Metabolic enzyme UAP1 mediates IRF3 pyrophosphorylation to facilitate innate immune response.

Post-translational modifications (PTMs) of proteins are crucial to guarantee the proper biological functions in immune responses. Although protein phosphorylation has been extensively studied, our current knowledge of protein pyrophosphorylation, which occurs based on phosphorylation, is very limited. Protein pyrophosphorylation is originally considered to be a non-enzymatic process, and its function in immune signaling is unknown. Here, we identify a metabolic enzyme, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), as a pyrophosphorylase for protein serine pyrophosphorylation, by catalyzing the pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 to promote robust type I interferon (IFN) responses. Uap1 deficiency significantly impairs the activation of both DNA- and RNA-viruse-induced type I IFN pathways, and the Uap1-deficient mice are highly susceptible to lethal viral infection. Our findings demonstrate the function of protein pyrophosphorylation in the regulation of antiviral responses and provide insights into the crosstalk between metabolism and innate immunity.

Palmitoylation prevents sustained inflammation by limiting NLRP3 inflammasome activation through chaperone-mediated autophagy.

As a key component of the inflammasome, NLRP3 is a critical intracellular danger sensor emerging as an important clinical target in inflammatory diseases. However, little is known about the mechanisms that determine the kinetics of NLRP3 inflammasome stability and activity to ensure effective and controllable inflammatory responses. Here, we show that S-palmitoylation acts as a brake to turn NLRP3 inflammasome off. zDHHC12 is identified as the S-acyltransferase for NLRP3 palmitoylation, which promotes its degradation through the chaperone-mediated autophagy pathway. Zdhhc12 deficiency in mice enhances inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock. Notably, several disease-associated mutations in NLRP3 are associated with defective palmitoylation, resulting in overt NLRP3 inflammasome activation. Thus, our findings identify zDHHC12 as a repressor of NLRP3 inflammasome activation and uncover a previously unknown regulatory mechanism by which the inflammasome pathway is tightly controlled by the dynamic palmitoylation of NLRP3.

S-palmitoylation regulates innate immune signaling pathways: molecular mechanisms and targeted therapies.

S-palmitoylation is a reversible posttranslational lipid modification that targets cysteine residues of proteins and plays critical roles in regulating the biological processes of substrate proteins. The innate immune system serves as the first line of defense against pathogenic invaders and participates in the maintenance of tissue homeostasis. Emerging studies have uncovered the functions of S-palmitoylation in modulating innate immune responses. In this review, we focus on the reversible palmitoylation of innate immune signaling proteins, with particular emphasis on its roles in the regulation of protein localization, protein stability, and protein-protein interactions. We also highlight the potential and challenge of developing therapies that target S-palmitoylation or de-palmitoylation for various diseases.

Microfluidics-Enabled Soft Manufacture of Materials with Tailorable Wettability.

Microfluidics and wettability are interrelated and mutually reinforcing fields, experiencing synergistic growth. Surface wettability is paramount in regulating microfluidic flows for processing and manipulating fluids at the microscale. Microfluidics, in turn, has emerged as a versatile platform for tailoring the wettability of materials. We present a critical review on the microfluidics-enabled soft manufacture (MESM) of materials with well-controlled wettability and their multidisciplinary applications. Microfluidics provides a variety of liquid templates for engineering materials with exquisite composition and morphology, laying the foundation for precisely controlling the wettability. Depending on the degree of ordering, liquid templates are divided into individual droplets, one-dimensional (1D) arrays, and two-dimensional (2D) or three-dimensional (3D) assemblies for the modular fabrication of microparticles, microfibers, and monolithic porous materials, respectively. Future exploration of MESM will enrich the diversity of chemical composition and physical structure for wettability control and thus markedly broaden the application horizons across engineering, physics, chemistry, biology, and medicine. This review aims to systematize this emerging yet robust technology, with the hope of aiding the realization of its full potential.

Droplet Bouncing: Fundamentals, Regulations, and Applications.

Droplet impact is a ubiquitous phenomenon in nature, daily life, and industrial processes. It is thus crucial to tune the impact outcomes for various applications. As a special outcome of droplet impact, the bouncing of droplets keeps the form of the droplets after the impact and minimizes the energy loss during the impact, being beneficial in many applications. A unified understanding of droplet bouncing is in high demand for effective development of new techniques to serve applications. This review shows the fundamentals, regulations, and applications of millimeter-sized droplet bouncing on solid surfaces and same/miscible liquids (liquid pool and another droplet). Regulation methods and current applications are summarized, and potential directions are proposed.

