CRYSTAL GROWTH & DESIGN
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2024
·
IF 3.2
Min Yu,Jian-Qin Yan,Ling-Yang Wang,Zhi-Yong Wu,Meng-Yao Wu,Yong Sun,Yan-Tuan Li
The codrug efficacy increase approach is developed to improve the biopharmaceutical properties of the conventional antitumor drug 5-fluorouracil (Fu) through molecular salification by tapping the potential of biguanide agents in property optimization and further antitumor synergism. In this route, the biguanide phenformin (Phf) is noncovalently bonded with Fu through a proton transference procedure based on its acidic–alkalinity differences, thereby improving the physicochemical and pharmacokinetic behaviors of Fu and ultimately achieving enhanced efficacy by leveraging the synergized antitumor effect of Phf. Oriented by this, a novel codrug molecular salt, phenforminium 5-fluorouracilate (Fu-Phf), is assembled and systematically characterized for its precise structure employing single-crystal/powder X-ray diffraction and other analytical methods. The results revealed the presence of robust charge-assisted hydrogen bonds in the asymmetric unit, with its structural characteristics being internally hydrophilic and externally hydrophobic, which affects its in vitro physicochemical performances. Thereinto, the dissolubility and permeability of Fu are proven to be simultaneously improved after forming the molecular salt, which aligns positively with a series of theoretical predictions, including molecular electrostatic potential (MEP), reduced density gradient (RDG), frontier molecular orbitals (FMOs), and topological analysis based on the theory of atoms in molecules (AIMs). All of these result in improved in vivo pharmacokinetic performances of the molecular salt, leading to higher bioavailability over Fu alone. Encouragingly, the strengthened tumor inhibition properties of the Fu-Phf codrug are theoretically simulated through the molecular docking method and experimentally observed against selected cancer cell strains, showing significantly reduced IC50. Furthermore, the calculated CI values of less than 1.0 highlight the achievement of the synergistic effects of the two components in the codrug molecular salt. Consequently, this work introduces a fresh salification case of Fu, presenting promising potential for future development; simultaneously, it also provides insights into exploring the possibilities of biguanide medicine as antitumor reinforcement through dual-drug synergy and optimization strategies.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2024
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IF 9.4
Fuzheng Fu,Furui Hu,Zi Yu,Yongxin Liang,Tao Gan,Huayu Hu,Zuqiang Huang,Yanjuan Zhang
The existing photocatalytic systems are difficult to achieve high selectivity and conversion for the oxidation of 5-hydroxymethylfurfural (HMF) under mild conditions. MnO 2 exhibits notable tunability in valence state, but its photocatalytic oxidation efficiency is limited by the poor absorption in near-infrared region, insufficient oxygen adsorption, and slow charge transfer. To overcome these limitations, an innovative MnO 2 @Bi 2 MoO 6 /kaolinite (MnO 2 @BMO/KL) composite photocatalyst was synthesized by the hydrothermal and co-precipitation techniques, and the as-prepared photocatalyst was used for selective photocatalytic oxidation of HMF to produce 2,5-diformylfuran (DFF). The combination of MnO 2 , three-dimensional layered Bi 2 MoO 6 (BMO), and kaolinite enhanced electron transport and oxygen adsorption. The incorporation of kaolinite as a support material led to the structural transformation of BMO, while the in-situ grown amorphous MnO 2 trapped and accelerated electron transfer to adsorbed O 2 , thus efficiently segregating the photo-generated charges to enhance the utilization rate. MnO 2 @BMO/KL achieved almost complete conversion of HMF (>99.0 %) and a DFF yield of 83.0 % after 6 h of visible light irradiation. Additionally, MnO 2 @BMO/KL exhibited excellent structural stability over 6 cycles. The synergistic action of singlet oxygen ( 1 O 2 ) and superoxide ( • O 2 − ) was crucial in promoting the selective oxidation of HMF, while minimal generation of hydroxyl radical (•OH) reduced the risk of overoxidation. This study provides new insights into the development of economical and stable non-precious metal photocatalysts for highly selective conversion of biomass-derived chemicals.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Hao Li,Xue Liu,Yang Xiao,Kun Cao
