Search

Background: Dural arteriovenous fistula (DAVF), characterized by abnormally direct connections between meningeal arteries and meningeal veins or dural venous sinuses, is a rare subtype among the intracranial arteriovenous malformations. Although the clinical manifestations of DAVF are very variable depending on the locations and size of venous drainage, parkinsonism and urinary incontinence are rarely reported. Here, we present a rare case with parkinsonism and urinary incontinence secondary to DAVF. Case presentation: A 50-year-old man was admitted for a progressively worsening weakness of his left lower limb over a year with urinary incontinence for four months. Neurological examination revealed rigidity and bradykinesia of the left upper limb without an obvious tremor. Magnetic resonance imaging exhibited diffuse white matter hyperintensities in bilateral centrum semiovale. Cranial magnetic resonance venography revealed extensive tortuous venous malformations. Digital subtraction angiography exhibited multiple bilaterally distributed DAVF in the superior sagittal sinus, supplied by bilateral occipital arteries and superficial temporal arteries. In the one year follow-up, the patient with multiple DAVF bilaterally distributed was completely cured after endovascular treatment according to the symptoms and the follow-up imaging results. Conclusion: this report enriches the clinical presentations of DAVF with parkinsonism and urinary incontinence, which is a crucial diagnostic clue to be aware of the possibility. Moreover, these rare symptoms can be relieved by timely endovascular treatment.

Background Hereditary spastic paraplegia is a heterogeneous group of clinically and genetically neurodegenerative diseases characterized by progressive gait disorder. Hereditary spastic paraplegia can be inherited in various ways, and all modes of inheritance are associated with multiple genes or loci. At present, more than 76 disease-causing loci have been identified in hereditary spastic paraplegia patients. Here, we report a novel mutation in SPAST gene associated with hereditary spastic paraplegia in a Chinese family, further enriching the hereditary spastic paraplegia spectrum. Methods Whole genomic DNA was extracted from peripheral blood of the 15 subjects from a Chinese family using DNA Isolation Kit. The Whole Exome Sequencing of the proband was analyzed and the result was identified in the rest individuals. RaptorX prediction tool and Protein Variation Effect Analyzer were used to predict the effects of the mutation on protein tertiary structure and function. Results Spastic paraplegia has been inherited across at least four generations in this family, during which only four HSP patients were alive. The results obtained by analyzing the Whole Exome Sequencing of the proband exhibited a novel disease-associated in-frame deletion in the SPAST gene, and this mutation also existed in the rest three HSP patients in this family. This in-frame deletion consists of three nucleotides deletion (c.1710_1712delGAA) within the exon 16, resulting in lysine deficiency at the position 570 of the protein (p.K570del). This novel mutation was also predicted to result in the synthesis of misfolded SPAST protein and have the deleterious effect on the function of SPAST protein. Conclusion In this case, we reported a novel mutation in the known SPAST gene that segregated with HSP disease, which can be inherited in each generation. Simultaneously, this novel discovery significantly enriches the mutation spectrum, which provides an opportunity for further investigation of genetic pathogenesis of HSP.

The high energy footprint of commodity gas purification and increasing demand for gases require new approaches to gas separation. Kinetic separation of gas mixtures through molecular sieving can enable separation by molecular size or shape exclusion. Physisorbents must exhibit the right pore diameter to enable separation, but the 0.3-0.4 nm range relevant to small gas molecules is hard to control. Herein, dehydration of the ultramicroporous metal-organic framework Ca-trimesate, Ca(HBTC)⋅H

Tissue reperfusion is a serious therapeutic strategy of ischemic stroke in addition to recanalization. In this work, we aimed to establish new urokinase-based therapeutics in order to dissolve large vessel thrombus together with microthrombi for stroke implications. Formulations consisted of free urokinase (UK), polyethylene glycol–crosslinked urokinase nanogel (PEG-UK), and a 1:1 mixture of UK and PEG-UK (PEG-UK+UK) were tested both in vitro and in vivo. In vitro experiments confirmed the pH-dependent release of PEG-UK in the PEG-UK+UK formulation. It was activated at pH 6.50, an environmental pH in the infarct brain tissue, owing to the dynamic crosslink property of PEG-UK. In vivo tests on a thromboembolic stroke rat model showed that the formulations containing UK, i.e., free UK and PEG-UK+UK, demonstrated better neurological scores and smaller infarction volumes within the time window, in which the PEG-UK+UK formulation relatively performed better. On the other hand, the formulations containing PEG-UK, i.e., PEG-UK and PEG-UK+UK, gained sufficient thrombolytic efficiency beyond the time window. Further investigation on the mechanism revealed that PEG-UK could reduce microthrombus in distal microcirculation, and its destructive effect was also less than that of free UK. The PEG-UK+UK formulation actually provided a “dual targeting” delivery of UK to both the large vessels and the microcirculation, which was beneficial to the treatment of cerebral ischemic stroke both within and beyond the therapeutic time window.

