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BACKGROUND: Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients. METHODS: In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation. RESULTS: From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P < 0.01). In addition, another 30 patients were enrolled to evaluate the biofilm formation on catheters after catheter insertion in the patients' urethra (10 groups, 3 each). The results of scanning electron microscopy (SEM) showed that bacterial biofilm formed on the 5th day in the placebo group, while no bacterial biofilm formed on the 5th day in the JUC group. In addition, no adverse reactions were reported using JUC Spray Dressing. CONCLUSION: Continued indwelling urinary catheters for 5 days resulted in bacterial biofilm formation, and pretreatment of urethral catheters with JUC Spray Dressing can prevent bacterial biofilm formation by forming a physical antimicrobial film, and significantly reduce the incidence of CAUTI. This is the first report of a study on inhibiting bacterial biofilm formation on the catheters in CAUTI patients.
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Biopelículas , Infecciones Relacionadas con Catéteres , Infecciones Urinarias , Humanos , Biopelículas/crecimiento & desarrollo , Infecciones Urinarias/prevención & control , Infecciones Urinarias/microbiología , Infecciones Relacionadas con Catéteres/prevención & control , Infecciones Relacionadas con Catéteres/microbiología , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Catéteres Urinarios/efectos adversos , Catéteres Urinarios/microbiología , Cateterismo Urinario/efectos adversos , Anciano , Adulto , China , Vendajes , Infección Hospitalaria/prevención & controlRESUMEN
The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. The compounds exhibit modest activity against EGFR triple mutants (EGFR19del/T790M/C797S). Compound b demonstrated slightly improved inhibition activity against PC-9 Del19/T790M/C797S (IC50â¯=â¯496.3â¯nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.
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Smooth muscle cell (SMC) phenotypic modulation, primarily driven by PDGFRß signaling, is implicated in occlusive cardiovascular diseases. However, the promotive and restrictive regulation mechanism of PDGFRß and the role of protein tyrosine phosphatase non-receptor type 14 (PTPN14) in neointimal hyperplasia remain unclear. Our study observes a marked upregulation of PTPN14 in SMCs during neointimal hyperplasia. PTPN14 overexpression exacerbates neointimal hyperplasia in a phosphatase activity-dependent manner, while SMC-specific deficiency of PTPN14 mitigates this process in mice. RNA-seq indicates that PTPN14 deficiency inhibits PDGFRß signaling-induced SMC phenotypic modulation. Moreover, PTPN14 interacts with intracellular region of PDGFRß and mediates its dephosphorylation on Y692 site. Phosphorylation of PDGFRßY692 negatively regulates PDGFRß signaling activation. The levels of both PTPN14 and phospho-PDGFRßY692 are correlated with the degree of stenosis in human coronary arteries. Our findings suggest that PTPN14 serves as a critical modulator of SMCs, promoting neointimal hyperplasia. PDGFRßY692, dephosphorylated by PTPN14, acts as a self-inhibitory site for controlling PDGFRß activation.
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Hiperplasia , Miocitos del Músculo Liso , Neointima , Receptor beta de Factor de Crecimiento Derivado de Plaquetas , Transducción de Señal , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genética , Animales , Hiperplasia/metabolismo , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Humanos , Neointima/metabolismo , Neointima/patología , Ratones , Fosforilación , Masculino , Proteínas Tirosina Fosfatasas no Receptoras/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Vasos Coronarios/patología , Vasos Coronarios/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologíaRESUMEN
Mutations in fibrillin 1 (FBN1) is the main cause of Marfan syndrome (MFS) with thoracic aortic aneurysm (TAA) as the main complication. Activation of the complement system plays a key role in the formation of thoracic and abdominal aortic aneurysms. However, the role of the complement system in MFS-associated aortic aneurysms remains unclear. In this study, we observed increased levels of complement C3a and C5a in the plasma of MFS patients and mouse, and the increased deposition of the activated complement system product C3b/iC3b was also observed in the elastic fiber rupture zone of 3-month-old MFS mice. The expression of C3a receptor (C3aR) was increased in MFS aortas, and recombinant C3a promoted the expression of cytokines in macrophages. The administration of a C3aR antagonist (C3aRA) attenuated the development of thoracic aortic aneurysms in MFS mice. The increased inflammation response and matrix metalloproteinases activities were also attenuated by C3aRA treatment in MFS mice. Therefore, these findings indicate that the complement C3a/C3aR inhibition alleviates the formation of aortic aneurysm in Marfan syndrome mice.
