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The relation between obesity and stroke outcome has been disputed. This study was aimed to determine the association of body mass index (BMI) with mortality and functional outcome in patients with acute ischemic stroke. Data were from a national, multi-centre, prospective, hospital-based register: the ChinaQUEST (Quality Evaluation of Stroke Care and Treatment) study. Of 4782 acute ischemic stroke patients, 282 were underweight (BMI 2), 2306 were normal-weight (BMI 18.5 to 2), 1677 were overweight (BMI 24 to 2) and 517 were obese (BMI ≥ 28 kg/m2). The risks of death at 12 months and death or high dependency at 3 and 12 months in overweight (HR: 0.97, 95% CI: 0.78–1.20; OR: 0.93, 95% CI: 0.80–1.09; OR: 0.95, 95% CI: 0.81–1.12) and obese patients (HR: 1.07, 95% CI: 0.78–1.48; OR: 0.96, 95% CI: 0.75–1.22; OR: 1.06, 95% CI: 0.83–1.35) did not differ from normal-weight patients significantly after adjusting for baseline characteristics. Underweight patients had significantly increased risks of these three outcomes. In ischemic stroke patients, being overweight or obese was not associated with decreased mortality or better functional recovery but being underweight predicted unfavourable outcomes.

Stroke is a major cause of mortality and long-term disability worldwide. The study of biomarkers and pathogenesis is vital for early diagnosis and treatment of stroke. In the present study, a continuous-flow normal-phase/reversed-phase two-dimensional liquid chromatography-quadrupole time-of-flight mass spectrometry (NP/RP 2D LC-QToF/MS) method was employed to measure lipid species in human plasma, including healthy controls and lacunar infarction (LI) patients. As a result, 13 lipid species were demonstrated with significant difference between the two groups, and a "plasma biomarker model" including glucosylceramide (38:2), phosphatidylethanolamine (35:2), free fatty acid (16:1), and triacylglycerol (56:5) was finally established. This model was evaluated as an effective tool in that area under the receiver operating characteristic curve reached 1.000 in the discovery set and 0.947 in the validation set for diagnosing LI patients from healthy controls. Besides, the sensitivity and specificity of disease diagnosis in validation set were 93.3% and 96.6% at the best cutoff value, respectively. This study demonstrates the promising potential of NP/RP 2D LC-QToF/MS-based lipidomics approach in finding bio-markers for disease diagnosis and providing special insights into the metabolism of stroke induced by small vessel disease. Graphical abstract Flow-chart of the plasma biomarker model establishment through biomarker screening and validation.

It is essential to extract dynamic information about a patient's heart from a medical X-ray angiography image sequence for a quantitative medical diagnosis. As the motions included in the angiography sequences are the mixture of various motion signals, such as the body's integral translation, respiratory motion, cardiac impulse, and tremor, automatic separation of these signals challenges the effectiveness of the image information processing method. This paper has proposed an optimal time-frequency domains iteration separation algorithm for multi-motion parameters (TFISA-MMP) to obtain the physiological parameters including the translation. The main procedures of the TFISA-MMP algorithm include three parts. First, the algorithm automatically extracted a set of relatively stable branch points from the coronary artery angiography image, and then automatically tracked these branch points in the sequence image to obtain their motion curves that changed with the time. Second, with the guidance of the multi-motion parameter model, the initial values of each component were estimated based on Discrete Fourier Transformation (DFT). Moreover, the initial values of each motion component were optimized using the global mean square minimum error between the estimated reconstructed signal and original signal and the local mean square minimum error in the frequency domain for each frequency component. Finally, these motion components were estimated by minimizing the residual signal between the original signal and the reconstructed signal via the loop iteration to obtain the estimated optimal motion components, such as two-dimensional (2D) heartbeat, tremor, respiratory motion, and translational motion. Both visible human coronary model simulation experiments and the clinical experiments of single-arm X-ray angiography images of many individuals verified the correctness, validity, and clinical applicability of the separation method.

China has experienced rapid urbanization in recent decades along with dramatic economic growth. Previous studies have shown that urbanization has both positive and negative effects on health. However, there is a lack of research on the overall effects of urbanization on the epidemic transition of environmental health risks considering various pathways in China. In the present study, we studied the contributions of different aspects of urbanization in China to epidemic transitions using provincial and multi-year (1995, 2000, 2005, and 2010) panel data. Statistical models with fixed and random effects were developed to explore the impacts of different urbanization indicators on the overall epidemic transition of environmental health (general model) and the changes in cause-specific mortality rates of typical diseases (cause-specific models). The results show that the impacts of non-communicable diseases continue to grow during the urbanization process in China. The ratio of communicable disease-related mortality to non-communicable disease-related mortality continues to decrease over time. The general model shows that the improved medical conditions (coefficient = −0.0011, P = 0.037), the improved urban infrastructure (e.g., tap water supply) (coefficient = −0.00065, P

While recent assessments have quantified the burden of air pollution at the national scale in China, air quality managers would benefit from assessments that disaggregate health impacts over regions and over time. We took advantage of a new 10 × 10 km satellite-based PM2.5 dataset to analyze spatial and temporal trends of air pollution health impacts in China, from 2004 to 2012. Results showed that national PM2.5 related deaths from stroke, ischemic heart disease and lung cancer increased from approximately 800,000 cases in 2004 to over 1.2 million cases in 2012. The health burden exhibited strong spatial variations, with high attributable deaths concentrated in regions including the Beijing–Tianjin Metropolitan Region, Yangtze River Delta, Pearl River Delta, Sichuan Basin, Shandong, Wuhan Metropolitan Region, Changsha–Zhuzhou–Xiangtan, Henan, and Anhui, which have heavy air pollution, high population density, or both. Increasing trends were found in most provinces, but with varied growth rates. While there was some evidence for improving air quality in recent years, this was offset somewhat by the countervailing influences of in–migration together with population growth. We recommend that priority areas for future national air pollution control policies be adjusted to better reflect the spatial hotspots of health burdens. Satellite-based exposure and health impact assessments can be a useful tool for tracking progress on both air quality and population health burden reductions. Keywords: Air pollution, PM2.5, Health burden, Temporal, Spatial, China

