The NEDD8-activating enzyme inhibitor MLN4924 reduces ischemic brain injury in mice.

Blood-brain barrier (BBB) breakdown and inflammation occurring at the BBB have a key, mainly a deleterious role in the pathophysiology of ischemic stroke. Neddylation is a ubiquitylation-like pathway that is critical in various cellular functions by conjugating neuronal precursor cell-expressed developmentally down-regulated protein 8 (NEDD8) to target proteins. However, the roles of neddylation pathway in ischemic stroke remain elusive. Here, we report that NEDD8 conjugation increased during acute phase after ischemic stroke and was present in intravascular and intraparenchymal neutrophils. Inhibition of neddylation by MLN4924, also known as pevonedistat, inactivated cullin-RING E3 ligase (CRL), and reduced brain infarction and improved functional outcomes. MLN4924 treatment induced the accumulation of the CRL substrate neurofibromatosis 1 (NF1). By using virus-mediated NF1 silencing, we show that NF1 knockdown abolished MLN4924-dependent inhibition of neutrophil trafficking. These effects were mediated through activation of endothelial P-selectin and intercellular adhesion molecule-1 (ICAM-1), and blocking antibodies against P-selectin or anti-ICAM-1 antibodies reversed NF1 silencing-induced increase in neutrophil infiltration in MLN4924-treated mice. Furthermore, we found that NF1 silencing blocked MLN4924-afforded BBB protection and neuroprotection through activation of protein kinase C δ (PKCδ), myristoylated alanine-rich C-kinase substrate (MARCKS), and myosin light chain (MLC) in cerebral microvessels after ischemic stroke, and treatment of mice with the PKCδ inhibitor rottlerin reduced this increased BBB permeability. Our study demonstrated that increased neddylation promoted neutrophil trafficking and thus exacerbated injury of the BBB and stroke outcomes. We suggest that the neddylation inhibition may be beneficial in ischemic stroke.

In vitro antifungal activity of lasiodiplodin, isolated from endophytic fungus Lasiodiplodia pseudotheobromae J-10 associated with Sarcandra glabra and optimization of culture conditions for lasiodiplodin production.

A macrolide antibiotic, lasiodiplodin was isolated from the endophytic fungus (EF) Lasiodiplodia pseudotheobromae J-10 associated with the medicinal plant Sarcandra glabra. In vitro antifungal assay demonstrated the inhibitory activity of lasiodiplodin against the growth of six phytopathogenic fungi, with the IC50 values ranging between 15.50 and 52.30 µg/mL. The highest antifungal activities were recorded against Exserohilum turcicum, Colletotrichum capsici, and Pestalotiopsis theae, with IC50 values of 15.50, 15.90, and 17.55 µg/mL, respectively. The underlying mechanism of the antifungal activity of lasiodiplodin against E. turcicum included the alteration of its colony morphology and disturbance of its cell membrane integrity. In addition, the optimization of L. pseudotheobromae J-10 culture conditions increased lasiodiplodin yield to 52.33 mg/L from 0.59 mg/L at pre-optimization. This is the first report on the isolation and identification of antifungal compound from the EF L. pseudotheobromae J-10 associated with S. glabra, as well as on the optimization of L. pseudotheobromae J-10 culture conditions to increase lasiodiplodin yield. The results of this study support that lasiodiplodin is a natural compound with high potential bioactivity against phytopathogens, and provide a basis for further study of the EF associated with S. glabra.

Ultrasound Assessment of Entheseal Sites and Anterior Chest Wall in Ankylosing Spondylitis: A Cross-Sectional Study.

