JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Wei Yang,Yu Li,Ruzhen Feng,Peiyao Liang,Kefan Tian,Lingli Hu,Kejing Wang,Tianming Qiu,Jingyuan Zhang,Xiance Sun,Xiaofeng Yao
Perfluorooctane sulfonate (PFOS), a listed persistent organic pollutant, poses risks to human health and is closely linked to chronic metabolic diseases. Although the role of mitochondrial fission in these diseases has garnered attention, whether and how PFOS induces mitochondrial fission remains obscure. Here, we found that PFOS induced mitochondrial fission, as demonstrated by the fragmentation of mitochondria and the upregulation of dynamin-related protein 1 (DRP1), phospho-DRP1 and mitochondrial fission protein 1 (FIS1) in human hepatocytes MIHA and mice liver. Blocking the calcium transfer from lysosomes to mitochondria that was executed by transient receptor potential mucolipin 1 (TRPML1) of lysosomes and voltage-dependent anion channel 1 (VDAC1) of mitochondria, did not affect PFOS-induced mitochondrial fission. In contrast, knockdown of TRPML1 or VDAC1 reversed this process. Knockdown of mitochondrial calcium uniporter (MCU), rather than inhibiting its activity, effectively alleviated PFOS-induced mitochondrial fission. Additionally, PFOS increased MCU oligomers without affecting MCU monomer. Inhibiting autophagy reversed the MCU oligomerization. Further investigation unveiled the interactions of MCU with VDAC1, TRPML1, mitochondrial Fo complex subunit F2 (ATP5J2) and DRP1 in PFOS-exposed mice liver and MIHA cells. We also discovered that knockdown of ATP5J2 alleviated PFOS-induced mitochondrial fission. Ulteriorly, PFOS upregulated ATP5J2 that underwent oligomerization. Knockdown of MCU reversed the increase in ATP5J2. Our study uncovers the presence and molecular basics of lysosomes-regulated mitochondrial fission under PFOS exposure, explains the regulatory pathways on MCU and ATP5J2 oligomerization and their pivotal roles in mitochondrial fission, highlighting the involvement of mitochondrial fission in PFOS-related health risks.
研究领域:
细胞生物学
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毒理学
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代谢疾病研究
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Zizhang Wang,Hao Li,Yuxiang Weng
Previously, OsNIN8 initiated sucrose signal for cell division in radicle and seed development in rice. Here, a set of genes were induced in starved sprouts after sucrose treatment and 14 genes were screened between ZH11 and nin8 as reporters of sucrose signal. Expressions of reporter depended on levels of OsNIN8 in overexpression and RNAi lines. Further, OsNIN8 interacted with OsFKBP12, a regulator of TOR signal for cell division, and OsFKBP12 interacted with OsTOR (OsTORKD). However, interactions of OsFKBP12 with OsNIN8 or OsTORKD were a loose binding depending on hydrophobicity of OsFKBP12 C-terminus in Y2H. In addition, OsFKBP12 associating with OsNIN8 was endothermic but with OsNIN8m was exothermic. Knockout OsFKBP12 reappeared nin8 phenotypes and complementation the knockout with C-termini of OsFKBP12 worsened the phenotypes. Treatment with TOR inhibitors caused short radicle and OsTOR RNAi repeated low seed-setting of the phenotypes. So, OsFKBP12 transduced sucrose signal from OsNIN8 to TOR pathway.
研究领域:
植物学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Phillips Aaron F.,Zhang Rumin,Jaffe Mia,Schulz Ryan,Carty Marysol Chu,Verma Akanksha,Feinberg Tamar Y.,Arensman Michael D.,Chiu Alan,Letso Reka,Bosco Nazario,Queen Katelyn A.,Racela Allison R.,Stumpff Jason,Andreu-Agullo Celia,Bettigole Sarah E.,Depetris Rafael S.,Drutman Scott,Su Shinsan M.,Cogan Derek A.,Eng Christina H.
