Sequence- and Structure-Specific tRNA Dihydrouridylation by hDUS2.

The post-transcriptional reduction of uridine to dihydrouridine (D) by dihydrouridine synthase (DUS) enzymes is among the most ubiquitous transformations in RNA biology. D is found at multiple sites in tRNAs, and studies in yeast have proposed that each of the four eukaryotic DUS enzymes modifies a different site; however, the molecular basis for this exquisite selectivity is unknown, and human DUS enzymes have remained largely uncharacterized. Here we investigate the substrate specificity of human dihydrouridine synthase 2 (hDUS2) using mechanism-based cross-linking with 5-bromouridine (5-BrUrd)-modified oligonucleotide probes and in vitro dihydrouridylation assays. We find that hDUS2 exclusively modifies U20 across diverse tRNA substrates and identify a minimal GU sequence within the tRNA D loop that underlies selective substrate modification. Further, we use our mechanism-based platform to screen small molecule inhibitors of hDUS2, a potential anticancer target. Our work elucidates the principles of substrate modification by a conserved DUS and provides a general platform for studying RNA modifying enzymes with sequence-defined activity-based probes.

A minimal sequence motif drives selective tRNA dihydrouridylation by hDUS2.

The post-transcriptional reduction of uridine to dihydrouridine (D) by dihydrouridine synthase (DUS) enzymes is among the most ubiquitous transformations in RNA biology. D is found at multiple sites in tRNAs and studies in yeast have proposed that each of the four eukaryotic DUS enzymes modifies a different site, however the molecular basis for this exquisite selectivity is unknown and human DUS enzymes have remained largely uncharacterized. Here we investigate the substrate specificity of human dihydrouridine synthase 2 (hDUS2) using mechanism-based crosslinking with 5-bromouridine (5-BrUrd)-modified oligonucleotide probes and in vitro dihydrouridylation assays. We find that hDUS2 modifies U20 in the D loop of diverse tRNA substrates and identify a minimal GU motif within the tRNA tertiary fold required for directing its activity. Further, we use our mechanism-based platform to screen small molecule inhibitors of hDUS2, a potential anti-cancer target. Our work elucidates the principles of substrate modification by a conserved DUS and provides a general platform to studying RNA modifying enzymes with sequence-defined activity-based probes.

All-fiber laser system for all-optical 87Rb Bose Einstein condensate to space application.

In the development of the Cold Atom Physics Research Rack (CAPR) on board the Chinese Space Station, the laser system plays a critical role in preparing the all-optical 87 R b Bose-Einstein condensates (BECs). An all-fiber laser system has been developed for CAPR to provide the required optical fields for atom interaction and to maintain the beam pointing in long-term operation. The laser system integrates a 780 nm fiber laser system and an all-fiber optical control module for sub-Doppler cooling, as well as an all-fiber 1064 nm laser system for evaporative cooling. The high-power, single-frequency 780 nm lasers are achieved through rare-Earth doped fiber amplification, fiber frequency-doubling, and frequency stabilization technology. The all-fiber optical control module divides the output of the 780 nm laser system into 15 channels and regulates them for cooling, trapping, and probing atoms. Moreover, the power consistency of each pair of cooling beams is ensured by three power tracking modules, which is a prerequisite for maintaining stable MOT and molasses. A high-power, compact, controlled-flexible, and highly stable l064 nm all-fiber laser system employing two-stage ytterbium-doped fiber amplifier (YDFA) technology has been designed for evaporative cooling in the optical dipole trap (ODT). Finally, an all-optical 87 R b BEC is realized with this all-fiber laser system, which provides an alternative solution for trapping and manipulating ultra-cold atoms in challenging environmental conditions.

Characterization of laser cooling in microgravity via long-term operations in TianGong-2 space lab.