To translate scientific evidence into policy decisions, a universal, integrate and rapid–calculation model is needed for estimating the air quality associated health co–benefits of climate change mitigation strategies. This study developed such a greenhouse gas policy assessment model (GHG–PAM) based upon the annually published energy balances tables. To examine the applicability of this model, we select Suzhou, one of the national low-carbon pilot cities located in the east of China, as a case study. It was determined that carbon dioxide (CO2) emissions in Suzhou would increase from 148 million tons in 2010 to 297, 284, 180, and 173 million tons in 2020 under Business As Usual (BAU), Industrial Structure Dominated (ISD), Technology Dominated (TD), and Integrate Carbon Reduction (ICR) scenarios, of which only ICR scenario meets its carbon intensity target. Under the ICR scenario, the implementation of greenhouse gas policies reduces the air pollution associated burden of diseases, measured by Disability-Adjusted Life Years (DALY), by 44.1% in 2020 compared to BAU, although even with this scenario the burden of diseases would still be higher than that in 2010. In addition, the model can also identify sectors and industries with greater health co–benefits per unit CO2 emission reduction, which provides a useful guide for Suzhou's climate policy makers to formulate cost–effective measures. However, it should be carefully used where there is a mismatch between sectors with high potential for CO2 emission reductions and sectors with high health co–benefits per unit CO2 emission reduction.

Metal-organic frameworks (MOFs) are promising materials for carbon dioxide (CO2) adsorption and storage; however, many details regarding CO2 dynamics and specific adsorption site locations within MOFs remain unknown, restricting the practical uses of MOFs for CO2 capture. The intriguing α-magnesium formate (α-Mg3(HCOO)6) MOF can adsorb CO2 and features a small pore size. Using an intertwined approach of 13C solid-state NMR (SSNMR) spectroscopy, 1H-13C cross-polarization SSNMR, and computational molecular dynamics (MD) simulations, new physical insights and a rich variety of information have been uncovered regarding CO2 adsorption in this MOF, including the surprising suggestion that CO2 motion is restricted at elevated temperatures. Guest CO2 molecules undergo a combined localized rotational wobbling and non-localized twofold jumping between adsorption sites. MD simulations and SSNMR experiments accurately locate the CO2 adsorption sites; the mechanism behind CO2 adsorption is the distant interaction between the hydrogen atom of the MOF formate linker and a guest CO2 oxygen atom, which are ca. 3.2 A apart.

Early X-ray fiber diffraction studies have established that the spontaneous gel formation of guanosine 5′-monophosphate (5′-GMP) under slightly acidic conditions (e.g., pH 5) results from self-assembly of 5′-GMP into a helical structure in which hydrogen-bonded guanine bases form a continuous helix with 15 nucleotides per 4 turns. For more than five decades, the sense of this helix is believed to be left-handed. Using multinuclear solid-state NMR and IR spectroscopic methods, we have finally determined the long-missing structural details of this helix. First, we found that this 5′-GMP helix is right-handed containing exclusive C3′-endo sugar puckers. Second, we showed that the central channel of this helix is free of Na+ ions, which is in sharp contrast to the helix formed by 5′-GMP at pH 8 where the central channel is filled with Na+ ions.

Introduction: In this study we investigated the relationships between anti-ganglioside antibodies and Guillain–Barre syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Methods: Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. Results: In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. Conclusions: These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470–475, 2017

Small-pore molecular sieve SAPO-34 is well-known as the most promising and effective catalyst for the conversion of methanol to olefins (MTO). In this paper, we have investigated the formation of SAPO-34 under different dry gel conversion (DGC) conditions using two types of synthesis gels with one containing hydrofluoric acid (HF) and the other not. Particular attention was paid to the Si incorporation and distribution in final SAPO-34 products. The results indicate that under DGC (with HF) conditions SAPO-34 is formed from the transformation of a highly crystalline, layered prephase that is held by covalent bonds. The final SAPO-34 product is a mixture of triclinic and trigonal phases containing six framework Si species. The Si distribution in triclinic and trigonal SAPO-34 is drastically different. The majority of Si species are located in the aluminosilicate domains in trigonal phase. Conversely, under DGC (without HF) conditions, the crystallization of SAPO-34 involves three transformational stages. I...

Background and Purpose— We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. Methods— A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. Results— The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (P =0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril–folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56–0.84; P P =0.982). The effect was greater among participants with elevated total cholesterol ( P for interaction=0.024). Conclusions— Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00794885.

In this work, the synthesis of nanoscale CuInS2 and CuInSe2 was developed using molecular precursors of the type [(Ph3P)2CuIn(ER)4] (E = S, Se) and solvothermal reactions. Various conditions were investigated including the use of different precursors, reaction temperatures, reaction times and the addition of a secondary chalcogen source to mixtures. After optimizing conditions, nanoparticles of CuInS2 and CuInSe2 were isolated with controlled sizes in the range of 2–5 nm (wurtzite structure), which ultimately tuned the band gap energies of the materials. Characterization methods including powder X-ray diffraction, electron microscopy, and optical spectroscopy were used to investigate their structures and photophysical properties.

