RESUMO
The paraventricular nucleus of the thalamus (PVT) is involved in drug addiction-related behaviors, and morphine is a widely used opioid for the relief of severe pain. Morphine acts via opioid receptors, but the function of opioid receptors in the PVT has not been fully elucidated. Here, we used in vitro electrophysiology to study neuronal activity and synaptic transmission in the PVT of male and female mice. Activation of opioid receptors suppresses the firing and inhibitory synaptic transmission of PVT neurons in brain slices. On the other hand, the involvement of opioid modulation is reduced after chronic morphine exposure, probably because of desensitization and internalization of opioid receptors in the PVT. Overall, the opioid system is essential for the modulation of PVT activities.SIGNIFICANCE STATEMENT Opioid receptors modulate the activities and synaptic transmission in the PVT by suppressing the firing rate and inhibitory synaptic inputs. These modulations were largely diminished after chronic morphine exposure.
Assuntos
Analgésicos Opioides , Receptores Opioides , Masculino , Feminino , Camundongos , Animais , Analgésicos Opioides/farmacologia , Núcleo Hipotalâmico Paraventricular/fisiologia , Tálamo , Transmissão Sináptica , Morfina/farmacologiaRESUMO
BACKGROUND: Growth charts are an important method for evaluating a child's health, growth, and nutritional status. It is essential to monitor the growth of children and adolescents using growth charts. OBJECTIVES: To present body mass index (BMI)-for-age references reflecting children's growth in Shanxi. We also compare our new data with growth references of other cities of China and World Health Organization (WHO) growth standards. METHODS: A stratified cluster random sampling method was used to recruit 5461 children and adolescents aged 6-17 years. Height and weight were measured and BMI was calculated. The LMS method was used to calculate the percentile values of body mass index by sex and age. Smoothed BMI-for-age growth curves were presented for both sexes and compared with reference data from other cities of China and WHO. RESULTS: BMI centiles increased with age but with different patterns in both boys and girls. The centile curves from the 3rd to the 50th had a slight increase, while a sharp increase was seen from 11 to 17 years in boys and from 6 to 14 years in girls in the higher centiles. In comparison with other cities of China, the values for the 50th percentile are higher than those reported for children from China 2009, Shanghai, Changsha and China 2010 in both sexes. In comparison with WHO growth references, Chinese girls and boys had higher values in all percentiles, whereas curves of girls look roughly the same. The medians for BMI in Shanxi increase linearly from 6 to 17 years in boys. CONCLUSIONS: The BMI percentiles of children aged 6-17 years in Shanxi differed significantly from the growth reference curves of other cities of China and WHO. Recommending the provision of BMI reference curves for local children and adolescents to assess their growth and development and monitor their nutritional status. Early detection of overweight and obesity in children provides a scientific basis for the prevention and control of overweight and obesity in children.
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Índice de Massa Corporal , Gráficos de Crescimento , Organização Mundial da Saúde , Humanos , Adolescente , Criança , China , Masculino , Feminino , Valores de Referência , Estatura , Peso CorporalRESUMO
The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation, cognition, reward, as well as maternal and reproductive behaviors. Dopamine is a neurotransmitter that binds to G-protein-coupled receptors. Dopamine also works together with other neurotransmitters and various neuropeptides to maintain the balance of synaptic functions. The dysfunction of the dopamine system leads to several conditions, including Parkinson's disease, Huntington's disease, major depression, schizophrenia, and drug addiction. The ventral tegmental area (VTA) has been identified as an important relay nucleus that modulates homeostatic plasticity in the midbrain dopamine system. Due to the complexity of synaptic transmissions and input-output connections in the VTA, the structure and function of this crucial brain region are still not fully understood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region.
