脊椎动物体节形成的分节时钟调控机制

脊椎动物胚胎发育早期中胚层细胞的分节时钟控制着体节的周期性形成。体节是沿身体轴的重复结构,最终发育形成椎骨和肋骨。如果分节时钟受到干扰,体节形成就会出现缺陷,从而导致身体发育异常,最终产生脊柱先天性疾病。参与体节发育的主要模型是时钟和波前模型。中胚层分化由组合梯度系统调节,该系统涉及成纤维细胞生长因子（FGF）、Wnt/β-catenin和视黄酸（RA）信号通路。FGF信号和Wnt/β-catenin信号控制后中胚层处于未分化状态,RA信号则诱导前中胚层细胞分化导致体节成熟。因此相反的信号梯度在特定位点达到平衡。当分子振荡器从尾芽起始表达并以行波模式向前传播至信号平衡临界点时,将启动分节时钟程序,触发Mesp2等分化基因表达,表现为未成熟的前体节中胚层发育形成一对体节。随着细胞二维培养体系和时事报告系统的成熟,研究人员成功在体外将干细胞诱导分化至中胚层并实现了分节时钟的二维可视化振荡。研究表明,细胞通信中的耦合延迟可以保持相邻细胞之间同步振荡,因此导致体节边界和双侧对称形成。此后研究人员在体外重建了诱导多能干细胞的三维培养系统,再现了具有前-后（AP）轴特征的体节样结构的形成。这为解码分节时钟网络调控机理、探索体节双侧对称形成以及不同物种发育速率的代谢调控机制提供了一个宝贵的研究体系。同时为探索病理性体节缺陷发展中的失调机制创造了一个平台。     

Micro‐ and Nano‐Structured Vanadium Pentoxide (V2O5) for Electrodes of Lithium‐Ion Batteries

Vanadium pentoxide (V₂O₅) has played important roles in lithium‐ion batteries due to its unique crystalline structure. To assist researchers understanding the roles this material plays, a comprehensive and critical review is conducted based on about 250 publications. Here, we report basics and applications of micro‐ and nano‐materials of V₂O₅ and V₂O₅‐based composites. The comparative and statistical analysis leads to the discovery of several interesting phenomena. The V₂O₅ electrodes with two lithium ions have a favorable capacity performance with reversible phase formation. The excellent capacity retention is displayed in the V₂O₅ electrodes with one lithium ion inserted. In the case of three lithium ions insertion, it was found that the irreversible formation of the phase ω in Li_xV₂O₅ leads to its control. In addition, effects of additives on electrode performance, circuitry models of performance, as well as reaction routes are studied. Two unprecedented concepts of the “high capacity band” and “empirical total capacity retention” are proposed though the comprehensive statistical analysis of the reviewed data. This review provides a comprehensive collection of information of state‐of‐the‐art and recent advancement in V₂O₅ and V₂O₅‐based composite materials for electrodes. Researchers could use the information to design and develop advanced electrodes for future batteries.     

Cyclic AMP-dependent signaling system is a primary metabolic target for non-thermal effect of microwaves on heart muscle hydration

Previously, we have suggested that cell hydration is a universal and extra-sensitive sensor for the structural changes of cell aqua medium caused by the impact of weak chemical and physical factors. The aim of present work is to elucidate the nature of the metabolic messenger through which physiological solution (PS) treated by non-thermal (NT) microwaves (MW) could modulate heart muscle hydration of rats. For this purpose, the effects of NT MW–treated PS on heart muscle hydration, [³H]-ouabain binding with cell membrane, ⁴⁵Ca²⁺ uptake and intracellular cyclic nucleotides contents in vivo and in vitro experiments were studied. It is shown that intraperitoneal injections of both Sham-treated PS and NT MW–treated PS elevate heart muscle hydration. However, the effect of NT MW–treated PS on muscle hydration is more pronounced than the effect of Sham-treated PS. In vitro experiments NT MW–treated PS has dehydration effect on muscle, which is not changed by decreasing Na⁺ gradients on membrane. Intraperitoneal injection of Sham- and NT MW–treated PS containing ⁴⁵Ca²⁺ have similar dehydration effect on muscle, while NT MW–treated PS has activation effect on Na⁺/Ca²⁺ exchange in reverse mode. The intraperitoneal injection of NT MW–treated PS depresses [³H]-ouabain binding with its high-affinity membrane receptors, elevates intracellular cAMP and decreases cGMP contents. Based on the obtained data, it is suggested that cAMP-dependent signaling system serves as a primary metabolic target for NT MW effect on heart muscle hydration.     

The conduction system and expressions of hyperpolarization-activated cyclic nucleotide-gated cation channel 4 and connexin43 expressions in the hearts of fetal day 13 mice

We investigated the development of the sinus node of the heart conduction system by localizing hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin43 (Cx43) in the hearts of fetal day 13 mice. Horizontal serial sections of day 13 whole fetuses were stained by hematoxylin and eosin and immunofluorescence to identify myocardial cells that express HCN4, hyperpolarization-activated cyclic nucleotide-gated cation channel 2 (HCN2) and Cx43. Expression levels of HCN4 and Cx43 were determined by quantitative RT-PCR in both fetal day 13 and adult mice. We found that both Cx43 and HCN4 expressions were located on the cell membranes in the hearts of fetal day 13 mice, but Cx43 was distributed throughout the myocardial cells. HCN4 expression was concentrated mainly in the left dorsal epicardium of the right atrium where Cx43 expression was low or absent. Quantitative RT-PCR demonstrated that HCN4 expression was significantly higher and HCN2 expression was significantly lower in fetal day 13 mice than in adults. We found no statistically significant difference in Cx43 expression between fetal day 13 mice and adults. HCN4 stained myocardial cells in the left dorsal epicardium of the right atrium are the origin of the sinus node and the remainder of the heart conduction system.     

