Molecular Genetics & Genomic Medicine
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2023
·Vol. 11
·期 5
·e2150
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IF 2
Fang Wang,Haiqin Cheng,Qin Zhang,Jin Guo
Background Rare mutations in multiple genes have been associated with human neural tube defects (NTDs), but their causative roles in NTDs disease are poorly understood. Insufficiency of the ribosomal biogenesis gene treacle ribosome biogenesis factor 1( Tcof1 ) results in cranial NTDs and craniofacial malformations in mice. Here, we aimed to identify genetic association of TCOF1 with human NTDs. Methods High-throughput sequencing targeted on TCOF1 was performed on samples from 355 human cases affected by NTDs and 225 controls from a Han Chinese population. Results Four novel missense variants were found in the NTD cohort. Cell-based assays indicated that the p.(A491G) variant carried by an individual, who shows anencephaly and single-nostril abnormality, attenuates production of total proteins, suggesting a loss-of-function mutation in ribosomal biogenesis. Importantly, this variant promotes nucleolar disruption and stabilizes p53 protein, highlighting an unbalancing effect on cell apoptosis. Conclusions This study explored the functional impact of a missense variant in TCOF1 , implicating a set of novel causative biological factors involved in the pathogenicity of human NTDs, particularly whom combined with craniofacial abnormality.
研究领域:
遗传学
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分子生物学
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神经发育障碍
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Redox Biology
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2025
·
IF 11.9
Xue Wang,Xin Liu,Yumei Fan,Ke Tan,Jiaqi Gao,Yuejiao Wang,Ziyi Zhang,Shuyue Liu,Xiaofan Wang,Ke Tan,Baohua Wang,Pengxiu Cao
Pulmonary fibrosis (PF) involves persistent activation of fibroblasts and excessive deposition of extracellular matrix, with limited therapeutic options. Pulmonary iron overload has been identified in PF and is associated with the progression of PF. However, the underlying signaling pathway remains unclear. This study demonstrated that iron accumulates in the mouse lung from day 7 post-bleomycin (BLM) instillation until harvest, coinciding with the activation of pulmonary fibroblasts and the onset of fibrogenesis. Iron supplementation promoted the G 1 /S cell cycle transition and proliferation of fibroblasts, and worsened PF, whereas iron deficiency demonstrated the opposite effects. Mechanistically, both iron and reactive oxygen species (ROS) suppress Forkhead box F1 (FOXF1) expression. FOXF1 overexpression upregulates the expression of antioxidant proteins, including ferredoxin 1 (FDX1) and heme oxygenase-1 (HO-1). Both FOXF1 overexpression and FDX1 overexpression reduced cellular labile iron pool (LIP), ROS levels, and collagen synthesis in human pulmonary fibroblasts. Sonic hedgehog (SHH) signaling elevated intracellular iron, fibroblast proliferation, and its own secretion, establishing a sustained SHH/iron amplifying loop. These findings identify an iron/ROS–FOXF1 positive feedback loop and an SHH–iron self-promoting pathway that drive sustained elevated iron levels and persistent fibroblast activation and fibrogenesis, thereby deepening our understanding of the iron signaling in PF.
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JOURNAL OF MAGNETIC RESONANCE IMAGING
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2025
·Vol. 62
·期 4
·1219-1229
·
IF 3.5
Kai Huang,Xiao-Zhu Hao,Cai-Xia Fu,Zhong Yang,Yan Ren,Xue Yang,Shi-Ji Zhang,Mei-Lin Zhu,Zhen-Wei Yao,Da-Xiu Wei,Ye-Feng Yao
Background Glycine (Gly) is a key metabolic intermediate in the proliferation of tumor cells. Monitoring the concentration of Gly in tumor tissues is of great importance for understanding the growth status of tumors. At present, magnetic resonance spectroscopy (MRS) is the only method to non-invasively measure Gly concentration in human tissues. However, in conventional MR spectra the 1 H signal of Gly overlaps with those of other molecules. This makes conventional MRS difficult to accurately measure the Gly concentration in human tissues. Purpose To develop a pulse sequence, Gly-MRS, which can accurately measure Gly concentrations without the influence of the signal overlapping from other molecules in subjects with glioma. Study Type Prospective. Subjects/Phantoms A phantom of the glycine (Gly), myo-inositol (MI) and glutamate (Glu) mixture aqueous solution and 6 phantoms of Gly aqueous solution (pH = 7.2 ± 0.1), 6 subjects with glioma (3 females and 3 males, BMI: 20 ± 4 kg/m 2 , age: 50 ± 10 years). Field Strength/Sequence 3 Tesla/A Gly-targeted magnetic resonance spectroscopy pulse sequence, Gly-MRS, using Point-RESolved Spectroscopy (PRESS) for single voxel signal selection. Assessment By applying the developed pulse sequences to the phantoms and the subjects with glioma, the Gly 1 H signals were successfully selectively probed. Quantification of the signals yields the concentrations of Gly in the regions of the tumor tissues of the subjects with glioma. Statistical Tests Numerical data only. Results The Gly 1 H signals were detected in the tumor regions of 6 subjects with glioma, at a mean concentration of 5.20 mM (standard deviation, ± 3.29 mM). One subject exhibited a clear spatial distribution in the Gly concentrations in the tumor regions. Data Conclusion The Gly-MRS pulse sequence developed in this work might be useful for the accurate in vivo detection of the 1 H signal of Gly in gliomas of human beings. Evidence Level 2. Technical Efficacy Stage 3.
