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BACKGROUND: Severe neonatal hyperbilirubinemia could lead to kernicterus and neonatal death. This study aimed to analyze the association between single nucleotide polymorphisms in genes involved in bilirubin metabolism and the incidence of severe hyperbilirubinemia. METHODS: A total of 144 neonates with severe hyperbilirubinemia and 50 neonates without or mild hyperbilirubinemia were enrolled in 3 institutions between 2019 and 2020. Twelve polymorphisms of 5 genes (UGT1A1, SLCO1B1, SLCO1B3, BLVRA, and HMOX1) were analyzed by PCR amplification of genomic DNA. Genotyping was performed using an improved multiplex ligation detection reaction technique based on ligase detection reaction. RESULTS: The frequencies of the A allele in UGT1A1-rs4148323 and the C allele in SLCO1B3-rs2417940 in the severe hyperbilirubinemia group (30.2% and 90.6%, respectively) were significantly higher than those in the controls (30.2% vs.13.0%, 90.6% vs. 78.0%, respectively, both p < 0.05). Haplotype analysis showed the ACG haplotype of UGT1A1 were associated with an increased hyperbilirubinemia risk (OR 3.122, p = 0.001), whereas the GCG haplotype was related to a reduced risk (OR 0.523, p = 0.018). CONCLUSION: The frequencies of the A allele in rs4148323 and the C allele in rs2417940 are highly associated with the incidence of severe hyperbilirubinemia in Chinese Han neonates. TRIAL REGISTRATION: Trial registration number:ChiCTR1800020424; Date of registration:2018-12-29.
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Hiperbilirrubinemia Neonatal , Polimorfismo de Nucleótido Simple , Recién Nacido , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Alelos , Hiperbilirrubinemia Neonatal/genética , Glucuronosiltransferasa/genética , China/epidemiología , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/genética , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismoRESUMEN
OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.
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Inteligencia Artificial , Laringoscopía , Leucoplasia , Pliegues Vocales , Humanos , Pliegues Vocales/diagnóstico por imagen , Pliegues Vocales/patología , Laringoscopía/métodos , Masculino , Leucoplasia/diagnóstico , Leucoplasia/patología , Femenino , Persona de Mediana Edad , Anciano , Diagnóstico por Computador/métodos , Aprendizaje Automático , Diagnóstico Diferencial , Adulto , Algoritmos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/diagnóstico por imagenRESUMEN
Visible-light sensitive and bi-functionally favored CO2 reduction (CRR)/evolution (CER) photocathode catalysts that can get rid of the utilization of ultraviolet light and improve sluggish kinetics is demanded to conquer the current technique-barrier of traditional Li-CO2 battery. Here, a kind of redox molecular junction sp2c metal-covalent organic framework (i.e. Cu3-BTDE-COF) has been prepared through the connection between Cu3 and BTDE and can serve as efficient photocathode catalyst in light-assisted Li-CO2 battery. Cu3-BTDE-COF with redox-ability, visible-light-adsorption region, electron-hole separation ability and endows the photocathode with excellent round-trip efficiency (95.2 %) and an ultralow voltage hysteresis (0.18â V), outperforming the Schiff base COFs (i.e. Cu3-BTDA-COF and Cu3-DT-COF) and majority of the reported photocathode catalysts. Combined theoretical calculations with characterizations, Cu3-BTDE-COF with the integration of Cu3 centers, thiazole and cyano groups possess strong CO2 adsorption/activation and Li+ interaction/diffusion ability to boost the CRR/CER kinetics and related battery property.
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The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.
