Structural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism.

Ribonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the ß-CASP and the ß-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.

A bibliometric and visualization study of global research trends in sacral Tarlov cyst from 2000 to 2022.

Background: Symptomatic sacral Tarlov cyst (STC) exerts a significant negative impact on the patient's quality of life, highlighting the significance of the increasing number of studies on STC. However, bibliometric analyses in this research field are scarce. Thus, this study aims to provide a comprehensive knowledge structure and identify the research trends of STC through bibliometrics. Methods: Articles related to STC from 2000 to 2022 were sourced from the Web of Science Core Collection database. VOSviewer 1.6.16, CiteSpace 6.1.6, GraphPad Prism 8.2.1 and R-package "bibliometrix" were used to analyse the data and generate knowledge maps. Results: A total of 930 studies on STC from 2000 to 2022 were included. The findings revealed a consistent yet upward trend in the number of annual publications in this field. The United States, China and Turkey were the most prolific and influential countries contributing to this field, with the University of Illinois, the University of Maryland and the National Institute of Standards & Technology being the most notable research institutions. Key journals include World Neurosurgery [Impact Factor (IF) = 2.210], Journal of Vascular Surgery (IF = 4.860) and Journal of Neurosurgery-Spine (IF = 3.467). Additionally, Tarlov Mj, Tarlov E and Zachariah Mr exhibit the highest number of publications, making them the leading authors in this field. A twenty-year retrospection of research trends using keyword analysis reveals four principal directions, namely "definition", "pathogenesis", "diagnosis" and "treatment". Currently, therapeutic surgical intervention is the key treatment for this disease, with future treatments primarily hinging on minimally invasive methodologies rooted in microendoscopic and endoscopic techniques. Conclusion: This pioneering, comprehensive scientific bibliometric study provides a holistic summary of STC research trends and hot spots spanning the past 22 years. The results identify existing research frontiers and chart maps for future studies, serving as a valuable reference for scholars vested in this field.

A new mechanism of the interfacial water film dominating low ice friction.

It is generally accepted that ice is slippery due to an interfacial water film wetting the ice surface. Despite the current progress in research, the mechanism of low ice friction is not clear, and especially little is known about the behavior of this surface water film under shear and how the sheared interfacial water film influences ice friction. In our work, we investigated the ordering and diffusion coefficient of the interfacial water film and the friction of ice sliding on an atomically smooth solid substrate at the atomic level using molecular dynamics simulations. There are two layers of water molecules at the ice-solid interface that exhibit properties very different from bulk ice. The ice-adjacent water layer is ice-like, and the solid-adjacent water layer is liquid-like. This liquid-like layer behaves in the manner of "confined water," with high viscosity while maintaining fluidity, leading to the slipperiness of the ice. Furthermore, we found that the interfacial water exhibits shear thinning behavior, which connects the structure of the interfacial water film to the coefficient of friction of the ice surface. We propose a new ice friction mechanism based on shear thinning that is applicable to this interfacial water film structure.

Toward a Multifunctional Light-Driven Biomimetic Mudskipper-Like Robot for Various Application Scenarios.

The systematicness, flexibility, and complexity of natural biological organisms are a constant stream of inspiration for researchers. Therefore, mimicking the natural intelligence system to develop microrobotics has attracted broad interests. However, developing a multifunctional device for various application scenarios has great challenges. Herein, we present a bionic multifunctional actuation device─a light-driven mudskipper-like actuator that is composed of a porous silicone elastomer and graphene oxide. The actuator exhibits a reversible and well-integrated response to near-infrared (NIR) light due to the photothermal-induced contractile stress in the actuation film, which promotes generation of cyclical and rapid locomotion upon NIR light being switched on and off, such as bending in air and crawling in liquid. Furthermore, through rational device design and modulation of light, the mechanically versatile device can float and swim controllably following a predesigned route at the liquid/air interface. More interestingly, the actuator can jump from liquid medium to air with an extremely short response time (400 ms), a maximum speed of 2 m s-1, and a height of 14.3 cm under the stimulation of near-infrared light. The present work possesses great potential in the applications of bioinspired actuators in various fields, such as microrobots, sensors, and locomotion.

