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BACKGROUND AND AIMS: Incident heart failure (HF) among individuals with chronic kidney disease (CKD) incurs hospitalizations that burden patients and health care systems. There are few preventative therapies, and the Pooled Cohort equations to Prevent Heart Failure (PCP-HF) perform poorly in the setting of CKD. New drug targets and better risk stratification are urgently needed. METHODS: In this analysis of incident HF, SomaScan V4.0 (4638 proteins) was analysed in 2906 participants of the Chronic Renal Insufficiency Cohort (CRIC) with validation in the Atherosclerosis Risk in Communities (ARIC) study. The primary outcome was 14-year incident HF (390 events); secondary outcomes included 4-year HF (183 events), HF with reduced ejection fraction (137 events), and HF with preserved ejection fraction (165 events). Mendelian randomization and Gene Ontology were applied to examine causality and pathways. The performance of novel multi-protein risk models was compared to the PCP-HF risk score. RESULTS: Over 200 proteins were associated with incident HF after adjustment for estimated glomerular filtration rate at P < 1 × 10-5. After adjustment for covariates including N-terminal pro-B-type natriuretic peptide, 17 proteins remained associated at P < 1 × 10-5. Mendelian randomization associations were found for six proteins, of which four are druggable targets: FCG2B, IGFBP3, CAH6, and ASGR1. For the primary outcome, the C-statistic (95% confidence interval [CI]) for the 48-protein model in CRIC was 0.790 (0.735, 0.844) vs. 0.703 (0.644, 0.762) for the PCP-HF model (P = .001). C-statistic (95% CI) for the protein model in ARIC was 0.747 (0.707, 0.787). CONCLUSIONS: Large-scale proteomics reveal novel circulating protein biomarkers and potential mediators of HF in CKD. Proteomic risk models improve upon the PCP-HF risk score in this population.
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Insuficiencia Cardíaca , Proteómica , Insuficiencia Renal Crónica , Humanos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/metabolismo , Masculino , Femenino , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Persona de Mediana Edad , Medición de Riesgo/métodos , Incidencia , Anciano , Biomarcadores/metabolismo , Biomarcadores/sangre , Tasa de Filtración Glomerular/fisiología , Análisis de la Aleatorización MendelianaRESUMEN
BACKGROUND: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed. METHODS: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels. RESULTS: Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m2 of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P10], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m2; 95% CI, -0.29 to 2.54; P10, 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m2; 95% CI, -0.12 to 2.33; P10, 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m2; 95% CI, -1.43 to 1.92) and accurate (P10, 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C. CONCLUSIONS: The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).
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Creatinina/sangre , Cistatina C/sangre , Tasa de Filtración Glomerular , Grupos Raciales , Insuficiencia Renal Crónica/etnología , Adulto , Anciano , Algoritmos , Población Negra , Estudios Transversales , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/fisiopatología , Estados UnidosRESUMEN
The semiparametric Cox proportional hazards model, together with the partial likelihood principle, has been widely used to study the effects of potentially time-dependent covariates on a possibly censored event time. We propose a computationally efficient method for fitting the Cox model to big data involving millions of study subjects. Specifically, we perform maximum partial likelihood estimation on a small subset of the whole data and improve the initial estimator by incorporating the remaining data through one-step estimation with estimated efficient score functions. We show that the final estimator has the same asymptotic distribution as the conventional maximum partial likelihood estimator using the whole dataset but requires only a small fraction of computation time. We demonstrate the usefulness of the proposed method through extensive simulation studies and an application to the UK Biobank data.
