Projections from the ventral tegmental area to zona incerta regulate fear generalization in a mouse model of PTSD.

Generalized fear is a maladaptive behavior in which non-threatening stimuli elicit a fearful response. The ventral tegmental area (VTA) has been demonstrated to play important roles in fear response and fear memory generalization, but the precious neural circuit mechanism is still unclear. Here, we demonstrated that VTA-zona incerta (ZI) glutamatergic projection is involved in regulating high-intensity threatening training induced generalization and anxiety. Combining calcium signal recording and chemogentics, our work reveals that VTA glutamatergic neurons respond to closed arm entering in the model of PTSD. Inhibition of VTA glutamatergic neurons or the glutamatergic projection to ZI could both relieve fear generalization and anxiety. Together, our study proves the VTA - ZI glutamatergic circuit is involved in mediating fear generalization and anxiety, and provides a potential target for treating post-traumatic stress disorder.

A crossover study to evaluate the pharmacokinetics and bioequivalence of hydroxychloroquine tablets in healthy Chinese subjects.

AIMS: Hydroxychloroquine (HCQ) has a high variability and a long half-life in the human body. The purpose of this study was to evaluate the bioequivalence of a generic HCQ tablet (test preparation) versus a brand HCQ tablet (reference preparation) under fasting and fed conditions in a crossover design. MATERIALS AND METHODS: This was an open-label, two-period randomized, single-dose, crossover study in 47 healthy Chinese subjects who were sequentially and randomly allocated either to the fed group (high-fat meal; n = 23) or the fasting group (n = 24). Participants in each group were randomized to the two arms to receive either a single 200-mg dose of the test preparation or a 200-mg dose of the reference preparation. The application of the two preparations in each patient was separated by a 28-day washout period, regarded as sufficiently long to avoid significant interference from residual drug in the body. Whole blood samples were collected over 72 hours after drug administration. RESULTS: A total of 23 subjects completed both the fed and the fasting parts of the trial. There were no significant differences in Cmax, AUC0-72h, and T1/2 between the test and reference preparation (p < 0.05). Food had no significant effect on Cmax and T1/2 (p < 0.05), but AUC0-72h values were significantly reduced under fed condition compared to fasting condition (p < 0.05). The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of Cmax and AUC0-72h were 0.84 - 1.05 and 0.89 - 0.98 in the fed study, and 0.97 - 1.07 and 0.97 - 1.05 in the fasting study, respectively. The carryover effect due to non-zero blood concentrations resulted in higher AUC0-72h values in the second period for both test and reference formulations and had no effect on the statistical results. No serious adverse events were reported. CONCLUSION: The investigation demonstrated that the test and reference preparations are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese subjects.

A metal-organic framework-supported dinuclear iron catalyst for hydroboration of carbonyl compounds.

Preparation of catalytically active dinuclear transition metal complexes with an open coordination sphere is a challenging task because the metal sites tend to be "saturated" with excess donor atoms around during synthesis. By isolating the binding scaffolds with the metal-organic framework (MOF) skeleton and installing metal sites through post-synthetic modification, we succeed in constructing a MOF-supported metal catalyst, namely FICN-7-Fe2, with dinuclear Fe2 sites. FICN-7-Fe2 effectively catalyses the hydroboration of a broad range of ketone, aldehyde, and imine substrates with a low loading of 0.05 mol%. Remarkably, kinetic measurements showed that FICN-7-Fe2 is 15 times more active than its mononuclear counterpart FICN-7-Fe1, indicating that cooperative substrate activation on the two Fe centres significantly enhances the catalysis.

Global Transcriptomic Profile Analysis of Genes Involved in Lignin Biosynthesis and Accumulation Induced by Boron Deficiency in Poplar Roots.

To uncover the transcriptomic mechanism of lignin accumulation caused by boron deficiency (BD), Nanlin895 (Populus × euramericana "Nanlin895") was subjected to control (CK, 0.25 mg·L-1) and BD (0 mg·L-1) treatments for 3 days. RNA-Seq was carried out to survey the expression patterns of the lignin-regulated biosynthetic genes in response to BD. The results showed that 5946 genes were identified as differentially expressed genes (DEGs), 2968 (44.2%) of which were upregulated and 3318 (55.8%) of which were downregulated in response to BD. Among them, the expression of lignin monomer biosynthetic (PAL, CCR, CAD, COMT, F5H, PER/LAC) and modulated genes, for example, transcription factors (MYBs) and hormone signal regulating genes (GIDs, histidine kinase 1, coronatine-insensitive protein 1), were upregulated, and some hormone signal regulating genes, such as AUXs and BR-related (sterol methyltransferases), were downregulated under BD treatment. There are also some genes that were screened as candidates for an association with wood formation, which will be used for the further analysis of the function of lignin formation. These results provide an important theoretical basis and reference data in plant for further research on the mechanism of lignin accumulation under BD.