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Both genetic and epigenetic information must be transferred from mother to daughter cells during cell division. The mechanisms through which information about chromatin states and epigenetic marks like histone 3 lysine 27 trimethylation (H3K27me3) are transferred have been characterized in animals; these processes are less well understood in plants. Here, based on characterization of a dwarf rice (Oryza sativa) mutant (dwarf-related wd40 protein 1, drw1) deficient for yeast CTF4 (CHROMOSOME TRANSMISSION FIDELITY PROTEIN 4), we discovered that CTF4 orthologs in plants use common cellular machinery yet accomplish divergent functional outcomes. Specifically, drw1 exhibited no flowering-related phenotypes (as in the putatively orthologous Arabidopsis thaliana eol1 mutant), but displayed cell cycle arrest and DNA damage responses. Mechanistically, we demonstrate that DRW1 sustains normal cell cycle progression by modulating the expression of cell cycle inhibitors KIP-RELATED PROTEIN 1 (KRP1) and KRP5, and show that these effects are mediated by DRW1 binding their promoters and increasing H3K27me3 levels. Thus, although CTF4 orthologs ENHANCER OF LHP1 1 (EOL1) in Arabidopsis and DRW1 in rice are both expressed uniquely in dividing cells, commonly interact with several Polycomb complex subunits, and promote H3K27me3 deposition, we now know that their regulatory functions diverged substantially during plant evolution. Moreover, our work experimentally illustrates specific targets of CTF4/EOL1/DRW1, their protein-proteininteraction partners, and their chromatin/epigenetic effects in plants.
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Arabidopsis/metabolismo , Proteínas de Unión al ADN/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas del Grupo Polycomb/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Homología de Secuencia de Aminoácido , Núcleo Celular/metabolismo , Daño del ADN , ADN Polimerasa I/metabolismo , Flores/fisiología , Histonas/metabolismo , Lisina/metabolismo , Metilación , Mutación/genética , Oryza/anatomía & histología , Oryza/citología , Fenotipo , Proteínas de Plantas/genética , Unión Proteica , Fase SRESUMEN
The discharge of chromium-containing wastewater in industrial production causes resource loss and damage to the ecological environment. Currently, various phenolamine materials have been used to remove chromium, but their harsh adsorption conditions bring many difficulties. For example, ideal chromium removal is only achieved at low pH. In this study, we synthesized catechol/m-phenylenediamine nanospheres (CMN) and combined CMN with Fe(II) for Cr removal from aqueous solutions, and Fe(II) comes from FeSO4·7H2O. CMN was characterized and analyzed by field-emission scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS), transmission electron microscopy (TEM), Fourier transformed infrared (FTIR), X-ray diffraction (XRD), X-ray photoelectron (XPS). The adsorption performance was studied through a series of adsorption experiments. When C0 = 900 mg/L and pH = 6, the maximum adsorption capacity obtained in the experiment was 977.1 mg/g. It maintains excellent adsorption properties in acidic, neutral and alkaline environments. The results of the adsorption mechanism showed that the ultra-high adsorption capacity of CMN and Fe(II) for Cr was the result of the synergistic effect of adsorption and reduction, including electrostatic attraction, reduction and coprecipitation. CMN is expected to be an ideal adsorbent for Cr removal in aqueous solution due to its low cost, high biocompatibility and high efficiency in Cr removal.
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Nanosferas , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Agua , Cromo/análisis , Adsorción , Catecoles , Compuestos Ferrosos , Espectroscopía Infrarroja por Transformada de Fourier , Concentración de Iones de Hidrógeno , CinéticaRESUMEN
Taste masking is critical to improving the compliance of pediatric oral dosage forms. However, it is challenging for extremely bitter lisdexamfetamine dimesylate (LDX) with a long half-life and given in large dose. The present study aims to develop an immediate-release, taste-masked lisdexamfetamine chewable tablet. Lisdexamfetamine-resin complexes (LRCs) were prepared using the batch method. The molecular mechanism of taste masking was explored by PXRD, PLM, STA, and FT-IR. The results showed that taste masking was attributed to the ionic interaction between drug and the resin. The ion exchange process conformed to first-order kinetics. The rate-limiting step of drug release was the diffusion of ions inside the particles, and the concentration of H+ was the key factor for immediate release. The masking efficiency of the prepared LRCs in saliva exceeded 96%, and the drug could be completely released within 15 min in aqueous HCl (pH 1.2). Furthermore, the SeDeM expert system was used for the first time to comprehensively study the powder properties of LRCs and to quickly visualize their defects (compressibility, lubricity/stability, and lubricity/dosage). The selection of excipients was targeted rather than traditional screening, thus obtaining a robust chewable tablet formulation suitable for direct compression. Finally, the difference between chewable tablets containing LRCs and chewable tablets containing lisdexamfetamine dimesylate was compared by in vitro dissolution test, electronic tongue, and disintegration test. In conclusion, an immediate-released, child-friendly lisdexamfetamine chewable tablets without bitterness was successfully developed by the QbD approach, using the SeDeM system, which may help in further development of chewable tablets.
