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1.
BMC Nephrol ; 25(1): 181, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778257

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients admitted to intensive care unit (ICU) and mortality rates for this condition are high. To reduce the high incidence of short-term mortality, reliable prognostic indicators are required to facilitate early diagnosis and treatment of AKI. We assessed the ability of plasma proenkephalin (p­PENK) and plasma neutrophil gelatinase-associated lipocalin (p­NGAL) to predict 28-day mortality in AKI patients in intensive care. METHODS: This prospective study, carried out between January 2019 and December 2019, comprised 150 patients (100 male) diagnosed with AKI after excluding 20 patients discharged within 24 h and those with missing hospitalization data. Blood samples were collected to determine admission p-PENK and p-NGAL levels. The study outcome was 28­day mortality. RESULTS: The mean patient age was 68 years (female, 33%). The average P­PENK and p­NGAL levels were 0.24 ng/µL and 223.70 ng/mL, respectively. P­PENK levels >0.36 ng/µL and p­NGAL levels >230.30 ng/mL were used as critical values to reliably indicate 28­day mortality for patients with AKI (adjusted hazard ratios 0.785 [95% confidence interval 0.706-0.865, P<0.001] and 0.700 [95% confidence interval 0.611-0.789, P<0.001], respectively). This association was significant for mortality in patients in intensive care with AKI. Baseline p-PENK (0.36 ng/µL) and p-NGAL (230.30 ng/mL) levels and their respective cut-off values showed clinical value in predicting 28-day mortality. CONCLUSION: Serum PENK and NGAL levels, when used in conjunction, improved the accuracy of predicting 28-day mortality in patients with AKI while retaining sensitivity and specificity.


Assuntos
Injúria Renal Aguda , Biomarcadores , Encefalinas , Unidades de Terapia Intensiva , Lipocalina-2 , Humanos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/diagnóstico , Masculino , Feminino , Lipocalina-2/sangue , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Encefalinas/sangue , Biomarcadores/sangue , Precursores de Proteínas/sangue , Prognóstico , Valor Preditivo dos Testes , Idoso de 80 Anos ou mais , Mortalidade Hospitalar
2.
J Integr Neurosci ; 23(6): 118, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38940085

RESUMO

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.


Assuntos
Citoesqueleto de Actina , Etanol , Hipocampo , Microtúbulos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Masculino , Etanol/farmacologia , Etanol/administração & dosagem , Camundongos , Camundongos Endogâmicos C57BL , Depressores do Sistema Nervoso Central/farmacologia , Depressores do Sistema Nervoso Central/administração & dosagem , Modelos Animais de Doenças , Comportamento Animal/efeitos dos fármacos
3.
Appetite ; 191: 107048, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37804604

RESUMO

Memory about food and eating is crucial in regulating appetite and eating behaviors. Successfully stopping vivid imagination of delicious food could help reduce food craving and thus reduce the possibility of further intake. Memory inhibition is a cognitive process that involves intentional suppression of certain memories coming to consciousness. Successful memory suppression derives from inhibitory control. Although considerable work has consistently observed the impairment in motor or response inhibitory control among individuals with obesity, there has been a lack of investigation into the influence of bodyweight status on memory inhibitory control. To fill this gap, current study investigated behavioral and neurophysiological correlates of memory suppression in young women. Using Think/No-Think task and event-related potentials among 47 females, we found that participants with higher visceral adipose tissue (VAT) showed a tendency towards decreased suppression ability for memories related to food but not memories related to nonfood items. In depth analysis showed that decrease in the differences in P2 amplitudes between suppression vs. retrieval of food-related memories mediated the impairment of suppression ability by high VAT. We then tested whether individual differences in memory suppression ability as well as ERP correlates predicted future BMI or VAT change over 1-year follow-up. Results showed that P2 amplitudes when retrieving food-related memory could predict VAT change at 1-year follow-up among participants with healthy BMI. These observations suggest a hypersensitivity inference hypothesis underlying memory control impairments. To be specific, deficits in memory suppression may be in part resulted from elevated sensitivity to the cues coupling with food-related memory. It extends previous studies of memory suppression with food rewards and provides the first evidence to help understand the relationship between inhibitory control on food-related memory and obesity.

