JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Hang Zhang,Yujie Zhang,Yinping Geng,Xuanlong Zhen,Xiaodi Wang,Qiange Yin,Peng Zhang,Yuanyuan Li,Mengzhen Zhang,Yi-chao Zheng,Bing-rui Liu,Hui-min Liu,Hai-wei Xu
Gastric cancer is one of the major health threats to human beings and has a low response rate to emerging immunotherapy. We herein reported a novel indole-based LSD1-targeted antigastric agent 7ae, which was able to enhance the sensitivity of gastric cancer cells to a T-cell-mediated immune response. It exhibited potent LSD1 inhibitory activity (IC50 = 0.080 ± 0.002 μM) and reduced the expression of PD-L1, which in turn promoted the T-cell killing response in gastric cancer cells. As a result, 7ae acted as an active LSD1 inhibitor, exerting excellent anti-invasion and anti-migration effects in gastric cancer cells and leading to significant suppression of the growth of xenograft gastric tumors without obvious toxicity in vivo. Collectively, 7ae has been demonstrated to be a novel, potent LSD1 inhibitor with the potential to be used as an antigastric agent, as well as a useful tool compound for exploratory studies of T-cell-mediated immunity and/or immunotherapy in gastric cancer.
研究领域:
肿瘤学
·
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL RESEARCH
·
2023
·Vol. 33
·期 12
·923-939
·
IF 44.1
Liu Rui,Zeng Lin-Wen,Li Hui-Fang,Shi Jun-Ge,Zhong Bo,Shu Hong-Bing,Li Shu
Combination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γ c ). PD-1 ligation also activates SHP2, which dephosphorylates γ c Y357 , leading to impairment of γ c family cytokine-triggered signaling. Conversely, PD-1 blockade restores γ c level and activity, thereby sensitizing CD8 + T cells to IL-2. We also identified Pitavastatin Calcium as an inhibitor of MARCH5, which combined with PD-1 blockade and IL-2 significantly improves the efficacy of anti-tumor immunotherapy in mice. Our findings uncover the mechanisms by which PD-1 signaling antagonizes γ c family cytokine-triggered immune activation and demonstrate that the underlying mechanisms can be exploited for increased efficacy of combination immunotherapy of cancer.
研究领域:
免疫学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Song Ruilian,Wang Yixiang,Li Yanjun,Wang Qifei,Zhang Siyu,Sun Dongfa,Sun Genlou,Sun Longqing,Ren Xifeng
Although metabolites of barley grains have been analyzed, the changes in metabolite abundance and gene expression regulation mechanisms during barley grain development have not been elucidated. Here, we explore the dynamic accumulation patterns of metabolites in barley grains at six different developmental stages by analyzing high-resolution metabolomic and transcriptomic data from Huadamai6 and Huaai11. We detect 986 metabolites and 18,868 co-expressed genes. Meanwhile, we identify 1057 mQTLs associated with 553 metabolites in a double haploid (DH) population derived from these two cultivars, and integrate metabolome, transcriptome, and mQTL information to construct a global co-expression regulatory network of barley grain metabolism. Using this dataset, we excavate transcription factors and structural genes that regulate flavonoid metabolism pathway, and also reveal the complex mechanism of HvC1-1 and HvMYC-1 regulating grain color differentiation in the DH population. Our findings reveal the metabolic regulatory network of barley grains development, and provide valuable resources for future nutritional quality improvement and molecular design breeding of barley.