Chromosome instability is a prevalent vulnerability of cancer cells that has yet to be fully exploited therapeutically. To identify genes uniquely essential to chromosomally unstable cells, we mined the Cancer Dependency Map for genes essential in tumor cells with high levels of copy number aberrations. We identify and validate KIF18A, a mitotic kinesin, as a vulnerability of chromosomally unstable cancer cells. Knockdown of KIF18A leads to mitotic defects and reduction of tumor growth. Screening of a chemical library for inhibitors of KIF18A enzymatic activity identified a hit that was optimized to yield VLS-1272, which is orally bioavailable, potent, ATP non-competitive, microtubule-dependent, and highly selective for KIF18A versus other kinesins. Inhibition of KIF18A’s ATPase activity prevents KIF18A translocation across the mitotic spindle, resulting in chromosome congression defects, mitotic cell accumulation, and cell death. Profiling VLS-1272 across >100 cancer cell lines demonstrates that the specificity towards cancer cells with chromosome instability differentiates KIF18A inhibition from other clinically tested anti-mitotic drugs. Treatment of tumor xenografts with VLS-1272 results in mitotic defects leading to substantial, dose-dependent inhibition of tumor growth. The strong biological rationale, robust preclinical data, and optimized compound properties enable the clinical development of a KIF18A inhibitor in cancers with high chromosomal instability.
研究领域:
肿瘤学
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分子生物学
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遗传学
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药物研发
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产品关联
DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
·
2022
·Vol. 44
·期 2
·470-482
·
IF 2.976
Jiawang Tao,Yan Chen,Yuanqi Zhuang,Ruzhi Wei,Anteneh Getachew,Tingcai Pan,Fan Yang,Yinxiong Li
Liver regeneration is a complicated biological process orchestrated by various liver resident cells. Hepatic cell proliferation and reconstruction of the hepatic architecture involve multiple signaling pathways. It has been reported that the Hh signal is involved in liver regeneration. However, the signal transduction pathways and cell types involved are ill studied. This study aimed to investigate hedgehog signal response cell types and the specific molecular mechanism involved in the process of liver regeneration. Partial hepatectomy (PH) of 70% was performed on ICR (Institute of Cancer Research) mice to study the process of liver regeneration. We found that the hedgehog signal was activated significantly after PH, including hedgehog ligands, receptors and intracellular signaling molecules. Ligand signals were mainly expressed in bile duct cells and non-parenchymal hepatic cells, while receptors were expressed in hepatocytes and some non-parenchymal cells. Inhibition of the hedgehog signal treated with vismodegib reduced the liver regeneration rate after partial hepatectomy, including inhibition of hepatic cell proliferation by decreasing Cyclin D expression and disturbing the cell cycle through the accumulation of Cyclin B. The current study reveals the important role of the hedgehog signal and its participation in the regulation of hepatic cell proliferation and the cell cycle during liver regeneration. It provides new insight into the recovery of the liver after liver resection.Keywords:vismodegib;smoothened;liver regeneration;hedgehog signaling;mitosis
研究领域:
分子生物学
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细胞生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
NEW PHYTOLOGIST
·
2025
·Vol. 245
·期 6
·2512-2526
·
IF 8.1
Lei Li,Qianqian Hu,Yi Zhao,Ting Jiang,Huaihao Yang,Binglian Zheng
Summary In plants, sperm cell formation involves two rounds of pollen mitoses, in which the microspore initiates the first pollen mitosis (PMI) to produce a vegetative cell and a generative cell, then the generative cell continues the second mitosis (PMII) to produce two sperm cells. DUO1, a R2R3 Myb transcription factor, is activated in the generative cell to promote S-G2/M transition during PMII. Loss-of-function of DUO1 caused a complete arrest of PMII. Despite the importance of DUO1, how DUO1 is regulated is largely unexplored. We previously demonstrated that ARID1, an ARID transcription factor, stimulates DUO1 transcription. Here, we show that cell proliferation suppressor RBR1 interacts with ARID1 to stabilize DUO1. While the C-terminus of RBR1 is dispensable for vegetative growth, it plays a crucial role in reproductive development and facilitates interaction with ARID1. Moreover, DUO1 is a short-lived protein, ARID1 promotes the RBR1–DUO1 interaction, and RBR1 stabilizes DUO1 in a proteasome-dependent manner. Thus, RBR1 promotes DUO1-dependent PMII progression via antagonizing its repressive role in the cell cycle factors CDKA;1 and CYCB1;1. Collectively, we uncover that ARID1 and RBR1 act in concert to regulate DUO1 at both the transcriptional and posttranscriptional levels, balancing cell specification and cell division.
