INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2023
·
IF 5.8
Ji Wang,Yanhao Zhang,Shuo Dong,Wenhui Zha,Chao Liu,Yang Wang,Yuhao Jiang,Hanlei Xing,Xinsong Li
Lipid nanoparticles (LNPs)-based mRNA vaccines have shown great potential in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. However, it remains still a challenge to improve the delivery efficiency of LNPs and the long-term stability of their mediated mRNA vaccines. Herein, a novel ionizable lipid 2-hexyldecyl 6-(ethyl(3-((2-hexyldecyl)oxy)-2-hydroxypropyl)amino)hexanoate (HEAH) derived LNPs were developed for delivering the receptor binding domain (RBD) mRNAs. In vitro cell assays confirmed that the ionizable lipid HEAH with one ether bond and one ester bond derived LNPs possessed higher mRNA delivery efficiency compared with the approved ALC-0315 with two ester bonds used in the BNT162b2 vaccine. Notably, the HEAH-derived LNPs powder lyophilized did not significantly change for 30 days after storage at 37 °C indicating good thermostability. After two RBD mRNAs of Delta and Omicron variants were encapsulated into the HEAH-derived LNPs, a bivalent mRNA vaccine was obtained as a nanoparticle formulation. Importantly, the bivalent mRNA vaccine not only resisted Delta and Omicron and also generated protective antibodies against ancestral SARS-CoV-2. The HEAH-mediated bivalent vaccine induced stronger humoral and cellular immunity than those of the ALC-0315 group. Taken together, the ionizable lipid HEAH-derived LNPs show outstanding potential in improving the delivery efficiency of mRNA and the stability of mRNA vaccine.
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高影响因子
CYTOKINE
·
2025
·
IF 3.7
Yuxi Huang,Piaorong Zeng,Tianmin Liu,Mei Xu,Wenyi Tang,Fangyuan Cheng,Zhijuan Zhou,Bairong Chen,Kan Liu,TouKun Chong,Jian Chen
Background Takotsubo syndrome (TTS) and sepsis often co-occur with poor outcomes, yet their underlying molecular mechanisms remain to be elucidated. Transcriptomic analysis is employed to detect diagnostic biomarkers and reveal shared pathophysiological mechanisms in sepsis-associated TTS. Methods Myocardial gene expression data (TTS, sepsis, and controls) from GEO were analyzed to identify shared differentially expressed genes. WGCNA and PPI networks were used for candidate gene selection. Key genes were further refined using random forest and LASSO algorithms. Immune cell infiltration was assessed using CIBERSORT. Myocardial injury and gene expression in rat models were evaluated using HE staining, TUNEL assay, immunohistochemistry, qPCR, and Western blotting. Clinical validation was conducted using plasma samples from the China TTS Registry. t -tests and ANOVA were conducted via GraphPad Prism 8 software. A P -value < 0.05 was considered statistically significant. Results Lipocalin-2 (LCN2) was recognized as an important biomarker through WGCNA, PPI network analysis, and machine learning algorithms, showing strong predictive performance. Its expression was significantly associated with neutrophil infiltration and myocardial injury in TTS. Consistent with the bioinformatics findings, the TTS-sepsis comorbidity model showed elevated mRNA and protein levels of LCN2 in myocardial tissue, accompanied by increased neutrophil infiltration and severe cardiac injury. Clinical validation confirmed elevated plasma LCN2 levels in patients with sepsis-associated TTS, correlating with neutrophil counts, NT-proBNP, and cTnI levels. Conclusion LCN2 is identified as a key inflammatory mediator linking neutrophil-driven inflammation to myocardial injury in sepsis-associated TTS, with dual potential as a diagnostic biomarker and therapeutic target.
