Structural Insights of a cis-Epoxysuccinate Hydrolase Facilitate the Development of Robust Biocatalysts for the Production of l-(+)-Tartrate.

l-(+)-Tartaric acid plays important roles in various industries, including pharmaceuticals, foods, and chemicals. cis-Epoxysuccinate hydrolases (CESHs) are crucial for converting cis-epoxysuccinate to l-(+)-tartrate in the industrial production process. There is, however, a lack of detailed structural and mechanistic information on CESHs, limiting the discovery and engineering of these industrially relevant enzymes. In this study, we report the crystal structures of RoCESH and KoCESH-l-(+)-tartrate complex. These structures reveal the key amino acids of the active pocket and the catalytic triad residues and elucidate a dynamic catalytic process involving conformational changes of the active site. Leveraging the structural insights, we identified a robust BmCESH (550 ± 20 U·mg-1) with sustained catalytic activity even at a 3 M substrate concentration. After six batches of transformation, immobilized cells with overexpressed BmCESH maintained 69% of their initial activity, affording an overall productivity of 200 g/L/h. These results provide valuable insights into the development of high-efficiency CESHs and the optimization of biotransformation processes for industrial uses.

Grain Boundary Defect Engineering in Rutile Iridium Oxide Boosts Efficient and Stable Acidic Water Oxidation.

Proton exchange membrane water electrolysis (PEMWE) is considered a promising technology for coupling with renewable energy sources to achieve clean hydrogen production. However, constrained by the sluggish kinetics of the anodic oxygen evolution reaction (OER) and the acidic abominable environment render the grand challenges in developing the active and stable OER electrocatalyst, leading to low efficiency of PEMWE. Herein, we develop the rutile-type IrO2 nanoparticles with abundant grain boundaries and the continuous nanostructure through the joule heating and sacrificial template method. The optimal candidate (350-IrO2) demonstrates remarkable electrocatalytic activity and stability during the OER, presenting a promising advancement for efficient PEMWE. DFT calculations verified that grain boundaries can modulate the electronic structure of Ir sites and optimize the adsorption of oxygen intermediates, resulting in the accelerated kinetics. 350-IrO2 affords a rapid OER process with 20 times higher mass activity (0.61 A mgIr -1) than the commercial IrO2 at 1.50 V vs. RHE. Benefiting from the reduced overpotential and the preservation of the stable rutile structure, 350-IrO2 exhibits the stability of 200 h test at 10 mA cm-2 with only trace decay of 11.8 mV. Moreover, the assembled PEMWE with anode 350-IrO2 catalyst outputs the current density up to 2 A cm-2 with only 1.84 V applied voltage, long-term operation for 100 h without obvious performance degradation at 1 A cm-2.

Effect of continuous measurement and adjustment of endotracheal tube cuff pressure on postoperative sore throat in patients undergoing gynecological laparoscopic surgery: a randomized controlled trial.

BACKGROUND: Postoperative sore throat (POST) is a common complication following endotracheal tube removal, and effective preventive strategies remain elusive. This trial aimed to determine whether actively regulating intraoperative cuff pressure below the tracheal capillary perfusion pressure threshold could effectively reduce POST incidence in patients undergoing gynecological laparoscopic procedures. METHODS: This single-center, randomized controlled superiority trial allocated 60 patients scheduled for elective gynecological laparoscopic procedures into two groups: one designated for cuff pressure measurement and adjustment (CPMA) group, and a control group where only cuff pressure measurement was conducted without any subsequent adjustments. The primary outcome was POST incidence at rest within 24 h post-extubation. Secondary outcomes included cough, hoarseness, postoperative nausea and vomiting (PONV) incidence, and post-extubation pain severity. RESULTS: The incidence of sore throat at rest within 24 h after extubation in the CPMA group was lower than in the control group, meeting the criteria for statistically significant superiority based on a one-sided test (3.3% vs. 26.7%, P < 0.025). No statistically significant differences were observed in cough, hoarseness, or pain scores within 24 h post-extubation between the two groups. However, the CPMA group had a higher incidence of PONV compared to the control group. Additionally, the control group reported higher sore throat severity scores within 24 h post-extubation. CONCLUSIONS: Continuous monitoring and maintenance of tracheal tube cuff pressure at 18 mmHg were superior to merely monitoring without adjustment, effectively reducing the incidence of POST during quiet within 24 h after tracheal tube removal in gynecological laparoscopic surgery patients. TRIAL REGISTRATION: The study was registered at www.chictr.org.cn (ChiCTR2200064792) on 18/10/2022.

Resveratrol Attenuates Ankylosing Spondylitis in Mice by Inhibiting the TLR4/NF-κB/NLRP3 Pathway and Regulating Gut Microbiota.

Ankylosing spondylitis (AS) is an autoimmune disease associated with disturbed gut microbiota. Currently, the treatments and outcomes of AS are not satisfactory. It is reported that resveratrol (RES) is a major phytoalexin with anti-inflammatory, antibacterial and some other pharmacological effects. However, there are no studies on the role of RES in AS. Therefore, this study aimed to explore the effect and mechanism of RES on AS. Proteoglycan and complete freund's adjuvant were used to conduct an AS mouse model, and then the AS mice were gavaged with RES (20 mg/kg and 50 mg/kg) daily for 4 weeks. Subsequently, the effect of RES on AS mice was assessed by detecting disease severity, inflammatory cytokines, NLRP3 inflammasome, TLR4/NF-κB pathway, intestinal mucosal barrier function, intestinal microbial barrier function. The assessment results indicated that RES could significantly relieve progression and severity of AS, inhibit the expression of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, interleukin-17A, interferon-γ), and promote the expression of anti-inflammatory cytokines (interleukin-4). RES intervention caused the inhibition of NLRP3 inflammasome and TLR4/NF-κB pathway. In terms of intestinal barrier function, experimental results found RES increased zonula occludens-1 and occludin expression, and additionally, changed the composition of the gut microbiota by increasing levels of Lactobacillus and Bifidobacterium and reducing levels of Enterococcus faecalis and Escherichia coli. Collectively, RES protects PG-induced AS mice by inhibiting inflammatory responses and TLR4/NF-κB/NLRP3 pathway, restoring intestinal mucosal barrier function, and regulating the composition of the gut microbiota. In other words, RES is a potential candidate for the treatment of AS.

Incidence of accidental falls and development of a fall risk prediction model among elderly patients with diabetes mellitus: A prospective cohort study.

AIMS: To investigate the incidence of accidental falls and develop a fall risk prediction tool in elderly patients with diabetes mellitus. BACKGROUND: The risk of fall in elderly patients with diabetes is higher than that in the general elderly, there is fewer fall assessment tools for elderly patients with diabetes. DESIGN: A prospective cohort study. METHODS: Between June and September 2019, a total of 1007 elderly patients with diabetes were enrolled from a tertiary specialist diabetes hospital in Tianjin and were prospectively followed up for 6 months to determine outcomes of accidental falls through telephone. Demographic and diseases related factors were collected at baseline. Incidence of falls was investigated, and a nomogram was developed based on logistic regression model. SPSS 21.0 and R 3.6.3 were used to analyse the data. The article was reported in accordance with STROBE guidelines. RESULTS: Among 1007 elderly patients, 950 finished the follow-up. A total of 133 falls occurred in 93 patients during the follow-up period, with a fall rate of 9.79%. Diabetic peripheral neuropathy, walking aids, depression, fall history, fatigue and sex were independent predictors of accidental fall in diabetes elderly patients. The sensitivity and specificity of the predictive model were 73.12% and 52.63%, respectively, and a fall risk prediction nomogram was developed based on the regression model. CONCLUSIONS: A nomogram including 6 easily available prediction factors (diabetic peripheral neuropathy, walking aids, depression, fall history within 1 year, fatigue, sex) was developed, and it can be used in safety management among Chinese elderly patients diagnosed with diabetes. RELEVANCE TO CLINICAL PRACTICE: Nomogram can be used to identify diabetic elderly patients at high risk of accidental falls.

Engineering the Substrate Specificity of a P450 Dimerase Enables the Collective Biosynthesis of Heterodimeric Tryptophan-Containing Diketopiperazines.

Heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are an important class of bioactive secondary metabolites. Biosynthesis offers a practical opportunity to access their bioactive structural diversity, however, it is restricted by the limited substrate scopes of the HTDKPs-forming P450 dimerases. Herein, by genome mining and investigation of the sequence-product relationships, we unveiled three important residues (F387, F388 and E73) in these P450s that are pivotal for selecting different diketopiperazine (DKP) substrates in the upper binding pocket. Engineering these residues in NasF5053 significantly expanded its substrate specificity and enabled the collective biosynthesis, including 12 self-dimerized and at least 81 cross-dimerized HTDKPs. Structural and molecular dynamics analysis of F387G and E73S revealed that they control the substrate specificity via reducing steric hindrance and regulating substrate tunnels, respectively.

Millefeuille-Inspired Thermal Interface Materials based on Double Self-Assembly Technique for Efficient Microelectronic Cooling and Electromagnetic Interference Shielding.

Owing to the increasing power density of miniaturized and high-frequency electronic devices, flexible thermal interface materials (TIMs) with the electromagnetic interference (EMI) shielding property are in urgent demand to maintain the system performance and reliability. Recently, carbon-based TIMs receive considerable attention due to the ultrahigh intrinsic thermal conductivity (TC). However, the large-scale production of such TIMs is restricted by some technical difficulties, such as production-induced defects of graphite sheets, poor microstructure architecture within the matrix, and nonnegligible interfacial thermal resistance result from the strong phono scattering. In this work, inspired by the structure and production process of millefeuille cakes, a unique double self-assembly strategy for fabricating ultrahigh thermal conductive TIMs with superior EMI shielding performance is demonstrated. The percolating and oriented multilayered microstructure enables the TIM to exhibit an ultrahigh in-plane TC of 233.67 W m-1 K-1 together with an outstanding EMI shielding effectiveness of 79.0 dB (at 12.4 GHz). In the TIM evaluation system, a nearly 45 °C decrease is obtained by this TIM when compared to the commercial material. The obtained TIM achieves the desired balance between thermal conduction and EMI shielding performance, indicating broad prospects in the fields of military applications and next-generation thermal management systems.

Protein-bound calcium phosphate in uremic rat serum: a quantitative study.

Protein-bound calcium (prCa) constitutes about 40% of serum total calcium, in which albumin is the most dominant protein. Given the chemical interaction between calcium and phosphate (Pi), the increased serum Pi in chronic kidney disease may cause changes in the composition and structure of the prCa fraction. Here, we report the phosphate binding on the protein-bound calcium in uremic rat serum. Using adenine-fed rats as a uremic model, we separated the calcium and phosphate fractions in rat serum by ultrafiltration, and found that the level of protein-bound phosphate (prPi) in the uremic serum was markedly higher than in control. The elevated prPi level was comparable to the prCa level, consistent with the presence of protein-bound calcium phosphate pr(Ca)j-m(CaPi)m. We then confirmed its presence by ex vivo X-ray absorption near-edge structure spectroscopy, revealing the discrete state of the calcium phosphate clusters associated with protein. Finally, in a quantitative investigation using Ca- and Pi-boosted serum, we discovered the threshold concentration for the Pi binding on prCa, and determined the binding constant. The threshold, while preventing Pi from binding to prCa in normal condition, allows the reaction to take place in hyperphosphatemia conditions. The protein-bound calcium phosphate could act as a link between the metabolism of serum proteins and the homeostasis of phosphate and calcium, and it deserves further investigation whether the molar ratio of (prPi/prCa)⋅100% may serve as a serum index of the vascular calcification status in chronic kidney disease.

Correction to: Protein-bound calcium phosphate in uremic rat serum: a quantitative study.

In the original article, few equations and units were published incorrectly.

Ex vivo detection of calcium phosphate and calcium carbonate in rat blood serum.

