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Introduction: The Tarlov cysts are pathological enlargements of the cerebrospinal fluid spaces between the endoneurium and perineurium, which can cause intolerable sciatic pain, motor impairment of lower limbs, and bladder/bowel dysfunction. Currently, the treatment results are unsatisfactory due to the low cure rates and extensive surgical trauma. Thus, there is an ongoing exploration of surgical techniques for Tarlov treatment. In the current study, we present a novel neuroendoscopic-assisted technique that combines the fenestration, leakage sealing, and tamponade of the Tarlov cyst. Methods: Between January 2020 and December 2021, a total of 32 Tarlov patients were enrolled and received neuroendoscopic-assisted surgery. Their pre- and post-surgical Visual Analogue Scale (VAS) scores, major complaints, and MR imaging were recorded for comparison. Results: 27 of 32 patients (84.4%) patients demonstrated immediate pain relief as their VAS scores decreased from 5.6 ± 1.5 to 2.5 ± 1.1 (p < 0.01) on the first day after surgery. At the 3-month follow-up, the patients' average VAS score continued to decrease (1.94 ± 0.8). Meanwhile, saddle paresthesia, urinary incontinence, and constipation were relieved in 6 (50%), 4 (80%), and 5 (41.7%), respectively, according to patients self-report. No surgical-related complication was observed in any of the cases. Discussion: We conclude that neuroendoscopic-assisted surgery is an effective surgical method for symptomatic Tarlov cysts with minimized complications.
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OBJECTIVE: This study compared the clinical therapeutic efficacy of syringo-subarachnoid shunt placement with direct tube and T-tube via the dorsal root entry zone (DREZ) approach for treatment of eccentric syringomyelia. METHODS: A retrospective study was performed of 41 patients with idiopathic or secondary eccentric syringomyelia from November 2011 to December 2022. Syringo-subarachnoid shunt placement with direct tube or T-tube via the DREZ approach was performed. The modified Japanese Orthopaedic Association low back pain scale was used to investigate the severity of clinical symptoms. Magnetic resonance imaging was used to investigate therapeutic efficacyï¼reduction of the cavity volume by >10% was considered an improvement and 50% was considered a significant improvement). RESULTS: Incision length of the spinal cortex in the direct tube group was shorter than in the T-tube group (3.10 ± 0.28 cm vs. 5.03 ± 0.19 cm), with a significant difference between the 2 groups (t = -52.56, P < 0.001). Modified Japanese Orthopaedic Association score 3 months postoperatively was significantly better than the preoperative score in both the direct tube groupï¼t = 40.954, P < 0.001ï¼ and the T-tube groupï¼t = 24.769, P < 0.001ï¼. Statistical comparison revealed there was no difference in imaging improvement between the direct tube group and T-tube group 3 months (χ2 = 0.20, P = 0.655) and 12 months (χ2 = 0.21, P = 0.647) postoperatively. CONCLUSIONS: Syringo-subarachnoid shunt placement with direct tube via the DREZ approach for treatment of eccentric syringomyelia is safer than with T-tube via the DREZ approach due to smaller incision length and less of a space-occupying effect with same therapeutic efficacy.
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Derivaciones del Líquido Cefalorraquídeo , Siringomielia , Humanos , Siringomielia/cirugía , Siringomielia/diagnóstico por imagen , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Derivaciones del Líquido Cefalorraquídeo/métodos , Resultado del Tratamiento , Raíces Nerviosas Espinales/cirugía , Raíces Nerviosas Espinales/diagnóstico por imagen , Espacio Subaracnoideo/cirugía , Espacio Subaracnoideo/diagnóstico por imagen , Anciano , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: In several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance remains unclear. RESULTS: We report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range in drdd mutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity. CONCLUSIONS: We propose a new model for GbM in regulating gene expression plasticity, including a novel type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state.