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DIAMOND AND RELATED MATERIALS
·
2025
·
IF 5.1
Chenjie Liu,Yijin Wang,Wenlong Xu,Ming Zhou,Fuliang Meng,Xianfeng Meng
In light of electromagnetic pollution caused by the excessive or unregulated use of electromagnetic waves (EMWs), there is an urgent requirement to identify economical EMWs absorption materials. However, the facing challenge lies in the precise design of microstructure and the controlled tuning of electromagnetic parameters. Herein, natural cottonwood fiber was converted into carbon fiber (CF) through optimized pyrolysis, followed by the synthesis of CFs@Co 3 O 4 /Co(OH) 2 composites via in situ hydrothermal method. Ingenious structural design, multi-faceted synergy and heterogeneous interfaces endowed the CFs@Co 3 O 4 /Co(OH) 2 composites with exceptional impedance matching and electromagnetic loss, showing outstanding EMWs absorption ability. The CFs@Co 3 O 4 /Co(OH) 2 sample (CF S @Co-25) with 2.5 mm thickness displayed a maximum reflection loss ( RL max ) of −78.7 dB and an effective absorption bandwidth ( EAB ) of 9.9 GHz. At 3.0 mm matching thickness, the impedance matching value ( Z ) reached 0.99, with an RL max of −105.3 dB. This work offers a scalable and economical approach to developing high-performance carbon-based EMWs absorbers.
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JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Qiuyue Fu,Yue Pan,Peixi Wu,Zhuoxian Cao,Liu Shi,Lan Huang,Kui Cheng,Zhipeng Chen
Capitalizing on the advantages of Toll-like receptor 2 (TLR2) small-molecule agonists combining high potency and low toxicity in cancer therapy, we designed and synthesized a novel series of thiourea-based TLR2 small-molecule agonists and identified a low-toxicity TLR1/2-specific small molecule agonist SMU-C409 (EC50 = 65 ± 3 nM). SMU-C409 incorporates key optimizations: a carbonyl conservation strategy eliminates carboxylesterase-mediated degradation, and a quinoline (N-heterocycle) enables salt formation that boosts solubility by 3.4-fold (free base) and 5.5-fold (hydrochloride) relative to the lead compound SMU-C80 (EC50 = 43 ± 5 nM), while retaining potent agonistic activity and exhibiting superior plasma stability, which is critical for favorable pharmacokinetics and efficacy. Mechanistically, SMU-C409 activates TLR1/2, recruits MyD88, induces NF-κB phosphorylation, and stimulates TNF-α/IL-1β secretion; in vitro studies confirm robust immune cell activation and antitumor immunomodulation. SMU-C409 overcomes core limitations of TLR2 agonists while maintaining high potency, positioning it as a promising candidate for advancing cancer immunotherapy.
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高影响因子
INTERNATIONAL DENTAL JOURNAL
·
2025
·Vol. 76
·期 1
·109304
·
IF 3.7
Zhaoxia Yu,Shihui Jiang,Xinxin Li,Xingjiao Li,Guanhua Wang,Xiaohua Dai,Xiaoli Lian,Yan Yan,Yue Wang,Zhimou Yang,Huiru Zou
Objectives Enamel matrix derivative (EMD) is widely recognized for its ability to induce osteogenic and odontogenic differentiation. However, the complex composition of EMD frequently results to inconsistent experimental and clinical outcomes. Amelogenin, a key component of EMD, plays crucial roles in tooth germ development as well as in the repair and regeneration of dental tissue. In this study, an amelogenin peptide was investigated on the proliferation and odontogenic differentiation of human dental pulp cells (HDPCs). Methods The amelogenin peptide with the amino acid sequence KWYQNMIR was synthesized using solid-phase techniques. HDPCs were stimulated with various concentrations of the peptide. CCK-8 assays, alkaline phosphatase (ALP) activity measurements, quantitative reverse transcription-polymerase chain reaction, Western blot analysis, Alizarin red staining, and scanning electron microscopy were used to assess the effects. Results The amelogenin peptide concentrations of 100 nM and 1 μM significantly enhanced HDPC proliferation at 5 and 7 days ( P < .01), with 1 μM exhibiting the most pronounced effect. Treatment with 1 μM amelogenin peptide enhanced ALP activity in HDPCs at 7 and 14 days ( P < .01) and markedly upregulated the mRNA expression of DSPP, DMP-1 , and RUNX-2 . Western blot analysis revealed that 1 μM amelogenin peptide enhanced the protein expression of DSPP, DMP-1, and ALP in HDPCs at 7 and 14 days. Additionally, it promoted calcium deposition and mineralized nodule formation at 28 days. Importantly, the amelogenin peptide upregulated the phosphorylation level of ERK1/2 (p-ERK1/2), and the application of an ERK1/2 inhibitor suppressed HDPC differentiation. Conclusions The amelogenin peptide stimulates both the proliferation and odontogenic differentiation of HDPCs via the ERK1/2 pathway. These findings suggest that the amelogenin peptide may have significant implications for regenerative dentistry, particularly in the context of dentine-pulp complex regeneration.
