Nature Communications
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2024
·Vol. 15
·期 1
·1-24
·
IF 14.7
Ren Xijiao,Xue Rui,Luo Yan,Wang Shuang,Ge Xinyue,Yao Xuemei,Li Liqi,Min Junxia,Li Menghuan,Luo Zhong,Wang Fudi
Radio-immunotherapy exploits the immunostimulatory features of ionizing radiation (IR) to enhance antitumor effects and offers emerging opportunities for treating invasive tumor indications such as melanoma. However, insufficient dose deposition and immunosuppressive microenvironment (TME) of solid tumors limit its efficacy. Here we report a programmable sequential therapeutic strategy based on multifunctional fusogenic liposomes (Lip@AUR-ACP-aptPD-L1) to overcome the intrinsic radio-immunotherapeutic resistance of solid tumors. Specifically, fusogenic liposomes are loaded with gold-containing Auranofin (AUR) and inserted with multivariate-gated aptamer assemblies (ACP) and PD-L1 aptamers in the lipid membrane, potentiating melanoma-targeted AUR delivery while transferring ACP onto cell surface through selective membrane fusion. AUR amplifies IR-induced immunogenic death of melanoma cells to release antigens and damage-associated molecular patterns such as adenosine triphosphate (ATP) for triggering adaptive antitumor immunity. AUR-sensitized radiotherapy also upregulates matrix metalloproteinase-2 (MMP-2) expression that combined with released ATP to activate ACP through an “and” logic operation-like process (AND-gate), thus triggering the in-situ release of engineered cytosine-phosphate-guanine aptamer-based immunoadjuvants (eCpG) for stimulating dendritic cell-mediated T cell priming. Furthermore, AUR inhibits tumor-intrinsic vascular endothelial growth factor signaling to suppress infiltration of immunosuppressive cells for fostering an anti-tumorigenic TME. This study offers an approach for solid tumor treatment in the clinics.
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RESPIRATORY RESEARCH
·
2024
·Vol. 25
·期 1
·1-16
·
IF 4.7
Wang Han,Du Xiaohui,Liu Wenwen,Zhang Congcong,Li Ying,Hou Jingwen,Yu Yi,Li Guiru,Wang Qi
BackgroundEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs.MethodsWe established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment.ResultsBetulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts.ConclusionsBA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers.Graphical abstract
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Biotechnology for Biofuels and Bioproducts
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2024
·Vol. 17
·期 1
·1-16
·
IF 3.3
Wei Xiaoyu,Yang Lijie,Chen Zhen,Xia Wenhao,Chen Yongbin,Cao Mingfeng,He Ning
Background The structural diversity of extracellular polymeric substances produced by microorganisms is attracting particular attention. Poly-gamma-glutamic acid (γ-PGA) is a widely studied extracellular polymeric substance from Bacillus species. The function of γ-PGA varies with its molecular weight (Mw). Results Herein, different endogenous promoters in Bacillus licheniformis were selected to regulate the expression levels of pgdS , resulting in the formation of γ-PGA with Mw values ranging from 1.61 × 10 3 to 2.03 × 10 4 kDa. The yields of γ-PGA and exopolysaccharides (EPS) both increased in the pgdS engineered strain with the lowest Mw and viscosity, in which the EPS content was almost tenfold higher than that of the wild-type strain. Subsequently, the compositions of EPS from the pgdS engineered strain also changed. Metabolomics and RT-qPCR further revealed that improving the transportation efficiency of EPS and the regulation of carbon flow of monosaccharide synthesis could affect the EPS yield. Conclusions Here, we present a novel insight that increased pgdS expression led to the degradation of γ-PGA Mw and changes in EPS composition, thereby stimulating EPS and γ-PGA production. The results indicated a close relationship between γ-PGA and EPS in B. licheniformis and provided an effective strategy for the controlled synthesis of extracellular polymeric substances.
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Microbiome
·
2024
·Vol. 12
·期 1
·1-19
·
IF 13.8
Zhang Yujun,Gao Yan,Li Chen,Zhang Yong-An,Lu Yuanan,Ye Jing,Liu Xueqin
Background Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. Results Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. Conclusions This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish.