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Metilación de ADN , Plantas , Plantas/genética , Evolución Biológica , Expresión Génica , CromatinaRESUMEN
This paper focuses on the development trend of industrial carbon emissions in Bengbu city, Anhui Province in the next ten years, and how to help the industry reach the carbon peak as soon as possible. The research process and conclusions are as follows: (1) Through literature review and carbon emission index method, five main factors affecting industrial carbon emission are identified. (2) The resistance model is used to analyze the main resistance factors of industrial carbon emission reduction in Bengbu city. (3) Based on the existing data of Bengbu city from 2011 to 2020, the grey prediction EGM (1,1) model is used to predict the industrial carbon emissions of Bengbu city from 2021 to 2030. The results show that among the five factors, the urbanization rate has the most significant impact on industrial carbon emissions, while energy intensity has the least impact. Bengbu's industrial carbon emissions will continue to increase in the next decade, but the growth rate will be flat. Based on the findings of the analysis, specific recommendations on urbanization development, energy structure, and industrial structure of Bengbu city are put forward.
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Plants as sessile organisms are challenged by numerous biotic and abiotic stresses. Stomatal guard cells on the leaf surface are at the frontline of biotic and abiotic stress responses. Mitogen-activated protein kinase 4 (MPK4) has higher expression levels in guard cells than in mesophyll cells. The specific functions of MPK4 in guard cells are unknown. In this study, when MPK4 was overexpressed in Arabidopsis, bacterial entry of Pseudomonas syringae (Pst) into the plants was significantly decreased. The MPK4 overexpression plants had a similar trend of stomatal movement as wild-type Col-0, but had a smaller stomatal aperture than the Col-0, highlighting MPK4 plays a role in stomatal immune response. This function of the MPK4 requires its kinase activity because the MPK4 kinase-dead mutant did not have a significant difference in stomatal aperture compared to the Col-0. To understand MPK4 functions in guard cells, we investigated MPK4-associated protein complexes in guard cells using affinity purification mass spectrometry. A total of 145 proteins were identified to be in the MPK4-complex. Ten potential MPK4-interacting proteins were cloned and tested for physical interactions with the MPK4 using a yeast two hybrid (Y2H) system. Four proteins were newly identified to interact directly with the MPK4. SIGNIFICANCE: MPK4 is highly abundant in stomatal guard cells, but its specific functions in guard cells are largely unknown. Through a bacterial entry assay of MPK4 overexpression plants, we found that MPK4 may play an important role in stomatal immune response. To understand the molecular mechanisms underlying the MPK4 functions in guard cells, we characterized the MPK4-associated protein complex in guard cells. Many of the 145 identified proteins were involved in plant immunity and development. Four of the proteins were newly identified to interact directly with the MPK4. This work has provided additional evidence for the MPK4 function as a positive regulator for stomatal immunity. The guard cell MPK4 protein complex and the four new interacting proteins were revealed. Whether MPK4 directly phosphorylates these interacting proteins deserves further investigation. These newly discovered proteins have chartered exciting directions toward understanding new functions of the MPK4 kinase.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Estomas de Plantas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Arabidopsis/metabolismo , FosforilaciónRESUMEN
Historically, xenia effects were hypothesized to be unique genetic contributions of pollen to seed phenotype, but most examples represent standard complementation of Mendelian traits. We identified the imprinted dosage-effect defective1 (ded1) locus in maize (Zea mays) as a paternal regulator of seed size and development. Hypomorphic alleles show a 5-10% seed weight reduction when ded1 is transmitted through the male, while homozygous mutants are defective with a 70-90% seed weight reduction. Ded1 encodes an R2R3-MYB transcription factor expressed specifically during early endosperm development with paternal allele bias. DED1 directly activates early endosperm genes and endosperm adjacent to scutellum cell layer genes, while directly repressing late grain-fill genes. These results demonstrate xenia as originally defined: Imprinting of Ded1 causes the paternal allele to set the pace of endosperm development thereby influencing grain set and size.
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Impresión Genómica , Zea mays , Alelos , Endospermo/genética , Semillas/genética , Zea mays/genéticaRESUMEN
The phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a key role in the pathological process of atherosclerosis (AS), and TRPM7 is involved in this process. In this study, we verified whether circRNAs participate in the phenotypic transformation of VSMCs by regulating TRPM7 in AS. The RNA-sequencing data of atherosclerosis were downloaded and analysed from the GEO database. Only hsa_circ_0021155 related to TRPM7 was differentially expressed in AS. circRNA distribution and expression were observed via FISH and PCR. CCK8, scratch test and Transwell assay were used to observe the proliferation and migration of cells. Western blot was performed to examine changes in α-actin, calponin, SMMHC and TRPM7 proteins. The expression of hsa_circ_0021155 against has-miR-4459/miR-3689c was verified via PCR. The ceRNA relationship of TPRM7-miR4459-circ0021155 was verified via dual luciferase assay, and the effects of miR4459 mimic/inhibitor on the proliferation of cells were further observed. The expression of hsa_circ_0021155 and OX-LDL was increased in VSMCs. hsa_circ_0021155 promoted the expression of TRPM7 and inhibited the protein expression of α-actin, calponin and SMMHC. In addition, it promoted the proliferation and migration of cells and inhibited the expression of miR-3689c and miR-4459 but did not affect miR-4756-5p. The dual luciferase assay showed that circ0021155-miR4459-TRPM7 mRNA was highly compatible and could be mutually regulated by a ceRNA network. In conclusion, hsa_circ_0021155 regulates the proliferation, migration and phenotype transformation of VSMCs induced by OX-LDL via the miR-4459/TRPM7 axis. hsa_circ_0021155 and TRPM7 may offer novel therapeutic targets for atherosclerosis.
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Aterosclerosis , MicroARNs , Canales Catiónicos TRPM , Actinas/metabolismo , Apoptosis/genética , Aterosclerosis/genética , Aterosclerosis/patología , Movimiento Celular/genética , Proliferación Celular/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Músculo Liso Vascular/metabolismo , Fenotipo , Proteínas Serina-Treonina Quinasas , ARN Circular/genética , ARN Mensajero , Canales Catiónicos TRPM/genéticaRESUMEN
Recent breakthroughs in transcriptome analysis and gene characterization have provided valuable resources and information about the maize endosperm developmental program. The high temporal-resolution transcriptome analysis has yielded unprecedented access to information about the genetic control of seed development. Detailed spatial transcriptome analysis using laser-capture microdissection has revealed the expression patterns of specific populations of genes in the four major endosperm compartments: the basal endosperm transfer layer (BETL), aleurone layer (AL), starchy endosperm (SE), and embryo-surrounding region (ESR). Although the overall picture of the transcriptional regulatory network of endosperm development remains fragmentary, there have been some exciting advances, such as the identification of OPAQUE11 (O11) as a central hub of the maize endosperm regulatory network connecting endosperm development, nutrient metabolism, and stress responses, and the discovery that the endosperm adjacent to scutellum (EAS) serves as a dynamic interface for endosperm-embryo crosstalk. In addition, several genes that function in BETL development, AL differentiation, and the endosperm cell cycle have been identified, such as ZmSWEET4c, Thk1, and Dek15, respectively. Here, we focus on current advances in understanding the molecular factors involved in BETL, AL, SE, ESR, and EAS development, including the specific transcriptional regulatory networks that function in each compartment during endosperm development.
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Endospermo/metabolismo , Zea mays/genética , Endospermo/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiologíaRESUMEN
Maize (Zea mays) is a leading cereal crop in the world. The maize kernel is the storage organ and the harvest portion of this crop and is closely related to its yield and quality. The development of maize kernel is initiated by the double fertilization event, leading to the formation of a diploid embryo and a triploid endosperm. The embryo and endosperm are then undergone independent developmental programs, resulting in a mature maize kernel which is comprised of a persistent endosperm, a large embryo, and a maternal pericarp. Due to the well-characterized morphogenesis and powerful genetics, maize kernel has long been an excellent model for the study of cereal kernel development. In recent years, with the release of the maize reference genome and the development of new genomic technologies, there has been an explosive expansion of new knowledge for maize kernel development. In this review, we overviewed recent progress in the study of maize kernel development, with an emphasis on genetic mapping of kernel traits, transcriptome analysis during kernel development, functional gene cloning of kernel mutants, and genetic engineering of kernel traits.
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Pentatricopeptide repeat (PPR) proteins were identified as site-specific recognition factors for RNA editing in plant mitochondria and plastids. In this study, we characterized maize (Zea mays) kernel mutant defective kernel 53 (dek53), which has an embryo lethal and collapsed endosperm phenotype. Dek53 encodes an E-subgroup PPR protein, which possesses a short PLS repeat region of only seven repeats. Subcellular localization analysis indicated that DEK53 is localized in the mitochondrion. Strand- and transcript-specific RNA-seq analysis showed that the dek53 mutation affected C-to-U RNA editing at more than 60 mitochondrial C targets. Biochemical analysis of mitochondrial protein complexes revealed a significant reduction in the assembly of mitochondrial complex III in dek53. Transmission electron microscopic examination showed severe morphological defects of mitochondria in dek53 endosperm cells. In addition, yeast two-hybrid and luciferase complementation imaging assays indicated that DEK53 can interact with the mitochondrion-targeted non-PPR RNA editing factor ZmMORF1, suggesting that DEK53 might be a functional component of the organellar RNA editosome.
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Regulación de la Expresión Génica de las Plantas , Zea mays , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN Mitocondrial , Semillas/genética , Semillas/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMEN
OBJECTIVES: Although COVID-19 is known to be caused by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study was conducted to study whether air quality index (AQI), four ambient air pollutants (PM2.5, PM10, NO2 and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26th to Feb 29th in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R2=0.13, p<0.05) and XiaoGan (R2=0.223, p<0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM2.5 and NO2 in both cities. In Wuhan, the tightest correlation was observed between NO2 and COVID-19 incidence (R2=0.329, p<0.01). In XiaoGan, in addition to the PM2.5 (R2=0.117, p<0.01) and NO2 (R2=0.015, p<0.05), a notable correlation was also observed between the PM10 and COVID-19 incidence (R2=0.105, p<0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p<0.05). CONCLUSIONS: AQI, PM2.5, NO2, and temperature are four variables that could promote the sustained transmission of COVID-19.
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Contaminación del Aire/efectos adversos , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Temperatura , Betacoronavirus , COVID-19 , Monóxido de Carbono/efectos adversos , China/epidemiología , Ciudades , Infecciones por Coronavirus/transmisión , Humanos , Incidencia , Dióxido de Nitrógeno/efectos adversos , Pandemias , Material Particulado/efectos adversos , Neumonía Viral/transmisión , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3-L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.
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MicroARNs/genética , Neuralgia/genética , Análisis de Secuencia de ARN , Animales , Secuencia de Bases , Modelos Animales de Enfermedad , Masculino , MicroARNs/metabolismo , Neuralgia/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de SeñalRESUMEN
The maize (Zea mays) defective kernel 33 (dek33) mutant produces defective and occasionally viviparous kernel phenotypes. In this study, we cloned Dek33 by positional cloning and found that it encodes a pyrimidine reductase in riboflavin biosynthesis. In dek33, a single-base mutation (G to A) in the C-terminal COG3236 domain caused a premature stop codon (TGA), producing a weak mutant allele with only a truncated form of the DEK33 protein that occurred at much lower levels that the completed WT form, and with a reduced riboflavin content. The dek33 mutation significantly affected oil-body formation and suppressed endoreduplication. It also disrupted ABA biosynthesis, resulting in lower ABA content that might be responsible for the viviparous embryo. In addition, our results indicated that the COG3236 domain is important for the protein stability of DEK33. Yeast two-hybrid experiments identified several proteins that interacted with DEK33, including RGLG2 and SnRK1, suggesting possible post-translational regulation of DEK33 stability. The interaction between DEK33 and these proteins was further confirmed by luciferase complementation image assays. This study provides a weak mutant allele that can be utilized to explore cellular responses to impaired riboflavin biosynthesis during seed development. Our findings indicate that the COG3236 domain might be an essential regulatory structure for DEK33 stability in maize.
