Hydrogen-Bonded Supramolecular Nanotrap Enabling the Interfacial Activation of Hosted Enzymes.

Engineering nanotraps to immobilize fragile enzymes provides new insights into designing stable and sustainable biocatalysts. However, the trade-off between activity and stability remains a long-standing challenge due to the inevitable diffusion barrier set up by nanocarriers. Herein, we report a synergetic interfacial activation strategy by virtue of hydrogen-bonded supramolecular encapsulation. The pore wall of the nanotrap, in which the enzyme is encapsulated, is modified with methyl struts in an atomically precise position. This well-designed supramolecular pore results in a synergism of hydrogen-bonded and hydrophobic interactions with the hosted enzyme, and it can modulate the catalytic center of the enzyme into a favorable configuration with high substrate accessibility and binding capability, which shows up to a 4.4-fold reaction rate and 4.9-fold conversion enhancements compared to free enzymes. This work sheds new light on the interfacial activation of enzymes using supramolecular engineering and also showcases the feasibility of interfacial assembly to access hierarchical biocatalysts featuring high activity and stability simultaneously.

Construction of Hollow Ultrasmall Co3O4 Nanoparticles Immobilized in BN for CO2 Conversion.

Rational design and fabrication of metal-organic framework-derived metal oxide (MO) materials featuring a hollow structure and active support can significantly enhance their catalytic activity for specific reactions. Herein, a series of Co3O4 nanoparticles (NPs) immobilized in boron nitride (denoted as Co3O4@BN) with highly open and precisely controllable structures were constructed by an in situ self-assembly method combined with a controlled annealing process. The obtained Co3O4@BN not only possesses a hollow structure but also shows highly dispersed Co3O4 NPs and high loadings of up to 34.3 wt %. Owing to the ultrafine particle size and high dispersity, the optimized Co3O4@BN exhibits high catalytic activity for the cycloaddition of CO2 to epoxides under mild conditions (i.e., 100 °C and CO2 balloon), resulting in at least 4.5 times higher yields (99%) of styrene carbonate than that of Co3O4 synthesized by the pristine ZIF-67. This strategy sheds light on the rational design of hollow MO materials for various advanced applications.

Discovery of highly functionalized grayanane diterpenoids from the flowers of Rhododendron molle as potent analgesics.

A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1-38), including twelve novel analogues molleblossomins A-L (1-12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2ß,3ß:9ß,10ß-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1-38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure-activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.

Study on preparation of UV-CDs/Zeolite-4A/TiO2 composite photocatalyst coupled with ultraviolet-irradiation and their application of photocatalytic degradation of dyes.

In this work, ultraviolet irradiation was employed to assist in the preparation of a novel photocatalyst composite in the form of carbon dots/zeolite-4A/TiO2, using coal tailings as the source of silicon-aluminum and carbon. The composite was designed for the degradation of methylene blue under 500 W of UV light irradiation. Zeolite-4A was used as a support for the well-dispersed carbon dots and TiO2 nanoparticles. The as-prepared composites were subjected to thorough characterization, confirming the successful formation of zeolite-4A with a cube structure, along with the loading of TiO2 and coal-based CDs in the composites. The experimental results demonstrated that the UV-CZTs nanocomposites exhibited a remarkable removal efficiency of 90.63% within 90 min for MB. The corresponding rate constant was exceptionally high at 0.0331 min-1, surpassing that of the Dark-CZTs and pure TiO2. This significant enhancement was possibly due to the synergistic effect of adsorption photocatalysis of the UV-CZTs, combined with the excellent electron-accepting capabilities of the coal-based CDs, which led to highly improved charge separation. An investigation of the spent photocatalyst's recyclability revealed that it retained a remarkable 82.94% MB removal efficiency after five consecutive cycles, signifying the stability of the composite. Trapping experiments also elucidated the primary reactive species responsible for MB degradation, which were identified as photo-generated holes and ⸱O2- species. By this process, the hydroxyl radicals generated in the system successfully promoted the transformation of coal tailings to coal-based zeolite and coal-based CDs. Coal-based zeolite served as an excellent carrier of titanium dioxide, which improved its dispersibility. The inhibition of e--h+ recombination of titanium dioxide by introducing coal-based CDs improved the photocatalytic ability of titanium dioxide. Through this study, coal tailings, as a coal processing waste, were transformed into high-value materials, and relevant photocatalytic composite materials could be prepared with broad application prospects.