研究领域:
肿瘤学
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神经影像学
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代谢组学
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分子影像
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放射学
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Nanoscale
·
2020
·Vol. 12
·期 20
·11119-11129
·
IF 6.895
Yang Liu,Xiaomin Li,Xiaoyan Niu,Licheng Yu,Weizhou Sha,Wei Wang,Zhi Yuan
Due to the complicated environment and high tissue hydraulic pressure in tumors that easily pumps the nanomedicines back to the systemic circulation, the concentration of released photosensitizers (PSs) retained in a tumor by a traditional nano-delivery system is very low, causing an unsatisfactory photodynamic therapy (PDT) effect. Therefore, we prepared a pH/H2O2-responsive nano-system (ZnP-OC-M) through modified porphyrin PS units with a long-unsaturated oleoyl chloride chain, and by the further introduction of hydrophilic hydroxyl groups and MnO2 through a cis-addition reaction between the unsaturated double bonds of oleoyl chloride and dilute KMnO4 solution. Making use of the sensitivity of MnO2 to the H2O2 in the acid environment of tumor cells, ZnP-OC-M selectively realized responsive disintegration and O2 generation. More importantly, the rich amphiphilic PS units were shedded simultaneously and spontaneously completed the self-assembly into nanofibers in situ by helical stacking, which displayed a 1.85-fold higher retention effect of PSs in vivo compared with free PS groups and showed a great tumor inhibition effect in enhancing PDT. This nanosystem effectively solves the problem of the low retention abilities leading to a poor PS concentration in a tumor, prolonging the treatment time window efficiently after only a single administration and achieving the purpose of PDT enhancement.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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Evidence-based Complementary and Alternative Medicine
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2016
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IF 1.931
Fei Wu,Yi Li,Haibo Song,Yuan Zhang,Yuzhu Zhang,Miao Jiang,Fang Wang,Qian Mu,Wen Zhang,Liang Li,Dongqi Tang
Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves of Ampelopsis grossedentata. Previous studies have demonstrated the anti-inflammatory and antioxidative effects of Dihydromyricetin both in vitro and in vivo, but little is known about the effects of Dihydromyricetin on cisplatin-induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin-induced oxidative stress, as well as protecting against cisplatin-induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin.
研究领域:
药理学
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毒理学
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肿瘤学
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分子生物学
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Communications Chemistry
·
2021
·Vol. 4
·期 1
·1-12
·
IF 6.581
Ge Xuan,Hu Qiaodan,Yang Fan,Xu Jun,Han Yanfeng,Lai Pingsheng,Qin Jingyu,Li Jianguo
The crystallization processes of titanates are central to the fabrication of optical and electrical crystals and glasses, but their rich polymorphism is not fully understood. Here, we show when and how polymorphic selection occurs during the crystallization of barium titanate (BaTiO 3 , BT) using in situ high energy synchrotron X-ray diffraction and ab initio molecular dynamic simulation. An anomalous structure transition is found in molten BT during cooling across the cubic-hexagonal transition temperature, which enables nucleation selection of BT by manipulating the undercooling: a cubic phase is preferred if nucleation is triggered at large undercooling, whereas a hexagonal phase is promoted at small undercooling. We further reveal that the nucleation selection between the cubic and the hexagonal phase is regulated by the intrinsic structure property of the melt, in particular, the degree of polymerization between Ti-O polyhedra. These findings provide an innovative perspective to link the polymorphic crystallization to the non-isomorphic structure transition of the melt beyond the conventional cognition of structural heredity.