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Ácido Abscísico/metabolismo , Gotas Lipídicas/metabolismo , Oxidorreductasas/genética , Reguladores del Crecimiento de las Plantas/genética , Proteínas de Plantas/genética , Riboflavina/genética , Zea mays/genética , Oxidorreductasas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/metabolismo , Pirimidinas/metabolismo , Riboflavina/biosíntesis , Semillas/genética , Semillas/crecimiento & desarrollo , Semillas/metabolismo , Zea mays/crecimiento & desarrollo , Zea mays/metabolismoRESUMEN
RATIONALE: Posterior reversible encephalopathy syndrome (PRES) was termed by Hinchey in 1996. Patients have a reversible vasogenic brain edema in imaging and acute neurological symptoms such as headache, seizures, encephalopathy, and visual disturbances when suffering from hypertension, pre-eclampsia/eclampsia, renal failure, immunosuppressive medications, autoimmune disorders, sepsis, thrombocytopaenia, hypocalcaemia, alcohol withdrawal, and many other potential causes. de Havenon A et al have proposed a new syndrome named PRES with spinal cord involvement (PRES-SCI). The patients with PRES-SCI have similar symptoms these of PRES. Patients have neurologic signs with the spinal cord involved and lesions in magnetic resonance imaging (MRI) extending to the cervicomedullary junction, usually with extreme elevation in blood pressure and a history of hypertensive retinopathy. We administrated a young patient whose condition was consistent with PRES-SCI except for the hemisphere lesions. PATIENT CONCERNS: A 20-year-old Asian male patient was admitted for a 1 week history of blurred vision and weakness of the limbs. He has had poorly controlled hypertension for 1 year before admission. In emergency room, his blood pressure could raise to 260/140mmHg. Neurological examinations and cerebral spinal fluid tests were negative. The MRI of the brain and spinal cord showed reversible lesions in the medulla and upper cervical spinal cord that extended to the lower thoracic spine. DIAGNOSIS: Taking into account the characteristic lesions in the MRI as well as the reversible course upon treatment, he was diagnosed PRES-SCI. INTERVENTIONS: He was treated with medicines for the hypertension. OUTCOMES: His symptoms rapidly improved and finally the lesions on the MRI of the brain and spianl cord disappeared. LESSONS: Clinicians should suspect PRES-SCI when patients have mild or no neurologic signs accompanied with extreme elevation in blood pressure and lesions in spinal cord. Spinal lesions alone may be a subtype of PRES-SCI.
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Síndrome de Leucoencefalopatía Posterior/complicaciones , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Enfermedades de la Médula Espinal/complicaciones , Enfermedades de la Médula Espinal/diagnóstico por imagen , Antihipertensivos/uso terapéutico , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Masculino , Síndrome de Leucoencefalopatía Posterior/tratamiento farmacológico , Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: It has been widely understood that well-trained doctors are crucial for a high-quality public health system and safe patient care. Thus, in 2011, China initiated its first national residency training program, called the China Standardized Training for Resident Doctor (C-STRD), for medical graduates to prepare qualified doctors for the medical care system with increasing demands. So far, no studies have specifically address the prevalence of stress and its determinants among residents enrolled in the C-STRD. PARTICIPANTS AND METHODS: The research is performed in two stages. In stage I, the authors conducted a pilot study and met 112 C-STRD residents in person. Based on the preliminary data, a revised questionnaire was adopted in stage II, during which the authors conducted a multi-institutional, cross-sectional survey of 340 participants from 11 hospitals in Shanghai in a self-administered manner. RESULTS: The results showed that C-STRD residents were overall under severe stress as their mean PSS score was 27.5 ± 4.9, which was higher than the threshold of high stress (PSS = 20). Specifically, the PSS score for the residents with Bachelor (MB), Master (MM) and Doctoral of Medicine (MD) educational degree were 26.6 ± 4.1, 27.8 ± 3.5 and 27.1 ± 5.2, respectively (P>0.05). Their stress was mainly associated with their financial income status and workload, as these two factors caused more severe burden than other listed stressors (P<0.05). Specially, the residents indicated that their montly payroll amout were as low as $590.2 ± 127 while no benefit package and allowance were given. Surprisingly, wage arrears up to 5.3 month were reported by 36 (10%) participants. Workload survey showed the residents has high work intensity and inadequate rest. Since no stress management program was provided, the majority of residents tended to cope their stress with unhealthy strategies, such as mesmerizing in TV/computer (88.2%) and overeating (59.7%). CONCLUSION: The C-STRD residents are at high risk of perceived stress. Although there was a difference in perception of stress for workload and career future among different educational degree owners, low financial income is the major stressor among all C-STRD residents. Unhealthy stress management strategies were adopted by all residents due to lack of appropriate stress-relieving intervention.