研究领域:
植物学
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遗传学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Physical Chemistry C
·
2019
·
IF 4.309
Xiaolei Lu,Shuxian Wang,Shuxin Liu,Peng Du,Zhengmao Ye,Xuefei Geng,Xin Cheng
Ca2SiO4 is a phase-change material, and γ- and β-Ca2SiO4 usually coexist in the sintered product. The overlap of the diffraction data between the two polymorphs makes the relevant phase identification difficult. In this work, the Eu3+ rear-earth fluorescence probe is introduced in the preparation of Ca2SiO4, and the obtained result indicates that the introduction of Eu3+ ions facilitates the increase in the content of β-Ca2SiO4 in the final product. In addition, the differences of the local coordination environments between the two Ca2SiO4 phases obviously influence the crystal-field splittings of Eu3+ ions, especially in the 5D0 → 7F0 nondegenerate and 5D0 → 7F1 magnetic dipole transition regions. On the basis of the excitation from the Eu3+–O2– charge-transfer band, the low-temperature spectral changes are systematically discussed. The transition area ratios of 5D0 → 7F0/5D0 → 7F2 and 5D0 → 7F1/5D0 → 7F2 present a positive and negative correlation with the increase of the excitation wavelength, respectively. The four nonequivalent 5D0 → 7F0 emission peaks with low to high wavelengths are identified as Eu3+ ion-occupied Ca(β-2) (571.8 nm), Ca(β-1) (573.8 nm), Ca(γ-2) (577.6 nm), and Ca(γ-1) (578.9 nm) sites. Besides, the relationship between the phase content of γ-Ca2SiO4 and the spectral change for the 5D0 → 7F0 emissions of the Eu3+ ions is also built. It is fitted by an exponential correlation function and is quite suitable for the prediction of the phase content of γ-Ca2SiO4 based on the measured spectra. The findings in this study manifest the promising application of the Eu3+ fluorescent probe in phase identification and enrich the analysis method in inorganic phase-change materials.
研究领域:
材料科学
·
无机化学
✓ 已验证
DOI
高影响因子
MedComm
·
2024
·Vol. 5
·期 11
·e688
·
IF 10.7
Yuejia Chen,Du Guo,Xin Wang,Changbin Zhang,Yatian Chen,Qinghua Luo,Yujiao Chen,Lili Yang,Zhibo Zhang,Tian Hong,Zhengyu Zhang,Haohao Dong,Shenghai Chang,Jianping Hu,Xiaodi Tang
The filamentous temperature-sensitive (Fts) protein FtsEX plays a pivotal role in Escherichia coli ( E. coli ) cell division by facilitating the activation of peptidoglycan hydrolysis through the adaptor EnvC. FtsEX belongs to the type VII ATP-binding cassette (ABC) transporter superfamily, which harnesses ATP energy to induce mechanical force, triggering a cascade of conformational changes that activate the pathway. However, the precise mechanism by which FtsEX initiates mechanotransmission remains elusive. Due to the inherent instability of this type of ABC transporter protein in vitro, the conformation of FtsEX has solely been determined in the stabilized ATP-bound state. To elucidate the dynamics of FtsEX, we characterized FtsEX and EnvC of various functional structures through cryo-electron microscopy (cryo-EM) and homology modeling. We validated the structures by molecular dynamics simulations. By site-directed mutagenesis and phenotype screening, we also identified the functional residues involved in allosteric communication between FtsE and FtsX as well as FtsX and EnvC. Additionally, we discovered a potential role of phospholipids in stabilizing the complex conformation during mechanotransmission. This comprehensive exploration significantly enhances our understanding of the intricate mechanisms governing bacterial cell division and unveils potential molecular targets for developing innovative antimicrobial drugs to combat antibiotic resistance.