The invention of laser cooling has fundamentally influenced the research frontier of atomic physics and quantum physics, and recently an intense focus has been on the studies of cold atom physics in microgravity environments. Herein, we report the results of our laser cooling experiment in TianGong-2 space lab, which operated for 34 consecutive months in orbit. Over such an extended operation time, the quality of laser cooling did not experience any significant decline, while the properties of laser cooling in orbital microgravity were systematically studied. In particular, we demonstrate magneto-optical trapping and polarization-gradient cooling in orbit and carefully examine their performances. A comparison of the in-orbit and on-ground results indicates that a higher cooling efficiency exists in microgravity, including a smaller loss rate during the trapping and cooling process and lower ultimate temperature of laser-cooled atoms. Our progress has laid the technical foundations for future applications of cold atoms in space missions with operation times of the order of years.

Design and operation of a transportable 87Rb atomic fountain clock.

A transportable fountain clock with high reliability is important for high-precision time-frequency measurements. Because of its relatively small cold atoms' collision frequency shift and ease of attaining high quantum state preparation efficiency, the rubidium atomic fountain clock has an indicated higher stability and reliability. This paper reports the design and operation of a transportable rubidium atomic fountain clock developed by the Shanghai Institute of Optical and Fine Mechanics, Chinese Academy of Science. After being transported more than 1000 km from Shanghai to the Changping Campus of the National Institute of Metrology, China, the optical platform and other hardware of the fountain clock did not need to be adjusted. The rubidium fountain clock maintained a stability of 4.0 × 10-13τ1/2, reaching 5.0 × 10-16 at 300 000 s. After transportation, the rubidium fountain clock and a cesium fountain clock (NIM5) were operated together against the reference frequency of a hydrogen maser. In three separate operating periods, over a total of nearly three months, the average frequency repeatability of the rubidium fountain was less than 3.8 × 10-15.

A Reductive Supramolecular Hydrogel: A Platform for Facile Fabrication of Diverse Metal-Nanoparticle-Decorated Conductive Networks with Spatiotemporal Control.

Nanoparticle-hydrogel hybrid composites have a great potential for a broad range of applications, such as antibacterial materials, stimuli-responsive materials and catalysis. A novel supramolecular hydrogel system was developed using an amino acid based amphiphile containing a terminal pyrrole moiety as a gelator. The pyrrole moiety could serve as both reducing agent and monomer, and a variety of metal precursors penetrating into the hydrogel could be reduced in situ into metal nanoparticles while the pyrrole moieties preorganized in hydrogel were oxidized into polyprroles, affording metal-nanoparticle-decorated covalent conductive networks. This strategy allows the facile fabrication of diverse mono- or multimetallic nanoparticle-polymer networks from one hydrogel by a simple reaction-diffusion approach. More importantly, besides homogeneous composites, unique multisegment heterogeneous systems with spatiotemporal control were also easily accessible. Furthermore, based on the same multifunctional molecule, the fabrication of hierarchically pore-structured metal-nanoparticles-polymers as well as metal-nanoparticles-carbon structures was also realized.

Metabolic Activity Phenotyping of Single Cells with Multiplexed Vibrational Probes.

Quantitative measurements of metabolic activities of individual cells are essential to understanding questions in diverse fields in biology. To address this challenge, we present a method, termed metabolic activity phenotyping (MAP), to probe metabolic fluxes by utilizing multiplexed vibrational metabolic probes. With specifically designed single-whole-cell confocal micro-Raman spectroscopy, quantitative measurement of lipid and protein synthesis activity was achieved with high throughput (several orders of magnitude improvement over a commercial confocal system). In addition, metabolic heterogeneity upon various drug treatments was also revealed and evaluated at the single-cell level. We further demonstrated that MAP was more robust than the label-free Raman methods and was able to make the correct classification among diverse cancer types and breast cancer subtypes by exploring the dimension of metabolism. The capability of MAP to explore metabolic profiles at the single-cell level makes it a valuable tool for basic single-cell studies as well as other screening applications.

When Prussian Blue Meets Porous Gold Nanoparticles: A High Signal-to-Background Surface-Enhanced Raman Scattering Probe for Cellular Biomarker Imaging.