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Transtorno Depressivo Maior , Neuropeptídeos , Humanos , Dopamina , Área Tegmentar Ventral , NeurotransmissoresRESUMO
Direct synthesis of dimethyl carbonate (DMC) from CO2 plays an important role in carbon neutrality, but its efficiency is still far from the practical application, due to the limited understanding of the reaction mechanism and rational design of efficient catalyst. Herein, abundant electron-enriched lattice oxygen species were introduced into CeO2 catalyst by constructing the point defects and crystal-terminated phases in the crystal reconstruction process. Benefitting from the acid-base properties modulated by the electron-enriched lattice oxygen, the optimized CeO2 catalyst exhibited a much higher DMC yield of 22.2 mmol g-1 than the reported metal-oxide-based catalysts at the similar conditions. Mechanistic investigations illustrated that the electron-enriched lattice oxygen can provide abundant sites for CO2 adsorption and activation, and was advantageous of the formation of the weakly adsorbed active methoxy species. These were facilitating to the coupling of methoxy and CO2 for the key *CH3OCOO intermediate formation. More importantly, the weakened adsorption of *CH3OCOO on the electron-enriched lattice oxygen can switch the rate-determining-step (RDS) of DMC synthesis from *CH3OCOO formation to *CH3OCOO dissociation, and lower the corresponding activation barriers, thus giving rise to a high performance. This work provides insights into the underlying reaction mechanism for DMC synthesis from CO2 and methanol and the design of highly efficient catalysts.
RESUMO
The majority of NMDA receptors (NMDARs) in the brain are composed of 2 GluN1 and 2 GluN2 subunits. The inclusion or exclusion of 1 N-terminal and 2 C-terminal domains of GluN1 results in 8 splicing variants that exhibit distinct temporal and spatial patterns of expression and functional properties. However, previous functional analyses of Grin1 variants have been done using heterologous expression and the in vivo function of Grin1 splicing is unknown. Here we show that N-terminal splicing of GluN1 has important functions in the maturation of excitatory synapses. The inclusion of exon 5 of Grin1 is up-regulated in several brain regions such as the thalamus and neocortex. We find that deletion of Grin1 exon 5 disrupts the developmental remodeling of NMDARs in thalamic neurons and the effect is distinct from that of Grin2a (GluN2A) deletion. Deletion of Grin2a or exon 5 of Grin1 alone partially attenuates the shortening of NMDAR-mediated excitatory postsynaptic currents (NMDAR-EPSCs) during early life, whereas deletion of both Grin2a and exon 5 of Grin1 completely abolishes the developmental change in NMDAR-EPSC decay time. Deletion of exon 5 of Grin1 leads to an overproduction of excitatory synapses in layer 5 pyramidal neurons in the cortex and increases seizure susceptibility in adult mice. Our findings demonstrate that N-terminal splicing of GluN1 has important functions in synaptic maturation and neuronal network excitability.
Assuntos
Processamento Alternativo/genética , Potenciais Pós-Sinápticos Excitadores/genética , Proteínas do Tecido Nervoso/genética , Células Piramidais/fisiologia , Receptores de N-Metil-D-Aspartato/genética , Convulsões/genética , Sinapses/genética , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Subunidades Proteicas/genética , Convulsões/fisiopatologiaRESUMO
OBJECTIVES: Acute lung injury (ALI) is a devastating lung disease characterized by uncontrolled pulmonary inflammation and oxidative stress. Currently, no effective therapeutic strategies are available for ALI and its prognosis remains poor. The present study aims to investigate the role and potential mechanism of microRNA-30d-5p (miR-30d-5p) in the progression of ALI. METHODS: Mice were intravenously treated with miR-30d-5p agomir, antagomir or their respective controls for 3 consecutive days and then were exposed to a single intratracheal injection of lipopolysaccharide (LPS) for 12 h at a dosage of 5 mg/kg to induce ALI. To inhibit adenosine monophosphate-activated protein kinase α (AMPKα) or phosphodiesterase 4 D (PDE4D), compound C (CpC) and rolipram were used. RESULTS: miR-30d-5p expression in the lungs was significantly inhibited by LPS treatment. miR-30d-5p agomir significantly alleviated, while miR-30d-5p antagomir aggravated pulmonary inflammation, oxidative damage, and dysfunction in ALI mice. Besides, we found that miR-30d-5p agomir ameliorated LPS-induced ALI via activating AMPKα and that the inhibition of AMPKα by CpC completely abolished these beneficial effects of miR-30d-5p agomir. Further findings validated that PDE4D downregulation was required for the activation of AMPKα by miR-30d-5p agomir. CONCLUSION: miR-30d-5p ameliorates LPS-induced ALI via activating AMPKα and it is a valuable therapeutic candidate in the treatment of ALI.