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Macrodatos , Biobanco del Reino Unido , Humanos , Modelos de Riesgos Proporcionales , Probabilidad , Simulación por ComputadorRESUMEN
BACKGROUND: The current endpoints for therapeutic trials of hospitalized COVID-19 patients capture only part of the clinical course of a patient and have limited statistical power and robustness. METHODS: We specify proportional odds models for repeated measures of clinical status, with a common odds ratio of lower severity over time. We also specify the proportional hazards model for time to each level of improvement or deterioration of clinical status, with a common hazard ratio for overall treatment benefit. We apply these methods to Adaptive COVID-19 Treatment Trials. RESULTS: For remdesivir versus placebo, the common odds ratio was 1.48 (95% confidence interval (CI) = 1.23-1.79; p < 0.001), and the common hazard ratio was 1.27 (95% CI = 1.09-1.47; p = 0.002). For baricitinib plus remdesivir versus remdesivir alone, the common odds ratio was 1.32 (95% CI = 1.10-1.57; p = 0.002), and the common hazard ratio was 1.30 (95% CI = 1.13-1.49; p < 0.001). For interferon beta-1a plus remdesivir versus remdesivir alone, the common odds ratio was 0.95 (95% CI = 0.79-1.14; p = 0.56), and the common hazard ratio was 0.98 (95% CI = 0.85-1.12; p = 0.74). CONCLUSIONS: The proposed methods comprehensively characterize the treatment effects on the entire clinical course of a hospitalized COVID-19 patient.
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Adenosina Monofosfato , Alanina , Antivirales , Azetidinas , Tratamiento Farmacológico de COVID-19 , Hospitalización , Pirazoles , Sulfonamidas , Humanos , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Antivirales/uso terapéutico , Sulfonamidas/uso terapéutico , Azetidinas/uso terapéutico , Pirazoles/uso terapéutico , Resultado del Tratamiento , Purinas/uso terapéutico , SARS-CoV-2 , COVID-19 , Quimioterapia Combinada , Modelos de Riesgos Proporcionales , Oportunidad Relativa , Ensayos Clínicos Controlados Aleatorios como Asunto/métodosRESUMEN
AIMS: Chronic kidney disease (CKD) is widely prevalent and independently increases cardiovascular risk. Cardiovascular risk prediction tools derived in the general population perform poorly in CKD. Through large-scale proteomics discovery, this study aimed to create more accurate cardiovascular risk models. METHODS AND RESULTS: Elastic net regression was used to derive a proteomic risk model for incident cardiovascular risk in 2182 participants from the Chronic Renal Insufficiency Cohort. The model was then validated in 485 participants from the Atherosclerosis Risk in Communities cohort. All participants had CKD and no history of cardiovascular disease at study baseline when â¼5000 proteins were measured. The proteomic risk model, which consisted of 32 proteins, was superior to both the 2013 ACC/AHA Pooled Cohort Equation and a modified Pooled Cohort Equation that included estimated glomerular filtrate rate. The Chronic Renal Insufficiency Cohort internal validation set demonstrated annualized receiver operating characteristic area under the curve values from 1 to 10 years ranging between 0.84 and 0.89 for the protein and 0.70 and 0.73 for the clinical models. Similar findings were observed in the Atherosclerosis Risk in Communities validation cohort. For nearly half of the individual proteins independently associated with cardiovascular risk, Mendelian randomization suggested a causal link to cardiovascular events or risk factors. Pathway analyses revealed enrichment of proteins involved in immunologic function, vascular and neuronal development, and hepatic fibrosis. CONCLUSION: In two sizeable populations with CKD, a proteomic risk model for incident cardiovascular disease surpassed clinical risk models recommended in clinical practice, even after including estimated glomerular filtration rate. New biological insights may prioritize the development of therapeutic strategies for cardiovascular risk reduction in the CKD population.
