Optical sensing nanostructures for porous silicon rugate filters

Porous silicon rugate filters [PSRFs] and combination PSRFs [C-PSRFs] are emerging as interesting sensing materials due to their specific nanostructures and superior optical properties. In this work, we present a systematic study of the PSRF fabrication and its nanostructure/optical characterization. Various PSRF chips were produced with resonance peaks that are adjustable from visible region to near-infrared region by simply increasing the periods of sine currents in a programmed electrochemical etching method. A regression analysis revealed a perfect linear correlation between the resonant peak wavelength and the period of etching current. By coupling the sine currents with several different periods, C-PSRFs were produced with defined multiple resonance peaks located at desired positions. A scanning electron microscope and a microfiber spectrophotometer were employed to analyze their physical structure and feature spectra, respectively. The sensing properties of C-PSRFs were investigated in an ethanol vapor, where the red shifts of the C-PSRF peaks had a good linear relationship with a certain concentration of ethanol vapor. As the concentration increased, the slope of the regression line also increased. The C-PSRF sensors indicated the high sensitivity, quick response, perfect durability, reproducibility, and versatility in other organic gas sensing

Indocyanine Green-Loaded Polydopamine-Reduced Graphene Oxide Nanocomposites with Amplifying Photoacoustic and Photothermal Effects for Cancer Theranostics

Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments

Synthesis of surfactant-free Cu–Pt dendritic heterostructures with highly electrocatalytic performance for methanol oxidation reaction

A facile and free surfactant strategy is explored to synthesize Cu–Pt bimetallic nano-heterostructures with dendritic exterior. For comparison, the Cu–Pt coral-like nanoparticles are fabricated by using CTAC as a surfactant. The well-designed Cu–Pt dendritic spherical heterostructures exhibit superior enhanced electrocatalytic activity and stability toward methanol oxidation reaction in alkaline media, compared to the Cu–Pt coral-like nanoparticles and the commercial Pt/C, respectively. The advanced technique for fabricating Cu–Pt dendritic spherical heterostructures could pave a way to pursue low-cost Pt-based catalysts, maintaining highly promoted electrocatalytic performance and durability

Acidochromic organic photovoltaic integrated device

Tremendous efforts have been devoted to boosting the power conversion efficiency (PCE) of organic solar cells (OSCs) via the introduction of cathode interlayers (CILs). However, CIL materials have limited diversity and the development of multifunctional devices is largely neglected. Herein, an acidochromic organic photovoltaic integrated device is firstly proposed by introducing an acid-sensitive stimulating-reaction organic molecule as both the CIL of OSCs and the sensor of monitoring environmental acidity. The oxazolidine unit of acidochromic molecule can form a ring-opening structure after acid treatment, resulting in the remarkable color change with the direct reflection of pH value of ecological environment. The additive-free PM6:Y6 OSCs using the acidochromic molecule as the CIL achieve an excellent PCE of above 15.29 %, which is 47 % higher than that of the control device. The PCE can even maintain above 92 % after treating CIL with various strong acids (pH = 1). Moreover, the color of acidified films and the degraded performance of acidified OSCs can be easily restored by alkaline treatment. The successful application of CIL in other highly efficient photovoltaic systems proves its good universality. This work triggers the promising application of acidochromic molecules in solar cells as CIL with the additional function of recognition of acid environment

Quantum mechanics in an evolving Hilbert space

Many basis sets for electronic structure calculations evolve with varying external parameters, such as moving atoms in dynamic simulations, giving rise to extra derivative terms in the dynamical equations. Here we revisit these derivatives in the context of differential geometry, thereby obtaining a more transparent formalization, and a geometrical perspective for better understanding the resulting equations. The effect of the evolution of the basis set within the spanned Hilbert space separates explicitly from the effect of the turning of the space itself when moving in parameter space, as the tangent space turns when moving in a curved space. New insights are obtained using familiar concepts in that context such as the Riemann curvature. The differential geometry is not strictly that for curved spaces as in general relativity, a more adequate mathematical framework being provided by fiber bundles. The language used here, however, will be restricted to tensors and basic quantum mechanics. The local gauge implied by a smoothly varying basis set readily connects with Berry's formalism for geometric phases. Generalized expressions for the Berry connection and curvature are obtained for a parameter-dependent occupied Hilbert space spanned by nonorthogonal Wannier functions. The formalism is applicable to basis sets made of atomic-like orbitals and also more adaptative moving basis functions (such as in methods using Wannier functions as intermediate or support bases), but should also apply to other situations in which nonorthogonal functions or related projectors should arise. The formalism is applied to the time-dependent quantum evolution of electrons for moving atoms. The geometric insights provided here allow us to propose new finite-difference time integrators, and also better understand those already proposed

Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate

人类遗传学家James V. Neel在1962年首次提出了“节俭基因”这一概念，认为现今人类导致包括肥胖症、糖尿病和高血压等代谢障碍的基因是因为生理系统为了适应远古环境食物富足和食物缺乏的周期性改变而筛选出的，可以让远古人类在食物富足的短暂时期中快速增肥，以应对随时将到来的食物缺乏时期。这类基因在当时环境下有很大的优越性，但对于当今食物富足的社会则截然相反。这篇论文中林圣彩教授团队揭示了乙酰转移酶TIP60通过乙酰化脂肪合成途径的代谢酶lipin 1并促进其向内质网转运，从而提高脂肪合成速率，揭示了TIP60作为一个“节俭基因”的功能和作用机制。该研究阐明了脂肪合成途径中首个受蛋白质乙酰化修饰调控的途径，揭示了TIP60作为经典转录调控因子之外的又一重要生物学功能，为开发防治肥胖症及其相关代谢紊乱疾病提供了新的药物作用靶点。博士后李阳、博士生宋林涛和硕士生孙玉是该论文的共同第一作者。【Abstract】Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser86 phosphorylation site of acetyltransferase Tip60 (Tip60SA/SA) display remarkably reduced body fat mass, and Tip60SA/SA females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1. Inhibition of Tip60 activity strongly blocks fatty acid-induced TAG synthesis while Sirt1 suppression leads to increased adiposity. Genetic analysis of loss-of-function mutants in Saccharomyces cerevisiae reveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis.This work was supported by grants from the National Natural Science Foundation of China (#31690101, #31430094, #31600961 and #31571214) and National Key Research and Development Project of China (2016YFA0502001). 该研究受到了国家自然科学基金和中国国家重点研发计划项目的资助