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Hiperbilirrubinemia Neonatal , Kernicterus , Recién Nacido , Humanos , Lactante , Estados Unidos , Niño , Hiperbilirrubinemia Neonatal/terapia , Bilirrubina , Hiperbilirrubinemia/terapia , Kernicterus/etiología , Kernicterus/prevención & control , Medición de Riesgo , Edad GestacionalRESUMEN
In December 2022, the American Academy of Pediatrics released a clinical guideline for point-of-care ultrasonography (POCUS) in the neonatal intensive care unit (NICU). The guideline outlined the development and current status of POCUS in the NICU, and summarized the key elements and implementation guidelines for successful implementation of POCUS in the NICU. This article provides an overview of the key points of the clinical guideline and analyzes the current status of POCUS in China, providing a reference for the implementation of POCUS in neonatal care in China.
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Unidades de Cuidado Intensivo Neonatal , Sistemas de Atención de Punto , Recién Nacido , Humanos , Estados Unidos , Niño , Ultrasonografía , ChinaRESUMEN
Carbon neutrality has been received extensive attention in the field of wastewater treatment. The optimal management of wastewater treatment plants (WWTPs) has great significance and urgency since the serious energy and materials waste. In this study, a full-view management method based on artificial neural networks (ANNs) for energy and material savings in WWTPs was established. More than 5 years of historical operating data from two typical plants (size 40,000 t/d and 10,000 t/d) located in Chongqing, China, were obtained, and public data in the service area of each plant were systematically collected from open channels. These abundant historical and public data were used to train two ANNs (GRA-CNN-LSTM model and PCA-BPNN model) to predict the inlets/outlets wastewater quality and quantity. The overall average prediction accuracy of inlets/outlets wastewater indicators are greater than 92.60% and 93.76%, respectively. By combining the two models, more appropriate process operation strategies can be obtained 2 weeks in advance, with more than 11.20% and 16.91% reduction of energy and material costs, respectively. This proposed method can provide full-view decision support for the optimal management of WWTPs and is also expected to support carbon emission control and carbon neutrality in the field of wastewater treatment.
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Aguas Residuales , Purificación del Agua , Carbono , Redes Neurales de la Computación , Eliminación de Residuos Líquidos/métodosRESUMEN
BACKGROUND: The platelet to lymphocyte ratio (PLR) is a novel biomarker to predict the prognosis of acute myocardial infarction (AMI) patients. AIM: The study aimed to evaluate the in-hospital outcomes of elderly patients with AMI and assessed the prognostic value of PLR on in-hospital adverse events. METHODS: A total of 1,001 patients were divided into an older group (n = 560) and a younger group (n = 441) based on age ≥ 60 years and successfully underwent primary percutaneous coronary intervention (PCI) within 12 h after presentation. Total white blood cells (WBCs), neutrophils, lymphocytes, and platelets counts were measured at admission. RESULTS: The incidence of heart rupture, acute heart failure, total adverse events, and death resulting from all events were significantly higher in patients ≥ 60 years than in younger patients, whereas the incidence of postoperative angina and reinfarction were similar between groups. Regarding blood counts, total white blood cells, neutrophils, lymphocytes, and platelets were lower in the older group than in the younger group. The platelet-to-lymphocyte ratio (PLR) was significantly higher in the older group. In receiver operating characteristic curve analysis, high PLR > 147 predicted adverse events (specificity 72% and sensitivity 63%). In multiple logistic regression analysis, age, hypertension, and PLR were identified as independent predictors of adverse events. CONCLUSIONS: The in-hospital outcomes of elderly patients with acute myocardial infarction were poor. PLR was an independent risk factor for in-hospital adverse events, which suggested that strong inflammation and prothrombotic status may contribute to the poor prognoses of elderly patients.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Anciano , Plaquetas , Humanos , Recuento de Linfocitos , Linfocitos , Neutrófilos , Recuento de Plaquetas , Pronóstico , Estudios RetrospectivosRESUMEN
Necrotizing enterocolitis (NEC) is a lethal gastrointestinal tract disease that occurs in premature infants. Adenosine receptor A2B (A2BR) regulates the inflammation cytokine secretion and immune cell infiltration in the colonic pathophysiology conditions. In the present study, we aim to determine the roles of A2BR in the development of NEC. A NEC rat model was established and treated with A2BR agonist-BAY60-6583 or A2BR antagonist-PSB1115. Animals in the control group were free from any interventions. Our results showed that the inhibition of A2BR PSB1115 improved intestinal injury and inflammation in newborn NEC rats. The expression levels of caspase-3 and the ratio of apoptotic cells were upregulated in NEC rats, and these indices were downregulated after treating with PSB1115 but further upregulated by BAY60-6583. Meanwhile, a similar trend was also witnessed in the changes of MPO activities and proinflammatory cytokines including IL-6, IFN-γ, and TNF-α. However, the anti-inflammatory cytokine IL-10 in the NECP group was significantly higher than that in the NEC and NECB groups (p < 0.05, respectively). Moreover, the expression of Ki67 was significantly increased in the NECP group as compared with those of the NEC and the NECB groups (p < 0.05, respectively). Collectively, our study suggested that the inhibition of A2BR attenuates NEC in the neonatal rat, at least partially through the modulation of inflammation and the induction of epithelial cell proliferation.