Profiling cellular biomarkers without the interference of endogenous signals could facilitate the investigation of complex intracellular biological events and provide new possibilities for precision disease diagnosis. Herein, a surface-enhanced Raman scattering (SERS) probe with a high signal-to-background ratio (SBR) for cellular biomarker imaging is constructed. The probes are prepared by incorporating Prussian blue (PB) with porous gold nanoparticles (p-Au NPs). Due to their rich built-in Raman hotspots, the p-Au NPs are excellent SERS substrates that can significantly amplify the signals of the incorporated PB. In parallel, PB shows a single peak in the cellular silent region, where the signals from the probes and endogenous molecules can be completely resolved without the need of complex spectral unmixing. As a consequence, the combination of probe signal enhancement and background elimination endows the SERS probes with an extremely high SBR. To evaluate their performance in biomarker imaging, the high-SBR SERS probes are utilized to profile folic acids at a single-cell level. This background-free, high-precision imaging technique is conducive to early diagnosis and therapeutic response of cancer that is of great importance in clinical settings.

Space qualified microwave source for cold atom clock operating in orbit.

The space cold atom clock (CAC) suffers more degradation of frequency stability from the local oscillator noise compared with fountain clocks operating on the ground because of the larger dead time of the clock cycle. Therefore, low phase noise is required for the microwave source of the space CAC in addition to robustness, compactness, and adaptability to the space environment. This paper presents the design and measurements of a low-phase-noise space qualified microwave source for the cold atom clock experiment in space CAC operating in the Tiangong-2 Chinese space laboratory. At frequencies near the carrier, a phase noise level of 10-6.7 × f -1.5 rad2/Hz (f is the Fourier frequency) is achieved. This guarantees a frequency stability of 1.4 × 10-13 τ -1/2 (τ is the average time in seconds) for the typical space CAC operation cycle.

In-orbit operation of an atomic clock based on laser-cooled 87Rb atoms.

Atomic clocks based on laser-cooled atoms are widely used as primary frequency standards. Deploying such cold atom clocks (CACs) in space is foreseen to have many applications. Here we present tests of a CAC operating in space. In orbital microgravity, the atoms are cooled, trapped, launched, and finally detected after being interrogated by a microwave field using the Ramsey method. Perturbing influences from the orbital environment on the atoms such as varying magnetic fields and the passage of the spacecraft through Earth's radiation belt are also controlled and mitigated. With appropriate parameters settings, closed-loop locking of the CAC is realized in orbit and an estimated short-term frequency stability close to 3.0 × 10-13τ-1/2 has been attained. The demonstration of the long-term operation of cold atom clock in orbit opens possibility on the applications of space-based cold atom sensors.

Guanidinium-Based Polymerizable Surfactant as a Multifunctional Molecule for Controlled Synthesis of Nanostructured Materials with Tunable Morphologies.

Rationally and efficiently controlling the morphology of nanomaterials plays a crucial role in significantly enhancing their functional properties and expending their applications. In this work, a strategy for controlled synthesis of diverse nanostructured materials with tunable morphologies was developed using a guanidinium-based surfactant with a polymerizable pyrrole unit as a multifunctional molecule that can serve not only as a structure-directing agent for mesostucture formation but also as a monomer and carbon source. The unique self-assembly behavior of the guanidinium head group under different conditions allows the synthesized surfactants to form different aggregates and thus to produce silica nanomaterials with multiple morphologies (such as sphere, disk, fiber, and cocoon) in conjunction with sol-gel chemistry. Besides the mesostructured silicates, by further exploring the polymerization and carbonization features of pyrrole units that were densely packed in the formed silica nanochannels, diverse nanostructured materials such as mesostructured conducting polymers, carbon materials, and metal-nanoparticle (NP)-decorated forms could also be easily obtained in one-pot fashion for various applications, such as energy storage and catalysis. As a demonstration, carbon nanotubes and Pd-NP-doped hollow carbon spheres were fabricated, which exhibited good specific capacitance (101.7 F g-1) at the scan rates of 5 mV s-1 and excellent catalytic performance (100% conversion for three cycles) in the Suzuki C-C coupling reaction, respectively. All of the results indicate that our strategy may open a new avenue for efficiently accessing diverse nanostructured materials with tunable morphologies for wide applications.

Efficient Construction of Well-Defined Multicompartment Porous Systems in a Modular and Chemically Orthogonal Fashion.