Ionic Liquid-Mediated Dynamic Polymerization for Facile Aqueous-Phase Synthesis of Enzyme-Covalent Organic Framework Biocatalysts.

Utilizing covalent organic framework (COF) as a hypotoxic and porous scaffold to encapsulate enzyme (enzyme@COF) has inspired numerous interests at the intersection of chemistry, materials, and biological science. In this study, we report a convenient scheme for one-step, aqueous-phase synthesis of highly crystalline enzyme@COF biocatalysts. This facile approach relies on an ionic liquid (2 µL of imidazolium ionic liquid)-mediated dynamic polymerization mechanism, which can facilitate the in situ assembly of enzyme@COF under mild conditions. This green strategy is adaptive to synthesize different biocatalysts with highly crystalline COF "exoskeleton", as well evidenced by the low-dose cryo-EM and other characterizations. Attributing to the rigorous sieving effect of crystalline COF pore, the hosted lipase shows non-native selectivity for aliphatic acid hydrolysis. In addition, the highly crystalline linkage affords COF "exoskeleton" with higher photocatalytic activity for in situ production of H2 O2 , enabling us to construct a self-cascading photo-enzyme coupled reactor for pollutants degradation, with a 2.63-fold degradation rate as the poorly crystalline photo-enzyme reactor. This work showcases the great potentials of employing green and trace amounts of ionic liquid for one-step synthesis of crystalline enzyme@COF biocatalysts, and emphasizes the feasibility of diversifying enzyme functions by integrating the reticular chemistry of a COF.

Negatively charged phospholipids accelerate the membrane fusion activity of the plant-specific insert domain of an aspartic protease.

Various plants use antimicrobial proteins/peptides to resist phytopathogens. In the potato, Solanum tuberosum, the plant-specific insert (PSI) domain of an aspartic protease performs this role by disrupting phytopathogen plasma membranes. However, the mechanism by which PSI selects target membranes has not been elucidated. Here, we studied PSI-induced membrane fusion, focusing on the effects of lipid composition on fusion efficiency. Membrane fusion by the PSI involves an intermediate state whereby adjacent liposomes share their bilayers. We found that increasing the concentration of negatively charged phosphatidylserine (PS) phospholipids substantially accelerated PSI-mediated membrane fusion. NMR data demonstrated that PS did not affect the binding between the PSI and liposomes but had seminal effects on the dynamics of PSI interaction with liposomes. In PS-free liposomes, the PSI underwent significant motion, which was suppressed on PS-contained liposomes. Molecular dynamics simulations showed that the PSI binds to PS-containing membranes with a dominant angle ranging from -31° to 30°, with respect to the bilayer, and is closer to the membrane surfaces. In contrast, PSI is mobile and exhibits multiple topological states on the surface of PS-free membranes. Taken together, our data suggested that PS lipids limit the motion of the anchored PSI, bringing it closer to the membrane surface and efficiently bridging different liposomes to accelerate fusion. As most phytopathogens have a higher content of negatively charged lipids as compared with host cells, these results indicate that the PSI selectively targets negatively charged lipids, which likely represents a way of distinguishing the pathogen from the host.

Pore-Engineered Hydrogen-Bonded Supramolecular Fluorosensor for Ultrasensitive Determination of Copper Ions.

The selective quantification of copper ions (Cu2+ ) in biosamples holds great importance for disease diagnosis, treatment, and prognosis since the Cu2+ level is closely associated with the physiological state of the human body. While it remains a long-term challenge due to the extremely low level of free Cu2+ and the potential interference by the complex matrices. Here, a pore-engineered hydrogen-bonded organic framework (HOF) fluorosensor is constructed enabling the ultrasensitive and highly selective detection of free Cu2+ . Attributing to atomically precise functionalization of active amino "arm" within the HOF pores and the periodic π-conjugated skeleton, this porous HOF fluorosensor affords high affinity toward Cu2+ through double copper-nitrogen (Cu─N) coordination interactions, resulting in specific fluorescence quenching of the HOF as compared with a series of substances ranging from other metal ions, metabolites, amino acids to proteins. Such superior fluorescence quenching effect endows the Cu2+ quantification by this new HOF sensor with a wide linearity of 50-20 000 nm, a low detection limit of 10 nm, and good recoveries (89.5%-115%) in human serum matrices, outperforming most of the reported approaches. This work highlights the practicability of hydrogen-bonded supramolecular engineering for designing facile and ultrasensitive biosensors for clinical free Cu2+ determination.

