Ultrasonic neuromodulation mediated by mechanosensitive ion channels: current and future

Ultrasound neuromodulation technology is a promising neuromodulation approach, with the advantages of noninvasiveness, high-resolution, deep penetration and good targeting, which aid in circumventing the side effects of drugs and invasive therapeutic interventions. Ultrasound can cause mechanical effects, activate mechanosensitive ion channels and alter neuronal excitability, producing biological effects. The structural determination of mechanosensitive ion channels will greatly contribute to our understanding of the molecular mechanisms underlying mechanosensory transduction. However, the underlying biological mechanism of ultrasonic neuromodulation remains poorly understood. Hence, this review aims to provide an outline of the properties of ultrasound, the structures of specific mechanosensitive ion channels, and their role in ultrasound neuromodulation

Exact results for the criticality of quench dynamics in quantum Ising models

Based on the obtained exact results we systematically study the quench dynamics of a one-dimensional spin-1/2 transverse field Ising model with zero- and finite-temperature initial states. We focus on the magnetization of the system after a sudden change of the external field and a coherent time-evolution process. With a zero-temperature initial state, the quench magnetic susceptibility as a function of the initial field strength exhibits strongly similar scaling behaviors to those of the static magnetic susceptibility, and the quench magnetic susceptibility as a function of the final field strength shows a discontinuity at the quantum critical point. This discontinuity remains robust and always occurs at the quantum critical point even for the case of finite-temperature initial systems, which indicates a great advantage of employing quench dynamics to study quantum phase transitions.Comment: 5 pages, 3 figure

Screening of Human Tumor Antigens for CD4+ T Cell Epitopes by Combination of HLA-Transgenic Mice, Recombinant Adenovirus and Antigen Peptide Libraries

BACKGROUND: As tumor antigen-specific CD4+ T cells can mediate strong therapeutic anti-tumor responses in melanoma patients we set out to establish a comprehensive screening strategy for the identification of tumor-specific CD4+ T cell epitopes suitable for detection, isolation and expansion of tumor-reactive T cells from patients. METHODS AND FINDINGS: To scan the human melanoma differentiation antigens TRP-1 and TRP-2 for HLA-DRB1*0301-restricted CD4+ T cell epitopes we applied the following methodology: Splenocytes of HLA-DRB1*0301-transgenic mice immunized with recombinant adenovirus encoding TRP-1 (Ad5.TRP-1) or TRP-2 (Ad5.TRP-2) were tested for their T cell reactivity against combinatorial TRP-1- and TRP-2-specific peptide libraries. CD4+ T cell epitopes thus identified were validated in the human system by stimulation of peripheral blood mononuclear cells (PBMC) from healthy donors and melanoma patients. Using this strategy we observed that recombinant Ad5 induced strong CD4+ T cell responses against the heterologous tumor antigens. In Ad5.TRP-2-immunized mice CD4+ T cell reactivity was detected against the known HLA-DRB1*0301-restricted TRP-2(60-74) epitope and against the new epitope TRP-2(149-163). Importantly, human T cells specifically recognizing target cells loaded with the TRP-2(149-163)-containing library peptide or infected with Ad5.TRP-2 were obtained from healthy individuals, and short term in vitro stimulation of PBMC revealed the presence of epitope-reactive CD4+ T cells in melanoma patients. Similarly, immunization of mice with Ad5.TRP-1 induced CD4+ T cell responses against TRP-1-derived peptides that turned out to be recognized also by human T cells, resulting in the identification of TRP-1(284-298) as a new HLA-DRB1*0301-restricted CD4+ T cell epitope. CONCLUSIONS: Our screening approach identified new HLA-DRB1*0301-restricted CD4+ T cell epitopes derived from melanoma antigens. This strategy is generally applicable to target antigens of other tumor entities and to different HLA class II molecules even without prior characterization of their peptide binding motives