The ability to resolve glycans while attached to tryptic peptides would greatly facilitate glycoproteomics, as this would enable site-specific glycan characterization. Peptide/glycopeptide separations are typically performed using reversed-phase liquid chromatography (RPLC), where retention is driven by hydrophobic interaction. As the hydrophilic glycans do not interact significantly with the RPLC stationary phase, it is difficult to resolve glycopeptides that differ only in their glycan structure, even when these differences are large. Alternatively, glycans interact extensively with the stationary phases used in hydrophilic interaction chromatography (HILIC), and consequently, differences in glycan structure have profound chromatographic shifts in this chromatographic mode. Here, we evaluate HILIC for the separation of isomeric glycopeptide mixtures that have the same peptide backbone but isomeric glycans. Hydrophilic functional groups on both the peptide and the glycan interact with the HILIC stationary phase, and thus, changes to either of these moieties can alter the chromatographic behavior of a glycopeptide. The interactive processes permit glycopeptides to be resolved from each other based on differences in their amino acid sequences and/or their attached glycans. The separations of glycans in HILIC are sufficient to permit resolution of isomeric N-glycan structures, such as sialylated N-glycan isomers differing in α2-3 and α2-6 linkages, while these glycans remain attached to peptides.

Myeloid-derived growth factor (MYDGF) is a paracrine-acting protein that is produced by bone marrow-derived monocytes and macrophages to protect and repair the heart after myocardial infarction (MI). This effect can be used for the development of protein-based therapies for ischemic tissue repair, also beyond the sole application in heart tissue. Here, we report the X-ray structure of MYDGF and identify its functionally relevant receptor binding epitope. MYDGF consists of a 10-stranded β-sandwich with a folding topology showing no similarities to other cytokines or growth factors. By characterizing the epitope of a neutralizing antibody and utilizing functional assays to study the activity of surface patch-mutations, we were able to localize the receptor interaction interface to a region around two surface tyrosine residues 71 and 73 and an adjacent prominent loop structure of residues 97–101. These findings enable structure-guided protein engineering to develop modified MYDGF variants with potentially improved properties for clinical use., Myeloid-derived growth factor (MYDGF) is an angiogenic growth factor with therapeutic potential for ischemic tissue repair and the receptor is still unknown. Here the authors present the crystal structure of human MYDGF and identify its functional epitope through mutagenesis studies.

Endoplasmic reticulum (ER) stress is essential for brain ischemia/reperfusion (I/R) injury. However, whether it contributes to I/R-induced blood-brain barrier (BBB) injury remains unclear. cilostazol exerts protective effects toward I/R-induced BBB injury, with unclear mechanisms. This study explored the potential role of ER stress in I/R-induced endothelial cell damage and determined whether the therapeutic potential of cilostazol, with respect to I/R-induced endothelial cell damage, is related to inhibition of ER stress. We found that exposing brain endothelial cells (bEnd.3) to oxygen-glucose deprivation/reoxygenation (OGD/R) significantly activated ER stress and diminished the barrier function of cell monolayers; treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) or cilostazol prevented OGD/R-induced ER stress and preserved barrier function. Furthermore, OGD/R induced the expression and secretion of matrix metalloproteinase-9 and nuclear translocation of phosphorylated NF-κB. These changes were partially reversed by 4-PBA or cilostazol treatment. In vivo, 4-PBA or cilostazol significantly attenuated I/R-induced ER stress and ameliorated Evans blue leakage and tight junction loss. These results demonstrate that I/R-induced ER stress participates in BBB disruption. Targeting ER stress could be a useful strategy to protect the BBB from ischemic stroke, and cilostazol is a promising therapeutic agent for this process.-Nan, D., Jin, H., Deng, J., Yu, W., Liu, R., Sun, W., Huang, Y. Cilostazol ameliorates ischemia/reperfusion-induced tight junction disruption in brain endothelial cells by inhibiting endoplasmic reticulum stress.

The Plasmodium vivax Duffy-binding protein (DBP) is a prime target of the protective immune response and a promising vaccine candidate for P. vivax malaria. Naturally acquired immunity (NAI) protects against malaria in adults residing in infection-endemic regions, and the passive transfer of malarial immunity confers protection. A vaccine that replicates NAI will effectively prevent disease. Here, we report the structures of DBP region II in complex with human-derived, neutralizing monoclonal antibodies obtained from an individual in a malaria-endemic area with NAI. We identified protective epitopes using X-ray crystallography, hydrogen–deuterium exchange mass spectrometry, mutational mapping and P. vivax invasion studies. These approaches reveal that naturally acquired human antibodies neutralize P. vivax by targeting the binding site for Duffy antigen receptor for chemokines (DARC) and the dimer interface of P. vivax DBP. Antibody binding is unaffected by polymorphisms in the vicinity of epitopes, suggesting that the antibodies have evolved to engage multiple polymorphic variants of DBP. The human antibody epitopes are broadly conserved and are distinct from previously defined epitopes for broadly conserved murine monoclonal antibodies. A library of globally conserved epitopes of neutralizing human antibodies offers possibilities for rational design of strain-transcending DBP-based vaccines and therapeutics against P. vivax. The structures of two neutralizing human monoclonal antibodies against Plasmodium vivax Duffy-binding protein (DBP) isolated from an individual with naturally acquired immunity, bound to DBP, reveal how such antibodies prevent parasite entry into reticulocytes.