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Dimesilato de Lisdexanfetamina , Gusto , Humanos , Niño , Resinas de Intercambio Iónico/química , Excipientes , Espectroscopía Infrarroja por Transformada de Fourier , Solubilidad , Comprimidos , Composición de Medicamentos/métodos , Administración OralRESUMEN
The ubiquitin 26S proteasome system (UPS) is critical for enabling plants to alter their proteomes to integrate internal and external signals for the photoperiodic induction of flowering. We previously demonstrated that HAF1, a C3HC4 RING domain-containing E3 ubiquitin ligase, is essential to precisely modulate the timing of Heading Date1 accumulation and to ensure appropriate photoperiodic responses under short-day conditions in rice (Oryza sativa). However, how HAF1 mediates flowering under long-day conditions remains unknown. In this study, we show that OsELF3 (EARLY FLOWERING3) is the direct substrate of HAF1 for ubiquitination in vitro and in vivo. HAF1 is required for maintaining the circadian rhythm of OsELF3 accumulation during photoperiodic responses in rice. In addition, the haf1 oself3 double mutant headed as late as oself3 plants under long-day conditions. An amino acid variation (L558S) within the interaction domain of OsELF3 with HAF1 greatly contributes to the variation in heading date among japonica rice accessions. The japonica accessions carrying the OsELF3(L)-type allele are found at higher latitudes, while varieties carrying the OsELF3(S)-type allele are found at lower latitudes. Taken together, our findings suggest that HAF1 precisely modulates the diurnal rhythm of OsELF3 accumulation to ensure the appropriate heading date in rice.
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Oryza/fisiología , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ritmo Circadiano , Epistasis Genética , Flores/metabolismo , Flores/fisiología , Regulación de la Expresión Génica de las Plantas , Luz , Mutación , Fotoperiodo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Complejo de la Endopetidasa Proteasomal/metabolismo , Dominios Proteicos , Nicotiana/genética , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
BACKGROUND: Cadmium is a recognized human carcinogen, raising global concern for its ubiquitously environmental exposure on public health. Diabetogenic effects of cadmium have been suggested in previous studies, but the longitudinal associations of chronic cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus have not been fully elucidated. OBJECTIVE: To investigate the effects of long-term cadmium exposure on the fasting blood glucose changes and type 2 diabetes mellitus risk in a longitudinal prospective study of China. METHODS: A total of 3521 urban adults were included as baseline study population from the Wuhan-Zhuhai cohort, and followed up three years later. Urinary cadmium concentrations were determined repeatedly during the follow-up of a three-year period. The within-person and between-person variability of urinary cadmium concentrations over three years was estimated using multilevel random-effects mixed models. Multivariate regression models were performed to evaluate the associations of cadmium exposure with fasting blood glucose changes and type 2 diabetes mellitus risk. RESULTS: The geometric means of creatinine-corrected urinary cadmium concentration at baseline were 1.13 µg/g creatinine, which were close to the levels of follow-up (1.14 µg/g creatinine). The intra-class correlation coefficient of creatinine-corrected urinary cadmium concentrations was 0.71, achieving good reproducibility of cadmium over three years. With adjustment for potential confounders, each one-unit increase in log10-transformed cadmium was associated with a 0.11 (95%CI: 0.03 to 0.19) elevation in fasting blood glucose concentration, and was associated with a 42% (95%CI: 1.16 to 1.73) increase in risk of prevalent type 2 diabetes mellitus. Upward trends of fasting blood glucose changes and type 2 diabetes mellitus incidence were observed with increasing cadmium exposure. Individuals with the highest urinary cadmium exposure had a significant increase in fasting blood glucose change at follow-up [ß (95% CI): 0.49 (0.31-0.67)]. Risk of incident type 2 diabetes mellitus were gradually elevated across increasing quartiles of cadmium exposure, though associations did not reach statistical significance (P = 0.15). CONCLUSIONS: Our findings suggested that relatively high chronic cadmium exposure for general population adults might contribute to elevated changes of fasting blood glucose resulting in the development of type 2 diabetes mellitus.