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Adipoquinas , Aneurisma de la Aorta Torácica , Complemento C3a , Fibrilina-1 , Síndrome de Marfan , Receptores de Complemento , Animales , Femenino , Humanos , Masculino , Ratones , Adipoquinas/genética , Aorta Torácica/patología , Aneurisma de la Aorta Torácica/prevención & control , Aneurisma de la Aorta Torácica/etiología , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Complemento C3a/antagonistas & inhibidores , Complemento C3a/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fibrilina-1/genética , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Síndrome de Marfan/tratamiento farmacológico , Ratones Endogámicos C57BL , Receptores de Complemento/antagonistas & inhibidores , Receptores Acoplados a Proteínas G , Transducción de SeñalRESUMEN
Fractionated corn bran was processed to maximize ethanol production from starch, cellulose, and xylan. After various bench-scale experiments, an optimized process with dilute acid pretreatment (1.5 % w/w H2SO4) at 90 °C for 60 min was utilized followed by enzymatic hydrolysis using cellulase and hemicellulase for 48 hr. After simultaneous saccharification (regarding starch) and fermentation at 150 L using an engineered yeast, which consumes both glucose and xylose to make ethanol, the 86 % total sugar conversion yield was achieved, including conversions of 95 % for starch, 77 % for cellulose and 77 % for xylan. Also, an accurate mass balance was formulated for ethanol-producing carbohydrates including starch, cellulose, and xylan from feedstock to final ethanol. A highly efficient process of converting corn fiber to ethanol was successfully scaled up to 150 L.
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Etanol , Fermentación , Zea mays , Etanol/metabolismo , Zea mays/química , Hidrólisis , Saccharomyces cerevisiae/metabolismo , Almidón/química , Almidón/metabolismo , Celulosa/química , Biotecnología/métodos , XilanosRESUMEN
Background: Adolescents are vulnerable to mental disorders due to physiological, psychosocial, and cognitive changes during this critical developmental stage. Depression, in particular, can lead to high-risk behaviors such as self-injury (SI) and suicide. This study aims to estimate the pooled prevalence of SI behaviors among adolescents with depression. Materials and methods: We systematically searched databases including EMBASE, Scopus, PubMed, and Web of Sciences for relevant articles published on adolescents with depression from January 1, 2000, to January 1, 2024. The quality assessment of the studies was conducted using the Joanna Briggs Institute (JBI) criteria. The global prevalence of SI was calculated based on a random effects model using Stata software version 17. Results: Our analysis included 29 studies involving 12,934 adolescents. The lifetime prevalence of SI was 52% (95% Confidence Interval [CI]: 41-64), while the period prevalence was 57% (95% CI: 49-64). Notably, a significant relationship was observed between the prevalence of SI and the year of publication of articles (p = 0.002). Furthermore, publication bias was not significant for both lifetime prevalence (p = 0.281) and period prevalence (0.358). Conclusion: The prevalence of self-injurious behaviors in adolescents with depression is alarmingly high, with more than half of adolescents having engaged in these high-risk behaviors during their lifetime or within the last year. Given the associated risk of suicide, it is crucial to identify individuals at risk and provide timely interventions.
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Depresión , Conducta Autodestructiva , Humanos , Conducta Autodestructiva/epidemiología , Adolescente , Prevalencia , Depresión/epidemiología , Femenino , Masculino , Conducta del Adolescente/psicologíaRESUMEN
SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.
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COVID-19 , Senescencia Celular , Células Gigantes , Insuficiencia Cardíaca , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/virología , Animales , Células Gigantes/virología , Células Gigantes/metabolismo , Células Gigantes/patología , COVID-19/metabolismo , COVID-19/complicaciones , COVID-19/virología , COVID-19/patología , Humanos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Ratones , Vesículas Extracelulares/metabolismoRESUMEN
During the process of muscle regeneration post-injury in adults, muscle stem cells (MuSCs) function is facilitated by neighboring cells within the pro-regenerative niche. However, the precise mechanism triggering the initiation of signaling in the pro-regenerative niche remains unknown. Using single-cell RNA sequencing, 14 different muscle cells are comprehensively mapped during the initial stage following injury. Among these, macrophages and fibro-adipogenic progenitor cells (FAPs) exhibit the most pronounced intercellular communication with other cells. In the FAP subclusters, the study identifies an activated FAP phenotype that secretes chemokines, such as CXCL1, CXCL5, CCL2, and CCL7, to recruit macrophages after injury. Il1rl1, encoding the protein of the interleukin-33 (IL-33) receptor, is identified as a highly expressed signature surface marker of the FAP phenotype. Following muscle injury, autocrine IL-33, an alarmin, has been observed to activate quiescent FAPs toward this inflammatory phenotype through the IL1RL1-MAPK/NF-κB signaling pathway. Il1rl1 deficiency results in decreased chemokine expression and recruitment of macrophages, accompanied by impaired muscle regeneration. These findings elucidate a novel mechanism involving the IL-33/IL1RL1 signaling pathway in promoting the activation of FAPs and facilitating muscle regeneration, which can aid the development of therapeutic strategies for muscle-related disorders and injuries.
