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Lijing Guo,1,2,* Shihua Chen,1,2,* Liping Ou,1,2,* Shangmei Li,1 Zhen-Nan Ye,1,2 Hua-Feng Liu1,2 1Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China; 2Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen-Nan Ye; Hua-Feng Liu, Email yezhennan12@mails.ucas.ac.cn; hf-liu@263.netAbstract: Alpha-ketoglutarate (AKG) is a key intermediate of various metabolic pathways including tricarboxylic acid (TCA) cycle, anabolic and catabolic reactions of amino acids, and collagen biosynthesis. Meanwhile, AKG also participates in multiple signaling pathways related to cellular redox regulation, epigenetic processes, and inflammation response. Emerging evidence has shown that kidney diseases like diabetic nephropathy and renal ischemia/reperfusion injury are associated with metabolic disorders. In consistence with metabolic role of AKG, further metabolomics study demonstrated a dysregulated AKG level in kidney diseases. Intriguingly, earlier studies during the years of 1980s and 1990s indicated that AKG may benefit wound healing and surgery recovery. Recently, interests on AKG are arising again due to its protective roles on healthy ageing, which may shed light on developing novel therapeutic strategies against age-related diseases including renal diseases. This review will summarize the physiological and pathological properties of AKG, as well as the underlying molecular mechanisms, with a special emphasis on kidney diseases.Keywords: alpha-ketoglutarate, kidney diseases, metabolism, diabetic nephropathy, acute kidney injury

Among social-emotional stimuli, emotional faces occupy an important position, which specifically refer to human faces with certain facial expressions. The visual working memory is a limited workspace where information can be saved online and can be accessed and operated by advanced cognitive function during the maintenance period. A large number of behavioral and electrophysiological studies have shown that there are differences in visual working memory performance of different emotional faces. Specifically, angry faces can enhance the visual working memory performance; fearful faces may cause some damage to visual working memory; sad faces will impair face recognition encoding in visual working memory. However, the visual working memory of happy emotional faces is mainly reflected in the choice of attention compared with other emotional faces, and the time is slightly delayed compared with that of angry faces. This paper sorts out the relevant research on the differences in visual working memory performance produced by different emotional faces as stimuli, and tries to summarize the possible reasons for these differences. peerReviewed

The visual working memory is a limited storage system in which people could flexibly process the representations to complete the task. Among studies on the capacity of visual working memory, the representation unit is a prior subject. Previous research employs the change-detection paradigm and the recall paradigm to explore the nature of representations when features of diverse dimensions and different-level features of the same dimension are stored in the visual working memory. These studies elicit two binary hypotheses: the object-based representation hypothesis backs that those diverse features are bound on the object and form a whole, while the feature-based representation hypothesis supports that independent feature representations have a specific capacity limitation on each dimension. Besides, as a target-drive memory system, the visual working memory receives an undeniable impact from the experiment process and the task demand. By comparing and concluding previous debates on the representation unit, we attempt to reach a united explanation of two hypotheses. This benefits our comprehension of the capacity of visual working memory. The exploration of relevant problems might consider the impact of task demand to improve the experimental design. peerReviewed

Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors. However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are not well understood. Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US. Our analysis reveals that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally long complementarity-determining region 3 loop of the heavy chain, which is distinct from the known binding epitopes of anti-PD-1 mAbs with structural evidences. The glycan modifications of PD-1 could be observed in three potential N-linked glycosylation sites, while no substantial influences were detected to the binding of toripalimab. These findings benefit our understanding of the binding mechanisms of toripalimab to PD-1 and shed light for future development of biologics targeting PD-1. Atomic coordinates have been deposited in the Protein Data Bank under accession code 6JBT.

There is a negative correlation between the quality and quantity of memory representations in visual working memory, and this negative correlation is seen as a trade-off between quantity and quality. However, it is unclear whether this trade-off is entirely stimulus-driven or can be controlled voluntarily by individuals according to task demands, which has led to a debate on the mechanism of memory resource allocation. This paper systematically reviews the development of research on whether the trade-off between quantity and quality is subject to individual voluntary control, and point out this voluntary control is influenced by the exposure duration and working memory capacity, and some suggestions for future research are proposed. peerReviewed

Visual working memory is a memory system with limited capacity, thus internal attention plays a crucial role in selecting, controlling, and maintaining its stored content. Retro-cues are an important tool to study the influence of internal attention on visual working memory. Retro-cues are an important paradigm for studying the influence of internal attention on visual working memory. Depending on the different content of the cue, it can be divided into object-based retro-cue and dimension-based retro-cue and there are significant differences between them. The emergence of dimension-based retro-cue in recent years has become one of the hot topics of research. There are articles summarizing the research contents of object-based retro-cue, but the contents and progress of research on dimension-based retro-cue have not been sorted out and summarized. In this paper, we find that compared with object-based retro-cue, dimension-based retro-cue is more global, fragile; the effect of dimension-based retro-cue is influenced by visual dimensions, the number of memory sequences, individual differences and other factors; and the intrinsic mechanism of retro-cue benefits may be based on the reasons of preventing memory from time-based decay or taking non-target objects as the cost. Finally, we make suggestions for future directions and research. peerReviewed