5-Norbornene- exo -2,3-dicarboxylic anhydride ( exo -NDA), widely used in the synthesis of medicine and pesticide, was primarily obtained through the subsequent thermal isomerization of 5-norbornene- endo -2,3-dicarboxylic anhydride ( endo -NDA) synthesized from cyclopentadiene (CPD) and maleic anhydride (MAH). Herein, density functional theory (DFT) was employed to elucidate the transition states and reaction pathways of different configurations. The endo -path exhibited a lower energy barrier, and the exo -isomer demonstrates greater structural stability. It was found that both high temperature and solvent polarity influenced the generation of NDA with different configurations. Due to considering solubility of MAH, an acetone/ethylbenzene mixed solvent was chosen for the reaction instead. According to the DFT calculations, we developed continuous-flow microreactor for high-efficiency one-pot synthesis of the isomers with exo / endo ratio of up to 1.19:1 as well as almost 100 % conversion and 98 % selectivity just in 2 min at 260 °C and 4 MPa, which CPD was generated in situ to participate in a series of Diels-Alder reactions instead of dicyclopentadiene as raw material existed at room temperature. Moreover, excessive or insufficient pressure in the reaction system should elevate byproduct formation, resulting in a decrease in reaction selectivity, as could prolonged residence time.
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eLife
·
2024
·
IF 6.4
Lu Yang,Zijin Lin,Ruijing Mu,Wenhan Wu,Hao Zhi,Xiaodong Liu,Hanyu Yang,Li Liu
Blood–brain barrier (BBB) prevents neurotoxins from entering central nervous system. We aimed to establish and characterize an in vitro triple co-culture BBB model consisting of brain endothelial cells hCMEC/D3, astrocytoma U251 cells, and neuroblastoma SH-SY5Y cells. Co-culture of SH-SY5Y and U251 cells markedly enhanced claudin-5 and VE-cadherin expression in hCMEC/D3 cells, accompanied by increased transendothelial electrical resistance and decreased permeability. Conditioned medium (CM) from SH-SY5Y cells (S-CM), U251 cells (U-CM), and co-culture of SH-SY5Y and U251 cells (US-CM) also promoted claudin-5 and VE-cadherin expression. Glial cell line-derived neurotrophic factor (GDNF) levels in S-CM and US-CM were significantly higher than CMs from hCMEC/D3 and U-CM. Both GDNF and US-CM upregulated claudin-5 and VE-cadherin expression, which were attenuated by anti-GDNF antibody and GDNF signaling inhibitors. GDNF increased claudin-5 expression via the PI3K/AKT/FOXO1 and MAPK/ERK pathways. Meanwhile, GDNF promoted VE-cadherin expression by activating PI3K/AKT/ETS1 and MAPK/ERK/ETS1 signaling. The roles of GDNF in BBB integrity were validated using brain-specific Gdnf silencing mice. The developed triple co-culture BBB model was successfully applied to predict BBB permeability. In conclusion, neurons enhance BBB integrity by upregulating claudin-5 and VE-cadherin expression through GDNF secretion and established triple co-culture BBB model may be used to predict drugs’ BBB permeability.
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Foods
·
2024
·Vol. 13
·期 17
·2756
·
IF 4.7
Linlin He,Yuqian Yan,Gang Zhang,Yanna Zhao,Fa Zhao,Zhuang Ding,Zhengping Wang
Folates, a crucial B-group vitamin, serve as a significant functional food supplement. Nevertheless, considerable obstacles persist in improving folates stability in liquid products. In this study, folic acid (FA) and 5-methyltetrahydrofolate (MTFA), two approved sources of folates, were encapsulated with sodium caseinate (NaCas) to enhance their stability. The protective effect of NaCas on folate molecules was investigated using experimental and computational methods. Meanwhile, the influence of divalent calcium ion (Ca2+) on the properties of the NaCas-MTFA complex was examined to evaluate the potential application of calcium 5-methyltetrahydrofolate (CaMTFA). Fluorescence tests showed both folates had static quenching behavior and bound to NaCas with a binding constant of 104–105M−1. Hydrophobic interactions were crucial in NaCas-FA complex formation, while hydrogen bonding drove NaCas-MTFA binding. The encapsulation of caseinate notably slowed down the degradation of folates under both light and dark conditions. Moreover, the addition of a low concentration of Ca2+did not adversely impact the binding mechanism of the NaCas-MTFA complex or the degradation curve of MTFA. The results of this study could serve as a valuable resource for the utilization of caseinates in incorporating folates, specifically MTFA, in the creation of natural liquid dietary supplements.