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Lipopolissacarídeos/toxicidade , MicroRNAs/biossíntese , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Camundongos , MicroRNAs/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
Increasing evidence has validated the essential regulation of long non-coding RNAs (lncRNAs) in the biological process of tumours. LncRNA PXN-AS1 has been discovered to be as a tumour suppressor in pancreatic cancer; however, its function and mechanism remain greatly unknown in glioblastoma (GBM). Our present study indicated that PXN-AS1 was highly expressed in GBM tissues and cells. Besides, the knock-down of PXN-AS1 was closely associated with the inhibitory proliferation and inducing apoptosis of GBM cells. PXN-AS1 inhibition was also found to restrain GBM tumour growth. Importantly, SOX9 functioned as a transcription factor and activated PXN-AS1 expression, and overexpressed PXN-AS1 rescued the inhibitory role of down-regulated SOX9 in GBM cell growth. Subsequently, it was discovered that PXN-AS1 activated Wnt/ß-catenin pathway. DKK1 was widely known as an inhibitor gene of Wnt/ß-catenin pathway, and its expression was negatively associated with PXN-AS1 and SOX9. Interestingly, we found that PXN-AS1 could recruit EZH2 to mediate the H3K27me3 level of DKK1 promoter. Restoration experiments manifested that DKK1 knock-down counteracted PXN-AS1 depletion-mediated repression in GBM cell growth. All facts pointed out that PXN-AS1 might be of importance in exploring the therapeutic strategies of GBM.
Assuntos
Neoplasias Encefálicas/genética , Carcinogênese/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Glioblastoma/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , RNA Longo não Codificante/metabolismo , Fatores de Transcrição SOX9/metabolismo , Animais , Apoptose/genética , Sequência de Bases , Neoplasias Encefálicas/patologia , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Glioblastoma/patologia , Humanos , Masculino , Metilação , Camundongos Endogâmicos BALB C , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genéticaRESUMO
OBJECTIVE: Gastric polyps (GPs) are masses of cells that form on the lining inside stomach. The diagnosis and treatment of GPs are vital, since some cases may cause malignant. Endoscopic techniques have led to earlier detection of GPs, the incidence of GPs are projected to continue rising. The treatment of GPs and investigation are specific to the possible presentation, pathology, and malignant. This paper is to investigate risk factors related to GPs patients in China. MATERIALS AND METHODS: Total of 2048 patients who underwent gastrointestinal endoscopy from January 2014 to December 2014 were studied. Data collected included gender, age, education level, BMI, eating habits and other lifestyle behaviors. Data were assessed by both univariate and multiple logistic regression analyses. RESULTS AND DISCUSSION: Of these, 181 patients had GPs. The univariate statistical test found significant differences between age and education level ([Formula: see text]=92.87, p = .00, and[Formula: see text]=92.93, p = .00, respectively). Also, significant differences of the type of drinking water, regular eating habits, eating quickly, consumption of a high-salt, meat-based dietary, hard diet, hot food eating, watching television while meal, eating leftovers, vegetable/fruit intake, cigarette smoking and alcohol consumption were noticed (p < .05). The multiple logistic regression analysis showed that age, dietary habits, eating styles, eating hot food or leftovers and fruit intake were associated with the development of GPs. CONCLUSIONS: Age and unhealthy lifestyle behaviors such as irregular eating habits, eating quickly, hot food, leftovers meals and a lower intake of fruit were independent risk factors for GPs.
