Durative sleep fragmentation with or without hypertension suppress rapid eye movement sleep and generate cerebrovascular dysfunction.

Either hypertension or chronic insomnia is the risk factor of developing vascular dementia. Durative hypertension can induce vascular remodeling and is used for modeling small vessel disease in rodents. It remains undetermined if the combination of hypertension and sleep disturbance exacerbates vascular dysfunction or pathologies. Previously, we found chronic sleep fragmentation (SF) dampened cognition in young mice without disease predispositions. In the current study, we superimposed SF with hypertension modeling in young mice. Angiotensin II (AngII)-releasing osmotic mini pumps were subcutaneously implanted to generate persistent hypertension, while sham surgeries were performed as controls. Sleep fragmentation with repetitive arousals (10 s every 2 min) during light-on 12 h for consecutive 30 days, while mice undergoing normal sleep (NS) processes were set as controls. Sleep architectures, whisker-stimulated cerebral blood flow (CBF) changes, vascular responsiveness as well as vascular pathologies were compared among normal sleep plus sham (NS + sham), SF plus sham (SF + sham), normal sleep plus AngII (NS + AngII), and SF plus AngII (SF + AngII) groups. SF and hypertension both alter sleep structures, particularly suppressing REM sleep. SF no matter if combined with hypertension strongly suppressed whisker-stimulated CBF increase, suggesting the tight association with cognitive decline. Hypertension modeling sensitizes vascular responsiveness toward a vasoactive agent, Acetylcholine (ACh, 5 mg/ml, 10 µl) delivered via cisterna magna infusion, while SF exhibits a similar but much milder effect. None of the modeling above was sufficient to induce arterial or arteriole vascular remodeling, but SF or SF plus hypertension increased vascular network density constructed by all categories of cerebral vessels. The current study would potentially help understand the pathogenesis of vascular dementia, and the interconnection between sleep and vascular health.

Evaluation of glymphatic-meningeal lymphatic system with intravenous gadolinium-based contrast-enhancement in cerebral small-vessel disease.

OBJECTIVE: To investigate the feasibility of using noninvasive neuroimaging methods in visualizing and evaluating the clearance of the glymphatic-meningeal lymphatic system (GMLS) in patients with arteriosclerotic cerebral small-vessel disease (CSVD) and controls. METHODS: This observational study recruited patients with high-burden CSVD and controls (age 50-80 years). At multiple time points before and after intravenous administration of a contrast agent, three-dimensional (3D) brain volume T1-weighted imaging and 3D Cube T2-fluid attenuated inversion recovery imaging were performed to visualize and assess the clearance of the glymphatics and meningeal lymphatic vessels (mLVs). We measured the signal intensity ratio (SIR) of four regions of interest representing the glymphatics and mLVs at each time point. The clearance rate at 24 h (CR24h) and changes in the SIR from baseline to 24 h (∆SIR) were defined as the clearance function. The analysis of variance was used to evaluate the group differences after adjusting for hypertension. RESULTS: A total of 20 CSVD patients and 15 controls were included. Cortical periarterial enhancement and the enhancement of enlarged perivascular spaces in the basal ganglia were respectively observed in 11 (55.00%) and 16 (80.00%) CSVD patients, but in none of controls. All CSVD patients and most of controls (80.00%) showed cortical perivenous enhancement. Para-sinus enhancement was observed in all participants. CSVD patients showed lower CR24h and higher ∆SIR of the glymphatics and mLVs (all p < 0.05). CONCLUSION: The impaired drainage of the GMLS in patients with high-burden CSVD could be visually evaluated using noninvasive neuroimaging methods with intravenous gadolinium-based contrast-enhancement. CLINICAL RELEVANCE STATEMENT: Dynamic intravenous contrast-enhanced MRI could visually evaluate the impaired drainage of the glymphatic-meningeal lymphatic system in patients with high-burden cerebral small-vessel disease and could help to explore a new therapeutic target. KEY POINTS: • Signal intensity changes in regions representing the glymphatic-meningeal lymphatic system (GMLS) can reflect the drainage function based on contrast-enhanced 3D-FLAIR and 3D T1-weighted MRI. • Impaired drainage of the GMLS in patients with high-burden CSVD can be visually evaluated using dynamic intravenous contrast-enhanced MRI. • This direct, noninvasive technique could serve as a basis for further GMLS studies and could help to explore a new therapeutic target in CSVD patients.

