RESUMO
Odorant-binding proteins (OBPs) play key roles in host plant location by insects, and can accordingly serve as important targets for the development of attractants. In this study, we detected the high expression of SlitOBP34 in male antennae of Spodoptera litura. Subsequently, the fluorescence competitive binding experiments displayed that the SlitOBP34 protein has binding affinity for different ligands. Then, protein-ligand interaction analyses found the presence of six amino acid residues may serve as key recognition sites. Further electroantennographic and biobehavioral assessments revealed that the electrophysiological responses of male antennae were evoked in response to stimulation with the six identified host volatiles, and that these volatiles attracted male moths to varying extents. Notably, low concentrations of benzaldehyde, 1-hexanol, and cis-3-hexenyl acetate were found to have significant attractant effects on male moths, thereby identifying these three host volatiles as potential candidates for the development of male attractants. These findings advance our current understanding of the olfactory-encoded mechanisms of host plants selection in S. litura and have enabled us to develop novel adult attractants for controlling the pest in the future.
Assuntos
Antenas de Artrópodes , Proteínas de Insetos , Receptores Odorantes , Spodoptera , Compostos Orgânicos Voláteis , Animais , Spodoptera/efeitos dos fármacos , Masculino , Receptores Odorantes/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/farmacologia , Antenas de Artrópodes/metabolismo , Hexanóis/farmacologia , Hexanóis/metabolismo , Acetatos/metabolismo , Acetatos/farmacologia , BenzaldeídosRESUMO
Riptortus pedestris (bean bug), a common soybean pest, has a highly developed olfactory system to find hosts for feeding and oviposition. Chemosensory proteins (CSPs) have been identified in many insect species; however, their functions in R. pedestris remain unknown. In this study, quantitative real time-polymerase chain reaction (qRT-PCR) revealed that the expression of RpedCSP12 in the adult antennae of R. pedestris increased with age. Moreover, a significant difference in the expression levels of RpedCSP12 was observed between male and female antennae at one and three days of age. We also investigated the binding ability of RpedCSP12 to different ligands using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP12 only bound to one aggregation pheromone, (E)-2-hexenyl (Z)-3-hexenoate, and its binding decreased with increasing pH. Furthermore, homology modelling, molecular docking, and site-directed mutagenesis revealed that the Y27A, L74A, and L85A mutants lost their binding ability to (E)-2-hexenyl (Z)-3-hexenoate. Our findings highlight the olfactory roles of RpedCSP12, providing insights into the mechanism by which RpedCSPs bind to aggregation pheromones. Therefore, our study can be used as a theoretical basis for the population control of R. pedestris in the future.
Assuntos
Heterópteros , Feromônios , Animais , Feminino , Simulação de Acoplamento Molecular , Heterópteros/genética , Glycine maxRESUMO
Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3'-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.
Assuntos
Variações do Número de Cópias de DNA , Adolescente , Variações do Número de Cópias de DNA/genética , Humanos , Masculino , Mutação/genética , Fenótipo , Sequenciamento do ExomaRESUMO
Based on previous research, a new coassembly formed by a porphyrin derivative (IPETPP), which contains a flexible substituent of m-phthalic acid, is observed with coronene (COR) molecules at a higher concentration. Besides, a fresh IPETPP self-assembly formed at a lower concentration and another new coassembly with COR molecules are obtained. Moreover, the addition of a series of bipyridines alters the diamond arrangement of IPETPP, which enhances the stability of the two-component structures. It is unprecedented that bipyridine derivatives break intermolecular hydrogen bonds containing m-phthalic acid substituents. All the coassemblies are investigated by scanning tunneling microscopy on a highly oriented pyrolytic graphite. Combined with density functional theory, the formation mechanism of the assembled structures is revealed. These results would contribute to understanding the interfacial crystal behaviors and probably provide an efficient pathway to regulate the binary structures.