TMEM16F mediated phosphatidylserine exposure and microparticle release on erythrocyte contribute to hypercoagulable state in hyperuricemia.

The link between hyperuricemia (HUA) and the risk of venous thromboembolism (VTE) has been well established. However, the mechanisms of thrombus generation and the effect of HUA on procoagulant activity (PCA) of erythrocytes remain unclear no matter in uremia or hyperuricemia. Here, phosphatidylserine (PS) exposure, microparticles (MPs) release, cytosolic Ca2+, TMEM16F expression, reactive oxygen species (ROS) and lipid peroxidation of erythrocyte were detected by flow cytometer. PCA was assessed by coagulation time, purified coagulation complex and fibrin production assays. The fibrin formation was observed by scanning electron microscopy (SEM). We found that PS exposure, MPs generation, TMEM16F expression and consequent PCA of erythrocyte in HUA patients significantly increased compared to those in healthy volunteers. Furthermore, high UA induced PS exposure, and MPs release of erythrocyte in concentration and time-dependent manners in vitro, which enhanced the PCA of erythrocyte and was inhibited by lactadherin, a PS inhibitor. Additionally, using SEM, we also observed compact fibrin clots with highly-branched networks and thin fibers supported by red blood cells (RBCs) and RBC-derived MPs (RMPs). Importantly, we demonstrated UA enhanced the production of ROS and lipid peroxidation and reduced the generation of glutathione (GSH) of erythrocyte, which enhanced TMEM16F activity and followed PS externalization and RMPs formation. Collectively, these results suggest that Ca2+-dependent TMEM16F activation may be responsible for UA-induced PS exposure and MPs release of RBC, which thereby contribute to the prothrombotic risk in HUA.

Hyperuricemia enhances procoagulant activity of vascular endothelial cells through TMEM16F regulated phosphatidylserine exposure and microparticle release.

The link between serum uric acid (SUA) and the risk of venous thromboembolism (VTE) is well established. Recent data suggested a causative role of UA in endothelial cells (ECs) dysfunction. However, the molecular mechanism of high UA on thrombogenesis is unknown. We investigate whether high UA induce phosphatidylserine (PS) externalization and microparticle (MP) shedding in cultured EC, and contribute to UA-induced hypercoagulable state. In the present study, we demonstrate that UA induces PS exposure and EMP release of EC in a concentration- and time-dependent manner, which enhances the procoagulant activity (PCA) of EC and inhibited over 90% by lactadherin in vitro. Furthermore, hyperuricemic rat model was used to evaluate the development of thrombi following by flow stasis in the inferior vena cava (IVC). Hyperuricemia group is more likely to form large and hard thrombi compared with control. Importantly, we found that TMEM16F expression is significantly upregulated in UA-treated EC, which is crucial for UA-induced PS exposure and MP formation. Additionally, UA increases the generation of reactive oxygen species (ROS), lipid peroxidation, and cytosolic Ca2+ concentration in EC, which might contribute to increased TMEM16F expression. Using confocal microscopy, we also observed disruption of the actin cytoskeleton, suggesting that depolymerization of actin filaments might be required for TMEM16F activation and followed by PS exposure and membrane blebbing in UA-treated EC. Our results demonstrate a thrombotic role of EC in hyperuricemia through TMEM16F-mediated PS exposure and MPs release.

Magnetic Field-Assisted Fission of a Ferrofluid Droplet for Large-Scale Droplet Generation.

With the presence of an external magnetic field, a ferrofluid droplet exhibits a rich variety of interesting phenomena notably different from nonmagnetic droplets. Here, a ferrofluid droplet impacting on a liquid-repellent surface is systematically investigated using high-speed imaging. The pre- and post-impact, including the droplet stretching, maximum spreading diameter, and final impact modes, are shown to depend on the impact velocity and the magnitude of the external magnetic field. A scaling relation involving the Weber and magnetic Bond numbers is fitted to predict the maximum spreading diameter based on the magnetic field-induced effective surface tension. The impact outcome is also investigated and classified into three patterns depending on the occurrence of the rim interface instability and the fission phenomenon. Two types of fission (i.e., evenly and unevenly distributed sizes of the daughter droplets) are first identified, and the corresponding mechanism is revealed. Last, according to Rayleigh-Taylor instability, a semiempirical formula is proposed to estimate the number of the daughter droplets in the regime of evenly distributed size, which agrees well with the experimental data. The present study can provide more insight into large-scale droplet generation with monodispersive sizes.