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高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-9
·
IF 14.7
Yao Yueliang,Tse Yuen Cheong,Lai Samuel Kin-Man,Shi Yixiang,Low Kam-Hung,Au-Yeung Ho Yu
Responsive synthetic receptors for adaptive recognition of different ionic guests in a competitive environment are valuable molecular tools for not only ion sensing and transport, but also the development of ion-responsive smart materials and related technologies. By virtue of the mechanical chelation and ability to undergo large-amplitude co-conformational changes, described herein is the discovery of a chameleon-like [2]catenane that selectively binds copper(I) or sulfate ions and its associated co-conformational mechanostereochemical switching. This work highlights not only the advantages and versatility of catenane as a molecular skeleton in receptor design, but also its potential in constructing complex responsive systems with multiple inputs and outputs.
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高影响因子
JOURNAL OF MOLECULAR STRUCTURE
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2024
·
IF 4
Yuying Du,Yuanyuan Gao,Yanlong Gu,Li Lv,Ning Zhu,Limin Han,Xing Zeng
Owing to the diverse implication of carbazole scaffolds in medicinal chemistry, photoelectronic materials and chromophores, the molecules containing the carbazole motif have attracted significant attention over the years. In this work, the vibronic contributions to carbazole structures could facilely change the solvatochromic effect, absorption wavelength, emission wavelength, and Stokes shifts of six 2-carbonyl carbazole ketones fluorophores. Among them, the structure of 1-(1-methyl- 9H -carbazol-2-yl)ethanone (3a) were confirmed from single crystal XRD studies. The ratiometric detection of Fe(III) ion of 2-carbonyl carbazole ketone 3a were investigated. Furthermore, it was speculated that chemosensor 3a toward the recognition of Fe 3+ cation was dependent on its rigid structure and good coplanarity of the conjugated system, strong intramolecular charge-transfer of 3a .
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Crystals
·
2024
·Vol. 14
·期 1
·91
·
IF 2.4
Fan Zhang,Hua Hao,Minghe Cao,Zhonghua Yao,Shuai Fu,Hanxing Liu
Piezoelectric ceramics with excellent piezoelectric properties and a high Curie temperature are important for numerous electromechanical devices in a broad range of temperature environments. In this work, the relaxor ferroelectric Pb(Yb1/2Nb1/2)O3end member was selected to be introduced into a BiScO3-PbTiO3high-temperature piezoelectric ceramic to reduce the dielectric loss and improve the piezoelectric properties while slightly reducing the Curie temperature. The phase structure and dielectric, ferroelectric and piezoelectric properties of 0.025Pb(Yb1/2Nb1/2)O3-(0.975−x)BiScO3-xPbTiO3(0.60 ≤x≤ 0.63) ceramics were systematically analyzed, and the best electrical properties were observed in the morphotropic phase boundary regionx= 0.61 withd33= 370 pC/N,kp= 44%,Pr= 33.9 μC/cm2. Importantly, no significant depolarization was observed in thex= 0.61 ceramic from room temperature to 290 °C, demonstrating its good thermal stability and potential applications in a wide range of temperature environments.
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iScience
·
2024
·
IF 4.6
WenYe Liu,Xi Liu,LingYa Li,ZhiPeng Tai,GuoLiang Li,Jing-Xia Liu
Summary Enhancers of polycomb 1 (EPC1) and 2 (EPC2) are involved in multiple biological processes as components of histone acetyltransferases/deacetylase complexes and transcriptional cofactors, and their dysfunction was associated with developmental defects and diseases. However, it remains unknown how their dysfunction induces hematopoietic stem and progenitor cell (HSPC) defects. Here, we show that depletion of EPC1 / 2 significantly reduced the number of hematopoietic stem and progenitor cells (HSPCs) in the aorta-gonad mesonephros and caudal hematopoietic tissue regions by impairing HSPC proliferation, and consistently downregulated the expression of HSPC genes in K562 cells. This study demonstrates the functions of EPC1 / 2 in regulating histone H3 acetylation, and in regulating DLST (dihydrolipoamide S-succinyltransferase) via H3 acetylation and cooperating with transcription factors serum response factor and FOXR2 together, and in the subsequent HSPC emergence and proliferation. Our results demonstrate the essential roles of EPC1 / 2 in regulating H3 acetylation, and DLST as a linkage between EPC1 and EPC2 with mitochondria metabolism, in HSPC emergence and proliferation.