4.
Health Qual Life Outcomes ; 18(1): 229, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32664966

RESUMO

BACKGROUND: The aim of this longitudinal study was to identify risk factors for posttraumatic stress disorder (PTSD) in inpatients injured in the Ludian earthquake and examine the relationship between PTSD symptoms and health-related quality of life (HRQoL) following the earthquake. METHODS: Three assessments were performed during an 18-month follow-up period. In total, one-hundred forty-seven inpatients of one-hundred seventy-four inpatients (85% of the initial sample) underwent all the assessments. Injured inpatients admitted to the No. 1 People's Hospital of Zhaotong City after a severe earthquake (6.5 on the Richter scale) were enrolled in the study and assessed using the Posttraumatic Stress Disorder Checklist-Civilian Version, Clinician-Administered Posttraumatic Stress Disorder Scale, and Medical Outcomes Study Short Form-36 Scale. RESULTS: At the first, third and eighteenth months after the earthquake, the prevalence rates for PTSD were 23, 14, and 7%, respectively. In a regression model, bereavement, history of major diseases, and severe injury in the earthquake were associated with severe PTSD symptoms. HRQoL was negatively correlated with PTSD symptoms. Compared to that of Chinese norms, participants' HRQoL was significantly lower in all eight HRQoL domains of the Medical Outcomes Study Short Form-36 Scale. CONCLUSIONS: The findings suggest that a substantial proportion of inpatients injured in the earthquake experienced severe PTSD symptoms and poor HRQoL. Therefore, early preventive programs and interventions should be implemented following disasters, to reduce PTSD and improve HRQoL in injured individuals.


Assuntos
Povo Asiático/psicologia , Terremotos/estatística & dados numéricos , Pacientes Internados/psicologia , Qualidade de Vida/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Sobreviventes/psicologia , Adulto , Povo Asiático/estatística & dados numéricos , China , Desastres/estatística & dados numéricos , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Sobreviventes/estatística & dados numéricos
5.
Molecules ; 25(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979084

RESUMO

Based on a foregoing gram-scale laboratory process, an efficient scale-up preparation process of 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49-API), a new acute pyelonephritis candidate drug, was developed and validated aiming to reduce by-products and achieve better impurity profiles. Meanwhile, the polymorph of LM49-API and process-related impurities were also investigated. Ultimately, the optimal reaction conditions were verified by evaluating the impurity profiles and their formation during the synthesis. Six process-related impurities were synthesized and identified, being useful for the quality control of LM49-API. Its finalized preparation process was further validated at 329-410 g scale-up production in 53.4-57.1% overall yield with 99.95-99.98% high-performance liquid chromatography (HPLC) purity, and it is currently viable for commercial production. LM49-API-imC and LM49-API-imX were identified as the main single impurities in LM49-API, with the content controlled to be less than 0.03%.


Assuntos
Antifúngicos/uso terapêutico , Pielonefrite/microbiologia , Cloreto de Alumínio/química , Animais , Cromatografia Líquida de Alta Pressão
6.
Qual Life Res ; 28(2): 509-513, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30251129

RESUMO

PURPOSE: Disasters may impair people's quality of life (QoL) indirectly through disaster risk perception. We intended to address this point by analyzing the correlation between disaster experience and QoL with a test of the mediating effects of risk perception at the example of earthquake. METHODS: We employed the 2013 Taiwan Social Change Survey data as the data source (N = 1481). Unadjusted ordinal logistic regression models examined the correlation of disaster experience with QoL and earthquake risk perception at first. Another set of ordinal regressions were conducted to explore the mediating effect of earthquake risk perception between earthquake experience and QoL. RESULTS: Earthquake experience had negative impact on QoL measured by self-reported happiness, general health status, and life satisfaction. People who had earthquake experience perceived higher earthquake risk compared to those who had never experienced an earthquake. Risk perception measured by perceived likelihood of future earthquake as a mediating factor for the impact of earthquake experience on QoL from the dimensions of both self-reported happiness and life satisfaction was confirmed. CONCLUSIONS: Findings are consistent with existing reports about the association between disaster experience and QoL. Research using multi-dimensional measures of disaster risk perception and QoL is needed to inform post-disaster recovery programs.