研究领域:
植物学
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遗传学
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生物信息学
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分子生物学
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作物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2025
·
IF 3.9
Guojun Lv,Linfang Jiang,Yan Chen,Xuyang Zou,Xubin Zhang,Fumin Wang
The addition of an additional mesoporous/macroporous templating agent inevitably has an adverse effect on the economy and greenness of the seed-assisted synthesis process for hierarchical zeolites; hence, the development of an efficient seed-assisted method for the synthesis of hierarchical zeolite without the addition of an additional additive is appealing. Herein, we reported the preparation of hierarchical TS-1 zeolite with a large amount of mesopores using a liquid–solid mixture seed-assisted method and its application as a heterogeneous catalyst in the oxidative desulfurization reactions. The characterization results disclosed that the liquid–solid mixture seed was more conducive to the formation of hierarchical TS-1 zeolite than liquid seed alone and solid seed alone. The formation process of hierarchical TS-1 zeolite with different crystallization times was investigated in detail, and accordingly, a possible two-stage crystallization mechanism was proposed. In addition, the synthesized hierarchical TS-1 zeolite showed remarkably enhanced catalytic activity in the oxidative desulfurization of dibenzothiophene (DBT) and 4,6-dimethyldibenzothiophene (4,6-DMDBT) in comparison to the conventional microporous TS-1 zeolite. This work provides some guidance for the development of a more efficient and greener seed-assisted synthesis method for hierarchical zeolites without the addition of any additional mesoporous/macroporous templating agent.
研究领域:
材料科学
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催化化学
·
环境工程
✓ 已验证
产品关联
DOI
高影响因子
APPLIED PHYSICS A-MATERIALS SCIENCE & PROCESSING
·
2020
·Vol. 126
·期 11
·1-14
·
IF 1.81
Shi Feng,Xiao En-Cai,Chen Guohua,Chen Ying
Non-stoichiometric Nd[Mg 0.5 Sn 0.5(1+ x ) ]O 3 (− 0.04 ≤ x ≤ + 0.04)—type samples were prepared using a traditional two-step solid-state sintering process. Their crystal structures, phase compositions, dielectric properties and lattice vibrational characteristics were identified in detail. The double perovskite Nd(Mg 0.5 Sn 0.5 )O 3 with a monoclinic structure was distinguished as the main crystalline phase, and pure phase was obtained when x < 0. The sample [Nd(Mg 0.5 Sn 0.49 )O 3 ] at x = − 0.02 shows the excellent dielectric properties: ε r = 18.74, Q × f = 47,979 GHz. The lattice vibrational characteristics were clarified with Raman and infrared active mode spectroscopy. The intrinsic properties were fitted by four-parameter semi-quantum model, which show that the low-frequency infrared modes yield a more significant contribution to permittivity and dielectric loss. Raman shifts of modes F 2g (A) and F 2g (B) correlate with dielectric constants negatively, which implies that the bond length has a positive correlation with permittivity. Full widths at half maximum of vibrational modes A 1g (O) correlate with dielectric loss values positively and correlate with the degree of order ( S ) negatively.
研究领域:
材料科学
·
物理学
✓ 已验证
DOI
高影响因子
CLINICAL AND EXPERIMENTAL HYPERTENSION
·
2025
·
IF 3.5
Hao Wang,Ke Zhou,Xiaoling Chen,Yao Tong,Qiuyan Jiang,Qiang She,Jun Xiao
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.
研究领域:
心血管病学
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分子药理学
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氧化应激生物学
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心肌缺血再灌注损伤
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信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ELECTROCHEMISTRY COMMUNICATIONS
·
2020
·
IF 4.333
Min Li,Ying Li
The conversion of solid Bi 2 O 3 to bismuth in a urea–1-methylimidazolium trifluoromethylsulfonate (urea–MIMTfO) electrolyte is studied for the first time. The electrochemical reduction behavior of solid Bi 2 O 3 was studied using a home-made graphite cavity working electrode. Cyclic voltammetry of the graphite cavity electrode confirms that solid Bi 2 O 3 is converted to metallic bismuth via a one-step process. Electrolysis experiments were carried out under constant voltages of 2.4 V, 2.6 V, and 2.8 V for various periods of time. Experimental results indicate that the urea–MIMTfO solution is a useful electrolyte for the electrochemical conversion of solid Bi 2 O 3 to metallic bismuth. This approach offers a green and straightforward method for the conversion of oxides to metals.
