostatic force to reduce the fouling of sodium alginate (SA) caused by Ca 2+ . The results show that 1 v/v% APIm was selected as the optimal dosage, accompanied by the highest water flux of 330.5 L·m -2 h −1 bar −1 and bovine serum albumin (BSA) rejection rate of 91.0 %. When the concentration of Ca 2+ was increased to 10 mM, the Ca 2+ catch amount increased to 48.25 mg/cm 2 . The main anti-fouling mechanism was that APIm captured a certain amount of Ca 2+ in situ, destroyed the complex structure of sodium alginate (SA) and Ca 2+ . Then the fouling layer was easy to be removed by physical cleaning. At the concentration of 10 mM Ca 2+ , the membrane flux recovery rate of 1 v/v% APIm membrane was increased to 80.1 %. This study demonstrates a fouling control strategy for in-situ removal of Ca 2+ bound SA fouling, providing a new approach for the future development of UF membrane.
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高影响因子
Biomedical Materials
·
2024
·Vol. 19
·期 5
·055026
·
IF 3.9
Yu Yan,Aijia You,Xianxian Chen,Wenyi Huang,Xiaoting Lu,Cuijin Gu,Sen Ye,Jun Zhong,Haiting Huang,Yao Zhao,Yu Li,Chun Li
(+)4-cholesten-3-one has been proved to have potential wound healing effect in the process of wound regeneration. This study aimed to evaluate the effect of (+)4-cholesten-3-one/sodium alginate/gelatin on skin injury and reveal its potential molecular mechanism. First, we prepared sodium alginate/gelatin hydrogel (SA/Gel hydrogel) with different ratios and tested their characteristics. Based on these results, different concentrations of (+)4-cholesten-3-one were added into SA/Gel hydrogel. A full-thickness skin injury model was successfully established to evaluate wound healing activity in vivo. HE staining and Masson staining were used to evaluate the thickness of granulation tissue and collagen deposition level. Immunohistochemical staining and immunofluorescence staining were applied to detect the level of revascularization and proliferation in each group of wounds. Western blot, quantitative-PCR and immunofluorescence staining were used to detect the expression of proteins related to Wnt/β-catenin signaling pathway in each group of wounds. In vitro results showed that the hydrogel not only created a 3D structure for cell adhesion and growth, but also exhibited good swelling ability, excellent degradability and favorable bio-compatibility. Most importantly, in vivo experiments further indicated that (+)4-cholesten-3-one/SA/Gel hydrogel effectively enhanced wound healing. The effectiveness is due to its superior abilities in accelerating healing process, granulation tissue regeneration, collagen deposition, promoting angiogenesis, tissue proliferation, as well as fibroblast activation and differentiation. The underlying mechanism was related to the Wnt/β-catenin signaling pathway. This study highlighted that (+)4-cholesten-3-one/SA/Gel hydrogel holds promise as a wound healing dressing in future clinical applications.
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高影响因子
Soft Matter
·
2011
·Vol. 7
·期 11
·5200-5207
·
IF 4.457
Xi-Lian Wei,Zeng-Bin Wei,Xiu-Hong Wang,Zhong-Ni Wang,De-Zhi Sun,Jie Liu,Huai Hua Zhao
The aqueous mixtures of an anionic surfactant (sodium dodecyl benzene sulfonate, SDBS) and an ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate, [Bmim]BF4) within a certain range of compositions can spontaneously separate into two immiscible aqueous phases (ATPS): one surfactant-rich and the other ionic liquid-rich. The phase diagrams of the ternary system of the SDBS/[Bmim]BF4/water were drawn based on experimental data determined at 10.0, 20.0 and 30.0 °C, respectively. The borderlines of the different specific regions in the diagrams were determined using turbidity titration method. The narrow two-phase region aqueous were found to be close to the water - [Bmim]BF4 side. The formation conditions, compositions, and physicochemical properties of the aqueous two phases have been studied. The effects of temperature, surfactant and ionic liquid content on the phase separation time and phase volume ratio of the ATPS were also investigated. This phase separation phenomenon was found to be likely due to the existence of micelle aggregates with quite large size obtained by Transmission Electron Microscopy (TEM) and Steady-state Fluorescence Quenching Measurements (SFQM) methods.
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高影响因子
Neural Regeneration Research
·
2024
·Vol. 19
·期 10
·2270
·
IF 5.9
Qi Yize,Zhou Yao,Li Jiyang,Zhu Fangyuan,Guo Gengni,Wang Can,Yu Man,Wang Yijie,Ma Tengfei,Feng Shanwu,Zhou Li
Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.
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高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Jinkui Wang,Tong Bu,Qianqian Cui,Zizhe Li,Qing Xu,Zhixian Jiang,Yexuan Mao,Xianqing Huang,Lianjun Song,Dapeng Peng,Xiya Zhang
Simultaneous detection of carbofuran (CBF) and 3-hydroxy carbofuran (3-OH-CBF) in fruits and vegetables is important due to their high toxicity and widespread use in pest control. However, most lateral flow immunoassay (LFA) approaches only detection CBF. To overcome this limitation, two haptens, 6-((2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)oxy)hexanoic acid and 6-((((2,2-dimethyl-2,3-dihydroben zofuran-7-yl)oxy)carbonyl)amino)hexanoic acid, named H1 and H2, were designed for broad-spectrum antibody detection of CBF and 3-OH-CBF. The highly specific monoclonal antibody (mAb) 3F4 based on hapten H1 only recognized CBF, while broad-spectrum mAbs 1D3, 6B7 and 6E8 based on hapten H2 recognized both compounds. The carbon bond to the hydroxyl group of 3-OH-CBF adopts a 28.55° angle relative to the same carbon bond of CBF, explaining the specificity of the H1-based mAb against CBF. After optimizing the antigen-antibody combination, a sensitive colloidal gold-LFA (CG-LFA) strip was constructed based on mAb 1D3 and H2-BSA for CBF and 3-OH-CBF detection following simple sample pretreatment. The established LFA had a limit of detection of 0.49–6.63 ng/mL, and adequate recoveries (69.3–105.7 %) for CBF and 3-OH-CBF in 26 fruit and vegetable samples.