Assuntos
Desastres/estatística & dados numéricos , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Percepção , Inquéritos e Questionários
7.
Biomed Chromatogr ; 33(9): e4555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30990898

RESUMO

Bufadienolides are the main bioactive components of Venenum Bufonis (VB) and have been widely used to treat different types of human cancers for decades. The bufadienolide content in VB varies significantly in materials from different geographical origins. In this work, a new strategy for the quality assessment of VB was developed through quantitative analysis of multi-components by single marker (QAMS). Cinobufagin was selected as the internal reference substance; seven bufadienolides were separated and simultaneously determined based on relative correction factors. The correlation coefficient value (r ≥ 0.9936) between QAMS and the normal external standard method proved the consistency of the two methods. According to the outcomes of 30 batches of VB samples, the contents of the seven bufadienolides were used for further chemometric analysis. All of the samples of VB from various geographical origins were divided into three categories based on hierarchical cluster analysis and radar plot, which indicated the crucial influence of geographical origins on VB. This study showed that QAMS combined with chemometristry could be used to comprehensively evaluate and effectively control the quality of VB from different geographical origins.


Assuntos
Bufanolídeos/análise , Biomarcadores , Bufanolídeos/química , Bufanolídeos/classificação , Bufanolídeos/normas , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
8.
Zhongguo Zhong Yao Za Zhi ; 44(9): 1850-1856, 2019 May.
Artigo em Zh | MEDLINE | ID: mdl-31342712

RESUMO

As known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional Chinese medicines because of the extremely complex chemical compositions. This project is to screen the quality markers that can accurately control the quality of the Bufonis Venenum by exploring the intrinsic correlation of components. In this study,venom of Bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin were determined by HPLC-DAD. Then,the data obtained were analyzed by Spearman correlation analysis and principal component analysis( PCA). In addition,a stepwise regression analysis was used to establish a predictive model for the contents of the seven bufogenin components( independent variable) and the total contents of the bufogenin( dependent variable). The results indicated that there is a significant positive correlation between the contents of telocinobufagin and cinobufotalin,and there is a significant positive correlation between the contents of bufalin,cinobufagin and resibufogenin. In contrast,the contents of telocinobufagin and cinobufotalin are negatively correlated with the contents of bufalin,cinobufagin and resibufogenin. However,the correlation between gamabufotalin and bufotalin and other components are not obvious. Furthermore,further study found that there is a correlation between the sum of the contents of bufalin,cinobufagin and telocinobufagin and the total contents of the bufogenin. In fact,the application of bufalin,cinobufagin and telocinobufagin as the quality control indicators of the Bufonis Venenum can better reflect the quality characteristics of the Bufonis Venenum compared with the previous quality control indicators. The conclusions will provide a reference for the revision of the quality standards of the Bufonis Venenum.


Assuntos
Venenos de Anfíbios/química , Bufanolídeos/análise , Bufo bufo , Animais , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , Controle de Qualidade
9.
Cell Mol Life Sci ; 74(3): 487-493, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27614628

RESUMO

Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, as a renewable source of various functional cells in the human body, ESCs hold great promise for human cell therapy. During the rapid proliferation of ESCs in culture, DNA damage, such as DNA double-stranded breaks, will occur in ESCs. Therefore, to realize the potential of ESCs in human cell therapy, it is critical to understand the mechanisms how ESCs activate DNA damage response and DNA repair to maintain genomic stability, which is a prerequisite for their use in human therapy. In this context, it has been shown that ESCs harbor much fewer spontaneous mutations than somatic cells. Consistent with the finding that ESCs are genetically more stable than somatic cells, recent studies have indicated that ESCs can mount more robust DNA damage responses and DNA repair than somatic cells to ensure their genomic integrity.


