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1.
Plant Physiol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875160

ABSTRACT

Nine-carbon aldehydes and their relative alcohols (C9 aromas) are the main aroma compounds of cucumber (Cucumis sativus L.) fruits and provide a unique cucumber-like note. However, the key regulators of C9 aroma accumulation in cucumber fruit are poorly characterized. Based on C9 aroma dynamic analysis and transcriptome analysis during fruit development of two different cucumber inbred lines, Q16 and Q24, Lipoxygenase09 (CsLOX09) was identified as a candidate gene for C9 aroma accumulation. Additionally, Q24 with higher CsLOX09 expression accumulated more C9 aromas than Q16. To verify the function of CsLOX09, Cslox09 homozygote knockout lines were created. C9 aroma content decreased by 80.79%-99.16% in these mutants compared to the wild type. To further explore the reasons for the difference in CsLOX09 expression between Q16 and Q24 fruits, a co-expression network was constructed by integrating the C9 aroma-associated metabolism and transcriptomic data. Eighteen candidate transcription factors were highly correlated with the expression of CsLOX09. DNA binding with One Finger 1.8 (CsDof1.8) was confirmed to bind directly to the A/TAAAG motif of the CsLOX09 promoter through dual-luciferase, yeast one-hybrid, chromatin immunoprecipitation-qPCR and electrophoretic mobility shift assays. Furthermore, C9 aroma content and CsLOX09 expression were significantly increased in the CsDof1.8 overexpression lines. Overall, these data elucidate the metabolic regulation of C9 aromas in cucumber and provide a foundation for facilitating the regulation of flavor in cucumber breeding.

2.
Plant Cell ; 34(4): 1250-1272, 2022 03 29.
Article in English | MEDLINE | ID: mdl-35099538

ABSTRACT

Ethylene response factors (ERFs) are downstream components of ethylene-signaling pathways known to play critical roles in ethylene-controlled climacteric fruit ripening, yet little is known about the molecular mechanism underlying their mode of action. Here, we demonstrate that SlERF.F12, a member of the ERF.F subfamily containing Ethylene-responsive element-binding factor-associated Amphiphilic Repression (EAR) motifs, negatively regulates the onset of tomato (Solanum lycopersicum) fruit ripening by recruiting the co-repressor TOPLESS 2 (TPL2) and the histone deacetylases (HDAs) HDA1/HDA3 to repress the transcription of ripening-related genes. The SlERF.F12-mediated transcriptional repression of key ripening-related genes 1-AMINO-CYCLOPROPANE-1-CARBOXYLATE SYNTHASE 2 (ACS2), ACS4, POLYGALACTURONASE 2a, and PECTATE LYASE is dependent on the presence of its C-terminal EAR motif. We show that SlERF.F12 interacts with the co-repressor TPL2 via the C-terminal EAR motif and recruits HDAs SlHDA1 and SlHDA3 to form a tripartite complex in vivo that actively represses transcription of ripening genes by decreasing the level of the permissive histone acetylation marks H3K9Ac and H3K27Ac at their promoter regions. These findings provide new insights into the ripening regulatory network and uncover a direct link between repressor ERFs and histone modifiers in modulating the transition to ripening of climacteric fruit.


Subject(s)
Solanum lycopersicum , Co-Repressor Proteins/genetics , Co-Repressor Proteins/metabolism , Ethylenes/metabolism , Fruit/metabolism , Gene Expression Regulation, Plant/genetics , Histone Deacetylases/genetics , Histone Deacetylases/metabolism , Solanum lycopersicum/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism
3.
Plant J ; 115(6): 1746-1757, 2023 09.
Article in English | MEDLINE | ID: mdl-37326247

ABSTRACT

3-Dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) is a key rate-limiting enzyme that catalyzes the synthesis of the shikimate, which is an important metabolic intermediate in plants and animals. However, the function of SlDQD/SDH family genes in tomato (Solanum lycopersicum) fruit metabolites is still unknown. In the present study, we identified a ripening-associated SlDQD/SDH member, SlDQD/SDH2, that plays a key role in shikimate and flavonoid metabolism. Overexpression of this gene resulted in an increased content of shikimate and flavonoids, while knockout of this gene by CRISPR/Cas9 mediated gene editing led to a significantly lower content of shikimate and flavonoids by downregulation of flavonoid biosynthesis-related genes. Moreover, we showed that SlDQD/SDH2 confers resistance against Botrytis cinerea attack in post-harvest tomato fruit. Dual-luciferase reporter and EMSA assays indicated that SlDQD/SDH2 is a direct target of the key ripening regulator SlTAGL1. In general, this study provided a new insight into the biosynthesis of flavonoid and B. cinerea resistance in fruit tomatoes.


Subject(s)
Solanum lycopersicum , Solanum lycopersicum/genetics , Fruit/genetics , Fruit/metabolism , Botrytis/metabolism , Flavonoids/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant
4.
Small ; : e2310851, 2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38334256

ABSTRACT

Inspired by the timely emergence of silkworm pupae from their cocoons, silkworm chrysalis-like probiotic composites (SCPCs) are developed for the comprehensive therapy of inflammatory bowel disease (IBD), in which probiotics are enveloped as the "pupa" in a sequential layering of silk sericin (SS), tannic acid (TA), and polydopamine, akin to the protective "cocoon". Compared to unwrapped probiotics, these composites not only demonstrate exceptional resistance to the harsh gastrointestinal environment and exhibit over 200 times greater intestinal colonization but also safeguard probiotics from the damage of IBD environment while enabling probiotics sustained release. The probiotics, in synergy with SS and TA, provide a multi-crossed comprehensive therapy for IBD that simultaneously addresses various pathological features of IBD, including intestinal barrier disruption, elevated pro-inflammatory cytokines, heightened oxidative stress, and disturbances in the intestinal microbiota. SCPCs exhibit remarkable outcomes, including a 9.7-fold reduction in intestinal permeability, an 8.9-fold decrease in IL-6 levels, and a 2.9-fold reduction in TNF-α levels compared to uncoated probiotics. Furthermore, SCPCs demonstrate an impressive 92.25% reactive oxygen species clearance rate, significantly enhance the richness of beneficial intestinal probiotics, and effectively diminish the abundance of pathogenic bacteria, indicating a substantial improvement in the overall therapeutic effect of IBD.

5.
Sensors (Basel) ; 24(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38610342

ABSTRACT

In the field of intelligent connected vehicles, the precise and real-time identification of speed bumps is critically important for the safety of autonomous driving. To address the issue that existing visual perception algorithms struggle to simultaneously maintain identification accuracy and real-time performance amidst image distortion and complex environmental conditions, this study proposes an enhanced lightweight neural network framework, YOLOv5-FPNet. This framework strengthens perception capabilities in two key phases: feature extraction and loss constraint. Firstly, FPNet, based on FasterNet and Dynamic Snake Convolution, is developed to adaptively extract structural features of distorted speed bumps with accuracy. Subsequently, the C3-SFC module is proposed to augment the adaptability of the neck and head components to distorted features. Furthermore, the SimAM attention mechanism is embedded within the backbone to enhance the ability of key feature extraction. Finally, an adaptive loss function, Inner-WiseIoU, based on a dynamic non-monotonic focusing mechanism, is designed to improve the generalization and fitting ability of bounding boxes. Experimental evaluations on a custom speed bumps dataset demonstrate the superior performance of FPNet, with significant improvements in key metrics such as the mAP, mAP50_95, and FPS by 38.76%, 143.15%, and 51.23%, respectively, compared to conventional lightweight neural networks. Ablation studies confirm the effectiveness of the proposed improvements. This research provides a fast and accurate speed bump detection solution for autonomous vehicles, offering theoretical insights for obstacle recognition in intelligent vehicle systems.

6.
J Integr Plant Biol ; 66(6): 1227-1241, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38546046

ABSTRACT

Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body. Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding. In this study, we determined that SlAP2c, an APETALA2 (AP2) family member, acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato (Solanum lycopersicum). Knockout of SlAP2c in both the "MicroTom" and "Ailsa Craig" backgrounds resulted in greater lycopene accumulation, whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type. We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters. Moreover, SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS (TPL)2/4 and forms a complex with histone deacetylase (had)1/3, thereby reducing the histone acetylation levels of lycopene biosynthesis genes. Furthermore, SlAP2a, a homolog of SlAP2c, acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening. Therefore, we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato, laying the foundation for the manipulation of carotenoid metabolism in plants.


Subject(s)
Carotenoids , Gene Expression Regulation, Plant , Plant Proteins , Solanum lycopersicum , Solanum lycopersicum/genetics , Solanum lycopersicum/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Carotenoids/metabolism , Lycopene/metabolism , Promoter Regions, Genetic/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Fruit/metabolism , Fruit/genetics , Transcription, Genetic
7.
J Urban Health ; 100(4): 860-869, 2023 08.
Article in English | MEDLINE | ID: mdl-37550501

ABSTRACT

Little is known about the combined impact of the COVID-19 pandemic and other major disasters on mental health. Hurricane Harvey hit the Gulf Coast in 2017, resulting in substantial costs, significant levels of displacement, and approximately 100 deaths, and was followed in 2020 by the COVID-19 pandemic. We randomly sampled 1167 Houstonians from 88 designated super-neighborhoods and surveyed them about their demographics, event-specific traumas and stressors, and symptoms of current depression and post-traumatic stress disorder (PTSD). We estimated the prevalence of depression (5.8%) and PTSD (12.6%) more than three years after Hurricane Harvey, and assessed the relative influence of event-specific stressors and traumas on current mental health. Overall, we observed evidence for two key findings that are salient for residents of urban environments in the context of multiple disasters. First, stressors were primary influences on depression, whereas both stressors and traumas influenced PTSD. Second, the influences of stressors and traumas on depression and PTSD symptoms faded with time.


Subject(s)
COVID-19 , Cyclonic Storms , Disasters , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/psychology , Depression/epidemiology , Depression/psychology , Pandemics , COVID-19/epidemiology
8.
Sensors (Basel) ; 23(9)2023 Apr 22.
Article in English | MEDLINE | ID: mdl-37177392

ABSTRACT

Lightning localization is of great significance to weather forecasting, forest fire prevention, aviation, military, and other aspects. Traditional lightning localization requires the deployment of base stations and expensive measurement equipment. With the development of IoT technology and the continuous expansion of application scenarios, IoT devices can be interconnected through sensors and other technical means to ultimately achieve the goal of automatic intelligent computing. Therefore, this paper proposes a low-cost distributed thunder-localization system based on IoT smart devices, namely ThunderLoc. The main idea of ThunderLoc is to collect dual-microphone data from IoT smart devices, such as smartphones or smart speakers, through crowdsourcing, turning the localization problem into a search problem in Hamming space. We studied the dual microphones integrated with smartphones and used the sign of Time Difference Of Arrival (TDOA) as measurement information. Through a simple generalized cross-correlation method, the TDOA of thunderclaps on the same smartphone can be estimated. After quantifying the TDOA measurement from the smartphone node, thunder localization was performed by minimizing the Hamming distance between the binary sequence and the binary vector measured in a database. The ThunderLoc system was evaluated through extensive simulations and experiments (a testbed with 30 smartphone nodes). The extensive experimental results demonstrate that ThunderLoc outperforms the main existing schemes in terms of effectively locating position and good robustness.

9.
Sensors (Basel) ; 23(10)2023 May 12.
Article in English | MEDLINE | ID: mdl-37430632

ABSTRACT

In this study, an intelligent vehicle (IV) path tracking control method based on curvature optimisation is proposed to reduce the comprehensive performance conflict of the system. This system conflict is caused by the mutual restriction between the path tracking accuracy and the body stability during the movement of the intelligent automobile. First, the working principle of the new IV path tracking control algorithm is briefly introduced. Then, a three-degrees-of-freedom vehicle dynamics model and a preview error model considering vehicle roll are established. In addition, a path tracking control method based on curvature optimisation is designed to solve the deterioration of vehicle stability even when the path tracking accuracy of the IV is improved. Finally, the effectiveness of the IV path tracking control system is validated through simulations and the Hardware in the Loop (HIL) test with various conditions forms. Results clearly show that the optimisation amplitude of the IV lateral deviation is up to 84.10%, and the stability is improved by approximately 2% under the vx = 10 m/s and ρ = 0.15 m-1 condition; the optimisation amplitude of the lateral deviation is up to 66.80%, and the stability is improved by approximately 4% under the vx = 10 m/s and ρ = 0.2 m-1 condition; the body stability is improved by 20-30% under the vx = 15 m/s and ρ = 0.15 m-1 condition, and the boundary conditions of body stability are triggered. The curvature optimisation controller can effectively improve the tracking accuracy of the fuzzy sliding mode controller. The body stability constraint can also ensure the smooth running of the vehicle in the optimisation process.

10.
Am Heart J ; 251: 54-60, 2022 09.
Article in English | MEDLINE | ID: mdl-35525262

ABSTRACT

BACKGROUND: For ST-segment elevation myocardial infarction (STEMI) patients presenting 24 to 48 hours from symptom onset, whether early invasive strategy should be performed still remains controversial. METHODS: This is a prospective, open-label, multicenter, investigator initiated, randomized controlled trial (NCT04962178) to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset. A total of 366 patients will be included from 10 hospitals in mainland China. They will be randomly (1:1) divided into 2 groups: the early invasive strategy group (primary percutaneous coronary intervention, PPCI) and conservative strategy group (optimal medical therapy with primary PCI not performed). All patients will be followed for 1 month. The primary end point is myocardial infarction size on cardiac magnetic resonance (CMR). The secondary end points are as follows: (1) major adverse cardiovascular events (MACE), which is defined as a composite of cardiac death, recurrent myocardial infarction, ischemic driven target vessel revascularization and stroke; (2) other CMR end points, including microvascular obstruction, intramyocardial hemorrhage, myocardial area at risk, left ventricular ejection fraction, left ventricular end diastolic volume and left ventricular end systolic volume. DISCUSSION: This study is designed to evaluate the efficacy of early invasive strategy for STEMI patients within 24 to 48 hours of symptom onset and will add more evidence for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04962178. Registered on July 14, 2021.


Subject(s)
Anterior Wall Myocardial Infarction , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Arrhythmias, Cardiac/etiology , Humans , Multicenter Studies as Topic , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Myocardial Infarction/therapy , Percutaneous Coronary Intervention/adverse effects , Prospective Studies , Randomized Controlled Trials as Topic , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/surgery , Stroke Volume , Treatment Outcome , Ventricular Function, Left
11.
New Phytol ; 233(1): 373-389, 2022 01.
Article in English | MEDLINE | ID: mdl-34255862

ABSTRACT

Soluble sugars, organic acids and volatiles are important components that determine unique fruit flavor and consumer preferences. However, the metabolic dynamics and underlying regulatory networks that modulate overall flavor formation during fruit development and ripening remain largely unknown for most fruit species. In this study, by integrating flavor-associated metabolism and transcriptome data from 12 fruit developmental and ripening stages of Actinidia chinensis cv Hongyang, we generated a global map of changes in the flavor-related metabolites throughout development and ripening of kiwifruit. Using this dataset, we constructed complex regulatory networks allowing to identify key structural genes and transcription factors that regulate the metabolism of soluble sugars, organic acids and important volatiles in kiwifruit. Moreover, our study revealed the regulatory mechanism involving key transcription factors regulating flavor metabolism. The modulation of flavor metabolism by the identified key transcription factors was confirmed in different kiwifruit species providing the proof of concept that our dataset provides a suitable tool for clarification of the regulatory factors controlling flavor biosynthetic pathways that have not been previously illuminated. Overall, in addition to providing new insight into the metabolic regulation of flavor during fruit development and ripening, the outcome of our study establishes a foundation for flavor improvement in kiwifruit.


Subject(s)
Actinidia , Actinidia/genetics , Actinidia/metabolism , Fruit/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Metabolome , Plant Proteins/metabolism , Transcriptome/genetics
12.
Curr Microbiol ; 79(4): 124, 2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35258703

ABSTRACT

A novel Gram-negative, motile, aerobic, spiral-shaped bacterium designated D5T, was isolated from a coastal sediment collected in the Yellow Sea. Optimal growth occurred at 30 °C, pH 7.0-8.0 and in the presence of 1-3% (w/v) NaCl. Strain D5T contained ubiquinone 8 (Q-8) as the predominant respiratory quinone. The major fatty acids (> 10%) were C16:0, C16:1 ω7c/C16:1 ω6c and C18:1w7c/C18:1w6c. The main polar lipids were phosphatidylglycerol and phosphatidylethanolamine. The draft genome is 5.6 Mb in length, and DNA G + C content is 47.2 mol%. 16S rRNA gene sequences showed that strain D5T is most closely related to Oceanospirillum beijerinckii NBRC 15445T (97.8%, sequence similarity). However, the digital DNA-DNA hybridization (dDDH) value and average nucleotide identity (ANI) between strain D5T and O. beijerinckii is only 27.8% and 77.1%. Phylogenetic trees based on 16S rRNA gene sequences and whole genomes all indicated that strain D5T formed a separate branch in the genus Oceanospirillum. Combined results of the polyphasic analyses suggested that strain D5T represents a novel species in the genus Oceanospirillum, for which the name Oceanospirillum sediminis sp. nov. is proposed. The type strain is D5T (= MCCC 1K06061T = KCTC 62987T).