Nonspecular Reflection of Droplets.

The bouncing of droplets on super-repellent surfaces normally resembles specular reflection that obeys the law of reflection. Here, the nonspecular reflection of droplet impingement onto solid surfaces with a dimple for energy-efficient, omnidirectional droplet transport is reported. With the dimple of the radius being comparable to that of the droplet, all the symmetries in the law of reflection can be broken down so that the droplet is endowed with a translational velocity finely tunable in both its direction and magnitude simply by varying the radii of the droplet and the dimple, the impinging position, and droplet Weber number. Tailoring the initial and translational velocity of impinging droplets would steer their reflected trajectories at will, thus enabling versatile droplet manipulation including trapping, shedding, antigravity transport, targeted positioning, and on-demand coalescence of droplets.

Lubricant-Mediated Strong Droplet Adhesion on Lubricant-Impregnated Surfaces.

Lubricant-impregnated surfaces have recently emerged as a new type of multifunctional coating with a promising capability in exhibiting low friction or contact angle hysteresis. However, lubricant-infused surfaces severely suffer from the tensile droplet-lubricant adhesion. In this study, we show that lubricant-infused surfaces allow for a strong tensile droplet adhesion, which results in the generation of an offspring residual droplet when a droplet detaches from the surface. Such tensile liquid-liquid adhesion and the corresponding liquid residue are solely mediated by the lubricant, independent of the underlying surface topography. We reveal how the lubricant film mediates droplet adhesion by measuring the maximum adhesion force and liquid residue and theoretically analyzing Laplace pressure force from the droplet shape and surface tension force depending on the contact line. Further, the presence of lubricant-induced adhesion considerably compromises the advantages of lubricant-infused surfaces in some applications. The lubricant-triggered tensile adhesion hampers the loss-free droplet transfer away from the surfaces in the photoelectrically and magnetically driven droplet manipulation. In addition, we demonstrate that the lubricant-triggered adhesion plays a dominant role in attenuating the efficiency of fog harvesting by impeding the shedding of the intercepted droplets by comparing the onset time, droplet radius, and collection efficiency. These findings advance our fundamental understanding of droplet adhesion on lubricant-infused surfaces and significantly benefit the design of lubricant-infused surfaces for various applications.

Direct visualization of beam-resist interaction volume for sub-nanometer helium ion beam-lithography.

Interaction volume of beam-resist is a basis unit of beam-lithography, directly determines the critical parameters of beam-lithography. We have visualized the interaction volume at the state-of-the-art sub-10 nm scale by a spot irradiation of sub-nanometer helium ion beam into an approximately free-standing resist. The visualized interaction volume suggests helium ion beam has an excellent capability in nanofabrication. Specifically, helium ion beam-lithography is 1000 times more efficient than electron beam-lithography (EBL), owns a sub-4 nm resolution, can achieve a large pattern aspect ratio (greater than 8), and does not suffer from backscattering effect at a normal exposure dose. Furthermore, the interaction volume has been theoretically studied by considering the spatial distribution of energy deposited in the resist, and eventually lead to a model for pattern prediction and proximity effect corrections. We expect that, our approach to visualize the interaction volume may be applied to study other high resolution lithographic techniques such as x-ray lithography and EBL, and it may open new possibilities in other applications, like beam-imaging, beam-milling, and beam-modification.

CS-CNTs homojunctions prepared byin situgrowth of carbon nanotubes on the surface of porous carbon spheres for lithium-sulfur batteries.

Lithium-sulfur battery is expected to become a new generation of commercial battery owing to its ultra-high theoretical specific capacity, low-cost, and environmental benign. However, the inherent insulation of sulfur and the shuttle effect of lithium polysulfide between electrodes limit the application of lithium-sulfur battery. In order to solve these problems, we focus on the design of carbon-sulfur composite structure. Herein, CS-CNTs homojunctions featured with the carbon nanotubes (CNTs)in situgrown on carbon sphere (CS) is designed and synthesized by simple polymerization and heat treatment. The composites of CS with interconnected pore networks and CNTs with high conductivity not only offer a conductive framework to promote fast electron transmission, but also provide a larger space to load sulfur and effectively capture polysulfides. The CS-CNTs@S cathode shows better electrochemical performance compared with CS-CPs@S and CS@S. The first discharge specific capacity is 1053 mAh g-1at 0.1 C. After 200 cycles, the specific capacity still remains at 427 mAh g-1.