RESUMO
A three-component supramolecular co-assembly structure formed at the liquid-solid interface by employing a shape-persistent π-conjugated macrocycle (16mer) and two guest molecules (COR and C60) is demonstrated. Scanning tunneling microscopy (STM) observations revealed that 16mer can serve as a versatile host molecule that can co-assemble with both COR and C60 guest molecules to form stable two-component structures, where the COR guest molecule filled in the gap between the side chains of adjacent 16mer molecules, and the C60 guest molecule entered the inner cavity of 16mer. It was found that the adding sequence of COR and C60 guest molecules is crucial to the resulting co-adsorption structure in the three-component system. To obtain the intriguing 16mer-COR-C60 three-component co-assembly structure, the 16mer and COR two-component co-assembly structure should first be constructed on a HOPG surface, followed by addition of C60. Based on the analysis of the STM results and the density functional theory (DFT) calculations, the formation mechanism of the assembled structures was revealed.
RESUMO
The extraction, purification, structure and hepatoprotective activity of a homogenous polysaccharide (SPS60) from Sabia parviflora were investigated. SPS60 was screened after purification with Sephadex G-100 and showed the excellent hepatoprotective activity. Its structural characteristics were investigated by Time of flight mass spectrometry (TOF-MS), PMP Pre-column derivatization-HPLC (PMP-HPLC), nuclear magnetic resonance (NMR) spectroscopy and Atomic Force Microscopy (AFM). The results showed that SPS60 possessed the molecular weight of 16900 Da and the monosaccharide component was glucose, as well as a 1 â 6 glycosidic bond. The results of atomic force microscopy (AFM) show that SPS60 is a blocky sphere in solution. Furthermore, the SPS60 could significantly improve the survival rate of LO2 hepatocytes which were damaged by CCl4. Therefore, SPS60 may be an active substance of S. parviflora as a local functional tea.
Assuntos
Magnoliopsida/metabolismo , Polissacarídeos/química , Substâncias Protetoras/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologiaRESUMO
Macrocyclic self-assemblies have gained great interest for diversified structures and potential applications, such as catalysis, magnetism, photovoltaic devices, organic light-emitting diodes. Macrocycles can present regular assembly systems at the liquid/solid interface due to theπ-conjugated structures. Furthermore, suitable guest molecules can be selected for constructing multi-component supramolecular co-assemblies. This review mainly summarizes macrocyclic self-assembly structures with different shapes in recent years. All of the studies are completed with the assistance of scanning tunneling microscope at the liquid/solid interface.
RESUMO
BACKGROUND: 16p13.11 microduplication syndrome has a variable presentation and is characterized primarily by neurodevelopmental and physical phenotypes resulting from copy number variation at chromosome 16p13.11. Given its variability, there may be features that have not yet been reported. The goal of this study was to use a patient "self-phenotyping" survey to collect data directly from patients to further characterize the phenotypes of 16p13.11 microduplication syndrome. OBJECTIVE: This study aimed to (1) discover self-identified phenotypes in 16p13.11 microduplication syndrome that have been underrepresented in the scientific literature and (2) demonstrate that self-phenotyping tools are valuable sources of data for the medical and scientific communities. METHODS: As part of a large study to compare and evaluate patient self-phenotyping surveys, an online survey tool, Phenotypr, was developed for patients with rare disorders to self-report phenotypes. Participants with 16p13.11 microduplication syndrome were recruited through the Boston Children's Hospital 16p13.11 Registry. Either the caregiver, parent, or legal guardian of an affected child or the affected person (if aged 18 years or above) completed the survey. Results were securely transferred to a Research Electronic Data Capture database and aggregated for analysis. RESULTS: A total of 19 participants enrolled in the study. Notably, among the 19 participants, aggression and anxiety were mentioned by 3 (16%) and 4 (21%) participants, respectively, which is an increase over the numbers in previously published literature. Additionally, among the 19 participants, 3 (16%) had asthma and 2 (11%) had other immunological disorders, both of which have not been previously described in the syndrome. CONCLUSIONS: Several phenotypes might be underrepresented in the previous 16p13.11 microduplication literature, and new possible phenotypes have been identified. Whenever possible, patients should continue to be referenced as a source of complete phenotyping data on their condition. Self-phenotyping may lead to a better understanding of the prevalence of phenotypes in genetic disorders and may identify previously unreported phenotypes.