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The present study aimed to identify microRNAs (miRNAs) that are involved in neuropathic pain and predict their corresponding roles in the pathogenesis and development process of neuropathic pain. The rat model of neuropathic pain caused by spared nerve injury (SNI) was established in Sprague-Dawley male rats, followed by small RNA sequencing of the L3-L6 dorsal root ganglion. Real-time PCR was performed to validate the differently expressed miRNAs. Functional verification was performed by intrathecally injecting the animals with miRNA agomir. A total of 72 differentially expressed miRNAs were identified in the SNI rats, including 33 upregulated and 39 downregulated miRNAs. The results of qPCR further verified the expression levels of rno-miR-6215 (P=0.015), rno-miR-1224 (P=0.030), rno-miR-1249 (P=0.038), and rno-miR-488-3p (P=0.048), which were all significantly downregulated in the SNI rats compared to the control ones. The majority of differentially expressed miRNAs were associated with phosphorylation, intracellular signal transduction, and cell death. Target prediction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses suggested that these differentially expressed miRNAs targeted genes that are related to axon guidance, focal adhesion, and Ras and Wnt signaling pathways. Moreover, miR-1224 agomir significantly alleviated SNI-induced neuropathic pain. The current findings provide new insights into the role of miRNAs in the pathogenesis of neuropathic pain.
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Animales , Masculino , Ratas , Análisis de Secuencia de ARN , MicroARNs/genética , Neuralgia/genética , Secuencia de Bases , Transducción de Señal , Ratas Sprague-Dawley , MicroARNs/metabolismo , Modelos Animales de Enfermedad , Reacción en Cadena en Tiempo Real de la Polimerasa , Neuralgia/metabolismoRESUMEN
BACKGROUND/AIMS: Cyclin D1 (CCND1) is frequently overexpressed in malignant gliomas. We have previously shown ectopic overexpression of CCND1 in human malignant gliomas cell lines. METHODS: Quantitative reverse transcriptase PCR (qRT-PCR) and Western Blot (WB) was performed to investigate the expression of CCND1 in glioma tissues and cell lines. The biological function of CCND1 was also investigated through knockdown and overexpression of BCYRN1 in vitro. RESULTS: Here we reported that CCND1 expression was positively associated with the pathological grade and proliferative activity of astrocytomas, as the lowest expression was found in normal brain tissue (N = 3) whereas the highest expression was in high-grade glioma tissue (N = 25). Additionally, we found that the expression level of CCND1 was associated with IC50 values in malignant glioma cell lines. Forced inhibition of CCND1 increased temozolomide efficacy in U251 and SHG-44 cells. After CCND1 overexpression, the temozolomide efficacy decreased in U251 and SHG-44 cells. Colony survival assay and apoptosis analysis confirmed that CCND1 inhibition renders cells more sensitive to temozolomide treatment and temozolomide-induced apoptosis in U251 and SHG-44 cells. Inhibition of P-gp (MDR1) by Tariquidar overcomes the effects of CCND1 overexpression on inhibiting temozolomide-induced apoptosis. Inhibition of CCND1 inhibited cell growth in vitro and in vivo significantly more effectively after temozolomide treatments than single temozolomide treatments. Finally, inhibition of CCND1 in glioma cells reduced tumor volume in a murine model. CONCLUSION: Taken together, these data indicate that CCND1 overexpression upregulate P-gp and induces chemoresistance in human malignant gliomas cells and that inhibition of CCND1 may be an effective means of overcoming CCND1 associated chemoresistance in human malignant glioma cells.