A Facile Fabrication of Silver-Coated Copper Nanowires by Galvanic Replacement

We demonstrated a general strategy to fabricate silver-coated copper nanowires by a galvanic replacement, which is guided by the chemical principle that metal ions (silver ions) with a relatively high reduction potential can galvanically etch nanostructure made from a less metal (copper). Well-dispersed and high-yielded copper nanowires were initially synthesized and then introduced into silver-ammonia solution for the growth of silver nanocrystals on the nanowire surfaces under vigorous oscillation. The results of X-ray diffraction, scanning electron microscope, and transmission electron microscope revealed that the silver nanocrystals were uniformly distributed on the copper nanowire surfaces to form Cu-Ag heterostructures. The concentration of silver-ammonia solution and the time of replacement reaction determine the size and density of the silver nanocrystals. Our investigation might pave the way to the synthesis of other bimetallic nanostructures via a facile, fast, and economical route

Highly parallel and efficient single cell mRNA sequencing with paired picoliter chambers

单细胞转录组测序技术在单个细胞水平上对转录组进行高通量测序分析，从而揭示单个细胞内所有基因的表达情况，揭示细胞间的异质性，在发育生物学、免疫学、微生物学、神经科学、临床医学等领域有重要的应用前景。单细胞转录组测序的挑战在于如何高效地操控单个细胞，如何对大量的低拷贝数mRNA进行无偏倚扩增，如何避免背景游离mRNA的污染，以及如何同时对大量的单细胞进行并行测序以降低成本。化学化工学院杨朝勇教授课题组在高通量单细胞转录组测序新器件新方法研究方面取得重要进展.该工作由厦门大学、上海交通大学、美国斯坦福大学等多团队联合攻关完成。化学生物学系博士研究生张明霞、邹远和2011协同创新中心博士研究生许醒为论文的共同第一作者。ScRNA-seq has the ability to reveal accurate and precise cell types and states. Existing scRNA-seq platforms utilize bead-based technologies uniquely barcoding individual cells, facing practical challenges for precious samples with limited cell number. Here, we present a scRNA-seq platform, named Paired-seq, with high cells/beads utilization efficiency, cell-free RNAs removal capability, high gene detection ability and low cost. We utilize the differential flow resistance principle to achieve single cell/barcoded bead pairing with high cell utilization efficiency (95%). The integration of valves and pumps enables the complete removal of cell-free RNAs, efficient cell lysis and mRNA capture, achieving highest mRNA detection accuracy (R = 0.955) and comparable sensitivity. Lower reaction volume and higher mRNA capture and barcoding efficiency significantly reduce the cost of reagents and sequencing. The single-cell expression profile of mES and drug treated cells reveal cell heterogeneity, demonstrating the enormous potential of Paired-seq for cell biology, developmental biology and precision medicine.The authors thank the National Science Foundation of China (21927806, 21735004, 21521004, 21325522), the National Key R&D Program of China (2018YFC1602900), Innovative research team of high-level local universities in Shanghai, and the Program for Changjiang Scholars and Innovative Research Team in University (IRT13036) for their financial support.该研究工作得到国家重大科研仪器研制项目、国家基金委重点项目、创新研究群体项目等支持

Mendelian randomization analyses in cardiometabolic disease:the challenge of rigorous interpretations of causality

Mendelian randomization (MR) is a burgeoning field that involves the use of genetic variants to assess causal relationships between exposures and outcomes. MR studies can be straightforward; for example, genetic variants within or near the encoding locus that is associated with protein concentrations can help to assess their causal role in disease. However, a more complex relationship between the genetic variants and an exposure can make findings from MR more difficult to interpret. In this Review, we describe some of these challenges in interpreting MR analyses, including those from studies using genetic variants to assess causality of multiple traits (such as branched-chain amino acids and risk of diabetes mellitus); studies describing pleiotropic variants (for example, C-reactive protein and its contribution to coronary heart disease); and those investigating variants that disrupt normal function of an exposure (for example, HDL cholesterol or IL-6 and coronary heart disease). Furthermore, MR studies on variants that encode enzymes responsible for the metabolism of an exposure (such as alcohol) are discussed, in addition to those assessing the effects of variants on time-dependent exposures (extracellular superoxide dismutase), cumulative exposures (LDL cholesterol), and overlapping exposures (triglycerides and non-HDL cholesterol). We elaborate on the molecular features of each relationship, and provide explanations for the likely causal associations. In doing so, we hope to contribute towards more reliable evaluations of MR findings