Targeted Methotrexate Prodrug Conjugated With Heptamethine Cyanine Dye Improving Chemotherapy and Monitoring Itself Activating by Dual-Modal Imaging

Theranostic prodrug plays a vital role in reducing the side effects and evaluating the therapeutic efficiency of prodrug in vivo. In particular, small conjugate-based theranostic prodrugs have attracted much attention because of their clear and simple structures. In this work, we synthesized a novel tumor-targeting and glutathione-activated conjugate-based theranostic prodrug (Cy-SS-MTX). The prodrug was constructed by conjugating Cy (IR780) to methotrexate (MTX) via a disulfide bond. The Cy dye as targeting molecule bring prodrug to cancer cells and then the prodrug was activated by the high levels of glutathione in tumor. In cell experiments, the results showed the excellent ability of prodrug to target tumor. Meanwhile, the prodrug apparently improved the anti-tumor ability and hugely reduced toxicity of free MTX on normal cells. Furthermore, owing to intramolecular charge transfer between Cy and MTX, the Cy structure in the prodrug showed an absorption peak at 654 nm in UV-Vis spectroscopy. However, when the disulfide bond of prodrug was broken by glutathione, a new UV-Vis absorption peak at 802 nm of Cy structure in prodrug was arised. At the same time, the fluorescence (FL) emission peak at 750 nm (excitation at 640 nm) would turn into 808 nm (excitation at 745 nm). What's more, the photoacoustic (PA) signal with excitation at 680 and 808 nm also changed. The experimental results in vivo showed that the prodrug has been successfully utilized for real-timely tracking MTX activation by FL and PA imaging upon near infrared laser excitation and cancer targeting therapy. Our studies further encourage application of small conjugate-based prodrug based on tumor-targeted heptamethine cyanine dye as reporter group for targeted therapy and real-timely tracking activation of drug

ULK1/2 Constitute a Bifurcate Node Controlling Glucose Metabolic Fluxes in Addition to Autophagy

揭示了在外界能量供应缺乏时，细胞通过激活ULK1来介导葡萄糖分解代谢重编程以维持胞内的能量与氧化还原稳态的详细机制，并创新地发现了ULK1独立于自噬的关键功能。基于自噬和糖代谢与人类健康的重要相关性，该研究将很可能为我们预防和治疗各类代谢疾病提供新的思路和药物靶点。Metabolic reprogramming is fundamental to biological homeostasis, enabling cells to adjust metabolic routes after sensing altered availability of fuels and growth factors. ULK1 and ULK2 represent key integrators that relay metabolic stress signals to the autophagy machinery. Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1). Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels. These results identify ULK1/2 as a bifurcate-signaling node that sustains glucose metabolic fluxes besides initiation of autophagy in response to nutritional deprivation.State Key Program of National Natural Science of China， the 973 Program；National Natural Science Foundation of China for Fostering Talents in Basic Research ；the Foundation for Innovative Research Groups of the National Natural Science Foundation of China； and the 111 Project of Education of China

Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy

Src基因是哺乳动物中发现的第一个原癌基因，其编码的蛋白是一个酪氨酸激酶，在促进乳腺癌、肺癌等诸多肿瘤的发生、进展和恶化中起着重要的作用。在研究中，研究团队发现Src能够承接生长因子和肥胖微环境相关的因子如胰岛素和瘦素的信号，通过直接磷酸化lipin-1，增强其催化合成甘油脂的活性，提高细胞摄入的脂肪酸向甘油脂尤其是磷脂转化。进一步实验表明，Src磷酸化lipin-1能够加速乳腺癌细胞生长，促进小鼠模型中肿瘤的进展和转移。这项研究不但做出了对脂肪合成途径的调控机制的又一重要发现，还揭示了原癌基因Src可以承接癌细胞内外的活化信号，通过lipin-1为媒介重塑癌细胞脂代谢，使得肿瘤细胞具有增殖和转移的优势。该论文揭示了臭名昭著的原癌基因Src通过直接结合并磷酸化lipin-1（一种磷脂酸磷酸化酶，在脂质代谢中具有重要作用），以增强其酶活性，从而加速甘油酯的合成速率，进而促进乳腺癌的发生发展。 该研究由厦门大学生命科学学院、广州医科大学第五附属医院、第四军医大学西京医院和中山大学孙逸仙纪念医院等单位合作完成，厦门大学生命科学学院博士后宋林涛和广州医科大学第五附属医院刘志华教授为该论文的共同第一作者。【Abstract】Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1−/− mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.This work was supported by grants from the National Natural Science Foundation of China (#31822027, #31690101, #91854208, #31871168, #82002965), the Fundamental Research Funds for the Central Universities (#20720190084), Project “111” sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (#BP2018017), XMU Training Programme of Innovation and Entrepreneurship for Undergraduates (#2017Y0578, #2018Y1281) and China Postdoctoral Science Foundation (#2019M652254). 该研究也得到了国家自然科学基金，中央高校基础研究项目和中国博士后科学基金等的资助

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