ABSTRACT
Cerebral small vascular disease (CSVD) has a high incidence worldwide, but its pathological mechanisms remain poorly understood due to the lack of proper animal models. The current animal models of CSVD have several limitations such as high mortality rates and large-sized lesions, and thus it is urgent to develop new animal models of CSVD. Ultrasound can activate protoporphyrin to produce reactive oxygen species in a liquid environment. Here we delivered protoporphyrin into cerebral small vessels of rat brain through polystyrene microspheres with a diameter of 15 µm, and then performed transcranial ultrasound stimulation (TUS) on the model rats. We found that TUS did not affect the large vessels or cause large infarctions in the brain of model rats. The mortality rates were also comparable between the sham and model rats. Strikingly, TUS induced several CSVD-like phenotypes such as cerebral microinfarction, white matter injuries and impaired integrity of endothelial cells in the model rats. Additionally, these effects could be alleviated by antioxidant treatment with N-acetylcysteine (NAC). As control experiments, TUS did not lead to cerebral microinfarction in the rat brain when injected with the polystyrene microspheres not conjugated with protoporphyrin. In sum, we generated a rat model of CSVD that may be useful for the mechanistic study and drug development for CSVD.
ABSTRACT
Appropriate cell division and differentiation ensure normal anther development in angiosperms. BARELY ANY MERISTEM 1/2 (BAM1/2) and RECEPTOR-LIKE PROTEIN KINASE2 (RPK2), two groups of leucine-rich repeat receptor-like protein kinases, are required for early anther cell specification. However, little is known about the molecular mechanisms underlying these two RLK-mediated signaling pathways. Here, we show that CLAVATA3 INSENSITIVE RECEPTOR KINASEs (CIKs), a group of novel coreceptor protein kinase-controlling stem cell homeostasis, play essential roles in BAM1/2- and RPK2-regulated early anther development in Arabidopsis thaliana The archesporial cells of cik1/2/3 triple and cik1/2/3/4 quadruple mutant anthers perform anticlinal division instead of periclinal division. Defective cell division and specification of the primary and inner secondary parietal cells occur in these mutant anthers. The disordered divisions and specifications of anther wall cells finally result in excess microsporocytes and a lack of one to three parietal cell layers in mutant anthers, resembling rpk2 or bam1/2 mutant anthers. Genetic and biochemical analyses indicate that CIKs function as coreceptors of BAM1/2 and RPK2 to regulate archesporial cell division and determine the specification of anther parietal cells.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/physiology , Flowers/growth & development , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Arabidopsis/cytology , Arabidopsis Proteins/genetics , Cell Differentiation/genetics , Flowers/cytology , Flowers/metabolism , Gene Expression Regulation, Plant , Mutation , Phosphorylation , Plant Cells/physiology , Plants, Genetically Modified , Protein Kinases/genetics , Protein Serine-Threonine Kinases/geneticsABSTRACT
Given the important contributions of semiarid region to global land carbon cycle, accurate modeling of the interannual variability (IAV) of terrestrial gross primary productivity (GPP) is important but remains challenging. By decomposing GPP into leaf area index (LAI) and photosynthesis per leaf area (i.e., GPP_leaf), we investigated the IAV of GPP and the mechanisms responsible in a temperate grassland of northwestern China. We further assessed six ecosystem models for their capabilities in reproducing the observed IAV of GPP in a temperate grassland from 2004 to 2011 in China. We observed that the responses to LAI and GPP_leaf to soil water significantly contributed to IAV of GPP at the grassland ecosystem. Two of six models with prescribed LAI simulated of the observed IAV of GPP quite well, but still underestimated the variance of GPP_leaf, therefore the variance of GPP. In comparison, simulated pattern by the other four models with prognostic LAI differed significantly from the observed IAV of GPP. Only some models with prognostic LAI can capture the observed sharp decline of GPP in drought years. Further analysis indicated that accurately representing the responses of GPP_leaf and leaf stomatal conductance to soil moisture are critical for the models to reproduce the observed IAV of GPP_leaf. Our framework also identified that the contributions of LAI and GPP_leaf to the observed IAV of GPP were relatively independent. We conclude that our framework of decomposing GPP into LAI and GPP_leaf has a significant potential for facilitating future model intercomparison, benchmarking and optimization should be adopted for future data-model comparisons.