研究领域:
微生物学
·
结构生物学
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DOI
高影响因子
DEVELOPMENT
·
2025
·Vol. 152
·期 6
·
IF 3.6
Lin Zhen,Rong Bowen,Wu Meixia,Yan Junyi,Hong Tong,Hou Linjun,Tang Xinzhe,Liu Qiang,Peng Xiaozhong,Chen Yao,Lan Fei,Tong Ming-Han
ASH2L is a core component of KMT2 complexes, crucial for H3K4 trimethylation. However, its role in spermatogenesis remains elusive. Here, we demonstrate an essential role of Ash2l for meiotic prophase but dispensable for mitosis in differentiated spermatogonia. Using a germ cell-specific Ash2l knockout mouse model, we reveal that Ash2l deficiency leads to meiotic arrest and sterility in both sexes. Ash2l -deficient spermatocytes exhibit failures in chromosomal synapsis associated with persistent DMC1 foci and γH2AX, resulting in meiocyte loss due to apoptosis. Conversely, Ash2l -deficient differentiated spermatogonia show normal development. Mechanistically, Ash2l deficiency results in a global loss of H3K4me3 in promoter regions and significantly decreases expression of thousands of genes. Among these are genes involved in epigenetic silencing pathways, such as H3K9 di-methylation, DNA methylation and piRNA pathways, that are crucial for transposon repression during meiotic prophase I progression. Supporting this, we observe that Ash2l mutant spermatocytes display ectopic expression of LINE1-ORF1P. Our findings therefore reveal the previously unappreciated role of ASH2L-dependent H3K4me3 modification in spermatogenesis and provide clues to the molecular mechanisms in epigenetic disorders underlying male infertility.
研究领域:
分子生物学
·
生殖生物学
·
遗传学
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DOI
PubMed
高影响因子
PLANT BIOTECHNOLOGY JOURNAL
·
2025
·
IF 10.5
Mingyue Zhao,Jingming Wang,Xinyuan Hao,Jieyang Jin,Junwei Tang,Yueyue Wang,Mengting Zhang,Tingting Jing,Wilfried Schwab,Ting Gao,Xinchao Wang,Chuankui Song
Summary Cold stress severely limits tea plant ( Camellia sinensis ) productivity, yet the molecular mechanisms underlying cold adaptation remain elusive. Here, we identified a cold-inducible glycosyltransferase, CsUGT71A60, through integrative genome-wide association studies (GWAS) and proteomic profiling. Natural variation in CsUGT71A60 was strongly associated with cold tolerance, as evidenced by linkage disequilibrium analysis of flanking SNPs. Functional characterization revealed that CsUGT71A60 specifically catalyses the glycosylation of cis-zeatin to form cis-zeatin 9-O-glucoside in vitro and in vivo. Overexpression of CsUGT71A60 in Arabidopsis enhanced cold tolerance and agronomic traits, including germination rate, tiller number and seed weight, while delaying flowering. Transient silencing of CsUGT71A60 in tea plants disrupted cis-zeatin homoeostasis, impairing antioxidant defences and osmotic regulation under cold stress. Mechanistically, the transcription factor ARR (TEA021099) directly binds to CRM elements in the CsUGT71A60 promoter, activating its expression to fine-tune cytokinin signalling. This study unveils a dual-function glycosyltransferase that orchestrates stress tolerance and developmental plasticity, offering a strategic target for breeding climate-tolerance crops without yield penalties.