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PHYTOMEDICINE
·
2024
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IF 6.7
Tingwen Zhang,Yue Zhong,Yan Shi,Chengcheng Feng,Lu Xu,Zheng Chen,Xin Sun,Yan Zhao,Xialin Sun
Background The pathogenesis of acute liver injury (ALI) has been a pressing issue in the medical scientific community. We previously found that 5-O-methylvisammioside (MeV) from Saposhnikovia divaricata (Turcz.) Schischk has excellent anti-inflammatory properties. However, the mechanism by which MeV protects against ALI still needs to be deeply investigated. Purpose In the present study, we established an acetaminophen (APAP) -induced ALI mouse model and pre-protected the mice with MeV. Methods & Results Our findings indicate that MeV (5 and 10 mg/kg) lowered the blood levels of alanine aminotransferase and aspartate aminotransferase and reduced the infiltration of inflammatory cells in the liver. MeV initially showed an inhibitory effect on ALI. We then analyzed the molecular mechanisms underlying the effects of MeV by transcriptomic and metabolomic analyzes. Through transcriptomic analysis, we identified 4675 differentially expressed genes between the APAP+MeV group and the APAP-induced ALI group, which were mainly enriched in the MAPK pathway, the TNF pathway, and the NF-κB pathway. Through metabolomic analysis, we found that 249 metabolites in the liver were differentially regulated between the APAP+MeV group and the APAP- induced ALI group, which were mainly enriched in the arachidonic acid pathway. The mRNA expression levels of key genes (encoding TNF-α, p38, AP-1, RelB, IL-1β, and Ptges), as determined by RT-PCR analysis, were consistent with the RNA-seq data. The ELISA results indicate that MeV markedly decreased the serum levels of TNF-α and IL-1β in mice. Finally, the key proteins in the NF-κB and MAPK pathways were examined using immunoblotting. The results showed that MeV decreased IκB-α phosphorylation and inhibited the nuclear translocation of NF-κB. In addition, MeV reduced the hepatic inflammatory burst mainly by inhibiting the phosphorylation of p38 and JNK in the MAPK pathway. Conclusion The present study demonstrated (i) that MeV could ameliorate APAP-induced ALI by inhibiting arachidonic acid metabolism and the TNF, MAPK, and NF-κB pathways, and (ii) that MeV is a promising drug candidate for the prevention of ALI.
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JOURNAL OF ELECTROANALYTICAL CHEMISTRY
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2012
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IF 2.905
Xiaohua Zhu,Qifang Jiao,Chuyi Zhang,Xiaoxi Zuo,Xin Xiao,Yong Liang,Junmin Nan
The graphene and 5-[ o -(4-Bromine amyloxy) phenyl]-10,15,20-triphenylporphrin ( o -BrPETPP) composite (GR- o -BrPETPP) film is prepared on the glassy carbon electrode (GCE) with graphene oxide (GO) modifier through a consecutive cyclic voltammetry process, and then its electrocatalytic oxidation to indirubin is investigated. The as-prepared GR- o -BrPETPP film exhibits wrinkling paper-like structure and lower electron transfer resistance. In comparison with the o -BrPETPP/GCE and GCE, the GR- o -BrPETPP film electrode prepared for five cycles indicates an excellent electrocatalytic oxidation activity toward indirubin with about 2.2 and 13.3 times higher current response, respectively. In addition, in the 0.1 mol L −1 acetate buffer solution (pH = 4.6), the film electrode displays a linear relationship between the oxidation current and the indirubin concentration in the range from 5.0 × 10 −7 mol L −1 to 2.4 × 10 −5 mol L −1 , and presents a detection limit of 1.0 × 10 −7 mol L −1 ( S / N = 3) by differential pulse voltammetry (DPV) with 220 s accumulation. Especially, this film electrode also shows a comparative sensitivity with high-performance liquid chromatography (HPLC) for the determination of the indirubin extractive of herbal medicines, showing its practical prospect in the electrochemical determination of indirubin.
