Due to the advantages in efficacy and safety compared with traditional chemotherapy drugs, targeted therapeutic drugs have become mainstream cancer treatments. Since the first tyrosine kinase inhibitor imatinib was approved to enter the market by the US Food and Drug Administration (FDA) in 2001, an increasing number of small-molecule targeted drugs have been developed for the treatment of malignancies. By December 2020, 89 small-molecule targeted antitumor drugs have been approved by the US FDA and the National Medical Products Administration (NMPA) of China. Despite great progress, small-molecule targeted anti-cancer drugs still face many challenges, such as a low response rate and drug resistance. To better promote the development of targeted anti-cancer drugs, we conducted a comprehensive review of small-molecule targeted anti-cancer drugs according to the target classification. We present all the approved drugs as well as important drug candidates in clinical trials for each target, discuss the current challenges, and provide insights and perspectives for the research and development of anti-cancer drugs.

Abstract-Machine learning (ML) has been widely applied to the upper layers of wireless communication systems for various purposes, such as deployment of cognitive radio and communication network. However, its application to the physical layer is hampered by sophisticated channel environments and limited learning ability of conventional ML algorithms. Deep learning (DL) has been recently applied for many fields, such as computer vision and natural language processing, given its expressive capacity and convenient optimization capability. The potential application of DL to the physical layer has also been increasingly recognized because of the new features for future communications, such as complex scenarios with unknown channel models, high speed and accurate processing requirements; these features challenge conventional communication theories. This paper presents a comprehensive overview of the emerging studies on DL-based physical layer processing, including leveraging DL to redesign a module of the conventional communication system (for modulation recognition, channel decoding, and detection) and replace the communication system with a radically new architecture based on an autoencoder. These DL-based methods show promising performance improvements but have certain limitations, such as lack of solid analytical tools and use of architectures that are specifically designed for communication and implementation research, thereby motivating future research in this field.

Massive multiple-input multiple-output (MIMO) systems rely on channel state information (CSI) feedback to perform precoding and achieve performance gain in frequency division duplex (FDD) networks. However, the huge number of antennas poses a challenge to conventional CSI feedback reduction methods and leads to excessive feedback overhead. In this article, we develop a real-time CSI feedback architecture, called CsiNet-long short-term memory (LSTM), by extending a novel deep learning (DL)-based CSI sensing and recovery network. CsiNet-LSTM considerably enhances recovery quality and improves trade-off between compression ratio (CR) and complexity by directly learning spatial structures combined with time correlation from training samples of time-varying massive MIMO channels. Simulation results demonstrate that CsiNet-LSTM outperforms existing compressive sensing-based and DLbased methods and is remarkably robust to CR reduction.

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Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.

As a major component of cell membrane lipids, Arachidonic acid (AA), being a major component of the cell membrane lipid content, is mainly metabolized by three kinds of enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these three metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In the kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are the major metabolites generated from AA. An increased level of prostaglandins (PGs), TxA2 and leukotriene B4 (LTB4) results in inflammatory damage to the kidney. Moreover, the LTB4-leukotriene B4 receptor 1 (BLT1) axis participates in the acute kidney injury via mediating the recruitment of renal neutrophils. In addition, AA can regulate renal ion transport through 19-hydroxystilbenetetraenoic acid (19-HETE) and 20-HETE, both of which are produced by cytochrome P450 monooxygenase. Epoxyeicosatrienoic acids (EETs) generated by the CYP450 enzyme also plays a paramount role in the kidney damage during the inflammation process. For example, 14 and 15-EET mitigated ischemia/reperfusion-caused renal tubular epithelial cell damage. Many drug candidates that target the AA metabolism pathways are being developed to treat kidney inflammation. These observations support an extraordinary interest in a wide range of studies on drug interventions aiming to control AA metabolism and kidney inflammation.

The assembly of DNA fragments with homologous arms is becoming popular in routine cloning. For an in vitro assembly reaction, a DNA polymerase is often used either alone for its 3′-5′ exonuclease activity or together with a 5′-3′ exonuclease for its DNA polymerase activity. Here, we present a ‘T5 exonuclease DNA assembly’ (TEDA) method that only uses a 5′-3′ exonuclease. DNA fragments with short homologous ends were treated by T5 exonuclease and then transformed into Escherichia coli to produce clone colonies. The cloning efficiency was similar to that of the commercial In-Fusion method employing a proprietary DNA polymerase, but higher than that of the Gibson method utilizing T5 exonuclease, Phusion DNA polymerase, and DNA ligase. It also assembled multiple DNA fragments and did simultaneous site-directed mutagenesis at multiple sites. The reaction mixture was simple, and each reaction used 0.04 U of T5 exonuclease that cost 0.25 US cents. The simplicity, cost effectiveness, and cloning efficiency should promote its routine use, especially for labs with a budget constraint. TEDA may trigger further development of DNA assembly methods that employ single exonucleases.

We demonstrate a rational fabrication of hierarchical treated rape pollen as metal-free catalyst for visible-light-driven photocatalytic CO2 reduction.