The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential ...candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs.
In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study.
In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug-cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development.
The orthogonal frequency division multiplexing (OFDM) radar suffers from severe performance degradation in range-velocity estimation in high mobility scenarios. In this paper, a novel intercarrier ...interference (ICI)-free parameter estimation method for OFDM radar is proposed. By employing a scale discrete Fresnel transform (SDFnT), the OFDM radar signals are converted to the scale Fresnel domain, and the orthogonality of subcarriers can be recovered with the optimal scale factor. Furthermore, due to the compatibility of the SDFnT and the discrete Fourier Transform (DFT), the proposed method has low computational complexity and high feasibility for OFDM radar implementation. Simulation results show that the proposed SDFnT-based scheme effectively eliminates the ICI effect for single and multiple targets and achieves high accuracy delay-Doppler estimation for OFDM radar systems in circumstances of high velocity and low SNR with consistency and robustness.
The September 2022 Ms 6.8 Luding earthquake broke more than 230 years of seismic calm on the Moxi fault, providing a unique opportunity to understand its seismogenic environment, rupture dynamics, ...and seismic hazard. Using teleseismic body waves, regional strong‐motion observations, GNSS, and InSAR data, we decipher the spatiotemporal rupture evolution of the mainshock. Combining the elastic dislocation model with surface creep, we find that the coseismic slip correlates closely with a locked patch with a loading rate of 9.7 mm/yr, but the creeping rate is insufficient to make up the shallow slip deficit. Notably, the Luding earthquake ruptured only ∼1/4 of the Moxi seismic gap, and it further increased the stress in the unruptured northern part. We thus argue that the Moxi fault has the potential for magnitude 7+ earthquakes in the near future, although geodetic prediction may overestimate the actual seismic moment released by the coseismic rupture.
Plain Language Summary
The Xianshuihe fault is an area of intense tectonic activity on the Tibetan Plateau and plays an important role in accommodating the postcollisional convergence of the Eurasian and Indian plates. However, the Moxi fault, at the southeastern end of the Xianshuihe fault, has remained seismically quiescent since the last Ms 7.75 event in 1786. In September 2022, a Ms 6.8 Luding earthquake struck the Moxi seismic gap, resulting in destructive landslide damage, with 93 people dead and 25 missing. Using seismic and geodetic recordings, we recover its space‐time rupture process in detail. Our model reveals an asymmetric bilateral rupture with dominant propagation and maximum slip to the SSE. It is important to note that the 2022 Luding earthquake ruptured only the southern Moxi seismic gap, leaving the northern part unruptured. Based on the departure time of the last major earthquake and the slip rate obtained from the elastic dislocation model, we estimate the unreleased seismic energy of the Moxi fault, indicating that it still has the potential for strong earthquakes. Besides, the Luding earthquake further increased its seismic hazard through stress transfer. Therefore, we should pay great attention to the kinematic state of the Moxi fault at this time.
Key Points
The kinematic evolution of the Luding earthquake is revealed by seismic and geodetic observations
The coseismic slip asperity from 3 to 20 km depth correlates closely with the preseismic surface creep and locked patch
The unruptured Moxi seismic gap still has the potential for magnitude 7+ earthquakes and deserves further attention
Gas separation is crucial for industrial production and environmental protection, with metal-organic frameworks (MOFs) offering a promising solution due to their tunable structural properties and ...chemical compositions. Traditional simulation approaches, such as molecular dynamics, are complex and computationally demanding. Although feature engineering-based machine learning methods perform better, they are susceptible to overfitting because of limited labeled data. Furthermore, these methods are typically designed for single tasks, such as predicting gas adsorption capacity under specific conditions, which restricts the utilization of comprehensive datasets including all adsorption capacities. To address these challenges, we propose Uni-MOF, an innovative framework for large-scale, three-dimensional MOF representation learning, designed for multi-purpose gas prediction. Specifically, Uni-MOF serves as a versatile gas adsorption estimator for MOF materials, employing pure three-dimensional representations learned from over 631,000 collected MOF and COF structures. Our experimental results show that Uni-MOF can automatically extract structural representations and predict adsorption capacities under various operating conditions using a single model. For simulated data, Uni-MOF exhibits remarkably high predictive accuracy across all datasets. Additionally, the values predicted by Uni-MOF correspond with the outcomes of adsorption experiments. Furthermore, Uni-MOF demonstrates considerable potential for broad applicability in predicting a wide array of other properties.