Electromagnetic-acoustic splitter with a tunable splitting ratio based on copper plates.

Acoustic splitters and electromagnetic splitters can be applied in various fields (e.g., navigation and interference detection). However, there is still a lack of study of structures that can simultaneously split acoustic and electromagnetic beams. In this study, a novel, to the best of our knowledge, electromagnetic-acoustic splitter (EAS) based on copper plates is proposed, which can simultaneously produce identical beam-splitting effects for transverse magnetic (TM)-polarized electromagnetic and acoustic waves. Different from previous beam splitters, the beam splitting ratio of the proposed passive EAS can be simply tuned by changing the incident angle of the input beam, i.e., a tunable splitting ratio can be achieved without additional energy consumption. The simulated results verify that the proposed EAS can create two transmitted split beams with a tunable splitting ratio for both electromagnetic and acoustic waves. This may have applications in dual-field navigation/detection, which can provide additional information and higher accuracy compared with single-field navigation/detection.

Tunable Stress Relaxing Biomimetic Matrices: Hyaluronan/Hydroxyapatite Hybridization Mediates Assembly of Collagen Fibrils.

The alluring correlations of cellular behaviors with viscoelastic extracellular matrices have driven increasing endeavors directed toward the understanding of mechanical cues on cell growth and differentiation via preparing biomimetic scaffolds/gels with viscoelastic controllability. Indeed, systematic investigations, especially into calcium phosphate-containing biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic mineralization with confined ion diffusion and subsequent oxidization treatment. The collagen self-assembly was applied to fabricate tunable stress relaxing fibrillar matrices in the presence of OHAHs in which the incorporated hyaluronic acid with aldehyde groups acted to improve the component compatibility as well as to supplement the molecular interactions with the occurrence of a Schiff-base reaction. With the addition of varying OHAH contents, the self-assembly behavior of collagen was altered, and the obtained collagen-hybrid (CH) matrices presented a heterogeneous fibrillar structure interspersed with OHAHs, characterized by large fibrillar bundles coexisting with small fibrils. The OHAHs improved the hydrogel stability of pure collagen, and according to rheological and nanoindentation measurements, CH matrices also exhibited tunable stress relaxation rates, following an OHAH concentration-dependent fashion. The proliferation and spreading of MC3T3-E1 cells cultured onto such CH matrices were further found to increase with the stress relaxing rate of the matrices. The present study showed that the introduction of hydroxyapatite incorporated with active hyaluronic acid during collagen reconstitution was a simple and effective strategy to realize the preparation of tunable stress relaxing biomimetic matrices potentially used for further appraising the regulation of mechanical cues on cell behaviors.

Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death.

AIMS: The ryanodine receptor 2 (RyR2) is essential for cardiac muscle excitation-contraction coupling; dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we aimed to investigate the pathogenic basis of the mutation. METHODS AND RESULTS: We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon ß-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favour triggering ectopic beats and Ca2+ re-entry; similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca2+ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca2+, an elevated diastolic RyR2-mediated Ca2+ leak, and an imbalance between Ca2+ leak and reuptake. Structural analyses reveal that the mutation directly impacts RyR2-FK506 binding protein interaction. CONCLUSION: In this study, we have identified a novel mutation in RyR2 that is associated with sudden cardiac death. By characterizing the function defects of mutant RyR2 in animal, whole heat, and cardiomyocytes, we demonstrated the pathogenic basis of the disease-causing mutation and provided a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.

Post-colonoscopy cancer rate at a tertiary referral hospital in Australia: A data linkage analysis.