The total calcium (tCa) in blood serum comprises free Ca2+ ions (fCa), protein-bound calcium (prCa), and complexed calcium by small anions (cCa). The cCa fraction, in addition to fCa, has been indicated to have some physiological activity. However, there is little evidence for the structure of its constituents. Here we report an ex vivo detection of the cCa constituents by synchrotron X-ray absorption near-edge structure spectroscopy. We collected the data directly on rat blood serum and, by making use of the reference samples, derived a spectrum that exhibits the features of cCa constituents. Among the features are those of the complexes of calcium phosphate and calcium carbonate. The detected complexes in the cCa fraction are mainly Ca(η2-HPO4)(H2O)4 and Ca(η1-HCO3)(H2O)5+, in which HPO42- and HCO3- serve as bidentate and unidentate ligands, respectively. The remained H2O molecules on the coordination sphere of Ca2+ enable these complexes to behave partially like aquated Ca2+ ions in protein-binding. Besides, as the dominant part of prCa, albumin-bound calcium (albCa) exhibits a spectrum that closely resembles that of fCa, indicating weak interactions between the protein carboxyl groups and calcium. The weak-bound cCa and albCa, along with fCa and the relevant anions, compose a local chemical system that could play a role in maintaining the calcium level in blood.

Ionic-Liquid-Based CO2 Capture Systems: Structure, Interaction and Process.

The inherent structure tunability, good affinity with CO2, and nonvolatility of ionic liquids (ILs) drive their exploration and exploitation in CO2 separation field, and has attracted remarkable interest from both industries and academia. The aim of this Review is to give a detailed overview on the recent advances on IL-based materials, including pure ILs, IL-based solvents, and IL-based membranes for CO2 capture and separation from the viewpoint of molecule to engineering. The effects of anions, cations and functional groups on CO2 solubility and selectivity of ILs, as well as the studies on degradability of ILs are reviewed, and the recent developments on functionalized ILs, IL-based solvents, and IL-based membranes are also discussed. CO2 separation mechanism with IL-based solvents and IL-based membranes are explained by combining molecular simulation and experimental characterization. Taking into consideration of the applications and industrialization, the recent achievements and developments on the transport properties of IL fluids and the process design of IL-based processes are highlighted. Finally, the future research challenges and perspectives of the commercialization of CO2 capture and separation with IL-based materials are posed.

Pseudo-equilibrium equation of calcium phosphate precipitation from aqueous solution.

An X-ray amorphous phase is frequently present at the early stage of calcium phosphate crystallization, and the relevant solution chemistry is essential for understanding the mechanism of reaction. Here, we report a quantitative study of a series of reaction systems at pseudo-equilibrium states. We determined the composition of solutions and the quantities of the precipitate samples, and characterized the long- and short-range order of the precipitate using X-ray diffraction and synchrotron X-ray absorption near-edge structure spectroscopy, respectively. We found that, in a particle with multiple structural units, only a fraction of the units was able to reach pseudo-equilibrium with the solution composition, which represents the average number of surficial clusters per unit. These findings enabled us to propose a general form of the equilibrium constant equation. The equation fits the pseudo-equilibrium data well, and it converts to the "solubility product (Ksp)" and the conventional "reaction quotient" in two limit cases, respectively. Further, using a cube model, we derived a "particle equation" that reveals the connection between the particle structure and the form of equilibrium constant equation. The dependency of the form of pseudo-equilibrium equation on the structure and size of the precipitate reveals a fundamental relation in chemistry, and its applicability remains to be examined in other reaction systems, such as those involving nanocrystals and porous materials.

Generating Defect-Rich Bismuth for Enhancing the Rate of Nitrogen Electroreduction to Ammonia.

The electrochemical N2 fixation, which is far from practical application in aqueous solution under ambient conditions, is extremely challenging and requires a rational design of electrocatalytic centers. We observed that bismuth (Bi) might be a promising candidate for this task because of its weak binding with H adatoms, which increases the selectivity and production rate. Furthermore, we successfully synthesized defect-rich Bi nanoplates as an efficient noble-metal-free N2 reduction electrocatalyst via a low-temperature plasma bombardment approach. When exclusively using 1 H NMR measurements with N2 gas as a quantitative testing method, the defect-rich Bi(110) nanoplates achieved a 15 NH3 production rate of 5.453 µg mgBi -1 h-1 and a Faradaic efficiency of 11.68 % at -0.6 V vs. RHE in aqueous solution at ambient conditions.

In Situ Coupling of Strung Co4N and Intertwined N-C Fibers toward Free-Standing Bifunctional Cathode for Robust, Efficient, and Flexible Zn-Air Batteries.