Neuronal intranuclear inclusion disease (NIID) is a heterogenous neurodegenerative disorder named after its pathological features. It has long been considered a disease of genetic origin. Recently, the GGC repeated expansion in the 5'-untranslated region (5'UTR) of theFifteen patients with NIID were identified from five academic neurological centres. Biopsied skin samples were analysed by histological staining, immunostaining and electron microscopic observation. Whole-genome sequencing (WGS) and long-read sequencing (LRS) were initially performed in three patients with NIID. Repeat-primed PCR was conducted to confirm the genetic variations in the three patients and the other 12 cases.Our patients included 14 adult-onset patients and 1 juvenile-onset patient characterised by degeneration of multiple nervous systems. All patients were identified with intranuclear inclusions in the nuclei of fibroblasts, fat cells and ductal epithelial cells of sweat glands. The WGS failed to find any likely pathogenic variations for NIID. The LRS successfully identified that three patients with adult-onset NIID showed abnormalities of GGC expansion in 5'UTR of theOur findings provided evidence that confirmed the GGC repeated expansion in the 5'UTR of the

International audience; Model Based Systems Engineering (MBSE) is a promising solution to formalize and communicate information about the design of complex systems, in particular for the automotive industry which faces new challenges associated to autonomous driving. Numerical simulation is commonly used to support the design of these complex systems, but the possible relations with MBSE should be further investigated. This work, conducted with academic and industrial partners at the research institute IRT SystemX, aims at further bridging the gap between system architecture and numerical simulation. An industrial design problem related to the design of an autonomous vehicle passing traffic lights is used to validate and illustrate new methods and tools based on SysML. Their aim is to: 1) guide the formulation of a question requiring simulation, called solicitation, by the system architect 2) guide the design of a simulation architecture by the simulation architect with a special focus on the consistency with the system. A Java plugin was developed in the SysML editor Papyrus for the solicitation, and a SysML metamodel was defined for the simulation architecture. The solicitation associated to the industrial design problem is answered by a multiobjective optimization of the vehicle's cost and electrical consumption using a co-simulation between the tools Simulink and Amesim.

DNA replication is a stringently regulated cellular process. In proliferating cells, DNA replication-initiation proteins (RIPs) are sequentially loaded onto replication origins during the M-to-G(1) transition to form the pre-replicative complex (pre-RC), a process known as replication licensing. Subsequently, additional RIPs are recruited to form the pre-initiation complex (pre-IC). RIPs and their regulators ensure that chromosomal DNA is replicated exactly once per cell cycle. Origin recognition complex (ORC) binds to, and marks replication origins throughout the cell cycle and recruits other RIPs including Noc3p, Ipi1-3p, Cdt1p, Cdc6p and Mcm2-7p to form the pre-RC. The detailed mechanisms and regulation of the pre-RC and its exact architecture still remain unclear. In this study, pairwise protein-protein interactions among 23 budding yeast and 16 human RIPs were systematically and comprehensively examined by yeast two-hybrid analysis. This study tested 470 pairs of yeast and 196 pairs of human RIPs, from which 113 and 96 positive interactions, respectively, were identified. While many of these interactions were previously reported, some were novel, including various ORC and MCM subunit interactions, ORC self-interactions, and the interactions of IPI3 and NOC3 with several pre-RC and pre-IC proteins. Ten of the novel interactions were further confirmed by co-immunoprecipitation assays. Furthermore, we identified the conserved interaction networks between the yeast and human RIPs. This study provides a foundation and framework for further understanding the architectures, interactions and functions of the yeast and human pre-RC and pre-IC.

Microglia are the inherent immune effector cells in the central nervous system (CNS), are activated rapidly when the CNS is stimulated by ischaemia, infection, injury, etc. and participate in and aggravate the development of inflammatory reactions in the CNS. During the process of microglial activation, inflammatory factors such as TNF-α and IL-1β and an abundance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), are released by damaged nerve cells. LXW7 is a small molecule peptide and specifically binds with integrin αvβ3. Cerium oxide nanoparticles (nanoceria) are strong free radical scavengers and are widely used in many studies. In this research, a model of inflammation was established using lipopolysaccharide (LPS) to induce BV2 microglia activation, and the effects of CeO

Antibody-dependent cell-mediated cytotoxicity (ADCC) is an effector function of immunoglobulins (IgGs) involved in the killing of target cells by a cytotoxic effector cell. Recognition of IgG by Fc receptors expressed on natural killer cells, mostly FcγIII receptors (FcγRIII), underpins the ADCC mechanism, thus motivating investigations of these interactions. In this paper, we describe the combination of hydrogen deuterium exchange (HDX) and fast photochemical oxidation of proteins (FPOP) coupled with mass spectrometry (MS) to study the interactions between the human IgG1/FcγRIII complex. Using these orthogonal approaches, we identified critical peptide regions and residues involved in the recognition of IgG1 by FcγRIII. The footprinting results are consistent with the previously published crystal structure of the IgG1 Fc/FcγRIII complex. Additionally, our FPOP results reveal the conformational changes of the Fab domain upon Fc domain binding to FcγRIII. These data demonstrate the value of footprinting as part of a comprehensive toolbox for identifying the changes in the higher order structure of therapeutic antibodies in solution.

