Scientific Reports
·
2024
·Vol. 14
·期 1
·1-14
·
IF 3.8
Kong Chenfan,Sun Jianrong,Hu Xinzi,Li Guangzhi,Wu Song
Immune checkpoint inhibitors (ICIs) are effective agents for tumor immunotherapy. However, their clinical effectiveness is unsatisfactory due to off-target effects and a suppressive immune microenvironment. This study developed a nanodrug delivery system for bladder cancer (BCa) using PCL-MPEG and PCL-PEG-CHO to synthesize internal hydrophobic and external hydrophilic micelles (PP) that encapsulated water-insoluble astragaloside IV (PPA). The aldehyde group on the surface of PPA reacted with the amino group of aPD-L1, allowing the decoration of this antibody on the surface of the micelles. The resultingPPA@aPD-L1effectively piggybacked astragaloside IV and aPD-L1 antibody. These findings suggest that PPA@aPD-L1 is relatively stable in circulation and efficiently binds to BCa cells with the aid of aPD-L1. Additionally, this strategy prolongs the drug’s retention time in tumors. Compared to PBS, PP, and PPA with PPA + aPD-L1 groups, PPA@aPD-L1significantly prolonged the survival of mice with BCa and reduced tumor volume. Mechanistic studies showed that PPA inhibited the NF-κB and STAT3 signaling pathways in tumor cells. Additionally, PPA@aPD-L1increased IFN-γ and decreased IL-10 expression in bladder tumors, affecting the number and type of intratumorally infiltrating T cells. Our study presents a simple and effective drug delivery system that combines herbal monomers with ICIs. It has demonstrated a potent ability to suppress tumor growth and holds potential for future applications.
研究领域:
癌症治疗
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纳米技术
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药学
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免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2026
·
IF 4
Mengjun Sun,Chunliu Mi,Tiantian Dong,Jingwen Xue,Yan Lin,Shaolei Geng,Qiuli Sun,Xinjian Chang,Tianyun Wang
7,8-DHF enhances recombinant protein expression 1.5-1.6 fold and reduces antibody aggregation by 6.0% in CHO cells. • 7,8-DHF elevates NAD+ to activate SIRT1-PGC-1β, improving mitochondrial energy synthesis and reducing lactate. • 7,8-DHF upregulates BCL-2 and downregulates BAX/cleaved caspase-3, inhibiting apoptosis in CHO cells. • 7,8-DHF acts as a metabolic modulator to overcome aerobic glycolysis limitations in biopharmaceutical production. Chinese hamster ovary (CHO) cells serve as a critical mammalian system for producing therapeutic proteins in biopharmaceuticals. However, these cells exhibit highly active aerobic glycolysis during culture, which leads to reduced energy conversion efficiency and excessive lactic acid accumulation. This metabolic dysregulation can further impair cell growth and recombinant protein expression. Enhancing the endogenous NAD⁺ level is critical for improving cellular metabolism; however, current technical approaches face significant challenges. In the present study, we found that 7,8-dihydroxyflavone increased the expression of recombinant proteins in CHO cells by 1.6- and 1.5-fold, respectively, while reducing antibody aggregation by approximately 6.0%. Transcriptome and metabolic pathway analyses revealed that the elevated intracellular NAD⁺ content activated the SIRT1-PGC-1β pathway, which modulates mitochondrial energy synthesis and enhances antioxidant capacity while mitigating lactate accumulation in the glycolytic pathway. Furthermore, 7,8-dihydroxyflavone significantly inhibited apoptosis by upregulating BCL-2 expression and downregulating BAX and cleaved caspase-3 expression. Taken together, these findings indicate that 7,8-dihydroxyflavone may serve as a promising metabolic modulator for recombinant protein production.
