A5010099021- Environmental Changes in China
- Remote Sensing and Land Use
- Land Use and Ecosystem Services
- Rangeland Management and Livestock Ecology
- Plant Ecology and Soil Science
- Lung Cancer Treatments and Mutations
- Rural development and sustainability
- Environmental Quality and Pollution
- Environmental and Agricultural Sciences
- Karst Systems and Hydrogeology
- Soil erosion and sediment transport
- Geology and Paleoclimatology Research
- Hydrocarbon exploration and reservoir analysis
- Geoscience and Mining Technology
- Conservation, Biodiversity, and Resource Management
- Regional Development and Environment
- Plant Water Relations and Carbon Dynamics
- Protein Degradation and Inhibitors
- Forest, Soil, and Plant Ecology in China
- Lung Cancer Research Studies
- Ubiquitin and proteasome pathways
- Methane Hydrates and Related Phenomena
- Wildlife-Road Interactions and Conservation
- Peptidase Inhibition and Analysis
- Regional Economic and Spatial Analysis
BOE Technology Group (China)
2020-2025
Guizhou Normal University
2009-2024
Chongqing Normal University
2009-2024
China National Offshore Oil Corporation (China)
2020-2024
University of Michigan
2016-2024
Chang'an University
2024
Center for Drug Evaluation and Research
2020-2023
United States Food and Drug Administration
2020-2023
Lanzhou University
2019-2022
Lanzhou University Second Hospital
2019-2022
Human murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53 and has been pursued as an attractive cancer therapeutic target. Several potent, nonpeptide, small-molecule inhibitors MDM2 are currently in clinical development. In this paper, we report our design, synthesis, evaluation degraders based on proteolysis targeting chimera (PROTAC) concept. The most promising compound (MD-224) effectively induces rapid degradation at concentrations...
Inducing protein degradation by proteolysis targeting chimeras (PROTACs) has gained tremendous momentum for its promise to discover and develop new therapies. Based upon our previously reported PROTAC MDM2 degraders, we have designed synthesized additional analogues. Surprisingly, found that simple structural modifications of MD-222, a bona fide degrader, converts it into "molecular glue", as exemplified MG-277. MG-277 induces only moderate fails activate wild-type p53 but is highly potent...
On May 8, 2020, the FDA granted accelerated approval to selpercatinib for (i) adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), (ii) and pediatric ≥12 years of age advanced or RET-mutant medullary thyroid who require systemic therapy, (iii) therapy are radioactive iodine refractory (if is appropriate). Approval was on basis clinically important effects overall response rate (ORR) prolonged duration responses observed in a multicenter, open-label,...
Abstract. Although some scholars have studied soil erosion in karst landforms, analyses of the spatial and temporal evolution correlation with elements been insufficient. The lack research has led to an inaccurate assessment environmental effects, especially mountainous area Wuling China. Soil rocky desertification this influence survival sustainability a population 0.22 billion people. This paper analyzes spatiotemporal explores its relationship using GIS technology revised universal loss...
We report herein the design, synthesis, and evaluation of macrocyclic peptidomimetics that bind to WD repeat domain 5 (WDR5) block WDR5-mixed lineage leukemia (MLL) protein-protein interaction. Compound 18 (MM-589) binds WDR5 with an IC50 value 0.90 nM (Ki <1 nM) inhibits MLL H3K4 methyltransferase (HMT) activity 12.7 nM. potently selectively cell growth in human lines harboring translocations is >40 times better than previously reported compound MM-401. Cocrystal structures 16 complexed...
On June 15, 2020, the FDA granted accelerated approval to lurbinectedin for treatment of adult patients with metastatic small cell lung cancer (SCLC) disease progression on or after platinum-based chemotherapy. Approval was basis clinically meaningful effects overall response rate (ORR) and duration (DOR), safety profile observed in a multicenter, open-label, multicohort clinical trial (PM1183-B-005-14, NCT02454972), referred as Study B-005, advanced solid tumors. The included cohort 105...
On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or 21 (L858R) mutations, detected by an FDA-approved test. The approval was based on ADAURA study, which 682 NSCLC were randomized to receive (n = 339) placebo 343). Disease-free survival (DFS) overall population (stage IB-IIIA) improved for who received osimertinib, HR of 0.20; 95% confidence interval (CI), 0.15-0.27; P < 0.0001....
Ecosystem health is an essential characterization of landscape pattern ecological effects, and refined analysis the variability changes on ecosystem in mountainous areas great significance for synergistic development Man-Earth systems. This study constructed a research framework effects patterns based theory ecology topographic gradient. Taking Miaoling Mountains China as example, used spatial techniques to analyze process from 2000 2020 detected response by using rank correlation analysis....
With the rapid socioeconomic development and urbanization, global agroecosystems (AESs) have undergone varying degrees of transformation, conducting an in-depth study on how AESs are transforming in karst mountainous areas (KMAs) is essential. To further reveal transformation process KMAs, we proposed a theoretical framework for KMAs. Following "theory construction–empirical analysis–pattern evolution–mechanism revelation" research methodology, studied trend AES evolution "typical...
Human activities and landscape patterns are important representations of two major elements in the human-land system. Therefore, analyzing coupling characteristics human activity intensity is great significance to reveal evolution regional relationships. To fill hole on response pattern, mountainous pattern model was constructed, comprehensive dominant-recessive index (CHAI) proposed. Moreover, based AHP cumulative method, we quantitatively evaluated Fengjie County hinterland Three Gorges...
Abstract Systematic elucidation of the evolution trend karst rocky desertification (KRD) is great significance for correctly understanding its occurrence and development process, implementing effective comprehensive control measures. Based on existing studies, authors explore formation evolutionary mechanisms trends KRD in mountains Southwest China based literature field investigations. The factors driving are: single livelihood farmers mountain areas (KMA); land pressure, low carrying...
With the rapid development of urbanization and industrialization, rural functions in China's mountainous regions have tended to diversify, use sloping cultivated land has also evolved. Exploring coupling relationship between functional diversification evolution is great significance protection areas sustainable villages. We constructed a theoretical framework analyze interaction then verified it with Fengjie County, China. Our research results show that: overall agricultural production...
Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and regeneration. A major challenge iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate reprogramming ability towards fate by removing inhibitory roadblocks. Using mouse embryonic as starting cell source, first screened 47 development related epigenetic transcription factors, identified an...