Clinical and prognostic features of Heidenhain variant of Creutzfeldt-Jakob disease: A retrospective case series study.

BACKGROUND: Heidenhain variant of Creutzfeldt-Jakob disease (CJD) remains a diagnostic challenge in clinical practice. We aimed to describe the clinical and prognostic features of Heidenhain cases, through a case series study. METHODS: We retrospectively reviewed the definite or probable CJD cases admitted to two tertiary referral university hospitals over a decade to identify Heidenhain cases and investigated their survival status by telephone follow-up. Their clinical characteristics, neuroimaging features, electroencephalography (EEG) results, cerebrospinal fluid profiles, and PRNP gene mutations were also analyzed. RESULTS: Of a total of 85 CJD cases, 20 (24%) Heidenhain cases (11 women [55%]; median age, 64 years [range, 44-72 years]) were identified. The median survival time was 22 weeks (range, 5-155 weeks). The median duration of isolated visual symptoms was 3 weeks (range, 1-12 weeks). The most common early visual symptom was blurred vision (16/20, 80%), followed by diplopia (6/20, 30%). The prevalence significantly increased for complex visual hallucination (p = 0.005) and cortical blindness (p = 0.046) as the disease progressed. The positive rate of serial magnetic resonance images (20/20, 100%) was higher than that of serial EEGs (16/20, 80%). Two patients (2/10, 20%) had pathogenic PRNP mutations, E196A and T188K, respectively. Heidenhain cases with PRNP mutations had significantly longer survival time than those without PRNP mutations (p = 0.047). CONCLUSIONS: Besides blurred vision (80%), diplopia (30%) was also a frequent early visual symptom among Heidenhain cases. Heidenhain phenotype can occur in genetic CJD cases. PRNP mutation status might be an important prognostic factor for Heidenhain cases.

Biocontrol potential and antifungal mechanism of a novel Streptomyces sichuanensis against Fusarium oxysporum f. sp. cubense tropical race 4 in vitro and in vivo.

Most commercial banana cultivars are highly susceptible to Fusarium wilt caused by soilborne fungus Fusarium oxysporum f. sp. cubense (Foc), especially tropical race 4 (TR4). Biological control using antagonistic microorganism has been considered as an alternative method to fungicide. Our previous study showed that Streptomyces sp. SCA3-4 T had a broad-spectrum antifungal activity from the rhizosphere soil of Opuntia stricta in a dry hot valley. Here, the sequenced genome of strain SCA3-4 T contained 6614 predicted genes with 72.38% of G + C content. A polymorphic tree was constructed using the multilocus sequence analysis (MLSA) of five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB). Strain SCA3-4 T formed a distinct clade with Streptomyces mobaraensis NBRC 13819 T with 71% of bootstrap. Average nucleotide identity (ANI) values between genomes of strain SCA3-4 T and S. mobaraensis NBRC 13819 T was 85.83% below 95-96% of the novel species threshold, and named after Streptomyces sichuanensis sp. nov. The type strain is SCA3-4 T (= GDMCC 4.214 T = JCM 34964 T). Genomic analysis revealed that strain SCA3-4 T contained 36 known biosynthetic gene clusters of secondary metabolites. Antifungal activity of strain SCA3-4 T was closely associated with the production of siderophore and its extracts induced the apoptosis of Foc TR4 cells. A total of 12 potential antifungal metabolites including terpenoids, esters, acid, macrolides etc. were obtained by the gas chromatography-mass spectrometry (GC-MS). Greenhouse experiment indicated that strain SCA3-4 T could significantly inhibit infection of Foc TR4 in the roots and corms of banana seedlings and reduce disease index. Therefore, strain SCA3-4 T is an important microbial resource for exploring novel natural compounds and developing biopesticides to manage Foc TR4. KEY POINTS: • Strain SCA3-4 T was identified as a novel species of Streptomyces. • Siderophore participates in the antifungal regulation. • Secondary metabolites of strain SCA3-4 T improves the plant resistance to Foc TR4.

