CLINICA CHIMICA ACTA
·
2024
·
IF 3.2
Xiao Bao,Yuxia Yang,Wenbin Niu,Yimin Wang,Hao Shi,Yangyun Zou,Yidong Liu,Cheng Wan,Jun Ren,Sijia Lu,Yingpu Sun
Background Chromosome abnormalities are a leading cause of conception failure and pregnancy loss. While traditional cytogenetics technologies like karyotyping have been helpful in identifying structural variations (SVs), they face challenges in detecting complex rearrangements and cryptic structures. In this study, we developed a new method called chromosome conformation based karyotyping (C-MoKa) to comprehensively detect different types of chromosomal abnormalities in patients with conception failure and pregnancy loss. Methods A total of 70 clinical samples exhibiting known results of SVs, mosaic aneuploidies, copy number variations (CNVs) and uniparental disomy (UPD) were included in our cohort and underwent C-MoKa analysis. The results obtained from different techniques, including karyotyping, CNV-seq, and CMA were compared and analyzed. Results Distinct chromosomal conformation patterns of various variations were observed and analyzed in clinical samples. Our C-MoKa method not only validated all the findings of karyotyping, CNV-seq and CMA, but also provided more detailed results. It demonstrated superior fragment resolution (<500 Kb) and more precise breakpoints (>100 kb). Moreover, C-MoKa showed higher sensitivity in decoding intricate rearrangements in a single test. Conclusions Our results highlight the potential utility of C-MoKa in precisely unraveling SVs, mosaic aneuploidies, CNVs, and UPD in clinical settings, which can significantly impact further clinical decision-making.
研究领域:
遗传学
·
生殖医学
·
分子生物学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Yuan Zhuang,Siyi Yuan,Jiemin Liu,Yan Zhang,Hao Du,Chuandong Wu,Peng Zhao,Haiying Chen,Yipu Pei
Volatile organic compound (VOC) emissions are a global environmental concern because of their potential health risks. The removal of refractory VOCs calls for advanced technologies with powerful oxidative ability and high mass transfer efficiency. In this study, a yolk-shell Fe 3 O 4 @C/Fenton system was designed to improve octane removal efficiency. The octane removal efficiency at equilibrium was increased by 24.7% relative to that of the Fe 3 O 4 /Fenton system, and the main intermediate or byproduct levels decreased by 89.4%. The yolk-shell Fe 3 O 4 @C displayed higher catalytic and mass transfer efficiencies for octane degradation than Fe 3 O 4 . A synergistic effect of mass transfer enhancement and catalytic oxidation was observed in the yolk-shell Fe 3 O 4 @C/Fenton system. The mechanism of the synergistic effect of mass transfer and octane degradation, a regional reaction theory for the yolk-shell structure, and octane removal pathways were proposed and supported by the octane removal results and byproducts detection and measurement. This yolk-shell Fe 3 O 4 @C/Fenton system provides an effective and advanced way to treat refractory and hydrophobic VOCs, and its preparation can be extended to other high-efficiency core-shell structure catalyst-carbon materials.
