Background: Depression is a common and potentially life-threatening mental illness, and currently, there is a lack of effective treatment. It has been reported that dehydrocorydaline (DHC) can inhibit monoamine transporter uptake in depressed CUMS mice, but more possible mechanisms of action remain to be further studied.Methods: C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for five consecutive weeks. The mice were administrated with dehydrocorydaline or fluoxetine (FLU) for four consecutive weeks. Behavioral tests including sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST) were applied. In parallel, hematoxylin and eosin (H&E) staining and Nissl staining were used to explore the effect of DHC on pathological changes in the hippocampus. The concentrations of depression-related factors (5-HT and DA) and inflammatory factors (TNF-α, IL-6, and IL-1β) in the hippocampus and serum were assessed by ELISA assay. NLRP3 inflammasome pathway-related proteins (NLRP3, IL-18, IL-1 IL-1α, and caspase-1) were detected by western blot. The activation of microglia and astrocytes was subjected to immunofluorescent staining. Additionally, microglia were treated with DHC (100 mg/L) for 24 h following incubation with 100 ng/ml LPS for 12 h. ov-NC or ov-NLRP3 plasmid was transfected into microglia 6 h before LPS induction for exploring the effect of NLRP3 overexpression on DHC-inhibited microglia activation. Then, conditioned media of microglia were collected from each group, followed by intervention of astrocytes for 24 h to explore the effect of NLRP3 overexpression of microglia on astrocyte activation.Results:In vivo administration of DHC was found to ameliorate depressive-like behaviors and attenuate neuron damage of CUMS mice. DHC increased neurotransmitter concentration, reduced the proinflammatory factor levels, attenuated NLRP3 inflammasome activation, and decreased A1 astrocyte and microglia activation in the hippocampus of CUMS mice. Furthermore, in vivo results showed that activated microglia induced activation of A1 astrocytes but not A2 astrocytes.Conclusion: Taken together, we provided evidence that DHC exhibited antidepressive effects on CUMS mice possibly via NLRP3 inflammasome-mediated astrocyte activation.

A meta-dehydrogenative alkylation of arenes with cyclic ethers, ketones, and esters catalyzed by ruthenium is achieved in the presence of a di-tert-butyl peroxide (DTBP) oxidant. Interestingly, when quinoline and isoquinoline are employed as the directing group, or a chain ether as alkylation reagent, the system produces Minisci reaction products. Mechanistic study indicates that meta-dehydrogenative alkylation is a radical process initiated by DTBP with the assistance of a C Ar −Ru bond ortho/para-directing effect.

Background We examined for the first time the imaging characteristics of Holmes tremor (HT) through multimodal 3D medical imaging. Case presentation Three patients with Holmes tremor who visited the Affiliated Hospital of Chengdu University of TCM from August 2018 to April 2021 were retrospectively investigated to summarize their clinical and imaging data. Results Holmes tremor in two of the three patients was caused by hypertensive cerebral hemorrhage and in the third patient induced by hemorrhage due to ruptured brain arteriovenous malformations. HT occurred 1 to 24 months after the primary disease onset and manifested as a tremor in the contralateral limb, mostly in the upper portion. Cranial MRI showed that the lesions involved the thalamus in all three patients. The damaged thalamic nuclei included the ventral anterior nucleus, ventral lateral nucleus and ventromedial lateral nucleus, and the damaged nerve fibers included left thalamocortical tracts in one patient. In the other two patients, the damaged thalamic nuclei included the centromedian and dorsomedial nucleus, and the damaged nerve fibers included left cerebellothalamic and thalamocortical tracts. One patient showed significant improvement after treatment with pramipexole while the other two patients exhibited a poor response, one of whom had no response to the treatment with pramipexole and was only significantly relieved by clonazepam. Conclusion We used multimodal 3D medical imaging for the first time to analyze the pathogenesis of HT and found that multiple thalamic nuclei were damaged. The damaged nuclei and nerve fiber tracts of two patients were different from those of the third patient, with different clinical manifestations and therapeutic effects. Therefore, it is speculated that there may be multiple pathogeneses for HT.

Substituent effects of fused six, and five‐membered aromatic rings are investigated on the stability, aromaticity, charge distribution, nucleophilic (N), and electrophilic (ω) characters of 20 singlet (s) and triplet (t) Hammick carbenes, at B3LYP/AUG‐cc‐pVTZ and M06‐2X/AUG‐cc‐pVTZ. Results display: (a) The higher thermodynamic and kinetic stability is revealed by carbenes situated between two nitrogen and/or two oxygen heteroatoms of two substituted rings, in a “W” arrangement toward the carbenic center; (b) Regardless of the arrangement, the order of thermodynamical and kinetic stabilization for fused rings is pyrrole > furan > thiophene > phosphole. (c) The substituted Hammick carbenes with two fused heterocyclics, in a given arrangement, show more stability than unsubstituted Hammick carbene; (d) While two five‐membered heterocyclic rings stabilize their corresponding substituted carbenes, two benzene rings destabilize Hammick carbene; (e) In all structures, s species emerges as ground state, exhibiting more stability than its t state; (f) The scrutinized s carbenes show higher N and lower ω than their corresponding t states.

Background: Insomnia as one of the dominant diseases of traditional Chinese medicine (TCM) has been extensively studied in recent years. To explore the novel approaches of research on TCM diagnosis and treatment, this paper presents a strategy for the research of insomnia based on machine learning. Methods: First of all, 654 insomnia cases have been collected from an experienced doctor of TCM as sample data. Secondly, in the light of the characteristics of TCM diagnosis and treatment, the contents of research samples have been divided into four parts: the basic information, the four diagnostic methods, the treatment based on syndrome differentiation and the main prescription. And then, these four parts have been analyzed by three analysis methods, including frequency analysis, association rules and hierarchical cluster analysis. Finally, a comprehensive study of the whole four parts has been conducted by random forest. Results: Researches of the above four parts revealed some essential connections. Simultaneously, based on the algorithm model established by the random forest, the accuracy of predicting the main prescription by the combinations of the four diagnostic methods and the treatment based on syndrome differentiation was 0.85. Furthermore, having been extracted features through applying the random forest, the syndrome differentiation of five zang-organs was proven to be the most significant parameter of the TCM diagnosis and treatment.Conclusions: The results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment.