Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.

Experimental generation of the polycyclic tornado circular swallowtail beam with self-healing and auto-focusing.

In this paper, the polycyclic tornado circular swallowtail beam (PTCSB) with autofocusing and self-healing properties is generated numerically and experimentally and their properties are investigated. Compared with the circular swallowtail beam (CSB), the optical distribution of the PTCSB presents a tornado pattern during the propagation. The number of spiral stripes, as well as the orientation of the rotation, can be adjusted by the number and the sign of the topological charge. The Poynting vectors and the orbital angular momentum are employed to investigate the physical mechanism of beam-rotating. In addition, we also introduce a sector-shaped opaque obstacle to investigate the self-healing property of the PTCSB, passing through it with different center angles and discuss the influence of the scaling factor along the propagation direction. Our results may expand the potential applications in the optical spanner and material processing.

Circular Mathieu and Weber autofocusing beams.

In this Letter, the new classes of non-paraxial autofocusing beams are introduced for the first time, to the best of our knowledge. We investigate both numerically and experimentally non-paraxial circular Mathieu and Weber autofocusing beams based on the solutions of the Helmholtz equation in elliptical and parabolic coordinates, respectively. The results show that such beams can significantly shorten the focus distance, and eliminate the intense oscillation effectively after the focusing point. The focal length and the peak intensity can be controlled by tunable parameters. In addition, we further experimentally realize their application of such beams in optical trapping.

Value of thrombus imaging in predicting the outcomes of patients with large-vessel occlusive strokes after endovascular therapy.

BACKGROUND: Acute ischemic stroke leads to serious long-term disability and high mortality, especially in patients with large-vessel occlusive strokes. Nowadays, endovascular therapy is considered as an alternative treatment for these patients. Several studies have used thrombus characteristics based on non-contrast computed tomography (NCCT) and computed tomography angiography (CTA) to predict prognosis in ischemic stroke. We conducted a systematic review to identify potential imaging predictive factors for successful recanalization and improved clinical outcome after endovascular therapy in patients with large-vessel occlusion (LVO) in anterior arterial circulation. METHODS: The PubMed databases were searched for related studies reported between September 18, 2009, and September 18, 2019. RESULTS: We selected 11 studies on revascularization and 12 studies on clinical outcome. Patients with thrombus of higher Hounsfield unit (HU), shorter length, higher clot burden score, and increased thrombus permeability may achieve higher recanalization and improved clinical outcome, but the matter is still under debate. CONCLUSION: Imaging of thrombus can be used as an aseessment tool to predict the outcomes and it needs further studies in the future.

Novosphingobium meiothermophilum sp. nov., isolated from a hot spring.

A moderately thermophilic, aerobic, Gram-stain-negative, non-spore-forming, rod-shaped and yellow-pigmented bacterium, designated strain SYSU G00007T, was isolated from a hot spring slurry sample. Optimum growth was observed at 37-45 °C and pH 7. Pairwise comparison of the 16S rRNA gene sequence of strain SYSU G00007T and other Novosphingobium species showed sequence similarities ranging from 93.7 to 97.9 %. Strain SYSU G00007T showed highest sequence identity to Novosphingobium subterraneum DSM 12447T (97.9 %). The average nucleotide identities and digital DNA-DNA hybridization values between strain SYSU G00007T and its closely related phylogenetic neighbours were below 81 and 31 %, respectively, indicating that strain SYSU G00007T represented a novel species of the genus Novosphingobium. The DNA G+C content of strain SYSU G00007T was 64.3 % (genome). The major respiratory quinone was ubiquinone Q-10. The polar lipid profile included diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, two sphingoglycolipids, two unidentified phospholipids, two unidentified aminophospholipids and two unidentified polar lipids. Spermidine was the only polyamine detected. The major fatty acids were C19 : 0cyclo ω8c, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The results obtained from phylogenetic, chemotaxonomic and phenotypic analyses support the conclusion that strain SYSU G00007T represents a novel species of the genus Novosphingobium, for which we proposed the name Novosphingobiummeiothermophilum sp. nov. The type strain is SYSU G00007T (=KCTC 52672T=CCTCC AB2017010T).

Calidifontimicrobium sediminis gen. nov., sp. nov., a new member of the family Comamonadaceae.

