Objectives: Xiaochaihutang (XCHT) has been used in China for thousands of years to treat ‘Shaoyang syndrome’, which involves depressive-like symptoms. However, no studies were conducted to demonstrate its antidepressant effect and mechanism. This study was designed to confirm the antidepressant effect of XCHT and explore its mechanism using the pharmacological methods. Methods: Ultra-HPLC and mass spectrometry was used to identify the chemical constituents of XCHT. Forced swimming test (FST) and tail suspension test (TST) were used to determine the antidepressant-like activity of XCHT in mice and rats. The possible mechanism of XCHT was elucidated by the reserpine-induced hypothermia and 5-hydroxytryptophan (5-HTP)-induced head-twitch in mice. The levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in prefrontal cortex and hippocampus tissue of both mice and rats. Moreover, the extracellular 5-HT in rat hippocampus was assessed by using microdialysis coupled to HPLC with electrochemical detection. Key findings: Forty-four components were detected in XCHT. XCHT significantly reduced immobility time in the TST and the FST, antagonized reserpine-induced depressive-like behaviours, increased 5-HTP-induced head-twitches, elevated 5-HT and 5-HIAA levels, and increased 5-HT turnover at doses that did not affect general activity. Conclusions: These data demonstrate that XCHT has therapeutic effects in animal models of depression by enhancing the serotoninergic system in the prefrontal cortex and hippocampus.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

The anti-seizure effect of oleamide, an endogenous sleep-inducing fatty acid amide, was studied in mice. Oleamide, in the dose range 43.7–700.0 mg kg−, significantly and dose-dependently inhibited the seizures induced by pentylenetetrazole. However, oleamide showed no inhibitory action on the seizures induced by picrotoxin, strychnine, caffeine or semicarbazide. These results provide the first evidence for the anti-seizure effect of oleamide, and suggest that this effect may be selective to the seizure model induced by pentylenetetrazole.

A composite strategy is proposed to address the optimal power management for a hybrid powered compound-wing aircraft, which integrates bang–bang regulation with optimal demand chasing regulation. The electro-gasoline hybrid power system enhances the overall flight endurance of vertical take-off and landing compound-wing aircraft. The power consumption in level flight appears to be much lower than that in hovering, enabling the hybrid power system to simultaneously energize and charge the battery pack. In order to minimize fuel consumption and battery pack degradation during level cruise flight, a power management strategy that serves for both battery charging and thrust energizing is worthy of careful consideration. To obtain the desired features and design the regularity strategy of the power system, linear and nonlinear models are established based on the configuration of an electro-gasoline series hybrid power system installed in the proposed aircraft, with mathematical modelling of key components and units. A notable feature of semi-fixing for battery voltage and engine rotational speed has been qualitatively identified and subsequently quantitatively validated on the testbench. After conducting simulations and comparing with other strategies, the composite strategy demonstrates appropriate fuel consumption and battery degradation, effectively achieving cost minimization. Testbench evaluation confirms the effectiveness of this proposed power management strategy. Furthermore, the practicality of the hybrid power system and its associated level flight composite power management strategy are validated by tests conducted on a 30 kg aircraft prototype, thereby showcasing the potential to enhance flight performance.