Dynamic regimes of electrified liquid filaments.

We investigate the dynamics of an electrified liquid filament in a nozzle-to-substrate configuration with a close separation. The interplay between compressive viscous and electrostatic stresses dictates previously undocumented transitions between dynamic regimes of "jetting," "coiling," and "whipping." In particular, the onsets of both coiling and whipping instabilities are significantly influenced by the minimum radius along the liquid filament. Using a low-interfacial-tension system, we unravel the physics behind the transitions between jetting, coiling, and whipping of an electrified filament for a range of liquid properties and geometric parameters. Our results enrich the overall physical picture of the electrically forced jets, and provide insights for the emerging high-resolution instability-assisted printing of materials such as folded assemblies and scaffolds.

Complex three-dimensional microparticles from microfluidic lithography.

Complex 3D microparticle, as an emerging and attractive field, has attracted more and more attention due to its versatile morphologies and broad range of applications. In this review, we provide an overall recent progress in 3D microparticles fabricated by microfluidic lithography. This review will focus on the synthesis mechanisms, synthesis process, the resultant 3D microparticles, and their applications. Finally, we will look into the future trends in complex 3D microparticles. This review will be beneficial for researchers in numerous fields, including functional materials, sensors, encryption, and biomedical engineering.

Microfluidic Encapsulation of Phase-Change Materials for High Thermal Performance.

Microencapsulation of phase-change materials (PCMs) can prevent leakage of PCMs and enhance heat transfer with an increased surface area to volume ratio and thus benefit their pragmatic applications. However, the available methods have difficulties in microencapsulating PCMs with a tunable size, structure, and composition at will, thereby failing to accurately and flexibly tailor the thermal properties of microencapsulated PCMs (MEPCMs). Here, the microfluidic encapsulation of PCMs was presented for precisely fabricating MEPCMs with tunable thermal properties. The versatile fabrication of both organic and inorganic MEPCMs was demonstrated with high monodispersity, energy storage capacity, encapsulation efficiency, thermal stability, reliability, and heat charging and discharging rates. Notably, the inorganic MEPCMs exhibit an energy storage capacity of 269.3 J/g and a charging rate of 294.7 J/(g min), surpassing previously reported values. Owing to their high thermal performance, MEPCMs have been used for anticounterfeit applications. Droplet-based microfluidic fabrication opens up a new avenue for versatile fabrication of MEPCMs with well-tailored thermal properties, thus benefitting their applications.

Nakamurella antarctica sp. nov., isolated from Antarctica South Shetland Islands soil.

A pale-yellow bacterial strain, designated S14-144T, was isolated from tundra soil sampled near the Antarctic Peninsula, South Shetland Islands (62° 22' 34″ S, 59° 42' 34″ W). The cells were strictly aerobic, Gram-stain-positive, non-motile and coccoid-shaped. Growth occurred at 4-28 °C, at pH 5.0-9.0 and in the presence of 0-5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S14-144T formed a lineage within the genus Nakamurella and shared the highest 16S rRNA gene sequence similarity with Nakamurella deserti 12Sc4-1T (96.5 %) and Nakamurella silvestrisS20-107T (96.4 %). The average nucleotide identity value between the genomes of strain 14-144T and the type strain of the species, N. deserti, was 72.0 % . The DNA G+C content of strain S14-144T was 61.6 mol% . The major cellular fatty acids of strain S14-144T were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and C16 : 0. The strain contained MK-8(H4) as the predominant respiratory quinone, phosphatidylethanolamine and diphosphatidylglycerol as the major polar lipids, rhamnose, ribose and glucose as the major whole-cell sugars, and meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. On the basis of the phylogenetic, phenotypic and chemotaxonomic analysis, strain S14-144T is considered to represent a novel species of the genus Nakamurella, for which the name Nakamurella antarctica sp. nov. is proposed. The type strain is S14-144T (=CCTCC AB 2015345T=KCTC 39796T).

Deinococcus psychrotolerans sp. nov., isolated from soil on the South Shetland Islands, Antarctica.