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Aterosclerosis , Enfermedades Cardiovasculares , Insuficiencia Renal Crónica , Humanos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Proteómica , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Medición de Riesgo , Aterosclerosis/complicaciones , Tasa de Filtración Glomerular/fisiología , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: Bariatric surgery (BS) is an effective approach in treating obesity and ameliorating T2DM with obesity. Our previous studies demonstrated that duodenal-jejunal bypass (DJB) altered long non-coding RNAs (lncRNAs) in the gastrointestinal system, which is associated with modulation of lipid metabolism, and glycemic control through entero-pancreatic axis and gut-brain axis. The adipose non-coding RNA expression profile and the underlying competing endogenous RNA (ceRNA) regulatory network pattern post DJB needs further research and investigation. RESULTS: In this study, we compared the lncRNAs, circular RNAs (circRNAs) and messenger RNAs (mRNAs) expression in adipose tissues between the sham group and the DJB group. 2219 differentially expressed mRNAs (DEmRNAs), 722 differential expression of lncRNAs (DElncRNAs) and 425 differential expression of circRNAs (DEcircRNAs) were identified. GO terms and KEGG pathways analysis of the DEmRNAs implied that the dysregulated adipose mRNAs were associated with lipid, amino acid metabolism, insulin resistance, and extra cellular matrix (ECM)-related pathways. Moreover, via analyzing ceRNA regulatory networks of DElncRNAs and DEcircRNAs, 31 hub DE mRNAs, especially Mpp7, 9330159F19Rik, Trhde. Trdn, Sorbs2, were found on these pathways. CONCLUSIONS: The role of DJB in adipose tends to remodel ECM and improve the energy metabolism through the ceRNA regulatory network.
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MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Endógeno Competitivo , ARN Circular/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Obesidad , Redes Reguladoras de GenesRESUMEN
Betaine, a methyl donor, plays a crucial role in lipid metabolism. Previous studies have shown that appropriate betaine supplementation in a high-fat diet reduces triglycerides (TG) of serum and hepatopancreas in fish. However, the underlying mechanism remains unclear. This study examined whether betaine can enhance the secretion of very low-density lipoprotein (VLDL) and sought to identify the specific mechanisms through which this enhancement occurs. A lipid accumulation model was established in gibel carp and L8824 cells using a high-fat diet and oleic acid, respectively. Different doses of betaine (1, 4, and 16 g/kg in the diet; 400 µmol in cell culture) were administered, and measurements were taken for lipid deposition, gene expression of HNF4α, MTTP, and ApoB, as well as the regulation of Mttp and Apob promoters by HNF4α. The results showed that betaine supplementation mitigated lipid droplet accumulation, TG levels, and VLDL production induced by the high-fat diet in gibel carp hepatopancreas and L8824 cells. Moreover, betaine not only increased VLDL content in the cell culture supernatant but also reversed the inhibitory effects of the high-fat diet on protein expression of MTTP, ApoB, and HNF4α in both gibel carp hepatopancreas and L8824 cells. Additionally, HNF4α exhibits transactivating activity on the promoter of Mttp in gibel carp. These findings suggest that betaine supplementation exerts its effects through the HNF4α/MTTP/ApoB pathway, promoting the assembly and secretion of VLDL and effectively reducing lipid accumulation in the hepatopancreas of farmed gibel carp fed a high-fat diet.
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Shaerhu (SEH) coal is abundant in Xinjiang, China. The utilization of SEH suffers from severe ash deposition, slagging, and fouling problems due to its high-chlorine-alkaline characteristics. The co-combustion of high-alkaline coal and other type coals containing high Si/Al oxides has been proven to be a simple and effective method that will alleviate ash-related problems, but the risk of heavy metals (HMs) contamination in this process is nonnegligible. Hence, the volatilization rates and chemical speciation of Pb, Cu, and Zn in co-combusting SEH and a high Si/Al oxides coal, i.e., Yuanbaoshan (YBS) coal were investigated in this study. The results showed that the addition of SEH increased the volatilization rates of Pb, Cu, and Zn during the co-combustion at 800°C from 23.70%, 23.97%, and 34.98% to 82.31%, 30.01%, and 44.03%, respectively, and promoted the extractable state of Cu and Zn. In addition, the interaction between SEH and YBS inhibited the formation of the Pb residue state. SEM-EDS mapping results showed that compared to Zn and Cu, the signal intensity of Pb was extremely weak in regions where some of the Si and Al signal distributions overlap. The DFT results indicated that the O atoms of the metakaolin (Al2O3â 2SiO2) (001) surface were better bound to the Zn and Cu than Pb atoms after adsorption of the chlorinated HMs. These results contribute to a better understanding of the effects of high-alkaline coal blending combustion on Pb, Cu, and Zn migration and transformation.
