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.

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.

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.

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.

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.

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.

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.

Discovery of Niphimycin C from Streptomyces yongxingensis sp. nov. as a Promising Agrochemical Fungicide for Controlling Banana Fusarium Wilt by Destroying the Mitochondrial Structure and Function.

Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is the most destructive soil-borne fungal disease. Tropical race 4 (Foc TR4), one of the strains of Foc, can infect many commercial cultivars, which represents a threat to global banana production. Currently, there are hardly any effective chemical fungicides to control the disease. To search for natural product-based fungicides for controlling banana Fusarium wilt, we identified a novel strain Streptomyces yongxingensis sp. nov. (JCM 34965) from a marine soft coral, from which a bioactive compound, niphimycin C, was isolated using an activity-guided method. Niphimycin C exhibited a strong antifungal activity against Foc TR4 with a value of 1.20 µg/mL for EC50 and obviously inhibited the mycelial growth and spore germination of Foc TR4. It caused the functional loss of mitochondria and the disorder of metabolism of Foc TR4 cells. Further study showed that niphimycin C reduced key enzyme activities of the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). It displayed broad-spectrum antifungal activities against the selected 12 phytopathogenic fungi. In pot experiments, niphimycin C reduced the disease indexes in banana plantlets and inhibited the infection of Foc TR4 in roots. Hence, niphimycin C could be a promising agrochemical fungicide for the management of fungal diseases.

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.

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.

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.

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.

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.

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.

Identification and Antifungal Mechanism of a Novel Actinobacterium Streptomyces huiliensis sp. nov. Against Fusarium oxysporum f. sp. cubense Tropical Race 4 of Banana.

Banana is an important fruit crop. Fusarium wilt caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) seriously threatens the global banana industry. It is difficult to control the disease spread using chemical measures. In addition, commercial resistant cultivars are also lacking. Biological control is considered as a promising strategy using antagonistic microbes. Actinomycetes, especially Streptomyces, are potential sources of producing novel bioactive secondary metabolites. Here, strain SCA2-4 T with strong antifungal activity against Foc TR4 was isolated from the rhizospheric soil of Opuntia stricta in a dry hot valley. The morphological, physiological and chemotaxonomic characteristics of the strain were consistent with the genus Streptomyces. Based on the homology alignment and phylogenetic trees of 16S rRNA gene, the taxonomic status of strain SCA2-4 T exhibited a paradoxical result and low bootstrap value using different algorithms in the MEGA software. It prompted us to further discriminate this strain from the closely related species by the multilocus sequence analysis (MLSA) using five house-keeping gene alleles (atpD, gyrB, recA, rpoB, and trpB). The MLSA trees calculated by three algorithms demonstrated that strain SCA2-4 T formed a distinct clade with Streptomyces mobaraensis NBRC 13819 T . The MLSA distance was above 0.007 of the species cut-off. Average nucleotide identity (ANI) values between strain SCA2-4 T genome and two standard strain genomes were below 95-96% of the novel species threshold. Strain SCA2-4 T was assigned to a novel species of the genus Streptomyces and named as Streptomyces huiliensis sp. nov. The sequenced complete genome of SCA2-4 T encoded 51 putative biosynthetic gene clusters of secondary metabolites. Genome alignment revealed that ten gene clusters were involved in the biosynthesis of antimicrobial metabolites. It was supported that strain SCA2-4 T showed strong antifungal activities against the pathogens of banana fungal diseases. Extracts abstracted from the culture filtrate of strain SCA2-4 T seriously destroyed cell structure of Foc TR4 and inhibited mycelial growth and spore germination. These results implied that strain SCA2-4 T could be a promising candidate for biological control of banana Fusarium wilt.

Biocontrol Ability and Mechanism of a Broad-Spectrum Antifungal Strain Bacillus safensis sp. QN1NO-4 Against Strawberry Anthracnose Caused by Colletotrichum fragariae.

Strawberry is a very popular fruit with a special taste, color, and nutritional value. Anthracnose caused by Colletotrichum fragariae severely limits fruit shelf life during post-harvest storage. Use of traditional chemical fungicides leads to serious environment pollution and threatens food safety. Biocontrol is considered as a promising strategy to manage the post-harvest fruit diseases. Here, strain QN1NO-4 isolated from noni (Morinda citrifolia L.) fruit exhibited a high antifungal activity against C. fragariae. Based on its physicochemical profiles and phylogenetic tree of the 16S rRNA sequence, strain QN1NO-4 belonged to the genus Bacillus. The average nucleotide identity (ANI) calculated by comparing two standard strain genomes was below 95-96%, suggesting that the strain might be a novel species of the genus Bacillus and named as Bacillus safensis sp. QN1NO-4. Its extract effectively reduced the incidence of strawberry anthracnose of harvested fruit. Fruit weight and TSS contents were also maintained significantly. The antifungal mechanism assays indicated that the extract of the test antagonist inhibited mycelial growth and spore germination of C. fragariae in vitro. Cells of strain QN1NO-4 demonstrated the cytoplasmic heterogeneity, disappeared organelles, and ruptured ultrastructure. Notably, the strain extract also had a broad-spectrum antifungal activity. Compared with the whole genome of strain QN1NO-4, several functional gene clusters involved in the biosynthesis of active secondary metabolites were observed. Fifteen compounds were identified by gas chromatography-mass spectrometry (GC-MS). Hence, the fruit endophyte B. safensis sp. QN1NO-4 is a potential bio-agent identified for the management of post-harvest disease of strawberry fruit.

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.

Acetobacter orientalis XJC-C with a high lignocellulosic biomass-degrading ability improves significantly composting efficiency of banana residues by increasing metabolic activity and functional diversity of bacterial community.

Banana residues are an important energy resource after fruit harvesting. The optionally dumping and burning causes severely environmental problems. Traditional compost efficiency was limited by lignocellulosic composition of banana residues. Inoculation with cellulase-producing microbes provides an efficient strategy for improving degradation of lignocellulosic materials. In our study, a newly isolated cellulolytic bacterium Acetobacter orientalis XJC-C with a salt and high temperature resistance was identified from a marine soft coral. By contrast, the strain can biodegrade different lignocellulosic agricultural residues, especially banana straw. The highest cellulolytic and ligninolytic enzyme activities were detected during composting at 40 days. Compared with the negative and positive control groups, the lignin degradation rate reached 76.24% in the A. orientalis XJC-C group, increased by 47.08% and 21.85%, respectively. Moreover, the strain improved significantly the metabolic activity and functional diversity of bacterial community. Hence, A. orientalis XJC-C will be a promising candidate for degrading lignocellulosic agricultural residues.