Flexible power sources with high energy density are crucial for the realization of next-generation flexible electronics. Theoretically, rechargeable flexible zinc-air (Zn-air) batteries could provide high specific energy, while their large-scale applications are still greatly hindered by high cost and resources scarcity of noble-metal-based oxygen evolution reaction (OER)/oxygen reduction reaction (ORR) electrocatalysts as well as inferior mechanical properties of the air cathode. Combining metallic Co4N with superior OER activity and Co-N-C with perfect ORR activity on a free-standing and flexible electrode could be a good step for flexible Zn-air batteries, while lots of difficulties need to be overcome. Herein, as a proof-of-concept experiment, we first propose a strategy for in situ coupling of strung Co4N and intertwined N-C fibers, by pyrolyzation of the novel pearl-like ZIF-67/polypyrrole nanofibers network rooted on carbon cloth. Originating from the synergistic effect of Co4N and Co-N-C and the stable 3D interconnected conductive network structure, the obtained free-standing and highly flexible bifunctional oxygen electrode exhibits excellent electrocatalytic activity and stability for both OER and ORR in terms of low overpotential (310 mV at 10 mA cm(-2)) for OER, a positive half-wave potential (0.8 V) for ORR, and a stable current density retention for at least 20 h, and especially, the obtained Zn-air batteries exhibit a low discharge-charge voltage gap (1.09 V at 50 mA cm(-2)) and long cycle life (up to 408 cycles). Furthermore, the perfect bendable and twistable and rechargeable properties of the flexible Zn-air battery particularly make it a potentially power portable and wearable electronic device.

Experimental demonstration of compact spoof localized surface plasmons.

In recent years, the study of generating and detecting localized surface plasmons (LSPs) has been expanded from the optical regime to microwave regime. In this Letter, the compact spoof LSPs are introduced through both numerical simulations and near-field measurements. It is observed that the compact LSP structure could effectively reduce the resonant frequency with a stronger resonance strength (GdBsm) and a higher Q-factor. Both electric near-field and surface-current distributions are monitored to examine the resonance processes of the LSP particle.

[Effect of Tripterygium wilfordii glycosides combined with gestrinone on endometriosis and serum cytokine expression].

To study the effect of Tripterygium wilfordii glycosides and gestrinone on endometriosis and serum cytokine expression, 135 cases of endometriosis patients were divided into treatment group(n=69) and control group(n=68). The observation group was orally given with T. wilfordii glycosides, 20 mg, tid, for 4 weeks. Then, the dose decreased to 10 mg/time, tid. T. wilfordii glycosides combined with gestrinone capsule(2.5 mg) were given in the 1st and 4th day of a menstrual cycle. Later, the administration was fixed at two times every week. The course of treatment lasted for 3 months. The control group was treated with gestrinone capsule(according to the same intake method). The serum-related cytokine levels before and after treatment were determined, and the clinical efficacy was observed. The results showed the total effective rate of the observation group was 89.71%, which was obviously higher than that of the control group(74.63%), with statistically significant differences(P<0.05). After treatment, TDS showed varying degrees of decreases, with a better effect in the observation group (P<0.01). Before treatment, serum TGF-ß, IL-10 and IL-4 level had no significant difference. After treatment, all of these cytokines decreased, particularly for the observation decreased(P<0.01). Before and after treatment, serum IL-17 had no obvious difference between the two groups. This study suggested that the integrated traditional Chinese medicine and western medicine has an obvious clinical efficiency in endometriosis. Its mechanism may be related to the effective regulation of cytokines.

A Biodegradable Polydopamine-Derived Electrode Material for High-Capacity and Long-Life Lithium-Ion and Sodium-Ion Batteries.

Polydopamine (PDA), which is biodegradable and is derived from naturally occurring products, can be employed as an electrode material, wherein controllable partial oxidization plays a key role in balancing the proportion of redox-active carbonyl groups and the structural stability and conductivity. Unexpectedly, the optimized PDA derivative endows lithium-ion batteries (LIBs) or sodium-ion batteries (SIBs) with superior electrochemical performances, including high capacities (1818 mAh g(-1) for LIBs and 500 mAh g(-1) for SIBs) and good stable cyclabilities (93 % capacity retention after 580 cycles for LIBs; 100 % capacity retention after 1024 cycles for SIBs), which are much better than those of their counterparts with conventional binders.

