Trapping endoplasmic reticulum with amphiphilic AIE-active sensor via specific interaction of ATP-sensitive potassium (KATP)

The current aggregation-induced emission luminogens (AIEgens) sometimes suffer from poor targeting selectivity due to undesirable aggregation in the hydrophilic biosystem with ‘always-on’ fluorescence or unspecific aggregation in the lipophilic organelle with prematurely activated fluorescence. Herein, we report an unprecedented ‘amphiphilic AIEgen’ sensor QM-SO₃-ER based on the AIE building block of quinoline-malononitrile (QM). The introduced hydrophilic sulfonate group can well control the specific solubility in a hydrophilic system with desirable initial ‘fluorescence-off’ state. Moreover, the incorporated p-toluenesulfonamide group plays two roles: enhancing the lipophilic dispersity, and behaving as binding receptor to the adenosine triphosphate (ATP)-sensitive potassium (K_ATP) on the endoplasmic reticulum (ER) membrane to generate the docking assay confinement effect with targetable AIE signal. The amphiphilic AIEgen has for the first time settled down the predicament of unexpected ‘always-on’ fluorescence in the aqueous system and the untargetable aggregation signal in the lipophilic organelle before binding to ER, thus successfully overcoming the bottleneck of AIEgens'' targetability.     

Status of Vitamin D Receptor Gene Polymorphism and 25-Hydroxy Vitamin D Deficiency with Essential Hypertension

Essential hypertension (EH) is a multifactorial and complex disease with high rate of incidence and associated co-morbidities. Previous studies do not provide unanimous results for the risk of hypertension and association with Fok I genotype frequency and serum vitamin D levels. Hence, this study was undertaken to determine the status of Fok I vitamin D receptor (VDR) gene polymorphism along with vitamin D levels and blood pressure in patients with EH. Four hundred (200 controls and 200 cases of essential hypertension) participants from general Indian population were enrolled in this study. Peripheral blood samples were collected for genotyping Fok I-VDR gene polymorphism using PCR–RFLP method whereas 25-OH vitamin D levels in serum were quantified using high performance liquid chromatography (HPLC). Significantly reduced 25-OH vitamin D levels were observed in patients with EH (24.04 ± 8.62 vs 50.46 ± 15.46) compared to control subjects (p = 0.0001). Homozygous recessive genotype ‘ff’ frequency was increased by 8.06 fold (CI: 3.71–17.47, p = 0.0001) in patients with EH compared to dominant ‘FF’ genotype frequency. In conclusion, recessive ‘ff’ genotype frequency correlates with reduced serum vitamin D levels and results in significantly increased systolic and diastolic blood pressures leading to predisposition of EH.     

Integrated ‘all-in-one’ strategy to stabilize zinc anodes for high-performance zinc-ion batteries

Many optimization strategies have been employed to stabilize zinc anodes of zinc-ion batteries (ZIBs). Although these commonly used strategies can improve anode performance, they simultaneously induce specific issues. In this study, through the combination of structural design, interface modification, and electrolyte optimization, an ‘all-in-one’ (AIO) electrode was developed. Compared to the three-dimensional (3D) anode in routine liquid electrolytes, the new AIO electrode can greatly suppress gas evolution and the occurrence of side reactions induced by active water molecules, while retaining the merits of a 3D anode. Moreover, the integrated AIO strategy achieves a sufficient electrode/electrolyte interface contact area, so that the electrode can promote electron/ion transfer, and ensure a fast and complete redox reaction. As a result, it achieves excellent shelving-restoring ability (60 hours, four times) and 1200 cycles of long-term stability without apparent polarization. When paired with two common cathode materials used in ZIBs (α-MnO₂ and NH₄V₄O₁₀), full batteries with the AIO electrode demonstrate high capacity and good stability. The strategy of the ‘all-in-one’ architectural design is enlightened to solve the issues of zinc anodes in advanced Zn-based batteries.     

