MEDICAL ONCOLOGY
·
2025
·Vol. 42
·期 10
·1-13
·
IF 3.5
Liu Yuankai,Li Xiu,Wang Haitao,Yang Qiong
Myelodysplastic syndrome (MDS) is a group of blood disorders characterized by impaired maturation of erythroid cells. Mutations in the U2 small nuclear RNA auxiliary factor 1 ( U2AF1 ) gene, particularly S34 (S34F/Y) and Q157 (Q157P/R), have been identified in 5–10% of MDS patients. By analyzing U2AF1 expression in hematopoietic stem progenitor cells and different blood cells in the GEO database, we have found the expression pattern of U2AF1 showed a significant stage specificity during normal erythropoiesis. To explore the specific impact of U2AF1 alterations on cellular function, we transduced K562 cells with lentivirus carrying four different types of U2AF1 mutants. Our results showed that these mutations significantly inhibited the growth of K562 cells. Mutations at the S34 sites (S34F and S34Y) reduced the mRNA expression levels of erythroid-related transcription factors GATA1 , NF-E2 , EKLF, and GFI-1B. The proportion of cells with CD71 low CD235a hig decreased, as well as the content of hemoglobin in K562 cells. In contrast, mutations at the Q157 site had opposite effects on these expression levels in K562 cells. Furthermore, we classified patients' risk ratings into three categories based on IPSS-R: moderate high-risk MDS, high-risk MDS, and very high-risk MDS. A total of 12 patients were analyzed, including 5 at moderate high-risk and 3 patients carrying mutations. Among 3 high-risk individuals, only one carried a mutation. 4 individuals at very high-risk, with 0 patients carrying the mutation. MDS patients with U2AF1 mutations (S34F, S34Y, Q157P, R156H) had significantly lower white blood cell, hemoglobin, and platelet counts than the MDS patients without these alterations. We hypothesize that treatment with Azacitidine (AZA) may lead to better recovery levels of hemoglobin and platelets for patients with U2AF1 mutations. Meanwhile, we found that U2AF1 -mutated MDS patients have better responsiveness to demethylating drugs. We isolated and cultured peripheral blood mononuclear cells (PBMCs) carrying the U2AF1 S34F mutation from a high-risk MDS patient with a 7q chromosome deletion. The demethylating drug AZA could significantly inhibit their proliferation and induce apoptosis in the MDS PBMCs. In summary, our research demonstrated the following: (1) The effect of U2AF1 mutation on erythrocyte differentiation that S34 mutation inhibits the differentiation process, but the Q157 mutation promotes the differentiation process. (2) The level of erythrocyte changes in U2AF1 -mutated MDS patients should receive more attention. (3) It also showed that demethylating drugs have promising therapeutic effects in treating MDS patients carrying U2AF1 mutations. Graphical abstract
研究领域:
血液学
·
肿瘤学
·
分子生物学
·
遗传学
·
转化医学
·
表观遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANICA CHIMICA ACTA
·
2020
·
IF 2.304
Li Li,Feifei Xing,Shourong Zhu
Two N 3 O 3 macrocyclic compounds with rigid chromogenic 1,8-dihydroxylenanthraquione and flexible diethylenetriamine/dipropenetriamine (L1 and L2), were synthesized and characterized. L1/L2 can interact with alkaline, alkaline-earth, as well as Zn 2+ , Pb 2+ , and Al 3+ chloride/perchloride evidenced by their DPV change and 1 H NMR spectra. Unexpectedly, both L1 and L2 can show chromogenic response to Na + , K + , and TBA + hydroxide (but not LiOH). Large cavity L2 can show chromic response to Ca(OH) 2 and Ba(OH) 2 , but L1 can only respond to Ca(OH) 2 in DMSO. L1 and L2 form 1:1 and 2:1 (Host:Guest) complex respectively with NaCl, NaOH, TBAOH in DMF/DMSO. Both hosts bind smaller Zn 2+ and Al 3+ in 2:1 in DMSO. L2 can form L2·TBAOH greenish yellow complex that gradually transformed to red L2 2 ·TBAOH in two steps in DMSO. Different from other macrocycles, L1 and L2 are ion-pair hosts that recognize cation and OH − via carbonyl groups.