研究领域:
环境科学
·
化学工程
·
材料科学
·
催化
·
污染控制
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 10
·2489
·
IF 4.183
Siqi Zhang,Qiaoling Song,Xueting Wang,Zhiqiang Wei,Rilei Yu,Xin Wang,Tao Jiang
c-Met is a transmembrane receptor tyrosine kinase and an important therapeutic target for anticancer drugs. In this study, we designed a small library containing 300 BISAs molecules that consisted of carbohydrates, amino acids, isothiourea, tetramethylthiourea, guanidine and heterocyclic groups and screened c-Met targeting compounds using docking and MM/GBSA. Guided by virtual screening, we synthesised a series of novel compounds and their activity on inhibition of the autophosphorylation of c-Met and its downstream signalling pathway proteins were evaluated. We found a panel of benzisoselenazolones (BISAs) obtained by introducing isothiourea, tetramethylthiourea and heterocyclic groups into the C-ring of Ebselen, including7a,7b,8a,8band12c(with IC50values of less than 20 μM in MET gene amplified lung cancer cell line EBC-1), exhibited more potent antitumour activity than Ebselen by cell growth assay combined with in vitro biochemical assays. In addition, we also tested the antitumour activity of three cancer cell lines without MET gene amplification/activation, including DLD1, MDA-MB-231 and A549. The neuroblastoma SK-N-SH cells with HGF overexpression which activates MET signalling are sensitive to MET inhibitors. The results reveal that our compounds may be nonspecific multitarget kinase inhibitors, just like type-II small molecule inhibitors. Western blot analysis showed that these inhibitors inhibited autophosphorylation of c-MET, and its downstream signalling pathways, such as PI3K/AKT and MARK/ERK. Results suggest that bensoisoselenones can be used as a scaffold for the design of c-Met inhibiting drug leads, and this study opens up new possibilities for future antitumour drug design.Keywords:virtual screening;benzoisoselenone;c-Met inhibition;docking;molecular dynamics simulation
研究领域:
药理学
·
分子生物学
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癌症研究
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 13
·4508-4515
·
IF 7.367
Na Lu,Min Zhang,Lei Ding,Jing Zheng,Caixia Zeng,Yanli Wen,Gang Liu,Ali Aldalbahi,Jiye Shi,Shiping Song,Xiaolei Zuo,Lihua Wang
Herein, we have developed a simple and facile method to synthesize yolk–shell nanostructured Fe3O4@C nanoparticles (NPs) as a multifunctional biosensing platform for the label-free colorimetric detection of H2O2 and glucose. It was demonstrated that Fe3O4@C yolk–shell nanostructures (YSNs) retained the magnetic properties that can be used for separation and concentration. Also importantly, the Fe3O4@C YSNs exhibited an intrinsic peroxidase-like activity that could quickly catalyze the enzyme substrate in the presence of H2O2 and produce a blue color. Compared to other similar ferric oxide-based NPs with different structures, Fe3O4@C YSNs exhibited greatly enhanced catalytic activities due to their unique structural features. Moreover, steady-state kinetics indicated the catalytic behaviors in agreement with the classic Michaelis–Menten models. Taking advantage of the high catalytic activity, Fe3O4@C YSNs were employed as novel peroxidase mimetics for label-free, rapid, sensitive, and specific colorimetric sensing of H2O2 and glucose, suggesting that Fe3O4@C YSNs have the potential for construction of portable sensors in the application of point-of-care (POC) diagnosis and on-site tests.
研究领域:
纳米技术
·
生物化学
·
分析化学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 9
·期 1
·1901203
·
IF 6.27
Haiying Ji,Guangxi Wu,Yongyong Li,Kun Wang,Xiaomei Xue,Shasha You,Shengming Wu,Tianbin Ren,Bin He,Xueyin Shi
Elevated low-density lipoprotein cholesterol (LDL-C) increases the risk of atherosclerotic cardiovascular disease. Peptide-based PCSK9 vaccines have shown a promising prospect of reducing LDL-C. In peptide vaccine (pVax) design, the peptide antigens need to conjugate with carrier protein (CP). However, CP incorporation can induce undesirable anti-CP antibodies, which sterically mask peptide epitopes from being recognized by specific B cells and impair subsequent therapeutically antibody production. This epitopic suppression has posed a barrier in clinical translation of conjugate vaccines all along. A model CP (keyhole limpet hemocyanin, KLH) is herein camouflaged with serum albumin (SA) into hybrid nanocarriers (SA@N), with PCSK9 peptide being anchored onto the surface to form nanovaccine (SA@NVax). Such camouflage of KLH via high “self” SA coverage is able to inhibit KLH from extracellular immune recognition and prevent detectable anti-KLH antibody production. Furthermore, the nanovaccine around 70 nm stabilized by intermolecular disulfide network is ideal for internalization and biodegradation by antigen presenting cells as well as better retention in draining lymph nodes and spleen. As expected, the SA@NVax efficiently primes higher anti-PCSK9 IgG antibody titer than PCSK9 pVax.