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高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2014
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IF 2.468
Wei Wei,Yongfang Feng,Xi Zhang,Xi Cao,Fengqin Feng
To obtain high purity of 1,3-Dioleoyl-2-palmitoylglycerol (OPO), an important structured triglyceride for infant formula, a facile method was established. Tripalmitin (PPP) was firstly synthesized, and then OA was incorporated into the sn -1 and 3 position of the PPP glycerol backbone by acidolysis catalyzed using sn -1,3 regiospecific lipases. Two kinds of widely used immobilized sn -1,3 regiospecific lipases, Lipozyme TL IM and Lipozyme RM IM, were investigated in both solvent ( n -hexane) and solvent-free system. The results showed that Lipozyme TL IM and Lipozyme RM IM were suitable for solvent system and solvent-free system respectively. Other reaction conditions (enzyme load, substrate molar ratio, temperature, reaction time) were optimized. The palmitic acid (PA) at the sn -2 position of the obtained triacylglycerols (TAGs) under optimized conditions were 92.92% and 86.62%, and OPO contents in the final products were 32.34% and 40.23% in the solvent and solvent-free system respectively. Special emphasis was given to test the reusability of the two immobilized lipases, results showed that Lipozyme TL IM was almost non-reusable, while Lipozyme RM IM could keep its activity for at least 15 times (about 60 h). These results provide a guide for the industrial production of high purity OPO by facile method.
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JOURNAL OF MOLECULAR LIQUIDS
·
2019
·
IF 4.561
Subramanian Siva,Changzhu Li,Haiying Cui,Lin Lin
Isoeugenol is a natural dual antioxidant/prooxidant. In this research, the inclusion complex (IC) of isoeugenol with 2-hydroxypropyl- β -cyclodextrin (HP β CD) was prepared via the ultrasound (US) method. The US assisted isoeugenol/HP β CD-IC was investigated by various characterization techniques such as UV–Vis absorption, fluorescence, powder X-ray diffraction, Fourier transform infrared spectroscopy , thermal gravimetric analysis and differential scanning calorimetry . Absorption, fluorescence and infrared studies indicated that the alkyl chain of isoeugenol was deeply included in the HP β CD cavity. Through determinations of phase solubility and water solubility studies, significant enhancement of isoeugenol water solubility was confirmed after IC formation with the HP β CD. Thermal data proved that the IC formation significantly enhanced the thermal stability of isoeugenol. Antioxidant test results indicated that isoeugenol/HP β CD-IC exhibited better antioxidant activity than free isoeugenol due to its solubility enhancement. Furthermore, the isoeugenol/HP β CD-IC showed higher antibacterial activity of 96 ± 0.2% and 97 ± 0.5% against Staphylococcus aureus and Escherichia coli bacteria, respectively.
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高影响因子
DALTON TRANSACTIONS
·
2015
·Vol. 44
·期 41
·18012-18018
·
IF 4.197
Yongfeng Liu,Yaxiong Yang,Xin Zhang,You Li,Mingxia Gao,Hongge Pan
The thermal dehydrogenation process of the KOH-containing Mg(NH2)2–2LiH system was systematically investigated by identifying changes in the structure and composition of its components by XRD and FTIR. During ball milling, the added KOH reacts with Mg(NH2)2 and LiH to produce MgO, KH and Li2K(NH2)3. During the initial heating process (<120 °C), the newly formed KH and Li2K(NH2)3 react with Mg(NH2)2 and LiH to yield MgNH, LiNH2 and Li3K(NH2)4 along with hydrogen release. Raising the temperature to 185 °C results in a reaction between Mg(NH2)2, MgNH and LiH that gives Li2Mg2N3H3 as the product and further releases hydrogen. As the temperature is increased to 220 °C, Li2Mg2N3H3 reacts with LiNH2 and LiH to produce Li2MgN2H2 and H2. Meanwhile, two parallel reactions between Li2Mg2N3H3, Li3K(NH2)4 and LiH also generate additional hydrogen. Specifically, the KH and Li2K(NH2)3, formed in situ during ball milling, serve as reactants in the dehydrogenation reaction of the Mg(NH2)2–2LiH system, which is responsible for the significantly improved thermodynamics and kinetics of hydrogen storage.
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