Two Gram-stain-negative and facultative anaerobic bacteria, designated strains SYSU G00088T and YIM 73032, were isolated from sediment samples collected from hot springs in Tibet, China. Based on the analyses of the 16S rRNA gene sequences, the two isolates were observed to be a member of the family Comamonadaceae, sharing highest pairwise sequence identity with type strains of Piscinibacter defluvii SH-1T (97.8  and 97.7 %, respectively). They were able to grow in the temperature range of 37-50 °C, pH 5.0-9.0 and in the presence of up to 0.5 % (w/v) NaCl. Both strains were positive for catalase and oxidase reactions. Cells of the novel isolates were short-rods and motile by means of a polar flagellum. The chemotaxonomic features of the two strains include ubiquinone 8 as the respiratory isoprenologue, diphosphatidylglycerol, phosphatidylethanolamine and phoshatidylglycerol as the known polar lipids, and C16 : 0 and C17 : 0cyclo as major fatty acids. The genomic DNA of strains SYSU G00088T and YIM 73032 had G+C contents of 71.8 and 71.9%, respectively. Based on the analyses of the phylogenetic, chemotaxonomic, morphological and genomic data, the two isolates are considered to represent a novel species of a new genus, for which the name Calidifontimicrobium sediminis gen. nov., sp. nov. is proposed. The type strain of Calidifontimicrobium sediminis is SYSU G00088T (=KCTC 52671T=CGMCC 1.13597T).

Thermus caldilimi sp. nov., a thermophilic bacterium isolated from a geothermal area.

A Gram-stain negative, aerobic bacterium, designated strain YIM 78456T, was isolated from a hot spring sediment, Ngamring county, Tibet, south-west China. The taxonomic position of the isolate was investigated by a polyphasic approach. The novel isolate was found to be aerobic and rod-shaped. Colonies were observed to be pale yellow and circular. The strain was found to grow at pH 7.0-8.0 (optimum, pH 7.0), 45-65 °C (optimum, 55 °C) and in the presence of up to 1.5% NaCl. Comparison of the 16S rRNA gene sequence of strain YIM 78456T and other members of the genus Thermus showed sequence similarities ranging from 90.3 to 97.3%, with strain YIM 78456T showing close sequence similarity to Thermus caliditerrae YIM 77925T (97.3%). The phylogenetic trees based on 16S rRNA gene sequences showed that strain YIM 78456T forms a distinct clade with T. caliditerrae YIM 77925T. The predominant menaquinone was identified as MK-8 and the DNA G+C content was determined to be 65.1 mol%. The major cellular fatty acids (> 10%) were identified as iso-C15:0, anteiso-C15:0 and iso-C17:0. The polar lipids were found to consist of an aminophospholipid, a phospholipid and glycolipids. On the basis of the morphological and chemotaxonomic characteristics, as well as genotypic data, it is proposed that strain YIM 78456T represents a novel species of the genus Thermus, for which the name Thermus caldilimi sp. nov. is proposed. The type strain is YIM 78456T (= KCTC 52948T = NBRC 113036T).

Thermus sediminis sp. nov., a thiosulfate-oxidizing and arsenate-reducing organism isolated from Little Hot Creek in the Long Valley Caldera, California.

Thermus species are widespread in natural and artificial thermal environments. Two new yellow-pigmented strains, L198T and L423, isolated from Little Hot Creek, a geothermal spring in eastern California, were identified as novel organisms belonging to the genus Thermus. Cells are Gram-negative, rod-shaped, and non-motile. Growth was observed at temperatures from 45 to 75 °C and at salinities of 0-2.0% added NaCl. Both strains grow heterotrophically or chemolithotrophically by oxidation of thiosulfate to sulfate. L198T and L423 grow by aerobic respiration or anaerobic respiration with arsenate as the terminal electron acceptor. Values for 16S rRNA gene identity (≤ 97.01%), digital DNA-DNA hybridization (≤ 32.7%), OrthoANI (≤ 87.5%), and genome-to-genome distance (0.13) values to all Thermus genomes were less than established criteria for microbial species. The predominant respiratory quinone was menaquinone-8 and the major cellular fatty acids were iso-C15:0, iso-C17:0 and anteiso-C15:0. One unidentified phospholipid (PL1) and one unidentified glycolipid (GL1) dominated the polar lipid pattern. The new strains could be differentiated from related taxa by ß-galactosidase and ß-glucosidase activity and the presence of hydroxy fatty acids. Based on phylogenetic, genomic, phenotypic, and chemotaxonomic evidence, the novel species Thermus sediminis sp. nov. is proposed, with the type strain L198T (= CGMCC 1.13590T = KCTC XXX).