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jiajun Yu,Xiao Wang,Shijie Yang,Xiaofeng Xie,Jing Sun
Ligand functionalization could effectively modulate the local electron distribution of MOFs, thus improving their performance in both the capturing and photocatalytic oxidization of various VOCs. In this work, a series of Fc-CHO/NU-X (X = 1, 2, 3, 4) were obtained through the ligand functionalization of reo -NH 2 -UiO-66 (denoted as NU) with ferrocenecarboxaldehyde (Fc-CHO) as the modifier. By altering the local charge distribution and inducing Fe-OH and cyclopentadienyl rings as new adsorption sites, Fc-CHO altered the adsorption behavior of both aromatic and oxygenated VOCs and consequently their degradation pathways. The introduction of electron-donating Fc-CHO enhanced the ligand to metal charge transfer (LMCT), accelerated the electron-hole separation and therefore promoted the effective formation of oxidative radicals, facilitating the effective oxidation of acetaldehyde. Direct charge transfer through p-p interaction enabled the ring-opening and deep oxidation of toluene. The degradation efficiencies of toluene and acetaldehyde increased from 25 % and 28 % (NU) to 80 % (Fc-CHO/NU-3) and 65 % (Fc-CHO/NU-2), respectively. Positive effects of Fc-CHO functionalization were also observed during the removal of acetaldehyde-toluene mixtures and the synergistic effect between acetaldehyde and toluene was revealed. This work provides new ideas and novel materials for the purification of in-door air pollutants.
研究领域:
环境化学
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材料科学
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光催化
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纳米技术
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空气净化
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Hongyu Zhu,Sen Yang,Jingyang Zhao,Liuyang Wang,Chenghao Gao,Yanan Sheng,Xuan Lin,Zhiguo Su,Kiichi Sato,Zhongyu Hu,Songping Zhang
All-trans retinoic acid (Ra) has been demonstrated to enhance the establishment of systemic and intestinal immunity for codelivered antigens; however, the extremely poor water solubility of Ra significantly limits its application in vaccines. Herein, leveraging the advantages of ionic liquids in modifying the physicochemical properties of small-molecule drugs, we synthesized a novel ionic liquid composed of choline and retinoic acid ([Cho][Ra]). Compared to Ra, [Cho][Ra] exhibited an 18165-fold increase in solubility at pH 7.4 and an acid-responsive Ra release behavior. The [Cho][Ra] was then formulated with the SARS-CoV-2 RBD antigen, and its adjuvant effects were comprehensively evaluated. The in vitro cellular studies indicated that at 50 μg Ra equivalent dose, the [Cho][Ra]@RBD showed significantly higher than RBD along in activation of BMDC and the expression of gut homing molecules, including C–C motif chemokine receptor 9 (CCR9, 10.55 folds), α4β7 integrin (13.29 folds), and lymph node migration molecule CCR7 (82.68 folds). Animal experiments showed that compared to RBD alone, [Cho][Ra]@RBD promoted the establishment of mucosal immunity in the intestines in mice at the early stage following subcutaneous immunization and elicited higher serum antibody levels. Furthermore, compared to RBD and Alum@RBD, [Cho][Ra]@RBD enhanced the formation of CD4+ TCM and CD8+ TCM cells, indicating stronger cellular immune responses. In summary, [Cho][Ra] showed potential adjuvant effects in enhancing the humoral and cellular immune responses, as well as in the establishment of intestinal mucosal immunity for RBD antigen without the need for delivery system, thereby offering promising prospects for applying Ra in vaccines.
研究领域:
免疫学
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药剂学
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分子药理学
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疫苗学
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纳米医学
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药物递送
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转化医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Zhongyu Jing,Wenli Su,Yu Fan
The development of a new system for the electrochemical carbon dioxide reduction reaction (ECO 2 RR) to methane (CH 4 ) is challenging, and novel conductive metal organic frameworks (c-MOFs) for efficient ECO 2 RR to CH 4 are critical to this system. Here, we report a novel c-MOF, copper-pyromellitic dianhydride-2-methylbenzimidazole (Cu-PD-2-MBI), in which the introduction of electron-withdrawing 2-methylbenzimidazole (2-MBI) into the copper-pyromellitic dianhydride (Cu-PD) interlayer elevated the valence of copper (Cu) ions, which improved the ECO 2 RR performance of Cu-PD-2-MBI. Cu-PD-2-MBI was tested in a flow cell, and the Faradaic efficiency of CH 4 reached 73.7 %, with a corresponding partial current density of −428.3 mA·cm −2 at −1.3 V, which was higher than those of most reported Cu-based catalysts. Further exploration via theoretical calculations indicated that the intercalated 2-MBI in Cu-PD-2-MBI induced a shift in the d-band center in the Cu sites from −2.63 to −1.86 eV and reduced the formation energy of the *COOH and *CHO intermediates in the process of generating CH 4 compared with those of the reference Cu-PD catalyst.