研究领域:
材料科学
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凝聚态物理
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DOI
高影响因子
Cell Reports
·
2023
·
IF 8.8
Yingqi Liu,Xuemei Yao,Youbo Zhao,De Fang,Lei Shi,Li Yang,Guanbin Song,Kaiyong Cai,Liqi Li,Qin Deng,Menghuan Li,Zhong Luo
The tumor microenvironment (TME) plays decisive roles in disabling T cell-mediated antitumor immunity, but the immunoregulatory functions of its biophysical properties remain elusive. Extracellular matrix (ECM) stiffening is a hallmark of solid tumors. Here, we report that the stiffened ECM contributes to the immunosuppression in TME via activating the Rho-associated coiled-coil-containing protein kinase (ROCK)-myosin IIA-filamentous actin (F-actin) mechanosignaling pathway in tumor cells to promote the generation of TRIM14-scavenging nonmuscle myosin heavy chain IIA (NMHC-IIA)-F-actin stress fibers, thus accelerating the autophagic degradation of cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) to deprive tumor cyclic GMP-AMP (cGAMP) and further attenuating tumor immunogenicity. Pharmacological inhibition of myosin IIA effector molecules with blebbistatin (BLEB) or the RhoA upstream regulator of this pathway with simvastatin (SIM) restored tumor-intrinsic cGAS-mediated cGAMP production and enhanced antitumor immunity. Our work identifies that ECM stiffness is an important biophysical cue to regulate tumor immunogenicity via the ROCK-myosin IIA-F-actin axis and that inhibiting this mechanosignaling pathway could boost immunotherapeutic efficacy for effective solid tumor treatment.
研究领域:
癌症生物学
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免疫学
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细胞生物学
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生物物理学
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EARTH AND PLANETARY SCIENCE LETTERS
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2021
·
IF 5.255
Ye Wan,Xiaolin Wang,I-Ming Chou,Xiaochun Li
Sulfate is a common and important component in the mineralizing fluids of some world-class rare earth element (REE) deposits. However, the roles of sulfate during the transport and mineralization of REEs remain unclear and need further investigation. In this study, liquid–liquid immiscibility is proposed to be a potential mechanism for the enrichment of REE in hydrothermal fluids based on a series of experiments. REEs were considerably concentrated into the separated dense liquid phase, whereas the remaining light liquid phase was depleted in REEs. In situ Raman spectroscopic analyses characterized more complicated REE 3+ -SO 4 2 − complexes and some bisulfate species in addition to the documented REESO 4 + and REE(SO 4 ) 2 − ; the newly proposed sulfate species can transport one third of the total REEs at >200 °C. Therefore, the transport capacity of sulfate was underestimated in previous studies. Overall, the presence of sulfate can significantly fertilize the REE-mineralizing fluids.
研究领域:
地质学
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地球化学
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DOI
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
·
IF 6.8
Yijing Han,Qianqian Zhang,Lizhu Chen,Jianmin Zhao,Dinglong Yang
Deltamethrin (DLM), a broad-spectrum pesticide, has been proven to have toxic effects on aquatic organisms. Here, we detected the formation of extracellular traps (ETosis) formation in Manila clam ( Ruditapes philippinarum ) hemocytes stimulated by three concentrations of DLM (0.01, 0.1 and 1 μg/mL) in vitro, and explored the underlying mechanisms induced by this pesticide. Extracellular DNA structure observation and quantitative results indicated that DLM exposure could obviously induce hemocytes ETosis, especially under high concentration of DLM induction. Moreover, DLM increased the levels of myeloperoxidase (MPO) and reactive oxygen species (ROS) in a dose-dependent manner, and enhanced the mRNA expression of several ROS-related genes. DPI (NADPH oxidase inhibitor) and ABAH (MPO inhibitor) could substantially inhibit DLM-induced extracellular traps (ETs), suggesting that the induced ETs release was caused by the induction of the ROS burst and MPO production. In addition, three concentrations of DLM-induced ETs were also accompanied by mitochondrial dysfunction, such as increasing the production of mitochondrial ROS, leading to a decrease in mitochondrial membrane potential (MMP) and activation of mitochondrial permeability transition pore (MPTP). Taken together, these results will shed new light on the immunotoxicity of DLM in clams and perhaps lays the foundation for health assessment in bivalves.