Subject(s)
Geologic Sediments , Oceanospirillaceae , Phylogeny , Seawater , Bacterial Typing Techniques , DNA, Bacterial/genetics , Fatty Acids/chemistry , Geologic Sediments/microbiology , Oceanospirillaceae/classification , Oceanospirillaceae/isolation & purification , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Seawater/microbiology , Sequence Analysis, DNA , Ubiquinone/chemistry
13.
Article in English | MEDLINE | ID: mdl-32929885

ABSTRACT

Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A, that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.


Subject(s)
Autism Spectrum Disorder/genetics , Brain Diseases/genetics , Developmental Disabilities/genetics , Epilepsy/genetics , Intellectual Disability/genetics , Munc18 Proteins/genetics , NAV1.2 Voltage-Gated Sodium Channel/genetics , Autism Spectrum Disorder/pathology , Brain Diseases/pathology , Case-Control Studies , Developmental Disabilities/pathology , Epilepsy/pathology , Humans , Intellectual Disability/pathology , Neurodevelopmental Disorders/classification , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/pathology
14.
J Neuroinflammation ; 17(1): 305, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-33059746

ABSTRACT

BACKGROUND: Neuroinflammation is a principal element in Alzheimer's disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. METHODS: APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aß), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. RESULTS: In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aß and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. CONCLUSIONS: FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.


Subject(s)
Alzheimer Disease/prevention & control , Anti-Inflammatory Agents/therapeutic use , Caffeic Acids/therapeutic use , Glucosides/therapeutic use , Inflammation Mediators/antagonists & inhibitors , Memory Disorders/prevention & control , NF-kappa B/antagonists & inhibitors , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Animals , Anti-Inflammatory Agents/pharmacology , Brain/drug effects , Brain/metabolism , Caffeic Acids/pharmacology , Cell Line , Dose-Response Relationship, Drug , Glucosides/pharmacology , Inflammation Mediators/metabolism , Male , Memory Disorders/genetics , Memory Disorders/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microglia/drug effects , Microglia/metabolism , NF-kappa B/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Signal Transduction/drug effects , Signal Transduction/physiology
15.
J Neuroinflammation ; 17(1): 309, 2020 Oct 18.
Article in English | MEDLINE | ID: mdl-33070776

ABSTRACT

BACKGROUND: Endoplasmic reticulum (ER) stress is involved in the progression of Alzheimer's disease (AD). Verbascoside (VB), an active phenylethanoid glycoside that was first isolated from Verbascum sinuatum (the wavyleaf mullein), possesses anti-inflammatory, antioxidative, and anti-apoptotic effects. The purpose of this study was to elucidate the beneficial effects of VB in amyloid ß (Aß)1-42-damaged human glioma (U251) cells and in APPswe/PSEN1dE9 transgenic (APP/PS1) mice. METHODS: U251 cells were co-incubated with 10 µM of Aß1-42 and treated with VB. The protective effects of VB were investigated by using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay, flow cytometry, fluorescence staining, and transmission electron microscopy. APP/PS1 transgenic mice were treated for 6 weeks with VB. Learning and memory were evaluated using a Morris water maze test. Immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, thioflavin-S staining, and proteomics analysis were performed to study the potential neuroprotective mechanism. Enzyme-linked immunosorbent assays and western blot were performed to analyze altered protein levels of brain lysates in APP/PS1 mice and/or Aß1-42-damaged U251 cells. RESULTS: In Aß1-42-damaged U251 cells, VB significantly improved cell viability, inhibited apoptosis, reduced calcium accumulation and the intracellular concentrations of reactive oxygen species, and improved the morphology of mitochondria and ER. In APP/PS1 mice, 6-week administration of VB significantly improved memory and cognition. VB inhibited apoptosis, reduced the deposition of Aß, reduced the formation of neurofibrillary tangles formed by hyperphosphorylated tau protein, and downregulated the expression levels of 4-hydroxynonenal and mesencephalic astrocyte-derived neurotrophic factor in the brains of APP/PS1 mice. Proteomics analysis of mouse hippocampus suggested that the neuroprotective effect of VB may be related to the reduction of ER stress. This was indicated by the fact that VB inhibited the three branches of the unfolded protein response, thereby attenuating ER stress and preventing apoptosis. CONCLUSIONS: The results confirmed that VB possesses significant neuroprotective effects, which are related to the reduction of ER stress. These findings support the status of VB as a potentially effective treatment for AD and warrant further research.