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Cloro , Metales Pesados , Cloro/química , Plomo , Incineración , Ceniza del Carbón/química , Carbón Mineral , Metales Pesados/química , Óxidos , ZincRESUMEN
Developing various nanocomposite microwave absorbers is a crucial means to address the issue of electromagnetic pollution, but remains a challenge in satisfying broadband absorption at low thickness with dielectric loss materials. Herein, an ultra-broadband microwave metamaterial absorber (MMA) based on hollow carbon/MXene/Mo2 C (HCMM) is fabricated by a multi-scale design strategy. The microscopic 1D hierarchical microtube structure of HCMM contributes to break through the limit of thickness, exhibiting a strong reflection loss of -66.30 dB (99.99997 wave absorption) at the thinnest matching thickness of 1.0 mm. Meanwhile, the strongest reflection loss of -87.28 dB is reached at 1.4 mm, superior to most MXene-based and Mo2 C-based microwave absorbers. Then, the macroscopic 3D structural metasurface based on the HCMM is simulated, optimized, and finally manufactured. The as-prepared flexible HCMM-based MMA realizes an ultra-broadband effective absorption in the range of 3.7-40.0 GHz at a thickness of 5.0 mm, revealing its potential for practical application in the electromagnetic compatibility field.
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Cutaneous melanoma is a highly aggressive and malignant skin cancer, and its high recurrence rate and drug resistance increase the difficulty of treating advanced-stage patients. Studies have revealed that treatment via stimulation of alpha-1 adrenergic receptor (ADRA1) subtypes inhibits melanoma growth in mice. However, the associations between alpha-1D adrenergic receptor (ADRA1D) and cutaneous melanoma are poorly understood. Tissue specimens from 16 pairs of patients with a pigmented nevus and cutaneous melanoma were analyzed for ADRA1D expression using immunohistochemical staining. Western blotting and RT-qPCR were carried out in order to detect ADRA1D expression levels in melanoma cells and human epidermal melanocytes (HEMs), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) levels in HUVECS. A375 cells were transfected with a lentivirus overexpressing ADRA1D. Wound-healing, Transwell, and cell proliferation assays were utilized to identify the ADRA1D effect on the migration, invasion, and proliferation of the two groups of A375 cells in vitro. In order to evaluate the function of ADRA1D in vivo, a melanoma xenograft model was developed in immunodeficient mice. ADRA1D was low expressed in cutaneous melanoma tissues. Overexpression of ADRA1D inhibited the tubulation and migration of HUVECs in vitro. Overexpression of ADRA1D significantly decreased the HIF-1α and VEGF expression. Overexpression of ADRA1D inhibited the invasion and proliferation of A375 melanoma cells in vitro and reduced its angiogenesis in vivo. ADRA1D inhibits cutaneous melanoma growth and angiogenesis. It attenuates melanoma cell proliferation and invasion. Meanwhile, its anti-angiogenic effect is achieved by negatively regulating the HIF-1α/VEGF axis in melanoma tissue, thereby attenuating the growth of cutaneous melanoma and reducing the potential of metastasis.