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Enterocolitis Necrotizante/tratamiento farmacológico , Enterocolitis Necrotizante/metabolismo , Receptor de Adenosina A2B/metabolismo , Agonistas del Receptor de Adenosina A2/uso terapéutico , Aminopiridinas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inmunohistoquímica , Interferón gamma/metabolismo , Interleucina-6/metabolismo , Masculino , Peroxidasa/metabolismo , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de Peso/efectos de los fármacosRESUMEN
MAIN CONCLUSION: The 5-leaf-stage rape seedlings were more insensitive to Pi starvation than that of the 3-leaf-stage plants, which may be attributed to the higher expression levels of ethylene signaling and sugar-metabolism genes in more mature seedlings. Traditional suppression subtractive hybridization (SSH) and RNA-Seq usually screen out thousands of differentially expressed genes. However, identification of the most important regulators has not been performed to date. Here, we employed two methods, namely, a two-round SSH and two-factor transcriptome analysis derived from the two-factor ANOVA that is commonly used in the statistics, to identify development-associated inorganic phosphate (Pi) starvation-induced genes in Brassica napus. Several of these genes are related to ethylene signaling (such as EIN3, ACO3, ACS8, ERF1A, and ERF2) or sugar metabolism (such as ACC2, GH3, LHCB1.4, XTH4, and SUS2). Although sucrose and ethylene may counteract each other at the biosynthetic level, they may also work synergistically on Pi-starvation-induced gene expression (such as PT1, PT2, RNS1, ACP5, AT4, and IPS1) and root acid phosphatase activation. Furthermore, three new transcription factors that are responsive to Pi starvation were identified: the zinc-finger MYND domain-containing protein 15 (MYND), a Magonashi family protein (MAGO), and a B-box zinc-finger family salt-tolerance protein. This study indicates that the two methods are highly efficient for functional gene screening in non-model organisms.
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Brassica napus/genética , Regulación de la Expresión Génica de las Plantas , Fosfatos/deficiencia , Transducción de Señal , Factores de Transcripción/genética , Transcriptoma , Análisis de Varianza , Brassica napus/crecimiento & desarrollo , Brassica napus/fisiología , Etilenos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Fosfatos/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Análisis de Secuencia de ARN , Técnicas de Hibridación Sustractiva , Factores de Transcripción/metabolismoRESUMEN
The phenomenon of delayed flowering after the application of nitrogen (N) fertilizer has long been known in agriculture, but the detailed molecular basis for this phenomenon is largely unclear. Here we used a modified method of suppression-subtractive hybridization to identify two key factors involved in N-regulated flowering time control in Arabidopsis thaliana, namely ferredoxin-NADP(+)-oxidoreductase and the blue-light receptor cryptochrome 1 (CRY1). The expression of both genes is induced by low N levels, and their loss-of-function mutants are insensitive to altered N concentration. Low-N conditions increase both NADPH/NADP(+) and ATP/AMP ratios, which in turn affect adenosine monophosphate-activated protein kinase (AMPK) activity. Moreover, our results show that the AMPK activity and nuclear localization are rhythmic and inversely correlated with nuclear CRY1 protein abundance. Low-N conditions increase but high-N conditions decrease the expression of several key components of the central oscillator (e.g., CCA1, LHY, and TOC1) and the flowering output genes (e.g., GI and CO). Taken together, our results suggest that N signaling functions as a modulator of nuclear CRY1 protein abundance, as well as the input signal for the central circadian clock to interfere with the normal flowering process.