Microorganisms with efficient organic matter degradation ability are essential for organic waste treatment. In this study, a thermophilic bacterium, Bacillus thermoliquefaciens, was identified to h...

Background: Extraventricular neurocytoma (EVN) is a rare central neurocytoma with neoplasms occurring in the brain parenchyma outside the ventricular system with similar biological behaviours and histopathological characteristics. Cases of EVN reported in the brainstem and cerebellum are fairly rare. In addition, very few cases with radiotherapy as the only treatment have been reported, and their outcomes were unclear.Case presentation: We reported an EVN of the brainstem and cerebellum confirmed by pathology in a 43-year-old male presenting with unprovoked nausea and dizziness. The patient showed a favourable outcome with only radiotherapy during the 2-year follow-up.Conclusions: Patients who have EVN may have a favourable prognosis with radiotherapy without surgery.

BackgroundsAn ongoing outbreak of novel coronavirus pneumonia (Covid-19) hit Wuhan and hundreds of cities, 29 territories in global. We present a method for scale estimation in dynamic while most of the researchers used static parameters.MethodsWe use historical data and SEIR model for important parameters assumption. And according to the time line, we use dynamic parameters for infection topology network building. Also, the migration data is used for Non-Wuhan area estimation which can be cross validated for Wuhan model. All data are from public.ResultsThe estimated number of infections is 61,596 (95%CI: 58,344.02-64,847.98) by 25 Jan in Wuhan. And the estimation number of the imported cases from Wuhan of Guangzhou was 170 (95%CI: 161.27-179.26), infections scale in Guangzhou is 315 (95%CI: 109.20-520.79), while the imported cases is 168 and the infections scale is 339 published by authority.ConclusionsUsing dynamic network model and dynamic parameters for different time periods is an effective way for infections scale modeling.

Purpose: We aimed to investigate the prevalence and clinical relevance of the parent artery plaque in acute lacunar stroke. Methods: This prospective, multi-center, observational study included patients with first-ever ischemic stroke within 72 hours of symptom onset. Patients were evaluated by three-dimensional T1-weighted high-resolution magnetic resonance imaging (HR-MRI) and conventional MRI sequences. We examined the presence of intracranial plaque, infarction patterns, and infarct volumes in all the patients with acute lacunar stroke. The outcome measurement was 90-day poor functional outcome (modified Rankin Scale >2). Results: Of the 756 patients included, 341(45.1%) patients had an acute lacunar stroke. There were 201 (58.9%, 201/341) patients with an infarct in deep basal ganglia area. Among them, 64 (31.8%, 64/201) patients had middle cerebral artery (MCA) plaques identified on HR-MRI. The patients with MCA plaque had a similar infarct volume ( 0.93ml vs. 0.88ml , p =0.9) with those without MCA plaque. However, they more likely had an infarct involving posterior limb of internal capsule (42.2%, 27/64 vs. 25.5%, 35/137, p =0.017 ) and had a higher prevalence of cerebral microbleed (68.8%, 44/64 vs. 40.1%, 55/137, p p =0.002) . After adjusting for age and National Institute of Health Stroke Scale (NIHSS) at admission, the presence of MCA plaque was independently associated with 90-day poor functional outcome (OR:3.44, [95% CI,1.26-9.42]). There were 102 (29.9%, 102/341) patients with an infarct in pons. Among them, 66 (64.7%, 66/102) patients had basilar artery (BA) plaques. Patients with BA plaque had a higher prevalence of moderate to severe BG-PVS (42.4%, 28/66 vs. 22.2%, 8/36, p =0.041). There were no differences between the patients with and without BA plaque regarding infarction volume and 90-day functional outcome. Conclusions: Parent artery plaque is common in patients with acute lacunar stroke. We propose the deep basal ganglia area infarct with MCA plaque as a unique lacunar stroke subtype with poor prognosis. Our data did not show the presence of BA plaque have an effect on the lacunar stroke prognosis.

Additional file 1: Supplementary Table. Laboratory results and vital signs for each group before and after treatment (safety set)

peer-reviewed The full text of this article will not be available in ULIR until the embargo expires on the 25/05/2021 The high energy footprint of commodity gas purification and ever-increasing demand for gases require new approaches to gas separation. Kinetic separation of gas mixtures through molecular sieving can enable “ideal” separation through molecular size or shape exclusion. Physisorbents must exhibit just the right pore diameter to enable such ideal separation, but the 0.3-0.4 nm range relevant to small gas molecules is hard to control with precision. Herein, we report that dehydration of the ultramicroporous metal-organic framework Ca-trimesate, Ca(HBTC).H2O (H3BTC = trimesic acid), bnn-1-Ca-H2O, affords a narrow pore variant, Ca(HBTC), bnn-1-Ca. Whereas bnn-1-Ca-H2O (pore diameter 0.34 nm) exhibits ultra-high CO2/N2, CO2/CH4 and C2H2/C2H4 binary selectivities, bnn-1-Ca (pore diameter 0.31 nm) offers ideal selectivities for H 2 /CO 2 and H2/N2 under cryogenic conditions. Ca-trimesate, the first physisorbent to exhibit H2 sieving under cryogenic conditions, could be prototypal for a potentially general approach to exert precise control over pore diameter in physisorbents.