研究领域:
生物技术
·
免疫学
·
药学
·
心血管疾病
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2013
·Vol. 8
·期 3
·e59882
·
IF 3.73
Lushan Yu,Yan Jiang,Lu Wang,Rong Sheng,Yongzhou Hu,Su Zeng
BYZX, [(E)-2-(4-((diethylamino)methyl)benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one], belongs to a series of novel acetylcholinesterase inhibitors and has been synthesized as a new chemical entity for the treatment of Alzheimer’s disease symptoms. When incubated with human liver microsomes (HLMs), BYZX was rapidly transformed into its metabolites M1, M2, and M3. The chemical structures of these metabolites were identified using liquid chromatography tandem mass spectrometry and nuclear magnetic resonance, which indicated that M1 was an N -desethylated and C = C hydrogenation metabolite of BYZX. M2 and M3 were 2 precursor metabolites, which resulted from the hydrogenation and desethylation of BYZX, respectively. Further studies with chemical inhibitors and human recombinant cytochrome P450s (CYPs), and correlation studies were performed. The results indicated that the N -desethylation of BYZX and M2 was mediated by CYP3A4 and CYP2C8. The reduced form of β-nicotinamide adenine dinucleotide 2′-phosphate was involved in the hydrogenation of BYZX and M3, and this reaction occurred in the HLMs and in the human liver cytosol. The hydrogenation reaction was not inhibited by any chemical inhibitors of CYPs, but it was significantly inhibited by some substrates of α,β-ketoalkene C = C reductases and their inhibitors such as benzylideneacetone, dicoumarol, and indomethacin. Our results suggest that α,β-ketoalkene C = C reductases may play a role in the hydrogenation reaction, but this issue requires further clarification.
研究领域:
药理学
·
生物化学
·
阿尔茨海默病研究
✓ 已验证
DOI
PubMed
高影响因子
ULTRASOUND IN MEDICINE AND BIOLOGY
·
2020
·
IF 2.514
Yao Liu,Yijin Fan,Huajun Tang,Chengzhi Li
The purpose of this study was to investigate the therapeutic effects of focused ultrasound on the expression of notch1, c-fos and transforming growth factor-β3 (TGF-β3) in genital skin of SD rats with vulvar lichen simplex chronicus (LSC). Fifty-six female SD rats with LSC were randomly divided into therapy and sham groups. The therapy group was exposed to focused ultrasound. The sham group received the same therapy with an instrument that had no power output. Four wk after a singly focused ultrasound therapy, histologic analyses revealed that recovered SD rats accounted for 75% of SD rats in the therapy group and 10.7% in the sham group. Total collagen fiber density in the superficial layer of dermis in the therapy group was significantly lower than that in the sham group. Notch1 and c-fos protein expression in the therapy group was significantly lower than that in the sham group, with the opposite effect present for TGF-β3. Focused ultrasound therapy may inhibit superficial collagen fibrosis in the dermis by affecting expression of notch1, c-fos and TGF-β3 in vulvar skin tissue and consequently reduce the recurrence rate of LSC.
研究领域:
皮肤病学
·
治疗超声
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Jiali Jiang,He Li,Jianxing Huang,Kun Li,Jing Zeng,Yang Yang,Jiaqi Li,Yunhui Wang,Jing Wang,Jinbao Zhao
The Li3VO4@C microsphere composite was first reported as a novel cathode material for rechargeable aluminum-ion batteries (AIBs), which manifests the initial discharge capacity of 137 mAh g–1 and and remains at 48 mAh g–1 after 100 cycles with almost 100% Coulombic efficiency. The detailed intercalation mechanism of Al into the orthorhombic Li3VO4 is investigated by ex situ X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) of Li3VO4@C electrodes and the nuclear magnetic resonance aluminum spectroscopy (27Al NMR) of ionic liquid electrolytes in different discharge/charge states. First-principle calculations are also carried out to investigate the structural change as Al inserts into the framework of Li3VO4. It is revealed that the Al/Li3VO4@C battery goes through electrochemical dissolution and deposition of metallic aluminum in the anode, as well as the insertion and deinsertion of Al3+ cations in the cathode in the meantime. The rechargeable AIBs fabricated in this work are of low cost and high safety, which may make a step forward in the development of novel cathode materials based on the acidic ionic liquid electrolyte system.