研究领域:
植物学
·
遗传学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS
·
2014
·Vol. 14
·期 12
·22971-22981
·
IF 2.048
Zhenzhu Zheng,Juan Hu,Zhaodong He
A label-free split G-quadruplex and graphene oxide (GO)-based fluorescence platform has been designed to distinguishPseudostellaria heterophylla(PH) from its adulterants based on the differences in their nrDNA ITS sequences. Herein, GO has been first introduced to capture G-rich probes with 2:2 split mode and then decrease the background signal. As T-DNA exists, the probes leave the GO surface to form double-stranded structures followed by the formation of the overhanging G-rich sequence into a G-quadruplex structure, which combines quinaldine red specifically to produce a strong fluorescence signal. In addition, this strategy allows detection of T-DNA in a wide range of concentrations from 1.0 × 10−8to 2.0 × 10−6mol·L−1with a detection limit of 7.8 × 10−9mol·L−1. We hope that the split G-quadruplex/GO platform can be utilized to further develop gene identification sensors in Traditional Chinese Medicine or other analysis areas.Keywords:split G-quadruplex;graphene oxide;fluorescence;Pseudostellaria heterophylla
研究领域:
中药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SOLID STATE COMMUNICATIONS
·
2016
·
IF 1.458
Wentao Li,Xiangting Ren,Yanwei Huang,Zhenhai Yu,Zhongying Mi,Nobumichi Tamura,Xiaodong Li,Fang Peng,Lin Wang
Pressure-induced phase transformation and fluorescent properties of ErF 3 were investigated here using in-situ synchrotron X-ray diffraction and photoluminescence up to 32.1 GPa at room temperature. Results showed that ErF 3 underwent a reversible pressure-induced phase transition from the β-YF 3 –type to the fluocerite LaF 3 -type at 9.8 GPa. The bulk moduli B 0 for low- and high-pressure phases were determined to be 130 and 208 GPa, respectively. Photoluminescencent studies showed that new emission lines belonging to the transition of 2 H 11/2 → 4 I 15/2 , 4 S 3/2 → 4 I 15/2 , and 4 F 9/2 → 4 I 15/2 appeared during phase transition, suggesting pressure-induced electronic band splitting. Remarkably, significant pressure-induced enhancement of photoluminescence was observed, which was attributed to lattice distortion of the material under high pressure.
研究领域:
材料科学
·
光学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 8
·2550
·
IF 4.927
Lingzhi Liang,Xia Ren,Junyi Xu,Yurong Ma,Yunlin Xue,Tao Zhuang,Guisen Zhang
Olanzapine is a commonly used drug in the treatment of schizophrenia, but its clinical application has been restricted by metabolic-related side effects. In order to mitigate the weight gain side effects caused by olanzapine, other drugs with different targets were selected for combined use and evaluated in animal models of schizophrenia. SEP-363856 is a novel psychotropic agent which is under phase III clinical trials for schizophrenia treatment. The aim of the research was to evaluate whether co-administration of olanzapine and SEP-363856 exerts synergistic anti-schizophrenic effects in the apomorphine (APO)-induced climbing test, the MK-801-induced hyperactivity test, and the Morris water maze test, and therefore reduces the weight gain side effects induced by olanzapine. Through isobolographic analysis, the results showed a synergistic interaction in the climbing test; the experimental ED30(3 mg/kg) was significantly smaller (p< 0.05) than the theoretical ED30(5 mg/kg). Additionally, such potentiating effects appeared additive in the MK-801 challenge experiment. Co-treatment with an effective dose of olanzapine and a low dose of SEP-363856 reversed MK-801-induced cognitive impairment symptoms in mice. Moreover, combination treatment with olanzapine and SEP-363856 controls sustained weight gain in mice with chronic exposure to olanzapine. These results support further clinical trials to test the effectiveness of co-treatment of olanzapine and SEP-363856 for controlling symptoms and weight gain in patients with schizophrenia during antipsychotic treatments.Keywords:olanzapine;SEP-363856;schizophrenia;synergistic;side effects
研究领域:
神经科学
·
药理学
·
精神病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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