Metal-organic frameworks (MOFs) are a class of important porous materials with many current and potential applications. Their applications almost always involve the interaction between host framework and guest species. Therefore, understanding of host-guest interaction in MOF systems is fundamentally important. Solid-state NMR spectroscopy is an excellent technique for investigating host-guest interaction as it provides information complementary to that obtained from X-ray diffraction. In this work, using MOF α-Mg3 (HCOO)6 as an example, we demonstrated that 13 C chemical shift tensor of organic linker can be utilized to probe the host-guest interaction in MOFs. Obtaining 13 C chemical shift tensor components (δ11 , δ22 , and δ33 , where δ11 ≥ δ22 ≥ δ33 ) in this MOF is particularly challenging as there are six coordinatively equivalent but crystallographically non-equivalent carbons in the unit cell with very similar local coordination environment. Two-dimensional magic-angle-turning experiments were employed to measure the 13 C chemical shift tensors of each individual crystallographically non-equivalent carbon in three microporous α-Mg3 (HCOO)6 samples with different guest species. The results indicate that the δ22 component (with its direction approximately being co-planar with the formate anion and perpendicular to the C-H bond) is more sensitive to the adsorbate molecules inside the MOF channel due to the weak C-H···O hydrogen bonding or the ring current effect of benzene. The 13 C isotropic chemical shift, on the other hand, seems much less sensitive to the subtle changes in the local environment around formate linker induced by adsorption. The approach described in this study may be used in future studies on host-guest interaction within MOFs.

Loading metal guests within metal–organic frameworks (MOFs) via secondary functional groups is a promising route for introducing or enhancing MOF performance in various applications. In this work, 14 metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ba2+, Zn2+, Co2+, Mn2+, Ag+, Cd2+, La3+, In3+, and Pb2+) have been successfully introduced within the MIL-121 MOF using a cost-efficient route involving free carboxylic groups on the linker. The local and long-range structure of the metal-loaded MOFs is characterized using multinuclear solid-state NMR and X-ray diffraction methods. Li/Mg/Ca-loaded MIL-121 and Ag nanoparticle-loaded MIL-121 exhibit enhanced H2 and CO2 adsorption; Ag nanoparticle-loaded MIL-121 also demonstrates remarkable catalytic activity in the reduction of 4-nitrophenol.

The properties and applications of metal–organic frameworks (MOFs) are strongly dependent on the nature of the metals and linkers, along with the specific conditions employed during synthesis. Al-fumarate, trademarked as Basolite A520, is a porous MOF that incorporates aluminum centers along with fumarate linkers and is a promising material for applications involving adsorption of gases such as CO2. In this work, the solvothermal synthesis and detailed characterization of the gallium- and indium-fumarate MOFs (Ga-fumarate, In-fumarate) are described. Using a combination of powder X-ray diffraction, Rietveld refinements, solid-state NMR spectroscopy, IR spectroscopy, and thermogravimetric analysis, the topologies of Ga-fumarate and In-fumarate are revealed to be analogous to Al-fumarate. Ultra-wideline 69Ga, 71Ga, and 115In NMR experiments at 21.1 T strongly support our refined structure. Adsorption isotherms show that the Al-, Ga-, and In-fumarate MOFs all exhibit an affinity for CO2, with Al-fumarate bei...

Objective We aimed to evaluate the value of 3D pseudocontinuous arterial spin-labeling (pCASL) perfusion imaging detected crossed cerebellar diaschisis (CCD) at different stages of intracerebral hemorrhage (ICH). Materials and methods We assessed bilateral cerebral blood flow (CBF) values of different brain regions and the relationships between the CCD and clinical status of 16 ICH patients. Results The ICH patients had significantly lower CBF values in the contralateral cerebellum in acute, subacute and chronic stages. The subacute CCD had a significant correlation with clinical status. Conclusions 3D pCASL may be an ideal tool to study the phenomenon and clinical consequences of ICH with CCD.

Calcium-based metal-organic frameworks (MOFs) are of high importance due to their low cost and bio-compatible metal centers. Understanding the local environment of calcium in these materials is critical for unraveling the origins of specific MOF properties. 43 Ca solid-state NMR spectroscopy is one of the very few techniques that can directly characterize calcium metal centers, however, the 43 Ca nucleus is a very challenging target for solid-state NMR spectroscopy due to its extremely low natural abundance and resonant frequency. In this work, natural abundance 43 Ca solid-state NMR spectroscopy, at a high magnetic field of 21.1 T, has been employed to characterize several calcium-based MOFs. We demonstrate that 43 Ca NMR spectra and quantum chemical calculations can probe the local structure of calcium metal centers within MOFs, investigate the presence of guests, and monitor phase changes.