研究领域:
电化学
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材料科学
·
催化
·
环境科学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2023
·
IF 11.4
Guangrong Sun,Pei Guo,Han Yeong Kaw,Meijiao Zhou,Wei Wang
Constant efforts have been devoted to exploring new disinfection byproducts in drinking water causally related to adverse health outcomes. In this study, five halogenated nucleobases were identified as emerging disinfection byproducts in drinking water, including 5-chlorouracil, 6-chlorouracil, 2-chloroadenine, 6-chloroguanine, and 5-bromouracil. We developed a solid phase extraction–ultraperformance liquid chromatography–tandem mass spectrometry method with the limits of detection (LOD) and recoveries ranging between 0.04–0.86 ng/L and 54–93%, respectively. The detection frequency of the five halogenated nucleobases ranged from 73 to 100% with a maximum concentration of up to 65.3 ng/L in the representative drinking water samples. The cytotoxicity of the five identified halogenated nucleobases in Chinese hamster ovary (CHO-K1) cells varied with great disparity, in which the cytotoxicity of 2-chloroadenine (IC50 = 9.4 μM) is appropriately three times higher than emerging DBP 2,6-dichloro-1,4-benzoquinone (IC50 = 42.4 μM), indicating the significant toxicological risk of halogenated nucleobase-DBPs. To the best of our knowledge, this study reports the analytical method, occurrence, and toxicity of halogenated nucleobase-DBPs for the first time. These findings will provide a theoretical basis for further research on probing the relationship between its mutagenicity and human health risk.
研究领域:
环境科学
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毒理学
·
分析化学
·
水处理
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2017
·
IF 6.216
Peng Hu,Xiaopeng Liang,Muhammad Yaseen,Xiaodan Sun,Zhangfa Tong,Zhongxing Zhao,Zhenxia Zhao
A novel mechano-chemical strategy using dopamine to modify UiO-66(Zr) by N-coordination was proposed to enhance its competitive adsorption for acetaldehyde, chlorobenzene/H 2 O, both thermodynamically and kinetically. The newly synthesized material was characterized by SEM, EDX, XPS, PXRD, FT-IR, TGA/DTG and BET techniques. Results showed that N was successfully grafted into UiO-66(Zr) frameworks through coordination interaction with Zr-O clusters resulting in M-UiO-66(Zr-N 3.0 ). The obtained M-UiO-66(Zr-N 3.0 ) exhibited a significant increase in adsorption of chlorobenzene (4.94 mmol/g) and acetaldehyde (9.42 mmol/g) compared to parent UiO-66(Zr) and UiO-66(Zr)-NH 2 . The H 2 O adsorption uptake of M-UiO-66(Zr-N 3.0 ) decreased by 20% that of UiO-66(Zr) and 47% of UiO-66(Zr)-NH 2 indicating higher hydrophobicity of the modified material. Kinetic performance indicated that diffusivity of chlorobenzene on M-UiO-66(Zr-N 3.0 ) was about 7.8 and 40 times higher than that of the parent UiO-66(Zr) and UiO-66(Zr)-NH 2 respectively and 15.4 times higher than that of H 2 O on itself. Based on the results, the current N-modification strategy can be deemed as an efficient way to improve MOFs competitive adsorption towards VOCs under humid conditions and it might play active role in industries involving adsorbent applications.
