A5103255193- RNA modifications and cancer
- RNA Research and Splicing
- Particle Accelerators and Free-Electron Lasers
- RNA and protein synthesis mechanisms
- Advanced X-ray Imaging Techniques
- Particle accelerators and beam dynamics
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Gyrotron and Vacuum Electronics Research
- Crystallography and Radiation Phenomena
- Metabolism and Genetic Disorders
- RNA Interference and Gene Delivery
- interferon and immune responses
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Neurological Disease Mechanisms and Treatments
- Liver physiology and pathology
- Genetic Neurodegenerative Diseases
- Electron and X-Ray Spectroscopy Techniques
- Autophagy in Disease and Therapy
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Magnetism in coordination complexes
- Metal complexes synthesis and properties
Hangzhou Normal University
2023-2025
Chongqing Medical University
2024
Children's Hospital of Chongqing Medical University
2024
Jiangxi Maternal and Child Health Hospital
2024
Guangdong Province Women and Children Hospital
2019-2024
Brookhaven National Laboratory
1992-2023
First Affiliated Hospital Zhejiang University
2023
Suzhou Research Institute
2016-2022
Tongji University
2006-2022
Tongji Hospital
2022
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated 9,624 tumors across 33 cancer types using multiple fusion calling tools. identified a total 25,664 fusions, with 63% validation rate. Integration gene expression, copy number, and annotation data revealed that involving oncogenes tend to exhibit increased whereas tumor suppressors have the opposite effect. For kinases, we found 1,275 intact kinase domain, proportion which varied...
Recurrent mutations in the spliceosome are observed several human cancers, but their functional and therapeutic significance remains elusive. SF3B1, most frequently mutated component of cancer, is involved recognition branch point sequence (BPS) during selection 3' splice site (ss) RNA splicing. Here, we report that common tumor-specific splicing aberrations induced by SF3B1 establish aberrant ss as frequent defect. Strikingly, mutant utilizes a BPS differs from used wild-type requires...
Hotspot mutations in splicing factor genes have been recently reported at high frequency hematological malignancies, suggesting the importance of RNA cancer. We analyzed whole-exome sequencing data across 33 tumor types The Cancer Genome Atlas (TCGA), and we identified 119 with significant non-silent mutation patterns, including over-representation, recurrent loss function (tumor suppressor-like), or hotspot profile (oncogene-like). Furthermore, analysis revealed altered events associated...
Abstract Pladienolide, herboxidiene and spliceostatin have been identified as splicing modulators that target SF3B1 in the SF3b subcomplex. Here we report PHF5A, another component of this subcomplex, is also targeted by these compounds. Mutations PHF5A-Y36, SF3B1-K1071, SF3B1-R1074 SF3B1-V1078 confer resistance to modulators, suggesting a common interaction site. RNA-seq analysis reveals PHF5A-Y36C has minimal effect on basal but inhibits global action modulators. Moreover, alters...
Abstract Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence complementary immune evasion mechanisms. Here, we report that PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying in MIBC. Recurrent mutations RXRα at serine 427 (S427F/Y), through conformational activation heterodimer, and focal amplification/overexpression...
Mutations in estrogen receptor alpha (ERα) that confer resistance to existing classes of endocrine therapies are detected up 30% patients who have relapsed during treatments. Because a significant proportion therapy-resistant breast cancer metastases continue be dependent on ERα signaling, there remains critical need develop the next generation antagonists can overcome aberrant activity. Through our drug-discovery efforts, we identified H3B-5942, which covalently inactivates both wild-type...
Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark cancer. Small molecule modulators have been introduced into clinical trials to treat solid tumors leukemia bearing recurrent mutations. Nevertheless, further investigation the molecular mechanisms that may enlighten therapeutic strategies for highly desired. Here, using unbiased functional approaches, we report sensitivity modulation anti-apoptotic BCL2 family key mechanism...