OBJECTIVES: The study was designed to evaluate entheseal sites and anterior chest wall (ACW) of patients with ankylosing spondylitis (AS) using ultrasound (US) and investigate the correlation between disease activity and US score. METHODS: This prospective cross-sectional study included 104 patients with AS and 50 control subjects. Each patient underwent US scanning of 23 entheses and 11 sites of the ACW. The US features, including hypoechogenicity, thickness, erosion, calcification, bursitis, and Doppler signal, were evaluated. Disease activity was assessed based on C reactive protein (CRP), erythrocyte sedimentation rate (ESR), disease activity score-C reactive protein (ASDAS-CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: The most commonly involved entheses on US were the Achilles tendon (AT) and quadriceps tendon (QT). The most involved site of ACW was the sternoclavicular joint (SCJ). Compared with the control group, significant differences were observed in the AS group in the rates of US enthesitis and ACW in AT (P = .01), SCJ (P = .00), and costochondral joint (CCJ) (P = .01). Patients with high or very high disease activity had a higher erosion score (P = .02). The erosion score was weakly positively associated with CRP, ESR, BASDAI, ASDAS-CRP, and ASDAS-ESR (correlation coefficient: 0.22-0.45). CONCLUSIONS: The most commonly involved entheseal sites on US were AT and QT, while the site of ACW was SCJ. The US assessment of AS should take the ACW into account. High disease activity might indicate erosion in AS.

The extraction and identification of active components of the sex pheromones of Asian citrus psyllid, Diaphorina citri.

In this study, we extracted and identified the active components of the Asian citrus psyllid, Diaphorina citri sex pheromones to provide a basis for further development of sex attractants. Under laboratory conditions, mating activity in D. citri started 3 d after emergence, which peaked at 6-7 d, and mating activity had no obvious peak during the observed period 7:00-21:00 h. Additionally, D. citri males were attracted to the emanations from conspecific females, especially to the n-hexane extracts of the pheromone. A total of 17 compounds were identified from the n-hexane extracts of female and male D. citri by gas chromatography-mass spectrometer (GC-MS). Among them, 13 compounds were identified from the female D. citri n-hexane extracts, of which 7 (dichloromethane, acetic acid, toluene, butyl acetate, ethyl carbamoylacetate, α-pinene, and 1-nonanal) were not found in the male D. citri n-hexane extracts. In addition, a total of 33 compounds were identified from the solid phase microextraction (SPME) volatiles of the male and female D. citri adults. Among these, 17 compounds were identified from the female D. citri volatiles, of which 6 (cycloheptatriene, 5-methyl-2-phenylindole, 1-dodecanol, cis-11-hexadecena, dodecyl aldehyde, and nerylacetone) were not identified in the volatiles of the D. citri males. It was found that males were significantly attracted to 0.1-10 µL/mL acetic acid and 1-nonanal with the selection rates ranging from 62.04%-70.56% and 62.22%-67.22%, respectively. Therefore, the results of this study suggest that acetic acid and 1-nonanal might be the active compounds of the female D. citri sex pheromones.

Identification of sex pheromone of red swamp crayfish Procambarus clarkii and exploration of the chemosensory mechanism of their antennae.

Red swamp crayfish, Procambarus clarkii, is a globally invasive species, which has caused great damage to biodiversity, agriculture, and fishing. Therefore, the development of effective management methods, such as pheromone control, is necessary for biological control and biodiversity protection. However, the components of P. clarkii sex pheromones have not yet been explored, and the chemosensory mechanism of the P. clarkii antennae after stimulation by sex pheromone also remains unknown. In this study, we isolated and identified the candidate bioactive component of the female P. clarkii sex pheromone using ultrafiltration centrifugation, semi-preparative liquid phase separation and omics technologies and conducted bioassays to determine its attraction ability. Meanwhile, RNA-Seq technology was used to analyze the potential chemosensory mechanism of antennae. Our results indicated that the male P. clarkii were uniaxially attracted to the female crude conditioned water (FCW), medium fraction (MF, isolated by ultrafiltration centrifugation), and preparative fragment 6 of females (PFF6, isolated by semi-preparative liquid phase separation). Metabolomic analysis revealed the presence of 18 differential metabolites between the PFF6 and PFM6 samples, among which 15 were significantly upregulated in the PFF6 sample. Bioassay test also showed that mestranol, especially at concentrations of 10-5-10-2 mol∙l-1, could significantly attract P. clarkii males; therefore, mestranol was identified as the candidate sex pheromone component of P. clarkii females. Furthermore, RNA-Seq results showed that most differentially expressed genes (DEGs) enriched in lipid metabolism and signal transduction pathways were up-regulated in P. clarkii males. In addition, high expressions of Ca2+-binding protein and ion transporting ATPases may enhance the sensitivity of the antennae of P. clarkii males towards sex pheromones. Our study provides data on P. clarkii sex pheromone composition and reveals the molecular mechanism of sex pheromone response in P. clarkii. Moreover, our study provides a referable method for the isolation of candidate bioactive molecules from the P. clarkii sex pheromone.