Rhabdanaerobium thermarum gen. nov., sp. nov., a novel anaerobic bacterium isolated from a hot spring.

A novel Gram-stain-positive, obligately anaerobic and thermophilic bacterium, strain SYSU GA15001T, was isolated from a sample collected from a hot spring located in Tengchong, China. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain SYSU GA15001T belonged to the family Eubacteriaceae, and was closely related to 'Irregularibacter muris' 2PG-426-CC4.2T (93.6 % similarity), Garciella nitratireducens DSM 15102T (93.2 %) and Alkalibacter saccharofermentans Z-78920T (89.7 %). Cells were rods and motile by means of a subpolar flagellum. Spores were formed in old cultures. Optimum growth was observed at 45 °C, at pH 7 and in the presence of 1.5 % (w/v) NaCl. The strain utilized d-arabinose, dulcitol, d-galactose, glucose, lactose, maltose, d-mannose, raffinose, l-rhamnose, d-sorbitol, xylitol, l-alanine, l-arginine, glycine, l-isoleucine, l-leucine, dl-methionine, NH4Cl, l-proline and l-threonine as sole carbon/nitrogen sources. Additionally, complex substrates including beef extract, peptone, starch and yeast extract can also be used as sole energy sources. The major fatty acid methyl esters were C14 : 0, anteiso-C15 : 0 and C18 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, an unidentified polar lipid, three unidentified phospholipids and an unidentified glycolipid. The DNA G+C content was determined to be 35.6 mol%. Strain SYSU GA15001T was physiologically and phylogenetically distinguishable from its closely related genera, and merits assignment as representing the type species of a new genus Rhabdanaerobium, with the name Rhabdanaerobium thermarum gen. nov., sp. nov. The type strain of the type species is SYSU GA15001T (=CGMCC 1.5219T=KCTC 15623T).

Ginsenoside Rk1 prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease via activating silence information regulator 3-mediated Nrf2/HO-1 signaling pathway.

Objectives: Ginsenoside Rk1, a novel ginsenoside isolated from red ginseng, has anti-inflammatory and anti-tumor activities. This study was designed to elucidate the role of RK1 in an in vitro 1-methyl-4-phenylpyridinium (MPP+) cell model and an in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of Parkinson's disease (PD).Methods: The grasping test, pole-climbing test, and rotarod test were performed to measure the effects of RK1 on MPTP-induced motor disorders. The expression of tyrosine hydroxylase (TH) and IBA-1 were evaluated by western blotting. CCK-8 and flow cytometry  assays were utilized to assess cell viability and apoptosis. Reactive oxygen species (ROS), Lactate dehydrogenase (LDH), and superoxide dismutase (SOD) were detected to analyze the effects of RK1 on oxidative stress. The levels of inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA).Results: The results showed that RK1 allayed motor deficit elicited by MPTP in a mouse model. RK1 administration augmented tyrosine hydroxylase (TH) expression in the brain striatum and substantia nigra (SN) of MPTP-treated mice. Moreover, RK1 pretreatment promoted viability and suppressed apoptosis in MPP+-induced PC-12 cells. Further, RK1 also attenuated MPP+-stimulated oxidative stress and inflammatory response in PC-12 cells. Besides, RK1 augmented the level of SIRT3, and SIRT3 deletion counteracted RK1-induced repression on MPP+-elicited apoptosis, oxidative stress, and inflammatory response in PC-12 cells via modulating the Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)  pathway.Conclusions: RK1 might exert neuroprotective effects against MPP+/MPTP-induced neurotoxicity via activating SIRT3-mediated Nrf2/HO-1 signaling. RK1 might be a promising candidate against PD.

Effects of SC99 on cerebral ischemia-perfusion injury in rats: Selective modulation of microglia polarization to M2 phenotype via inhibiting JAK2-STAT3 pathway.