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Comportamento Alimentar , Comportamentos de Risco à Saúde , Pólipos , Gastropatias , Adulto , Idoso , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos/epidemiologia , Pólipos/etiologia , Pólipos/patologia , Fatores de Risco , Gastropatias/epidemiologia , Gastropatias/etiologia , Gastropatias/patologiaRESUMO
UNLABELLED: It is generally thought that neurons in the thalamic reticular nucleus (TRN) form GABAergic synapses with other TRN neurons and that these interconnections are important for the function of the TRN. However, the existence of such intrinsic connections is controversial. We combine two complementary approaches to examine intrinsic GABAergic connections in the TRN of the mouse. We find that optogenetic stimulation of TRN neurons and their axons evokes GABAergic IPSCs in TRN neurons in mice younger than 2 weeks of age but fails to do so after that age. Blocking synaptic release from TRN neurons through conditional deletion of vesicular GABA transporter has no effect on spontaneous IPSCs recorded in TRN neurons aged 2 weeks or older while dramatically reducing GABAergic transmission in thalamic relay neurons. These results demonstrate that except for a short period after birth, the TRN of the mouse lacks intrinsic GABAergic connections. SIGNIFICANCE STATEMENT: The thalamic reticular nucleus has a critical role in modulating information transfer from the thalamus to the cortex. It has been proposed that neurons in the thalamic reticular nucleus are interconnected through GABAergic synapses and that these connections serve important functions. Our results show that except for the first 2 weeks after birth, the thalamic reticular nucleus of the mouse lacks intrinsic GABAergic connections.
Assuntos
Neurônios GABAérgicos/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Rede Nervosa/fisiologia , Núcleos Talâmicos/citologia , Animais , Channelrhodopsins , Estimulação Elétrica , Feminino , Glutamato Descarboxilase/metabolismo , Técnicas In Vitro , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Rede Nervosa/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Parvalbuminas/genética , Técnicas de Patch-Clamp , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/genética , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismoRESUMO
Primary tumors of the central nervous system (CNS) are classified into over 100 different histological types. The most common type of glioma is derived from astrocytes, and the most invasive glioblastoma (WHO IV) accounts for over 57% of these tumors. Glioblastoma (GBM) is the most common and fatal tumor of the CNS, with strong growth and invasion capabilities, which makes complete surgical resection almost impossible. Despite various treatment methods such as surgery, radiotherapy, and chemotherapy, glioma is still an incurable disease, and the median survival time of patients with GBM is shorter than 15 months. Thus, molecular mechanisms of GBM characteristic invasive growth need to be clarified to improve the poor prognosis. Glutamate ionotropic receptor kainate type subunit 1 (GRIK1) is essential for brain function and is involved in many mental and neurological diseases. However, GRIK1's pathogenic roles and mechanisms in GBM are still unknown. Single-nuclear RNA sequencing of primary and recurrent GBM samples revealed that GRIK1 expression was noticeably higher in the recurrent samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of GRIK1 correlated with poor prognosis of GBM, consistent with The Cancer Genome Atlas database. Knockdown of GRIK1 retarded GBM cells growth, migration, and invasion. Taken together, these findings show that GRIK1 is a unique and important component in the development of GBM and may be considered as a biomarker for the diagnosis and therapy in individuals with GBM.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioblastoma/metabolismo , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Recidiva Local de Neoplasia/genética , Glioma/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Glioma remains one of the most challenging primary brain malignancies to treat. Long noncoding RNAs (lncRNAs) and mRNAs (mRNAs) are implicated in regulating the malignant phenotypes of cancers including glioma. This study aimed to elucidate the functions and mechanisms of lncRNA LINC00265 and mRNA IFI30 in the pathogenesis of glioma. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed the upregulated expression of LINC00265 and IFI30 in glioma cells compared to normal human astrocytes. Western blot (WB) quantified the associated proteins. Glioma stemness and epithelial-to-mesenchymal transition (EMT) were assessed by aldehyde dehydrogenase 1 (ALDH1) activity, sphere formation, and WB. Mechanistic and rescue assays evaluated the LINC00265/miR-let-7d-5p/IFI30/ZNF384/IGF2BP2 axis. The results demonstrated that LINC00265 and IFI30 were highly expressed in glioma cells, promoting stemness and EMT. ZNF384 was identified as a transcription factor that upregulates IFI30. Moreover, LINC00265 elevated ZNF384 by sponging miR-let-7d-5p and recruiting IGF2BP2. In conclusion, LINC00265 and IFI30 act as oncogenes in glioma by driving stemness and EMT, underscoring their potential as therapeutic targets.
