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BACKGROUND: Poor mood states pose the most frequent mental health, creating a considerable burden to global public health. Sedentary behavior is an essential factor affecting mood states, however, previous measures to reduce sedentary time in Chinese young adults have focused only on increasing physical activity (PA). Sedentary, PA, and sleep make up a person's day from the standpoint of time use. It is not known whether reallocating sedentary time to different types of PA (e.g. daily PA and structured PA) or sleep during an epidemic has an effect on mood states. Therefore, this study aimed to examine the association between replacing sedentary time with different types of PA or sleep during the pandemic and the mood states of Chinese young adults and to further examine whether this association varies across sleep populations and units of replacement time. METHOD: 3,579 young adults aged 18 to 25 years living in China and self-isolating at home during the COVID-19 outbreak were invited to complete an online questionnaire between February from 23 to 29, 2020. Subjects' PA, sedentary time, and mood states were assessed using the International Physical Activity Questionnaire and the Chinese version of the Profile of Mood States, respectively. Participants also reported sleep duration and some sociodemographic characteristics. Participants were divided into short sleepers (< 7 h/d), normal sleepers (7-9 h/d), and long sleepers (> 9 h/d) based upon their reported sleep duration. Relevant data were analyzed using Pearson correlation analysis and isotemporal substitution model (ISM). RESULTS: Sedentary time was negatively associated with mood states in Chinese young adults during the pandemic (r = 0.140) and correlated strongest among short sleepers (r = 0.203). Substitution of sedentary time with structured PA was associated with good mood states (ß=-0.28, 95% CI: -0.49, -0.08). Additionally, substituting sedentary time with daily PA (e.g. occupational PA, household PA) was also associated with good mood states among normal sleepers (ß=-0.24, 95% CI: -0.46, -0.02). The substitution of sedentary time with sleep could bring mood benefits (ß=-0.35, 95% CI: -0.47, -0.23). This benefit was particularly prominent among short sleepers. Furthermore, for long sleepers, replacing sedentary time with sleep time also resulted in significant mood benefits (ß=-0.41, 95% CI: -0.69, -0.12). The longer the duration of replacing sedentary behavior with different types of PA or sleep, the greater the mood benefits. CONCLUSIONS: A reallocation of as little as 10 min/day of sedentary time to different types of PA or sleep is beneficial for the mood states of young adults. The longer the reallocation, the greater the benefit. Our results demonstrate a feasible and practical behavior alternative for improving mood states of Chinese young adults.
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Afeto , COVID-19 , Exercício Físico , Pandemias , Comportamento Sedentário , Sono , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Masculino , Adulto Jovem , Feminino , China/epidemiologia , Adulto , Sono/fisiologia , Exercício Físico/psicologia , Adolescente , Inquéritos e Questionários , SARS-CoV-2RESUMO
Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The sodium channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.
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Analgésicos , Canal de Sódio Disparado por Voltagem NAV1.8 , Sulfonamidas , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia , Sulfonamidas/síntese química , Animais , Humanos , Canal de Sódio Disparado por Voltagem NAV1.8/metabolismo , Relação Estrutura-Atividade , Benzenossulfonamidas , Estrutura Molecular , Camundongos , Relação Dose-Resposta a Droga , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Bloqueadores do Canal de Sódio Disparado por Voltagem/química , Bloqueadores do Canal de Sódio Disparado por Voltagem/síntese químicaRESUMO
BACKGROUND: Parental Educational Attainment and children's 24-h behaviors significantly influenced children's hyperactivity symptoms. This study aimed to examine the mediating role of children's 24-h behavior changes due to the COVID-19 pandemic between Parental Educational Attainment and children's hyperactivity index. It also aimed to investigate the associations between Children's Physical Activity, digital media use, sleep, and hyperactivity index between two clusters of Parental Educational Attainments. The goal was to provide targeted behavioral optimization recommendations for caregivers to reduce the risk of children's hyperactivity. METHODS: The study was a collaborative extension of the International iPreschooler Surveillance Study Among Asians and otheRs project and the Chinese Children and Adolescent Sports Health Promotion Action Project. The Parent-Surveillance of Digital Media in Childhood Questionnaire® and the Abbreviated Rating Scales from the Conners Parent