研究领域:
材料科学
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环境科学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Yuanping Hao,Changqing Yuan,Jing Deng,Weiping Zheng,Yanjing Ji,Qihui Zhou
Soft-tissue trauma emergency caused by natural disasters and traffic accidents is highly prevalent, which can result in massive bleeding, pathogen infection, and even death. Although numerous tissue adhesives can bind to tissue surfaces and cover wounds, most of them still have several deficiencies, including long gelation time, poor adhesive strength, and anti-infection, making them inappropriate for use as first-aid bandages. Herein, injectable and self-healing four-arm-PEG-CHO/polyethyleneimine (PEI) tissue adhesives as liquid first-aid supplies are developed via the dynamic Schiff base reaction for trauma emergency. It is found that the prepared hydrogel adhesives exhibit short and controlled gelation time (9∼88 s), strong adhesive strength, and excellent antibacterial ability. Their hemostatic and antimicrobial performances can be tailored by the mass ratio of four-arm-PEG-CHO/PEI. Moreover, in vitro biological assays display that the developed tissue adhesives possess satisfactory cyto/hemocompatibility. Importantly, in vivo the designed adhesives show fast hemostatic capacity and excellent anti-infection as compared to commercial Prontosan gel. Thus, this work indicates that the four-arm-PEG-CHO/PEI first-aid tissue adhesives display great potential for wound emergency management.
研究领域:
材料科学
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生物医学工程
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急诊医学
·
组织工程
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产品关联
DOI
PubMed
高影响因子
GREEN CHEMISTRY
·
2025
·
IF 9.2
Yahui Jiang,Haichuan He,Dan Xia,Hongwei Zhang,Shirui Tan,Li Luo,Yifan Kong,Liu Deng,You-Nian Liu
Cu-based catalysts are widely employed in the electrocatalytic CO2 reduction reaction (CO2RR) toward multi-carbon (C2+) products due to their unique electronic structures. However, Cu-based catalysts are prone to reconstruction under working conditions. Self-reduction and undesirable reconstruction have limited the activity and selectivity of these catalysts. Understanding their reconstruction behavior is crucial for elucidating reaction mechanisms and rationally designing catalysts. In this study, Br-doped Cu-base catalysts were employed to investigate the influence of dopants on catalyst surface reconstruction during CO2RR. Characterizations confirmed that during CO2RR, partial Br− leached from the precursor, while residual bromide ions in the Cu matrix created a bromine-rich environment on the catalyst surface, stabilizing Cu0/Cu+ active sites. The reconstructed catalyst exhibited superior selectivity for C2+ products and higher current density. In situ characterization and theoretical calculations demonstrated that the interaction between Br and Cu atoms suppressed complete Cu reduction. Furthermore, the asymmetric coupling pathway via *CO and *CHO intermediates dominated C2+ product formation, with significantly reduced Gibbs free energy of key intermediates compared to undoped CuO. Notably, halogen doping was validated as a universal strategy—Cu–Cl and Cu–F catalysts similarly enhanced C2+ production while exhibiting analogous reconstruction behavior. This study provided deep insights into catalyst surface reconstruction and offered effective strategies for designing high-performance catalysts for CO2RR.
研究领域:
电化学
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催化
·
材料科学
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环境化学
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能量转换
·
表面科学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
·
IF 3.4
Xin Zheng,Wei Wu,Yurou Li,Wupei Pan,Yinan Xu,Lianwei Zhong,Yinjie Jiang,Jie Zhou
Matrine (MT), an alkaloid extracted from Sophora flavescens , is widely used in traditional Chinese medicine. However, its clinical application is limited by its toxic effects. In this study, we explored the function of the activating transcription factor 4 /cystathionine γ-lyase (ATF4/CTH) pathway in MT-induced cardiac injury. Our results indicated that MT significantly decreased cysteine (Cys) and glutathione (GSH) levels, leading to mitochondrial dysfunction and apoptosis characterised by ROS accumulation, mPTP opening, ΔΨm disruption, and caspase-9/3 activation. However, caspase-3 inhibition and GSH supplementation alleviated these toxic effects. NAC similarly protected against MT-induced apoptosis by providing Cys as a substrate for GSH synthesis, whereas BSO abolished this protection by inhibiting GSH biosynthesis. Additionally, MT suppressed both ATF4 expression and its transcriptional activity, leading to reduced mRNA and protein levels of the downstream target gene CTH, and consequently diminished CTH-dependent Cys production. Overexpression of either ATF4 or CTH attenuated MT-induced apoptosis by restoring intracellular Cys and GSH levels. CTH knock-down completely abrogated the protective effects of ATF4 overexpression, whereas CTH overexpression retained its efficacy, even in the absence of ATF4. These results indicated that MT-induced suppression of the ATF4/CTH pathway causes GSH deficiency, leading to mitochondria-dependent apoptosis and cardiotoxicity.