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Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Ciclina D1/genética , Glioblastoma/tratamiento farmacológico , Temozolomida/uso terapéutico , Adulto , Antineoplásicos Alquilantes/farmacología , Apoptosis/efectos de los fármacos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/genética , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Temozolomida/farmacologíaRESUMEN
The cyclin family protein CCNG2 has an important inhibitory role in cancer initiation and progression, but the exact mechanism is still unknown. In this study, we examined the relationship between CCNG2 and the malignancy of astrocytomas and whether the AKT pathway, which is upregulated in astrocytomas, may inhibit CCNG2 expression. CCNG2 expression was found to be negatively associated with the pathological grade and proliferative activity of astrocytomas, as the highest expression was found in control brain tissue (N = 31), whereas the lowest expression was in high-grade glioma tissue (N = 31). Additionally, CCNG2 overexpression in glioma cell lines, T98G and U251 inhibited proliferation and arrested cells in the G0/G1 phase. Moreover, CCNG2 overexpression could increase glioma cells apoptosis. In contrast, AKT activity increased in glioma cells that had low CCNG2 expression. Expression of CCNG2 was higher in cells treated with the AKT kinase inhibitor MK-2206 indicating that the presence of phosphorylated AKT may inhibit the expression of CCNG2. Inhibition of AKT also led to decreased colony formation in T98G and U251 cells and knocked down of CCNG2 reversed the result. Finally, overexpression of CCNG2 in glioma cells reduced tumor volume in a murine model. To conclude, low expression of CCNG2 correlated with the severity astrocytoma and CCNG2 overexpression could induce apoptosis and inhibit proliferation. Inhibition of AKT activity increased the expression of CCNG2. The present study highlights the regulatory consequences of CCNG2 expression and AKT activity in astrocytoma tumorigenesis and the potential use of CCNG2 in anticancer treatment.
RESUMEN
Mitochondrial group II introns require the participation of numerous nucleus-encoded general and specific factors to achieve efficient splicing in vivo Pentatricopeptide repeat (PPR) proteins have been implicated in assisting group II intron splicing. Here, we identified and characterized a new maize seed mutant, defective kernel 37 (dek37), which has significantly delayed endosperm and embryo development. Dek37 encodes a classic P-type PPR protein that targets mitochondria. The dek37 mutation causes no detectable DEK37 protein in mutant seeds. Mitochondrial transcripts analysis indicated that dek37 mutation decreases splicing efficiency of mitochondrial nad2 intron 1, leading to reduced assembly and NADH dehydrogenase activity of complex I. Transmission Electron Microscopy (TEM) revealed severe morphological defects of mitochondria in dek37 Transcriptome analysis of dek37 endosperm indicated enhanced expression in the alternative respiratory pathway and extensive differentially expressed genes related to mitochondrial function. These results indicated that Dek37 is involved in cis-splicing of mitochondrial nad2 intron 1 and is required for complex I assembly, mitochondrial function, and seed development in maize.
Asunto(s)
Regulación de la Expresión Génica de las Plantas , Intrones , Proteínas Mitocondriales/genética , Proteínas de Plantas/genética , Empalme del ARN , Semillas/genética , Zea mays/genética , Clonación Molecular , Mitocondrias/genética , Mutación , NADH Deshidrogenasa/metabolismo , Fenotipo , Filogenia , Transporte de ProteínasRESUMEN
To adapt to the environment and survive, most animals can control their behaviors by making decisions. The process of decision-making and responding according to cues in the environment is stable, sustainable, and learnable. Understanding how behaviors are regulated by neural circuits and the encoding and decoding mechanisms from stimuli to responses are important goals in neuroscience. From results observed in Drosophila experiments, the underlying decision-making process is discussed, and a neural circuit that implements a two-choice decision-making model is proposed to explain and reproduce the observations. Compared with previous two-choice decision making models, our model uses synaptic plasticity to explain changes in decision output given the same environment. Moreover, biological meanings of parameters of our decision-making model are discussed. In this paper, we explain at the micro-level (i.e., neurons and synapses) how observable decision-making behavior at the macro-level is acquired and achieved.