Metal-organic frameworks (MOFs) are promising gas adsorbents. Knowledge of the behavior of gas molecules adsorbed inside MOFs is crucial for advancing MOFs as gas capture materials. However, their behavior is not always well understood. In this work, carbon dioxide (CO2) adsorption in the microporous α-Zn3(HCOO)6 MOF was investigated. The behavior of the CO2 molecules inside the MOF was comprehensively studied by a combination of single-crystal X-ray diffraction (SCXRD) and multinuclear solid-state magnetic resonance spectroscopy. The locations of CO2 molecules adsorbed inside the channels of the framework were accurately determined using SCXRD, and the framework hydrogens from the formate linkers were found to act as adsorption sites. 67Zn solid-state NMR (SSNMR) results suggest that CO2 adsorption does not significantly affect the metal center environment. Variable-temperature 13C SSNMR experiments were performed to quantitatively examine guest dynamics. The results indicate that CO2 molecules adsorbed inside the MOF channel undergo two types of anisotropic motions: a localized rotation (or wobbling) upon the adsorption site and a twofold hopping between adjacent sites located along the MOF channel. Interestingly, 13C SSNMR spectroscopy targeting adsorbed CO2 reveals negative thermal expansion (NTE) of the framework as the temperature rose past ca. 293 K. A comparative study shows that carbon monoxide (CO) adsorption does not induce framework shrinkage at high temperatures, suggesting that the NTE effect is guest-specific.

The alteration of safety-secured yeast is a crucial step before scale applications. Based on previous studies, Pichia pastoris showed great potential and value to improve its biocontrol ability. The original sequences of antimicrobial peptide Ac-AMP2 and MiAMP1 were optimized according to the preference of Pichia pastoris and ligated into pPICZαA plasmid which is emerged as a high-performance vector for transformation and expression. The results of RT-qPCR and Western blotting could imply that pPICZαA/Ac-AMP2 and pPICZαA/MiAMP1 were successfully overexpressed in Pichia pastoris GS115. The peptide concentration of GS115/Ac-AMP2 reached a maximum value of 210 mg L−1 at 60 h while GS115/MiAMP1 was 220 mg L−1 at 96 h. The biocontrol experiment indicated that the recombinant strain GS115/Ac-AMP2 and GS115/MiAMP1 could highly suppress the pathogen Penicillium expansum in vivo, which was respectively 42 % (GS115/Ac-AMP2) and 29.2 % (GS115/MiAMP1) of incidence disease lower than the sterile distilled water treatment. In the case of the experimental results considered, the modified GS115/Ac-AMP2 and GS115/MiAMP1 might be promising biological agent in postharvest applications.

Lithium halide electrolytes with high ion conductivity and good cathode compatibility have shown great potential for solid-state batteries. Li3YBr6, with a conductivity of 0.39 mS/cm at room temperature, synthesized by mechanical milling (BM-Li3YBr6), which can be further increased by heat treatment. The annealing parameters are tailored to obtain pure Li3YBr6 (AN-Li3YBr6) with a higher conductivity of 3.31 mS/cm by annealing the BM-Li3YBr6 at 500 °C for 5 h. The higher conductivity of AN-Li3YBr6 compared to the previously-reported results is due to the lower activation energy. NMR and simulation results show that the lithium ion migration between Li-1 and Li-2 sites along the [001] direction is the major obstacle for lithium diffusion in AN-Li3YBr6. The K- and L3-edge X-ray absorption near-edge structure (XANES) of Y for BM-Li3YBr6 and AN-Li3YBr6 showed that Y exists with similar local structures. The increased vibrations of AN-Li3YBr6 due to increased temperatures increase the rate of lithium jumping from one site to another, yielding higher lithium ion mobility. Lithium nuclear density maps prove that the mobile lithium on the 4g(Li) site is more sensitive to the varying temperatures. Both BM- and AN-Li3YBr6 are incompatible with Li, however, an annealing process can improve the electrochemical stability. Both the experimental and simulation results confirm the anode incompatibility between In and AN-Li3YBr6. To mitigate the cathode and anode incompatibility with AN-Li3YBr6, a LiNbO3 coating layer and a Li5.7PS4.7Cl1.3 buffer layer are introduced at the cathode side and anode side, respectively, to assemble all-solid-state batteries with improved capacity and cyclability.

Stabilizing G-quadruplex (G4) structures formed in the c-MYC oncogene promoter represents a fundamental strategy for cancer therapy. However, most G4 stabilizers lack selectivity over various G4s in the genomes. By investigating the binding characteristics of a conjugated imidazole/carbazole (IZCZ-3) molecule with the G4s of c-MYC, c-KIT, and telomere through molecular docking and molecular dynamics simulations, the present study demonstrates that though the binding affinities between IZCZ-3 and the monomeric G4s are inconsistent with the experimental data, the dimeric c-MYC and c-KIT G4s can be targeted by IZCZ-3 through forming concomitant π-π stacking interactions with the intermolecular assembly producing significant contributions to the binding affinity. In the intermolecular dimeric G4-IZCZ-3 binding complexes, IZCZ-3 prefers the c-MYC G4 that has two exposed G-tetrads per monomer over the single G-tetrad-exposed c-KIT G4 by creating more aggregation effects. Taking the aggregation effects into account, the binding affinity order of IZCZ-3 follows c-MYC G4 > c-KIT G4 > telomeric G4, agreeing well with the experimental observation. Thus, the selectivity of IZCZ-3 for c-MYC G4 probably comes from its role in stabilizing the sandwichlike intermolecular aggregates, providing a framework for the development of selective stabilizers targeting c-MYC G4.

Metal–organic frameworks (MOFs) have shown great promise for the adsorption and separation of gases, including the greenhouse gas CO2. In order to improve performance and realize practical applications for MOFs as CO2 adsorbents, a deeper understanding of the number and type of CO2 adsorption mechanisms must be unlocked, along with fine details of CO2 motion within MOFs. Using several complementary characterization methods is a promising protocol for comprehensively investigating the various host–guest interactions between MOFs and CO2. In this work, a combination of solid state NMR (SSNMR) and single crystal X-ray diffraction (SCXRD) has been utilized to reveal both the location and dynamics of adsorbed CO2 within the related PbSDB and CdSDB MOFs, as well as to probe the role of metal centers in CO2 adsorption. 13C SSNMR experiments targeting CO2 reveal the number of unique adsorption sites and the types of CO2 dynamics present, as well as their associated motional rates and angles. 111Cd and 207Pb SSNMR...