Assuntos
Dano ao DNA , Reparo do DNA , Células-Tronco Embrionárias/metabolismo , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Células-Tronco Embrionárias/citologia , Instabilidade Genômica , Humanos
10.
Sensors (Basel) ; 18(10)2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30347740

RESUMO

Interferometric fiber-optic sensors are often organized in the form of large-scale arrays by lending the technique of time division multiplexing (TDM) to reduce the system cost. Discriminating the time windows for different sensor units is the prerequisite to successfully demodulate the sensing message, but it traditionally calls for a very time-consuming manual calibration process. To combat this problem, a novel automatic time window locating method is proposed in this paper. It introduces the concept of shape function and carries out the cross-correlation operation between the shape function and the sensor signal. The shape function is defined as the function whose curve profile reflects the main data characteristics of the sensor signal. The time window information is then extracted from the correlation result. This whole process is carried out automatically by the interrogation controller of the sensor system without any manual intervene. Experiments are conducted to validate this method. The proposed method can greatly reduce the complexity of locating time windows in large-scale TDM sensor arrays, and make the practical use of the TDM scheme much more convenient.

11.
Anal Chem ; 89(3): 1793-1800, 2017 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-28208275

RESUMO

Development of comprehensive, three-dimensional (3D) gas chromatography with time-of-flight mass spectrometric detection (GC3/TOFMS) is described. This instrument provides four dimensions (4D) of chemical selectivity and includes significant improvements to total selectivity (mass spectrometric and chromatographic), peak identification, and operational temperature range relative to previous models of the GC3 reported. The new instrumental design and data output are evaluated and illustrated via two samples, a 115-component test mixture and a diesel fuel spiked with several compounds, for the purpose of illustrating the chemical selectivity benefits of this instrumental platform. Useful approaches to visualize the 4D data are presented. The GC3/TOFMS instrument experimentally achieved total peak capacity, nc,3D, ranging from 5000 to 9600 (x̅ = 7000, s = 1700) for 10 representative analytes for 50 min separations with component dimensional peak capacities averaging 406, 3.6, and 4.9 for 1D, 2D, and 3D, respectively. Particularly, GC3/TOFMS achieved a combined 2D × 3D peak capacity ranging from 10 to 26 (x̅ = 17.6, s = 5.0), which is similar to what is achieved by 2D alone in a GC × GC operating at equivalent modulation period conditions. The analytical benefits of employing three varied chemical selectivities in the 3D separation coupled with TOFMS are illustrated through the separation and detection of 1,6-dichlorohexane and cyclohexyl isothiocyanate as part of the diesel fuel analysis.

12.
FASEB J ; 30(7): 2500-10, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27006451

RESUMO

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of the cellular antioxidant response and xenobiotic metabolism. Activation of the Nrf2 signaling pathway has been demonstrated to confer protection against environmental insults and prevent disease or inhibit the progression of diseases related to oxidative stress. In an attempt to identify novel improved Nrf2 inducers for systemic protection against tissue damage by environmental insults, we identified artemisitene as a novel Nrf2 activator using antioxidant responsive element luciferase assay in MDA-MB-231 cells. Further studies suggest that artemisitene activates Nrf2 by decreasing Nrf2 ubiquitination and increasing its stability. In Nrf2 wild-type mice, systemic administration of artemisitene strongly inhibits bleomycin-induced lung damage. Artemisitene represents a novel class of Nrf2 inducer, and artemisitene-based therapeutic approach targeting Nrf2 may also provide antioxidant protection for humans against tissue damage by toxic chemicals.-Chen, W., Li, S., Li, J., Zhou, W., Wu, S., Xu, S., Cui, K., Zhang, D. D., Liu, B. Artemisitene activates the Nrf2-dependent antioxidant response and protects against bleomycin-induced lung injury.