Cucumber gray mold caused by Botrytis cinerea is considered one of the most serious cucumber diseases. With the advent of Hi-seq technology, it is possible to study the plant-pathogen interaction at ...the transcriptome level. To the best of our knowledge, this is the first application of RNA-seq to identify cucumber and B. cinerea differentially expressed genes (DEGs) before and after the plant-pathogen interaction. In total, 248,908,688 raw reads were generated; after removing low-quality reads and those containing adapter and poly-N, 238,341,648 clean reads remained to map the reference genome. There were 3,512 cucumber DEGs and 1,735 B. cinerea DEGs. GO enrichment and KEGG enrichment analysis were performed on these DEGs to study the interaction between cucumber and B. cinerea. To verify the reliability and accuracy of our transcriptome data, 5 cucumber DEGs and 5 B. cinerea DEGs were chosen for RT-PCR verification. This is the first systematic transcriptome analysis of components related to the B. cinerea-cucumber interaction. Functional genes and putative pathways identified herein will increase our understanding of the mechanism of the pathogen-host interaction.
As a major grain-producing region in China, the North China Plain (NCP) faces serious challenges such as water shortage and land subsidence. In late 2014, the Central Route of the South-to-North ...Water Diversion Project (SNWD-C) began to provide NCP with water resources. However, the effectiveness of this supply in mitigating land subsidence remains a pivotal and yet unassessed aspect. In this paper, we utilized various geodetic datasets, including the Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow On (GRACE-FO), Global Navigation Satellite System (GNSS) and leveling data, to conduct a spatial-temporal analysis of the equivalent water height (EWH) and vertical ground movement in the NCP. The results reveal a noteworthy decline in EWH from 2011 to 2015, followed by a slight increase with minor fluctuations from 2015 to 2020, demonstrating a strong correlation with the water resources supplied by the SNWD-C. The GRACE-derived surface deformation rate induced by hydrological loading is estimated to be <1 mm/yr. In comparison, GNSS-derived vertical ground movements exhibit considerable regional differences during the 2011–2020 period. Substantial surface subsidence is evident in the central and eastern NCP, contrasting with a gradual uplift in the front plain of the Taihang Mountains. Three-stage leveling results indicate that the rate of subsidence in the central and eastern plains is gradually increasing with the depression area expanding from 1960 to 2010. Based on these geodetic results, it can be inferred that the SNWD-C’s operation since 2014 has effectively mitigated the reduction in terrestrial water storage in the NCP. However, land subsidence in the NCP persists, as the subsidence rate does not turn around in sync with the change in EWH following the operation of SNWD-C. Consequently, it’s necessary to maintain and enforce existing policies, including controlling groundwater exploitation and water resources supply (e.g., SNWD-C) to curtail the exacerbation of land subsidence in the NCP. Additionally, continuous monitoring of land subsidence by GRACE, GNSS, leveling and other geodetic techniques is crucial to enable timely policy adjustments based on monitoring results.