We described a female patient with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis occurring sequentially with neuromyelitis optica spectrum disorders (NMOSD). The 19-year-old patient initially presented a diencephalic syndrome with aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) and brain lesions which involving bilateral medial temporal lobes and periependymal surfaces of the third ventricle on magnetic resonance imaging (MRI). Ten months later, the patient developed cognitive impairment, psychiatric symptoms and dyskinesia with left basal ganglia lesions on brain MRI. Meanwhile, the anti-NMDAR antibodies were positive in the patient's serum and cerebrospinal fluid, while the screening tests for an ovarian teratoma and other tumors were all negative. Hence, the patient was diagnosed NMOSD and anti-NMDAR encephalitis followed by low-dose rituximab treatment with a good response. This case was another evidence for demyelinating syndromes overlapping anti-NMDAR encephalitis in Chinese patients.

The objective of this study was to evaluate the efficacy and safety of intravenous vinpocetine administration as part of a comprehensive treatment for acute cerebral infarction in a Chinese population. 610 acute cerebral infarction patients were randomized into two groups: the vinpocetine group (469 patients) received cytidine disphosphate choline 0.4–0.5 g in combination with aspirin 75–100 mg or clopidogrel 75 mg once daily, plus vinpocetine 30 mg intravenously once daily for 7 days, while the control group (141 patients) received cytidine disphosphate choline 0.4–0.5 g in combination with aspirin 75–100 mg or clopidogrel 75 mg once daily for 7 days. Additionally, patients received medications for symptoms such as hypertension, hyperglycemia, hyperlipidemia, and intracranial hypertension when necessary. Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale, and Barthel Index (BI) scores and transcranial doppler (TCD) were assessed at baseline, 7, 14, and 90 days after treatment. Adverse events (AEs) and abnormalities in blood, urine, liver, and kidney function were monitored. MMSE, NIHSS, and BI scores were significantly higher in the vinpocetine group than in the control group 90 days after treatment, indicating significantly improved cognitive skill, neurological function, and quality of life (QOL) in the vinpocetine group versus the control group. Importantly, such effects of vinpocetine were maintained over time. In addition, TCD monitoring showed significantly increased cerebral blood flow associated with vinpocetine versus control. No significant difference in safety was noted between the two groups. When used as part of treatment for acute cerebral infarction, vinpocetine improves patients’ cerebral blood flow, cognitive quality, neurological functions, and QOL. Vinpocetine could be an effective and safe component of treatment regimen for acute cerebral infarction.

This paper presents the first example of high-silica and siliceous zeolite synthesis in the urea/choline chloride mixture as a deep eutectic solvent (DES) using F– as the mineralizing agent. A urea/choline chloride mixture was previously used as solvent to prepare AlPO4-based microporous materials SIZ-2 and AlPO-CJ2. However, generating these materials depends on the formation of ammonium ion as a structure-directing agent (SDA) that is the side product of urea decomposition. In the present study, we show that several highly siliceous zeolites with targeted topologies (MFI, BEA, MEL, and MTN) can be purposely synthesized by adding SDAs of choice rather than relying on solvent decomposition. The Si atoms in zeolite Beta synthesized in a urea/choline chloride mixture exhibit exceptionally high local ordering as shown in a 29Si MAS NMR spectrum. The synthesis of ZSM-11 using eutectic solvents or ionic liquid has not been reported. The major challenge in ZSM-11 synthesis is the intergrown structure formed with ZSM-5 due to the high similarity in their topologies. The present work shows that preparation of pure ZSM-11 can be achieved in urea/choline chloride DES using either DPHMII or DECDMPI as SDA. Using a urea/choline chloride mixture rather than alcohol-based traditional nonaqueous solvents is the key for the success of preparing phase-pure ZSM-11 free of any MFI intergrowths. This is because some alcohols can serve as SDA for MFI. The use of urea/choline chloride based DES eliminates the potential templateing effect of solvent for MFI formation. For MTN zeolite, morphology may be controlled in urea/choline chloride by choosing different SDAs. The disadvantage of this system is the long reaction times.

Background Although chronic kidney disease has been linked to cerebral small-vessel disease (CSVD), a definite relationship between them has not been established. This study assessed whether low estimated glomerular filtration is associated with risk of different subtypes of CSVDs. Methods Electronic databases were systematically searched for studies reporting an odds ratio of the association between low estimated glomerular filtration and CSVD risk. Sixteen studies, including 10,534 participants, were identified. A fix effects model was applied and odds ratios (ORs) with 95% confidence intervals were presented. Results Overall, risk of CSVDs was greater in individuals with low estimated glomerular filtration (OR = 2.20). Stratified analyses consistently showed significant associations across different subtypes, with pooled OR being greatest in subjects with silent cerebral infarction (SCI) (OR = 2.71) and cerebral microbleed (OR = 2.70). A pooled estimate of studies showing OR as a continuous variable showed results consistent with the former analysis (OR = .98 per standard deviation decrease) in low estimated glomerular filtration. Conclusions This study revealed that low estimated glomerular filtration was significantly associated with risk of CSVDs. Low estimated glomerular filtration was most strongly associated with SCI (OR = 2.71) among subtypes of CSVDs.