Genetic interaction between NS4A and NS4B for replication of Japanese encephalitis virus.

Flavivirus NS4A and NS4B are important membrane proteins for viral replication that are assumed to serve as the scaffold for the formation of replication complexes. We previously demonstrated that a single Lys-to-Arg mutation at position 79 in NS4A (NS4A-K79R) significantly impaired Japanese encephalitis virus (JEV) replication. In this study, the mutant virus was subject to genetic selection to search for the potential interaction between NS4A and other viral components. Sequencing of the recovered viruses revealed that, in addition to an A97E change in NS4A itself, a Y3N compensatory mutation located in NS4B had emerged from independent selections. Mutagenesis analysis, using a genome-length RNA and a replicon of JEV, demonstrated that both adaptive mutations greatly restored the replication defect caused by NS4A-K79R. Our results, for the first time to our knowledge, clearly showed the genetic interaction between NS4A and NS4B, although the mechanism underlying their interaction is unknown.

Inhibition of enterovirus 71 by adenosine analog NITD008.

Enterovirus 71 (EV71) is a major viral pathogen in China and Southeast Asia. There is no clinically approved vaccine or antiviral therapy for EV71 infection. NITD008, an adenosine analog, is an inhibitor of flavivirus that blocks viral RNA synthesis. Here we report that NITD008 has potent antiviral activity against EV71. In cell culture, the compound inhibits EV71 at a 50% effective concentration of 0.67 µM and a 50% cytotoxic concentration of 119.97 µM. When administered at 5 mg/kg in an EV71 mouse model, the compound reduced viral loads in various organs and completely prevented clinical symptoms and death. To study the antiviral mechanism and drug resistance, we selected escape mutant viruses by culturing EV71 with increasing concentrations of NITD008. Resistance mutations were reproducibly mapped to the viral 3A and 3D polymerase regions. Resistance analysis with recombinant viruses demonstrated that either a 3A or a 3D mutation alone could lead to resistance to NITD008. A combination of both 3A and 3D mutations conferred higher resistance, suggesting a collaborative interplay between the 3A and 3D proteins during viral replication. The resistance results underline the importance of combination therapy required for EV71 treatment. Importance: Human enterovirus 71 (EV71) has emerged as a major cause of viral encephalitis in children worldwide, especially in the Asia-Pacific region. Vaccines and antivirals are urgently needed to prevent and treat EV71 infections. In this study, we report the in vitro and in vivo efficacy of NITD008 (an adenosine analog) as an inhibitor of EV71. The efficacy results validated the potential of nucleoside analogs as antiviral drugs for EV71 infections. Mechanistically, we showed that mutations in the viral 3A and 3D polymerases alone or in combination could confer resistance to NITD008. The resistance results suggest an intrinsic interaction between viral proteins 3A and 3D during replication, as well as the importance of combination therapy for the treatment of EV71 infections.

ZnO/ZnS heterostructured nanorod arrays and their efficient photocatalytic hydrogen evolution.

Semiconducting heterostructures have been widely applied in photocatalytic hydrogen evolution due to their variable band gaps and high energy conversion efficiency. As typical semiconducting heterostructures, ZnO/ZnS heterostructured nanorod arrays (HNRAs) have been obtained through a simple anion-exchange process in this work. Structural characterization indicates that the heterostructured nanorods (HNRs) are all composed of hexagonal wurtzite ZnO core and cubic zinc-blende ZnS shell. As expected, the as-obtained one-dimensional heterostructures not only lower the energy barrier but also enhance the separation ability of photogenerated carriers in photocatalytic hydrogen evolution. Through comparisons, it is found that 1D ZnO/ZnS HNRAs exhibit much better performance in photocatalytic hydrogen evolution than 1D ZnO nanorod arrays (NRAs) and 1D ZnS NRAs. The maximum H2 production is 19.2 mmol h(-1) for 0.05 g catalyst under solar-simulated light irradiation at 25 °C and the corresponding quantum efficiency is 13.9 %, which goes beyond the economical threshold of photocatalytic hydrogen evolution technology.