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Proteínas de Arabidopsis/fisiología , Arabidopsis/fisiología , Criptocromos/fisiología , Ferredoxina-NADP Reductasa/metabolismo , Flores/fisiología , Nitrógeno/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Adenosina Trifosfato/metabolismo , Relojes Circadianos , Mutación , NADP/metabolismo , Técnicas de Hibridación SustractivaRESUMEN
Cadmium (Cd) is one of the hazardous environmental pollutants, and it can be harmful to human health through consumption of food-plants capable of bioaccumulating Cd. Therefore, lowering cadmium accumulation in plants is highly desirable. Here, a rice cultivar 'Qisanzhan' was studied using differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Fifty-six differentially expressed genes were found in the root tips of 4-leaf stage rice seedlings exposed to 4 and 12 h of 50 µmol/L Cd(NO3)2 in a nutrient solution using DDRT-PCR. Further validation using semi-quantitative RT-PCR showed that the expression patterns of 16 genes were consistent with those found in DDRT-PCR. These genes encode receptor-like protein kinase, pleiotropic drug resistance protein, aquaporin protein, plasma membrane ATPase, etc. The differentially genes identified here can be used to obtain a better understanding of the molecular mechanisms of Cd absorption and accumulation in plants.
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Cadmio/toxicidad , Regulación de la Expresión Génica/efectos de los fármacos , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Estrés Fisiológico/efectos de los fármacos , Perfilación de la Expresión Génica , Humanos , Oryza/genética , Proteínas de Plantas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Plantones/efectos de los fármacos , Plantones/metabolismo , Estrés Fisiológico/genéticaRESUMEN
Higher alcohols significantly influence the quality and flavor profiles of Chinese Baijiu. ILV1-encoded threonine deaminase, LEU1-encoded α-isopropylmalate dehydrogenase, and LEU2-encoded ß-isopropylmalate dehydrogenase are involved in the production of higher alcohols. In this work, ILV1, LEU1, and LEU2 deletions in α-type haploid, a-type haploid, and diploid Saccharomyces cerevisiae strains and ILV1, LEU1, and LEU2 single-allele deletions in diploid strains were constructed to examine the effects of these alterations on the metabolism of higher alcohols. Results showed that different genetic engineering strategies influence carbon flux and higher alcohol metabolism in different manners. Compared with the parental diploid strain, the ILV1 double-allele-deletion diploid mutant produced lower concentrations of n-propanol, active amyl alcohol, and 2-phenylethanol by 30.33, 35.58, and 11.71%, respectively. Moreover, the production of isobutanol and isoamyl alcohol increased by 326.39 and 57.6%, respectively. The LEU1 double-allele-deletion diploid mutant exhibited 14.09% increased n-propanol, 33.74% decreased isoamyl alcohol, and 13.21% decreased 2-phenylethanol production, which were similar to those of the LEU2 mutant. Furthermore, the LEU1 and LEU2 double-allele-deletion diploid mutants exhibited 41.72 and 52.18% increased isobutanol production, respectively. The effects of ILV1, LEU1, and LEU2 deletions on the production of higher alcohols by α-type and a-type haploid strains were similar to those of double-allele deletion in diploid strains. Moreover, the isobutanol production of the ILV1 single-allele-deletion diploid strain increased by 27.76%. Variations in higher alcohol production by the mutants are due to the carbon flux changes in yeast metabolism. This study could provide a valuable reference for further research on higher alcohol metabolism and future optimization of yeast strains for alcoholic beverages.