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JOURNAL OF GENE MEDICINE
·
2017
·Vol. 19
·期 12
·e2998
·
IF 2.524
Yunna Chen,Li Sun,Dongdong Guo,Ziteng Wu,Weidong Chen
Background Drug resistance cancer cells have become a major problem in chemotherapy. To solve this problem, the co-delivery of small interefering RNA (siRNA) and 5-fluorouracil chitosan nanoparticles was employed, aiming to reverse the multidrug resistance of gastric cancer SGC-7901 cells in vitro . Methods Chitosan nanoparticles were prepared using an ionic gel method. siRNA nanoparticles were characterized by gel retardation assays. Particle size and zeta potential were measured to confirm nanoparticle formation. The transfection efficiency of siRNA was determined by flow cytometry and high-content screening. Western blotting and a quantitative real-time-polymerase chain reaction were used to assess the silencing efficiency of siRNA. Accumulation and efflux experiments for rhodamine-123, cell migration experiments, cell sensitivity analyses and cell apoptosis assays were used to determine whether siRNA could reverse multidrug resistance. A systemic toxicity assay was used to evaluate the safety of nanoparticles. Results Compared to naked siRNA, the co-delivery system demonstrated a higher transfection efficiency and gene silencing efficiency by inhibiting the efflux of P-glycoprotein and cell migration. Moreover, the combination treatment with siRNA and 5-fluorouracil co-delivered by chitosan nanoparticles can increase the sensitivity of drug resistance cells and cell apoptosis. Finally, the safety of nanoparticles was evaluated in vivo and the results obtained suggested that nanoparticles did not have any obvious toxicity. Conclusions Co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles is an attractive strategy for overcoming multidrug resistance.
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CERAMICS INTERNATIONAL
·
2024
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IF 5.1
Sehreish Abrar,Faisal Nazeer,Abdul Malik,Yanhai Cheng,Ahmed M. Fouda
Materials with a thermal expansion coefficient compatible with silicon carbide based ceramic matrix composites and low thermal conductivity at higher temperatures are crucial for developing environmental barrier coatings (EBCs) for aero-engines. Lately, high entropy silicate engineering has been a promising approach to develop optimized EBC materials. The solid solution reaction method was adopted for the fabrication of high entropy multicomponent (Dy 1/5 Er 1/5 Tm 1/5 Yb 1/5 Y 1/5 ) 2 SiO 5 or (5RE 1/5 ) 2 SiO 5 monosilicate. Scanning electron microscopy and X-ray diffraction show the homogenous distribution and a single-phase solution of (5RE 1/5 ) 2 SiO 5 monosilicate. Differential scanning calorimetry testing was done at 1450 °C which shows no exo/endothermic reaction has occurred. The value of the coefficient of thermal expansion (6 ppm/°C) up to temperature 1500 °C and low thermal conductivity values for (5RE 1/5 ) 2 SiO 5 monosilicate were observed (1.1–1.4 W/m°C) in the temperature range between 25 and 1500 °C. The water vapor corrosion resistance of (5RE 1/5 ) 2 SiO 5 monosilicate further confirms that the material is suitable for EBC applications due to the synergistic effect of different rare earth radii and stable crystal structure with a negligible weight loss value of 0.0005 mg/cm 2 after 150 h corrosion time under 90 % H 2 O and 10 % O 2 at 1300 °C. The results of this work suggest that (5RE 1/5 ) 2 SiO 5 monosilicate can be used as a promising candidate for environmental barrier coatings.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2024
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IF 4.9
Jin Wang,Xu Guo,Qixiang Zhou,Yan Cai,Bing Lu,Yang Wang,Yong Yao
