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Background and purposeThe ring finger protein 213 gene (RNF213) p.R4810K variant increased the risk of acute ischaemic stroke (AIS) attributable to intracranial arterial stenosis (ICAS) in the Japanese and Korean populations. In this study, we aimed to examine the prevalence of theRNF213p.R4810K variant in Chinese patients with AIS or transient ischaemic attack and identify the phenotype of the carriers.MethodsWe analysed data from the Third China National Stroke Registry. All included participants were divided into two groups by carrier status of the p.R4810K variant. The aetiological classification was conducted according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. The presence of ICAS and extracranial arterial stenosis (ECAS) was defined as 50%–99% stenosis or occlusion of any intracranial and extracranial artery. Logistic regression models and Cox regression models were used to evaluate the association of the p.R4810K variant with TOAST classification, stenosis phenotypes and clinical outcomes.ResultsA total of 10 381 patients were enrolled, among which 56 (0.5%) had the heterozygote GA genotype for p.R4810K. The variant carriers were younger (p=0.01), and more likely to suffer from peripheral vascular disease (p=0.04). The p.R4810K variant was associated with large-artery atherosclerosis (LAA) (adjusted OR=1.94, 95% CI 1.13 to 3.33), anterior circulation stenosis (adjusted OR=2.12, 95% CI 1.23 to 3.65) and ECAS (adjusted OR=2.29, 95% CI 1.16 to 4.51). Nevertheless, the p.R4810K variant was not associated with recurrence, poor functional outcome and mortality at 3 months and 1 year.ConclusionsTheRNF213p.R4810K variant was associated with LAA, anterior circulation stenosis and ECAS in Chinese patients. Given the low carrying rate and only 1-year follow-up information, caution should be taken to interpret our findings in no statistically significant association between the p.R4810K variant and stroke prognosis in Chinese patients.

Hyperterpenoid A (1) and B (2), two pairs of enantiomers, with an unprecedented 6/6/4/6/6 polycyclic skeleton, along with one known compoud hypermonone A (3) were isolated from Hypericum beanii. The racemate (±)-1 and (±)-2 were successfully separated into the two optically pure enantiomers (ee ≥ 99%) using a preparative HPLC system. Their absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction method. The related plausible biogenetic pathways were presented. Compound 1-3 showed significant neuroprotective activity and potential anti-inflammatory activity. The result that (+)-2 and (-)-2 presented different anti-inflammatory properties, may lead us to new discovery of structure activity relationship between racemates, enantiomers, and diastereomers, as well as further research regarding the binding of drugs to target proteins.

Background and Purpose: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687]) but not in the high-risk group ( P >0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I-K (1-3), along with a known analogue hyphenrone X (4), were isolated from the aerial part of Hypericum pseudohenryi. The structures of the new compounds were elucidated by NMR spectroscopy and ECD calculation. The anti-inflammatory activity of the compounds was evaluated. Compounds 1-3 showed mild anti-inflammatory activity while hyphenrone X showed prominent anti-inflammatory activity.[Formula: see text].

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of Hypericum genus of Guttiferae family, and possessed intriguing chemical structures and appealing biolog...

Background and purposePrevious studies have reported conflicting results as to whether women have poorer functional outcome than men after thrombolytic therapy. This study aims to investigate the relationship between sex differences and the prognosis of intravenous thrombolysis in Chinese patients with acute ischaemic stroke.MethodsThe patients enrolled in this study were from the Chinese Acute Ischemic Stroke Thrombolysis Monitoring and Registration study. The primary outcome was poor functional outcome, defined as a 3-month modified Rankin score of 3–6. The safe outcome was symptomatic intracranial haemorrhage (SICH) and mortality within 7 days and 90 days. Multiple Cox regression model was used to correct the potential covariates to evaluate the association between sex disparities and prognosis. Furthermore, the interaction of preonset Rankin scores, baseline National Institute of Health Stroke Scale (NIHSS) scores and Trial of Org 10172 in Acute Stroke Treatment (TOAST) types was statistically analysed.ResultsA total of 1440 patients were recruited, including 541 women and 899 men. The baseline information indicated that women were older at the time of onset (66.2±11.2 years vs 61.0±11.3 years, pConclusionsFor Chinese patients with ischaemic stroke, although women are older and more severe at the time of onset, the prognosis after intravenous thrombolysis is not significantly different from men.