β-Elemene (β-ELE), derived from Curcuma wenyujin, has anticancer effect on non-small cell lung cancer (NSCLC). However, the potential target and detail mechanism were still not clear. TFEB is master regulator of lysosome biogenesis. Ferroptosis, a promising strategy for therapy could be triggered via suppression glutathione peroxidase 4 (GPX4). Weather TFEB-mediated degradation contributes to GPX4 decline how β-ELE modulates this process are To observe action TFEB, role in induced...
The maize Hm1 gene encoding the NADPH-dependent HC-toxin reductase is capable of detoxifying fungus Cochliobolus carbonum . Here, we conducted metabolic and biochemical analysis in transgenic rice plants overexpressing an reductase-like ( YK1 gene). Methods employing NADPH oxidation capillary electrophoresis mass spectrometry confirmed that possessed dihydroflavonol-4-reductase activity vitro vivo overexpression both suspension-cultured cells increased NAD(H) NADP(H) levels by causing...
A method for conditioning electron beams is proposed to enhance gain in resonant electron-beam devices by introducing a correlation between betatron amplitude and energy. This reduces the axial-velocity spread within beam, thereby eliminates an often severe constraint on beam emittance. Free-electron-laser performance with conditioned examined analysis performed of conditioner consisting periodic arry ``FODO'' channels idealized microwave cavitites excited ${\mathrm{TM}}_{210}$ mode....
Rationale: TFEB activation is associated with prolonged survival in LUAD patients, suggesting potential benefits of agonists treatment. In this study, we identify ginkgetin (GK), derived from Ginkgo folium, as a natural agonist, which has demonstrated promising anticancer effects our previous research. been shown to promote GPX4 degradation, inducing ferroptosis; however, the specific E3 ligases, deubiquitinating enzymes (DUBs), and types polyubiquitination chains involved remain unclear....
The excessive activation of the microglia leads to release inflammatory factors that contribute neuronal cell loss and neurodegeneration in Parkinson's Disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) belongs a newly found (NTFs) family has been reported promote survival PD models. However, effects MANF on neuroinflammation remain unclear. AAV8-MANF virus was constructed determine whether high expression can protect neuroinflammation-induced dopaminergic rats with...
The aim of this study was to understand newer nurses' perception and expectations their work environment, professional institutional satisfaction, motivating/decision-making factors around nursing intent leave positions.
A total synthesis of the natural product 6-deoxypladienolide D (1) has been achieved. Two noteworthy attributes are a late-stage allylic oxidation which proceeds with full chemo-, regio-, and diastereoselectivity (2) development scalable cost-effective synthetic route to support drug discovery efforts. 6-Deoxypladienolide demonstrates potent growth inhibition in mutant SF3B1 cancer cell line, high binding affinity SF3b complex, pre-mRNA splicing.
Transfection activities of two series synthetic glycerol backbone-based cationic lipids were studied as gene delivery carriers. The variable length hydrocarbon chains, diverse quaternary ammonium heads, different linkage, well alternative anion combined with them allowed to find how these factors affect on their performance. structure-function relationship the was discussed, and transfection efficiency some liposomes superior or parallel that commercial agents.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, chaperon like heat shock protein was proved to be involved in the MANF induced survival pathway 6-OHDA treated SHSY-5Y cells. However, ER relative transcriptome, signaling cascades still investigated. The involvement of HSP70, 70kd member need further verified. cell apoptosis assayed by MTT, TUNEL staining and western...
In this paper, we explore a method to manipulate low energy electron bunches in space charge dominated regime, and use design linac bunch compressors compress regime. the method, effects instead of avoiding them; i.e., forces generate required chirp ordinary which uses rf accelerating system chirp. We redefine concepts dispersion function beta functions regime guide optimization. Using study (5--22 MeV) compressor produce short ($\ensuremath{\sim}150\text{ }\mathrm{fs}$) small size...