Subject(s)
Grassland , Models, Biological , Carbon Cycle , China , Photosynthesis/physiology , Plant Leaves/physiology , Plant Stomata , Plant Transpiration , Soil , Time FactorsABSTRACT
BACKGROUND: Oxidized Low-Density Lipoprotein (ox-LDL) is crucial in the recrudescence and prognosis of acute ischemic stroke (AIS). We aimed to probe into the influence of cumulative ox-LDL exposure on the 90-day prognosis of AIS. METHODS: Patients with AIS were recruited in this research. AIS severity at admission was estimated with infarct volumes and National Institute of Health Stroke Scale (NIHSS) scores. AIS prognosis was assessed using Modified Rankin Scale (mRS) scores at 90 days and the change in NIHSS scores from admission to discharge. Cumulative ox-LDL exposure was defined as ox-LDL level (pg/mL) multiplied by age(y). Multivariate logistic regression analysis was employed to reveal the correlation between exposure factors and the prognosis of AIS. The prognostic prediction ability of cumulative ox-LDL exposure was compared with cumulative LDL exposure by the receiver operating characteristic curve (ROC). RESULTS: Higher cumulative ox-LDL exposure was related to worse prognosis, including neurological worsening at discharge (NIHSS increasing more than 2 points) (OR = 3.02, 95% CI, 1.30-6.98, P = 0.01) and poor functional prognosis at 90 days (mRS ≥ 3) (OR = 21.21, 95% CI, 4.72-95.36, P < 0.001). As multivariate regression analysis showed, significantly increased cumulative ox-LDL exposure was relevant to poor functional prognosis at 90 days (OR = 9.92, 95% CI, 1.23-79.76, P = 0.031), but not with neurological worsening at discharge (P = 0.414). ROC curve revealed that cumulative ox-LDL exposure had a higher predictive value (AUC = 0.843, P < 0.001) for functional prognosis of AIS than cumulative LDL exposure (AUC = 0.629, P = 0.023). CONCLUSION: Cumulative ox-LDL exposure has a positive correlation with poor prognosis at 90 days of AIS, and has a more accurate predictive ability than cumulative LDL exposure.
Subject(s)
Ischemic Stroke , Lipoproteins, LDL , Aged , Female , Humans , Male , Middle Aged , Brain Ischemia/diagnosis , Brain Ischemia/drug therapy , Brain Ischemia/blood , Cohort Studies , Ischemic Stroke/diagnosis , Ischemic Stroke/blood , Lipoproteins, LDL/blood , Prognosis , Aged, 80 and overABSTRACT
Objective: To evaluate the application value of combined detection of serum homocysteine (Hcy), Toll-like receptor 4 (TLR4), and C-reactive protein (CRP) in the diagnosis of cerebral small vessel disease (CSVD). Methods: 90 patients with CSVD admitted to our hospital within the past year were identified as the research subjects, and the patients with cognitive dysfunction were assigned to the experimental group, and those with normal cognitive function were assigned to the control group according to the evaluation of cognitive dysfunction by the Montreal Cognitive Assessment (MoCA), with 45 cases in each group. Results: The experimental group obtained remarkably elevated Hcy levels than the control group (P < 0.05). The patient's cognitive dysfunction is mainly attributed to the impact of serum Hcy. TLR4 and Hcy were negatively correlated with MoCA scores (P > 0.05). In comparison with the control group, the experimental group had significantly higher levels of Hcy, serum CRP, and interleukin (IL)-6 (P < 0.05). Conclusion: The combined detection of serum Hcy, TLR4, and CRP features a high clinical value in the diagnosis of CSVD, which contributes to the prevention and treatment of cognitive dysfunction in patients.
ABSTRACT
OBJECTIVE: To evaluate the effects of a combination of Yinyanghuo (Herba Epimedii Brevicornus) (HEB) and Cheqianzi (Semen Plantaginis) (SP) on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats (SHRs), and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor (ACE2/Ang [1-7]/Mas receptor) axis in this process. METHODS: A total of 24 SHRs were randomly assigned to three groups: SHR-control, low-dose (12.5 g/kg) and high-dose (25 g/kg) HEB+SP (HEBSP). Eight Wistar-Kyoto rats were used as normal controls. HEBSP was administered by oral gavage for 28 d. Erectile function was measured once a week using the Heaton test. After 4 weeks of treatment, the corpus cavernosum was harvested from each rat to measure nitric oxide (NO), nitric oxide synthase (eNOS) and Ang (1-7) levels, as well as ACE2, Mas receptor and neuronal nitric oxide synthase (nNOS) protein expression. RESULTS: After 4 weeks of treatment, HEBSP significantly increased erectile function in the treated group compared with SHR-control group (P < 0.01). Additionally, HEBSP treatment significantly increased cavernosal levels of Ang (1-7), eNOS and NO. Moreover, HEBSP significantly elevated the expression levels of ACE2, Mas receptor and nNOS. These beneficial effects were elevated in the high-dose HEBSP group. CONCLUSION: HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang (1-7)/Mas receptor axis, eNOS and nNOS pathways.