AIDA directly connects sympathetic innervation to adaptive thermogenesis by UCP1

AIDA最早是由林圣彩教授团队首先鉴定和命名的。2007年林圣彩教授团队与孟安明院士团队合作发现AIDA在斑马鱼体轴发育中的功能(Rui, 2007)。2018年，林圣彩教授团队首次发现了AIDA在哺乳动物中的功能，即AIDA介导的内质网降解途径通过降解脂肪合成途径中的关键酶，而限制膳食脂肪在肠道的吸收这一内在抵御肥胖(Luo, 2018)。而本次成果揭示了AIDA在棕色脂肪组织中特定的功能。这些工作将AIDA引入了脂质应激代谢的重要环节，包括脂质吸收和依赖于脂质的产热过程。该论文的共同第一作者为生命科学学院博士生史猛和硕士生黄晓羽，林圣彩教授和林舒勇教授则为共同通讯作者。【Abstract】The sympathetic nervous system–catecholamine–uncoupling protein 1 (UCP1) axis plays an essential role in non-shivering adaptive thermogenesis. However, whether there exists a direct effector that physically connects catecholamine signalling to UCP1 in response to acute cold is unknown. Here we report that outer mitochondrial membrane-located AIDA is phosphorylated at S161 by the catecholamine-activated protein kinase A (PKA). Phosphorylated AIDA translocates to the intermembrane space, where it binds to and activates the uncoupling activity of UCP1 by promoting cysteine oxidation of UCP1.Adipocyte-specific depletion of AIDA abrogates UCP1-dependent thermogenesis, resulting in hypothermia during acute cold exposure. Re-expression of S161A-AIDA, unlike wild-type AIDA, fails to restore the acute cold response in Aida-knockout mice.The PKA–AIDA–UCP1 axis is highly conserved in mammals, including hibernators. Denervation of the sympathetic postganglionic fibres abolishes cold-induced AIDA-dependent thermogenesis. These findings uncover a direct mechanistic link between sympathetic input and UCP1-mediated adaptive thermogenesis.We thank Y. Li, E. Gnaiger, T. Kuwaki, J. R. B. Lighton, E. T. Chouchani and D. Jiang for technical instruction; X. Li and X.-D. Jiang (Core Facility of Biomedical, Xiamen University) for raising the p-S161-AIDA antibody; the Xiamen University Laboratory Animal Center for the mouse in vitro fertilization service and all the other members of S.C.L. laboratory for their technical assistance. This work was supported by grants from the National Key Research and Development Project of China (grant no. 2016YFA0502001) and the National Natural Science Foundation of China (grant nos 31822027, 31871168, 31690101, 91854208 and 82088102), the Fundamental Research Funds for the Central Universities (grant nos 20720190084 and 20720200069), Project ‘111’ sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (grant no. BP2018017), the Youth Innovation Fund of Xiamen (grant no. 3502Z20206028), the Natural Science Foundation of Fujian Province of China (grant no. 2017J01364) and XMU Training Program of Innovation and Entrepreneurship for Undergraduates (grant no. 2019×0666). 该工作得到了厦门大学实验动物中心和生物医学学部仪器平台的重要协助和国家重点研究和发展项目，国家自然科学基金，厦门大学校长基金等的支持