研究领域:
有机化学
·
分析化学
✓ 已验证
DOI
高影响因子
JOURNAL OF POLYMER SCIENCE
·
2025
·
IF 3.6
Jianda Niu,Jigen Xie,Yang Chen,Hongli Xu,Jingqi Ji,Zhixian Dong,Jinbao Xu,Caihong Lei
Taking into account the challenges associated with the low ionic conductivity and restricted electrochemical stability range in all solid polymer electrolytes (ASSPEs)-based lithium metal batteries (LMBs), it becomes crucial to design effective ASSPEs to address these issues. The aza-Michael reaction represents a fundamental organic chemical process, which is noted for its mild conditions, high efficiency, and broad applicability to various substrates. Herein, the aza-Michael reaction was employed to synthesize a conductive amorphous poly(ether ester)-based ASSPE (PGT-SPE). The resulting PGT-SPE features a cross-linked architecture, creating an advantageous environment for lithium-ion transport and maintaining superior flexibility. These electrolytes demonstrate a remarkable ionic conductivity of 3.53 × 10 −5 S cm −1 at 30°C, an impressive t Li + $$ {t}_{Li^{+}} $$ (0.50), and robust electrochemical stability, reaching up to 4.9 V. Moreover, the LFP/PGT-SPE/Li battery setup, incorporating the newly developed PGT-SPE, achieves a high specific capacity and maintains exceptional cyclic performance, retaining 80% of its capacity after 100 cycles at a rate of 0.1C. This breakthrough in ASSPEs synthesis paves the way for advancements in LMB technology, promising enhanced performance and reliability. Graphical All solid polymer electrolyte (ASSPE) by facile aza-Michael reaction were prepared to achieve high ionic conductivity and Li-ion transference number. The flexible ASSPE demonstrates significant improvements in both mechanical strength, thermal stability, and electrochemical stability window. The assembled LMBs exhibit low interfacial resistance, Li dendrite suppression, high specific capacity, excellent cyclic performance, and durability.
✓ 已验证
产品关联
DOI
高影响因子
Polymer Chemistry
·
2018
·Vol. 9
·期 7
·869-877
·
IF 4.927
Bo Pang,Jingzhe Zhang,Minglei Pang,Peijian Zhao,Zhen Yang,Shengyu Feng,Jie Zhang
A new synthesis strategy was presented to prepare a polyurea–polysiloxane–polyether copolymer (PUA). A new block soft segment (b-SS) was synthesised via an aza-Michael addition reaction of acryloxymethyl-terminated polydimethylsiloxane (AT-PDMS) and amine-terminated polyoxypropylene (PPO). The hard segment (HS) was formed from bis(4-isocyanato cyclohexyl)methane (HMDI) and a 2-methyl-1,5-diaminopentane chain extender. The copolymers are tough and easily processed thermoplastic elastomers. The properties and structures of the polyurea–polysiloxane–polyether copolymers were investigated by dynamic mechanic analysis (DMA), small angle X-ray scattering (SAXS), atomic force microscopy (AFM) and macroscopy mechanical testing. The DMA results of the polyurea–polysiloxane–polyether copolymers show that temperature insensitive rubbery plateaus exist between −50 °C and 80 °C, which are independent of the HS wt% and the molecular weight of PDMS. The viscoelastic behavior of the polyurea–polysiloxane–polyether copolymers was correlated with the molecular weight of PDMS used for the b-SS. The polyurea–polysiloxane–polyether copolymers display improved mechanical strength (16 MPa) compared with the published results of PDMS-based siloxane-urea segmented copolymers (11–13 MPa). The studies reveal that the mild microphase separation between the hard and soft segments leads to improved mechanical strength of the polyurea–polysiloxane–polyether copolymers. In addition, for these copolymers, the introduction of b-SS is effective in avoiding a sharp phase separation assuming that the molecular weight of PDMS in the b-SS is appropriate.