The selective synthesis of the zinc-acetato-phosphinidene cluster [Zn

Silicoaluminophosphates (SAPOs) are microporous frameworks with Bronsted acid sites that can be used as acidic catalysts. A firm understanding of SAPO structure, formation, and crystallinity is nec...

The urokinase-type plasminogen activator (uPA) loaded hollow nanogels (nUK) were synthesized by a one-step reaction of glycol chitosan and aldehyde capped poly (ethylene oxide). The resultant formulation is sensitive to diagnostic ultrasound (US) of 2 MHz. Herein, we evaluated the in vivo sonothrombolysis performance of the nUK on acute ischemic stroke rat model which was established by suture embolization of middle cerebral artery (MCA). Via intravenous (i.v.) administration, the experimental data prove a controlled release of the therapeutic protein around the clots under ultrasound stimulation, leading to enhanced thrombolysis efficiency of the nUK, evidenced from smaller infarct volume and better clinical scores when compared to the i.v. dose of free uPA no matter with or without US intervention. Meanwhile, the preservation ability of the nanogels not only prolonged the circulation duration of the protein, but also resulted in the better blood-brain barrier protection of the nUK formulation, showing no increased risk on the hemorrhagic transformation than the controls. This work suggests that the nUK is a safe sonothrombolytic formulation for the treatment of acute ischemic stroke., Graphical abstract Image 1, Highlights • Ultrasonic responsive urokinase (uPA)-loaded hollow nanogels (nUK) were synthesized for stroke treatment. • Acute ischemic stroke rat model was established by suture embolization of middle cerebral artery. • The nUK enhanced the sonothrombolytic efficacy and led to better BBB protection compared to the free uPA.

Summary Background No treatment has consistently shown efficacy in slowing disability progression in patients with secondary progressive multiple sclerosis (SPMS). We assessed the effect of siponimod, a selective sphingosine 1-phosphate (S1P) receptor 1,5 modulator, on disability progression in patients with SPMS. Methods This event-driven and exposure-driven, double-blind, phase 3 trial was done at 292 hospital clinics and specialised multiple sclerosis centres in 31 countries. Using interactive response technology to assign numbers linked to treatment arms, patients (age 18–60 years) with SPMS and an Expanded Disability Status Scale score of 3·0–6·5 were randomly assigned (2:1) to once daily oral siponimod 2 mg or placebo for up to 3 years or until the occurrence of a prespecified number of confirmed disability progression (CDP) events. The primary endpoint was time to 3-month CDP. Efficacy was assessed for the full analysis set (ie, all randomly assigned and treated patients); safety was assessed for the safety set. This trial is registered with ClinicalTrials.gov, number NCT01665144. Findings 1651 patients were randomly assigned between Feb 5, 2013, and June 2, 2015 (1105 to the siponimod group, and 546 to the placebo group). One patient did not sign the consent form, and five patients did not receive study drug, all of whom were in the siponimod group. 1645 patients were included in the analyses (1099 in the siponimod group and 546 in the placebo). At baseline, the mean time since first multiple sclerosis symptoms was 16·8 years (SD 8·3), and the mean time since conversion to SPMS was 3·8 years (SD 3·5); 1055 (64%) patients had not relapsed in the previous 2 years, and 918 (56%) of 1651 needed walking assistance. 903 (82%) patients receiving siponimod and 424 (78%) patients receiving placebo completed the study. 288 (26%) of 1096 patients receiving siponimod and 173 (32%) of 545 patients receiving placebo had 3-month CDP (hazard ratio 0·79, 95% CI 0·65–0·95; relative risk reduction 21%; p=0·013). Adverse events occurred in 975 (89%) of 1099 patients receiving siponimod versus 445 (82%) of 546 patients receiving placebo; serious adverse events were reported for 197 (18%) patients in the siponimod group versus 83 (15%) patients in the placebo group. Lymphopenia, increased liver transaminase concentration, bradycardia and bradyarrhythmia at treatment initiation, macular oedema, hypertension, varicella zoster reactivation, and convulsions occurred more frequently with siponimod than with placebo. Initial dose titration mitigated cardiac first-dose effects. Frequencies of infections, malignancies, and fatalities did not differ between groups. Interpretation Siponimod reduced the risk of disability progression with a safety profile similar to that of other S1P modulators and is likely to be a useful treatment for SPMS. Funding Novartis Pharma AG.

This paper describes the conformational analysis of 1,2-dichloroethane adsorbed into three different metal-organic frameworks, MIL-53(Al), MIL-68(In), MIL-53-NH2(Al), by using FT-Raman spectroscopy in combination with powder XRD and TGA. For non-polar frameworks, the main guest-host interactions are van der Waal interactions between the C H bonds of 1,2-dichloroethane (DCE) and the π system of terephthalate ligands. The polar framework of MIL-53-NH2 is able to stabilize the gauche conformation of DCE at room temperature. The conformational enthalpy of each system was determined through variable temperature FT-Raman spectroscopy. Furthermore, the line-width of the Raman bands provides information regarding the molecular motion of the halocarbons at various temperatures inside the framework.