Assuntos
Neoplasias Encefálicas , Glioma , MicroRNAs , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , RNA não Traduzido/genéticaRESUMO
The song of zebra finch is stable in life after it was learned successfully. Vocal plasticity is thought to be a motor exploration that can support continuous learning and optimization of performance. The activity of RA, an important pre-motor nucleus in songbird's brain, influences the song directly. This variability in adult birdsong is associated with the activity of NMDA receptors in LMAN-RA synapses, but the detailed mechanism is unclear. The control of gain refers to modulation of a neuron's responsiveness to input and is critically important for normal sensory, cognitive, and motor functions. Here, we observed the change of gain in RA projection neurons after exogenous NMDA was applied to activate NMDA receptors using the whole-cell current clamp recording. We found that NMDA substantially increased the slope (gain) of the firing rate-current relationship in RA projection neurons. The AMPA receptor-dependent excitability played a crucial role in the modulation of gain by NMDA. These results suggested that NMDA receptors may regulate the dynamics of RA projection neurons by input-output gain.
Assuntos
N-Metilaspartato/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Prosencéfalo/citologia , Prosencéfalo/fisiologia , Potenciais de Ação/fisiologia , Fatores Etários , Animais , Tentilhões , Masculino , N-Metilaspartato/metabolismo , Rede Nervosa/metabolismo , Vias Neurais/fisiologia , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/fisiologia , Aves Canoras , Vocalização Animal/fisiologiaRESUMO
Background: Some recent studies have reported the role of circular RNAs (circRNAs) in modulating the tumorigenesis of human malignancies. Nevertheless, the expression characteristics, biological functions, and regulatory mechanism of circ_0000189 in glioma are unclear. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression levels of circ_0000189, miR-192-5p, and ZEB2 mRNA in glioma tissues and cells. The association between the expression of circ_0000189 and the clinicopathological indicators and the features of magnetic resonance imaging (MRI) images of glioma patients were analyzed. Western blot was utilized to evaluate ZEB2 expression and epithelial-mesenchymal transition (EMT-)-related proteins (E-cadherin, N-cadherin, as well as Vimentin) in glioma cells. Cell proliferation was assessed employing cell counting kit-8 (CCK-8) and EdU experiments. Flow cytometry was used to detect the apoptotic rate of the cells. Cell migration and invasion were accessed employing Transwell assay. Moreover, dual luciferase reporter gene assay and RNA immunoprecipitation assay were employed to investigate the targeting relationship between miR-192-5p and circ_0000189, miR-192-5p, and ZEB2. Subcutaneous tumorigenesis experiment and lung metastasis experiment in nude mice were conducted to verify the regulatory function of circ_0000189 on the proliferation and metastasis of glioma cells in vivo. Results: circ_0000189 was markedly overexpressed in glioma tissues and cell lines. Its high expression was associated with poor clinical pathological indicators and adverse MRI signs. Gain-of-function experiments and loss-of-function experiments confirmed that circ_0000189 overexpression facilitated the proliferation and migration, as well as invasion of glioma cells, and suppressed apoptosis, and facilitated epithelial-mesenchymal transition (EMT) process. Compared to the control group, knocking down circ_0000189 suppressed the malignant phenotypes of glioma cells both in vivo and in vitro. Working as a competitive endogenous RNA, circ_0000189 directly targeted miR-192-5p, and repressed its expression, and circ_0000189 positively modulated ZEB2 expression indirectly via repressing miR-192-5p. Conclusion: circ_0000189 facilitates the progression of glioma by modulating miR-192-5p/ZEB2 axis.
Assuntos
Glioma , MicroRNAs , Animais , Caderinas , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células/genética , Glioma/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Mensageiro , Vimentina , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genéticaRESUMO
The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAcBLA) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAcPVT) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAcBLA neurons impairs reward seeking behavior, while silencing of NAcPVT or NAcPVTâLH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion.
Assuntos
Núcleo Accumbens , Alcaloides Opiáceos , Camundongos , Animais , Núcleo Accumbens/metabolismo , Recompensa , Área Tegmentar Ventral/fisiologia , Neurônios DopaminérgicosRESUMO
OBJECTIVES: Escherichia coli is a common pathogen causing invasive bacterial infections in neonates. In recent years, clinical antimicrobial susceptibility testing has demonstrated an increased rate of drug-resistant E. coli infections. This study aimed to analyse the resistance characteristics of E. coli against common antimicrobial agents, and perform multilocus sequence typing (MLST) in clinical strains of E. coli collected from Chinese neonates. METHODS: Culture-positive specimens of E. coli were collected from neonates in seven class A tertiary hospitals located in seven cities across different provinces in China between November 2019 and October 2020. E. coli isolated from these specimens were subjected to antimicrobial susceptibility testing (by broth microdilution method), extended-spectrum ß-lactamase (ESBL) detection, and MLST. RESULTS: A total of 223 E. coli strains were isolated, with an overall resistance rate of 87.4%, an ESBL-positive rate of 48.0%, and a multidrug resistance rate of 42.2%. Among the 20 antimicrobial agents tested, E. coli strains showed the highest resistance rates against cefotaxime (59.2%), trimethoprim/sulfamethoxazole (56.5%), doxycycline (39.9%), ciprofloxacin (36.8%), and aztreonam (31.0%). The resistance rates of E. coli strains isolated from children's hospitals against piperacillin/tazobactam, cefotaxime, ciprofloxacin, trimethoprim/sulfamethoxazole, and carbapenems, were significantly higher than those of strains isolated from maternity and child health hospitals. The primary E. coli multilocus sequence types were ST1193, ST95, ST73, ST410, and ST131. The ESBL production rates and multidrug resistance rates of ST1193, ST410, and ST131 were significantly higher than those of ST95 and ST73. Significantly, more strains of E. coli ST1193 and ST410 were isolated from children's hospitals than from maternity and child health hospitals. CONCLUSIONS: The rates of antimicrobial agent resistance in E. coli isolates from hospitalised neonates in China were high. The increased number of strains of E. coli ST1193 and ST410 was the reason for higher resistance rates to multiple antimicrobial agents in E. coli from children's hospitals compared with those from maternal and child health hospitals.
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Infecções por Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Aztreonam , Carbapenêmicos , Cefotaxima , Criança , Ciprofloxacina , Doxiciclina , Resistência a Medicamentos , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Recém-Nascido , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Piperacilina , Gravidez , Tazobactam , Centros de Atenção Terciária , Combinação Trimetoprima e Sulfametoxazol , beta-LactamasesRESUMO
Direct neuronal reprogramming of somatic cells into induced neurons (iNs) has been recently established as a promising approach to generating neuron cells. Previous studies have reported that the biophysical cues of the in vitro microenvironment are potent modulators in the cell fate decision; thus, the present study explores the effects of a customized pattern (named colloidal self-assembled patterns, cSAPs) on iN generation from human fibroblasts using small molecules. The result revealed that the cSAP, composed of binary particles in a hexagonal-close-packed (hcp) geometry, is capable of improving neuronal reprogramming efficiency and steering the ratio of the iN subtypes. Cells exhibited distinct cell morphology, upregulated cell adhesion markers (i.e., SDC1 and ITGAV), enriched signaling pathways (i.e., Hippo and Wnt), and chromatin remodeling on the cSAP compared to those on the control substrates. The result also showed that the iN subtype specification on cSAP was surface-dependent; therefore, the defined physicochemical cue from each cSAP is exclusive. Our findings show that direct cell reprogramming can be manipulated through specific biophysical cues on the artificial matrix, which is significant in cell transdifferentiation and lineage conversion.
RESUMO
The brain continuously receives diverse information about the external environment and changes in the homeostatic state. The attribution of salience determines which stimuli capture attention and, therefore, plays an essential role in regulating emotions and guiding behaviors. Although the thalamus is included in the salience network, the neural mechanism of how the thalamus contributes to salience processing remains elusive. In this mini-review, we will focus on recent advances in understanding the specific roles of distinct thalamic nuclei in salience processing. We will summarize the functional connections between thalamus nuclei and other key nodes in the salience network. We will highlight the convergence of neural circuits involved in reward and pain processing, arousal, and attention control in thalamic structures. We will discuss how thalamic activities represent salience information in associative learning and how thalamic neurons modulate adaptive behaviors. Lastly, we will review recent studies which investigate the contribution of thalamic dysfunction to aberrant salience processing in neuropsychiatric disorders, such as drug addiction, posttraumatic stress disorder (PTSD), and schizophrenia. Based on emerging evidence from both human and rodent research, we propose that the thalamus, different from previous studies that as an information relay, has a broader role in coordinating the cognitive process and regulating emotions.