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Melanoma , Neoplasias Cutáneas , Humanos , Ratones , Animales , Melanoma/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Neoplasias Cutáneas/genética , Neovascularización Patológica/genética , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Línea Celular Tumoral , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Melanoma Cutáneo MalignoRESUMEN
Environmental bisphenol F (BPF) has a cyclic endocrine disruption effect, seriously threatening animal and human health. It is frequently detected in environmental samples worldwide. For BPF remediation, biological methods are more environmentally friendly than physicochemical methods. White-rot fungi have been increasingly studied due to their potential capability to degrade environmental pollutants. Phanerochaete sordida YK-624 has been shown to degrade BPF by ligninolytic enzymes under ligninolytic conditions. In the present study, degradation of BPF under non-ligninolytic conditions (no production of ligninolytic enzymes) was investigated. Our results showed that BPF could be completely removed after 7-d incubation. A metabolite of BPF, 4,4'-dihydroxybenzophenone (DHBP) was identified by mass spectrometry and nuclear magnetic resonance, and DHBP was further degraded by this fungus to form 4-hydroxyphenyl 4-hydroxybenzoate (HPHB). DHBP and HPHB were the intermediate metabolites of BPF and would be further degraded by P. sordida YK-624. We also found that cytochrome P450s played an important role in BPF degradation. Additionally, transcriptomic analysis further supported the involvement of these enzymes in the action of BPF degradation. Therefore, BPF is transformed to DHBP and then to HPHB likely oxidized by cytochrome P450s in P. sordida YK-624. Furthermore, the toxicological studies demonstrated that the order of endocrine-disrupting activity for BPF and its metabolites was HPHB > BPF > DHBP. KEY POINTS: ⢠White-rot fungus Phanerochaete sordida YK-624 could degrade BPF. ⢠Cytochrome P450s were involved in the BPF degradation. ⢠The order of endocrine disrupting activity was: HPHB > BPF > DHBP.
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Compuestos de Bencidrilo , Phanerochaete , Fenoles , Compuestos de Bencidrilo/metabolismo , Biotransformación , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Phanerochaete/metabolismo , Fenoles/metabolismoRESUMEN
Artificial photoresponsive nanochannels have attracted widespread attention because of their capacity to achieve ion transport through light modulation. Herein, a biosensor for ultrasensitive miRNA-155 detection is devised based on molybdenum disulfide (MoS2 ) modified porous anodic aluminum oxide (AAO) photoresponsive nanochannels by atomic layer deposition (ALD). According to the optimized experimental results, when the cycles of ALD, the wavelength, and the power of the excitation laser are 70 cycles, 450 nm, and 80 mW, respectively, the most supreme photocurrent performance of these photoresponsive nanochannels are obtained. AAO nanochannels modified with MoS2 can work as a photoelectrochemical (PEC) biosensor by generating photoexcitation current; what is more, the high channel density in AAO can magnify the ion current signal response effectively by aggrandizing the flux of electroactive species. By using AAO photoresponsive nanochannels with an average diameter of 150 nm as PEC biosensor, an ultrasensitive detection record ranging from 0.01 fM to 0.01 nM with a detection limit of 3 aM can be achieved. This work not only proposes a simple method for manufacturing semiconductor photoresponsive nanochannels, but also exhibits great potential in the ultrasensitive detection of biomolecules.
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Técnicas Biosensibles , MicroARNs , Óxido de Aluminio , Disulfuros , Límite de Detección , Molibdeno , PorosidadRESUMEN
PURPOSE: Many outcomes derived from electronic health records (EHR) not only are imperfect but also may suffer from exposure-dependent differential misclassification due to variability in the quality and availability of EHR data across exposure groups. The objective of this study was to quantify the inflation of type I error rates that can result from differential outcome misclassification. METHODS: We used data on gold-standard and EHR-derived second breast cancers in a cohort of women with a prior breast cancer diagnosis from 1993 to 2006 enrolled in Kaiser Permanente Washington. We simulated an exposure that was independent of the true outcome status. A surrogate outcome was then simulated with varying sensitivity and specificity according to exposure status. We estimated the type I error rate for a test of association relating this exposure to the surrogate outcome, while varying outcome sensitivity and specificity in exposed individuals. RESULTS: Type I error rates were substantially inflated above the nominal level (5%) for even modest departures from nondifferential misclassification. Holding sensitivity in exposed and unexposed groups at 85%, a difference in specificity of 10% between the exposed and unexposed (80% vs 90%) resulted in a 36% type I error rate. Type I error was inflated more by differential specificity than sensitivity. CONCLUSIONS: Differential outcome misclassification may induce spurious findings. Researchers using EHR-derived outcomes should use misclassification-adjusted methods whenever possible or conduct sensitivity analyses to investigate the possibility of false-positive findings, especially for exposures that may be related to the accuracy of outcome ascertainment.