Symptom Questionnaire were used to measure Parental Educational Attainment, children's behavior changes during the COVID-19 pandemic, and hyperactivity indexes. A total of 11,190 parents of 6-to-12-year-old children completed the online surveys in mainland China. A structural equation model was established by using Smart-PLS, and the linear regression model, and isotemporal substitution models were established by using a Compositional Data Analysis package with R program to achieve the research objectives. RESULTS: Changes in children's 24-h behaviors due to the COVID-19 pandemic had a significant mediation effect on the negative associations between Parental Educational Attainment and children's hyperactivity index (ß = 0.018, T = 4.521, p < 0.001) with a total effect (ß = -0.046, T = 4.521, p < 0.001) and a direct effect (ß = -0.064, T = 6.330, p < 0.001). Children's Digital Media use was significantly and negatively associated with hyperactivity index among all children. Reallocated time from digital media use to both sleep and physical activity decreased the hyperactivity index, and vice-versa. For parents without tertiary education (R2 = 0.09, p < 0.001), sleep was significantly and negatively associated with the hyperactivity index (ßilr-CSL = -0.06, p < 0.001); for parents with tertiary education (R2 = 0.07, p < 0.001), physical activity was significantly and negatively associated with the hyperactivity index (ßilr-CPA = -0.05, p < 0.001), and sleep was significantly and positively associated with the hyperactivity index (ßilr-CSL = 0.03, p < 0.001). A significant increase in the hyperactivity index was detected when physical activity time was reallocated to sleep, with a significant decrease in the opposite direction. CONCLUSIONS: Parental Educational Attainment and children's 24-h behaviors directly influenced children's hyperactivity index. However, a purposeful and targeted optimization of children's 24-h behaviors-namely, physical activity, digital media use, and sleep-could assist parents with different educational attainments to reduce their children's hyperactivity index and mitigate the risk of hyperactivity.
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Chronic pain is a serious problem that affects billions of people worldwide, but current analgesic drugs limit their use in chronic pain management due to their respective side effects. As a first-line clinical drug for chronic pain, COX-2 selective inhibitors can relieve mild to moderate pain, but they also have some problems. The most prominent one is that their analgesic intensity is not enough, and they cannot well meet the treatment needs of chronic pain. Therefore, there is an urgent need to develop COX-2 inhibitors with stronger analgesic intensity. In this article, we used virtual screening method to screen out the structurally novel COX-2 inhibitor for chronic pain management, and conducted a preliminary study on its mechanism of action using molecular dynamics simulation.
Assuntos
Dor Crônica , Inibidores de Ciclo-Oxigenase 2 , Humanos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Dor Crônica/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , FuranosRESUMO
The NaV1.8 channel, mainly found in the peripheral nervous system, is recognized as one of the key factors in chronic pain. The molecule VX-150 was initially promising in targeting this channel, but the phase II trials of VX-150 did not show expected pain relief results. By analyzing the interaction mode of VX-150 and NaV1.8, we developed two series with a total of 19 molecules and examined their binding affinity to NaV1.8 in vitro and analgesic effect in vivo. One compound, named 2j, stood out with notable activity against the NaV1.8 channel and showed effective pain relief in models of chronic inflammatory pain and neuropathic pain. Our research points to 2j as a strong contender for developing safer pain-relief treatments.
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Amidas , Neuralgia , Compostos Organotiofosforados , Humanos , Amidas/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Canal de Sódio Disparado por Voltagem NAV1.7 , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Piridonas/química , Piridonas/farmacologiaRESUMO
Carboxylesterase (CES), a main hydrolysis enzyme family in the human body, plays a crucial role in drug metabolism. Among them, CES1 and CES2 are the primary subtypes, and each exhibits distinct distribution and functions. However, convenient and non-invasive methods for distinguishing them and the real-time monitoring of CES2 are relatively rare, hindering the further understanding of physiological functions and underlying mechanisms. In this study, we have designed, synthesized, and evaluated the first selective bioluminescent probe (CBP 1) for CES2 with high sensitivity, high specificity and rapid reactivity. This probe offers a promising approach for the real-time detection of CES2 and its dynamic fluctuations both in vitro and in vivo.