Potential Biological Control of Endophytic Streptomyces sp. 5-4 Against Fusarium Wilt of Banana Caused by Fusarium oxysporum f. sp. cubense Tropical Race 4.

Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is one of the most disastrous fungal diseases. Biological control is a promising strategy for controlling Fusarium wilt of banana. To explore endophytic actinomycetes as biocontrol resources against Foc TR4, antagonistic strains were isolated from different tissues of medicinal plants. Here, a total of 144 actinomycetes were isolated and belonged to Nonomuraea, Kitasatospora, and Streptomyces. Forty-three isolates exhibited antifungal activities against Foc TR4. The strain labeled with 5-4 isolated from roots of Piper austrosinense had a broad-spectrum antifungal activity by the production of chitinase and ß-1,3-glucanase and was identified as Streptomyces hygroscopicus subsp. hygroscopicus 5-4. Furthermore, disease index of banana wilt was significantly reduced by application of strain 5-4 in comparison with application of Foc TR4 alone. Exogenous application of strain 5-4 increased the expression levels of defense genes such as (PAL), peroxidase (POD), pathogenesis-related protein 1 (PR-1), hydrolytic enzymes (ß-1,3-glucanase), lysin motif receptor kinase 1 (LYK-1), and mitogen-activated protein kinase 1 (MPK-1). The antifungal mechanism assay demonstrated that extracts of strain 5-4 inhibited spore gemination and hyphal growth of Foc TR4, and caused abnormally swollen, deformity, and rupture of Foc TR4 hypha. Thus, S. hygroscopicus subsp. hygroscopicus 5-4 could be used as a potential biological agent for controlling Fusarium wilt of banana.

The dynamic change of phenotypic markers of smooth muscle cells in an animal model of cerebral small vessel disease.

BACKGROUND: The pathological character of cerebral small vessel disease (CSVD) is the dysfunction of cerebral small arteries caused by risk factors. A switch from the contractile phenotype to the synthetic phenotype of vascular smooth muscle cells (SMCs) can decrease the contractility of arteries. The alteration of the vascular wall extracellular matrix (ECM) is found to regulate the process. We speculated that SMCs phenotype changes may also occur in CSVD induced by hypertension and the alteration of ECM especially fibronectin and laminin may regulate the process. METHOD: Male spontaneously hypertensive rats (SHR) were used as a CSVD animal model. SMCs phenotypic markers and the ECM expression of the cerebral small arteries of SHR at different ages were evaluated by immunofluorescence. The phenotype changes of primary brain microvascular SMCs cultured on laminin-coating dish or fibronectin-coating dish were evaluated by western blot. RESULT: A switch from the contractile phenotype to synthetic phenotype in SHR at 10 and 22 weeks of age was observed. Meanwhile, increased expression of fibronectin and a temporary decline of laminin was found in small arteries of SHR at 22 weeks. In vitro experiments also convinced that SMCs cultured on a fibronectin-coating dish failed to maintain contractile phenotype. While at 50 weeks, significant drops of both synthetic and contractile phenotypic markers were witnessed in SHR, with high expressions of four kinds of ECM. CONCLUSION: SMCs in cerebral small arteries exhibited a switch from the contractile phenotype to synthetic phenotype during the chronic process of hypertension and aging. Moreover, the change of fibronectin and laminin may regulate the process.

Decreased nocturnal heart rate variability and potentially related brain regions in arteriosclerotic cerebral small vessel disease.