研究领域:
材料科学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2021
·
IF 5.121
Yongwei Hao,Cuixia Zheng,Qingxia Song,Hongli Chen,Wenbin Nan,Lei Wang,Zhenzhong Zhang,Yun Zhang
Drug delivery with the help of nanoparticles could transport more payloads to tumour site. Owing to their limited accumulation and penetration in the tumour tissues, to increase delivery efficiency is currently still required for applying nanomedicine to treat tumour. Here, we initially report a pressure-driven accumulation of drug-loaded nanoparticles to tumours for efficient tumour therapy with a dry cupping device. The mesoporous Mn-doped silica based nanoparticles delivering 5-aza-2-deoxycytidine and docetaxel were prepared, characterised and used as a model nanomedicine to investigate the potential of dry cupping treatment. For this system, the Mn doping not only endowed the mesoporous silica nanoparticles biodegradability, but also made it much easier to bind a tumour targeting group, which is a G-quadruplex-forming aptamer AS1411. On tumour-bearing mice, the in vivo results demonstrated that the dry cupping treatment could substantially improve the distribution of nanomedicines at tumour site, resulting in enhanced treatment efficacy. Overall, this method enables the therapeutical nanoparticles accumulate to tumour through increasing the blood perfusion as well as altering the biological barrier, which opened up possibilities for the development of pressure-driven nanomedicine accumulation at tumour site.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemCatChem
·
2024
·Vol. 16
·期 21
·e202401010
·
IF 3.8
Ziwei Wu,Han Sun,Quanzheng Deng,Lu Han,Penggang Lv,Haijun Chen,Hongchang Duan,Kake Zhu
Graphical Mono-quaternary 1-(1-methylpropyl)-4-aza-1-azoniabicyclo[2.2.2]octane hydroxide is proposed to direct the Faujasite-to-Chabazite inter-zeolite conversion to generate 35–258 nm CHA crystals with Si/Al ratio of 7.2. The Cu-CHA zeolite exhibits superior hydrothermal stability and catalytic performance in standard NH 3 -SCR process. Cu-exchanged chabazite zeolite is the state-of-the-art used on-board catalyst for NO x selective reduction by ammonium (NH 3 -SCR), and the zeolite is currently generated in the presence of N , N , N -trimethyl-1-adamantylammonium hydroxide, serving as organic structure-directing agent (OSDA). The expensiveness of this OSDA increases the catalyst production cost, while its low degradability brings about environmental concerns in post treatment of waste water. Here, a new type OSDA, 1-(1-methylpropyl)-4-aza-1-azoniabicyclo[2.2.2]octane hydroxide, is proposed to direct Faujasite-to-Chabazite inter-zeolite conversion and generate chabazite with Si/Al ratio up to 7.2. The obtained zeolite possesses high hydrothermal stability for the high crystallinity, siliceous framework and low concentrations of Si(2Si, 2Al) sites. The Cu-form catalyst exhibits better catalytic performance in standard NH 3 -SCR process for the tiny crystallite size (35–258 nm) and formation of highly dispersed copper sites. The synthesis offers a new type of OSDA to fabricate zeolites and expands the toolkit to regulate their physicochemical properties.
研究领域:
材料科学
·
催化
·
无机化学
·
环境工程
✓ 已验证
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Yuling Li,Weiran Zhao,Xiang Xiang,YunLei Hu,Xiaoqiang Zhang,Wenjian Sun,Xiaoxuan Liu
Background Perturbed lipid metabolism in cellular environment plays an essential role in the progression of peripheral neuropathy, such as Charcot-Marie-Tooth disease type 1A (CMT1A). Current deep-profiling of lipidome still has certain limitations for high-throughput analysis of clinical samples, such as low sensitivity, extensive requirement of instrument modification, technician-dependent pretreatment and lack of method-adapted data-processing software. Results Herein, a new generation aza-Prilezhaev aziridination (APA) reagent has been designed for coupling with high-resolution liquid chromatography mass spectrometry (LC-MS) to conduct comprehensive untargeted deep lipidomics of CMT1A disease. It facilitates large-scale lipid structural annotations over a wide polarity range in a single run with high-sensitivity. With the developed method, an extensive library containing information on retention time, m / z , and MS/MS down to C=C location levels for 393 unsaturated lipids of CMT1A was created. Significant disease-related differences in C=C isomer profiles were observed from the comparison of plasma between CMT1A patients (N=9) and controls (N=8). Specifically, 40 different lipids were identified, predominantly comprising n-6, n-7, and n-9 C=C positional isomers. Significance This innovative methodology would offer substantial potential to enhance diagnosis and therapeutic strategies for CMT1A and other diseases based on lipid isomerization information.