Ultrasound features and differential diagnosis for superficial nodular fasciitis.

BACKGROUND: Nodular fasciitis (NF) has nonspecific clinical manifestations and is often misdiagnosed as sarcoma. The investigations of imaging methods for NF were limited. OBJECTIVE: To analyze the ultrasound (US) features of NF, and to evaluate the diagnostic value of US for NF. MATERIALS AND METHODS: A total of 61 NF patients were recruited retrospectively, and 551 lesions in the subcutaneous fat layer were included for comparison. We evaluated the ultrasound features of the patients and divided the NF cases into three types. Chi-square test or Fisher exact test were conducted to detect the potential difference in the distributions of three types in the two groups. RESULTS: Among the 61 NF cases, 65.6% were in the upper extremities (n = 40). The proportion of type 1, 2, and 3 were 57.4%, 24.6%, and 18.0%, respectively. NF were significantly more likely locating in the upper extremities than the other soft tissue tumors (p < 0.001). Type 1 and type 2 of sonographic features were significantly more commonly observed in NF than other soft tissue tumors among the three types (p < 0.001). CONCLUSION: The type 1 and type 2 of US features can help to distinguish NF from other lesions. US has great potential to improve the diagnostic accuracy and reduce the unnecessary surgery.

ADAMTS13 maintains cerebrovascular integrity to ameliorate Alzheimer-like pathology.

Blood-brain barrier (BBB) defects and cerebrovascular dysfunction contribute to amyloid-ß (Aß) brain accumulation and drive Alzheimer disease (AD) pathology. By regulating vascular functions and inflammation in the microvasculature, a disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) plays a significant protective effect in atherosclerosis and stroke. However, whether ADAMTS13 influences AD pathogenesis remains unclear. Using in vivo multiphoton microscopy, histological, behavioral, and biological methods, we determined BBB integrity, cerebrovascular dysfunction, amyloid accumulation, and cognitive impairment in APPPS1 mice lacking ADAMTS13. We also tested the impact of viral-mediated expression of ADAMTS13 on cerebrovascular function and AD-like pathology in APPPS1 mice. We show that ADAMTS13 deficiency led to an early and progressive BBB breakdown as well as reductions in vessel density, capillary perfusion, and cerebral blood flow in APPPS1 mice. We found that deficiency of ADAMTS13 increased brain plaque load and Aß levels and accelerated cerebral amyloid angiopathy (CAA) by impeding BBB-mediated clearance of brain Aß, resulting in worse cognitive decline in APPPS1 mice. Virus-mediated expression of ADAMTS13 attenuated BBB disruption and increased microvessels, capillary perfusion, and cerebral blood flow in APPPS1 mice already showing BBB damage and plaque deposition. These beneficial vascular effects were reflected by increase in clearance of cerebral Aß, reductions in Aß brain accumulation, and improvements in cognitive performance. Our results show that ADAMTS13 deficiency contributes to AD cerebrovascular dysfunction and the resulting pathogenesis and cognitive deficits and suggest that ADAMTS13 may offer novel therapeutic opportunities for AD.

Hippocampal alpha-synuclein mediates depressive-like behaviors.