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Hidrolases de Éster Carboxílico , Humanos , Hidrolases de Éster Carboxílico/metabolismoRESUMO
Agaricus bisporus is the most widely cultivated edible mushroom in the world with a only around three hundred years known history of cultivation. Therefore, it represents an ideal organism not only to investigate the natural evolutionary history but also the understanding on the evolution going back to the early era of domestication. In this study, we generated the mitochondrial genome sequences of 352 A. bisporus strains and 9 strains from 4 closely related species around the world. The population mitogenomic study revealed all A. bisporus strains can be divided into seven clades, and all domesticated cultivars present only in two of those clades. The molecular dating analysis showed this species origin in Europe on 4.6 Ma and we proposed the main dispersal routes. The detailed mitogenome structure studies showed that the insertion of the plasmid-derived dpo gene caused a long fragment (MIR) inversion, and the distributions of the fragments of dpo gene were strictly in correspondence with these seven clades. Our studies also showed A. bisporus population contains 30 intron distribution patterns (IDPs), while all cultivars contain only two IDPs, which clearly exhibit intron loss compared to the others. Either the loss occurred before or after domestication, that could suggest that the change facilitates their adaptation to the cultivated environment.
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Agaricus , Genoma Mitocondrial , Agaricus/genética , Europa (Continente)RESUMO
Studies show that the quality of life (QoL) of preschoolers is closely related to physical activity (PA), sedentary behaviour (SB), and sleep (SL). Yet many researchers looked at these 24-h movement behaviours as behaviours that are independent of one another when examining the association of QoL with these behaviours. The main purpose of the present study was to describe the temporal trends in PA, SB, and SL in preschoolers and the concomitant association with QoL of children. Annual cross-sectional data on QoL and 24-h movement behaviours of 8045 Singaporean preschoolers were collected from 2018 to 2021. Compositional analysis, linear regression, and isotemporal replacement approaches were used to examine changes in PA, SB, and SL from 2018-2021 and how these changes were associated with QoL. Temporal trends in movement behaviours showed that PA and SL decreased after 2020. During 2018-2021, the association of PA and QoL in preschoolers was characterised by a 'U' curve (ßPA-2018 = 3.06, p < 0.001; ßPA-2019 = 1.43, p < 0.05; ßPA-2020 = -0.43, p > 0.05; ßPA-2021 = 2.82, p < 0.001), while SL and QoL were characterised by an inverted 'U' curve (ßSL-2018 = -2.39, p < 0.001; ßSL-2019 = -0.27, p > 0.05; ßSL-2020 = 2.00, p < 0.01; ßSL-2021 = -0.21, p > 0.05). SB was significantly and negatively associated with QoL after 2020, with 2020 identified as the inflection point for the change in SB (ßSB-2018 = 0.67, p > 0.05; ßSB-2019 = -1.16, p > 0.05; ßSB-2020 = -1.56, p < 0.01; ßSB-2021 = -2.61, p < 0.01). Using a time re-allocation technique to treat the 2021 data, reallocating time from SB to PA or to SL predicted improvements in QoL of preschoolers (Pall < 0.05). The study provided useful information on the temporal trends in PA, SB, SL, and QoL of preschoolers over four years. Additionally, these data provided insights into how changes in QoL are predicted by changes in duration in the 24-h movement behaviours.
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Qualidade de Vida , Comportamento Sedentário , Criança , Humanos , Estudos Transversais , Exercício Físico , SonoRESUMO
OBJECTIVE: Diffusion-weighted imaging lesions (DWILs) are associated with unfavorable outcome in intracerebral hemorrhage (ICH). We proposed a novel predictive nomogram incorporating DWILs. METHODS: A total of 738 patients with primary ICH in a tertiary hospital were prospectively enrolled as a training cohort. DWILs were defined as remote focal hyperintensities on DWI corresponding to low intensities on apparent diffusion coefficient images and remote from the focal hematoma. The outcome of interest was modified Rankin Scale scores of 4-6 at 90 days after onset. Multivariate logistic regression was used to construct a nomogram. Model performance was tested in the training cohort and externally validated with respect to discrimination, calibration, and clinical usefulness in another institute. Additionally, the nomogram was compared with the ICH score in terms of predictive ability. RESULTS: Overall, 153 (20.73%) and 23 (15.54%) patients developed an unfavorable outcome in the training and validation cohorts, respectively. The multivariate analysis revealed that age, National Institutes of Health Stroke Scale (NIHSS) score, anemia, infratentorial location, presence of DWILs, and prior ICH were associated with unfavorable outcome. Our ANAID-ICH nomogram was constructed according to the aforementioned variables; the area under the receiver operating characteristic curve was 0.842 and 0.831 in the training and validation sets, respectively. With regard to the 90-day outcome, the nomogram showed a significantly higher predictive value than the ICH score in both cohorts. CONCLUSIONS: The ANAID-ICH nomogram comprising age, NIHSS score, anemia, infratentorial location, presence of DWILs, and prior ICH may facilitate the identification of patients at higher risk for an unfavorable outcome.