Inhibition of Janus kinases 2-Signal transducers and activators of transcription3 (JAK2-STAT3) pathway has been shown to exert anti-inflammatory actions. SC99, a novel specific inhibitor targeting JAK2-STAT3 pathway, has been verified to negatively modulate platelet activation and aggregation in vitro. In current study, a middle cerebral artery occlusion and reperfusion (MCAO/R) model was established in Sprague Dawley rats and primary cultured microglia was exposed to oxygen and glucose deprivation (OGD/R) in vitro. Different dosages were employed to detect the effects of SC99 on cerebral ischemia-perfusion (I/R) injury and evaluate the underlying mechanisms. Our results showed that intracerebroventricular injection of SC99 (10 mmol/L, 15 µL) produced an effective inhibitory effect on the phosphorylation of JAK2 and STAT3. Correspondingly, SC99 ameliorated neuronal apoptosis and degeneration, neurobehavioral deficits, inflammatory response and brain edema. And SC99 promoted microglia polarization to an anti-inflammatory M2 phenotype. We concluded that SC99 could alleviate brain damage and play an anti-inflammatory action by promoting microglia polarization to an anti-inflammatory phenotype after I/R injury, which provides an emerging and promising alternative to protect the brain against MCAO/R injury in the future investigations.

Physiological and genomic properties of Thermus tenuipuniceus sp. nov., a novel slight reddish color member isolated from a terrestrial geothermal spring.

Two closely related, thermophilic bacteria, designated strains YIM 76954T and YIM 76947, were isolated from the Rehai Geothermal Field, Tengchong, Yunnan province, south-west China. Polyphasic approach and whole genome sequencing were used to determine the taxonomy status and genomic profiles of the novel strains. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two isolates were closely related to Thermus scotoductus SE-1T (97.1% sequence similarity), and T. amyloliquefaciens YIM 77409T (96.6%). The strains could be differentiated from most recognized Thermus species by their whitish to slight reddish colony color, distinct DNA fingerprinting profiles and low ANI values. Cells stained Gram-negative, rod-shaped of diameter 0.2-0.5µm and length 1.5-5.0µm. Growth occurred at 50-75°C, pH 6.0-9.0 and in the presence of up to 1.0% (w/v) NaCl concentration. Thiosulfate was found to enhance cell growth, besides improving the intensity of its colony color. Oxygen, nitrate, sulfur, and Fe(III) could be used as terminal electron acceptors for growth. MK-8 was the major respiratory menaquinone. Major fatty acids were iso-C17:0, iso-C15:0, anteiso-C17:0, and anteiso-C15:0. The genome size was 2.26Mbp with 65.5% average GC content. A total of 2374 genes was predicted, comprising 2322 protein-coding and 52 RNA genes. On the basis of the polyphasic evidence presented, it is proposed that strain YIM 76954T represents a novel species of the genus Thermus, for which the name Thermus tenuipuniceus sp. nov. is proposed. The type strain is YIM 76954T (=JCM 30350T=KCTC 4677T).

Hydrogen sulfide therapy in brain diseases: from bench to bedside.

Hydrogen sulfide (H2S) has been recognized and studied for nearly 300 years, but past researches mainly focus on its toxicity effect. During the past two decades, the majority of researches have reported that H2S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H2S is mainly produced by three enzymes, including cystathionine ß-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H2S had been firstly reported as a neuromodulator in the brain, because of its essential role in the facilitating hippocampal long-term potentiation at physiological concentration. It is subsequently reported that H2S may have relevance to neurologic disorders through antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent basic medical studies and preclinical studies on neurologic diseases have demonstrated that the administration of H2S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H2S is concentration-dependent, only a comparatively low dose of H2S can provide beneficial effect. Herein, we review the neuroprotevtive role of H2S therapy in brain diseases from its mechanism to clinical application in animal and human subjects, and therefore provide the potential strategies for further clinical treatment.

Advances in molecular mechanism of cardioprotection induced by helium.

Helium has been classified as a kind of inert gas that is not effortless to spark chemical reactions with other substances in the past decades. Nevertheless, the cognition of scientists has gradually changed accompanied with a variety of studies revealing the potential molecular mechanism underlying organ-protection induced by helium. Especially, as a non-anesthetic gas which is deficient of relevant cardiopulmonary side effects, helium conditioning is recognized as an emerging and promising approach to exert favorable effects by mimicking the cardioprotection of anesthetic gases or xenon. In this review we will summarize advances in the underlying biological mechanisms and clinical applicability with regards to the cardioprotective effects of helium.