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Neoplasias de la Mama/epidemiología , Registros Electrónicos de Salud/estadística & datos numéricos , Recurrencia Local de Neoplasia/epidemiología , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Farmacoepidemiología/estadística & datos numéricos , Anciano , Sesgo , Estudios de Cohortes , Simulación por Computador , Exactitud de los Datos , Interpretación Estadística de Datos , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Evaluación de Resultado en la Atención de Salud/métodos , Farmacoepidemiología/métodos , Sensibilidad y Especificidad , Washingtón/epidemiologíaRESUMEN
Plant shoot branching is pivotal for developmental plasticity and crop yield. The formation of branch meristems is regulated by several key transcription factors including REGULATOR OF AXILLARY MERISTEMS1 (RAX1), RAX2, and RAX3. However, the regulatory network of shoot branching is still largely unknown. Here, we report the identification of EXCESSIVE BRANCHES1 (EXB1), which affects axillary meristem (AM) initiation and bud activity. Overexpression of EXB1 in the gain-of-function mutant exb1-D leads to severe bushy and dwarf phenotypes, which result from excessive AM initiation and elevated bud activities. EXB1 encodes the WRKY transcription factor WRKY71, which has demonstrated transactivation activities. Disruption of WRKY71/EXB1 by chimeric repressor silencing technology leads to fewer branches, indicating that EXB1 plays important roles in the control of shoot branching. We demonstrate that EXB1 controls AM initiation by positively regulating the transcription of RAX1, RAX2, and RAX3. Disruption of the RAX genes partially rescues the branching phenotype caused by EXB1 overexpression. We further show that EXB1 also regulates auxin homeostasis in control of shoot branching. Our data demonstrate that EXB1 plays pivotal roles in shoot branching by regulating both transcription of RAX genes and auxin pathways.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Brotes de la Planta/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Proteínas de Arabidopsis/genética , Núcleo Celular/metabolismo , Silenciador del Gen , Homeostasis , Ácidos Indolacéticos/metabolismo , Meristema/metabolismo , Modelos Biológicos , Mutación/genética , Fenotipo , Hojas de la Planta/metabolismo , Brotes de la Planta/genética , Brotes de la Planta/ultraestructura , Proteínas Represoras/metabolismo , Factores de Transcripción/genética , Activación Transcripcional/genéticaRESUMEN
BACKGROUND: The white-rot fungus Phlebia sp. MG-60 shows valuable properties such as high ethanol yield from several lignocellulosic materials, although white-rot fungi commonly degrade woody components to CO2 and H2O. In order to identify genes involved in ethanol production by Phlebia sp. MG-60, we compared genes differentially expressed by the ethanol producing fungus Phlebia sp. MG-60 and the model white-rot fungus Phanerochaete chrysosporium under ethanol fermenting and non-fermenting conditions using next-generation sequencing technologies. RESULTS: mRNAs from mycelia of Phlebia sp. MG-60 and P. chrysosporium under fermenting and non-fermenting conditions were sequenced using the MiSeq system. To detect differentially expressed genes, expression levels were measured in fragments per kilobase of exon per million mapped reads (FPKM). Differentially expressed genes were annotated using BLAST searches, Gene Ontology classifications, and KEGG pathway analysis. Functional analyses of differentially expressed genes revealed that genes involved in glucose uptake, glycolysis, and ethanol synthesis were widely upregulated in Phlebia sp. MG-60 under fermenting conditions. CONCLUSIONS: In this study, we provided novel transcriptomic information on Phlebia sp. MG-60, and these RNA-seq data were useful in targeting genes involved in ethanol production for future genetic engineering.