Multi-spectroscopic and voltammetric evidences for binding,conformational changes of bovine serum albumin with thiamine

The interaction between thiamine hydrochloride (TA) and bovine serum albumin (BSA) was investigated by fluorescence, FTIR, UV–vis spectroscopic and cyclic voltammetric techniques under optimised physiological condition. The fluorescence intensity of BSA is gradually decreased upon addition of TA due to the formation of a BSA–TA complex. The binding parameters were evaluated and their behaviour at different temperatures was analysed. The quenching constants (K_sv) obtained were 2.6 × 10⁴, 2.2 × 10⁴ and 2.0 × 10⁴ L mol^?1 at 288, 298 and 308 K, respectively. The binding mechanism was static-type quenching. The values of ΔH° and ΔS° were found to be 26.87 kJ mol^?1 and 21.3 J K^?1 mol^?1, and indicated that electrostatic interaction was the principal intermolecular force. The changes in the secondary structure of BSA upon interaction with TA were confirmed by synchronous and 3-D spectral results. Site probe studies reveal that TA is located in site I of BSA. The effects of some common metal ions on binding of BSA–TA complex were also investigated.     

Characterization of three serotonin receptors from the small white butterfly,Pieris rapae

Serotonin (5-hydroxytryptamine, 5-HT) plays a key role in modulating diverse physiological processes and behaviors in both protostomes and deuterostomes. These functions are mediated through the binding of serotonin to its receptors, which are recognized as potential insecticide targets. We investigated the sequence, pharmacology and tissue distribution of three 5-HT receptors (Piera5-HT_1A, Piera5-HT_1B, Piera5-HT₇) from the small white butterfly Pieris rapae, an important pest of cultivated cabbages and other mustard family crops. Activation of Piera5-HT_1A or Piera5-HT_1B by 5-HT inhibited the production of cAMP in a dose-dependent manner. Stimulation of Piera5-HT₇ with 5-HT increased cAMP level significantly. Surprisingly, with the exception of 5-methoxytryptamine, agonists including α-methylserotonin, 8-Hydroxy-DPAT and 5-carboxamidotryptamine activated these receptors poorly. The results are consistent with previous findings in Manduca sexta. All three receptors were blocked by methiothepin, but ketanserin and yohimbine were not effective. The selective mammalian 5-HT receptor antagonists SB 216641 and SB 269970 displayed potent inhibition effects on Piera5-HT_1B and Piera5-HT₇ respectively. The results we achieved here indicate that the pharmacological properties of Lepidoptera 5-HT receptors are quite different from those in other insects and vertebrates and may contribute to development of new selective pesticides. This study offers important information on three 5-HT receptors from P. rapae that will facilitate further analysis of the functions of 5-HT receptors in insects.     

Dietary cyclic fatty acids derived from linolenic acid do not exhibit intrinsic toxicity in the rat during gestation

Heating oils and fats may lead to cyclization of polyunsaturated fatty acids, especially those showing multiple double bonds like linolenic acid. Cyclohexenyl and cyclopentenyl fatty acids are subsequently present in some edible oils and these were suspected to induce metabolic disorders. When fed during gestation in the rat, cyclic fatty acids were historically reported to induce high mortality of the neonates. Nevertheless, none of these studies have been performed with cyclic fatty acids fed as triacylglycerols, limiting the nutritional value of the conclusions. Therefore, we assessed the toxicity of a diet containing 0.7% of cyclic fatty acids fed as triacylglycerols during gestation and the first days of life in the rat. In this work, we report no deleterious effect of cyclic fatty acids in the mothers and neonates. However, cyclic fatty acids induced a tremendous insulinopenia in the mothers and pups that was associated with the reduction of food intake in the gestating females. Such a finding may be a plausible explanation for the adverse effects of cyclic fatty acids observed previously with higher doses of cyclic fatty acids. Based on present data, on previous ones showing elimination of cyclic fatty acids, and considering their low amounts in the diet, we suggest that cyclic fatty acids formed from cyclization of linolenic acid are not a major concern for human safety.     

Characteristics of HCN Channels and Their Participation in Neuropathic Pain

Neuropathic pain is induced by the injury to nervous systems and characterized by hyperalgesia, allodynia and spontaneous pain. The underlying mechanisms include peripheral and central sensitization resulted from neuronal hyperexcitability. A number of ion channels are considered to contribute to the neuronal hyperexcitability. Here, we particularly concentrate on an interesting ion channel, hyperpolarization-activated cyclic nucleotide gated (HCN) channels. We overview its biophysical properties, physiological functions, followed by focusing on the current progress in the study of its role in the development of neuropathic pain. We attempt to provide a comprehensive review of the potential valuable target, HCN channels, in the treatment of neuropathic pain. Special issue article in honor of Dr. Ji-Sheng Han. Yu-Qiu Jiang, Qian Sun, and Hui-Yin Tu—contributed equally to this paper.