Molecular Engineering Super-Robust Dry/Wet Adhesive with Strong Interface Bonding and Excellent Mechanical Tolerance.

Despite the fact that synthetic adhesives have achieved great progress, achieving robust dry/wet adhesion under harsh operating environments is still challenging. Herein, inspired from the extraordinary adhesion mechanism of nature mussel protein adhesive, the balanced design concept of co-adhesion and interfacial adhesion is proposed to prepare one kind of novel copolymer adhesive of [poly(dopamine methacrylamide-co-methoxethyl acrylate-co-adamantane-1-carboxylic acid 2-(2-methyl-acryloyloxy)-ethyl ester)] [p(DMA-co-MEA-co-AD)], named as super-robust adhesive (SRAD). The SRAD exhibits ultra-high interface bonding strengths in air (∼7.66 MPa) and underwater (∼2.78 MPa) against an iron substrate. Especially, a greatly tough and stable adhesion strength (∼2.11 MPa) can be achieved after immersing the bonded sample in water for half a year. Furthermore, the SRAD demonstrates surprising wet bonding robustness/tolerance even encountering harsh conditions such as fluid shearing, dynamic loading, and cyclic mechanical fretting. The great advantages of SRAD, such as strong interface bonding, stable wet adhesion underwater, and good mechanical tolerance, makes it demonstrate huge application potential in engineering sealants and underwater adhesion.

Supramolecular assembly inspired molecular engineering to dynamically tune non-Newtonian fluid:from quasi-static flowability-free to shear thickening.

Shear thickening fluids (STFs) have been the research focus for decades because of the prospect as a damping ingredient. However, their inherent liquid character confines their practical applications. In this work, inspired by the assembly engineering, novel gelatinous shear thickening fluids (GSTFs) are fabricated by integrating low molecular weight gelators (LMWGs) into STFs and investigated by rheological experiments. The results show that the apparent performances of GSTFs are determined by the LMWGs content. LMWGs inside GSTFs can assemble into three-dimensional network that can constraint the flowability of liquid molecular and their content dominate the density and strength of assembly network. At a moderate content, GSTFs exhibit desired properties with restricted quasi-static flowability and almost undamaged dynamic shear thickening character. While a higher content will disappear shear thickening and a lower content cannot gelate STFs. Besides, three different LMWGs are employed to gelate STFs and all they can gelate STFs in spite of the distinct minimum gelation concentration, indicating the universality for GSTFs preparation and the superiority of a reasonable molecular structure of LMWGs. Further, the temperature sweep experiments suggest that GSTFs can endure higher temperature without flowing due to its higher gel-sol transition temperature. Basing on these advanced mechanical properties, we believe that the GSTFs with more expected characters have significance for the study of non-Newtonian fluids and will broaden the special application field of STFs.

Novel Structures of Type 1 Glyceraldehyde-3-phosphate Dehydrogenase from Escherichia coli Provide New Insights into the Mechanism of Generation of 1,3-Bisphosphoglyceric Acid.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a highly conserved enzyme involved in the ubiquitous process of glycolysis and presents a loop (residues 208-215 of Escherichia coli GAPDH) in two alternative conformations (I and II). It is uncertain what triggers this loop rearrangement, as well as which is the precise site from which phosphate attacks the thioacyl intermediate precursor of 1,3-bisphosphoglycerate (BPG). To clarify these uncertainties, we determined the crystal structures of complexes of wild-type GAPDH (WT) with NAD and phosphate or G3P, and of essentially inactive GAPDH mutants (C150S, H177A), trapping crystal structures for the thioacyl intermediate or for ternary complexes with NAD and either phosphate, BPG, or G3P. Analysis of these structures reported here lead us to propose that phosphate is located in the "new Pi site" attacks the thioester bond of the thioacyl intermediate to generate 1,3-bisphosphoglyceric acid (BPG). In the structure of the thioacyl intermediate, the mobile loop is in conformation II in subunits O, P, and R, while both conformations coexist in subunit Q. Moreover, only the Q subunit hosts bound NADH. In the R subunit, only the pyrophosphate part of NADH is well defined, and NADH is totally absent from the O and P subunits. Thus, the change in loop conformation appears to occur after NADH is produced, before NADH is released. In addition, two new D-glyceraldehyde-3-phosphate (G3P) binding forms are observed in WT.NAD.G3P and C150A+H177A.NAD.G3P. In summary, this paper improves our understanding of the GAPDH catalytic mechanism, particularly regarding BPG formation.