The functional photoelectric materials based on bismuth oxyhalides (BiOX, X = Cl, Br and I) have been widely used in the field of photo-electrochemistry (PEC) due to their excellent physical, chemical and optical properties. Herein, a series of BiOX nanoflowers conjugated water-soluble pillar[5]arenes functionalized Au (Au@WP5/BiOX) modified PEC sensor are constructed and investigated for the PEC detection of serotonin. Upon exploring the physical properties, such as size, visible light absorption capacity, band gap and impedance, of the three BiOX materials, it is discovered that BiOBr is more effective in detecting 5-HT due to its high redox ability, moderate band gap (∼2.03 eV), and low impedance. BiOBr can provide a high and stable starting photocurrent compared to the other two bismuth oxyhalides. When used in acidic or neutral environments, 5-HT with a positive charge can undergo electrostatic adsorption and host-guest complexation behavior with WP5, which has a negative charge. By using WP5, the recognition ability of the material to 5-HT molecules can be enhanced, and the adsorption of 5-HT molecules on Au@WP5/BiOBr can be accelerated. The local surface plasmon resonance effect (LSPR) of gold nanoparticles (Au NPs) can accelerate the electrochemical reaction rate and charge transfer rate, which ultimately leads to the amplification of the photocurrent signal. As a result, the 5-HT detection sensor based on Au@WP5/BiOBr has a wide detection range from 0.01 to 100 μM and a low detection limit of 3 nM (S/N = 3) compared to other sensors, including Au@WP5/BiOCl and Au@WP5/BiOI. The proposed PEC sensor also exhibits good stability and selectivity, making it a promising strategy for detecting biological small molecules using pillar[5]arene functionalized PEC active materials.
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JOURNAL OF POWER SOURCES
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2024
·
IF 8.1
Shi Jia Li,Guang Tao Fei,Shao Hui Xu,Wen Chao Chen,Hai Yan Xu,Xiao Xuan Qu,Xin Feng Li,Hao Miao Ouyang
Poly (ethylene oxide) (PEO)-based solid-state electrolytes are the most researched and widely used polymer solid-state electrolytes, but their ionic conductivity, electrochemical stability window, and cycling stability all need further improvement. In this work, 15 Crown ether 5 and the high concentration of lithium salts are added into PEO solid-state electrolytes using a solution-casting approach. The resulting solid-state electrolyte exhibits an ionic conductivity of 3.14 × 10 −3 S cm −1 at 60 °C and an electrochemical stability window exceeding 5.2 V. The assembled Li//Li symmetric battery can be stably cycled for over 850 h at a current of 0.1 mA cm −2 , and the LiFePO 4 //Li battery has an initial discharge capacity of 144 mA h g −1 at 2C rate, retaining 85 % of its capacity after 800 cycles. By optimizing the solid-state electrolyte components, Li//Li symmetric batteries can achieve cycling stability for up to 2200 h, and LiFePO 4 //Li batteries can endure up to 2000 cycles at a 2C rate and 4800 cycles at a 5C rate. Moreover, the prepared solid-state electrolyte can be matched with a high-voltage cathode electrode, offering a wide range of potential applications and promising commercialization prospects.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Jie Li,Jikai Gao,Jiaying Ai,Ziyang Yin,Fuping Lu,Hui-Min Qin,Shuhong Mao
17α-Hydroxyprogesterone (17α-OH-PROG) is an important intermediate with a wide range of applications in the pharmaceutical industry. Strategies based on efficient electron transfer and cofactor regeneration were used for the production of 17α-OH-PROG. Here, CYP260A1, Fpr and Adx were expressed using a double plasmid system, resulting in higher biotransformation efficiency. Further optimization of reaction conditions and addition of polymyxin B increased the production of 17α-OH-PROG from 12.52 mg/L to 102.37 mg/L after 12 h of biotransformation. To avoid the addition of external 5-aminolevulinic acid (ALA) as a heme precursor for the P450 enzyme, a modified C5 pathway was introduced into the engineered strain, further reducing the overall process cost. The resulting whole-cell biocatalyst achieved the highest biotransformation yield of 17α-OH-PROG reported to date, offering a promising strategy for commercial application of P450 enzymes in industrial production of hydroxylated intermediates.
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