BACKGROUND: To assess heart rate variability (HRV) among patients with arteriosclerotic cerebral small vessel disease (CSVD) by comparing with control subjects, and to determine whether HRV parameters were related to structural alterations in brain regions involved in autonomic regulation among CSVD patients. METHODS: We consecutively recruited subjects aged between 50 and 80 years who visited the Stroke Prevention Clinic of our hospital and have completed brain magnetic resonance imaging examination from September 1, 2018 to August 31, 2019. Polysomnography and synchronous analyses of HRV were then performed in all participants. Multivariable binary logistic regression was used to identify the relationship between HRV parameters and CSVD. Participants were invited to further undergo three-dimensional brain volume scan, and the voxel based morphometry (VBM) analysis was used to identify gray matter atrophy. RESULTS: Among 109 participants enrolled in this study, 63 were assigned to the arteriosclerotic CSVD group and 46 to the control group. Lower standard deviation of normal-to-normal intervals (SDNN, OR = 0.943, 95% CI 0.903 to 0.985, P = 0.009) and higher ratio of low to high frequency power (LF/HF, OR = 4.372, 95% CI 1.033 to 18.508, P = 0.045) during the sleep period were associated with CSVD, independent of traditional cerebrovascular risk factors and sleep disordered breathing. A number of 24 CSVD patients and 21 controls further underwent three-dimensional brain volume scan and VBM analysis. Based on VBM results, SDNN during the awake time (ß = 0.544, 95% CI 0.211 to 0.877, P = 0.001) and the sleep period (ß = 0.532, 95% CI 0.202 to 0.862, P = 0.001) were both positively related with gray matter volume within the right inferior frontal gyrus only among CSVD patients. CONCLUSIONS: Decreased nocturnal HRV is associated with arteriosclerotic CSVD independent of traditional cerebrovascular risk factors and sleep disordered breathing. The structural atrophy of some brain regions associated with cardiac autonomic regulation sheds light on the potential relationship. TRIAL REGISTRATION: Trial registration number: ChiCTR1800017902 . Date of registration: 20 Aug 2018.

Postoperative Functional Outcomes and Prognostic Factors in Two Types of Adult Moyamoya Diseases.

BACKGROUND: To determine the functional outcomes in each period for adult ischemic and hemorrhagic Moyamoya disease (MMD) patients and identify prognostic factors. METHODS: The current retrospective study reviewed consecutive adult MMD patients surgically treated from January 2012 to June 2017. Perioperative clinical data were collected and follow-up was conducted via telephone interviews. Functional outcomes and prognostic factors were analyzed. RESULTS: A total of 219 ischemic MMD patients (268 hemispheres) and 157 hemorrhagic patients (193 hemispheres) were included. The median follow-up time was 18 months (3-69 months). MMD type had no significant effect on the modified Rankin Scale(mRS) score at discharge. Perioperative complications (P = 0.004) and the mRS score at baseline (P < 0.001) were risk factors correlated with the short-term functional outcomes in both groups, while diabetes mellitus (DM, P = 0.022) also played a role in the ischemic group. During the follow-up period, functional outcomes obviously improved in both groups, but two groups showed nonproportional cumulative curves for favorable functional outcomes (log-rank test, P = 0.483). Stroke recurrence (P < 0.001) and mRS at discharge (P < 0.001) were common factors related with long-term functional outcomes in two types of MMD patients. Particularly, female patients with ischemic MMD were more likely to have higher mRS scores (P = 0.028) and Suzuki stage was positively associated with long-term functional outcomes in hemorrhagic group (P = 0.044). CONCLUSIONS: MMD type had no significant effect on prognosis while both types of MMD patients showed overall significant improvements in functional outcomes after surgery. Different types of MMD patients have distinct prognostic factors for short-term and long-term functional outcomes.

Potential evaluation of CO2 storage and enhanced oil recovery of tight oil reservoir in the Ordos Basin, China.

Carbon -di-oxide (CO2) is regarded as the most important greenhouse gas to accelerate climate change and ocean acidification. The Chinese government is seeking methods to reduce anthropogenic CO2 gas emission. CO2 capture and geological storage is one of the main methods. In addition, injecting CO2 is also an effective method to replenish formation energy in developing tight oil reservoirs. However, exiting methods to estimate CO2 storage capacity are all based on the material balance theory. This was absolutely correct for normal reservoirs. However, as natural fractures widely exist in tight oil reservoirs and majority of them are vertical ones, tight oil reservoirs are not close. Therefore, material balance theory is not adaptive. In the present study, a new method to calculate CO2 storage capacity is presented. The CO2 effective storage capacity, in this new method, consisted of free CO2, CO2 dissolved in oil and CO2 dissolved in water. Case studies of tight oil reservoir from Ordos Basin was conducted and it was found that due to far lower viscosity of CO2 and larger solubility in oil, CO2 could flow in tight oil reservoirs more easily. As a result, injecting CO2 in tight oil reservoirs could obviously enhance sweep efficiency by 24.5% and oil recovery efficiency by 7.5%. CO2 effective storage capacity of Chang 7 tight oil reservoir in Longdong area was 1.88 x 10(7) t. The Chang 7 tight oil reservoir in Ordos Basin was estimated to be 6.38 x 10(11) t. As tight oil reservoirs were widely distributed in Songliao Basin, Sichuan Basin and so on, geological storage capacity of CO2 in China is potential.

Streptomyces-Secreted Fluvirucin B6 as a Potential Bio-Fungicide for Managing Banana Fusarium Wilt and Mycotoxins and Modulating the Soil Microbial Community Structure.

Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc TR4) is the most destructive soil-borne fungal disease. Until now, there has been a lack of effective measures to control the disease. It is urgent to explore biocontrol agents to control Foc TR4 and the secretion of mycotoxin. In this study, fluvirucin B6 was screened from Streptomyces solisilvae using an activity-guided method. Fluvirucin B6 exhibited strong antifungal activity against Foc TR4 (0.084 mM of EC50 value) and significantly inhibited mycelial growth and spore germination. Further studies demonstrated that fluvirucin B6 could cause the functional loss of mitochondria, the disorder of metabolism of Foc TR4 cells, and the decrease of enzyme activities in the tricarboxylic acid cycle and electron transport chain, ultimately inhibiting mycotoxin metabolism. In a pot experiment, the application of fluvirucin B6 significantly decreased the incidence of banana Fusarium wilt and the amount of Foc TR4 and controlled fungal toxins in the soil. Additionally, fluvirucin B6 could positively regulate the changes in the structure of the banana rhizosphere microbial community, significantly enriching beneficial microbes associated with disease resistance. In summary, this study identifies fluvirucin B6, which plays versatile roles in managing fungal diseases and mycotoxins.

Taxonomic identification and antagonistic activity of Streptomyces luomodiensis sp. nov. against phytopathogenic fungi.

Banana wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) is a devastating fungal disease. Biocontrol strategies hold immense potential for inhibiting the spread of Foc TR4. Here, 30 actinobacteria were isolated from soils and screened for their antagonistic activity against Foc TR4. Strain SCA4-21T was selected due to its strongest antagonistic activity against Foc TR4. Strain SCA4-21T also exhibited strong antagonistic activity against the other eight phytopathogenic fungi. The strain was identified as the genus Streptomyces according to its physiological, biochemical, and phenotypic characteristics. The phylogenetic trees of 16S rRNA sequences demonstrated that strain SCA4-21T formed a subclade with S. iranensis HM 35T and/or S. rapamycinicus NRRL B-5491T with low bootstrap values. Considering that 16S rRNAs did not provide sufficient resolution for species-level identification, the whole genome of strain SCA4-21T was sequenced. Multilocus sequence analysis (MLSA) based on five housekeeping gene alleles (atpD, gyrB, recA, rpoB, and trpB) revealed that strain SCA4-21T clustered into S. hygroscopicus subsp. hygroscopicus NBRC 13472T with 100% of bootstrap value. The analysis of the genome-based phylogeny also approved the results. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) were 91.26 and 44.30%, respectively, with values below the respective species level threshold of 95 and 70%. Hence, strain SCA 4-21T represented a novel species within the genus Streptomyces, named Streptomyces luomodiensis sp. nov. The type strain is SCA4-21T (=GDMCC4.340T = JCM36555T). By the CAZymes analysis, 348 carbohydrate-active enzymes (CAZymes) were detected, including 15 chitinases and eight ß-1,3-glucanases. The fermentation broth of strain SCA4-21T, exhibiting strong antagonistic activity against Foc TR4, demonstrated high activities of chitinase and ß-1,3-glucanase, which might be involved in antifungal activity. Our results showed an innovative potential biocontrol agent for managing plant fungal diseases, specifically banana fusarium wilt.