Alpha-synuclein (α-syn) which encoded by SNCA plays a critical role in the neurotransmission, vesicle dynamics, and neuroplasticity. Alteration to SNCA expression is associated with major depressive disorder. However, the pathogenic mechanism of SNCA in depression remains unknown. Herein, we reported that SNCA was up-regulated in the peripheral blood of major depressive disorder (MDD) patients and the depressive mice. Chronic restraint stress (CRS) also up-regulated the SNCA expression in the hippocampus. Moreover, over-expression of SNCA in the hippocampus triggered spontaneous depressive-like behaviors under the non-stressed conditions in mice, and knockout of SNCA could reverse CRS-induced depressive-like behaviors. SNCA led to synapse loss and neuronal cell death in the hippocampus possibly via complement-mediated microglial engulfment and inflammation, and thus contributed to the pathogenesis of depressive disorder. Overall, hippocampal SNCA and complement system are involved in the pathogenesis of depressive disorder and it provides a new perspective for the occurrence of depressive disorder.

ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery.

Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)-cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke. Deficiency of VWF or anti-VWF antibody treatment significantly increased microvessels, perfused capillary length, and reversed pericyte loss and BBB changes in Adamts13-/- mice. Furthermore, we observed that ADAMTS13 deficiency decreased angiopoietin-2 and galectin-3 levels in the isolated brain microvessels, whereas VWF deficiency had the opposite effect. Correlating with this, overexpression of angiopoietin-2 by adenoviruses treatment or administration of recombinant galectin-3 normalized microvascular reductions, pericyte loss, and BBB breakdown in Adamts13-/- mice. The vascular changes induced by angiopoietin-2 overexpression and recombinant galectin-3 treatment in Adamts13-/- mice were abolished by the vascular endothelial growth factor receptor-2 antagonist SU1498. Importantly, treating wild-type mice with recombinant ADAMTS13 at 7 days after stroke markedly increased neovascularization and vascular repair and improved functional recovery at 14 days. Our results suggest that ADAMTS13 controls key steps of ischemic vascular remodeling and that recombinant ADAMTS13 is a putative therapeutic avenue for promoting stroke recovery.

Updated incidence rates and risk factors of esophageal cancer in Nan'ao Island, a coastal high-risk area in southern China.

Esophageal cancer (EC) is one of the most common cancers in China. The purpose of this study was to investigate the updated incidence rates and risk factors of EC in Nan'ao Island, where the EC incidence rate was chronically the highest in southern China. To calculate the annual incidence rate, data on 338 EC cases from Nan'ao Cancer Registry system diagnosed during 2005-2011 were collected. A case-control study was conducted to explore the EC risk factors. One hundred twenty-five alive EC patients diagnosed during 2005-2011 and 250 controls were enrolled into the case-control study. A pre-test questionnaire on demography, dietary factors, drinking water treatment, and behavioral factors was applied to collect information of all participants. The average EC incidence rates during 2005-2011 were 66.09/105, 94.62/105, 36.83/105 for both genders, males and females, respectively, in Nan'ao Island. The EC incidence rate in males was 2.40- to 4.55-fold higher than that in females in the period from 2006 to 2011 (P < 0.05). Considering the onset age, males tend to be much younger than females and reached peak incidence rate at a younger age (P < 0.05). Drinking water treatment by filter (odds ratio [OR] = 0.28, 95% confidence interval [95% CI] = 0.13-0.58) and fruit consumption (OR = 0.55, 95% CI = 0.32-0.94) reduced the risk for EC. On the contrary, the pickled vegetables consumption (OR = 2.64, 95% CI = 1.46-4.76) and liquor drinking (OR = 2.32, 95% CI = 1.21-4.44) increased the risk for EC. These results may be of importance for future research on EC etiology and prevention strategies.