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高影响因子
CERAMICS INTERNATIONAL
·
2024
·
IF 5.1
Shuangyin Zhu,Shilin Jin,Jiamin Chen,Tao Pang,Lingwei Zeng,Lei Lei,Fengluan You,Daqin Chen
Greenlight is a sensitive band of the human eye, improving the luminous quality of the green part is crucial to the performance improvement of LED. However, the application prospects for Tb 3+ are greatly limited by its 4f-4f forbidden transition. In this study, we successfully synthesized Ba 2 MgY 2 (BO 3 ) 3 :Ce 3+ blue phosphor which effectively enhances its luminous properties through energy transfer. By introducing both Ce 3+ and Tb 3+ into the Ba 2 MgY 2 (BO 3 ) 3 matrix, an energy transfer efficiency of 50.6 % is achieved between these two ions, resulting in a remarkable 13.1-fold increase in Tb 3+ luminous intensity. The internal quantum efficiency (IQE) of the sample is measured at 63 %, while the external quantum efficiency (EQE) reaches 30 %. Furthermore, it exhibits good thermal stability and promising applications in temperature sensing due to the sensitivity and coordinated luminescence of Ce 3+ and Tb 3+ ions at different temperatures. Finally, when combined with a 365 nm chip, this sample produces a white LED (WLED) with a color rendering index (CRI) of 81.6 and a correlation color temperature (CCT) of 4330 K.
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高影响因子
Crystals
·
2024
·Vol. 15
·期 1
·31
·
IF 2.4
Zhongran Yao,Fen Qi,Qiang Sun,Lin Ye,Xiaowei Yang,Guojie Chao,Pei Tang,Kongjun Zhu
Lithium-conducting NASICON materials have emerged as a promising alternative to organic liquid electrolytes for high-energy-density Li-metal batteries, owing to their superior ionic conductivity and excellent air stability. However, their practical application is hindered by poor sintering characteristics and high grain boundary resistance. In this investigation, Li1.3Al0.3−xYxTi1.7(PO4)3(LAYTP-x,x= 0.00, 0.01, 0.03, 0.05, and 0.07) were successfully synthesized via conventional solid-state reaction to explore the impact of Y3+on both ionic conductivity and chemical stability. The structural, morphological, and transport properties of the samples were comprehensively characterized in order to identify the optimal doping concentration. All samples exhibited a NASICON structure with a uniform distribution of Y elements within the electrolyte. Due to its highest relative density (95.8%), the LAYTP-0.03 electrolyte demonstrated the highest total conductivity of 2.03 × 10−4S cm−1with a relatively low activation energy of 0.33 eV, making it suitable for solid-state batteries. When paired with the NCM811 cathode, the Li/LAYTP-0.03/NCM811 cell exhibited outstanding electrochemical performance: a high capacity of 155 mAh/g was achieved at 0.2C after 50 cycles with a Coulombic efficiency of approximately 100%, indicating highly reversible lithium plating/stripping facilitated by the LAYTP-0.03 electrolyte. These results suggest that the LAYTP-0.03 ceramic electrolyte could be a promising alternative for developing safe solid-state Li-metal batteries.
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高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·Vol. 31
·期 12
·e202403915
·
IF 3.7
Qi Pan,Wanliang Yang,Chen Wu,Dongjia Xie,Yuan Wang
Graphical A ploy(1,3-dioxolane) (PDOL) layer was constructed by a Al(OTf) 3 -induced in-situ solidification process between the interface of LATP and anode/cathode. The as-prepared PDOL as an “interfacial adhesive” can fill the gap between the LATP and the electrode, providing a better interfacial contact and reduced interfacial impedance. Such interfacial adhesive layer not only effectively prevents Li metal from reducing LATP but also provides intimate interface contact and limits unnecessary electron transport. Li 1.3 Al 0.3 Ti 1.7 (PO 4 ) 3 (LATP) as the solid-electrolyte has attracted much attention for Li-ion batteries. However, the unstable LATP/Li interface and the insufficient contact between the anode/cathode and LATP usually lead to the structural collapse of LATP and the large solid–solid interfacial resistance for Li+ transport. Herein, a poly(1,3-dioxolane) (PDOL) adhesive layer was constructed by a Al(OTf) 3 -induced in-situ solidification process between the interface of LATP and anode/cathode. Such PDOL interfacial adhesive layer alleviates adverse reduction reactions at the LATP/Li interface and provides stable and well-contacted bilateral electrode interfaces. Benefitting from the PDOL interfacial adhesive, the Li|adhesive-LATP|Li symmetric cells achieve a current density up to 0.7 mA cm −2 and exhibit a good cycling stability for more than 2750 h at 0.1 mA cm −2 , and the Li|adhesive-LATP|LiFePO4 solid-state batteries with interface modification exhibit a capacity of 158 mAh g −1 at 0.2 C with a retention of 94 % after 100 cycles.
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高影响因子
危险品化学品经营许可证（带存储）