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Hemorragia Cerebral , Nomogramas , Humanos , Prognóstico , Hemorragia Cerebral/patologia , Hematoma , Curva ROC , Estudos RetrospectivosRESUMO
Agaricus bisporus is widely consumed on the world market. The easy browning of mushroom surface is one of the most intuitive factors affecting consumer purchase. A certain cognition on browning mechanism has been made after years of research. At present, people slow down the browning of mushrooms mainly by improving preservation methods. In addition, breeding is also a reliable way. In the production practice, we have identified some browning-resistant varieties, and we selected a browning-resistant variety to compare with an ordinary variety to reveal the resistance mechanism. Using transcriptomics and metabolomics, the differences in gene expression and metabolite levels were revealed, respectively. The results showed that differentially expressed genes (DEGs) like AbPPO4, AbPPO3 and AbPPO2 were differently expressed and these DEGs were involved in many pathways related to browning. The expression of AbPPO expression play an important role in the browning of A. bisporus and multiple PPO family members are involved in the regulation of browning. However, the resistance to browning cannot be judged only by the expression level of AbPPOs. For metabolomics, most of the different metabolites were organic acids. These organic acids had a higher level in anti-browning (BT) than easy-browning varieties (BS), although the profile was very heterogeneous. On the contrary, the content of trehalose in BS was significantly higher than that in BT. Higher organic acids decreased pH and further inhibited PPO activity. In addition, the BS had a higher content of trehalose, which might play roles in maintaining PPO activity. The difference of browning resistance between BS and BT is mainly due to the differential regulation mechanism of PPO.
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Agaricus , Transcriptoma , Agaricus/química , Agaricus/genética , Humanos , Metabolômica , Melhoramento Vegetal , TrealoseRESUMO
BACKGROUND: We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease. METHODS: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes. RESULTS: The median age of onset for symptoms was 60 (range: 33-73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein-Barr virus (EBV)-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2). CONCLUSIONS: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease.
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Infecções por Vírus Epstein-Barr , Doença de Hashimoto , Adulto , Idoso , Autoanticorpos , Moléculas de Adesão Celular Neuronais , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Agaricus bisporus is the most widely cultivated edible mushroom in the world. Strain quality has an important influence on the yield of A. bisporus, with strains that exhibit aging being a common problem during cultivation. However, little is known about the aging mechanisms of A. bisporus strain. In this study, the normal A. bisporus As2796 strain was compared to the aging A. bisporus As2796Y strain (which was previously discovered during cultivation). In the aging As2796Y mycelia, the mycelial growth rate and fruiting body yield were decreased and the chitin level and cell wall thickness were increased. Additionally, intracellular vacuoles increased, there was cytoplasmic shrinkage, and the sterol level which stabilizes the cell membrane decreased, which led to cytoplasmic outflow and the exudation of a large amount of yellow water from the mycelia. Additionally, there was increased electrolyte leakage. Furthermore, gas chromatography-mass spectrometry (GC/MS) was used to profile the metabolic changes in the aging As2796Y mycelia compared to the normal As2796 mycelia. A total of 52 differential metabolites were identified (75% were downregulated and 25% were upregulated in As2796Y). The reduction of many metabolites decreased the mycelial viability and the ability to maintain cell stability. Overall, this study is the first to report on the morphologic and metabolic changes in aged A. bisporus mycelia, which will aid future research on the mechanisms underlying A. bisporus mycelial aging.Key points⢠Aging of Agaricus bisporus strains will greatly reduce the fruiting body yield.⢠Aging of Agaricus bisporus strains can significantly change the cell structure of mycelia.⢠Many metabolites in the mycelium of aging spawn As2796Y significantly changed.
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Agaricus , Ascomicetos , Parede Celular , MicélioRESUMO
Aim: To document the expression and function of RNF126 in lung adenocarcinoma (LAD). Materials & methods: A total of 102 LAD patients were enrolled in this retrospective study. The mRNA and protein levels of RNF126 were tested via RT-qPCR and immunohistochemical staining, respectively. Univariate and multivariate analyses were conducted to exploring the clinical significance of RNF126 in the prognosis. Knockdown and overexpression strategies were used to validate the tumor-related roles of RNF126 both in vitro and in vivo. Results: RNF126 was highly expressed and was an independent predictor of a poor prognosis for LAD patients. We also revealed that RNF126 knockdown suppressed proliferation of LAD cells and xenografts. Conclusion: RNF126 is a potential survival predictor and therapeutic target for LAD.