BACKGROUND AND AIM: Colorectal cancer (CRC) diagnosed following a cancer-negative colonoscopy is termed as post-colonoscopy CRC (PCCRC). The World Endoscopy Organization has recently standardized the definition of PCCRC-3Y (CRC developing within 3 years of a cancer-negative colonoscopy). In the present study, we sought to assess PCCRC-3Y rate, perform root-cause analyses, and identify factors associated with development of PCCRC at a tertiary referral hospital in Australia. METHODS: All patients undergoing colonoscopy from 2011 to 2018 were matched to a population-based cancer register. PCCRC-3Y rate was assessed for years 2011-2015. All PCCRC cases that developed within 6-48 months after a cancer-negative colonoscopy underwent root-cause analyses. Descriptive statistics were used to summarize data. RESULTS: Among 17 828 patients undergoing colonoscopy, 367 CRC cases were diagnosed during the study period. This included nine PCCRC cases, which developed at a median of 14 months (range 7-34 months) after cancer-negative colonoscopy. The PCCRC-3Y rate for years 2011-2015 was 2.16% (95% CI 0.91-5.15). All nine PCCRC cases were moderately or poorly differentiated adenocarcinomas; seven of nine were early-stage CRC (stages I and II) and six of nine probably represented missed lesions at index colonoscopy despite an apparently adequate examination. History of inflammatory bowel disease (IBD) (odds ratio [OR] 21.9, 95% confidence interval [CI] 4.6-103.7, P < 0.001) and diverticulosis (OR 5.4, 95% CI 1.4-20.5, P = 0.01) were significantly associated with development of missed CRC. CONCLUSIONS: In our tertiary referral colonoscopy cohort, PCCRC-3Y rate was 2.16% (95% CI 0.91-5.15). IBD and diverticulosis were significantly associated with risk of PCCRC. The majority of PCCRC lesions were likely missed at index colonoscopy, despite an apparently adequate examination.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

The Effect of Warm Acupuncture on EOS, IgE, Inflammatory Factors, and T Lymphocyte Subsets in Patients with Allergic Rhinitis of Lung Qi Deficiency and Cold-Type.

Objective: The purpose of this study was to investigate the effects of warming needle therapy on eosinophils, specific immunoglobulin E (IgE), inflammatory factors, and T lymphocyte subsets in patients with lung qi deficiency and cold-type allergic rhinitis (AR). Methods: A total of 155 patients with lung qi deficiency and cold-type AR from May 2021 to December 2022 were randomly divided into a study group of 76 cases and a control group of 79 cases. The control group received medication (chlorpheniramine and fluticasone), and the study group received medication combined with warming needle therapy. The efficacy, TCM syndrome score, eosinophils, IgE, inflammatory factors (interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-α)), T lymphocyte subsets (CD3+, CD4+, and CD8+), and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores were evaluated after 2 weeks of treatment. Results: The total effective rate in the study group was 92.11%, which was higher than that in the control group (77.22%) (P < .05). The TCM syndrome scores of the study group were lower than those of the control group after 1 and 2 weeks of treatment (P < .05). The positive rate of eosinophils in the study group was lower than that in the control group after 1 week (47.37% vs. 64.56%, P < .05) and after 2 weeks (21.05% vs. 37.97%, P < .05) of treatment. The serum levels of specific IgE, IL-6, IL-8, and TNF-α in the study group were lower than those in the control group after 1 and 2 weeks of treatment (P < .05). The peripheral blood levels of CD3+ and CD4+ were higher and the peripheral blood level of CD8+ was lower in the study group than in the control group after 1 and 2 weeks of treatment (P < .05). The RQLQ scores of the study group were lower than those of the control group after 1 and 2 weeks of treatment (P < .05). Conclusion: Warming needle therapy can effectively improve the clinical symptoms of patients with lung qi deficiency and cold-type AR, reduce inflammation, and enhance immune function.

Structural Characterization and Molecular Model Construction of High-Ash Coal from Northern China.

