Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Perinatal Combinational Exposure to Bisphenol A and a High-Fat Diet Contributes to Transgenerational Dysregulation of Cardiovascular and Metabolic Systems in Mice.

Both bisphenol A (BPA) and high-fat diet (HFD) exert unfavorable effects on animals and humans; moreover, they could affect the health of their offspring. BPA and HFD often coexist in modern lifestyles; however, the long-term effects of simultaneous exposure of mothers to BPA and HFD during the perinatal period on the cardiovascular and metabolic systems of the offspring remain unclear. This study aimed to examine the effect of simultaneous exposure of mothers to BPA and HFD on the risk of metabolic and cardiovascular abnormalities in offspring. Institute of Cancer Research female mice (F0) were exposed to BPA and fed with HFD before and during gestation until the end of lactation. F0 mice were mated with untreated males to produce the first generation (F1); subsequently, adult F1 males/females were mated with normal females/males to produce the second generation (F2). Combined maternal exposure to BPA and HFD caused myocardial hypertrophy and aortic tunica media thickening as well as increased the cross-sectional area of cardiomyocytes and blood pressure in the matrilineal F2 generation. These cardiovascular changes might be associated with reduced endothelial nitric oxide synthase (eNOS) levels. The patrilineal female F2 was more likely to be obese than the patrilineal male F2. Re-feeding with a HFD showed a more significant weight gain and reduced energy expenditure. However, the aforementioned effects were not observed with exposure to HFD or BPA alone during the perinatal period. Our findings suggest that perinatal combinational exposure to BPA and HFD could cause metabolic and cardiovascular disorders in the offspring, Further, our findings demonstrate that the synergistic effects of HFD and BPA could be transmitted to future generations in a sex-dependent manner.

Hippocampal overexpression of TREM2 ameliorates high fat diet induced cognitive impairment and modulates phenotypic polarization of the microglia.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share several common pathophysiological features. Rare variants of triggering receptor expressed on myeloid cells 2 (TREM2) increase the risk of developing AD, suggesting the involvement of TREM2 and innate immunity in AD development. It is still unknown whether TREM2 is related to cognitive impairment in T2DM. Here, we investigated the effects of the hippocampal overexpression of TREM2 on cognitive in long-term high-fat diet (HFD)-fed mice. Male C57BL/6J mice were maintained on HFD for 50 weeks. TREM2 was overexpressed in the hippocampus 36 weeks after HFD feeding using adeno-associated virus vector (AAV)-mediated gene delivery. The results showed that the HFD feeding induced rapid and persistent weight gain, glucose intolerance and significant impairments in learning and memory. Compared with AAV-con, AAV-TREM2 significantly ameliorated cognitive impairment without altering body weight and glucose homeostasis in HFD mice. The overexpression of TREM2 upregulated the synaptic proteins spinophilin, PSD95 and synaptophysin, suggesting the improvement in synaptic transmission. Dendritic complexity and spine density in the CA1 region were rescued after TREM2 overexpression. Furthermore, TREM2 markedly increased the number of iba-1/Arg-1-positive microglia in the hippocampus, suppressed neuroinflammation and microglial activation. In sum, hippocampal TREM2 plays an important role in improving HFD-induced cognitive dysfunction and promoting microglial polarization towards the M2 anti-inflammatory phenotype. Our study also suggests that TREM2 might be a novel target for the intervention of obesity/diabetes-associated cognitive decline.

Combinational exposure to Bisphenol A and a high-fat diet causes trans-generational Malfunction of the female reproductive system in mice.

Bisphenol A (BPA) is a common endocrine disruptor and a high-fat diet (HFD) also affects fertility. However, little is known about the long-term consequences of simultaneous exposure to BPA and a HFD on reproductive health. Herein, we assessed the effects of maternal exposure to BPA in combination with a HFD on reproductive function in subsequent generations of female mice and evaluated its effects on the hypothalamic-pituitary-gonadal axis. We found that the combination of maternal exposure to BPA and a HFD led to increased urine BPA levels, precocious puberty, altered estrous cyclicity, decreased follicle numbers, and altered hypothalamic Kiss1 methylation status in F1 and F2 mice. Therefore, we demonstrated that maternal exposure to BPA in combination with a HFD exerts a trans-generational effect on female reproduction.

The 'double-edged effect' of progress in energy-biased technology on energy efficiency: A comparison between the manufacturing sector of China and Japan.

Based on data of the manufacturing sector of China and Japan from 2003 to 2016, this paper attempts to measure the progresses in energy-biased technology and energy efficiency by constructing a threshold panel regression model with variables including foreign direct investment (FDI) and energy consumption structure to explain energy efficiency using energy-biased technology as the key explaining variable. The estimation indicates significant differences in the energy efficiency of China's and Japan's manufacturing industries. In general, Japan's total energy efficiency is higher than China's. The industry with more intensive technology has higher energy efficiency which rises much faster. The paper finds that the energy efficiency of China's manufacturing sector shows an upward trend in general, while Japan's fluctuates more, showing two peaks and two troughs. Our empirical results show that there is a threshold value of progress in energy-biased technology; below this, progress in energy-biased technology will have a positive effect on energy efficiency and beyond it, the effect will be negative. Since this effect is not one-way, we define it as a 'double-edged effect'. It is estimated that the level of energy-biased technology progress of most manufacturing industries in China is below the threshold value, indicating that the technology progress in China's manufacturing sector has not been excessively biased towards energy consumption, and the impact on energy efficiency is still positive. The China-Japan comparison shows that the threshold value for Japan's manufacturing sector is significantly lower than that for China's, indicating a marginal effect on the 'double-edged effect': The threshold value will decrease when energy efficiency reaches a certain level. Therefore, it is necessary to offset these negative externalities from technological progress with other factors such as by increasing FDI and improving energy consumption structure.

A comparative study of the vibro-impact capsule systems with one-sided and two-sided constraints.

This paper studies the dynamics of the vibro-impact capsule systems with one-sided and two-sided soft constraints under variations of various system and control parameters, including mass ratio, stiffness ratio, gap of contact, and amplitude and frequency of external excitation. The aim of this study is to optimise the progression speed and energy consumption of the capsule and minimise the required cabin length for prototype design used for engineering pipeline inspection. Our studies focus on three systems: the capsule with a right constraint, the capsule with a right and a weak left constraints, and the capsule with a right and a strong left constraints. Bifurcation analyses show that the behaviour of the capsule with one-sided constraint is mainly periodic, and the dynamic responses of the other two capsules with two-sided constraints become complex when the stiffness of the left constraint increases. Based on our extensive comparisons, the following optimisation strategies are recommended. When the capsule speed is paramount, one can employ the two-sided capsule with a weak left constraint under large amplitude of excitation. When energy consumption is taken into account, the one-sided capsule is preferable. When a miniaturized prototype is needed, the two-sided capsule with a strong left constraint is the best choice.