More is different: how aggregation turns on the light

The reductionist approach to science seeks to understand the behaviour of systems by studying their individual components. It has been an enormously productive approach, but it is also widely acknowledged now that in some systems the behaviour of interest is an emergent property that cannot be discerned in the separate parts. Biology is replete with such examples, from the flocking of birds to the way metabolic processes in cells rely on a dynamic interplay of proteins and other components.Yet molecular systems do not have to be particularly complex before their properties become more than the sum of the parts. A classic example is the appearance of bulk-like metallic behaviour in small clusters of metal atoms only once they exceed a certain critical size. One of the most striking instances became apparent in 2001, when Ben Zhong Tang of the Hong Kong University of Science and Technology and his co-workers found that heterocyclic silicon-containing molecules called siloles become luminescent as nanoscopic aggregates even though the individual molecules in dilute solution do not emit light [1]. This looked like the opposite of the well-known phenomenon of concentration quenching, in which energy transfer between fluorescent (generally organic) molecules quenches the emission, an effect explained in 1955 [2]. Aggregation-induced ‘switching off’ is intuitively understandable, but ‘switching on’ due to aggregation was more surprising.Yet this effect of ‘aggregation-induced emission’ (AIE), as Tang and colleagues called it, was apparently seen, but not understood, much earlier [3]. In the 1850s, George Stokes noted that some inorganic complexes were fluorescent in the condensed, solid state but not in solution. At first, AIE was seen as a curiosity and deemed likely to be rare. However, subsequent research has shown not only that it is a rather common effect but also that it can be considered just one manifestation of a wide range of behaviours that arise from aggregation—leading to the proposed field of ‘aggregate science’, manifesting at the supramolecular level of small clusters or groups of molecules held together by relatively weak interactions. The field might be considered to illustrate George Whitesides’ notion of a chemistry ‘beyond the molecule’ [4], which bridges disciplines ranging from colloid science to crystal growth, nanotechnology, liquid crystals, photochemistry and molecular biology. At the same time, it echoes the famous insight of physicist Philip Anderson about emergent phenomena and the hierarchical nature of science: ‘More is different’ [5]. An ability to switch properties on and off by controlling intermolecular interactions and aggregation suggests various applications, from optical device technologies to targeted drugs for cancer therapy [6].NSR spoke to Ben Zhong Tang about the origins and possibilities of the field.

NSR: It seems you noticed AIE in 2001 by accident. How did it come about? Tang: Yes, it was serendipity. Development of new light emitters for the fabrication of organic light-emitting diodes was a hot topic at that time. We were trying to make new luminophores [light-emitting molecules] with high efficiencies and novel structures. Attracted by the aesthetically pleasing molecular structures of siloles, I asked my students to prepare various silole compounds. One day, a student told me that he could not see any luminescence when he used a UV lamp to excite the solution of the silole compound he had made. This surprised me, because I myself prepared a silole compound when I was a PhD student and I remember that its crystal was luminescent. I sensed something strange and immediately rushed to the lab. After careful verification and discussion with the student, we concluded that both of us were correct: the silole solution was not luminescent (his observation was right) but the silole powder was emissive (my memory was right). The non-luminescent molecular species in the dilute solution were induced to emit light through formation of aggregates in the solid state. We termed the process aggregation-induced emission or AIE.

A mesoscopic aggregate can have a property that its molecular species does not exhibit at all.—Ben Zhong Tang

Open in a separate windowBen Zhong Tang of the Hong Kong University of Science and Technology, China (Courtesy of Ben Zhong Tang). NSR: The phenomenon seemed to defy conventional expectations. Did you have trouble persuading others—or yourselves!—that it was real? Tang: I initially thought the student might have done something wrong, for the phenomenon he observed was totally unexpected. The common belief in the community of photophysics research is that luminescence from an organic dye generally weakens when its molecules are aggregated, an effect often referred to as aggregation-caused quenching or ACQ. I was shocked when I realized that the silole luminogen was showing an anti-ACQ effect. Still, I felt lucky to encounter something ‘abnormal’. No matter how odd a phenomenon seems, if it can be repeatedly observed, it must be real. We repeated our experiments many times and we were eventually convinced that the AIE effect was true. We had trouble, however, to understand why the silole luminogen behaved in such a way that was diametrically opposed to conventional ACQ. NSR: Are there any historical precedents—experiments in which this effect might have been glimpsed previously, but not recognized as such? Tang: When we published our first AIE paper in 2001, we thought the photophysical effect was unprecedented. However, we gradually found out that similar phenomena had been previously observed by other scientists. For example, in 1853 George Stokes reported in a paper that some inorganic platinocyanide salts ‘are sensitive’ (meaning luminescent in modern terminology) ‘only in the solid state’ but ‘their solutions look like mere water’. Sadly, he didn’t follow it up. Other people have made similar observations in different dye systems, which were, however, not recognized as AIE processes. Partially because of this, we had great difficulty in finding relevant reference papers. As a matter of fact, Stokes’ report, published in the mid-19th century, was not known to us until the middle of 2018. However, we are not surprised by those early works, for we understand that science progresses not in an abrupt but in a continuous way. George Smith articulated this: ‘Very few research breakthroughs are novel. Virtually all of them build on what went on before.’ A discovery is often a happenstance. We happened to have ‘rediscovered’ a very old but largely unnoticed phenomenon. Luckily, we grasped the opportunity to see more and farther by standing on the shoulders of giants.     