High-ash coal, also known as low-grade coal, has becomes a viable alternative in recent years to high-quality coal because available resources have become increasingly scarce due to extensive mining activity. This work aims to provide a comprehensive understanding of the structural characteristics of high-ash coal and construct a plausible molecular structure to elucidate its chemical reactivity in future applications. Its properties were investigated using Solid-state 13C nuclear magnetic resonance (13C NMR), X-ray photoelectron spectroscopy analysis (XPS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). The molecular structure was constructed and validated using Material Studio, LAMMPS Software Package, and MATLAB program. The characterization results revealed that high-ash coal contains 72.15% aromatic carbon, significantly surpassing the percentage of aliphatic carbon (27.85%). The ratio of bridgehead carbon to peripheral aromatic carbon was calculated as 0.67, indicating that the pentacene is the main carbon skeleton form in the high-ash coal structure. Furthermore, oxygen-containing functional groups presented as C=O/O-C-O, C-O, and COO- within the structure along with pyridine and pyrrolic structures. Consequently, the molecular structure comprises pentacene with aliphatic carbon chains, such as methylene, that connect the benzene rings and form a three-dimensional network. The results of a simulated IR spectrum and contact angle simulation aligned with the experimental results, validating the molecular structure of high-ash coal. The chemical formula for the high-ash coal model was determined as C203H189N7O61S with a molecular weight of 3734.79.

Adsorption of Different Ionic Types of Polyacrylamide on Montmorillonite Surface: Insight from QCM-D and Molecular Dynamic Simulation.

This study investigates the interaction between montmorillonite and polyacrylamide (PAM) with different ionic types using quartz crystal microbalance with dissipation monitoring (QCM-D) and molecular dynamics (MD) simulations. The goal was to understand the effect of ionicity and ionic type on polymer deposition on montmorillonite surfaces. The results of the QCM-D analysis showed that a decrease in pH led to an increase in the adsorption of montmorillonite on the alumina surface. The ranking of adsorption mass on alumina and pre-adsorbed montmorillonite alumina surfaces was found to be cationic polyacrylamide (CPAM) > polyacrylamide (NPAM) > anionic polyacrylamide (APAM). The study also found that CPAM had the strongest bridging effect on montmorillonite nanoparticles, followed by NPAM, while APAM had a negligible bridging effect. The MD simulations showed that ionicity had a significant influence on the adsorption of polyacrylamides. The cationic functional group N(CH3)3+ had the strongest attraction interaction with the montmorillonite surface, followed by the hydrogen bonding interaction of the amide functional group CONH2, and the anionic functional group COO- had a repulsive interaction. The results suggest that at high ionicity levels, CPAM can be adsorbed on the montmorillonite surface, while at low ionicity levels, APAM may still be adsorbed with a strong coordination trend.

Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM.

The human mitochondrial alpha-ketoglutarate (α-KG) dehydrogenase complex (hKGDHc) is a well-studied macromolecular enzyme that converts α-KG to succinyl-CoA and NADH. Abnormalities of the complex lead to several diseases, including neurodegenerative disorders. Despite its importance in human metabolism and diseases, structural information on hKGDHc is not well defined. Here, we report the 2.92 Å resolution cryo-electron microscopy (EM) structure of its E1 component 2-oxoglutarate dehydrogenase (OGDH). The density map comprised residues 129-1,023, which is nearly the full length of OGDH. The structure clearly shows the active site and Ca2+ binding site of OGDH. This structural information will improve our understanding of the structure and function of hKGDHc and benefit pharmaceutical and basic science targeting this enzyme complex.

Detecting aerosol backscattering coefficient across the whole troposphere by the sidescattering lidar system with three CCD cameras.

Due to geometric overlap factor, the backscattering lidar is not suitable to detect atmospheric characteristics near the ground. A new sidescattering lidar system consisting of three CCD cameras and one CW laser is developed for the first time to measure the profiles of the backscattering coefficient of atmospheric aerosols across the whole troposphere, which has no detection blind zone near the ground. The aerosol relative phase function was detected by its horizontal CCD channel. The vertical distribution of aerosol backscattering coefficient across the whole troposphere was observed by the other two CCD cameras of vertical channel. The reasons for choosing three CCD cameras and their respective functions are analyzed in detail. Comparative experiments and continuous observations indicate that the new sidescattering lidar system including three CCD cameras is simple in structure and reliable in performance with low cost as well.

Converting Chrysotile Nanotubes into Magnesium Oxide and Hydroxide Using Lanthanum Oxycarbonate Hybridization and Alkaline Treatment for Efficient Phosphate Adsorption.