Auxin is a vital plant growth regulator and can also take a part in plant defense. The study focused on the efficacy of the major active form of auxin, indole-3-acetic acid (IAA), on inhibition of blue mold rot caused by Penicillium expansum in pear fruit wounds and the possible action mechanisms involved. Results indicated that IAA at 100–500 μg mL−1 significantly enhanced the resistance of pear fruit against blue mold rot when the treating interval was between 24 and 48 h, while it had no direct antifungal activities towards P. expansum in vitro. Moreover, IAA induced a significant increase on the activities of β-1,3-glucanase (GLU), chitinase (CHI) and phenylalanine ammonia-lyase (PAL) in pear fruit. Furthermore, the data revealed that the expressions of endoglu9, CHI4, PR1, PR4 and PAL were up-regulated substantially in pear fruit treated with IAA. The all findings highlight the efficiency of IAA on inducing the natural resistance of pear fruit against P. expansum and suggest that the mechanisms may be closely related to the elicitation of defense-related enzymes and genes.

As the first and most famous cryptocurrency-based blockchain technology, Bitcoin has attracted tremendous attention from both academic and industrial communities in the past decade. A Bitcoin network is comprised of two interactive parties: individual miners and mining pool managers, each of which strives to maximize its own utility. In particular, individual miners choose which mining pool to join and decide on how much mining power to commit under limited constraints on the mining budget and mining power capacity; managers of mining pools determine how to allocate the mining reward and how to adjust the membership fee. In this work we investigate the miners’ and mining pool managers’ decisions in repeated Bitcoin mining competitions by building a Monte-Carlo discrete-event simulation model. Our simulation model (i) captures the behavior of these two parties and how their decisions affect each other, and (ii) characterizes the system-level dynamics of the blockchain in terms of the mining difficulty level and total mining power. In addition, we study the sensitivity of system performance metrics with respect to various control parameters. Our analysis may provide useful guidelines to mining activity participants in the Bitcoin network.

ConspectusAn exciting advance in materials science is the discovery of hybrid organic–inorganic solids known as metal–organic frameworks (MOFs). Although they have numerous important applications, the local structures, specific molecular-level features, and guest behaviors underpinning desirable properties and applications are often unknown. Solid-state nuclear magnetic resonance (SSNMR) is a powerful tool for MOF characterization as it provides information complementary to that from X-ray diffraction (XRD). We describe our novel pursuits in the three primary applications of SSNMR for MOF characterization: interrogating the metal center, targeting linker molecules, and probing guests.MOFs have relatively low densities, and the incorporated metals are often quadrupolar nuclei, making SSNMR detection difficult. Recently, we examined the local structures of metal centers (i.e., 25Mg, 47/49Ti, 63/65Cu, 67Zn, 69/71Ga, 91Zr, 115In, 135/137Ba, 139La, 27Al) in representative MOFs by SSNMR at a high magnetic field...

Systematic 111Cd solid-state (SS) NMR experiments were performed to correlate X-ray crystallographic data with SSNMR parameters for a set of CdS-based materials, varying from molecular crystals of small complexes [Cd(SPh)4]2- and [Cd4(SPh)10]2- to superlattices of large monodisperse clusters [Cd54S32(SPh)48(dmf)4]4- and 1.9 nm CdS. Methodical data analysis allowed for assigning individual resonances or resonance groups to particular types of cadmium sites residing in different chemical and/or crystallographic environments. For large CdS frameworks, 111Cd resonances were found to form three groups. This result is noteworthy, since for related systems with size polydispersity and variations in composition, such as CdS or CdSe nanoparticles protected with an organic ligand shell, typically only two groups of resonances were observed. The generalized information obtained in this work can be used for the interpretation of 111/113Cd SSNMR data for large CdS clusters and nanoparticles, for which crystal structure analysis remains inaccessible. Comparison of the powder X-ray diffraction patterns for freshly prepared and dried superlattices of large CdS clusters revealed an interesting superstructure rearrangement that was not observed for the smaller frameworks.

The biologic activity of IgG molecules is modulated by its crystallizable fragment N-glycosylation, and thus, the analysis of IgG glycosylation is critical. A standard approach to analyze glycosylation of IgGs involves the release of the N-glycans by the enzyme peptide N-glycosidase F, which cleaves the linkage between the asparagine residue and innermost N-acetylglucosamine (GlcNAc) of all N-glycans except those containing a 3-linked fucose attached to the reducing terminal GlcNAc residue. The importance of obtaining complete glycan release for accurate quantitation led us to investigate the kinetics of this de-glycosylation reaction for IgG glycopeptides and to determine the effect of glycan structure and amino acid sequence on the rate of glycan release from glycopeptides of IgGs. This study revealed that the slight differences in amino acid sequences did not lead to a statistically different deglycosylation rate. However, statistically significant differences in the deglycosylation rate constants were observed between glycopeptides differing only in glycan structure (i.e., nonfucosylated, fucosylated, bisecting-GlcNAc, sialylated, etc.). For example, a single sialic acid residue was found to decrease the rate by a factor of 3. Similar reductions in rate were associated with the presence of a bisecting-GlcNAc. We predict the differences in release kinetics can lead to significant quantitative variations of the glycosylation study of IgGs.