A Gram-stain-negative, non-motile, strictly aerobic, coccus-shaped bacterium, designated S14-83T, was isolated from a soil sample collected from the South Shetland Islands of Antarctica. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain is a novel member of the genus Deinococcus, with Deinococcus alpinitundrae as its closest relative (96.1 % similarity). The DNA G+C content of the strain was 61.1 mol% and the major respiratory quinone was MK-8. Major cellular fatty acids were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and C16 : 0. As well as containing glycophospholipid, aminophospholipids and glycolipid as major polar lipids, there were also some unknown polar lipids. The diagnostic diamino acid in the cell-wall peptidoglycan was ornithine, corroborating the assignment of the strain to the genus Deinococcus. Strain S14-83T was shown to be extremely resistant to gamma radiation (>10 kGy) and UV light (460 Jm-2). On the basis of phylogenetic, chemotaxonomic and phenotypic data presented here, strain S14-83T represents a novel species of the genus Deinococcus, for which the name Deinococcus psychrotolerans sp. nov. is proposed. The type strain is S14-83T (=CCTCC AB 2015449T= DSM 105285 T).

Self-Assembly of TiO2 Nanofiber-Based Microcapsules by Spontaneously Evolved Multiple Emulsions.

We demonstrate hierarchical nest/crust-like colloidosomes composed of interlocked titanium dioxide (TiO2) nanofibers using spontaneously evolved n-butanol/water/ n-butanol (B/W/B) emulsions. We find two mechanisms to produce colloidosomes from B/W/B droplets due to their mutual solubility and dewetting discrepancy. Porous TiO2 colloidal capsules with loosely intertwined nanofibers were obtained after the dewetting of nanofiber-coated B/W/B droplets, while crustlike TiO2 colloidosomes with a thin shell and large hollow interior are developed from amphiphilic polymer-stabilized B/W/B droplets. We further investigate the effect of experimental parameters, including the initial droplet size, the nanofiber concentration, and the water/butanol ratios in butanol phases, on the droplet-to-colloidosome evolution and resultant morphology of colloidosomes. Our simple and versatile approach for fabricating TiO2 colloidosomes can be extended to a range of irregular colloidal particles, and the products have great potential to act as host systems in electrochemical catalysis, photothermal therapy, or filtration materials.

Deinococcus taklimakanensis sp. nov., isolated from desert soil.

A gamma- and UV radiation-tolerant, Gram-negative, short-rod-shaped bacterial strain, designated X-121T, was isolated from soil samples collected from the Taklimakan desert in Xinjiang, China. Strain X-121T showed the highest 16S rRNA gene sequence similarity with Deinococcus depolymerans TDMA-24T (94.7 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain X-121T is a member of a novel species belonging to the clade formed by members of the genus Deinococcus in the family Deinococcaceae. The DNA G+C content of strain X-121T was 63.6 mol%. The chemotaxonomic charateristics of strain X-121T were typical of members of the genus Deinococcus, with MK-8 being the predominant respiratory quinone, summed feature 3 (16 : 1ω7c,16 : 1ω6c), 16 : 0 and 17 : 1ω8c as major cellular fatty acid, several unidentified phosphoglycolipids and glycolipids as the dominant polar lipids, galactose as the predominant cell-wall sugar and the presence of peptidoglycan with l-ornithine. Strain X-121T is therefore identified as representing a novel species, for which the name Deinococcus taklimakanensis sp. nov. is proposed, with the type strain X-121T(=CCTCC AB 207228T=KCTC 33842T).

Mucilaginibacter antarcticus sp. nov., isolated from tundra soil.

The novel, pale yellow bacterial strain, designated S14-88T, was isolated from a tundra soil near Antarctic Peninsula, South Shetland Islands, and its taxonomic position was investigated by a genotypic and phenotypic analysis. Cells were facultatively anaerobic, Gram-stain-negative, non-motile and rod-shaped. Growth occurred at 4-28 °C (optimum at 15 °C), at pH 7.0-8.0 (optimum at 7.0) and with 0-0.6 % (w/v) NaCl (optimum, no NaCl). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S14-88T formed a lineage within the genus Mucilaginibacter. The 16S rRNA gene sequence similarity between strain S14-88T and the type strains of related species ranged from 92.2 to 96.5 %, and the 16S rRNA gene sequence of S14-88T showed highest similarity of 96.5 % to Mucilaginibacter soyangensis HME6664T. The major cellular fatty acids of strain S14-88T were iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The major respiratory quinone was menaquinone MK-7, and the main polar lipid was phosphatidylethanolamine. The DNA G+C content of strain S14-88T was 42.3 mol%. On the basis of the evidence presented in this study, strain S14-88T is considered to represent a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter antarcticus sp. nov. is proposed. The type strain is S14-88T (=CCTCC AB 2015321T=KCTC 52232T).