Effect of Electric Potential and Chain Length on Tribological Performances of Ionic Liquids as Additives for Aqueous Systems and Molecular Dynamics Simulations.

As pure lubricants, ILs performed very well by forming the classical self-assembly bilayer at the sliding interface. The interface mechanism is still not clear in a very polar, e.g., water-based lubricating system. In this work, the interfacial absorption and tribological behavior of carboxylic alkanolamine ionic liquids (CAILs) serving as aqueous lubricating additives were studied by applying positive and negative potentials on the friction pair, accompanied by the comprehensive discussion of data from critical micelle concentration, quartz crystal microbalance, ECR, and MD results. The results reveal that the adsorption behavior, unexpectedly, was affected by the high polarity of H2O, where a less dense double-layer structure is observed at the interface by model imitation. Conversely, the monomolecular adsorption layer constructed electrostatically between the polar head (-COO-) and the positive base dominates the tribofilm. Meanwhile, the cations are partially accumulating around anions in the presence of static electricity, which does not form a neat and dense one-to-one corresponding cation-anion pair. In the solution, the IL maintains a state of dissociation and minor agglomeration. Furthermore, an increase in alkyl chains contributes to the thickness of the protective film generated by CAILs on the sliding asperity. Eventually, the synergistic effect from physical adsorption and the tribochemical reaction is responsible for excellent lubricity and antiwear performance of CAILs.

Free-electron-driven beam-scanning terahertz radiation.

A beam-scanning terahertz (THz) radiation mechanism in a free-electron-driven grating system is proposed for THz applications. By loading a period-asynchronous rod array above the grating, the spoof surface plasmon (SSP) originally excited by the electron changes its radiation characteristics owing to the rod-induced Brillouin zone folding effect. The rod array functions as an antenna and converts the SSP into a spatial coherent THz radiation. The radiation frequency and direction can be precisely controlled by the electron energy. The field intensity of the radiation is increased approximately 20 times compared with that of the conventional Smith-Purcell radiation in the same frequency range. In addition, a microwave-band scaling prototype is fabricated and the frequency-controlled radiation is measured. Excellent agreement between the experimental and simulated results is obtained. This study paves the way for the development of on-chip THz sources for advanced communication and detection applications.

Structural and Functional Insights Into CmGH1, a Novel GH39 Family ß-Glucosidase From Deep-Sea Bacterium.

Glucosidases play key roles in many diseases and are limiting enzymes during cellulose degradation, which is an important part of global carbon cycle. Here, we identified a novel ß-glucosidase, CmGH1, isolated from marine bacterium Croceicoccus marinus E4A9T. In spite of its high sequence and structural similarity with ß-xylosidase family members, CmGH1 had enzymatic activity toward p-nitrophenyl-ß-D-glucopyranoside (p-NPG) and cellobiose. The K m and K cat values of CmGH1 toward p-NPG were 0.332 ± 0.038 mM and 2.15 ± 0.081 min-1, respectively. CmGH1 was tolerant to high concentration salts, detergents, as well as many kinds of organic solvents. The crystal structure of CmGH1 was resolved with a 1.8 Å resolution, which showed that CmGH1 was composed of a canonical (α/ß)8-barrel catalytic domain and an auxiliary ß-sandwich domain. Although no canonical catalytic triad residues were found in CmGH1, structural comparison and mutagenesis analysis suggested that residues Gln157 and Tyr264 of CmGH1 were the active sites. Mutant Q157E significantly increased its hydrolase activity up to 15-fold, whereas Y264E totally abolished its enzymatic activity. These results might provide new insights into understanding the different catalytic mechanism during evolution for ß-glucosidases and ß-xylosidases.

Significant and stable drag reduction with air rings confined by alternated superhydrophobic and hydrophilic strips.