Objective:To examine whether a change in serum total homocysteine (tHcy) levels is associated with first stroke risk in a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT).Methods:We analyzed 16,867 participants of the CSPPT with tHcy measurements at both baseline and exit visits. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction, and stroke. The percent decline in tHcy was calculated as [(baseline tHcy − exit tHcy)/baseline tHcy × 100].Results:Over the median treatment duration of 4.5 years, participants who developed a first stroke had a significantly lower percent decline in tHcy (β = −5.7; 95% confidence interval [CI] −8.8 to −2.6) compared to their counterparts. A 20% tHcy decline was associated with a reduction in stroke risk of 7% (hazard ratio [HR] 0.93; 95% CI 0.90–0.97). When percent decline in tHcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2–3 (HR 0.79; 95% CI 0.64–0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events. The beneficial effect associated with greater tHcy reduction was observed across strata for age, sex, treatment group (with vs without folic acid), MTHFR C677T genotypes, baseline tHcy and serum folate levels, and blood pressure control.Conclusions:Percent lowering in tHcy was significantly associated with a reduction in first stroke risk in Chinese adults with hypertension, and if further confirmed, may serve as a useful indicator for folic acid treatment efficacy on stroke prevention.Clinicaltrials.gov identifier:NCT00794885.

On the way to impel Rhodosporidium paludigenum to behave like a serviceable and beneficial biocontrol antagonist, it was found that adding different concentrations of N-acetylglucosamine (GlcNAc) during the culture can reduce the incidence of pears caused by Penicillium expansum. 0.1 % GlcNAc is an optimal concentration in the range of 0.001 %–2 %. R. paludigenum, cultivated and gathered from the medium with a final concentration of 0.1 % GlcNAc, declared the best impact on restraint on P. expansum on pears. This inhibitory effect is analogous to the consequence of spore germination experiments in vitro. The R. paludigenum gathered after GlcNAc induction, at the same time, displayed exceptional viability and vigour under different stress conditions, including sodium chloride (NaCl), calcofluor white (CFW), Congo red (CR) and sodium dodecyl sulfate (SDS). The enzyme activity and the relative gene expression levels of some antioxidant-related enzymes in R. paludigenum, including peroxisomal catalase (CAT), thioredoxin reductase (TrxR), glutathione peroxidase (GSH-PX), glutathione reductase (GR) and superoxide dismutase (SOD), were detected to be up-regulated in further testing. At the same time, the reactive oxygen species (ROS) remained at a low status.

A vibration isolator based on a tunable negative stiffness mechanism combines the advantages of high-static-low-dynamic stiffness (HSLDS) isolators to expand the isolation frequency band and variable stiffness isolators to suppress resonance. In this paper, a novel tunable negative stiffness spring using Maxwell normal stress (SMNS) is proposed. The stiffness tunable range and energy utilization efficiency are greatly improved due to the newly designed magnetic circuit. Moreover, the electromagnetic negative stiffness device has the advantages of no friction, no backlash, compact structure and easy control. An analytical model of the electromagnetic force is built based on magnetic circuit analysis, and the parameter analysis is performed. An HSLDS isolator is constructed by connecting the SMNS in parallel with a linear isolator. The stiffness and vibration isolation performance are measured. The experimental results show that the SMNS produces an online tunable negative stiffness, which expands the isolation bandwidth and significantly improves the vibration isolation performance.

The launch of China's new national urbanization plan, coupled with increasing concerns about air pollution, calls for better understandings of the nexus between urbanization and the air pollution–related health. Based on refined estimates of PM 2.5 related mortality in China, we developed an Urbanization–Excess Deaths Elasticity (U–EDE) indicator to measure the marginal PM 2.5 related mortality caused by urbanization. We then applied statistical models to estimate U–EDE and examined the modification effects of income on U–EDE. Urbanization in China between 2004 and 2012 led to increased PM 2.5 related mortality. A 1% increase in urbanization was associated with a 0.32%, 0.14%, and 0.50% increase in PM 2.5 related mortality of lung cancer, stroke, and ischemic heart disease. U–EDEs were modified by income with an inverted U curve, i.e., lower marginal impacts at the lowest and highest income levels. In addition, we projected the future U–EDE trend of China as a whole and found that China had experienced the peak of U–EDE and entered the second half of the inverted U–shaped curve. In the near future, national average U–EDE in China will decline along with the improvement of income level if no dramatic changes happen. However, the decreased U–EDE only implies that marginal PM 2.5 –related mortality brought by urbanization would decrease in China. Total health damage of urbanization will keep going up in the predictable future because the U–EDE is always positive.