研究领域:
材料科学
·
电化学
✓ 已验证
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Yanna Lin,Xueying Wang,Yuanling Sun,Yuxue Dai,Weiyan Sun,Xiaodong Zhu,Hao Liu,Rui Han,Dandan Gao,Chuannan Luo
In this work, target-responsive DNA hydrogel with high loading and good biocompatibility was used to construct chemiluminescent biosensor for specific detection of adenosine. Acrydite-modified adenosine aptamer (Acry-A-Apt), acrydite-modified single-strand DNA (Acry-ssDNA) and hemin aptamer (H-Apt) were used to prepared the DNA hydrogel, and the three single-strand DNA were partially complementary to each other. Thus, the DNA hydrogel only dissolved when adenosine and hemin were present simultaneously. HKUST-1 is a Cu-based MOFs with peroxidase-like activity. Au NPs were coated into cavities of HKUST-1 to obtain [email protected] , and the [email protected] had a stronger peroxidase-like activity than HKUST-1. [email protected] was coated in the DNA hydrogel. When only hemin was present, hemin bound to the H-Apt to form the G-quadruplex/hemin and the DNA hydrogel remained in the gel state. Therefore, the G-quadruplex/hemin was formed in the hydrogel and the excess hemin can be removed, avoiding background signal interference. Adenosine was then added and the preferential interaction between adenosine and adenosine aptamer resulted in complete dissolution of the DNA hydrogel. Subsequently, G-quadruplex/hemin and [email protected] were released simultaneously, enabling dual signal amplification of chemiluminescent biosensor, yielding a “signal on” readout. As a result, the biosensor could quantify adenosine from 4 × 10 −13 – 1.5 × 10 -10 mol/L with a detection limit as low as 1.04 × 10 −13 mol/L. The DNA hydrogel system provides a simple, sensitive and biocompatible method for the detection of adenosine which is useful in the field of biotechnology.
研究领域:
生物技术
·
分析化学
·
材料科学
✓ 已验证
DOI
高影响因子
Frontiers in Materials
·
2020
·
IF 2.705
Li Xinxi,Liu Long,Li Shumin,Guo Lin,Li Bin,Zhang Guoqing
Spinel lithium manganese oxide (LiMn2O4) based Li-ion battery (LIB) is attractive for hybrid/full electric vehicles because of its abundant resources and easy preparation. However, operation under an elevated temperature could cause severe capacity fading of the spinel cathodes. In this work, 1, 3-propane sultone (PS) is investigated as an electrolyte additive for improving the cyclability of the LiMn2O4/graphite LIB at elevated temperature. The charge and discharge measurement proves that PS can significantly enhance the cyclability of 053048-type LiMn2O4/graphite pouch cell at 60°C. Compared to the cell without additive, the capacity retention of the cell using electrolyte with 5% PS increases from 52 to 71% after 180 cycles. The improved cyclability is attributable to the modification of the solid electrolyte interface (SEI) on both positive and negative sides of the LiMn2O4/graphite cell by PS, which effectively prevents anode and cathode from structural breakdown and inhibits the electrolyte decomposition.
