Pd-Catalyzed Borylsilylative Cyclization of 1,6-Allenynes.

A Pd-catalyzed borylsilylative cyclization of 1,6-allenynes with PhMe2SiBpin was developed. This method provides a practical and general method to afford the carbocycles and heterocycles bearing silyl and boryl groups with excellent regioselectivities and stereoselectivities in high to excellent yields.

Wrist pulse signal based vascular age calculation using mixed Gaussian model and support vector regression.

Purpose: Vascular age (VA) is the direct index to reflect vascular aging, so it plays a particular role in public health. How to obtain VA conveniently and cheaply has always been a research hotspot. This study proposes a new method to evaluate VA with wrist pulse signal. Methods: Firstly, we fit the pulse signal by mixed Gaussian model (MGM) to extract the shape features, and adopt principal component analysis (PCA) to optimize the dimension of the shape features. Secondly, the principal components and chronological age (CA) are respectively taken as the independent variables and dependent variable to establish support vector regression (SVR) model. Thirdly, the principal components are fed into the SVR model to predicted the vascular aging of each subject. The predicted value is regarded as the description of VA. Finally, we compare the correlation coefficients of VA with pulse width (PW), inflection point area ratio (IPA), Ratio b/a (RBA), augmentation index (AIx), diastolic augmentation index (DAI) and pulse transit time (PTT) with those of CA with these six indices. Results: Compared with the CA, the VA is closer to PW (r = 0.539, P < 0.001 to r = 0.589, P < 0.001 in men; r = 0.325, P < 0.001 to r = 0.400, P < 0.001 in women), IPA (r = - 0.446, P < 0.001 to r = - 0.534, P < 0.001 in men; r = - 0.623, P < 0.001 to r = - 0.660, P < 0.001 in women), RBA (r = 0.328, P < 0.001 to r = 0.371, P < 0.001 in women), AIx (r = 0.659, P < 0.001 to r = 0.738, P < 0.001 in men; r = 0.547, P < 0.001 to r = 0.573, P < 0.001 in women), DAI (r = 0.517, P < 0.001 to r = 0.532, P < 0.001 in men; r = 0.507, P < 0.001 to r = 0.570, P < 0.001 in women) and PTT (r = 0.526, P < 0.001 to r = 0.659, P < 0.001 in men; r = 0.577, P < 0.001 to r = 0.814, P < 0.001 in women). Conclusion: The VA is more representative of vascular aging than CA. The method presented in this study provides a new way to directly and objectively assess vascular aging in public health.

Paternal fenvalerate exposure transgenerationally impairs cognition and hippocampus in female offspring.

The impairments of maternal fenvalerate exposure have been well documented in previous study, but little was known about the effects of paternal fenvalerate exposure. The current study aimed to assess the effects of paternal fenvalerate exposure on spatial cognition and hippocampus across generations. Adult male mice (F0) were orally administered with fenvalerate (0, 2 or 20 mg/kg) for 5 weeks. F0 males were mated with untreated-females to generate F1 generation. F1 males were mated with F1 control females to generate F2 generation. For F1 and F2 adult offspring, spatial learning and memory were detected by Morris water maze. Results showed that spatial learning and memory were impaired in F1 females but not F1 males derived from F0 males exposed to 20 mg/kg FEN. Furthermore, significant impairment of spatial learning and memory were found in F2 females but not F2 males derived from F0 males exposed to 20 mg/kg FEN. As expected, histopathology showed that neural density in hippocampal CA3 region was reduced in F1 and F2 females but not F1 and F2 males derived from F0 males exposed to 20 mg/kg FEN. Mechanistically, hippocampal thyroid hormone receptor alpha1 (TRα1) was down-regulated in F1 and F2 females derived from F0 males exposed to 20 mg/kg FEN. Correspondingly, hippocampal brain-derived neurotrophic factor, tropomyosin receptor kinase B and p75 neurotrophin receptor, three downstream genes of TR signaling, were down-regulated in F1 and F2 females. Taken together, the present study firstly found that paternal fenvalerate exposure transgenerationally impaired spatial cognition in a gender-dependent manner. Hippocampal TR signaling may, at least partially, contribute to the process of cognitive impairment induced by paternal fenvalerate exposure. Further exploration in the mode of action of fenvalerate is critically important to promote human health and environmental safety.

Direct repression of KNOX loci by the ASYMMETRIC LEAVES1 complex of Arabidopsis.

KNOTTED1-like homeobox (KNOX) genes promote stem cell activity and must be repressed to form determinate lateral organs. Stable KNOX gene silencing during organogenesis is known to involve the predicted DNA binding proteins ASYMMETRIC LEAVES1 (AS1) and AS2 as well as the chromatin-remodeling factor HIRA. However, the mechanism of silencing is unknown. Here, we show that AS1 and AS2 form a repressor complex that binds directly to the regulatory motifs CWGTTD and KMKTTGAHW present at two sites in the promoters of the KNOX genes BREVIPEDICELLUS (BP) and KNAT2. The two binding sites act nonredundantly, and interaction between AS1-AS2 complexes at these sites is required to repress BP. Promoter deletion analysis further indicates that enhancer elements required for BP expression in the leaf are located between the AS1-AS2 complex binding sites. We propose that AS1-AS2 complexes interact to create a loop in the KNOX promoter and, likely through recruitment of HIRA, form a repressive chromatin state that blocks enhancer activity during organogenesis. Our model for AS1-AS2-mediated KNOX gene silencing is conceptually similar to the action of an insulator. This regulatory mechanism may be conserved in simple leafed species of monocot and dicot lineages and constitutes a potential key determinant in the evolution of compound leaves.

Establishing leaf polarity: the role of small RNAs and positional signals in the shoot apex.

The flattening of leaves results from the juxtaposition of upper (adaxial) and lower (abaxial) domains in the developing leaf primordium. The adaxial-abaxial axis reflects positional differences in the leaf relative to the meristem and is established by redundant genetic pathways that interpret this asymmetry through instructive, possibly non-cell autonomous, signals. Small RNAs have been found to play a crucial role in this process, and specify mutually antagonistic fates. Here, we review both classical and recently-discovered factors that contribute to leaf polarity, as well as the candidate positional signals that their existence implies.