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Adenocarcinoma/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Ubiquitina-Proteína Ligases/genética , Células A549 , Adenocarcinoma/metabolismo , Adenocarcinoma/terapia , Animais , Biomarcadores Tumorais/metabolismo , Movimento Celular/genética , Sobrevivência Celular/genética , Progressão da Doença , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Terapêutica com RNAi/métodos , Estudos Retrospectivos , Ubiquitina-Proteína Ligases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
OBJECTIVE: To determine the risk factors for delayed radiographic resolution in children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and explore the most suitable time for interventional bronchoscopy. METHODS: This retrospective study involved 142 children with RMPP who were admitted to our hospital from 1 January 2015 to 31 December 2017. They were divided into a common resolution group and a delayed resolution group based on their chest radiograph series. RESULTS: Among the 142 patients, 67 showed common resolution on chest radiographs and 75 showed delayed resolution. Independent risk factors for delayed resolution were a clinical course of ≥11.5 days before the performance of interventional bronchoscopy, mucus plug formation, corticosteroid resistance, and atelectasis. When bronchoscopy was performed before the disease had been present for <11.5 days, the length of hospitalization, total fever duration, and duration of time until disappearance of coughing were shorter than those in children who underwent bronchoscopy after the disease had been present for ≥11.5 days. CONCLUSIONS: Corticosteroid resistance, the time to interventional bronchoscopy, atelectasis, and mucus plug formation were associated with delayed resolution on chest radiographs. Performance of interventional bronchoscopy before the clinical course has reached 11.5 days may help alleviate clinical symptoms and improve radiographic resolution.
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Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Broncoscopia , Criança , Humanos , Pneumonia por Mycoplasma/diagnóstico por imagem , Pneumonia por Mycoplasma/tratamento farmacológico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Dyslipidemia contributes to the development of nephrolithiasis in adults; however its relationship to urolithiasis in children remains debatable, and will be clarified in the present work. METHODS: A case-control study was performed involving 58 pediatric patients diagnosed with upper urinary tract stones as well as 351 controls. Age, gender, body mass index (BMI), serum calcium, serum uric acid, blood glucose, blood lipids, and compositions of stones were compared. RESULTS: According to the univariate analysis, uric acid was higher (P < 0.01) but serum calcium lower in the stone group than the control (P < 0.05). As for the blood lipids, non-high-density lipoprotein cholesterol (non-HDL-c) was significantly higher in the stone group as compared to the control (P < 0.01), while total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol did not show statistical difference between the two groups. In the multivariate analysis, only non-HDL-c and serum uric acid were increased in the stone group (P = 0.003 and P = 0.008). In the stone compositions' analysis, serum uric acid and non-HDL-c were associated with percentage of uric acid and pure calcium oxalate stones, respectively. CONCLUSION: Non-high-density lipoprotein cholesterol may act as a lipid risk factor for urolithiasis in children.
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Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/complicações , Lipoproteínas/sangue , Cálculos Urinários/sangue , Cálculos Urinários/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Medição de RiscoRESUMO
To explore the influence of serum lactate dehydrogenase (LDH) level on remote diffusion-weighted imaging lesions (rDWILs) after spontaneous intracerebral hemorrhage (ICH). A consecutive cohort of 160 patients with spontaneous ICH who had brain MRI within 4 weeks of ICH onset were collected and analyzed retrospectively. rDWILs showed high signal on diffusion-weighted image (DWI) while low signal on apparent diffusion coefficient (ADC), and at least 20 mm away from the hemorrhage focus. The blood samples were obtained within 24 h after ICH onset from all patients. Lactate dehydrogenase (LDH) levels in blood were collected from serum biochemical tests. We use multivariate logistic regression analyses to investigate the association between serum LDH level and rDWILs after ICH. The average serum LDH level was 186.5 ± 35.6 U/L. And this level was higher in patients who presented rDWILs than in those without rDWILs. With the best cut-off value of 191 by using receiver operating characteristic (ROC) analysis, elevated LDH was associated with the presence of rDWILs independently (OR = 1.024, 95%CI = 1.011-1.037, P < 0.001) in the bivariate logistic regression analysis with adjustment for age, sex, previous ischemic stroke/TIA, smoker, SBP on admission, hematoma volume, and intraventricular hemorrhage (IVH). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of LDH ≥ 191 U/L for rDWILs were 70.4%, 72.2%, 33.9%, 94.2%, respectively. Our study suggests serum LDH level has a significant correlation with rDWILs after spontaneous ICH. Patients with higher serum LDH level in 24 h after ICH onset may be a useful predictor for rDWILs occurrence.