Are hyoliths Palaeozoic lophophorates?

The phylogenetic position of hyoliths has long been unsettled, with recent discoveries of a tentaculate feeding apparatus (‘lophophore’) and fleshy apical extensions from the shell (‘pedicle’) suggesting a lophophorate affinity. Here, we describe the first soft parts associated with the feeding apparatus of an orthothecid hyolith, Triplicatella opimus from the Chengjiang biota of South China. The tuft-like arrangement of the tentacles of T. opimus differs from that of hyolithids, suggesting they collected food directly from the substrate. A reassessment of the feeding organ in hyolithids indicates that it does not represent a lophophore and our analysis of the apical structures associated with some orthothecids show that these represent crushed portions of the shell and are not comparable to the brachiopod pedicle. The new information suggests that hyoliths are more likely to be basal members of the lophotrochozoans rather than lophophorates closely linked with the Phylum Brachiopoda.     

Rose without prickle: genomic insights linked to moisture adaptation

Prickles act against herbivores, pathogens or mechanical injury, while also preventing water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remain poorly explored. Here, we generated a high-quality reference genome assembly for ‘Basye''s Thornless’ (BT), a prickle-free cultivar of Rosa wichuraiana, to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and with cultivar ‘Old Blush’ (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to improvements for horticultural markets.     

Protein designer David Baker: I like doing things that seem like magic

Search ‘de novo protein design’ on Google and you will find the name David Baker in all results of the first page. Professor David Baker at the University of Washington and other scientists are opening up a new world of fantastic proteins. Protein is the direct executor of most biological functions and its structure and function are fully determined by its primary sequence. Baker''s group developed the Rosetta software suite that enabled the computational prediction and design of protein structures. Being able to design proteins from scratch means being able to design executors for diverse purposes and benefit society in multiple ways. Recently, NSR interviewed Prof. Baker on this fast-developing field and his personal experiences.     

Science communication in China: a critical component of the global science powerhouse

China has attached a great significance to bringing science to the public—known as kepu (科普, ‘science popularization’) or kexue chuanbo (科学传播, ‘science dissemination’)—in recent years, partly in response to its unprecedented push for innovation in science and technology. In 2018, it spent 16 billion yuan (US$2.3 billion) on such endeavours, nearly 80% of which was government funding, according to a survey conducted by the Ministry of Science and Technology. With one science-education venue for every million people, approximately 76 million visits were made to the country''s 518 general-science museums and 142 million visits were made to 943 museums dedicated to a specific subject matter, such as the Geological Museum of China.In a forum chaired by National Science Review’s executive editor-in-chief, Mu-ming Poo, scientists, journalists and public-information officers discussed the differences in science communication between China and developed nations, the challenges and opportunities of raising scientific literacy in China, how it has played out in a wide range of controversial topics, from stem-cell research to climate change, and the importance of international collaboration. Tao Deng Director of the Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing, China Hepeng Jia Science journalist and science-communication scholar at Soochow University, Suzhou, China Brian Lin Director of the Editorial Content Strategy, EurekAlert!, American Association of the Advancement of Science, Washington DC, USA Joy Ma Manager of the Editorial Content, EurekAlert!, American Association of the Advancement of Science, Washington DC, USA Lai Xu Former chief editor of Guokr.com, Beijing, China Shi Yan Deputy director of the China Research Institute for Science Popularisation, Chinese Association of Science and Technology, Beijing, China Mu-ming Poo (Chair) Director of the Insitute of Neuroscience, Chinese Academy of Sciences, Shanghai, China     

A K+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification

Although molecular imaging probes have the potential to non-invasively diagnose a tumor, imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain elusive. Here, we demonstrate a potassium ion (K⁺) sensitive dual-mode nanoprobe (KDMN) for non-invasive tumor imaging and malignancy identification, which operates via a cascaded ‘AND’ logic gate controlled by inputs of magnetic resonance imaging (MRI) and fluorescence imaging (FI) signals. We encapsulate commercial K⁺ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles, which are subsequently coated with a K⁺-selective membrane that exclusively permits the passage of K⁺ while excluding other cations. The KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic administration. Spatial information of the tumor lesion is thus accessible via MRI and forms the first layer of the ‘AND’ gate. Meanwhile, the KDMN selectively captures K⁺ and prevents interference from other cations, triggering a K⁺-activated FI signal as the second layer of the ‘AND’ gate in the case of a malignant tumor with a high extracellular K⁺ level. This dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.     

MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3

Central precocious puberty (CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone (GnRH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a ‘brake’ of mammalian puberty onset, but the underlying mechanisms remain as yet unknown. Here, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3–MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.     

Solving the mystery of vanishing rivers in China

A major controversy was sparked worldwide by a recent national water census claiming that the number of Chinese rivers with watersheds ≥100 km² was less than half the previous estimate of 50 000 rivers, which also stimulates debates on the potential causes and consequences. Here, we estimated the number of rivers in terms of stream-segmentation characteristics described by Horton, Strahler and Shreve stream-order rules, as well as their mixed mode for named rivers recorded in the Encyclopedia of Rivers and Lakes in China. As a result, the number of ‘vanishing rivers’ has been found to be highly relevant to statistical specifications in addition to the erroneous inclusion of pseudo-rivers primarily generated in arid or frost-thaw areas. The modified Horton stream-order scheme reasonably depicts the configuration of complete natural streams from headwater to destination, while the Strahler largely projects the fragmentation of the named river networks associated with human aggregation to the hierarchical river systems.     

Post-ingestion conversion of dietary indoles into anticancer agents

There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3^′-diindolylmethane (LTr1) and 3,3^′-diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM produced from I3C via the formaldehyde-releasing (major) and CO₂-liberating (minor) pathways. In the large intestine, ‘endogenous’ I3C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H⁺-promotable steps. This work updates our understanding of the merits of I3C consumption and identifies LTr1 as a drug candidate.     

Ideal type-II Weyl points in topological circuits

Weyl points (WPs), nodal degenerate points in three-dimensional (3D) momentum space, are said to be ‘ideal’ if they are symmetry-related and well-separated, and reside at the same energy and far from nontopological bands. Although type-II WPs have unique spectral characteristics compared with type-I counterparts, ideal type-II WPs have not yet been reported because of a lack of an experimental platform with enough flexibility to produce strongly tilted dispersion bands. Here, we experimentally realize a topological circuit that hosts only topological bands with a minimal number of four ideal type-II WPs. By stacking two-dimensional (2D) layers of inductor-capacitor (LC) resonator dimers with the broken parity inversion symmetry (P), we achieve a strongly tilted band structure with two group velocities in the same direction, and topological surface states in an incomplete bandgap. Our results establish an ideal system for the further study of Weyl physics and other exotic topological phenomena.     

Evidence for oxygenation of Fe-Mg oxides at mid-mantle conditions and the rise of deep oxygen

As the reaction product of subducted water and the iron core, FeO₂ with more oxygen than hematite (Fe₂O₃) has been recently recognized as an important component in the D” layer just above the Earth''s core-mantle boundary. Here, we report a new oxygen-excess phase (Mg, Fe)₂O_3+δ (0 < δ < 1, denoted as ‘OE-phase’). It forms at pressures greater than 40 gigapascal when (Mg, Fe)-bearing hydrous materials are heated over 1500 kelvin. The OE-phase is fully recoverable to ambient conditions for ex situ investigation using transmission electron microscopy, which indicates that the OE-phase contains ferric iron (Fe³⁺) as in Fe₂O₃ but holds excess oxygen through interactions between oxygen atoms. The new OE-phase provides strong evidence that H₂O has extraordinary oxidation power at high pressure. Unlike the formation of pyrite-type FeO₂Hx which usually requires saturated water, the OE-phase can be formed with under-saturated water at mid-mantle conditions, and is expected to be more ubiquitous at depths greater than 1000 km in the Earth''s mantle. The emergence of oxygen-excess reservoirs out of primordial or subducted (Mg, Fe)-bearing hydrous materials may revise our view on the deep-mantle redox chemistry.     