Biocontrol mechanism of Bacillus siamensis sp. QN2MO-1 against tomato fusarium wilt disease during fruit postharvest and planting.

Tomato fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol) is a highly destructive disease, resulting in severe economic losses of global tomato production annually. An eco-friendly alternative to chemical fungicide using biological control agents (BCAs) is urgently needed. Here, Bacillus siamensis QN2MO-1 was isolated from Noli fruit and had a strong antagonistic activity against Fol in vitro and in vivo. Strain QN2MO-1 also exhibited a broad-spectrum antifungal activity against the selected 14 phytopathogenic fungi. The crude protein produced by strain QN2MO-1 could inhibit the spore germination of Fol and destroy the spore structure. It was closely related with the generation of chitinase and ß-1,3-glucanase secreted by strain QN2MO-1. In a pot experiment, the application of B. siamensis QN2MO-1 effectively alleviated the yellowing and wilting symptoms of tomato plants. The disease index and incidence rate were decreased by 72.72% and 80.96%, respectively. The rhizospheric soil in tomato plants owed a high abundance of microbial community. Moreover, strain QN2MO-1 also enhanced the plant growth and improved the fruit quality of tomato. Therefore, B. siamensis QN2MO-1 will be explored as a potential biocontrol agent and biofertilizer.

Clinical Reasoning: A 37-Year-Old Man Presenting With Intermittent Dizziness and Brief Choreiform Movements.

In this report, we describe the case of a 37-year-old man presenting with intermittent episodes of dizziness and choreiform movements. MRI of the head showed an acute infarction in the left cerebellar hemisphere and multiple chronic infarctions in the cerebellum and pons. Vessel imaging also showed dynamic stenoses in the posterior circulation. This case provides a framework for evaluating young patients with intermittent dizziness and recurrent strokes and highlights the need to combine anatomical angiographies or hemodynamic studies with head rotational behavior.

Predictors and outcome of early neurological deterioration after endovascular thrombectomy: a secondary analysis of the DIRECT-MT trial.

BACKGROUND: There is uncertainty regarding the predictors of early neurological deterioration (END) after endovascular thrombectomy in patients with acute ischemic stroke (AIS). Limited studies have focused on the effect of END on functional outcome. Our aim was to determine the predictors of END after endovascular thrombectomy in AIS and its effect on functional outcome at 90 days. METHODS: This is a secondary analysis of the DIRECT-MT trial. Patients who failed to complete endovascular thrombectomy were additionally excluded. END was defined as ≥4-point increase in National Institutes of Health Stroke Scale score between admission and 24 hours after endovascular thrombectomy. Multivariable logistic regression was used to identify predictors for END and its effect on the modified Rankin Scale (mRS) score at 90 days. RESULTS: Of 591 patients enrolled, 111 (18.8%) had postoperative END, which was associated with higher ordinal mRS score at 90 days (adjusted common OR (aOR) 6.968, 95% CI 4.444 to 10.926). Non-modifiable factors included baseline Alberta Stroke Program Early CT Score (aOR 0.883, 95% CI 0.790 to 0.987), systolic blood pressure (aOR 1.017, 95% CI 1.006 to 1.028), glucose level (aOR 1.178, 95% CI 1.090 to 1.273), collateral status (aOR 0.238, 95% CI 0.093 to 0.608), occlusion site (aOR 0.496, 95% CI 0.290 to 0.851) and the presence of an anterior communicating artery (aOR 0.323, 95% CI 0.148 to 0.707). Admission-to-groin puncture time (aOR 1.010, 95% CI 1.003 to 1.017), general anesthesia (aOR 2.299, 95% CI 1.193 to 4.444), number of passes (aOR 1.561, 95% CI 1.243 to 1.961) and contrast extravasation (aOR 6.096, 95% CI 1.543 to 24.088) were modifiable predictors for END. CONCLUSIONS: Postoperative END is associated with adverse functional outcome. Several non-modifiable and modifiable factors can predict END and support future treatment decision-making to improve the potential utility of endovascular thrombectomy. TRIAL REGISTRATION NUMBER: DIRECT-MT ClinicalTrials.gov NCT03469206.