研究领域:
材料科学
·
电化学
✓ 已验证
DOI
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
·
IF 3.8
Rui Feng,Zhou Fang,Wei Wang,Tianbo Li,Xiaoyan Hu,Xinlong Yan,Zhongdong Zhang
Direct hydroxylation of benzene to phenol is an environmentally friendly strategy to produce phenol compared with the conventional process. In this work, vanadium-modified titanium silicate-1 (TS-1) with enhanced Lewis acid and charge density were prepared as catalysts for efficient hydroxylation of benzene to phenol in the presence of hydrogen peroxide as an oxidant under mild conditions. The hierarchical TS-1 zeolites with a high framework Ti content were synthesized in the presence of NH4HCO3, and then vanadium doping was used to change the acidity and charge density. It was found that NH4HCO3 favored the titanium substitution of framework sites and nanocrystal stacking of TS-1. Vanadium doping increased the amount of Lewis acid sites and the charge density associated with the framework Ti. The enhancement in acid and electron characteristics boosted the intrinsic catalytic reactivity of Ti-OOH species, which further improved the performances toward benzene hydroxylation. The presented strategy and mechanistic results clarified the relationship between the structure and acidity in TS-1 zeolite. It was also verified that hydroxyl radicals (•OH) rather than superoxide radicals (•O2–) were the reactive agents responsible for the consecutive selective oxidation of benzene.
研究领域:
催化化学
·
环境科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yiran Qian,Xiaoxi Chang,Mingyang Sun,Yunqi Chen,Jiachen Zang,Chenyan Lv,Guanghua Zhao,Tuo Zhang
Bioactive peptides have attracted significant attention for their potential health benefits; however, their oral administration is challenged by degradation from digestive proteases and limited intestinal absorption. In this study, we demonstrated the exceptional gastrointestinal stability of ferritin nanocages, which remained largely intact after 30 min of simulated gastric digestion and were highly resistant to intestinal proteolysis. Consistent with in vitro findings, orally administered ferritin successfully reached the intestinal tract without significant degradation in mice. We engineered a fusion protein by linking a glucagon-like peptide-1 (GLP-1) motif to the C-terminus of heteropolymer ferritin, generating HLG. Through Caco-2 monolayer assays, we confirmed that HLG absorption occurs primarily via TfR1-mediated endocytosis, followed by lysosomal trafficking and subsequent release of bioactive GLP-1. Oral administration of HLG significantly reduced blood glucose levels and food intake in type 2 diabetic mice, whereas the GLP-1 analog exenatide alone showed no such effects. These findings highlight the potential of ferritin-based nanocages as an effective oral delivery platform for bioactive peptides.
研究领域:
纳米医学
·
药剂学
·
分子药理学
·
生物材料
·
消化系统疾病
·
药物递送
·
代谢性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2022
·Vol. 13
·期 1
·1-16
·
IF 17.694
Yuan Xiaoxiao,Wang Ruirui,Han Bing,Sun ChengJun,Chen Ruimin,Wei Haiyan,Chen Linqi,Du Hongwei,Li Guimei,Yang Yu,Chen Xiaojuan,Cui Lanwei,Xu Zhenran,Fu Junfen,Wu Jin,Gu Wei,Chen Zhihong,Fang Xin,Yang Hongxiu,Su Zhe,Wu Jing,Li Qiuyue,Zhang Miaoying,Zhou Yufeng,Zhang Lei,Ji Guang,Luo Feihong
Gut dysbiosis has been linked to type 1 diabetes (T1D); however, microbial capacity in T1D remains unclear. Here, we integratively profiled gut microbial functional and metabolic alterations in children with new-onset T1D in independent cohorts and investigated the underlying mechanisms. In T1D, the microbiota was characterized by decreased butyrate production and bile acid metabolism and increased lipopolysaccharide biosynthesis at the species, gene, and metabolite levels. The combination of 18 bacterial species and fecal metabolites provided excellently discriminatory power for T1D. Gut microbiota from children with T1D induced elevated fasting glucose levels and declined insulin sensitivity in antibiotic-treated mice. In streptozotocin-induced T1D mice, butyrate and lipopolysaccharide exerted protective and destructive effects on islet structure and function, respectively. Lipopolysaccharide aggravated the pancreatic inflammatory response, while butyrate activated Insulin1 and Insulin2 gene expression. Our study revealed perturbed microbial functional and metabolic traits in T1D, providing potential avenues for microbiome-based prevention and intervention for T1D.
研究领域:
微生物学
·
内分泌学
·
代谢组学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
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