BackgroundMendelian stroke causes nearly 7% of ischaemic strokes and is also an important aetiology of cryptogenic stroke. Identifying the genetic abnormalities in Mendelian strokes is important as it would facilitate therapeutic management and genetic counselling. Next-generation sequencing makes large-scale sequencing and genetic testing possible.MethodsA systematic literature search was conducted to identify causal genes of Mendelian strokes, which were used to construct a hybridization-based gene capture panel. Genetic variants for target genes were detected using Illumina HiSeq X10 and the Novaseq platform. The sensitivity and specificity were evaluated by comparing the results with Sanger sequencing.Results53 suspected patients of Mendelian strokes were analysed using the panel of 181 causal genes. According to the American College of Medical Genetics and Genomics standard, 16 likely pathogenic/variants of uncertain significance genetic variants were identified. Diagnostic testing was conducted by comparing the consistency between the results of panel and Sanger sequencing. Both the sensitivity and specificity were 100% for the panel.ConclusionThis panel provides an economical, time-saving and labour-saving method to detect causal mutations of Mendelian strokes.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (

High-order harmonic generation of the cyclo[18]carbon (C18) molecule under few-cycle circularly polarized laser pulse is studied by time-dependent density functional theory. Compared with the harmonic emission of the ring molecule C6H6 having similar ionization potential, the C18 molecule has higher efficiency and cutoff energy than C6H6 with the same laser field parameters. Further researches indicate that the harmonic efficiency and cutoff energy of the C18 molecule increase gradually with the increase of the laser intensity of the driving laser or decrease of the wavelength, both are larger than those of the C6H6 molecule. Through the analysis of the time-dependent evolution of the electronic wave packets, it is also found that the higher efficiency of harmonic generation can be attributed to the larger spatial scale of the C18 molecule, which leads to a greater chance for the ionized electrons from one atom to recombine with others of the parent molecule. Selecting the suitable driving laser pulse, it is demonstrated that high-order harmonic generation in the C18 molecule has a wide range of applications in producing circularly polarized isolated attosecond pulse.

Two new prenylaromadendrane-type diterpenoids, and three known analogues, were isolated from the ethanol extract of the gum resin of

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I-K (

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of

An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (1-2), and two new biosynthetic precursors, hyperbeanins R-S (3-4), were isolated from Hypericum beanii, together with three known analogs (5-7). Compound 1 was one of type A PPAPs featured with unusual bicyclo[5.3.1]hendecane core. The structures of isolates were established by NMR spectroscopic methods, experimental electronic circular dichroism (ECD) spectra and comparisons with known compounds. Compounds 5 and 6 showed obvious hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage.

Two new prenylaromadendrane-type diterpenoids, and three known analogues, were isolated from the ethanol extract of the gum resin of B. sacra Flueck. The structures of the new compounds were elucidated using 1 D and 2 D NMR spectroscopic analyses, mass spectrometric data, circular dichroism spectra, and comparison with the other compounds in the literature. One diterpenoid represents the first example of an acetoxyl-substituted prenylaromadendranoid in frankincense. All compounds exhibited notable cytotoxicity against human malignant glioma (U87-MG) cell line, with inhibitory rates exceeding that of the positive control 5-fluorouracil. However, nitric oxide inhibition induced by lipopolysaccarides was not observed in primary mouse peritoneal macrophages.

Seven previously unidentified polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives hypseudohenrins A-G, along with six known analogs, were isolated from the aerial portion of Hypericum pseudohenryi. Their structures were determined by NMR, ECD and X-ray crystallographic spectroscopy. These compounds were screened for anti-inflammatory activity, and hypseudohenrins B and G (at the concentration of 10 μM) showed NO production inhibition ratios of 52.56% and 54.01%, respectively, which imply good anti-inflammatory activity. In particular, uraloidin A exhibited an NO inhibition ratio of 90.61%, while that ratio of the positive control compound dexamethasone was 94.88%. Additionally, anti-cancer and neural-protective activities were screened, but none of these compounds showed desirable activity.