Assuntos
Variações do Número de Cópias de DNA , Família , Variação Biológica da População , Estudos de Coortes , Humanos , FenótipoRESUMO
Scanning tunneling microscopy (STM) was utilized to disclose four novel core-modified rubyrin self-assembly behaviors on the highly-oriented pyrolytic graphite (HOPG) surface, of which N2S4-OR(1)/N2Se4-OR(2) had no phenanthrene pyrrole ring and N2S4-OR(3)/N2Se4-OR(4) had phenanthrene-fused pyrrole rings and meso-aryl substituents. It was discovered that the core-modified rubyrin could self-assemble into either face-on or edge-on monolayer structures selectively at the liquid/HOPG interface in different solvents. There was an obvious solvent-dependent self-assembly for N2S4-OR(3)/N2Se4-OR(4), which adopted an edge-on and face-on structure in 1-phenyloctane and 1-heptanoic acid solvents, respectively, whereas N2S4-OR(1)/N2Se4-OR(2) showed no obvious difference in the assembly structure, which both adopted a face-on structure in the two solvents. Density functional theory (DFT) calculations were also utilized to reveal the relevant self-assembly mechanisms. This study shows a typical solvent effect regulating core-modified rubyrin self-assembly, which is essential for porphyrin-based functional devices' design and manufacture.
RESUMO
PURPOSE: This retrospective study analyzed the results of 23G vitrectomy for the treatment of intraocular hemorrhage in patients with Terson syndrome. The pathogenesis of Terson syndrome and the timing of vitrectomy are discussed. METHODS: Eight eyes of eight patients were included in the study. Intrasurgical images were acquired, and membranes peeled off during surgery were subjected to pathological staining. Postoperative examination included visual acuity, intraocular pressure, funduscopy, and optical coherence tomography angiography. RESULTS: The course of visual impairment in the patients ranged from < 1 to 5 months; visual acuity ranged from light perception to 20/1000. Surgeries in the eight patients were all successful, and no severe complications were observed. Visual acuity improved in each operative eye. Pathological staining revealed only fibrous connective tissue, and no nerve fibers in the membranes peeled off during surgery. Optical coherence tomography angiography revealed no changes in blood vessel density in the inner layer of the retina of the operative eye compared with the non-operative eye in each patient. CONCLUSIONS: Timely surgical intervention is necessary for the treatment of intraocular hemorrhage in patients with Terson syndrome. Clinical findings support the theory that intraocular blood results from stasis or rupture of retinal superficial peripapillary vessels caused by elevated intracranial pressure.
Assuntos
Hemorragia Subaracnóidea , Vitrectomia , Humanos , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/cirurgia , Síndrome , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/etiologia , Hemorragia Vítrea/cirurgiaRESUMO
The aim of this study was to observe the protective effect of water extract from Sabia parviflora on mice with acute liver injury induced by acetaminophen, and investigate its possible mechanism. Fifty-eight Kunming mice were divided into 6 groups, 8 in the normal group, 10 in the model group, 10 in the biphenyl diester group, and 10 each in the low, medium and high dose groups. After adaptive feeding for one week, the mice in normal group were intragastrically administered with an equal volume of 0.5% sodium carboxymethylcellulose sodium(CMC-Na), and the mice in other groups were intragastrically administered with corresponding drugs at 20 mL·kg~(-1) once a day. Then acetaminophen(200 mg·kg~(-1)) was administered after the above drug administration except the normal group. The behavior and signs of the experimental animals were observed every day and the samples were taken for experiments on the next day of the final administration. The liver mass and mass index were calculated. The blood was collected from the abdominal aorta and centrifuged to obtain the serum for detecting aspartate aminotransferase(AST) activity and alanine aminotransferase(ALT) activity. The liver tissue homogenate was used to detect superoxide dismutase(SOD) activity, glutathione(glutathione, r-glutamyl cysteingl+glycine, GSH) activity and malondialdehyde(MDA) content. Liver tissue was analyzed for histological analysis. The results showed that S. parviflora could alleviate the lipid peroxidation damage in the liver caused by acetaminophen, reduce the ALT and AST activities in serum, increase the levels of SOD and GSH in liver tissue, decrease the content of MDA in liver tissue, and inhibit the apoptosis. S. parviflora could also improve the live histopathological profile, protect liver cells and restore liver function. Among them, the high dose had the most significant effect and showed dose-effect relationship. This study indicated that S. parviflora had a significant protective effect on acetaminophen-induced liver injury in mice, and its mechanism may be related to its anti-oxidation effect and inhi-bitory effect on apoptosis.
Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Fígado/enzimologia , Malondialdeído/análise , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismoRESUMO
OBJECTIVE: To study the effects of life event and coping style on left-behind middle school student mental health. METHODS: 1405 left-behind middle school students were selected by multi-stage cluster random sampling method and investigated with Middle School Student Mental Health Scale (MSSMHS), Multidimensional Life Events Rating Questionnaire for Middle School Students (MLERQ) and Trait Coping Style Questionnaire (TCSQ). RESULTS: The mental health detection rate of left-behind middle school students was 26.33%. Life event have significant influence on mental health (F = 447.624, P = 0.000). The main effect for negative coping style on mental health was significant (F = 263.669, P = 0.000). Positive coping style have effect on mental health but the main effect was not significant (F = 2.436, P = 0.119). The interaction effect of life event and negative coping style was significant (F = 23.173, P = 0.000). CONCLUSION: Life event and coping style has a certain effect on left-behind middle school student mental health, but its mechanism is complicated and still uncertain.
Assuntos
Adaptação Psicológica , Acontecimentos que Mudam a Vida , Saúde Mental , China , Humanos , Estudantes , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To explore the relationship between sub-health status and social support and coping styles of left-behind middle school students in a reservoir area of Chongqing. METHOD: 2247 students were chosen from three middle school by multistage cluster random sampling in a reservoir of Chongqing, 1528 were left-behind students,719 were non-left students, surveyed with questionnaire by Multidimensional Sub-health Questionnaire of Adolescents (MSQA), Social Support Rating Scale (SSRS) and Trait Coping Style Questionnaire (TCSQ). RESULTS: Psychosomatic, physical and psychological sub-health state detection rate of left-behind middle school students (10. 73%, 8. 24%, 12. 43%) were higher than non-left students (9. 46%, 7. 37% and 10. 29%), but the difference was not statistically significant. Social subjective support, utilization of support and active coping style were protective factors for the sub-health status, grade and negative coping style were risk factors for the sub-health state. Grades, social support and coping style have significantly main effect on sub-health (P<0. 05), social support and negative coping have significantly interaction (P <0. 05). CONCLUSION: Sub-health problem is not prominent, negative coping has an important impact on the sub-health.
Assuntos
Adaptação Psicológica , Nível de Saúde , Transtornos Mentais/epidemiologia , Apoio Social , Estudantes/psicologia , Adolescente , China/epidemiologia , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Saúde Mental , Fatores de Risco , População Rural , Instituições Acadêmicas , Estudantes/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
Purpose: Circular RNAs (circRNAs) have been verified to participate in multiple biological processes and disease progression. Yet, the role of circRNAs in the pathogenesis of diabetic retinopathy (DR) is still poorly understood and deserves further study. This study aimed to investigate the role of circRNAs in the regulation of high glucose (HG)-induced apoptosis of retinal microvascular endothelial cells (RMECs). Methods: Epiretinal membranes from patients with DR and nondiabetic patients with idiopathic macular epiretinal membrane were collected for this study. The circRNA microarrays were performed using high-throughput sequencing. Hierarchical clustering, functional enrichment, and network regulation analyses were used to analyze the data generated by high-throughput sequencing. Next, RMECs were subjected to HG (25 mM) conditions to induce RMECs apoptosis in vitro. A series of experiments, such as Transwell, the Scratch wound, and tube formation, were conducted to explore the regulatory effect of circRNA on RMECs. Fluorescence in situ hybridization (FISH), immunofluorescence staining, and Western blot were used to study the mechanism underlying circRNA-mediated regulation. Results: A total of 53 differentially expressed circRNAs were found in patients with DR. Among these, hsa_circ_0000880 was significantly upregulated in both the diabetic epiretinal membranes and in an in vitro DR model of HG-treated RMECs. Hsa_circ_0000880 knockout facilitated RMECs vitality and decreased the paracellular permeability of RMECs under hyperglycemia. More importantly, silencing of hsa_circ_0000880 significantly inhibited HG-induced ROS production and RMECs apoptosis. Hsa_circ_0000880 acted as an endogenous sponge for eukaryotic initiation factor 4A-III (EIF4A3). Knockout of hsa_circ_0000880 reversed HG-induced decrease in EIF4A3 protein level. Conclusions: Our findings suggest that hsa_circ_0000880 is a novel circRNA can induce RMECs apoptosis in response to HG conditions by sponging EIF4A3, offering an innovative treatment approach against DR. Translational Relevance: The circRNAs participate in the dysregulation of microvascular endothelial function induced by HG conditions, indicating a promising therapeutic target for DR.