Assuntos
Antioxidantes/metabolismo , Artemisininas/farmacologia , Bleomicina/toxicidade , Lesão Pulmonar/induzido quimicamente , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Artemisininas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Estrutura Molecular , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
13.
Phys Rev Lett ; 112(1): 010504, 2014 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-24483878

RESUMO

Quantum physics allows for unconditionally secure communication between parties that trust each other. However, when the parties do not trust each other such as in the bit commitment scenario, quantum physics is not enough to guarantee security unless extra assumptions are made. Unconditionally secure bit commitment only becomes feasible when quantum physics is combined with relativistic causality constraints. Here we experimentally implement a quantum bit commitment protocol with relativistic constraints that offers unconditional security. The commitment is made through quantum measurements in two quantum key distribution systems in which the results are transmitted via free-space optical communication to two agents separated with more than 20 km. The security of the protocol relies on the properties of quantum information and relativity theory. In each run of the experiment, a bit is successfully committed with less than 5.68×10(-2) cheating probability. This demonstrates the experimental feasibility of quantum communication with relativistic constraints.

14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 31(1): 25-8, 2014 Feb.
Artigo em Zh | MEDLINE | ID: mdl-24510557

RESUMO

OBJECTIVE: To investigate the expression of placenta-derived RASSF1A gene in maternal plasma during first and second trimesters, and to explore its value for the prediction of pre-eclampsia. METHODS: For 325 pregnant women of the first trimester, free DNA of plasma samples was extracted at 7-12, 13-18, and 19-24 gestational weeks, respectively. Methylation-sensitive restriction enzyme digestion followed by fluorescence quantitative PCR (MSRE+ PCR) was employed for analyzing the concentrations of hypermethylated RASSF1A gene. Blood pressure, proteinuria and clinical feature were monitored at the same time. Those who had subsequently developed pre-eclampsia were selected as the pre-eclamptic group, 30 normal pregnant women were selected as the control group. Hypermethylated RASSF1A gene in maternal plasma was retrospectively analyzed. The relationship between clinical classification, type of pre-eclampsia and concentrations of the gene were further analyzed. RESULTS: Twenty-six out of the 325 pregnant women developed pre-eclampsia as their only complication. At 13-18 gestational weeks, the mean concentrations of fetus-specific RASSF1A sequences were 141.62 copies/mL in maternal plasma of pre-eclamptic pregnancies, which was significantly greater than that of the controls (98.90 copies/mL). Fetus-derived RASSF1A levels were 2.03 fold higher in pre-eclamptic subjects than controls at 19-24 gestational weeks. There was a significant difference in the level of hypermethylated RASSF1A gene between the mild and severe pre-clamptic subjects at 13-24 gestational weeks (P< 0.05). The concentrations of the sequences were significantly higher in early-onset severe pre-eclampsia than late-onset severe pre-eclampsia at 19-24 gestational weeks (P< 0.05). CONCLUSION: Altered expression of hypermethylated RASSF1A gene may be detected in maternal plasma during second trimester, which has important significance for early prediction of pre-eclampsia.


Assuntos
Placenta/metabolismo , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Proteínas Supressoras de Tumor/genética , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/metabolismo , Valor Preditivo dos Testes , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Proteínas Supressoras de Tumor/sangue
15.
Environ Pollut ; 351: 124081, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697251