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Etanol/metabolismo , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Polyporales/genética , Madera/metabolismo , Biomasa , Metabolismo de los Hidratos de Carbono , Fermentación , Proteínas Fúngicas/metabolismo , Perfilación de la Expresión Génica , Ontología de Genes , Glucosa/metabolismo , Secuenciación de Nucleótidos de Alto Rendimiento , Anotación de Secuencia Molecular , Phanerochaete/genética , Phanerochaete/metabolismo , Polyporales/metabolismoRESUMEN
Glyoxal oxidase (GLOX) is a source of the extracellular H2O2 required for the oxidation reactions catalyzed by the ligninolytic peroxidases. In the present study, the GLOX-encoding gene (glx) of Phanerochaete chrysosporium was cloned, and bee2 promoter of P. sordida YK-624 was used to drive the expression of glx. The expression plasmid was transformed into a P. sordida YK-624 uracil auxotrophic mutant (strain UV-64), and 16 clones were obtained as GLOX-introducing transformants. These transformants showed higher GLOX activities than wild-type P. sordida YK-624 and control transformants harboring marker plasmid. RT-PCR analysis indicated that the increased GLOX activity was associated with elevated recombinant glx expression. Moreover, these transformants showed higher ligninolytic activity than control transformants. These results suggest that the ligninolytic properties of white-rot fungi can be improved by recombinant expression of glx.
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Oxidorreductasas de Alcohol/metabolismo , Proteínas Fúngicas/metabolismo , Lignina/metabolismo , Phanerochaete/genética , Oxidorreductasas de Alcohol/genética , Células Clonales , Clonación Molecular , Proteínas Fúngicas/genética , Expresión Génica , Lignina/química , Phanerochaete/enzimología , Plásmidos/química , Plásmidos/metabolismo , Regiones Promotoras Genéticas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transformación BacterianaRESUMEN
Single nucleus ATAC-seq (snATAC-seq) experimental designs have become increasingly complex with multiple factors that might affect chromatin accessibility, including genotype, cell type, tissue of origin, sample location, batch, etc., whose compound effects are difficult to test by existing methods. In addition, current snATAC-seq data present statistical difficulties due to their sparsity and variations in individual sequence capture. To address these problems, we present a zero-adjusted statistical model, Probability model of Accessible Chromatin of Single cells (PACS), that can allow complex hypothesis testing of factors that affect accessibility while accounting for sparse and incomplete data. For differential accessibility analysis, PACS controls the false positive rate and achieves on average a 17% to 122% higher power than existing tools. We demonstrate the effectiveness of PACS through several analysis tasks including supervised cell type annotation, compound hypothesis testing, batch effect correction, and spatiotemporal modeling. We apply PACS to several datasets from a variety of tissues and show its ability to reveal previously undiscovered insights in snATAC-seq data.
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Fe(II)-induced phase transformations of secondary iron minerals have attracted considerable attention due to their influence on antimony (Sb) mobility. However, Fe(II)-induced natural multicomponent secondary iron mineral (nmSIM) transformations and the corresponding repartitioning of Sb on nmSIM under acidic conditions upon Fe(II) exposure have not been systematically examined. Herein, we investigated the effect of Fe(II) on nmSIM mineralogy and Sb mobility in Sb(V)-bearing nmSIM at pH 3.8 and 5.6 at various Fe(II) concentrations over 15 d. The Sb(V)-bearing nmSIM phase transformation occurred under both strongly and weakly acidic conditions without Fe(II) exposure, while the presence of Fe(II) significantly intensified the transformation, and substantial amounts of intermediary minerals, including jarosite, ferrihydrite, lepidocrocite and fougerite, formed during the initial reaction stage, especially at pH 5.6. X-ray diffraction (XRD) analyses confirmed that goethite and hematite were the primary final-stage transformation products of Sb(V)-bearing nmSIM, regardless of Fe(II) exposure. Throughout the Sb(V)-bearing nmSIM transformation at pH 3.8, Sb release was inversely related to the Fe(II) concentration in the initial stage, and after maximum release was achieved, Sb was gradually repartitioned onto the nmSIM. No Sb repartitioning occurred in the absence of Fe(II) at pH 5.6, but the introduction of Fe(II) suppressed Sb release and improved Sb repartitioning on nmSIM. This transformation was conducive to Sb reimmobilization on Sb(V)-bearing nmSIM due to the structural incorporation of Sb into the highly crystalline goethite and hematite generated by the Sb(V)-bearing nmSIM transformation, and no reduction of Sb(V) occurred. These results imply that Fe(II) can trigger mineralogical changes in Sb(V)-bearing nmSIM and have important impacts on Sb partitioning under acidic conditions. These new insights are essential for assessing the mobility and availability of Sb in acid mine drainage areas.