A microfluidic assembly approach was developed for efficiently producing hydrogel spheres with reactive multidomains that can be employed as an advantageous platform to create spherical porous networks in a facile manner with well-defined multicompartments and spatiotemporally controlled functions. This strategy allows for not only large scale fabrication of various robust hydrogel microspheres with controlled size and porosity, but also the domains embedded in hydrogel network could be introduced in a modular manner. Additionally, the number of different domains and their ratio could be widely variable on demand. More importantly, the reactive groups distributed in individual domains could be used as anchor sites to further incorporate functional units in an orthogonal fashion, leading to well-defined multicompartment systems. The strategy provides a new and efficient route to construct well-defined functional multicompartment systems with great flexibility and extendibility.

Chaperone-Assisted Formation of Cucurbit[8]uril-Based Molecular Porous Materials with One-Dimensional Channel Structure.

Exploiting "chaperone molecule" to navigate the successful assembly energy landscapes has been extensively used in biological systems, whereas in artifical supramolecular systems the "chaperone-assisted" assembly strategy to be used for the synthesis of materials with novel structures or the structures to be hardly prepared by "conventional" methods are still far from realizing the potential functions. In this work, we present a new example of small organic molecule acting as "chaperone molecule" in the facile formation of organic molecular porous materials. This porous material is composed of pure cucurbit[8]uril (CB[8]) macrocycle and possesses a honeycomb-like structure with an isolated and relatively large one-dimensional (1D) nanochannel. Moreover, it has good chemical and thermal stability, and shows a good adsorption capability for large molecule loading. Importantly, with the assistance of chaperone molecules, pure CB[8] could also be recycled even from a complex aqueous solution, demonstrating a powerful purification method of CB[8] from complex systems.

Pyrrole-Terminated Ionic Liquid Surfactant: One Molecule with Multiple Functions for Controlled Synthesis of Diverse Multispecies Co-Doped Porous Hollow Carbon Spheres.

Rationally and efficiently controlling chemical composition, microstructure, and morphology of carbon nanomaterials plays a crucial role in significantly enhancing their functional properties and expending their applications. In this work, a novel strategy for simultaneously controlling these structural parameters was developed on the base of a multifunctional precursor approach, in which the precursor not only serves as carbon source and structure-directing agent, but also contains two heteroatom doping sites. As exemplified by using pyrrole-terminated ionic liquid surfactant as such precursor, in conjunction with sol-gel chemistry this strategy allows for efficiently producing well-defined hollow carbon spheres with controlled microstructure and chemical compositions. Remarkably, the dual-doping sites in confined silica channels provide an exciting opportunity and flexibility to access various doped carbons through simply anion exchange or altering the used oxidative polymerization agent, especially the multispecies codoped materials by combination of the two doping modes. All the results indicate that the described strategy may open up a new avenue for efficiently synthesizing functional carbon materials with highly controllable capability.

Emulsion droplets as a dynamic interface for the direct and large-scale synthesis of ultrathin free-standing mesoporous silica films as well as 2D polymeric and carbon nanomaterials.

The efficient synthesis of free-standing mesostructured two-dimensional (2D) nanofilms with high-yield as well as good control of composite, mesophase structure, orientation of the pore channel and thickness represents a big challenge. In this work, it was serendipitously found that microemulsion droplets of tetraethylorthosilicate (TEOS) could serve as a novel dynamic interface for continuous growth of nanofilms. Based on this finding, a general, efficient strategy for the direct and large-scale synthesis of free-standing mesoporous silica films (FSMSFs) was developed. Remarkably, with the careful control of the synthesis conditions, the FSMSFs with high-yield as well as good control of composite, mesophase structure, orientation of the pore channel and thickness could be efficiently achievable. More importantly, by using polymerizable surfactants the preorganized monomers in the nanochannels of the resultant silica films could be further converted into 2D polymers and carbon nanomaterials as well as metal particle-decorated forms, as exemplified by using pyrrole-terminated surfactants, demonstrating a powerful method to create 2D inorganic, organic or hybrid functional nanomaterials.