Background The present study aimed to investigate the prevalence and risk factors for extracranial carotid artery stenosis (ECAS) and intracranial carotid artery stenosis (ICAS) simultaneously in asymptomatic Chinese pure rural population. Methods We analyzed 2589 asymptomatic subjects aged over 30 yr. by ultrasonography and transcranial Doppler simultaneously in 13 isolated villages by door-to-door investigation. Both ECAS and ICAS were defined as more than 50% stenosis. Demographics, medical history documentation, and investigation of biochemical results were performed for each subject. Univariate and multivariate logistic regression analyses were employed to assess the risk factors associated with ECAS and ICAS, respectively. Results One hundred twenty-two (4.7%) residents with ICAS and 56 (2.2%) with ECAS were found in 2589 subjects. Three factors emerged as independent risk factors for ICAS: age (95% confidence interval [CI] = 1.01–1.04, odds ratio [OR] = 1.07), hypertension (95% CI = 1.98–4.37, OR = 2.94), and diabetes mellitus (95% CI = 1.72–4.38, OR = 2.75). As for ECAS, five factors presented as independent risk factors: age (95% CI = 1.09–1.11, OR = 1.10), male sex (95% CI = 1.01–1.02, OR = 1.01), diabetes mellitus (95% CI = 1.10–2.12, OR = 1.53), systolic blood pressure (95% CI = 1.95–2.88, OR = 2.37), and total cholesterol (95% CI = 1.00–1.13, OR = 1.06). Conclusions ICAS and ECAS were relatively common among asymptomatic rural Chinese subjects. Although they shared similar risk factors, differences still existed between them.

A novel normal-phase UPLC-QToF MS method was developed for sphingolipids analysis, which was then applied to separate and identify seven classes of sphingolipids in plasma. The time-consuming of this novel method was much shorter than previous 2D LC–MS method, while the sensitivity, repeatability and resolution for sphingolipids analysis were better or comparable. Besides, the differences of lipids in human plasma among diabetes mellitus patients, diabetes mellitus associated with atherosclerosis patients and control subjects were also compared. Finally, 12 sphingolipids species were identified as the amounts of which in diabetes mellitus associated with atherosclerosis patients were significantly higher than them in diabetes mellitus patients (VIP >1.0, p value 1.5). As the isomers of GalCs and GluCs were successfully separated, it was found that five GluCs, rather than GalCs, were included in these 12 potential biomarkers. These results suggest the need to separate GalCs from GluCs, and also indicated that there may be some extra activation pathways of diabetes mellitus associated with atherosclerosis, different from the atherosclerosis pathway and the diabetes mellitus pathway, causing cardiovascular disease.

Ga-MIL-53 is a metal-organic framework (MOF) that exhibits a “breathing effect,” in which the pore size and overall MOF topology can be influenced by temperature, pressure, and host-guest interactions. The phase control afforded by this flexible framework renders Ga-MIL-53 a promising material for guest storage and sensing applications. In this work, the structure and behavior of four Ga-MIL-53 phases ( as , ht , enp and lt ), along with CO 2 adsorbed within Ga-MIL-53 at various loading levels, has been investigated using 69/71 Ga solid-state NMR (SSNMR) experiments at 21.1 T and 9.4 T. 69/71 Ga SSNMR spectra are observed to be very sensitive to distortions in the octahedral GaO 6 secondary building units within Ga-MIL-53; by extension, Ga NMR parameters are indicative of the particular crystallographic phase of Ga-MIL-53. The evolution of Ga NMR parameters with CO 2 loading levels in Ga-MIL-53 reveals that the specific CO 2 loading level offers a profound degree of control over the MOF phase, and the data also suggests that a re-entrant phase transition is present. Adsorption of various organic compounds within Ga-MIL-53 has been investigated using a combination of thermal gravimetric analysis (TGA), powder X-ray diffraction (pXRD) and 69/71 Ga SSNMR experiments. Notably, pXRD experiments reveal that guest adsorption and host-guest interactions trigger unambiguous changes in the long-range structure of Ga-MIL-53, while 69/71 Ga SSNMR parameters yield valuable information regarding the effect of the organic adsorbates on the local GaO 6 environments. This approach shows promise for the ultra-wideline investigation of other quadrupolar metal nuclei in MIL-53 ( e.g. , In-MIL-53) and MOFs in general, particularly in regards to adsorption-related applications.