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Toxicity identification plays a key role in maintaining human health, as it can alert humans to the potential hazards caused by long-term exposure to a wide variety of chemical compounds. Experimental methods for determining toxicity are time-consuming, and costly, while computational methods offer an alternative for the early identification of toxicity. For example, some classical ML and DL methods, which demonstrate excellent performance in toxicity prediction. However, these methods also have some defects, such as over-reliance on artificial features and easy overfitting, etc. Proposing novel models with superior prediction performance is still an urgent task. In this study, we propose a motifs-level graph-based multi-view pretraining language model, called 3MTox, for toxicity identification. The 3MTox model uses Bidirectional Encoder Representations from Transformers (BERT) as the backbone framework, and a motif graph as input. The results of extensive experiments showed that our 3MTox model achieved state-of-the-art performance on toxicity benchmark datasets and outperformed the baseline models considered. In addition, the interpretability of the model ensures that the it can quickly and accurately identify toxicity sites in a given molecule, thereby contributing to the determination of the status of toxicity and associated analyses. We think that the 3MTox model is among the most promising tools that are currently available for toxicity identification.
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Modelos Químicos , AlgoritmosRESUMEN
Chrysanthemum (Chrysanthemum morifolium, ground-cover Chrysanthemums), one of the important garden flowers, has a high ornamental and economic value. However, its ornamental value is significantly diminished by the low temperature experienced in northeastern China. Here, metabolomics and transcriptomics were performed on three Chrysanthemum cultivars before and after a low temperature to investigate the dynamic metabolite changes and the molecular regulatory mechanisms. The results showed that 1324 annotated metabolites were detected, among which 327 were identified as flavonoids derived from Chrysanthemum. The accumulation of metabolites and gene expression related to the flavonoid biosynthesis pathway significantly increased in the three cultivars under the low temperature, indicating flavonoid metabolism actively participates in the Chrysanthemum cold response. Specifically, the content of cyanidin and pelargonidin derivatives and the expression of anthocyanin biosynthesis genes significantly increases in XHBF, providing a reasonable explanation for the change in petal color from white to purple under the low temperature. Six candidate UDP-glycosyltransferase genes involved in the glycosylation of flavonoids were identified through correlation networks and phylogenetic analysis. CmNAC1, CmbZIP3, and other transcription factors potentially regulating flavonoid metabolism and responding to low temperatures were discovered by correlation analysis and weighted gene co-expression network analysis (WGCNA). In conclusion, this study elucidated the specific response of flavonoids to low temperatures in Chrysanthemums, providing valuable insights and metabolic data for investigating cold tolerance.
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Chrysanthemum , Flavonoides , Regulación de la Expresión Génica de las Plantas , Metabolómica , Transcriptoma , Chrysanthemum/genética , Chrysanthemum/metabolismo , Flavonoides/metabolismo , Metabolómica/métodos , Frío , Perfilación de la Expresión Génica/métodos , Flores/metabolismo , Flores/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Antocianinas/metabolismo , Respuesta al Choque por Frío , Redes Reguladoras de Genes , MetabolomaRESUMEN
BACKGROUND: Currently, no normal ultrasound data of the fetuses during the 20-40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20-40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. METHODS: Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. RESULTS: 417 normal fetuses were enrolled. A significant (P < 0.05) negative correlation with the gestational age was detected in the peak systolic velocity/peak diastolic velocity (S/D), pulsatility index (PI) and resistance index (RI) of the umbilical artery (UA). A relatively stable relationship with the gestational age was detected in the fetal weight%, S/D, PI and RI of the middle cerebral artery (MCA), peak systolic velocity (PSV) and velocity time integral (VTI) of the intra-abdominal UA, fetal heart to chest ratio, mitral valve (MV)- and tricuspid valve (TV)-E/A peak flow velocity, aortic isthmic Z-score and displacement, distance between the brachiocephalic artery-left common carotid artery (BA-LCCA) and LCCA-left subclavian artery (LSA), Z-score of aorta, ascending aorta (AAO), pulmonary artery (PA), main pulmonary artery (MPA), and descending aorta (DAO). A significant (P < 0.05) positive correlation with the gestational age was detected in the fetal biological data, MCA PSV and VTI, free-UA PSV and VTI and cardio-thoracic ratio, cardiac parameters, ductus arteriosus (DA) and isthmus diameter, aortic parameters, PA and MPA diameter, MPA PSV and VTI, isthmus flow volume and velocity and PA flow volume, DA and BA parameters, and LCCA and LSA parameters (flow volume, PSV, and VTI). CONCLUSION: A certain correlation and distribution trend is detected in the ultrasound parameters of normal fetuses, and the ratios among different parameters remain relative stable. These findings can be used for determination of abnormal growth of the fetuses in prenatal ultrasound scan.