Magnesium oxide and hydroxide nanomaterials comprise a class of promising advanced functional metal nanomaterials whose use in environmental and material applications is increasing. Several strategies to synthesize these nanomaterials have been described but are unsustainable and uneconomic. This work reports on a processing strategy that turns natural magnesium-rich chrysotile into magnesium oxide and hydroxide nanoparticles via nanoparticle hybridization and an alkaline process while enabling La-based nanoparticles to coat the chrysotile nanotube surfaces. The adsorbent's resulting hybrid nanostructure had an outstanding capacity for phosphate uptake (135.2 mg P g-1) and enhanced regeneration performance. Furthermore, the adsorbent featured wide applicability with respect to the coexistence of competitive anions and a broad range of pH conditions, and its high-performance phosphate removal from sewage effluent was also demonstrated. Spectroscopic and microscopic analyses revealed the scavenging ability of phosphate by the La-based and Mg-based nanoparticles and the multiple capture mechanisms involved, including surface complexation and ion exchange. This proposed approach expands chrysotile's potential use as a magnesium-rich nanomaterial and harbors great promise for the removal of pollutants in a variety of real-world settings.

Correlation between miRNA-124, miRNA-544a, and TNF-α levels in acute spinal cord injury.

STUDY DESIGN: Retrospective. OBJECTIVES: Acute spinal cord injury (ASCI) is caused by direct or indirect strikes from external forces on the spinal cord. Here, we investigated the correlation between the miR-124, miR-544a, and TNF-α levels in patients with ASCI, aiming to evaluate the potential usage of miR-124 and miR-544a in ASCI diagnosis. SETTING: University/hospital. METHODS: A total of 90 (58 male/32 female) ASIA patients and 15 (9 male/6 female) control patients (with acute limb trauma) were involved in the presented study. The ASIA patients were further subclustered based on the International Standards for the Neurological Classification of SCI (ISNCSCI) exam. 30 (18 male/12 female)cases were determined to have complete spinal cord injury (CSCI) and classified as ASIA grade A (Complete); 30 (20 male/10 female) cases were determined to have incomplete spinal cord injury (ISCI) and classified as ASIA grade B (sensory incomplete), C (motor incomplete), or D (motor incomplete); 30 (20 male/10 female) cases were determined to have normal neurological function (NNF) and classified as ASIA grade E (Normal). Plasma miR-124, miRNA-544a, and tumor necrosis factor-alpha (TNF-α) levels were measured from the blood samples collected 24 h, 48 h, and 72 h after trauma. RESULTS: The levels of miR-124 and miR-544a in the CSCI and ISCI groups were significantly higher than those of the NNF and the control group 24 h after injury (P < 0.05). The increased levels gradually declined from 24 h to 72 h after injury. The area under the receiver operating characteristic curve (ROC) of miR-124, miR-544a and TNF-α 24 h after trauma in patients with acute spinal cord injury were 0.948 [95% CI (0.890, 1.000)], 0.815 [95% CI (0.638, 0.994)] and 0.770 [95% CI (0.641, 0.879)], respectively. CONCLUSION: The miRNA-124 and miRNA-544a levels increased significantly in ASCI patients compared with control patients 24 h after injury. These increased levels gradually reduced from 24 h to 72 h after injury. There is a strong positive correlation between miRNA-124, miRNA-544a, and acute spinal cord injury. SPONSORSHIP: The present study was supported by a University-level project of Ningxia Medical University (Project Number: XY2017147).

Gestational Diabetes Mellitus: The Genetic Susceptibility Behind the Disease.

Gestational diabetes mellitus (GDM), a type of pregnancy-specific glucose intolerance or hyperglycemia, is one of the most common metabolic disorders in pregnant women with 16.9% of the global prevalence of gestational hyperglycemia. Not only are women with GDM likely to develop T2DM, but their children are also at risk for birth complications or metabolic disease in adulthood. Therefore, identifying the potential risk factors for GDM is very important in the prevention and treatment of GDM. Previous studies have shown that genetic predisposition is an essential component in the occurrence of GDM. In this narrative review, we describe the role of polymorphisms in different functional genes associated with increased risk for GDM, and available evidence on genetic factors in the risk of GDM is summarized and discussed.