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Bebidas Alcohólicas/microbiología , Ciclo del Carbono/genética , Etanol/metabolismo , Microbiología de Alimentos/métodos , Hidroliasas/genética , Ingeniería Metabólica/métodos , Redes y Vías Metabólicas/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Treonina Deshidratasa/genética , 3-Isopropilmalato Deshidrogenasa/genética , 3-Isopropilmalato Deshidrogenasa/metabolismo , China , Fermentación , Eliminación de Gen , Humanos , Hidroliasas/metabolismo , Saccharomyces cerevisiae/enzimología , Proteínas de Saccharomyces cerevisiae/metabolismo , Treonina Deshidratasa/metabolismoRESUMEN
BACKGROUND: Although a lot of studies have shown serum uric acid (SUA) could be a marker of adverse prognosis in patients with acute myocardial infarction, the role of SUA as a risk factor for myocardial infarction is controversial. This study aimed to evaluate the association between hyperuricemia and short-term outcomes of elderly patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS: Six hundred and seventy-three elderly patients (≥ 60 years) were divided into high-SUA-level group (group H: N = 168) and low-SUA-level group (group L: N = 505) according to the SUA levels on admission. The following primary end points were evaluated within 30 days of AMI. The adverse events included postoperative angina pectoris, heart failure (Killip class ≥ II), and death. The comparisons were made between two groups in clinical and angiographic characteristics. RESULTS: The incidences of postoperative angina pectoris, heart failure, and the total adverse cardiovascular events were significantly higher in group H than in group L. But the incidence of death was similar between groups. In group H, heart rate (HR), systolic and diastolic blood pressure, SUA, homocysteine (HCY), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and creatine kinase myocardial band (CKMB) peak were clearly higher compared with those in group L. The results of logistic regression showed that the incidence of 30-day adverse events was closely related to TG, HCY and SUA. CONCLUSIONS: An elevated SUA level may be related to the short-term outcomes and seems to be an independent predictor of 30-day cardiovascular events in elderly patients with STEMI.
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Hiperuricemia/epidemiología , Infarto del Miocardio/mortalidad , Anciano , Biomarcadores/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Homocisteína/sangre , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Factores de Riesgo , Triglicéridos/sangreRESUMEN
BACKGROUND: Transcriptome and proteome analyses on fruit pulp from the blood orange 'Zaohong' and the navel orange 'twenty-first century' were performed to study Citrus sinensis quality-related molecular changes during consecutive developmental periods, including young fruit, fruit-coloring onset and fruit delayed-harvest for two months, during which fruit remained on the trees. RESULTS: The time-course analysis for the fruit developmental periods indicated a complex, dynamic gene expression pattern, with the numbers of differentially expressed genes (DEGs) between the two cultivars being 119, 426 and 904 at the three continuous stages tested during fruit development and ripening. The continuous increase in total soluble solids over the course of fruit development was correlated with up-regulated sucrose phosphate synthase (SPS) transcription levels in both cultivars. Eleven differentially expressed genes between the two cultivars involved in the flavonoid pathway were significantly enriched at the onset of the fruit-coloring stage when anthocyanins were detected in blood orange alone. Among 5185 proteins, 65 up-regulated and 29 down-regulated proteins were co-expressed with their cognate mRNAs with significant transcription and protein expression levels when the fruits from the two cultivars were compared at the fruit delayed-harvest stage. Additionally, important genes participating in the γ-aminobutyric acid (GABA) shunt were activated in blood orange at two significant expression levels in the fruit delayed-harvest stage. Thus, organic acids in fruit continuously decreased during this stage. CONCLUSIONS: This research was the first to provide a more comprehensive understanding of the differentially expressed genes involved in anthocyanin, sucrose and citrate metabolism at the transcriptome and proteome levels in C. sinensis, especially during the fruit delayed-harvest stage.