Electrical Activity During Slow-Wave Sleep and the Relationship With Enlarged Perivascular Spaces in Arteriosclerotic Cerebral Small Vessel Disease.

PURPOSE: We sought to analyze EEG spectral power during slow-wave sleep among patients with arteriosclerotic cerebral small vessel disease (CSVD) compared with community-dwelling individuals. We also sought to determine the relationship between EEG activity and the severity of enlarged perivascular spaces (EPVSs). METHODS: Consecutive subjects with arteriosclerotic CSVD ( n = 36) and community-dwelling individuals ( n = 26) between 50 and 80 years of age were included. Nocturnal polysomnography was performed, and EEG spectral analysis was conducted during slow-wave sleep using the F4/M1 and C4/M1 channel. Regionalized EPVSs in the basal ganglia and centrum semiovale were assessed on a validated 4-point visual rating scale (0 = none, 1 = 1-10, 2 = 11-20, 3 = 21-40, and 4 = >40) using MRI. RESULTS: CSVD group showed lower delta:beta ratios in the frontal ( P = 0.017) and central ( P = 0.038) regions after adjusting for age, sex, mini-mental state examination score, and arousal index. The significance still remained in the frontal region when including age, sex, mini-mental state examination, and apnea-hypopnea index as covariates ( P = 0.037). Among patients with arteriosclerotic CSVD, decreased delta power ( P = 0.031) and theta power ( P = 0.034) in the frontal region were associated with a higher degree of EPVSs in the centrum semiovale rather than in the basal ganglia. Delta power in the central region showed an extremely weak association with EPVSs in the centrum semiovale ( P = 0.047). CONCLUSIONS: Among patients with arteriosclerotic CSVD, the intrusion of high-frequency EEG activity into slow-wave sleep was identified, and slow-wave activity during slow-wave sleep might be negatively associated with the severity of EPVSs in the centrum semiovale. Further studies are required to corroborate the conclusions.

A newly isolated Trichoderma Parareesei N4-3 exhibiting a biocontrol potential for banana fusarium wilt by Hyperparasitism.

Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense tropical race4 (Foc TR4) is one of the most destructive soil-borne fungal diseases and currently threatens banana production around the world. Until now, there is lack of an effective method to control banana Fusarium wilt. Therefore, it is urgent to find an effective and eco-friendly strategy against the fungal disease. In this study, a strain of Trichoderma sp. N4-3 was isolated newly from the rhizosphere soil of banana plants. The isolate was identified as Trichoderma parareesei through analysis of TEF1 and RPB2 genes as well as morphological characterization. In vitro antagonistic assay demonstrated that strain N4-3 had a broad-spectrum antifungal activity against ten selected phytopathogenic fungi. Especially, it demonstrated a strong antifungal activity against Foc TR4. The results of the dual culture assay indicated that strain N4-3 could grow rapidly during the pre-growth period, occupy the growth space, and secrete a series of cell wall-degrading enzymes upon interaction with Foc TR4. These enzymes contributed to the mycelial and spore destruction of the pathogenic fungus by hyperparasitism. Additionally, the sequenced genome proved that strain N4-3 contained 21 genes encoding chitinase and 26 genes encoding ß-1,3-glucanase. The electron microscopy results showed that theses cell wall-degrading enzymes disrupted the mycelial, spore, and cell ultrastructure of Foc TR4. A pot experiment revealed that addition of strain N4-3 significantly reduced the amount of Foc TR4 in the rhizosphere soil of bananas at 60 days post inoculation. The disease index was decreased by 45.00% and the fresh weight was increased by 63.74% in comparison to the control. Hence, Trichoderma parareesei N4-3 will be a promising biological control agents for the management of plant fungal diseases.

EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease.