RESUMO

Microcystin-leucine arginine (MC-LR) is a common cyantotoxin produced by hazardous cyanobacterial blooms, and eutrophication is increasing the contamination level of MC-LR in drinking water supplies and aquatic foods. MC-LR has been linked to colorectal cancer (CRC) progression associated with tumor microenvironment, however, the underlying mechanism is not clearly understood. In present study, by using GEO, KEGG, GESA and ImmPort database, MC-LR related differentially expressed genes (DEGs) and pathway- and gene set-enrichment analysis were performed. Of the three identified DEGs (CXCL1, GUCA2A and GDF15), CXCL1 was shown a positive association with tumor infiltration, and was validated to have a dominantly higher upregulation in MC-LR-treated tumor-associated macrophages (TAMs) rather than in MC-LR-treated CRC cells. Both CRC cell/macrophage co-culture and xenograft mouse models indicated that MC-LR stimulated TAMs to secrete CXCL1 resulting in promoted proliferation, migration, and invasion capability of CRC cells. Furtherly, IP-MS assay found that interaction between TAMs-derived CXCL1 and CRC cell-derived IGHG1 may enhance CRC cell proliferation and migration after MC-LR treatment, and this effect can be attenuated by silencing IGHG1 in CRC cell. In addition, molecular docking analysis, co-immunoprecipitation and immunofluorescence further proved the interactions between CXCL1 and IGHG1. In conclusion, CXCL1 secreted by TAMs can trigger IGHG1 expression in CRC cells, which provides a new clue in elucidating the mechanism of MC-LR-mediated CRC progression.


Assuntos
Quimiocina CXCL1 , Neoplasias Colorretais , Transdução de Sinais , Macrófagos Associados a Tumor , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Humanos , Animais , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Camundongos , Macrófagos Associados a Tumor/metabolismo , Microcistinas/toxicidade , Toxinas Marinhas , Linhagem Celular Tumoral , Progressão da Doença , Proliferação de Células/efeitos dos fármacos , Microambiente Tumoral
16.
Sci Adv ; 10(25): eadj0720, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896627

RESUMO

Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO2. The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.


Assuntos
Proteínas de Homeodomínio , Hipoventilação , Bulbo , Neurônios , Fatores de Transcrição , Hipoventilação/congênito , Hipoventilação/genética , Animais , Neurônios/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Bulbo/metabolismo , Apneia do Sono Tipo Central/genética , Fenótipo , Humanos
17.
Plant J ; 72(1): 129-41, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22680239

RESUMO

Xylem development is a process of xylem cell terminal differentiation that includes initial cell division, cell expansion, secondary cell wall formation and programmed cell death (PCD). PCD in plants and apoptosis in animals share many common characteristics. Caspase-3, which displays Asp-Glu-Val-Asp (DEVD) specificity, is a crucial executioner during animal cells apoptosis. Although a gene orthologous to caspase-3 is absent in plants, caspase-3-like activity is involved in many cases of PCD and developmental processes. However, there is no direct evidence that caspase-3-like activity exists in xylem cell death. In this study, we showed that caspase-3-like activity is present and is associated with secondary xylem development in Populus tomentosa. The protease responsible for the caspase-3-like activity was purified from poplar secondary xylem using hydrophobic interaction chromatography (HIC), Q anion exchange chromatography and gel filtration chromatography. After identification by liquid chromatography-tandem mass spectrometry (LC-MS/MS), it was revealed that the 20S proteasome (20SP) was responsible for the caspase-3-like activity in secondary xylem development. In poplar 20SP, there are seven α subunits encoded by 12 genes and seven ß subunits encoded by 12 genes. Pharmacological assays showed that Ac-DEVD-CHO, a caspase-3 inhibitor, suppressed xylem differentiation in the veins of Arabidopsis cotyledons. Furthermore, clasto-lactacystin ß-lactone, a proteasome inhibitor, inhibited PCD of tracheary element in a VND6-induced Arabidopsis xylogenic culture. In conclusion, the 20S proteasome is responsible for caspase-3-like activity and is involved in xylem development.


Assuntos
Peptídeo Hidrolases/isolamento & purificação , Populus/enzimologia , Complexo de Endopeptidases do Proteassoma/isolamento & purificação , Xilema/enzimologia , Apoptose , Arabidopsis/citologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/enzimologia , Caspase 3/isolamento & purificação , Caspase 3/metabolismo , Diferenciação Celular , Parede Celular/metabolismo , Lactonas/farmacologia , Oligopeptídeos/farmacologia , Peptídeo Hidrolases/metabolismo , Folhas de Planta/citologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/enzimologia , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/metabolismo , Caules de Planta/citologia , Caules de Planta/efeitos dos fármacos , Caules de Planta/enzimologia , Caules de Planta/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Populus/citologia , Populus/efeitos dos fármacos , Populus/crescimento & desenvolvimento , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma , Plântula/citologia , Plântula/efeitos dos fármacos , Plântula/enzimologia , Plântula/crescimento & desenvolvimento , Xilema/citologia , Xilema/crescimento & desenvolvimento
18.
Phys Rev Lett ; 111(13): 130502, 2013 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-24116758