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Citrus sinensis/genética , Proteoma , Transcriptoma , Citrus sinensis/crecimiento & desarrollo , Citrus sinensis/metabolismo , Frutas/genética , Frutas/crecimiento & desarrollo , Frutas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Acetate esters and higher alcohols greatly influence the quality and flavor profiles of Chinese Baijiu (Chinese liquor). Various mutants have been constructed to investigate the interactions of ATF1 overexpression, IAH1 deletion, and BAT2 deletion on the production of acetate esters and higher alcohols. The results showed that the overexpression of ATF1 under the control of the PGK1 promoter with BAT2 and IAH1 double-gene deletion led to a higher production of acetate esters and a lower production of higher alcohols than the overexpression of ATF1 with IAH1 deletion or overexpression of ATF1 with BAT2 deletion. Moreover, deletion of IAH1 in ATF1 overexpression strains effectively increased the production of isobutyl acetate and isoamyl acetate by reducing the hydrolysis of acetate esters. The decline in the production of higher alcohol by the ATF1 overexpression strains with BAT2 deletion is due to the interaction of ATF1 overexpression and BAT2 deletion. Mutants with varying abilities of producing acetate esters and higher alcohols were developed by genetic engineering. These strains have great potential for industrial application.
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Bebidas Alcohólicas , Fermentación , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Acetatos/metabolismo , Alcoholes/metabolismo , Hidrolasas de Éster Carboxílico/genética , Ésteres/metabolismo , Eliminación de Gen , Ingeniería Genética , Pentanoles/metabolismo , Proteínas/genética , Proteínas/metabolismo , Saccharomyces cerevisiae/genética , Transaminasas/genéticaRESUMEN
BACKGROUND: The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a highly conserved long non-coding RNA (lncRNA) gene. Previous studies showed that Malat1 is abundantly expressed in many tissues and involves in promoting tumor growth and metastasis by modulating gene expression and target protein activities. However, little is known about the biological function and regulation mechanism of Malat1 in normal cell proliferation. RESULTS: In this study we conformed that Malat1 is highly conserved across vast evolutionary distances amongst 20 species of mammals in terms of sequence, and found that mouse Malat1 expresses in tissues of liver, kidney, lung, heart, testis, spleen and brain, but not in skeletal muscle. After treating erythroid myeloid lymphoid (EML) cells with All-trans Retinoic Acid (ATRA), we investigated the expression and regulation of Malat1 during hematopoietic differentiation, the results showed that ATRA significantly down regulates Malat1 expression during the differentiation of EML cells. Mouse LRH (Lin-Rhodamine(low) Hoechst(low)) cells that represent the early-stage progenitor cells show a high level of Malat1 expression, while LRB (Lin - Hoechst(Low) Rhodamine(Bright)) cells that represent the late-stage progenitor cells had no detectable expression of Malat1. Knockdown experiment showed that depletion of Malat1 inhibits the EML cell proliferation. Along with the down regulation of Malat1, the tumor suppressor gene p53 was up regulated during the differentiation. Interestingly, we found two p53 binding motifs with help of bioinformatic tools, and the following chromatin immunoprecipitation (ChIP) test conformed that p53 acts as a transcription repressor that binds to Malat1's promoter. Furthermore, we testified that p53 over expression in EML cells causes down regulation of Malat1. CONCLUSIONS: In summary, this study indicates Malat1 plays a critical role in maintaining the proliferation potential of early-stage hematopoietic cells. In addition to its biological function, the study also uncovers the regulation pattern of Malat1 expression mediated by p53 in hematopoietic differentiation. Our research shed a light on exploring the Malat1 biological role including therapeutic significance to inhibit the proliferation potential of malignant cells.