Assuntos
Retinopatia Diabética , Membrana Epirretiniana , Humanos , Células Endoteliais , RNA Circular/genética , Hibridização in Situ Fluorescente , Retinopatia Diabética/genética , Apoptose/genética , Glucose/toxicidade , Fator de Iniciação 4A em Eucariotos , RNA Helicases DEAD-boxRESUMO
BACKGROUND: Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that seriously threatens human health. Rho GTPase-activating protein 4 (ARHGAP4) plays an important role in the occurrence and development of tumors. OBJECTIVE: The purpose of this study was to explore the role of ARHGAP4 in the progression of KIRC and its diagnostic and prognostic value. METHODS: Multiple analytical methods and in vitro cell assays were used to explore the expression of ARHGAP4 and its value in the progression, diagnosis and prognosis of KIRC. The biological function of ARHGAP4 was studied by GO analysis and KEGG pathway analysis, and then the relationship between ARHGAP4 and immune infiltration was analyzed. RESULTS: The expression of ARHGAP4 was significantly up-regulated in KIRC. We found that the high expression of ARHGAP4 was related to the progression of KIRC and suggested a poor prognosis. Compared with normal tissues, ARHGAP4 had a better diagnostic value in KIRC. The biological function of ARHGAP4 was related to immunity, and its expression was also closely related to tumor immune infiltration and immune checkpoints. CONCLUSIONS: Our study demonstrated that ARHGAP4 may be a biomarker, which is related to the progression, diagnosis and prognosis of KIRC. Its biological functions are related to tumor immune infiltration.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Proteínas Ativadoras de GTPase , Neoplasias Renais , Humanos , Prognóstico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/genética , Proteínas Ativadoras de GTPase/metabolismo , Proteínas Ativadoras de GTPase/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/imunologia , Neoplasias Renais/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Masculino , Feminino , Regulação para Cima , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Linhagem Celular TumoralRESUMO
PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.
Assuntos
Estenose das Carótidas , Corioide , Microvasos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Estenose das Carótidas/diagnóstico por imagem , Feminino , Masculino , Idoso , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/patologia , Pessoa de Meia-Idade , Microvasos/diagnóstico por imagem , Angiografia Digital/métodos , Estudos de Casos e Controles , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologiaRESUMO
Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.
Assuntos
Comportamento Alimentar , Proteínas de Insetos , Larva , Spodoptera , Animais , Spodoptera/metabolismo , Spodoptera/fisiologia , Spodoptera/genética , Spodoptera/crescimento & desenvolvimento , Larva/metabolismo , Larva/crescimento & desenvolvimento , Larva/fisiologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genéticaRESUMO
Splicing factor polyglutamine binding protein-1 (PQBP1) is abundantly expressed in the central nervous system during development, and mutations in the gene cause intellectual disability. However, the roles of PQBP1 in cancer progression remain largely unknown. Here, it is shown that PQBP1 overexpression promotes tumor progression and indicates worse prognosis in ovarian cancer. Integrative analysis of spyCLIP-seq and RNA-seq data reveals that PQBP1 preferentially binds to exon regions and modulates exon skipping. Mechanistically, it is shown that PQBP1 regulates the splicing of genes related to the apoptotic signaling pathway, including BAX. PQBP1 promotes BAX exon 2 skipping to generate a truncated isoform that undergoes degradation by nonsense-mediated mRNA decay, thus making cancer cells resistant to apoptosis. In contrast, PQBP1 depletion or splice-switching antisense oligonucleotides promote exon 2 inclusion and thus increase BAX expression, leading to inhibition of tumor growth. Together, the results demonstrate an oncogenic role of PQBP1 in ovarian cancer and suggest that targeting the aberrant splicing mediated by PQBP1 has therapeutic potential in cancer treatment.