研究领域:
电化学
·
材料科学
·
能源存储
·
无机化学
·
固体物理
·
纳米材料
·
电池技术
✓ 已验证
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2014
·Vol. 8
·期 3
·935-942
·
IF 0.941
Wei Zhang,Jiabo Hu,Quanhui Ma,Sanqiang Hu,Yanyan Wang,Xiangmei Wen,Yongbin Ma,Hong Xu,Hui Qian,Wenrong Xu
An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70˚C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 µg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 µg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70˚C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70˚C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70˚C short-term or liquid nitrogen cryopreservation.
研究领域:
干细胞生物学
·
细胞培养
·
低温生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Electronic Materials
·
2025
·Vol. 11
·期 8
·2400738
·
IF 5.3
Guodong Han,Song Zhao,Sai Sui,Bo Feng,Yudeng Wang,Junxiang Zhou,Zhuolun Li,Xiaoxia Tian,Yuxiang Jia,Jiafu Wang,Shaobo Qu
Metal–Organic-Frameworks (MOFs) are commonly used as microwave-absorbing materials after pyrolysis treatment. Rare researchers treat MOFs as non-conductive materials and use them as absorbing materials directly. In this paper, MOFs@P-C-800 composite materials are prepared adopt to hydrothermal and ultrasonic dispersion methods by regulating the morphological characteristics of MOFs and the content of P-C-800. As for the Co-BDC-P-C-800, the maximum reflection loss reaches −18.4 dB at 14.29 GHz and the effective absorption bandwidth (EAB) achieves 3.87 GHz from 13.5 to 17.37 GHz. After the contents of P-C-800 is adjusted, the Co-BDC-P-C-800 (0.05 g) exhibited excellent microwave absorption performance, the maximum RL value of −60 dB at 13 GHz with a thickness of 2.0 mm, and the EAB achieves 5.91 GHz from 12.02 to 17.93 GHz. This paper not only provides new application direction for MOFs, but also offers a promising direction for the research and development of absorbing materials.
研究领域:
材料科学
·
微波吸收材料
·
纳米复合材料
·
电磁功能材料
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Aging Neuroscience
·
2024
·
IF 4.1
Xue Weikang,Lei Ziyi,Liu Bin,Guo Hanxin,Yan Weiyi,Jin Youngnam N.,Yu Yanxun V.
Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integrate molecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Aβ1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Aβ1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Aβ1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calcium responses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Aβ1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Aβ in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches.
研究领域:
神经科学
·
分子生物学
·
神经退行性疾病
·
模式生物
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2024
·Vol. 31
·期 13
·19396-19408
·
IF 0
Pan Enzhuang,Xin Yue,Li Xueqing,Ping Kaixin,Li Xing,Sun Ying,Xu Xuhui,Dong Jingquan
As a broad-spectrum and efficient triazole fungicide, difenoconazole is widely used, which not only pollutes the environment but also exerts toxic effects on non-target organisms. The spleen plays an important role in immune protection as an important secondary lymphoid organ in carp. In this study, we assessed the protective impact of silybin as a dietary additive on spleen tissues of carp during exposure to difenoconazole. Sixty carp were separated into four groups for this investigation including control group, difenoconazole group, silybin group, and silybin and difenoconazole group. By hematoxylin-eosin staining, dihydroethidium staining, immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, quantitative real-time PCR assay, Western blot analysis, biochemical assays, and immune function indicator assays, we found that silybin could prevent difenoconazole-induced spleen tissue damage, oxidative stress, and immune dysfunction, and inhibited apoptosis of carp spleen tissue cells by suppressing the formation of p53-driven caspase-9-apoptotic protease activating factor-1-cytochrome C complex. The results suggested that silybin as a dietary additive could improve spleen tissue damage and immune dysfunction induced by difenoconazole in aquaculture carp.
研究领域:
环境毒理学
·
免疫学
·
水产养殖学
✓ 已验证
DOI