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Diferenciación Celular , Secuencia Conservada/genética , Evolución Molecular , Hematopoyesis , ARN Largo no Codificante/genética , Animales , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular , Regulación hacia Abajo/genética , Hematopoyesis/efectos de los fármacos , Humanos , Hígado/efectos de los fármacos , Hígado/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Ratones Endogámicos BALB C , Primates , Regiones Promotoras Genéticas/genética , Unión Proteica/efectos de los fármacos , ARN Largo no Codificante/metabolismo , Especificidad de la Especie , Transcripción Genética/efectos de los fármacos , Tretinoina/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.
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Genetic and physiological studies have revealed evidences for multiple signaling pathways by which the plastid exerts retrograde control over photosynthesis-associated-nuclear-genes. In this study we have examined the mechanisms of control of transcription by plastid signals, focusing on transcription factors. We have also further addressed the physical nature of plastid signals and the physiological role, in stress acclimation of this regulatory pathway. ABI4, a master Apetala 2 (AP2)-type transcription factor (TF), is targeted by multiple signalling pathways in plant cells, such as abscisic acid (ABA) signals, sugar signals and plastid signals derived from reactive oxygen species (ROS) and chlorophyll intermediates. ABI4 binds the promoter of target genes to prevent their transcription by competing with other competitive TFs. However, we found that once ABI4 bound the element (CCACGT), it may not be bound by other TFs, therefore making the signalling long-lasting. Downstream of ABI4, CBFA (CCAAT binding factor A) is a subunit of the HAP2/HAP3/HAP5 (Heme activator protein) trimeric transcription complex. CBFA however is a redundant HAP3 subunit. When emergency occurs (such as herbicide treatments or environmental stresses followed by ABA and ROS accumulation), the master transcription factor ABI4 down-regulates some TFs, like CBFA, and then some other TF subunits enter the transcription complex and transcriptional efficiency of stress-responsive genes (including the transcription co-factor CBP) is improved instantaneously. abi4, cbfA and cbp mutants showed weaker drought-tolerance after a herbicide norflurazon treatment, which indicated the physiological role of these key transcription factors.
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Ácido Abscísico/metabolismo , Arabidopsis/fisiología , Regulación de la Expresión Génica de las Plantas , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Adaptación Fisiológica , Arabidopsis/efectos de los fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sitios de Unión , Factor de Unión a CCAAT/genética , Factor de Unión a CCAAT/metabolismo , Regulación hacia Abajo , Sequías , Hemina/farmacología , Herbicidas/farmacología , Mutagénesis Insercional , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/genética , Hojas de la Planta/fisiología , Plantas Modificadas Genéticamente , Plastidios/fisiología , Regiones Promotoras Genéticas , Piridazinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Plantones/efectos de los fármacos , Plantones/genética , Plantones/fisiología , Estrés Fisiológico , Transactivadores , Factores de Transcripción/genéticaRESUMEN
BACKGROUND AND AIM: With the changes in diet structure and lifestyle, the incidence of fatty liver disease is increasing in China, especially in cities. The goal of the present study was to accurately determine the prevalence and risk factors of fatty liver disease in Beijing residents, China. METHODS: By using random multistage stratification and cluster sampling, residents aged > 20 years in Dongcheng District and Tongzhou District were recruited, and questionnaire survey, physical examination, detection of fasting glucose, blood lipids and liver biochemistry, and ultrasonography of the liver, gallbladder, and spleen were carried out. Database EpiData 3.0 was employed for data input, followed by statistical analysis with SPSS version 11.0. RESULTS: A total of 3762 residents were included in the present study including 2328 males and 1434 females with a mean age of 46.37 ± 14.28 years (range 20-92 years). Ultrasonography revealed fatty liver in 1486 residents with a prevalence of 39.5%. Moreover, non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease were found in 1177 (31.3%) and 309 (8.2%) residents, respectively. After adjustment of prevalence based on the age and gender constituents of Beijing residents, the standardized prevalence of overall fatty liver disease, NAFLD, and alcoholic fatty liver disease was 35.1%, 31.0%, and 4.1%, respectively. Binary logistic regression analysis revealed waist-to-hip ratio, diastolic pressure, fasting blood glucose, triglyceride, high-density lipoprotein cholesterol, and low density lipoprotein cholesterol were closely related to NAFLD. CONCLUSIONS: The Beijing residents have a high prevalence of fatty liver disease as much as 35.1%, which is characterized by NAFLD. Obesity, and glucose and lipid metabolism disorders are the main risk factors of fatty liver disease.