Assuntos
Deficiência Intelectual , Neoplasias Ovarianas , Feminino , Humanos , Proteína X Associada a bcl-2/genética , Proteínas de Ligação a DNA/genética , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Neoplasias Ovarianas/genética , Splicing de RNA/genética , Fatores de Processamento de RNA/genéticaRESUMO
PURPOSE: To determine the proteomic profiles of exosomes derived from vitreous humour (VH) obtained from proliferative diabetic retinopathy (PDR) patients and non-diabetic controls with idiopathic macular hole/epiretinal membrane. METHODS: Vitreal exosomes were isolated using differential ultracentrifugation, followed by characterisation performed using different techniques. A label-free proteomic analysis was conducted to determine the protein profiles of the exosomes. A parallel reaction monitoring (PRM) analysis was performed to verify the identified proteins and associated functional annotations were derived by gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Receiver operating characteristic (ROC) analysis was utilised to evaluate the diagnostic value of target proteins in distinguishing PDR from controls. RESULTS: Exosomes were successfully isolated from VH, and were well characterised by various techniques. The results of proteomic analysis showed that a total of 758 proteins were identified and 10 proteins were screened as differentially expressed proteins, significantly changed in the PDR group containing 4 elevated proteins and 6 reduced proteins. GO analysis indicated that these differential proteins were mainly involved in many metabolic pathways, including nicotinamide adenine dinucleotide metabolism, adenosine diphosphate metabolic process and glycolytic process. The KEGG analysis enriched the top five pathways including glycolysis/gluconeogenesis, fructose and mannose metabolism, biosynthesis of amino acids, hypoxia-inducible factor 1 signalling pathway and carbon metabolism. The differential proteins, namely, lactate dehydrogenase A, ficolin 3, apolipoprotein B and apolipoprotein M, were further verified by PRM and showed a consistent trend with label-free proteomic analysis. The ROC analysis identified these proteins as promising biomarkers for PDR diagnosis. CONCLUSIONS: Vitreal exosomes from patients with PDR contained few proteins unique to PDR; thus, exosomal proteins have great potential as disease biomarkers and therapeutic targets for PDR.
Assuntos
Diabetes Mellitus , Retinopatia Diabética , Exossomos , Humanos , Retinopatia Diabética/metabolismo , Proteômica/métodos , Exossomos/metabolismo , Corpo Vítreo/metabolismo , Biomarcadores/metabolismoRESUMO
Scientific territorial spatial planning is of great significance in the realization of the sustainable development goals in China, especially in the context of China's ecological civilization construction and territorial spatial planning. However, limited research has been carried out to understand the spatio-temporal change in EEQ and territorial spatial planning. In this study, Changsha County and six districts of Changsha City were selected as the research objects. Based on the remote sensing ecological index (RSEI) model, the spatio-temporal changes in the EEQ and spatial planning response in the study area during 2003-2018 were analyzed. The results reveal that (1) the EEQ of Changsha declined and then rose between 2003 and 2018, showing an overall decreasing trend. The average RSEI declined from 0.532 in 2003 to 0.500 in 2014 and then increased to 0.523 in 2018, with an overall decrease of 1.7%. (2) In terms of spatial pattern changes, the Xingma Group, the Airport Group and the Huangli Group in the east of the Xiangjiang River had the most serious EEQ degradation. The EEQ degradation of Changsha showed an expanding and polycentric decentralized grouping pattern. (3) Massive construction land expansion during rapid urbanization caused significant EEQ degradation in Changsha. Particularly, the areas with low EEQ were concentrated in the areas with concentrated industrial land. Scientific territorial spatial planning and strict control were conducive to regional EEQ improvement. (4) The prediction using the urban ecological model demonstrates that every 0.549 unit increase in NDVI or 0.2 unit decrease in NDBSI can improve the RSEI of the study area by 0.1 unit, thus improving EEQ. In the future territorial spatial planning and construction of Changsha, it is necessary to promote the transformation and upgrading of low-end industries into high-end manufacturing industries and control the scale of inefficient industrial land. The EEQ degradation caused by industrial land expansion needs to be noted. All of these findings can provide valuable information for relevant decision-makers to formulate ecological environment protection strategies and conduct future territorial spatial planning.