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AIMS: The aim of this study was to develop a Diabetes Mellitus Treatment Adherence Scale (DMTAS) to fill the gap in the internationally accepted comprehensive scale. METHODS: An initial item pool for the Diabetes Mellitus Treatment Adherence Scale (DMTAS) was generated based on a review of the literature and an open-ended interview. An expert group screened this initial item pool using an item-level content validity index. Then, pilot testing with 116 participants was conducted. After removing redundant and cross-loading items by exploratory factor analysis, 630 subjects were recruited to evaluate the reliability and validity of DMTAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, convergent validity, and discriminant validity analysis. RESULTS: The final DMTAS consisted of 19 items and six dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 23.07%, 12.28%, 9.50%, 8.25%, 7.85%, and 5.80%, and all six factors explained 66.75% of the variance in the 19 items. The items' factor loadings were all above 0.6. The results of the confirmatory factor analysis indicated that adequate fit indices (χ2 value to degrees of freedom = 3.62; root mean square error of approximation = 0.06; goodness-of-fit index = 0.92) were achieved. The Cronbach's alpha coefficient was 0.79, test-retest reliability was 0.73, and split-half reliability was 0.75. CONCLUSIONS: The DMTAS showed good validity and reliability to measure the out-of-hospital treatment adherence in patients with diabetes mellitus.
Assuntos
Diabetes Mellitus/terapia , Psicometria/métodos , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Estudos de Validação como AssuntoRESUMO
Inflammation and oxidative stress have indispensable roles in the development of acute lung injury (ALI). MicroRNA (miRNA/miR)3515p was initially identified as a myogenesisassociated miRNA; however, its role in lipopolysaccharide (LPS)induced ALI remains unclear. The aim of the present study was to investigate the role and potential mechanisms of miR3515p in ALI. ALI was induced through a single intratracheal injection of LPS for 12 h, and miR3515p agomir, antagomir or their corresponding negative controls were injected into the tail vein before LPS stimulation. Compound C, 2',5'dideoxyadenosine and H89 were used to inhibit AMPactivated protein kinase (AMPK), adenylate cyclase and protein kinase A (PKA), respectively. miR3515p levels in the lungs were significantly increased in response to LPS injection. miR3515p antagomir alleviated, while miR3515p agomir aggravated LPSinduced oxidative stress and inflammation in the lungs. The present results also demonstrated that miR3515p antagomir attenuated LPSinduced ALI via activating AMPK, and that the cAMP/PKA axis was required for the activation of AMPK by the miR3515p antagomir. In conclusion, the present study indicated that miR3515p aggravated LPSinduced ALI via inhibiting AMPK, suggesting that targeting miR3515p may help to develop efficient therapeutic approaches for treating ALI.
Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Inflamação/genética , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/genéticaRESUMO
To improve the intershaft seal performance of the dual-rotor turbofan engine and extend the life of the intershaft seal, a compliant cylindrical aerodynamic intershaft seal structure is proposed, which avoids the problem of leakage increase after tooth wear of intershaft labyrinth seal. According to the proposed seal structure, the force condition of the floating seal ring is analyzed, and an aeroelastic coupling method for the floating seal ring eccentricity is presented. And the leakage characteristics, with different seal structures and operating conditions are calculated and compared when the two rotors are under homodromy/counter-rotating condition. The results show that, for the dual-rotor cylindrical hydrodynamic gas film seal, the hydrodynamic effect under homodromy condition is enhanced greatly while the hydrodynamic effect is significantly weakened under counter-rotating condition; the rotational direction of rotors, seal width, rotor circular precession eccentricity, rotational speed and rotor radius all have pronounced influence on the seal performance. For the application of hydrodynamic form of compliant cylindrical intershaft seal, the seal performance under homodromy condition is better than that under counter-rotating condition.