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ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2023
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IF 11.4
Meijiao Zhou,Jinhua Li,Mine Du,Jun Wang,Han Yeong Kaw,Lizhong Zhu,Wei Wang
Xenobiotics were generally detoxified in organisms through interaction with endogenous molecules, which may also generate metabolites of increased toxicity. Halobenzoquinones (HBQs), a group of highly toxic emerging disinfection byproducts (DBPs), can be metabolized by reacting with glutathione (GSH) to form various glutathionylated conjugates (SG-HBQs). In this study, the cytotoxicity of HBQs in CHO-K1 cells showed a wavy curve as a function of increased GSH dosage, which was inconsistent with the commonly recognized progressive detoxification curve. We hypothesized that the formation and cytotoxicity of GSH-mediated HBQ metabolites contribute to the unusual wave-shaped cytotoxicity curve. Results showed that glutathionyl-methoxyl HBQs (SG-MeO-HBQs) were identified to be the primary metabolites significantly correlated with the unusual cytotoxicity variation of HBQs. The formation pathway was initiated by stepwise metabolism via hydroxylation and glutathionylation to produce detoxified hydroxyl HBQs (OH-HBQs) and SG-HBQs, followed by methylation to generate SG-MeO-HBQs of potentiated toxicity. To further verify the occurrence of the aforementioned metabolism in vivo, SG-HBQs and SG-MeO-HBQs were detected in the liver, kidney, spleen, testis, bladder, and feces of HBQ-exposed mice, with the highest concentration quantified in the liver. The present study supported that the co-occurrence of metabolism can be antagonistic, which enhanced our understanding of the toxicity and metabolic mechanism of HBQs.
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Geomechanics and Geophysics for Geo-Energy and Geo-Resources
·
2023
·Vol. 9
·期 1
·1-13
·
IF 5
Fengxiao Wang,Jinzhang Jia,Xiuyuan Tian
Methane explosions threaten the safety of industrial security in modern society. To suppress such explosions, experiments were made through using different masses of bentonite power driven by CO 2 within a pipe network set up in an independent way. The three factors, including the peak over-pressure of an explosion, the index of the explosion power, and the time length within which the first wave of flames reached the pipe network’s outlet, were measured to evaluate the performance. Moreover, an analysis on the mechanism of suppressing explosions was also conducted. According to the results, a gradual increase of the powder mass from 20 to 50 g could promote the effect of explosion suppression, but a further increase from50 g to 60 g only led to a slight improvement of the performance. Thus, it was concluded that the use of 50 g of bentonite powder worked best for the suppression of methane explosions when environmental conservation, energy saving as well as practicality were all taken into consideration. What was found in this study is supposed to shed theoretical light on how to transport methane safely with disaster risks reduced effectively.
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JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
·
2023
·
IF 4.4
Arakkaveettil Kabeer Farha,Zijun Li,Yijuan Xu,Matteo Bordiga,Zhongquan Sui,Harold Corke
The spread of multidrug resistant bacteria has fueled the development of new antibiotics to combat bacterial infections. Disrupting the quorum sensing (QS) mechanism with biomolecules is a promising approach against bacterial infections. Plants used in Traditional Chinese Medicine (TCM) represent a valuable resource for the identification of QS inhibitors. In this study, the in vitro anti-QS activity of 50 TCM-derived phytochemicals against the biosensor Chromobacterium violaceum CV026 was tested. Among the 50 phytochemicals, 7-methoxycoumarin, flavone, batatasin III, resveratrol, psoralen, isopsoralen, and rhein inhibited violacein production and showed good QS inhibitory effects. Batatasin III was selected as the best QS inhibitor based on drug-likeness, physicochemical properties, toxicity, and bioactivity score prediction analyses using SwissADME, PreADMET, ProtoxII, and Molinspiration. At 30 μg/ mL, Batatasin III inhibited violacein production and biofilm formation in C. violaceum CV026 by more than 69% and 54% respectively without affecting bacterial growth. The in vitro cytotoxicity evaluation by MTT assay demonstrated that batatasin III reduced the viability of 3T3 mouse fibroblast cells to 60% at 100 μg/mL. Furthermore, molecular docking studies showed that batatasin III has strong binding interactions with the QS-associated proteins CViR, LasR, RhlR, PqsE, and PqsR. Molecular dynamic simulation studies showed that batatasin III has strong binding interactions with 3QP1, a structural variant of CViR protein. The binding free energy value of batatasin III-3QP1 complex was −146.295 ± 10.800 KJ/mol. Overall results suggested that batatasin III could serve as a lead molecule that could be developed into a potent QS inhibitor.Communicated by Ramaswamy H. Sarma
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