Superhydrophobic surfaces have the potential to reduce the viscous drag of liquids by significantly decreasing friction at a solid-liquid interface due to the formation of air layers between solid walls and interacting liquids. However, the trapped air usually becomes unstable due to the finite nature of the domain over which it forms. We demonstrate for the first time that a large surface energy barrier can be formed to strongly pin the three-phase contact line of air/water/solid by covering the inner rotor of a Taylor-Couette flow apparatus with alternating superhydrophobic and hydrophilic circumferential strips. This prevents the disruption of the air layer, which forms stable and continuous air rings. The drag reduction measured at the inner rotor could be as much as 77.2%. Moreover, the air layers not only significantly reduce the strength of Taylor vortexes but also influence the number and position of the Taylor vortex pairs. This has strong implications in terms of energy efficiency maximization for marine applications and reduction of drag losses in, for example, fluid transport in pipelines and carriers.

Identification of residues important for the activity of aldehyde-deformylating oxygenase through investigation into the structure-activity relationship.

BACKGROUND: Aldehyde-deformylating oxygenase (ADO) is a key enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, cADO (cyanobacterial ADO) showed extreme low activity with the k cat value below 1 min-1, which would limit its application in biofuel production. To identify the activity related key residues of cADO is urgently required. RESULTS: The amino acid residues which might affect cADO activity were identified based on the crystal structures and sequence alignment of cADOs, including the residues close to the di-iron center (Tyr39, Arg62, Gln110, Tyr122, Asp143 of cADO-1593), the protein surface (Trp 178 of cADO-1593), and those involved in two important hydrogen bonds (Gln49, Asn123 of cADO-1593, and Asp49, Asn123 of cADO-sll0208) and in the oligopeptide whose conformation changed in the absence of the di-iron center (Leu146, Asn149, Phe150 of cADO-1593, and Thr146, Leu148, Tyr150 of cADO-sll0208). The variants of cADO-1593 from Synechococcus elongatus PCC7942 and cADO-sll0208 from Synechocystis sp. PCC6803 were constructed, overexpressed, purified and kinetically characterized. The k cat values of L146T, Q49H/N123H/F150Y and W178R of cADO-1593 and L148R of cADO-sll0208 were increased by more than two-fold, whereas that of R62A dropped by 91.1%. N123H, Y39F and D143A of cADO-1593, and Y150F of cADO-sll0208 reduced activities by ≤ 20%. CONCLUSIONS: Some important amino acids, which exerted some effects on cADO activity, were identified. Several enzyme variants exhibited greatly reduced activity, while the k cat values of several mutants are more than two-fold higher than the wild type. This study presents the report on the relationship between amino acid residues and enzyme activity of cADOs, and the information will provide a guide for enhancement of cADO activity through protein engineering.

Identifying two regimes of slip of simple fluids over smooth surfaces with weak and strong wall-fluid interaction energies.

The slip behavior of simple fluids over atomically smooth surfaces was investigated in a wide range of wall-fluid interaction (WFI) energies at low shear rates using non-equilibrium molecular dynamics simulations. The relationship between slip and WFI shows two regimes (the strong-WFI and weak-WFI regimes): as WFI decreases, the slip length increases in the strong-WFI regime and decreases in the weak-WFI regime. The critical value of WFI energy that separates these regimes increases with temperature, but it remains unaffected by the driving force. The mechanism of slip was analyzed by examining the density-weighted average energy barrier (ΔE¯) encountered by fluid atoms in the first fluid layer (FFL) during their hopping between minima of the surface potential. We demonstrated that the relationship between slip and WFI can be rationalized by considering the effect of the fluid density distribution in the FFL on ΔE¯ as a function of the WFI energy. Moreover, the dependence of the slip length on WFI and temperature is well correlated with the exponential factor exp(-ΔE¯/(kBT)), which also determines the critical value of WFI between the strong-WFI and weak-WFI regimes.

Effects of viscous heating and wall-fluid interaction energy on rate-dependent slip behavior of simple fluids.