In comparison to orthogonal frequency division multiplexing (OFDM), the OFDM linear frequency modulation (OFDM-LFM) signal has similar time-bandwidth product, lower peak-to-average power ratio, and ...higher sensitivity to Doppler frequency shift, making it a promising candidate waveform for multiple-in multiple-out (MIMO) radar applications. However, the OFDM-LFM signal is unsatisfactory in practical applications due to the challenges in waveform design and its non-stationary property, which significantly degrades the performance of current high-resolution subspace techniques for direction of departure (DoD) and direction of arrival (DoA) angle estimation. In this paper, we first proposed a novel OFDM-LFM waveform design method based on the scale discrete Fresnel transform (SDFnT), which efficiently generates orthogonal LFM signals with unlimited number of subcarriers and can be convieniently implemented using the fast Fourier transform (FFT). Then, for angle estimation in OFDM-LFM MIMO radars, we presented a new scale discrete Fresnel transform multiple signal classification (SDFnT-MUSIC) method. By converting the steering vector into the chirp domain and making it non-time-vary, high resolution angle estimation for OFDM-LFM wideband signals can be achieved. Simulation results shows that the proposed waveform design method requires less computational time than conventional method based based on the fractional Fourier transform (FrFT), whereas the proposed DoA-DoD estimation method outperform the FrFT-MUSIC method in terms of computational complexity and target angle estimate performance.
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Growing evidence has proven that T helper 17 (Th17) cells are one of the regulators of ...neuroinflammation mechanisms in MS disease. Researchers have demonstrated that some microRNAs (miRNAs) are associated with disease activity and duration, even with different MS patterns. miRNAs regulate CD4
T cells to differentiate toward various T cell subtypes including Th17 cells. In this review, we discuss the possible mechanisms of miRNAs in MS pathophysiology by regulating CD4
T cell differentiation into Th17 cells, and potential miRNA targets for current disease-modifying treatments.
Assimilable organic carbon (AOC) is one of the most important factors affecting the re-growth of microorganisms in drinking water. High AOC concentrations result in biological instability, but ...disinfection kills microbes to ensure the safety of drinking water. Free chlorine is an important oxidizing agent used during the disinfection process. Therefore, we explored the combined effects of AOC and free chlorine on bacterial growth in drinking water using flow cytometry (FCM). The initial AOC concentration was 168 μg.L(-1) in all water samples. Without free chlorine, the concentrations of intact bacteria increased but the level of AOC decreased. The addition of sodium hypochlorite caused an increase and fluctuation in AOC due to the oxidation of organic carbon. The concentrations of intact bacteria decreased from 1.1 × 10(5) cells.mL(-1) to 2.6 × 10(4) cells.mL(-1) at an initial free chlorine dose of 0.6 mg.L(-1) to 4.8 × 10(4) cells.mL(-1) at an initial free chlorine dose of 0.3 mg.L(-1) due to free chlorine originating from sodium hypochlorite. Additionally, free chlorine might be more obviously affected AOC concentrations than microbial growth did. These results suggested that AOC and free chlorine might have combined effects on microbial growth. In this study, our results showed concentrations determined by FCM were higher than those by HPC, which indicated that some E. coli detected by FCM might not be detected using HPC in drinking water. The level of free chlorine might restrain the consumption of AOC by inhibiting the growth of E. coli; on the other hand, chlorination might increase the level of AOC, thereby increase the potential for microbial growth in the drinking water network.
As a significant part of sustainable urban development proposed by the United Nations, urban planning is related to the ecological environment and transportation, especially affecting quality of life ...and social well-being. In the process of urban planning, the public express their opinions on open network platforms, resulting in large quantities of network public opinion data, which has important implications for evaluating urban planning. Based on the idea of geographical case-based reasoning (CBR), this paper constructs an expression framework for urban planning cases in the form of a 'case problem-case attribute-case result' triad. On this basis, this paper proposes a similarity calculation method of urban planning cases that integrates case attribute. Finally, based on an improvement to the traditional k-nearest neighbors method, the proposed public opinion feature calculation model considers similarity weights, which allow us to predict network public opinion features, including viewpoint-level emotional tendency and concerned groups of urban planning cases. The experimental result shows similarity weights (SWs) model could effectively improve the prediction accuracy, where the average MIC-F1 score reached more than 74%. Based on CBR, the proposed method can predict the development trends of public opinion in future planning cases, and provide scientific and reasonable decision support for urban planning.
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