Subject(s)
Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Drugs, Chinese Herbal/administration & dosage , Erectile Dysfunction/drug therapy , Erectile Dysfunction/metabolism , Peptide Fragments/metabolism , Angiotensin I/genetics , Angiotensin-Converting Enzyme 2/genetics , Animals , Drug Therapy, Combination , Erectile Dysfunction/genetics , Erectile Dysfunction/physiopathology , Humans , Male , Nitric Oxide Synthase Type I/genetics , Nitric Oxide Synthase Type I/metabolism , Penile Erection/drug effects , Peptide Fragments/genetics , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Up-Regulation/drug effectsABSTRACT
Herb borneol is usually used in clinics for the treatment of central nervous system illness, for its ability of blood-brain barrier permeability, although its poor water solubility and poor bioavailability limit its clinical application to some degree. In this study, we developed a novel nanoparticle combining the benefits of vitamin E d-É-tocopheryl poly(ethylene glycol) succinate (E-TPGS) (or TPGS) and guar gum to get TPGS-g-guar gum as a drug delivery system to carry borneol, which could improve the solubility of borneol and increase the drug-loading capacity efficiently. The results showed that TPGS-g-guar gum nanoparticles delivery system was suitable to carry borneol and release the drug effectively, and TPGS-g-guar gum/borneol nanoparticles would be a potential platform for improving the treatment of central nervous system illness and cerebrovascular disease.
Subject(s)
Blood-Brain Barrier/metabolism , Camphanes/administration & dosage , Central Nervous System Agents/administration & dosage , Galactans/chemistry , Mannans/chemistry , Nanocapsules/chemistry , Plant Gums/chemistry , Vitamin E/chemistry , 3T3 Cells , Animals , Biological Availability , Cell Survival , Drug Delivery Systems , Hemolysis , Humans , Mice , Micelles , Permeability , Solubility , Succinic Acid/chemistryABSTRACT
Continuous organ initiation and outgrowth in plants relies on the proliferation and differentiation of stem cells maintained by the CLAVATA (CLV)-WUSCHEL (WUS) negative-feedback loop1-3. Leucine-rich repeat receptor-like protein kinases (LRR-RLKs), including CLV1, BARELY ANY MERISTEMS and RECEPTOR-LIKE PROTEIN KINASE 2 (RPK2), a receptor-like protein CLV2 and a pseudokinase CORYNE (CRN) are involved in the perception of the CLV3 signal to repress WUS expression4-10. WUS, a homeodomain transcription factor, in turn directly activates CLV3 expression and promotes stem cell activity in the shoot apical meristem11,12. However, the signalling mechanism immediately following the perception of CLV3 by its receptors is poorly understood. Here, we show that a group of LRR-RLKs, designated as CLAVATA3 INSENSITIVE RECEPTOR KINASES (CIKs), have essential roles in regulating CLV3-mediated stem cell homeostasis. The cik1 2 3 4 quadruple mutant exhibits a significantly enlarged SAM, resembling clv mutants. Genetic analyses and biochemical assays demonstrated that CIKs function as co-receptors of CLV1, CLV2/CRN and RPK2 to mediate CLV3 signalling through phosphorylation. Our findings not only widen the understanding of the underlying mechanism of CLV3 signal transduction in regulating stem cell fate but also reveal a novel group of RLKs that function as co-receptors to possibly mediate multiple extrinsic and intrinsic signals during plant growth and development.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Protein Kinases/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant , Homeodomain Proteins/metabolism , Homeostasis , Membrane Proteins/genetics , Membrane Proteins/metabolism , Meristem/cytology , Meristem/genetics , Meristem/metabolism , Mutation , Phosphorylation , Plant Cells/metabolism , Plant Stems/cytology , Plant Stems/metabolism , Plants, Genetically Modified , Protein Kinases/genetics , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Signal TransductionABSTRACT
We proposed a new method of gist feature extraction for building recognition and named the feature extracted by this method as the histogram of oriented gradient based gist (HOG-gist). The proposed method individually computes the normalized histograms of multiorientation gradients for the same image with four different scales. The traditional approach uses the Gabor filters with four angles and four different scales to extract orientation gist feature vectors from an image. Our method, in contrast, uses the normalized histogram of oriented gradient as orientation gist feature vectors of the same image. These HOG-based orientation gist vectors, combined with intensity and color gist feature vectors, are the proposed HOG-gist vectors. In general, the HOG-gist contains four multiorientation histograms (four orientation gist feature vectors), and its texture description ability is stronger than that of the traditional gist using Gabor filters with four angles. Experimental results using Sheffield Buildings Database verify the feasibility and effectiveness of the proposed HOG-gist.
Subject(s)
Image Processing, Computer-Assisted , Orientation, Spatial , Pattern Recognition, Automated , Algorithms , Databases, Factual , Humans , Support Vector MachineABSTRACT
Receptor-like protein kinases (RLKs) are a large group of transmembrane proteins playing critical roles in cell-cell and cell-environment communications. Based on extracellular domain structures, RLKs were classified into more than 21 subfamilies, among which leucine-rich repeat RLKs (LRR-RLKs) belong to the largest subfamily in plants such as Arabidopsis and rice. In Arabidopsis, there are approximately 223 LRR-RLKs, but only about 60 of which have been functionally described to date. To systematically investigate the roles of LRR-RLKs in regulating plant growth, development, and stress adaptations, we generated promoter::GUS transgenic plants for all 223 LRR-RLK genes in Arabidopsis and analyzed their detailed expression patterns at various developmental stages. The results provide valuable resources for functionally elucidating this large and essential signaling protein subfamily.