Propagation des plasmons de surface dans des nanofils métalliques

Plasmonic circuitry is considered as a promising solution-effectivetechnology for miniaturizing and integrating the next generation ofoptical nano-devices. The realization of a practical plasmonic circuitry strongly depends on the complete understanding of the propagation properties of two key elements: surface plasmons and electrons. The critical part constituting the plasmonic circuitry is a waveguide which can sustain the two information-carriers simultaneously. Therefore, we present in this thesis the investigations on the propagation of surface plasmons and the co-propagation of surface plasmons and electrons in single crystalline metal nanowires. This thesis is therefore divided into two parts. In the first part, we investigate surface plasmons propagating in individual thick penta-twinned crystalline silver nanowires using dual-plane leakage radiation microscopy. The effective index and the losses of the mode are determined by measuring the wave vector content of the light emitted in the substrate. Surface plasmon mode is determined by numerical simulations and an analogy is drawn with molecular orbitals compound with similar symmetry. Leaky and bound modes selected by polarization inhomogeneity are demonstrated. We further investigate the effect of wire geometry (length, diameter) on the effective index and propagation losses. On the basis of the results obtained during the first part, we further investigate the effect of an electron flow on surface plasmon properties. We investigate to what extend surface plasmons and current-carrying electrons interfere in such a shared circuitry. By synchronously recording surface plasmons and electrical output characteristics of single crystalline silver and gold nanowires, we determine the limiting factors hindering the co-propagation of electrical current and surface plasmons in these nanoscale circuits. Analysis of wave vector distributions in Fourier images indicates that the effect of current flow on surface plasmons propagation is reflected by the morphological change during the electromigration process. We further investigate the possible crosstalk between co-propagating electrons and surface plasmons by applying alternating current biasPas de résumé en françai

Propagation des plasmons de surface dans des nanofils métalliques

Pas de résumé en françaisPlasmonic circuitry is considered as a promising solution-effectivetechnology for miniaturizing and integrating the next generation ofoptical nano-devices. The realization of a practical plasmonic circuitry strongly depends on the complete understanding of the propagation properties of two key elements: surface plasmons and electrons. The critical part constituting the plasmonic circuitry is a waveguide which can sustain the two information-carriers simultaneously. Therefore, we present in this thesis the investigations on the propagation of surface plasmons and the co-propagation of surface plasmons and electrons in single crystalline metal nanowires. This thesis is therefore divided into two parts. In the first part, we investigate surface plasmons propagating in individual thick penta-twinned crystalline silver nanowires using dual-plane leakage radiation microscopy. The effective index and the losses of the mode are determined by measuring the wave vector content of the light emitted in the substrate. Surface plasmon mode is determined by numerical simulations and an analogy is drawn with molecular orbitals compound with similar symmetry. Leaky and bound modes selected by polarization inhomogeneity are demonstrated. We further investigate the effect of wire geometry (length, diameter) on the effective index and propagation losses. On the basis of the results obtained during the first part, we further investigate the effect of an electron flow on surface plasmon properties. We investigate to what extend surface plasmons and current-carrying electrons interfere in such a shared circuitry. By synchronously recording surface plasmons and electrical output characteristics of single crystalline silver and gold nanowires, we determine the limiting factors hindering the co-propagation of electrical current and surface plasmons in these nanoscale circuits. Analysis of wave vector distributions in Fourier images indicates that the effect of current flow on surface plasmons propagation is reflected by the morphological change during the electromigration process. We further investigate the possible crosstalk between co-propagating electrons and surface plasmons by applying alternating current biasDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Synthesis, antibacterial and anticancer activity, and docking study of aminoguanidines containing an alkynyl moiety

Two series of aminoguanidines containing an alkynyl moiety were designed, synthesised, and screened for antibacterial and anticancer activities. Generally, the series 3a–3j with a 1,2-diphenylethyne exhibited better antibacterial activity than the other series (6a–6k) holding 1,4-diphenylbuta-1,3-diyne moiety antibacterial activity. Most compounds in series 3a–3j showed potent growth inhibition against the tested bacterial strains, with minimum inhibitory concentration (MIC) values in the range 0.25–8 µg/mL. Compound 3g demonstrated rapid and persistent bactericidal activity at 2 × MIC. The resistance study revealed that resistance of the tested bacteria towards 3g is not easily developed. Molecular docking studies revealed that compounds 3g and 6e bind strongly to the LpxC and FabH enzymes. Moreover, excellent activity of selected compounds against the growth of cancer cell lines A549 and SGC7901 was also observed, with IC50 values in the range 0.30–4.57 µg/mL. These findings indicate that compounds containing the aminoguanidine moiety are promising candidates for the development of new antibacterial and anticancer agents