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Corazón Fetal , Edad Gestacional , Ultrasonografía Prenatal , Humanos , Ultrasonografía Prenatal/métodos , Femenino , Corazón Fetal/diagnóstico por imagen , Corazón Fetal/fisiopatología , Embarazo , Velocidad del Flujo Sanguíneo/fisiología , Valores de Referencia , Adulto , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/embriología , Reproducibilidad de los ResultadosRESUMEN
Quinoa is a nutrient-dense pseudocereal that has garnered global attention for its potential to bolster food security and nutrition. Despite its celebrated status, the detailed nutritional profiles of various quinoa varieties remain poorly understood, which poses a significant barrier to the strategic cultivation and utilization of quinoa's genetic diversity to combat malnutrition. The impetus for this research lies in the urgent need to identify superior quinoa strains that can be tailored to meet specific nutritional requirements and adapt to diverse agro-ecological zones. Our findings reveal substantial variation in nutrient content across different quinoa varieties, highlighting the variety ZLZX-8 as a particularly nutrient-rich strain with the highest levels of protein, fat, essential fatty acids, amino acids, and key minerals such as Mg, K, and Zn. Moreover, ZLZX-8's exceptional antioxidant capacity suggests it may have additional health benefits beyond its macronutrient profile. In contrast, ZLZX-7 stands out for its dietary fiber and phenolic content, which are critical for digestive health and disease prevention, respectively. Meanwhile, ZLZX-5, with its high starch content, could be better suited for energy production in dietary applications. Notably, the study also uncovers a correlation between grain color and nutrient profile, with colored quinoa varieties exhibiting superior fiber, inositol, phenolic content, and antioxidant activity compared to their white counterparts. This work lays the groundwork for an informed selection of quinoa varieties that can enhance dietary quality, support local and global food systems, and contribute to the fight against malnutrition.
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The stigma of social networks may be more noticeable in collectivist societies like China, but research in this area has largely been overlooked due to a lack of reliable measurement. To address this gap, this study tested the psychometric properties of the Chinese version of the Perceptions of Stigmatization by Others for Seeking Help (PSOSH) scale in the Chinese general population, and tested its invariance across gender and prior therapy experience. In a national online survey, 640 adults completed the PSOSH and conceptually related scales: Self-stigma of Seeking Help (SSOSH), Stigma of Seeking Professional Psychological Help Scale (SSPPH, i.e., public stigma) and Attitudes toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF). Confirmatory factor analysis supported the unidimensional structure of the original PSOSH. The Cronbach's α coefficient was 0.84 and the 3-week test-retest reliability of was 0.77. The PSOSH showed moderate correlations with the three conceptually related scales, supporting its concurrent validity. Importantly, the PSOSH significantly predicted self-stigma scores, even when considering demographic variables and public stigma, supporting its incremental validity. The scale also demonstrated scalar invariance across gender and across subgroups who had vs. did not have previous therapy experience, supporting comparisons of latent means across these groups. The PSOSH is a reliable and valid instrument for assessing social network stigmatization of professional help-seeking in Chinese community samples.