Subject(s)
Alzheimer Disease/prevention & control , Amyloid beta-Peptides/toxicity , Endoplasmic Reticulum Stress/drug effects , Glucosides/therapeutic use , Neuroprotective Agents/therapeutic use , Peptide Fragments/toxicity , Phenols/therapeutic use , Alzheimer Disease/chemically induced , Alzheimer Disease/genetics , Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/genetics , Animals , Cell Line , Cell Survival/drug effects , Cell Survival/physiology , Dose-Response Relationship, Drug , Endoplasmic Reticulum Stress/physiology , Glucosides/pharmacology , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Male , Mice , Mice, Transgenic , Neuroprotective Agents/pharmacology , Phenols/pharmacology , Presenilin-1/genetics
16.
Genet Med ; 22(1): 170-180, 2020 01.
Article in English | MEDLINE | ID: mdl-31332282

ABSTRACT

PURPOSE: Elucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis. METHODS: A comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients. RESULTS: We observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1. CONCLUSIONS: Our findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.


Subject(s)
Autism Spectrum Disorder/genetics , Multifactorial Inheritance , Mutation, Missense , Sequence Analysis, DNA/methods , Autism Spectrum Disorder/psychology , Case-Control Studies , Female , Gene Regulatory Networks , Genetic Predisposition to Disease , Humans , Intelligence Tests , Loss of Function Mutation , Male , Models, Genetic
17.
Mol Biol Rep ; 47(6): 4477-4483, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32415505

ABSTRACT

The improper usage of antibiotics is known to cause widespread antibiotic resistance. In this study, the antibacterial effects of a polypeptide-enriched extract from the skin of the amphibian Rana chensinensis (RCP) were evaluated against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus and the fungus Candida albicans. The mechanisms underlying these effects were also studied, and the minimum inhibitory concentration of RCP was determined for each species. Analyses of the levels of adenosine triphosphates (ATPases), including Na+/K+-ATPase and Ca2+-ATPase, and scanning electron microscopy confirmed that RCP damaged the microbial cell walls and membranes. RCP perturbed microbial metabolism and particularly affected the tricarboxylic acid cycle (TCA), suggesting that this agent downregulated the levels of succinate dehydrogenase, malate dehydrogenase and ATPase activity in cells. Furthermore, RCP caused the leakage of genetic material from all four microbial strains. In conclusion, RCP effectively inhibited the growth of Gram-negative and Gram-positive bacteria and a fungal species by disrupting energy metabolic processes.


Subject(s)
Ranidae/metabolism , Skin/metabolism , Tissue Extracts/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Candida albicans/drug effects , Drug Resistance, Microbial/drug effects , Escherichia coli/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Peptides/pharmacology , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects
18.
J Phycol ; 56(6): 1676-1686, 2020 12.
Article in English | MEDLINE | ID: mdl-33448389

ABSTRACT

Wild Microcystis have highly diverse colonial structures and sizes, including variable colony geometry, cell arrangement, and diameter. These structural and dimensional variations may play an important role in continual, frequent Microcystis blooms during summer and autumn, the cause of which still remains unclear. Here, laboratory cultures and field investigations were applied to assess mechanisms that drive variation in structure and size, as well as factors that influence diversity. The results demonstrated that colonies grew to large sizes at the expense of their structure being loose and inhomogeneous. Furthermore, colonies may spontaneously change structure to relieve the constraints of size in return. Influencing factors (nutrient limits and turbulent shear) tended to promote these variations. Our work highlights that the diversity of Microcystis colonies may be a result of structural variations as survival strategies for gaining a higher upper size limit. Therefore, during seasonal successions, large colonies commonly have porous or loosely arranged structures, such as in M. aeruginosa. Additionally, this study hypothesized three possible transition routes for better understanding structural diversity and variations in Microcystis.