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Hígado Graso/epidemiología , Hígado Graso/etiología , Trastornos del Metabolismo de la Glucosa/complicaciones , Trastornos del Metabolismo de los Lípidos/complicaciones , Obesidad/complicaciones , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Glucemia , China/epidemiología , Dieta , Ayuno/sangre , Hígado Graso/diagnóstico por imagen , Hígado Graso Alcohólico/epidemiología , Femenino , Trastornos del Metabolismo de la Glucosa/sangre , Humanos , Estilo de Vida , Trastornos del Metabolismo de los Lípidos/sangre , Lípidos/sangre , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico , Prevalencia , Análisis de Regresión , Factores Sexuales , Encuestas y Cuestionarios , Ultrasonografía , Adulto JovenRESUMEN
This multicenter retrospective study was conducted to explore the effects of different courses and durations of invasive mechanical ventilation (MV) on the respiratory outcomes of very low birth weight infants (VLBWI) in China. The population for this study consisted of infants with birth weight less than 1500 g needing at least 1 course of invasive MV and admitted to the neonatal intensive care units affiliated with the Chinese Neonatal Network within 6 h of life from January 1st, 2019 to December 31st, 2020. Univariate and multivariate logistic regression analyses were performed to evaluate associations between invasive MV and respiratory outcomes. Adjusted odds ratios (ORs) were computed with the effects of potential confounders. (1) Among the 3183 VLBWs with a history of at least one course of invasive MV, 3155 (99.1%) met inclusion criteria and were assessed for the primary outcome. Most infants received one course (76.8%) and a shorter duration of invasive MV (62.16% with ventilation for 7 days or less). (2) In terms of the incidence of all bronchopulmonary dysplasia (BPD) (mild, moderate, and severe BPD), there were no significant differences between different invasive MV courses [For 2 courses, adjusted OR = 1.11 (0.88, 1.39); For 3 courses or more, adjusted OR = 1.07 (0.72, 1.60)]. But, with the duration of invasive MV prolonging, the OR of BPD increased [8-21 days, adjusted OR = 1.98 (1.59, 2.45); 22-35 days, adjusted OR = 4.37 (3.17, 6.03); ≥ 36 days, adjusted OR = 18.44 (10.98, 30.99)]. Concerning severe BPD, the OR increased not only with the course of invasive MV but also with the duration of invasive MV [For 2 courses, adjusted OR = 2.17 (1.07, 4.40); For 3 courses or more, adjusted OR = 2.59 (1.02, 6.61). 8-21 days, adjusted OR = 8.42 (3.22, 22.01); 22-35 days, adjusted OR = 27.82 (9.08, 85.22); ≥ 36 days, adjusted OR = 616.45 (195.79, > 999.999)]. (3) When the interaction effect between invasive MV duration and invasive MV course was considered, it was found that there were no interactive effects in BPD and severe BPD. Greater than or equal to three courses would increase the chance of severe BPD, death, and the requirement of home oxygen therapy. Compared with distinct courses of invasive MV, a longer duration of invasive MV (> 7 days) has a greater effect on the risk of BPD, severe BPD, death, and the requirement of home oxygen therapy.