研究领域:
神经病学
·
脂质组学
·
代谢组学
·
分子诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NORDIC PULP & PAPER RESEARCH JOURNAL
·
2022
·Vol. 37
·期 4
·636-648
·
IF 1.595
Yunfei Liao,Huiming Fan,Yongli Zhang,Hongyan Mou,Fengyu Li,Ziyin Zhou,Jianan Liu
PAAs can be further functionalized (hydroxylation and alkoxylation) by side chain substitution. In this study, we synthesized a SiPAAOH containing hydroxyl and siloxane groups based on the Aza-Michael addition reaction and applied it for reinforcement of aged paper. The results showed that the optimum conditions of SiPAAOH synthesis were as follows: the monomer molar ratio of APTES to EtA was 0.7:0.3, the solvent system for SiPAAOH reinforced aged paper was ethanol/water = 1:5 (v/v). The alkaline SiPAAOH could increase the pH of paper to 7.68, and to improve the amount of alkaline reserve to 200 mmol/kg. The whiteness and color difference of the treated paper were not significantly different from those of the untreated paper, and the mechanical properties of the paper were obviously improved. The results of contact angle and thermogravimetry showed that the SiPAAOH-treated paper was hydrophobicity and high temperature resistance.
研究领域:
材料科学
·
纸张保护
·
化学工程
✓ 已验证
DOI
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Shang JingJing,Xiong Chenwei,Jiang Wei,Yu Zhentang,Zhang Junjie,Zhang Yi,Han Long,Miao Kaisong,Yu Changlin,Huang Yong,Zhou Xindie
Background: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration
of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the
entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton
plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological
activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported.
However, its effect on chondrocytes in OA has yet to be determined.
Methods: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The
effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated
using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence
staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition
of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production
and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE)
staining and fluorescent dye BODIPY581/591 C11. in vivo, micro-CT imaging, hematoxylin
and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate
the effects of GAA on OA cartilage.
Results: The results showed that GAA treatment regulated the expression of chondrocyte extracellular
matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and
COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects
of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid
peroxidation levels and reversed the effect of IL-1β on the expression of ECM-related factors in
OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes
in OA by inhibiting GPX4 methylation.
Conclusion: Our findings revealed that GAA might be developed as a drug for treating OA clinically.
研究领域:
药理学
·
骨科
·
细胞生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR RESEARCH
·
2021
·Vol. 29
·期 7
·462-469
·
IF 2.227
Wang Lei,Yan Shijing,Zhang Lei,Mai Yuliang,Li Weihao,Pang Hao
The degradation and recycling of waste epoxy resin products is an urgent environmental problem. To solve this issue, we use acid-/base-degradable 1,1′,1″-(1,3,5-hexahydro-s-triazine-1,3,5-triyl) tris(3-ethylamino-propan-1-one) (TAHT-EA) as curing agent to introduce the hexahydro-s-triazine (HT) ring structure into the cross-linking network to prepare degradable epoxy resin. Specifically, 1,3,5-triacryloylhexahydro-1,3,5-triazine (TAHT) and ethylamine quickly complete the Aza-Michael addition reaction at the interface of chloroform and water droplets under the catalysis of water. The FTIR spectra, NMR spectrum and mass spectrum show that mono- and bis-addition products of ethylamine coexist in the product in which the content of the primary addition product reaches 97%. TAHT-EA can be decomposed by acid and base solutions. Through NMR analysis of the degradation products, it can be explained that the degradation mechanisms are different. The breaking of amide bonds and HT rings in acid solution and the cracking of amide bonds in base solution are speculated to be the main mechanisms under these two different circumstances, respectively. We tested the mechanical, thermal and degradation properties of the epoxy resin cured by TAHT-EA, and compared it with the epoxy resin cured by 4,4′-diaminodiphenylmethane and triethylenetetramine. TAHT-EA-cured epoxy resin shows comparable mechanical properties with Young’s modulus up to 2.05 GPa and tensile strength up to 70.9 MPa. What is more, it degrades completely by 1 M H + /OH − solution at 60 °C within 36 h. Nevertheless, it exhibited a relatively low crosslinked density (633 mol/m 3 ) and low heat resistance (the initial decomposition temperature is lower than 205 °C). Overall, TAHT-EA cured epoxy resin has the potential to gradually replace traditional thermosetting resin, thereby solving the environmental problems caused by discarded epoxy resin products.
研究领域:
材料科学
·
高分子化学
·
环境科学
·
可持续材料
✓ 已验证
产品关联
DOI
高影响因子
Bioactive Materials
·
2024
·
IF 18
Tian Zhang,Dongsheng Tang,Pengfei Wu,Shaoping Jiang,Yuquan Zhang,Abid Naeem,Yong Li,Chunhui Li,Bo Hu,Shuai Guo,Caixia Sun,Haihua Xiao,Ran Yan,Yuhua Weng,Yuanyu Huang
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.
研究领域:
肿瘤学
·
免疫治疗
·
药理学
·
生物医学工程
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）