Recombinant ADAMTS 13 Attenuates Brain Injury After Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Inflammatory responses and blood-brain barrier (BBB) dysfunction play important roles in brain injury after intracerebral hemorrhage (ICH). The metalloprotease ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin type I motif, member 13) was shown to limit inflammatory responses through its proteolytic effects on von Willebrand factor. In the present study, we addressed the role of ADAMTS 13 after experimental ICH. METHODS: ICH was induced in mice by intracerebral infusion of autologous blood. The peri-hematomal inflammatory responses, levels of matrix metalloproteinase-9 and intercellular adhesion molecule-1, pericyte coverage on brain capillaries, and BBB permeability were quantified at 24 hours. Functional outcomes, cerebral edema, and hemorrhagic lesion volume were quantified at day 3. RESULTS: Treatment with recombinant ADAMTS 13 (rADAMTS 13) reduced the levels of chemokines and cytokines, myeloperoxidase activity, and microglia activation and neutrophil recruitment after ICH. rADAMTS 13 also decreased interleukin-6 expression in brain endothelial cells stimulated by lipopolysaccharide, whereas recombinant von Willebrand factor reversed this effect. The anti-inflammatory effect of rADAMTS 13 was accompanied by reduced expression of intercellular adhesion molecule-1 and less activation of matrix metalloproteinase, enhanced pericyte coverage of brain microvessels, and attenuated BBB disruption. Furthermore, neutrophil depletion protected against BBB damage, and rADAMTS 13 treatment had no further beneficial effect. Finally, treatment of mice with rADAMTS 13 reduced cerebral edema and hemorrhagic lesion volume and improved neurological functions. CONCLUSIONS: Our findings reveal the importance of rADAMTS 13 in regulating pathological inflammation and BBB function and suggest that rADAMTS 13 may provide a new therapeutic strategy for ICH.

Natural dibenzo-α-pyrones and their bioactivities.

Natural dibenzo-α-pyrones are an important group of metabolites derived from fungi, mycobionts, plants and animal feces. They exhibit a variety of biological activities such as toxicity on human and animals, phytotoxicity as well as cytotoxic, antioxidant, antiallergic, antimicrobial, antinematodal, and acetylcholinesterase inhibitory properties. Dibenzo-α-pyrones are biosynthesized via the polyketide pathway in microorganisms or metabolized from plant-derived ellagitannins and ellagic acid by intestinal bacteria. At least 53 dibenzo-α-pyrones have been reported in the past few decades. This mini-review aims to briefly summarize the occurrence, biosynthesis, biotransformation, as well as their biological activities and functions. Some considerations related to synthesis, production and applications of dibenzo-α-pyrones are also discussed.

Enhanced production of botrallin and TMC-264 with in situ macroporous resin adsorption in mycelial liquid culture of the endophytic fungus Hyalodendriella sp. Ponipodef12.

Hyalodendriella sp. Ponipodef12, an endophytic fungus from the hybrid "Neva" of Populus deltoides × P. nigra, is a high producer of the bioactive dibenzo-α-pyrones botrallin and TMC-264. However, both the botrallin and TMC-264 produced by Hyalodendriella sp. Ponipodef12 were retained as both intracellular and extracellular products. The aim of this study was to evaluate an in situ macroporous resin adsorption for enhancement of botrallin and TMC-264 production in mycelial liquid culture of Hyalodendriella sp. Ponipodef12. Production of botrallin and TMC-264 was most effectively enhanced by macroporous resin DM-301 among the thirteen nonionic macroporous resins tested. The highest botrallin yield (51.47 mg/L, which was 2.29-fold higher than the control at 22.49 mg/L) was obtained by adding resin DM-301 at 4.38% (g/mL) to the culture broth on day 24 and allowing a period of 4 days for adsorption. The highest TMC-264 yield reached 47.74 mg/L, which was 11.76-fold higher than that of the control (4.06 mg/L), and was achieved by adding DM-301 resin at 4.38% (w/v) in the culture broth on day 24 and allowing a period of 6 days for adsorption. The results show that in situ resin adsorption is an effective strategy for enhancing production of botrallin and TMC-264, and also for facilitating their recovery from mycelial liquid culture of Hyalodendriella sp. Ponipodef12.

Separation and purification of bioactive botrallin and TMC-264 by a combination of HSCCC and semi-preparative HPLC from endophytic fungus Hyalodendriella sp. Ponipodef12.