研究领域:
毒理学
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分子生物学
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心血管研究
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药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2024
·
IF 3.3
Jun Yan,Yunfei Zhou,Jianwen Xu,Yihong Dong,Xun Yang,Xinxin Yang,Aodi Wu,Shuyuan Chang,Yumeng Wang,Qingxin Zhang,Tomii Ayaka,Lei Yu,Liuyang Zhao,Hongxue Meng,Dabin Liu
Lactylation is an emerging pathogenesis of hepatocellular carcinoma (HCC). However, the underlying mechanisms and biological significance remain poorly understood. The Carbonic anhydrase III (CA3) gene, previously defined as a binding protein of SQLE and involved in the NAFLD disease, has now been identified as a novel tumor suppressor in HCC. mRNA expression of CA3 is associated with a favorable prognosis and negatively correlated with serum lactate levels, whereas CA3 protein expression does not correlate with patient prognosis or serum lactate levels, suggested there has lactate-related post-translational modification of CA3 in HCC. Overexpression of CA3 induces cell apoptosis, thereby reducing intracellular reactive oxygen stress (ROS) through the inhibition of DUOX2 expression. The decreased lactylation level of CA3 protein at the K36 residues, induced by SQLE, results in the loss of the anti-cancer effect of CA3. Together, this study has demonstrated that CA3 is a novel tumor suppressor in HCC, and delactylation of CA3 represents a newly identified mechanism by which HCC cells evade growth suppressors.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Jie Zhou,Xin Zheng,Chen Xi,Xinyi Tang,Yinjie Jiang,Minjuan Xie,Xiaoyi Fu
Hexavalent chromium [Cr(VI)] is a highly hazardous heavy metal with multiple toxic effects. Occupational studies indicate that its accumulation in humans can lead to liver damage. However, the exact mechanism underlying Cr(VI)-induced hepatotoxicity remains unknown. In this study, we explored the role of CTH/H 2 S/Drp1 pathway in Cr(VI)-induced oxidative stress, mitochondrial dysfunction, apoptosis, and liver injury. Our data showed that Cr(VI) triggered apoptosis, accompanied by H 2 S reduction, reactive oxygen species (ROS) accumulation, and mitochondrial dysfunction in both AML12 cells and mouse livers. Moreover, Cr(VI) reduced cystathionine γ-lyase (CTH) and dynamin related protein 1 (Drp1) S-sulfhydration levels, and elevated Drp1 phosphorylation levels at Serine 616, which promoted Drp1 mitochondrial translocation and Drp1-voltage-dependent anion channel 1 (VDAC1) interactions, ultimately leading to mitochondria-dependent apoptosis. Elevated hydrogen sulfide (H 2 S) levels eliminated Drp1 phosphorylation at Serine 616 by increasing Drp1 S-sulfhydration, thereby preventing Cr(VI)-induced Drp1-VDAC1 interaction and hepatotoxicity. These findings indicated that Cr(VI) induced mitochondrial apoptosis and hepatotoxicity by inhibiting CTH/H 2 S/Drp1 pathway and that targeting either CTH/H 2 S pathway or Drp1 S-sulfhydration could serve as a potential therapy for Cr(VI)-induced liver injury.
研究领域:
毒理学
·
细胞生物学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
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