Aging and hypertension are major risk factors for cerebral small vessel disease (CSVD). Anti-hypertensive therapy has achieved effective; however, incomplete results in treating CSVD, suggesting the need for additional treatments. Targeting abnormal inflammatory responses has become a topic of research interest. Small artery remodeling is the main pathological feature of CSVD. Inhibition of the E-prostanoid 3 (EP3) receptor has been shown to attenuate vascular remodeling in peripheral organs; however, little is known about its role in CSVD. Therefore, we investigated whether the deletion of EP3 attenuates the development of CSVD in an animal model-- stroke-prone renovascular hypertensive rat (RHRsp). We found that the cerebral small arteries of RHRsp exhibited increased EP3 expression. Despite no alleviation of hypertension, the deletion of EP3 still attenuated the cerebral small artery remodeling of RHRsp, as evidenced by reduced overexpression of extracellular matrix (ECM) in the vessel. In vitro experiments indicated that EP3 deletion regulated the expression of ECM by downregulating TGF-ß1/Smad signaling. Furthermore, the Morris water maze test and magnetic resonance test demonstrated that EP3 knockout attenuated cognitive impairment of the RHRsp, possibly through increased cerebral blood flow. Together, our results indicate that the deletion of EP3 attenuates vascular remodeling and vascular cognitive impairment induced by hypertension, and blockade of the EP3 receptor may be a promising strategy for the treatment of CSVD.

The Association Between Glymphatic System Dysfunction and Cognitive Impairment in Cerebral Small Vessel Disease.

The mechanism of cognitive impairment in patients with cerebral small vessel disease (CSVD) remains unknown. The glymphatic system dysfunction, which has been demonstrated to influence cognitive impairment, can be evaluated by diffusion tensor image analysis along the perivascular space (ALPS index). We explored whether cognitive impairment in CSVD is associated with glymphatic clearance dysfunction. In this study, 133 patients with CSVD were enrolled and underwent neuropsychological test batteries as well as magnetic resonance imaging (MRI). They were then categorized into a CSVD with cognitive impairment (CSVD-CI) group and a cognitively normal CSVD (CSVD-CN) group. The ALPS index and four CSVD markers [white matter lesions (WMLs), cerebral microbleeds (CMBs), lacunes, and perivascular spaces (PVSs)] were also assessed. Univariate analysis showed that the ALPS index was significantly different between the CSVD-CN (n = 50) and CSVD-CI groups (n = 83) (p < 0.001). This difference remained significant (95% CI < 0.001-0.133) after adjusting for six common risk factors (age, education, hypertension, diabetes, smoking, and alcohol abuse) as well as CSVD markers. The ALPS index was independently linearly correlated with global cognitive function, executive function, attention function, and memory after adjusting for the aforementioned six risk factors or CSVD markers. Our results suggest that glymphatic system impairment is independently related to cognitive impairment in patients with CSVD.

Relation of middle cerebral artery flow velocity and risk of cognitive decline: A prospective community-based study.

OBJECTIVES: Hemodynamic parameters measured by the Transcranial Doppler Ultrasound (TCD) are related to cognitive impairment in many cross-sectional studies, but the longitudinal evidence is scarce. In this study, we aim to verify the association between flow velocity of Middle Cerebral Artery (MCA) and the longitudinal cognitive decline in community dwelling older adults. MATERIALS AND METHODS: Participants were administered TCD examination at the baseline. The Peak Systolic Velocity (PSV), Mean Flow Velocity (MFV), and Pulsatility Index (PI) of MCA segments on left middle (LmMCA), left proximal (LpMCA), right middle (RmMCA), and right proximal (RpMCA) were obtained. Mini-mental state examination (MMSE) were conducted at both baseline and follow-up. RESULTS: One hundred and thirteen participants without dementia were followed up for 6.3 years in average. The mean annual rate of decline in the MMSE score was 0.15 (min to max: -1.0 to 1.2). LpMCA PSV (ß = -0.0034, r = -0.231, P = 0.022) and LpMCA MFV (ß = -0.0049, r = -0.217, P = 0.031) were inversely associated with annual rate of decline in the MMSE score after adjusting for age, gender, education year, APOE ε4, obesity, hypertension, diabetes mellitus, stroke, and coronary heart disease. CONCLUSIONS: Blood flow velocity of left proximal MCA was inversely related to global cognitive decline. Cerebral blood flow velocity may impact the cognitive function.