Two dibenzo-α-pyrones, botrallin (1) and TMC-264 (2) were preparatively separated from crude ethyl acetate extract of the endophytic fungus Hyalodendriella sp. Ponipodef12, which was isolated from the hybrid 'Neva' of Populus deltoides Marsh × P. nigra L. using a combination of high-speed counter-current chromatography (HSCCC) and semi-preparative HPLC. Botrallin (1) with 74.73% of purity and TMC-264 (2) with 82.29% of purity were obtained through HSCCC by employing a solvent system containing n-hexane-ethyl acetate-methanol-water at a volume ratio of 1.2:1.0:0.9:1.0. It was the first time for TMC-264 (2) to be isolated from this fungus. TMC-264 (2) showed strong antimicrobial and antinematodal activity, and botrallin (1) exhibited moderate inhibitory activity on acetylcholinesterase.

Effect of amylose partial extraction on citrate esterification of potato starch and its role in structure and physicochemical modification.

This study examines the impact and influence of amylose on the starch esterification reaction through partial extraction of amylose. Citric acid was added for the esterification reaction, and then the esterified starches' multiscale structure, physicochemical, and functional properties were evaluated. As the extraction time of amylose increased, the amylose content in the starch decreased. Higher concentrations of citric acid will lead to samples with a higher degree of substitution, with DS rising from 0.203 % (0 h) to 0.231 % (3.5 h) at CA3 treatment. While removing amylose had minimal effects on the crystal structure of starch granules, it did decrease the ratio of A and B1 chains and the molecular weight of amylose. Acid hydrolysis exacerbated these changes upon the addition of citric acid. Furthermore, removing amylose followed by citrate esterification resulted in lower pasting viscosity, enthalpy of gelatinization (from 13.37 J to 2.83 J), and degree of short-range ordering. Also, digestion shows a decrease caused by the increasing content of slow-digesting starch. The presence of amylose in starch granules does affect the formation of starch esters, and removing it before esterification modification may improve production efficiency and reduce costs to some extent.

Effect of electron beam irradiation pretreatment and different fatty acid types on the formation, structural characteristics and functional properties of starch-lipid complexes.

The effects of different electron beam irradiation doses (2, 4, 8 KGy) and various types of fatty acids (lauric acid, stearic acid, and oleic acid) on the formation, structure, physicochemical properties, and digestibility of starch-lipid complex were investigated. The complexing index of the complexes was higher than 85 %, indicating that the three fatty acids could easily form complexes with starch. With the increase of electron beam irradiation dose, the complexing index increased first and then decreased. The highest complexing index was lauric acid (97.12 %), stearic acid (96.80 %), and oleic acid (97.51 %) at 2 KGy radiation dose, respectively. Moreover, the microstructure, crystal structure, thermal stability, rheological properties, and starch solubility were analyzed. In vitro digestibility tests showed that adding fatty acids could reduce the content of hydrolyzed starch, among which the resistant starch content of the starch-oleic acid complex was the highest (54.26 %). The lower dose of electron beam irradiation could decrease the digestibility of starch and increase the content of resistant starch.

Investigation of the role of sodium chloride on wheat starch multi-structure, physicochemical and digestibility properties during X-ray irradiation.

In this paper, different NaCl content was added to wheat starch and then subjected to X-ray irradiation to investigate the effect of salt on starch modification by irradiation. The results showed that the degradation of wheat starch intensified with the increase in irradiation dose. When irradiated at the same dose, wheat starch with sodium chloride produced shorter chains, lower molecular weight and amylose content, and higher crystallinity, solubility, and resistant starch than wheat starch without sodium chloride. The energy generated by X-rays dissociating sodium chloride caused damage to the glycoside bonds of the starch molecule. With a further increase in the mass fraction of NaCl, the hydrogen bonds of the starch molecules were broken, and the double helix structure was depolymerized, which exacerbated the extent of irradiation-modified wheat starch. At the same time, starch molecules will be rearranged to form a more stable structure.

Investigating the relationship between intracranial atherosclerotic plaque remodelling and diabetes using high-resolution vessel wall imaging.