pH-sensitive polyethylene glycol-conjugated urokinase nanogels (PEG-UKs) were previously reported to be a new form of UK nanogels that could release UK at certain pH values. In this study, we evaluated the effect of PEG-UK targeted to ischemic tissue with microcirculation failure in rat model of ischemic stroke and investigated the possible mechanisms of action.Surgeries were performed to induce persistent middle cerebral artery (MCA) occlusion in adult Sprague-Dawley rats. The pH distribution in the brain was mapped 1h after ischemia using a needle-type pH micro sensor. The release curve of active UK from PEG-UK was also mapped by a continuous measurement of the peripheral blood. The thrombolytic effects of PEG-UK, when it was administrated 1h after occlusion, including dynamic changes in the D-dimer level, neurological deficits and infarction volume, were observed. Next, the possible mechanisms underlying these effects were explored, including the BBB integrity and the extent of apoptosis and neurotoxicity. Additionally, the long-term effects of PEG-UK during the four weeks after treatment were evaluated using the dynamic changes in the body weights and clinical scores and the numbers of deaths and hemorrhagic transformations (HTs). To evaluate the systemic side effects of PEG-UK, the fluctuations of cytokines in the liver and kidney were evaluated.On average, MCA occlusion for 1h induced an approximately 0.49 decline in the pH value (from 7.12 to 6.73), and the lowest value was 6.32 in the predominantly affected region around the cortex. PEG suspended the release of UK from PEG-UK into the circulation. When it was administrated 1h after occlusion, PEG-UK treatment clearly reduced the severity of neurological deficits in the acute phase (P=0.001). The relative infarct volume also decreased significantly in PEG-UK rats (P0.001). As to the integrity of BBB, the EB leakage in the PEG-UK group was reduced (P=0.001). Maintenance of the expression of TIMP-1 (P=0.032) and claudin5 (P0.001) and inhibition of MMP9 upregulation (P0.001) were observed through both immunohistochemistry and Western blot in the PEG-UK group. Moreover, the expression of both NMDAR1 (P0.001) and Caspase9 (P=0.013) in PEG-UK-treated rats was reduced. As to the long-term prognosis, the rats in PEG-UK group recovered faster and better, and the numbers of deaths and HTs were not increased. No significant fluctuation in IL-1β and TNF-α was found in the PEG-UK-treated rats during the four post-treatment weeks. When PEG-UK was administrated 2.5h after occlusion, no clearly better outcomes were observed; however, the number of HTs was not increased.Treatment with PEG-UK decreased the severity of ischemic stroke by improving ischemic brain tissue and protecting the BBB and by inhibiting apoptosis and decreasing neurotoxicity. PEG-UK could further inhibit HT through its BBB protection effect. The administration of PEG-UK also improved the long-term prognosis and had no obvious systemic side effects in rats. Our data provide new insights into the thrombolytic treatment of ischemic stroke.

Metal–organic frameworks (MOFs) often exhibit high porosities and surface areas, making them ideal media for gas storage and carbon capture. MOF-74 is an intriguing porous MOF featuring one-dimensional honeycomb-shaped channels and open metal sites, and is able to adsorb poisonous CO. Variable-temperature (VT) 13C solid-state NMR (SSNMR) experiments focusing on 13CO adsorbed within M-MOF-74 (M = Mg, Zn) are a sensitive probe of guest motion, revealing valuable details regarding the dynamics of adsorbed CO within the MOF channels. 13C SSNMR experiments recorded at temperatures ranging from 153 to 373 K, along with accompanying simulations, unambiguously indicate that two types of dynamic CO motion are present in MOF-74: a localized wobbling of CO on the open metal site, and a non-localized hopping of CO molecules between adjacent open metal sites. The fine details of these motions, including the motional angles and rates, are revealed and discussed. The CO dynamics in MOF-74 are then compared and contrasted with those of CO2, illustrating the similarities and differences in motion between the two types of guest molecules across the experimental temperature range.

The protective effect of high-density lipoprotein (HDL) on endothelial function is impaired in patients with type 2 diabetes mellitus (T2DM), which may result in atherosclerotic complications. Naoxintong (NXT) is a compound preparation that includes Radix Astragali, Angelicae sinensis, Radix Paeoniae Rubra and Ligusticum wallichii. It is widely administered in China to prevent atherosclerotic complications. In the present study, NXT was administered to 69 patients with T2DM. HDLs were isolated from patient blood samples prior to and following the intervention. In vitro endothelial functions of HDL, including proliferation, migration, angiogenesis, and anti-apoptosis were investigated by bromodeoxyuridine, wound healing, Transwell and Matrigel tube formation assays on human umbilical vein endothelial cells (HUVECs). The results from the present study demonstrated that HUVECs treated with HDL isolated from diabetic patients following NXT therapy exhibited increased proliferative effects (10–27%; P

Microporous metal-organic frameworks (MOFs) have high surface areas and porosities, and are well-suited for CO2 capture. MIL-53 features corner-sharing MO4(OH)2 (M = Al, Ga, Cr, etc.) octahedra interconnected by benzenedicarboxylate linkers that form one-dimensional rhombic tunnels, and exhibits an excellent adsorption ability for guest molecules such as CO2. Studying the behavior of adsorbed CO2 in MIL-53 via solid-state NMR (SSNMR) provides rich information on the dynamic motion of guest molecules as well as their binding strengths to the MOF host, and sheds light on the specific guest adsorption mechanisms. Variable-temperature (13)C SSNMR spectra of (13)CO2 adsorbed within various forms of MIL-53 are acquired and analyzed. CO2 undergoes a combination of two motions within MIL-53; we report the types of motion present, their rates, and rotational angles. (1)H-(13)C CP SSNMR experiments are used to examine the proximity of (1)H atoms in the MOF to (13)C atoms in CO2 guests. By replacing (1)H with (2)H in MIL-53, the location of the CO2 adsorption site in MIL-53 is experimentally confirmed by (1)H-(13)C CP SSNMR. The binding strength of CO2 within these MIL-53 MOFs follows the order MIL-53-NH2 (Al) > MIL-53-NH2 (Ga) > MIL-53 (Al) > MIL-53 (Ga).