Background and purposeThe Trial of Org 10 172 in Acute Stroke Treatment (TOAST) system is the most widely used aetiological categorisation system in clinical practice and research. Limited studies have validated the accuracy of routine aetiological diagnosis of patients with ischaemic stroke according to the TOAST criteria when the reported subtype is assumed to be correct. We investigated the agreement between centralised and non-centralised (site-reported, at discharge) stroke subtypes in the Third China National Stroke Registry (CNSR-III), and analysed the influence of classification consistency on evaluation during hospitalisation and for secondary prevention strategy.MethodsAll patients with ischaemic stroke from the CNSR-III study with complete diffusion-weighted imaging data were included. We used multivariable Cox proportional-hazard regression models to evaluate the factors associated with consistency between centralised and non-centralised stroke subtypes. Sensitivity analyses were conducted of the subgroup of patients with complete information.ResultsThis study included 12 180 patients (mean age, 62.3 years; and women, 31.4%). Agreement between centralised and non-centralised subtype was the highest for the large-artery atherosclerosis subtype stroke (77.4% of centralised patients), followed by the small-vessel occlusion subtype (40.6% of centralised patients). Agreements for cardioembolism and stroke of other determined aetiology subtypes were 38.7% and 12.2%, respectively. Patient-level and hospital-level factors were associated with the inconsistency between centralised/non-centralised aetiological subtyping. This inconsistency was related to differences in secondary prevention strategies. Only 15.3% of the newly diagnosed patients with cardioembolism underwent centralised subtyping with indications to receive oral anticoagulants at discharge. In comparison, 51.3% of the consistent cardioembolism group and 42.0% of the centrally reassigned cardioembolism group with anticoagulation indications were prescribed oral anticoagulants.ConclusionsSubstantial inconsistency exists between centralised and non-centralised subtyping in China. Inaccurate aetiological subtyping could lead to inadequate secondary prevention, especially in patients with cardioembolic stroke.

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (

Background and purposeTransient ischaemic attack (TIA), transient symptoms with infarction (TSI) and diffusion-weighted imaging (DWI)-negative acute ischaemic stroke (AIS) share similar aetiologies but are considered to have a rather benign prognosis. We intended to investigate the association between intracranial atherosclerotic stenosis (ICAS), extracranial atherosclerotic stenosis (ECAS) and the prognosis of patients with TIA, TSI and DWI-negative AIS.MethodsClinical and imaging data of eligible participants were derived from the Chinese Intracranial Atherosclerosis study, according to symptom duration, acute infarction on DWI and discharge diagnosis. Based on the severity and location of arterial atherosclerosis, we categorised the study population into four groups: no or ResultsA total of 806 patients were included, 67.3% of whom were male. The median age of the study participants was 63 years. Patients in the concurrent ≥50% ICAS and ECAS subgroup had both a significantly higher 1-year recurrence rate (adjusted HR 3.4 (95% CI 1.15 to 10.04), p=0.027) and a higher risk of composite vascular events (adjusted HR 3.82 (95% CI 1.50 to 9.72), p=0.005).ConclusionsConcurrent ICAS and ECAS is associated with a higher possibility of 1-year recurrent stroke or composite vascular events. Large artery evaluation is necessary to assess patients with transient ischaemic symptoms or DWI-negative AIS. Progress in shortening the time interval between symptom onset and large vessel evaluation is needed.

Three new homoadamantane-type polyprenylated acylphloroglucinols, hyperacmosins E-G (1-3), with seven known compounds were isolated from the air-dried aerial parts of Hypericum asmosepalum. Their structures were determined by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of these compounds were evaluated. Compounds 4 and 8 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1–3), with four known compounds (4–7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins N–P (1–3), were isolated from the air-dried aerial parts of Hypericum asmosepalum. Especially, compound 1 possessed a rare hexacyclic core, which was formed via oxidation and radical cyclization. Their structures were established by NMR, HRMS (ESI), and experimental electronic circular dichroism (ECD) spectra. The plausible biogenetic pathways of 1-3 were proposed, which gave an insight for future biomimetic synthesis of the novel compounds.

Familial cerebral cavernous malformation (FCCM) is a vascular malformation disorder that closely associated with three identified genes: KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3. Here, we present a Chinese family affected by FCCM due to a novel KRIT1/CCM1 insertion mutation. The proband was hospitalized for sudden unconsciousness and underwent surgical treatment. The section of lesions showed classical cavernous-dilated vessels without intervening brain parenchyma, and hemosiderin-laden macrophages were accumulated in the surrounding tissue. In addition, magnetic resonance imaging (MRI) showed severe multiple cerebral cavernous malformation (CCM) lesions in cerebrum, brainstem, and cerebellum in other affected subjects. Especially, for the proband's mother, hundreds of lesions were presented, and a few lesions were found in the expanded lateral ventricle (Evans' index =0.33). Moreover, she showed the similar symptoms of hydrocephalus, including headache, dizziness, and diplopia. It was extremely rare in previous reports. To date, the genetic alterations leading to FCCM in Chinese population remain largely unknown. We investigated genetic defects of this family. Sequence analyses disclosed a novel heterozygous insertion mutation (c.1896_1897insT; p.Pro633SerfsTer22) in KRIT1/CCM1. Moreover, our real-time PCR results revealed that the mRNA level of KRIT1/CCM1 were significantly decreased in FCCM subjects (CCM family =0.42 ± 0.20 vs. healthy control =1.01 ± 0.16, P = 0.004). It indicated that this mutation could cause KRIT1/CCM1 functional mRNA deficiency. It may be closely related with the pathogenesis of FCCM. Our findings provided a new gene mutation profile which will be of great significance in early diagnosis and appropriate clinical surveillance of FCCM patients.

