A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Corticostriatal Neurons in the Anterior Auditory Field Regulate Frequency Discrimination Behavior.

The anterior auditory field (AAF) is a core region of the auditory cortex and plays a vital role in discrimination tasks. However, the role of the AAF corticostriatal neurons in frequency discrimination remains unclear. Here, we used c-Fos staining, fiber photometry recording, and pharmacogenetic manipulation to investigate the function of the AAF corticostriatal neurons in a frequency discrimination task. c-Fos staining and fiber photometry recording revealed that the activity of AAF pyramidal neurons was significantly elevated during the frequency discrimination task. Pharmacogenetic inhibition of AAF pyramidal neurons significantly impaired frequency discrimination. In addition, histological results revealed that AAF pyramidal neurons send strong projections to the striatum. Moreover, pharmacogenetic suppression of the striatal projections from pyramidal neurons in the AAF significantly disrupted the frequency discrimination. Collectively, our findings show that AAF pyramidal neurons, particularly the AAF-striatum projections, play a crucial role in frequency discrimination behavior.

Preparation and Enantioseparation of Biselector Chiral Stationary Phases Based on Amylose and Chitin Derivatives.

Amylose derivatives chiral stationary phases (CSPs), some of which are commercially available, are well known for their powerful enantioseparation performance. However, due to the dissolution or swelling properties of amylose derivatives, this type of CSPs prepared by coating method exhibit poor solvent tolerance and stability. In order to overcome the defect as well as maintain the chiral recognition capability of amylose tris(3,5-dimethylphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) with good stability and good chiral recognition capability was blended with the amylose derivative at different ratios, and the resulting blends were further coated onto 3-aminopropyl silica gel to obtain three biselector CSPs. Meanwhile, the corresponding individual selector CSPs were also prepared, respectively, for the sake of comparison with biselector CSPs. The chiral recognition capacity and solvent tolerance of five CSPs were systematically investigated. In addition, the influence of composition and interaction of amylose tris(3,5-dimethylphenylcarbamate) and chitin bis(3-chloro-4-methylphenylcarbamate) in the biselector CSPs on the chiral recognition and the elute orders of enantiomers was also discussed in detail.

Enantioseparation characteristics of tadalafil and its intermediate on chitin derived chiral stationary phases.

Due to the low solubility and swelling properties of chitin bis(arylcarbamate) in most organic solvents, the chiral stationary phases (CSPs) prepared from chitin derivatives can be analyzed with a wide range of solvents. In order to develop new CSPs of chitin derivatives with halogen groups, chitin was derivatized with three different phenyl isocyanates to obtain chitin bis(4-trifluoromethoxyphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) and chitin bis(4-chloro-3-trifluoromethylphenylcarbamate). Then, the three chitin derivatives were coated on macroporous 3-aminopropyl-functionalized silica gel to obtain three CSPs 1-3 respectively. These CSPs showed good enantioseparation capabilities towards tadalafil and its intermediate. Therefore, these CSPs are potentially applied for the enantioseparation and determination of tadalafil and its intermediate. It was also found that the retention times of some enantiomers were prolonged in the presence of their diastereoisomers or structural analogues and as a result, the resolution was improved to some extent. Hence, in the enantioseparation of a compound with two chiral centers, the resolution is hopefully improved by adding a diastereoisomer or a structural analogue.

Enantioseparation characteristics of biselector chiral stationary phases based on derivatives of cellulose and amylose.

Cellulose tris(4-methylphenylcarbamate) (CMPC) and cellulose tris(4-chlorophenylcarbamate) (CCPC) are well known for their powerful chiral recognition capability, and the chiral columns prepared from these two polymers have been commercialized. However, the chiral stationary phases (CSPs) can be only used in the mobile phases containing no more than 20% ethanol (referring to CMPC) or cannot be used in ethanol-containing mobile phases (referring to CCPC). In order to overcome the defect and to study the enantioseparation characteristics of biselector CSPs, CMPC, cellulose tris(phenylcarbamate) (CPC) and CCPC were, respectively, mixed with amylose tris(3,5-dimethylphenylcarbamte) (ADMPC) at a ratio of 1:1 (mol/mol) of glucose unit, and three new CSPs were prepared by coating the resulting blends on 3-aminopropyl silica gel. For the purpose of enantioseparation comparison, the corresponding single selector CSPs were also prepared with the individual derivatives of cellulose and amylose. The enantioseparation evaluation indicated that the biselector CSPs still bear excellent enantioseparation capability. The interaction between two polymers in each blend was investigated by using circular dichroism (CD) spectroscopy. Owing to the interaction, the durability of the biselector CSP derived from CMPC and ADMPC was significantly improved. The CSP could be analyzed with a mobile phase of 100% ethanol. And the biselector CSP derived from CCPC and ADMPC could safely work in a normal phase containing 30% ethanol. Therefore, the workable ranges of the mobile phases were broadened. The elution order on the biselector CSPs was generally dominated by the one on the corresponding single selector CSPs that provided a higher resolution. In addition, the suprastructure variation caused by the interaction between the individual polymers might also affect the enantioseparation of the biselector CSPs. The trends of the retention factors and the resolutions of partially racemic mixtures were discussed.