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AAPS PHARMSCITECH
·
2014
·Vol. 15
·期 3
·731-740
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IF 1.776
Zhang Jianbin,Lv Yan,Zhao Shan,Wang Bing,Tan Mingqian,Xie Hongguo,Lv Guojun,Ma Xiaojun
The objective of this study is to investigate the effect of lipolysis on the release of poorly water-soluble drug from SMEDDS in the perspective of drug core/shell location. For this purpose, four SMEDDS formulations with various core/shell properties were developed based on long-chain lipid or medium-chain lipid as well as different surfactant/oil ratios. Poorly water-soluble drugs, hymecromone and resveratrol, were significantly solubilized in all SMEDDS formulations and the diluted microemulsions. Fluorescence spectra analysis indicated that hymecromone was mainly located in the shell of microemulsions, while resveratrol was located in the core. The effect of lipolysis on the release rates of drugs with different core/shell locations were investigated by a modified in vitro drug release model. For the drug located in the shell, hymecromone, the release profiles were not affected during the lipolysis process and no significant differences were observed among four formulations. For the drug located in the core, resveratrol, the release rates were increased to various degrees depending on the extent of digestion. In conclusion, the drug core/shell location plays an important role for determining the effect of lipolysis on drug release from SMEDDS formulation.
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JOM
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2025
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IF 2.3
Chen Jialin,An Ming,Dai Mengnan,Li Shutao,Chen Yeqing,Song Rui,Song Jiaxing,Chen Longming,Zhong Xiting,Tian Quanwei
The properties of oxidants significantly affect the thermal and combustion properties of nanothermites, and alpha and beta-MnO 2 nanorods with similar morphological appearances were prepared using the hydrothermal method. Corresponding nanothermites were prepared employing the electrostatic spraying method and their thermal and combustion properties have been compared through TG-DSC and combustion tests. The aluminothermic reaction process was simulated by molecular dynamics, and the results showed that the β-MnO 2 /Al nanothermite first underwent β-MnO 2 thermal decomposition followed immediately by an aluminothermic reaction, whereas the α-MnO 2 /Al nanothermite underwent a direct aluminothermic reaction. In contrast, the α-MnO 2 /Al nanothermite could release more heat. According to thermal analysis, the activation energy of α-MnO 2 /Al nanothermite was 100.15 kJ mol − 1 higher than β-MnO 2 /Al nanothermite, indicating better stability. Combustion experiments showed that the combustion propagation rate of the α-MnO 2 /Al nanothermite was faster than the β-MnO 2 /Al nanothermite. The results have been verified and the reaction process has been exhibited using molecular dynamics to simulate the aluminothermic reaction process. The notable differences in the thermal and combustion properties of nanothermites containing MnO 2 with varying phases can be attributed to the distinct crystal structures of α-MnO 2 and β-MnO 2 . The alternating 1 × 1 and 2 × 2 tunnel structure of α-MnO 2 is more stable, whereas β-MnO 2 undergoes thermal decomposition before the aluminothermic reaction.
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Science China-Materials
·
2025
·
IF 7.4
Huang Fuxia,Liu Yifei,Wang Feng,Liu Ya,Guo Liejin
BiOI materials show significant potential for photocatalytic CO 2 reduction, but their limited CO 2 activation and poor charge carrier properties hinder conversion efficiency. In this study, we engineered BiOI-based photocatalysts with abundant crystal defects to enhance performance. X-ray diffraction (XRD), Raman spectroscopy, and high-resolution transmission electron microscopy (HRTEM) revealed lattice distortions and twin crystals in BiOI-LD and BiOI-TC. Ultraviolet-visible spectroscopy, micropore and chemisorption analyses, and photoluminescence spectroscopy demonstrated that crystal defects improved light absorption, CO 2 adsorption, charge transfer efficiency, and carrier lifetime. Electron paramagnetic resonance (EPR) spectroscopy showed increased superoxide radical generation in BiOI-TC, suggesting higher reactivity. Consequently, BiOI achieved a CH 3 CH 2 OH generation rate of 6.2 µmol g −1 h −1 with 100% selectivity. Key intermediates (*CO, *COCO, *CHO, *CH 2 ) for CH 3 CH 2 OH production were identified, and C 2 H 6 formation in BiOI-LD was linked to the generation of *CH 3 .
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Bone Research
·
2025
·Vol. 13
·期 1
·1-17
·
IF 15
Ni Yuehan,Wu Jiamiao,Liu Fengqi,Yi Yating,Meng Xiangjiao,Gao Xiang,Xiao Luyi,Zhou Weiwei,Chen Zexi,Chu Peng,Xing Dan,Yuan Ye,Ding Donghui,Shen Ge,Yang Min,Wu Ronjie,Wang Ling,Melo Luiza Martins Nascentes,Lin Sien,Cheng Xiaoguang,Li Gang,Tasdogan Alpaslan,Ubellacker Jessalyn M.,Zhao Hu,Fang Shentong,Shen Bo
Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR + ) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR + stromal cells, within optically cleared bone hemisections. Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae. The protocol entails tissue fixation, decalcification, and cryosectioning to reveal the marrow cavity. Completed within approximately 12 days, this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals. The bone hemisections are compatible with diverse antibody labeling strategies. Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software, assessing a spectrum of parameters. With proper storage, the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months. This protocol is robust, straightforward to implement, and highly reproducible, offering a valuable tool for tissue architecture and cellular interaction studies.