Mineral spring water is a top quality potable groundwater resource formed by long-term groundwater-rock interaction in aquifer. Mineral spring water is rich in minerals and trace elements which are beneficial for human health. Given the current serious water pollution and environment deterioration, it is of great significance to re-recognize the ecological and health effects of mineral water based on new scientific and technological achievement. The Wudalianchi scenic area in Heilongjiang Province has abundant mineral water and peloid resources, which supported the development of tourism and convalescence and have been used in medical and health care for more than 100 years. However, it is threatened by resource reduction, environmental pollution, and other problems. Here, we reviewed the formation process, distribution, hydro-biochemical characteristics and health effects of the Wudalianchi mineral springs, with particular focus on the advances of microbial studies in this area. We also proposed the future research prospective for the Wudalianchi mineral water. To better protect and utilize the Wudalianchi mineral water, it was recommended that a green eco-agriculture practice in reducing chemical fertilizers should be adapted in the surrounding farms of Wudalianchi. Along with the development of tourism and recuperation resources, it is necessary to establish a framework of pollution risk assessment and control, and strictly reduce potential emerging pollutants to eco-geological environment.矿泉水是地下水从含水层中经长期与岩石相互作用形成、富含有益于人体的丰富矿物质和微量元素的一类顶级饮用地下水资源.在水资源污染严重而且生态环境不断恶化的今天,基于新的科技认知手段重新认识矿泉水的生态和健康效应,具有重要意义.黑龙江省五大连池风景区拥有着五大连池旅游疗养业赖以生存和发展的优质矿泉水资源,并且被应用于医疗和保健方面已有百余年历史,但是面临着资源量减少、环境污染等问题的威胁.本文主要针对五大连池矿泉水的形成过程、分布规律、水化学和微生物特征及其健康效应等进行综合评述,侧重其微生物特征的研究进展,提出了未来五大连池矿泉的研究展望.为了更好地保护和利用五大连池矿泉水,建议五大连池周边农场发展绿色生态农业,减少化肥的施用;在开发旅游和疗养资源的同时,要严格建立污染风险的评估和管控体系,减少“新型”环境污染物对地质生态环境的可能污染.

Preparation of sludge-derived mesoporous carbon materials (SMCs) through pyrolysis of excess activated sludge from urban municipal sewage plants is an effective means of reducing pollution and utilizing a waste resource. This paper presented a method of SMC preparation in which calcium oxide (CaO), polyacrylamide (PAM), and chitosan (CAS) flocculating agents were used as pore-forming additives. Physical and chemical characterizations of the prepared SMCs were conducted by scanning electron microscopy (SEM), Brunauer–Emmett–Teller (BET), Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS). The prepared SMCs were used to adsorb a tetracycline (TC) antibiotic pollutant. The influences of pH, adsorption time, temperature, and pollutant concentration on TC adsorption capacity were determined. The experiments demonstrated that weakly acidic conditions were conducive to TC adsorption, which mainly occurs via electrostatic and π-π interactions. The TC adsorption process by SMCs conformed better to the pseudo-second-order models, indicating that chemical adsorption was the dominant adsorption process. The isothermal adsorption of TC by the SMCs conformed to the Freundlich model. This implied that TC easily adhered onto the SMC surfaces via multilayer homogeneous adsorption. Thermodynamic studies revealed that the adsorption of TC onto SMCs was spontaneous and endothermic.

A series of monodisperse macromolecules with A2–A1–D–A1–A2 structure based on benzodithiophene (BDT) and diketopyrrolopyrrole (DPP) BDT-4DPP, BDT-DPP-Rhod and BDT-DPP-CA were designed, theoretically calculated and synthesized, and compared with their parent molecules BDT-2DPP and BDTS-2DPP with A1–D–A1 structure. These molecules possessed highly planar molecular geometries and high crystallinity. These molecules exhibited good thermal stability with decomposition temperatures of 322–388 °C, strong visible and near-infrared absorption (500–1000 nm), and HOMO energy levels of −5.38 to −5.19 eV and LUMO energy levels of −3.69 to −3.46 eV. Relative to the parent molecules A1–D–A1, A2–A1–D–A1–A2 molecules exhibited red-shifted and stronger absorption. The charge transport properties of these molecules were investigated by organic field-effect transistors, and their hole mobilities were 0.036–1.12 cm−2 V−1 s−1. Replacing alkyl with alkylthio on BDT led to mobility enhancement by one order of magnitude.