RESUMO

Quantum key distribution is proven to offer unconditional security in communication between two remote users with ideal source and detection. Unfortunately, ideal devices never exist in practice and device imperfections have become the targets of various attacks. By developing up-conversion single-photon detectors with high efficiency and low noise, we faithfully demonstrate the measurement-device-independent quantum-key-distribution protocol, which is immune to all hacking strategies on detection. Meanwhile, we employ the decoy-state method to defend attacks on a nonideal source. By assuming a trusted source scenario, our practical system, which generates more than a 25 kbit secure key over a 50 km fiber link, serves as a stepping stone in the quest for unconditionally secure communications with realistic devices.

19.
FEBS J ; 290(11): 2786-2804, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35262281

RESUMO

The study of cerebellar development has been at the forefront of neuroscience since the pioneering work of Wilhelm His Sr., Santiago Ramón y Cajal and many others since the 19th century. They laid the foundation to identify the circuitry of the cerebellum, already revealing its stereotypic three-layered cortex and discerning several of its neuronal components. Their work was fundamental in the acceptance of the neuron doctrine, which acknowledges the key role of individual neurons in forming the basic units of the nervous system. Increasing evidence shows that the cerebellum performs a variety of homeostatic and higher order neuronal functions beyond the mere control of motor behaviour. Over the last three decades, many studies have revealed the molecular machinery that regulates distinct aspects of cerebellar development, from the establishment of a cerebellar anlage in the posterior brain to the identification of cerebellar neuron diversity at the single cell level. In this review, we focus on summarizing our current knowledge on early cerebellar development with a particular emphasis on the molecular determinants that secure neuron specification and contribute to the diversity of cerebellar neurons.


Assuntos
Cerebelo , Neurônios , Animais , Humanos , Cerebelo/anatomia & histologia , Cerebelo/citologia , Cerebelo/embriologia , Biologia do Desenvolvimento , Neurônios GABAérgicos/citologia , Homeostase , Neurônios/classificação , Neurônios/citologia , Neurônios/metabolismo , Neurociências , Análise de Célula Única
20.
Phys Med Biol ; 68(14)2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37364572

RESUMO

To achieve high spatial resolution of reconstructed images in positron emission tomography (PET), the size of the scintillation crystal element is set small in current PET systems, which greatly increases the inter-crystal scattering (ICS) frequency. The ICS is a type of Compton scattering of the gamma photons from one crystal element to its neighborhood element, which obscures the determination of the first interaction position. In this study, we propose a 1D U-Net convolutional neural network to predict the first interaction position, which provides a universal way to efficiently solve the ICS recovery problem. The network is trained using the dataset collected from the GATE Monte Carlo simulation. The 1D U-Net structure is applied due to its capability of synthesizing both low-level and high-level information, which shows superiority in solving the ICS recovery problem. After being well trained, the 1D U-Net can generate a prediction accuracy of 78.1%. Compared to the coincidence events only composed from two photoelectric gamma photons, the sensitivity is improved by 149%. The contrast-to-noise ratio of the reconstructed contrast phantom increases from 6.973 to 10.795 for the 16 mm hot sphere. Compared to the take-energy-centroid method, the spatial resolution of the reconstructed resolution phantom can obtain the best improvement of 33.46%. Compared with the previous deep learning method based on the fully connected network, the proposed 1D U-Net can work more stably with considerably fewer network parameters. The 1D U-Net network model shows good universality when predicting different phantoms, and the computation speed is fast.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Simulação por Computador , Fótons , Método de Monte Carlo , Imagens de Fantasmas
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