Subject(s)
Microcystis , Laboratories , Seasons
19.
Sheng Li Xue Bao ; 72(2): 255-261, 2020 Apr 25.
Article in Zh | MEDLINE | ID: mdl-32328620

ABSTRACT

Preclinical studies suggest that the GABAB receptor is a potential target for treatment of substance use disorders. Baclofen (BLF), a prototypical GABAB receptor agonist, is the only specific GABAB receptor agonist available for application in clinical addiction treatment. The nucleus accumbens shell (AcbSh) is a key node in the circuit that controls reward-directed behavior. However, the relationship between GABAB receptors in the AcbSh and memory reconsolidation was unclear. The aim of this study was to investigate the effect of intra-AcbSh injection of BLF on the reconsolidation of morphine reward memory. Male C57BL/6J mice were used to establish morphine conditioned place preference (CPP) model and carry out morphine reward memory retrieval and activation experiment. The effects of intra-AcbSh injection of BLF on morphine-induced CPP, reinstatement of CPP and locomotor activity were observed after environmental cues activating morphine reward memory. The results showed that intra-AcbSh injection of BLF (0.06 nmol/0.2 µL/side or 0.12 nmol/0.2 µL/side), rather than vehicle or BLF (0.01 nmol/0.2 µL/side), following morphine reward memory retrieval abolished morphine-induced CPP by disrupting its reconsolidation in mice. Moreover, this effect persisted for more than 14 days, which was not reversed by a morphine priming injection. Furthermore, intra-AcbSh injection of BLF without morphine reward memory retrieval had no effect on morphine-associated reward memory. Interestingly, administration of BLF into the AcbSh had no effect on the locomotor activity of mice during testing phase. Based on these results, we concluded that intra-AcbSh injection of BLF following morphine reward memory could erase morphine-induced CPP by disrupting its reconsolidation. Activating GABAB receptor in AcbSh during drug memory reconsolidation may be a potential approach to prevent drug relapse.


Subject(s)
Baclofen/administration & dosage , Conditioning, Classical , Morphine , Nucleus Accumbens/drug effects , Opioid-Related Disorders , Animals , GABA-B Receptor Agonists/administration & dosage , Locomotion , Male , Memory , Mice , Mice, Inbred C57BL , Reward
20.
Plant Cell Physiol ; 60(8): 1761-1777, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31099397

ABSTRACT

Brassinosteroid (BR) plays an important role in plant development and biotic and abiotic stress tolerance, but its specific function remains largely unknown in wheat (Triticum aestivum L.), preventing its utilization in this important crop. In this study, the function of BR and its underlying cytological role in wheat root development were comprehensively investigated. Our findings demonstrated that BR has a conserved function in regulating root length in wheat, and novel roles in regulating lateral root emergence and root diameter were uncovered. Analyses of BR homologous gene composition and evolutionary divergence demonstrated that the genetic framework of the wheat BR pathway was close to that of rice, but contained highly redundant homologous copies of genes from the subgenome A, B and D. These homologous copies showed active expression and shared a conserved BR response. The expression of wheat DWF4 and glycogen synthase kinase (GSK) genes in Arabidopsis confirmed that multiple homologous copies maintained their conserved function in regulating root development, highlighting their redundant status and indicating that a special challenge exists in wheat gene modification to deal with this high redundancy. However, our results suggested that the hypermorphic effect of T. aestivum GSK (TaGSK) genes with point mutations may be an effective approach to overcome this redundancy in the manipulation of BR signaling in wheat. Our study provides fundamental data uncovering the function of BR in wheat root development, the underlying genetic basis and a possible strategy to manipulate BR signaling in hexaploid wheat.


Subject(s)
Brassinosteroids/metabolism , Plant Proteins/metabolism , Plant Roots/metabolism , Triticum/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , Glycogen Synthase Kinases/genetics , Glycogen Synthase Kinases/metabolism , Plant Proteins/genetics , Plant Roots/genetics
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