Molecular dynamics simulations are used to investigate the rate and temperature dependence of the slip length in thin liquid films confined by smooth, thermal substrates. In our setup, the heat generated in a force-driven flow is removed by the thermostat applied on several wall layers away from liquid-solid interfaces. We found that for both high and low wall-fluid interaction (WFI) energies, the temperature of the fluid phase rises significantly as the shear rate increases. Surprisingly, with increasing shear rate, the slip length approaches a constant value from above for high WFI energies and from below for low WFI energies. The two distinct trends of the rate-dependent slip length are rationalized by examining S(G_{1}), the height of the main peak of the in-plane structure factor of the first fluid layer (FFL) together with D_{WF}, which is the average distance between the wall and FFL. The results of numerical simulations demonstrate that reduced values of the structure factor, S(G_{1}), correlate with the enhanced slip, while smaller distances D_{WF} indicate that fluid atoms penetrate deeper into the surface potential leading to larger friction and smaller slip. Interestingly, at the lowest WFI energy, the combined effect of the increase of S(G_{1}) and decrease of D_{WF} with increasing shear rate results in a dramatic reduction of the slip length.

Structure-oriented substrate specificity engineering of aldehyde-deformylating oxygenase towards aldehydes carbon chain length.

BACKGROUND: Aldehyde-deformylating oxygenase (ADO) is an important enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, ADO exhibits quite low chain-length specificity with respect to the substrates ranging from C4 to C18 aldehydes, which is not suitable for producing fuels with different properties or different chain lengths. RESULTS: Based on the crystal structures of cADOs (cyanobacterial ADO) with substrate analogs bound, some amino acids affecting the substrate specificity of cADO were identified, including the amino acids close to the aldehyde group and the hydrophobic tail of the substrate and those along the substrate channel. Using site-directed mutagenesis, selected amino acids were replaced with bulky ones introducing steric hindrance to the binding pocket via large functional groups. All mutants were overexpressed, purified and kinetically characterized. All mutants, except F87Y, displayed dramatically reduced activity towards C14,16,18 aldehydes. Notably, the substrate preferences of some mutants towards different chain-length substrates were enhanced: I24Y for n-heptanal, I27F for n-decanal and n-dodecanal, V28F for n-dodecanal, F87Y for n-decanal, C70F for n-hexanal, A118F for n-butanal, A121F for C4,6,7 aldehydes, V184F for n-dodecanal and n-decanal, M193Y for C6-10 aldehydes and L198F for C7-10 aldehydes. The impact of the engineered cADO mutants on the change of the hydrocarbon profile was demonstrated by co-expressing acyl-ACP thioesterase BTE, fadD and V184F in E. coli, showing that n-undecane was the main fatty alkane. CONCLUSIONS: Some amino acids, which can control the chain-length selectivity of substrates of cADO, were identified. The substrate specificities of cADO were successfully changed through structure-guided protein engineering, and some mutants displayed different chain-length preference. The in vivo experiments of V184F in genetically engineered E. coli proved the importance of engineered cADOs on the distribution of the fatty alkane profile. The results would be helpful for the production of fatty alk(a/e)nes in cyanobacteria with different properties.

Three-Dimensional Structure of a Simple Liquid at a Face-Centered-Cubic (001) Solid Surface Interface.

A liquid in the vicinity of a solid-liquid interface (SLI) may exhibit complex structures. In this study, we used molecular dynamics simulations demonstrating for the first time that the liquid adjacent to the SLI can have a two-level structure in some cases: a major structure and a minor structure. Through a time-averaging process of molecular motions, we identified the type of the liquid structure by calculating positions of the maximum liquid density in three spatial dimensions, and these positions were found to distribute in many dispersed zones (called high-density zones (HDZs)). The major structure appears throughout the SLI, while the minor structure only occurs significantly within the third layer. Instead of the previously reported body-centered cubic (BCC) or face-centered-cubic (FCC) types, the major structure was found to show a body-centered tetragonal (BCT) type. The adjacent HDZs are connected by specific junctions, demonstrating that atoms diffuse along some particular high probability paths from one HDZ to another. By considering the three-dimensional liquid density distribution from the continuum point of view, more complete details of the structure and diffusive behavior of liquids in the SLI are also possible to be revealed.