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Hemorragia Cerebral/sangue , Hemorragia Cerebral/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodos , L-Lactato Desidrogenase/sangue , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Agaricus blazei, a type of edible straw-rotting mushroom with somewhat sweet taste and fragrance of almonds, has attracted considerable scientific and practical attention. High-throughput Illumina PE150 and PacBio RSII platform were employed to generate a genomic sequence. De novo assembly generated 36 contigs with 38,686,133 bp in size, containing 10,119 putative predicted genes. Additionally, we also studied transcriptional regulation of the mycelia and the primordia for exploration of genes involved in fruiting body formation. Expression profiling analysis revealed that 2,164 genes were upregulated in mycelia and 1,557 in primordia. Functional enrichment showed that differentially expressed genes associated with response to stress, ribosome biogenesis, arginine biosynthesis, and steroid biosynthesis pathway were more active in fruiting body. The genome and transcriptome analysis of A. blazei provide valuable sequence resources and contribute to our understanding of genes related to the biosynthesis pathway of polysaccharide and benzaldehyde, as well as the fruiting body formation.
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Agaricus/genética , Agaricus/metabolismo , Perfilação da Expressão Gênica/métodos , Micélio/genética , Micélio/metabolismo , Sequência de Aminoácidos , DNA Fúngico , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação Fúngica da Expressão Gênica , Genes Fúngicos/genética , Polissacarídeos/metabolismo , Inquéritos e Questionários , Transcriptoma , beta-Glucanas/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is among the malignant tumors with highest mortality. The role of USP9X in the carcinogenesis of HCC has not yet been determined. In this study, USP9X was found significantly highly expressed in the intratumor tissues. Expression of intratumor USP9X was associated with tumor size and microvascular invasion while USP9X is independent risk factor of HCC disease-free survival and overall survival. In vitro studies revealed that knockdown of USP9X significantly inhibited the proliferation of HCC cells. Mechanically, USP9X promotes HCC cell proliferation by regulating the expression of beta-catenin. The results of the present study demonstrated that high expression of USP9X in intratumoral cells is associated with poor HCC prognosis, which may serve as a potential target for an adjuvant therapy.
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Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ubiquitina Tiolesterase/uso terapêutico , Ubiquitinas/uso terapêutico , beta Catenina/metabolismo , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Transfecção , Ubiquitina Tiolesterase/farmacologia , Ubiquitinas/farmacologiaRESUMO
AIM: To develop and validate a CpG-based classifier for preoperative discrimination of early and advanced-late stage colorectal cancer (CRC). METHODS: We identified an epigenetic signature based on methylation status of multiple CpG sites (CpGs) from 372 subjects in The Cancer Genome Atlas (TCGA) CRC cohort, and an external cohort (GSE48684) with 64 subjects by LASSO regression algorithm. A classifier derived from the methylation signature was used to establish a multivariable logistic regression model to predict the advanced-late stage of CRC. A nomogram was further developed by incorporating the classifier and some independent clinical risk factors, and its performance was evaluated by discrimination and calibration analysis. The prognostic value of the classifier was determined by survival analysis. Furthermore, the diagnostic performance of several CpGs in the methylation signature was evaluated. RESULTS: The eight-CpG-based methylation signature discriminated early stage from advanced-late stage CRC, with a satisfactory AUC of more than 0.700 in both the training and validation sets. This methylation classifier was identified as an independent predictor for CRC staging. The nomogram showed favorable predictive power for preoperative staging, and the C-index reached 0.817 (95% CI: 0.753-0.881) and 0.817 (95% CI: 0.721-0.913) in another training set and validation set respectively, with good calibration. The patients stratified in the high-risk group by the methylation classifier had significantly worse survival outcome than those in the low-risk group. Combination diagnosis utilizing only four of the eight specific CpGs performed well, even in CRC patients with low CEA level or at early stage. CONCLUSIONS: Our classifier is a valuable predictive indicator that can supplement established methods for more accurate preoperative staging and also provides prognostic information for CRC patients. Besides, the combination of multiple CpGs has a high value in the diagnosis of CRC.