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Chinese Medicine
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2025
·Vol. 20
·期 1
·1-14
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IF 5.7
Jiang Feng,Tang Jiayang,Wei Xiaoqi,Pan Hai,Fan Xinyi,Zhang Peng,Guo Shuzhen
Background Dilated cardiomyopathy (DCM) stands as one of the most prevalent and severe causes of heart failure. Inflammation plays a pivotal role throughout the progression of DCM to heart failure, while age acts as a natural predisposing factor for all cardiovascular diseases. These two factors often interact, contributing to cardiac fibrosis, which is both a common manifestation and a pathogenic driver of adverse remodeling in DCM-induced heart failure.MethodBulk RNA-seq, single-cell RNA-seq, Mendelian randomization analysis, animal model construction, and BMP6 knockdown were utilized to identify and validate potential specific markers and targets for intervention in DCM heart failure.Results We found that DCM hearts exhibit pronounced inflammatory cell infiltration and fibrosis. Both bulk RNA-seq and single-cell RNA-seq analyses revealed aberrant BMP6 expression specifically in fibroblasts. The ROC curve underscores the high specificity of BMP6 in relation to DCM, while Mendelian randomization analysis further confirms BMP6 as a protective factor against DCM. Notably, BMP6 knockdown led to a decrease in SMAD6 expression and a marked elevation in COL1A1 expression levels, indicating its antifibrotic role.Conclusion BMP6 emerges as a promising biomarker for DCM, and its functional role in exerting an antifibrotic effect underscores its potential as a therapeutic target.
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ENVIRONMENTAL MONITORING AND ASSESSMENT
·
2011
·Vol. 184
·期 5
·3085-3094
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IF 1.436
Li Yongfang,Yang Zhongzhi,Kong Xiaoduo,He Guangjie
As facile “environmental media”, the outdoor dust may reflect the changes of contaminants in environment more promptly. In the present study, selected organochlorine contaminants (OCs) include hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethanes (DDTs), hexachlorobenzene (HCB), and pentachlorobenzene (PeCB) were detected in 20 outdoor dust samples collected from Xinxiang City. The concentrations of ΣHCHs, ΣDDTs, HCB, and PeCB in dust were in the range of 0.18–5.05 ng/g dry weight, 0.44–13.50 ng/g dry weight, 0.13–51.61 ng/g dry weight and ND-0.74 ng/g dry weight, respectively. Long-range transport, historical use, and recent impact of impure pesticides might be the main sources of OCs in the outdoor dust. The results of this study indicated that impure pesticide application maybe an important source of DDTs and HCB in the environment.
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BIOLOGICAL PROCEDURES ONLINE
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2024
·Vol. 26
·期 1
·1-15
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IF 3.7
Wang Huizhi,Min Jingyu,Ding Yuntao,Yu Zhengyue,Zhou Yujing,Wang Shunyu,Gong Aihua,Xu Min
Background Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. Methods MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. Results MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. Conclusion MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.
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MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 5
·1-14
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IF 5.3
Bu Ziyun,Si Qiankang,Lu Xiaolin,Wang Pei,Wu Dezhen,Mei Yingying
A novel monolithic capillary column (AuNPs@CMIP(poly-Chitosan)@capillary) with hybridized chiral molecular imprinted polymers (CMIPs) as stationary phase was prepared using S-metolachlor (S-MET) as template, chitosan as functional monomer, glutaraldehyde as cross-linker, and aminated-gold nanoparticles (NH 2 -AuNPs) as nanocarriers. The capillary electrochromatography (CEC) system constructed by AuNPs@CMIP(poly-Chitosan)@capillary achieved the efficient chiral separation of MET (resolution (Rs) = 9.83) as well as separation of its various structural analogs (Rs > 1.58). In addition, AuNPs@CMIP(poly-Chitosan)@capillary exhibits satisfactory reproducibility and stability. The relative standard deviations (RSDs) of migration times and Rs for intra-day, inter-day, and inter-column were all less than 6.1%, and no significant decline in separation performance was observed after 21 days of storage. NH 2 -AuNPs, with their large specific surface area and stable structure, can provide abundant binding sites and play a supporting role, reducing the deformation and collapse of CMIPs’ cavities, and further ensuring the structural stability and separation performance of the stationary phase. Finally, parameters such as imprinting factor and selectivity factor were calculated by adsorption experiments, and the CEC separation mechanism was discussed. The chitosan CMIPs-based capillary monolithic column developed in this work has rarely been reported and is an innovative attempt, providing a feasible and promising approach for the development of CEC chiral monolithic stationary phases. Graphical abstract
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危险品化学品经营许可证（带存储）