Synchronization within synchronization: transients and intermittency in ecological networks

Transients are fundamental to ecological systems with significant implications to management, conservation and biological control. We uncover a type of transient synchronization behavior in spatial ecological networks whose local dynamics are of the chaotic, predator–prey type. In the parameter regime where there is phase synchronization among all the patches, complete synchronization (i.e. synchronization in both phase and amplitude) can arise in certain pairs of patches as determined by the network symmetry—henceforth the phenomenon of  ‘synchronization within synchronization.’ Distinct patterns of complete synchronization coexist but, due to intrinsic instability or noise, each pattern is a transient and there is random, intermittent switching among the patterns in the course of time evolution. The probability distribution of the transient time is found to follow an algebraic scaling law with a divergent average transient lifetime. Based on symmetry considerations, we develop a stability analysis to understand these phenomena. The general principle of symmetry can also be exploited to explain previously discovered, counterintuitive synchronization behaviors in ecological networks.     

Three Gorges Dam: friend or foe of riverine greenhouse gases?

Dams are often regarded as greenhouse gas (GHG) emitters. However, our study indicated that the world''s largest dam, the Three Gorges Dam (TGD), has caused significant drops in annual average emissions of CO₂, CH₄ and N₂O over 4300 km along the Yangtze River, accompanied by remarkable reductions in the annual export of CO₂ (79%), CH₄ (50%) and N₂O (9%) to the sea. Since the commencement of its operation in 2003, the TGD has altered the carbonate equilibrium in the reservoir area, enhanced methanogenesis in the upstream, and restrained methanogenesis and denitrification via modifying anoxic habitats through long-distance scouring in the downstream. These findings suggest that ‘large-dam effects’ are far beyond our previous understanding spatiotemporally, which highlights the fundamental importance of whole-system budgeting of GHGs under the profound impacts of huge dams.     

Precision spectroscopy of atomic helium

Helium is a prototype three-body system and has long been a model system for developing quantum mechanics theory and computational methods. The fine-structure splitting in the 2³P state of helium is considered to be the most suitable for determining the fine-structure constant α in atoms. After more than 50 years of efforts by many theorists and experimentalists, we are now working toward a determination of α with an accuracy of a few parts per billion, which can be compared to the results obtained by entirely different methods to verify the self-consistency of quantum electrodynamics. Moreover, the precision spectroscopy of helium allows determination of the nuclear charge radius, and it is expected to help resolve the ‘proton radius puzzle’. In this review, we introduce the latest developments in the precision spectroscopy of the helium atom, especially the discrepancies among theoretical and experimental results, and give an outlook on future progress.     

Shadow glass transition as a thermodynamic signature of β relaxation in hyper-quenched metallic glasses

One puzzling phenomenon in glass physics is the so-called ‘shadow glass transition’ which is an anomalous heat-absorbing process below the real glass transition and influences glass properties. However, it has yet to be entirely characterized, let alone fundamentally understood. Conventional calorimetry detects it in limited heating rates. Here, with the chip-based fast scanning calorimetry, we study the dynamics of the shadow glass transition over four orders of magnitude in heating rates for 24 different hyper-quenched metallic glasses. We present evidence that the shadow glass transition correlates with the secondary (β) relaxation: (i) The shadow glass transition and the β relaxation follow the same temperature–time dependence, and both merge with the primary relaxation at high temperature. (ii) The shadow glass transition is more obvious in glasses with pronounced β relaxation, and vice versa; their magnitudes are proportional to each other. Our findings suggest that the shadow glass transition signals the thermodynamics of β relaxation in hyper-quenched metallic glasses.     

The centrifugal viscometer

In this study, a viscometer, which can measure the viscosity of low-volume liquids (25 μl) within 30 s, was developed on a centrifugal platform. The centrifugal viscometer consists of a disk platform and a motor. Under disk rotation, centrifugal, Coriolis, and viscosity-induced drag forces result in deflection of liquid flow. The viscosity of the liquid sample is determined by the deflection angle of the liquid, which can be examined through image analysis or visual inspection. The viscosities of a series of Newtonian model fluids were tested by the centrifugal viscometer and the results showed good agreement with the ones tested by a conventional rotational viscometer. Since the centrifugal viscometer only requires a motor to function, the microfluidic disk can be produced in large quantities at a low cost through injection molding, and the deflection angle can be detected through visual inspection, it provides an inexpensive, easy to operate, and portable approach to measure low-volume liquid viscosity.