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Flexible sensors and actuators are the basis for realizing the Internet of Everything. This study identifies specific interfacial polarization and filler dispersion challenges in flexible sensors. A novel sandwich-structured flexible sensor with polydimethylsiloxane (PDMS)-filled Nb2CTx as the interlayer and poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)]-filled barium titanate (BTO) as the upper and lower layers was designed and fabricated. The thickness of the interlayer was optimized to be 6.2 µm, resulting in an ultrahigh sensitivity of 16.05 V/N and ultrashort response time of 626 µs. The interlayer achieved an oriented arrangement of the dipoles in the upper and lower piezoelectric films through interfacial polarization, enhancing the piezoelectric output and sensitivity. The proposed mechanism was confirmed by the dielectric properties, local piezoelectric response, cross-sectional potential simulation, and interfacial electrical calculations. Additionally, the sensor effectively distinguishes various body movements, facial micro-expressions, and throat vibrations during vocalization, and can be applied to ultrahigh-sensitive self-powered flexible piezoelectric pressure sensors.
RESUMEN
Dissolved organic matter (DOM), a ubiquitous and active ingredient, is extensively involved in the transformation and migration of environmental pollutants in aquatic ecosystems. However, its chemical composition in acid mine drainage (AMD)-impacted rivers remains poorly characterized, hindering our understanding of its role in the biogeochemistry of key elements in contaminated fluvial environments. Here, we investigated the concentration of dissolved organic carbon (DOC) and spectroscopic and molecular characteristics of DOM in a headwater river contaminated with polymetallic mine-derived AMD in southern China. Terrestrial humic-like (C1) and typically groundwater-supplied aromatic protein/tyrosine-like (C2) substances which were partially from AMD, were identified as the predominant fluorescent components in the river water. Notably, tryptophan-like (C3) substances originating from tailings pond spills were only occasionally detected in the river. Although DOM biogeochemical transformations and degradation occurred in the lateral soil-water riparian interface and longitudinal in-stream transport processes, the molecular compositions identified by FT-ICR MS showed a core set of molecular formulae in the lignin/saturated compound/tannin region of the van Krevelen diagram of the water samples across the rivers. The complexation of DOM with typical metals in AMD was investigated using fluorescence quenching experiments. The results showed that the highest binding ability of Fe(III) to C2 followed by C1, with both detected in the experimental water samples. Mg(II) and Ca(II) strengthened the binding of DOM-Fe(III) when the ferric/DOM ratio was low, while Cu(II) weakened the binding of DOM-Fe(III) due to competition. Ca(II) inhibited the binding of Fe(III) to C1 but promoted the binding of the complex to C2 when both Cu(II) and Mg(II) were present. Since DOM-Fe(III) complexation was associated with the cotransport of AMD-derived metals/metalloids in diverse aqueous environments with multiple co-existing ions (typically Ca(II) input for remediation), our study on the composition of DOM and its complexation with metals can contribute to managing and remediating AMD-impacted rivers.