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Background: With increasing gaps between the rich and poor, potential risk factors for class conflict have attracted increasing attention from researchers. Although cognitive factors are known to be significant predictors of class-conflict behavior, limited attention has been paid to competence stereotypes of the upper class. When considering economic inequality, people pay more attention to competence stereotypes of the upper class, which may have adverse effects. This study aimed to investigate the relationship between competence stereotypes held by the lower class about the upper class and class conflict, and to test the mediating role of intergroup envy in this relationship and the moderating role of upward social mobility belief. Methods: Data were collected from a convenience sample from a comprehensive university in China. Based on scores on subjective and objective class scales, 284 lower-class college students (103 males and 181 females) aged 18-24 were selected to participate (both their subjective and objective scores were lower than 3 points). Their endorsement of upper-class competence stereotypes, intergroup envy, upward social mobility beliefs, and class conflict were measured using a well-validated self-report questionnaire. Results: The main data were analyzed using correlation analysis, the SPSS macro PROCESS (Model 7), and simple slope analysis. The results show a significant positive correlation between competence stereotypes held by lower-class college students toward the higher class and class conflict, and this connection was mediated by intergroup envy. Moreover, the indirect effect of intergroup envy on this link was moderated by upward social mobility beliefs; this effect was stronger for college students with lower upward social mobility beliefs. Conclusion: This study broadens our understanding of how and when competence stereotypes among the lower class concerning the upper class are related to class conflict. Researchers and policymakers should pay special attention to competence stereotypes of the upper class, especially intergroup envy and class conflict among lower-class individuals with lower levels of upward social mobility beliefs.
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INTRODUCTION AND OBJECTIVES: Hypothermia commonly occurs in trauma patients. Evidence-based practices for hypothermia prevention are not strictly followed by all medical staff in the emergency department. This study aimed to assess compliance with evidence-based practices regarding goal-oriented temperature management for severely traumatized children in a Chinese hospital. METHODS: This project used the JBI Evidence Implementation Framework to translate evidence into practice. The Integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework was used to identify barriers to compliance with best practices. A goal-oriented temperature management strategy for trauma patients was developed based on the identified barriers, along with a simulation training module, and the supply of warming materials. Field observation, review of medical records, and interviews with medical staff and patients were used to assess baseline and follow-up audit compliance with best practices. RESULTS: Twelve criteria were audited in the baseline and follow-up audits, with 11 and 37 trauma patients, respectively. In the follow-up audit, compliance with all criteria increased, with a reduction in shivering and cold discomfort scores. Except for two patients who died, hypothermia did not occur in any of the patients. CONCLUSIONS: The JBI Evidence Implementation Framework was used to successfully improve compliance with best practices. Future audits should be conducted to sustain the evidence-based behavior of all medical staff. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A234.
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Jinmao Jiedu granule is a Chinese medicine preparation consisting of Actinidia valvata Dunn, Salvia chinensis Benth, Iphigenia indica Kunth, and chicken gizzard. For many years, it has been employed in adjuvant therapy for cancer, especially liver cancer. However, the potential toxicity of the granule has not been reported. The present study aimed to assess the repeated-dose toxicity of orally administered Jinmao Jiedu granules for Sprague-Dawley (SD) rats. SD rats were orally administered Jinmao Jiedu granules at doses of 2.85, 5.70, and 11.40 g/kg in a 28-day subchronic toxicity study. No adverse clinical signs associated with treatment were noted throughout the experiment. There were no treatment-related toxicity alterations in body weight, hematology, clinical biochemistry, urinalysis, necropsy, and histopathology in rats compared with the control group. The No Observed Adverse Effect Level (NOAEL) of the Jinmao Jiedu granule was higher than 11.40 g/kg/day in rats.
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Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/toxicidad , Medicamentos Herbarios Chinos/administración & dosificación , Ratas , Masculino , Administración Oral , Femenino , Nivel sin Efectos Adversos Observados , Peso Corporal/efectos de los fármacos , Pruebas de Toxicidad Subcrónica , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Small molecule antioxidants can inhibit or retard oxidation reactions and protect against free radical damage to cells, thus playing a key role in food, cosmetics, pharmaceuticals, the environment, as well as materials. Experimentally driven antioxidant discovery is a major paradigm, and computationally assisted antioxidants are rarely reported. In this study, a functional-group-based alternating multitask self-supervised molecular representation learning method is proposed to simultaneously predict the antioxidant activities of small molecules for eight commonly used in vitro antioxidant assays. Extensive evaluation results reveal that compared with the baseline models, the multitask FG-BERT model achieves the best overall predictive performance, with the highest average F1, BA, ROC-AUC, and PRC-AUC values of 0.860, 0.880, 0.954, and 0.937 for the test sets, respectively. The Y-scrambling testing results further demonstrate that such a deep learning model was not constructed by accident and that it has reliable predictive capabilities. Additionally, the excellent interpretability of the multitask FG-BERT model makes it easy to identify key structural fragments/groups that contribute significantly to the antioxidant effect of a given molecule. Finally, an online antioxidant activity prediction platform called AOP (freely available at https://aop.idruglab.cn/) and its local version were developed based on the high-quality multitask FG-BERT model for experts and nonexperts in the field. We anticipate that it will contribute to the discovery of novel small-molecule antioxidants.
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Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.