Rationale Stroke presents a serious health problem in China. Despite progresses made in recent years, there is still a lack of effective treatments for acute ischemic stroke (AIS) in clinical practices. Aims The Chinese Acute Ischemic Stroke Treatment Outcome Registry (CASTOR) is designed to evaluate the patterns and cost-effectiveness of current treatments for AIS in real-world settings in China. Design CASTOR is a prospective, multi-center study registered with ClinicalTrials.gov (NCT02470624) with a target sample size of 10,000 patients who are experiencing AIS. The patients are treated for AIS following the Chinese stroke guideline and local practice. Real-world data on treatment regimens, outcomes and costs are collected at baseline (Visit 1) and during subsequent visits (Visit 2 to Visit 5) after medication treatments. Outcome The primary objective of the present study is to analyze the current treatment status of AIS in real world settings. The secondary objectives include: 1) to compare the effectiveness of common treatment regimens, 2) to analyze the cost-effectiveness of different treatment regimens for AIS, 3) to analyze the incidence of adverse events and complications in enrolled patients with AIS, 4) to analyze the effect of Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification on the specific therapies during acute phase treatment period. Discussion In face of changing treatment patterns and increasing demand from medical insurers for cost-effectiveness data in China, a large-scale registry study examining the real-world patterns of AIS in hospitals is needed. The CASTOR study will help to find favorable cost-utility treatment regimens for AIS and improve the overall treatment outcome of Chinese patients with AIS. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1863-4) contains supplementary material, which is available to authorized users.

Isolation of lipophilic compounds by countercurrent chromatography (CCC) is a challenge because biphasic solvent systems in which these compounds distribute evenly are difficult to obtain. In this article we present novel applications of lipid compound isolation from natural sources. Conjugated linolenic acids (CLnAs, log KOW ∼7) were isolated from pomegranate oil using a solvent system consisting of n-heptane/methanol/water 100:91:9 (v/v/v). The CLnA fraction was free of other fatty acids but consisted of different isomers which were not resolved from each other. In the less polar range (log KOW ∼12), three tocotrienols (α-, γ- and δ-tocotrienol) were isolated from a vitamin E capsule produced from palm oil by using the solvent system n-hexane/acetonitrile/benzotrifluoride (BTF) at a ratio of 10:6.5:3.5 (v/v/v). Between 36 and 65 mg of each of the three tocotrienols were obtained in one injection with purities >97%. Advantages and disadvantages of the “BTF system” are discussed by comparing the phase composition with the simple n-hexane/acetonitrile system and by the fractionation of phytosterols (log KOW ∼9.5) from rapeseed oil.

Ceramide has been recognized as a second messenger that regulates several intracellular processes in neuronal cells. However, its role in neuronal autophagy is not fully understood. In this study, we used a human neuroblastoma cell line (SH-SY5Y) to investigate the mechanisms underlying C2-ceramide-mediated cell death and autophagy. C2-ceramide induced caspase-3-independent cell death. In addition, C2-ceramide induced autophagy, decreased the activation of Akt and mTOR, and increased the activation of JNK and ERK1/2. However, only inhibition of ERK1/2 with PD98059 prevented C2-ceramide-induced autophagy, indicating that the ERK1/2 pathway contributes to ceramide-induced autophagy. According to the results of the flow cytometric assays, C2-ceramide-induced cell death was increased by 3-methyadenine (3-MA) and decreased by rapamycin. Furthermore, the generation of reactive oxygen species (ROS) in the cells was increased by 3-MA and decreased by rapamycin. Based on these datas, autophagy protected SH-SY5Y cells from C2-ceramide-induced cell death by decreasing ROS production. Therapeutic strategies that regulate autophagy may be used in the treatment of neurological disorders associated with ceramide-induced cell death.

Background and Purpose— CD163, a receptor for hemoglobin, is involved in hemoglobin clearance after intracerebral hemorrhage (ICH). In contrast to microglial/macrophage CD163, neuronal CD163 hemoglobin has not been well studied. This study examined the expression of neuronal CD163 in a pig model of ICH and in vitro rat cortical neurons and the impact of deferoxamine on that expression. Methods— There were 2 parts to this study. In the in vivo part, piglets had injection of autologous blood into the right frontal lobe. The time course of CD163 expression and the effect of deferoxamine on the expression of CD163 after ICH were determined in the grey matter. In the in vitro part, the levels of CD163 and neuronal death and the effect of deferoxamine were examined in rat cortical neurons culture treated with hemoglobin. Results— CD163-positive cells were found, and the CD163 protein levels were upregulated in the ipsilateral grey matter after ICH. The CD163 levels peaked at days 1 and 3. The CD163-positive cells were colocated with NeuN-positive, heme oxygenase-2–positive, and terminal deoxynucleatidyl transferase dUTP nick end labeling–positive cells. Deferoxamine treatment attenuated ICH-induced CD163 upregulation and significantly reduced both brain CD163 and hemoglobin levels at day 3. Treating neuronal cultures with hemoglobin for 24 hours resulted in CD163 upregulation and increased cell death. Deferoxamine significantly attenuated the hemoglobin-induced neuronal death and CD163 upregulation. Conclusions— CD163 is expressed in neurons and upregulated after ICH. Deferoxamine reduced ICH-induced CD163 upregulation and brain cell death in vivo and hemoglobin-induced CD163 upregulation and neuronal death in vitro.