OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Bipedalism (using only two legs for walking) and having the capability to use tools have long been considered characteristic features that differentiate human beings from animals. Being able to walk upright freed up human hands, allowing us to reach, grasp, carry food, make and use tools, which greatly increased the survivability of our ancestors. Hand actions not only involve muscles and joints to execute actions but also require computations in the brain to analyze the visual environment and select the appropriate action, as well as formulate the action before execution and correct it in real-time during execution. Here, we review the behavioral and brain imaging research of human hand actions from a perspective of cognitive neuroscience. The review includes the research contents and methods of visually-guided action, existing theories, current debates, new evidence of existing theories, and the applications of action research in robotics and artificial intelligence.
Brain ; diagnostic imaging ; physiology ; Hand ; Humans ; Neuroimaging ; Psychomotor Performance

Background:Platinum?based chemotherapy is the ifrst?line treatment of non?small cell lung cancer (NSCLC); it is therefore important to discover biomarkers that can be used to predict the effcacy and toxicity of this treatment. Four important transporter genes are expressed in the kidney, including organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), ATP?binding cassette subfamily B member 1 (ABCB1), and ATP?binding cassette subfamily C member 2 (ABCC2), and genetic polymorphisms in these genes may alter the effcacy and adverse effects of platinum drugs. This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinum?based chemotherapy response and toxicity in NSCLC patients. Methods:A total of 403 Chinese NSCLC patients were recruited for this study. All patients were newly diagnosed with NSCLC and received at least two cycles of platinum?based chemotherapy. The tumor response and toxicity were evaluated after two cycles of treatment, and the patients’ genomic DNA was extracted. Seven single?nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum?based chemo?therapy toxicity and response. Results:OCT2 rs316019 was associated with hepatotoxicity (P=0.026) and hematological toxicity (P=0.039), and MATE1 rs2289669 was associated with hematological toxicity induced by platinum (P=0.016). In addition,ABCC2 rs717620 was signiifcantly associated with the platinum?based chemotherapy response (P=0.031).ABCB1 polymor?phisms were associated with neither response nor toxicity. Conclusion:OCT2 rs316019,MATE1 rs2289669, andABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum?based treatment in NSCLC patients. Trial registration Chinese Clinical Trial Registry ChiCTR?RNC?12002892