BACKGROUND: Intracranial atherosclerosis, a leading cause of stroke, involves arterial plaque formation. This study explores the link between plaque remodelling patterns and diabetes using high-resolution vessel wall imaging (HR-VWI). AIM: To investigate the factors of intracranial atherosclerotic remodelling patterns and the relationship between intracranial atherosclerotic remodelling and diabetes mellitus using HR-VWI. METHODS: Ninety-four patients diagnosed with middle cerebral artery or basilar artery atherosclerosis were enrolled. Their basic clinical data were collected, and HR-VWI was performed. The vascular area at the plaque (VAMLN) and normal reference vessel (VAreference) were delineated and measured using image postprocessing software, and the Remodelling index (RI) was calculated. According to the value of the RI, the patients were divided into a positive remodelling (PR) group, intermediate remodelling (IR) group, negative remodelling (NR) group, PR group and non-PR (N-PR) group. RESULTS: The PR group exhibited a higher prevalence of diabetes and serum cholesterol levels than the IR and NR groups [45.2%, 4.54 (4.16, 5.93) vs 25%, 4.80 ± 1.22 and 16.4%, 4.14 (3.53, 4.75), respectively, P < 0.05]. The diabetes incidence was also significantly greater in the PR group than in the N-PR group (45.2% vs 17.5%, P < 0.05). Furthermore, the PR group displayed elevated serum triglyceride and cholesterol levels compared to the N-PR group [1.64 (1.23, 2.33) and 4.54 (4.16, 5.93) vs 4.54 (4.16, 5.93) and 4.24 (3.53, 4.89), P < 0.05]. Logistic regression analysis revealed diabetes mellitus as an independent influencing factor in plaque-PR [odds ratio (95% confidence interval): 3.718 (1.207-11.454), P < 0.05]. CONCLUSION: HR-VWI can clearly show the morphology and signal characteristics of intracranial vascular walls and plaques. Intracranial atherosclerotic plaques in diabetic patients are more likely to show PR, suggesting poor plaque stability and a greater risk of stroke.

Enhancement of Palmarumycins C(12) and C(13) production in liquid culture of endophytic fungus Berkleasmium sp. Dzf12 after treatments with metal ions.

The influences of eight metal ions (i.e., Na+, Ca2+, Ag+, Co2+, Cu2+, Al3+, Zn2+, and Mn4+) on mycelia growth and palmarumycins C(12) and C(13) production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12 were investigated. Three metal ions, Ca2+, Cu2+ and Al3+ were exhibited as the most effective to enhance mycelia growth and palmarumycin production. When calcium ion (Ca2+) was applied to the medium at 10.0 mmol/L on day 3, copper ion (Cu2+) to the medium at 1.0 mmol/L on day 3, aluminum ion (Al3+) to the medium at 2.0 mmol/L on day 6, the maximal yields of palmarumycins C(12) plus C(13) were obtained as 137.57 mg/L, 146.28 mg/L and 156.77 mg/L, which were 3.94-fold, 4.19-fold and 4.49-fold in comparison with that (34.91 mg/L) of the control, respectively. Al3+ favored palmarumycin C(12) production when its concentration was higher than 4 mmol/L. Ca2+ had an improving effect on mycelia growth of Berkleasmium sp. Dzf12. The combination effects of Ca2+, Cu2+ and Al3+ on palmarumycin C(13) production were further studied by employing a statistical method based on the central composite design (CCD) and response surface methodology (RSM). By solving the quadratic regression equation between palmarumycin C(13) and three metal ions, the optimal concentrations of Ca2+, Cu2+ and Al3+ in medium for palmarumycin C(13) production were determined as 7.58, 1.36 and 2.05 mmol/L, respectively. Under the optimum conditions, the predicted maximum palmarumycin C(13) yield reached 208.49 mg/L. By optimizing the combination of Ca2+, Cu2+ and Al3+ in medium, palmarumycin C(13) yield was increased to 203.85 mg/L, which was 6.00-fold in comparison with that (33.98 mg/L) in the original basal medium. The results indicate that appropriate metal ions (i.e., Ca2+, Cu2+ and Al3+) could enhance palmarumycin production. Application of the metal ions should be an effective strategy for palmarumycin production in liquid culture of the endophytic fungus Berkleasmium sp. Dzf12.