The unique structural topology of metal-organic framework (MOF) MIL-68, featuring two types of channels with distinct pore sizes, makes it a promising candidate for application in gas storage and separation. In this study, the behavior of as-made and activated MIL-68(In) was investigated in a diamond-anvil cell under high pressure by in situ IR spectroscopy. The framework exhibits high stability under compression up to 9 GPa, whereas the bridging OH groups appear to be very sensitive to compression. Pressure-induced structural modifications were found to be completely reversible for as-made MIL-68(In) but irreversible for the activated framework. Moreover, the addition of Nujol as pressure-transmitting medium makes the framework more resilient to pressure. Finally, when loaded with CO2, the framework exhibited interesting differential binding affinities with CO2 in the hexagonal and triangular pores at different pressures. The pressure-enhanced CO2 storage behavior and the guest-host interaction mechanism between CO2 and the MOF framework were explored with the aid of Monte Carlo simulations. These studies demonstrated great potential for MIL-68(In) in gas-storage applications that require extreme loading pressures.

Crystalline FeAlO3/FeAl2O4 nanonets were synthesized by a modified template-assisted approach using anodic aluminum oxide (AAO) as a reactive and sacrificial template to direct and promote interfacial reaction growth (IRG). The as-prepared nanonets replicate the morphology of the porous AAO template and contain mixed FeAlO3 and FeAl2O4. To extend the applicability of the sacrificial-template-assisted IRG approach, porous anodic titanium oxide (ATO) was used as template in place of AAO, giving rise to Zn2TiO4 nanonet/nanotube and PbTiO3 nanonet/nanotube. These latter products are polycrystalline due to the polycrystalline nature of the ATO template. Growth mechanism for the formation of the Zn2TiO4 and PbTiO3 nanostructures is proposed. The present study shows that the IRG approach can be extended to fabricate patterned complex oxide nanomaterials that may find applications in a wide range of nanotechnologies such as electronics, photonics and spintronics.

Metal-organic frameworks (MOFs) are versatile materials that incorporate metal centers along with organic linkers in highly ordered, intricate structures. MIL-53 is a MOF that exhibits a “breathing effect,” where the pore size and MOF topology are profoundly influenced by the identity and binding mechanism of guest molecules. This phenomenon renders MIL-53 a promising candidate for sensing applications. In this report, the adsorption of various organic compounds within MIL-53 is investigated using a combination of complementary techniques. Thermal gravimetric analysis experiments confirm loading of the guest molecules and yield insight into adsorption interactions and strengths. Significant guest-induced changes in the crystal structure of MIL-53 are revealed by powder X-ray diffraction experiments; specific unique phases of MIL-53 are related to the identity of the guest molecule and its binding mechanism to the framework. 27Al and 13C solid-state NMR experiments probe the interaction between guest molecules and MIL-53. The relationship between the nature of the guest, the structure of MIL-53, and 27Al NMR parameters is explored. 27Al NMR parameters are sensitive to the host-guest binding mechanism (i.e., hydrogen-bonding or π–π stacking interactions) and yield valuable information regarding the influence of the adsorbates on the local aluminum environment. This combination of physical characterization techniques is a useful probe of guest adsorption and the breathing effect within MIL-53 and should prove useful for investigation of related MOFs.

The lithium ion conductivity of lithium argyrodite can be improved by introducing Cl to tailor the S/Cl disorder in the structure. An ultrafast room temperature lithium ion conductivity of up to 6.4 mS/cm was achieved for Li5.7PS4.7Cl1.3. The synthesis parameters for Li7-xPS6-xClx (x = 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9) are systematically investigated to obtain pure lithium argyrodite phase with high ionic conductivity. AC impedance spectroscopy and 7Li spin-lattice relaxation NMR are utilized to show the enhancement of lithium ion conductivity caused by the incorporation of Cl. Ab initio molecular dynamics (AIMD) simulations proved that the introduction of Cl can effectively decrease the energy barriers for lithium ion migration in both short and long diffusion length scales. All-solid-state lithium batteries using LiNbO3-coated LiNi0.8Mn0.1Co0.1O2 cathode and Li5.7PS4.7Cl1.3 solid electrolyte display high discharge capacities and excellent cycling performances at relatively high current densities. EIS and galvanostatic intermittent titration technique (GITT) further confirm that the improved electrochemical performance can be attributed to the mitigation of voltage polarization and reduction of the interfacial resistance between the cathode and solid electrolyte.

When permanent magnets are surrounded by ferromagnetic materials, the magnetic field lines are rerouted in the air gap between them, which provides an approach for the optimum design of the eddy current damper. To improve the conventional tubular eddy current damper design, an enhanced eddy current damper with a ferromagnetic shaft and a ferromagnetic layer is successfully developed in this study. It is passive, cost-efficient and reliable, significantly boosting the damping effect without occupying extra space. To explore the benefits of the ferromagnetic material, analytical models of the magnetic field distributions are derived to estimate the damping coefficient. In addition, the ferromagnetic material configuration and dimensions of the proposed eddy current damper are optimized for better vibration suppression. The experiment results agree reasonably well with the theoretical models and finite element predictions, and demonstrate the effectiveness and efficiency of this innovative design, which realizes a remarkable improvement in the damping coefficient, from 70.5 N s m−1 to 143.2 N s m−1.