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Cadmio , Diabetes Mellitus Tipo 2 , Adulto , Glucemia , China/epidemiología , Diabetes Mellitus Tipo 2/inducido químicamente , Diabetes Mellitus Tipo 2/epidemiología , Ayuno , Humanos , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
The aim of this study was to investigate the effect of various parameters on the stability of butorphanol tartrate injection and to screen the optimal packaging material. The effect of the headspace oxygen levels, ampoule color, manufacturer, and size on the stability of butorphanol tartrate formulation were evaluated. The headspace oxygen levels controlled by nitrogen purging were found to be particularly effective in improving stability of the butorphanol formulation, especially below 2%. Although it is a photolabile drug, butorphanol tartrate was getting degraded at much higher extent in amber color ampoules in comparison to clear ampoules. The degradation by oxidation was found to be a free radical-mediated process catalyzed by the presence of iron ions leached from the amber ampoules. The ampoule manufacturers also had a significant effect on the stability of butorphanol. Two-milliliter ampoules provided a better stability of the butorphanol tartrate injection than 1mL ampoules as 2-mL ampoules had the lower headspace oxygen level at the same level of oxygen content. The oxidation mechanism of the butorphanol tartrate injection was investigated under various conditions, which include iron powder spiking, removal of excipients, exposure to oxygen/nitrogen, exposure to stainless steel and at different pH. Iron powder spiking, presence of citric acid, exposure to oxygen, exposure to stainless steel, and high pH accelerated the oxidative degradation. The effect of oxygen, iron ion and citric acid is in agreement with a metal-catalyzed oxidation mechanism called Udenfriend reaction. Based on the formulation test results, limiting headspace oxygen level, ampoule color, manufacturer, size, controlling iron ion contamination, and pH are recommended for formulation development. In conclusion, it can be suggested that this study can lead to a better understanding of the degradation mechanism of butorphanol tartrate; hence, it would contribute to the development of butorphanol tartrate injection with improved stability. Virous packaging materials have different effects on the stability of butorphanol tartrate injection, and the leached iron of packaging ampoules and stainless steel can trigger Udenfriend reaction with butorphanol tartrate and citric acid (CA), which lead to the oxydative degradation of butorphanol tartrate injection.
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Analgésicos Opioides/química , Butorfanol/química , Contaminación de Medicamentos/prevención & control , Embalaje de Medicamentos/normas , Hierro/análisis , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/metabolismo , Butorfanol/administración & dosificación , Butorfanol/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Embalaje de Medicamentos/métodos , Estabilidad de Medicamentos , Inyecciones Subcutáneas , Hierro/metabolismo , Oxidación-ReducciónRESUMEN
BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is related to decreased lung function. However, whether oxidative damage is involved in this relationship remains unclear. This study was aimed to explore the potential mediating role of oxidative DNA or lipid damage in the association between PAH exposure and lung function. METHODS: The urinary levels of monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) and lung function parameters were measured among 3367 participants from the baseline of the Wuhan-Zhuhai cohort. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-iso-PGF2α) were determined to evaluate the individuals' oxidative DNA and lipid damage degrees, respectively. Linear mixed models were used to investigate the associations of urinary OH-PAHs, 8-OHdG and 8-iso-PGF2α with lung function parameters. Mediation analysis was further conducted to assess the potential role of oxidative damage in the association between urinary OH-PAHs and lung function. RESULTS: Each one-percentage increase in the sum of urinary OH-PAHs, high-molecular-weight or low-molecular-weight OH-PAHs (Æ©OH-PAHs, Æ©HMW OH-PAH or Æ©LMW OH-PAHs, respectively) was associated with a 0.2152-, 0.2076- or 0.1985- ml decrease in FEV1, and a 0.1891-, 0.2195- or 0.1634- ml decrease in FVC, respectively. Additionally, significantly positive dose-response relationships of Æ©OH-PAHs, Æ©HMW OH-PAH and Æ©LMW OH-PAHs with urinary 8-OHdG or 8-iso-PGF2α, as well as an inverse dose-response relationship between urinary 8-OHdG and FVC, were observed (all P for trend < 0.05). Mediation analysis indicated that urinary 8-OHdG mediated 14.22% of the association between Æ©HMW OH-PAH and FVC. CONCLUSION: Higher levels of oxidative DNA damage might be involved in the decreased levels of FVC caused by high-molecular-weight PAH exposure.
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Daño del ADN , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/efectos adversos , Pulmón/fisiología , Estrés Oxidativo , Hidrocarburos Policíclicos Aromáticos/efectos adversos , 8-Hidroxi-2'-Desoxicoguanosina/orina , Adulto , Anciano , Biomarcadores/orina , China , Estudios de Cohortes , Dinoprost/análogos & derivados , Dinoprost/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función RespiratoriaRESUMEN
The photoperiodic response is one of the most important factors determining heading date in rice (Oryza sativa). Although rhythmic expression patterns of flowering time genes have been reported to fine-tune the photoperiodic response, posttranslational regulation of key flowering regulators has seldom been elucidated in rice. Heading date 1 (Hd1) encodes a zinc finger transcription factor that plays a crucial role in the photoperiodic response, which determines rice regional adaptability. However, little is known about the molecular mechanisms of Hd1 accumulation during the photoperiod response. Here, we identify a C3HC4 RING domain-containing E3 ubiquitin ligase, Heading date Associated Factor 1 (HAF1), which physically interacts with Hd1. HAF1 mediates ubiquitination and targets Hd1 for degradation via the 26S proteasome-dependent pathway. The haf1 mutant exhibits a later flowering heading date under both short-day and long-day conditions. In addition, the haf1 hd1 double mutant headed as late as hd1 plants under short-day conditions but exhibited a heading date similar to haf1 under long-day conditions, thus indicating that HAF1 may determine heading date mainly through Hd1 under short-day conditions. Moreover, high levels of Hd1 accumulate in haf1. Our results suggest that HAF1 is essential to precise modulation of the timing of Hd1 accumulation during the photoperiod response in rice.
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Flores/fisiología , Oryza/fisiología , Proteínas de Plantas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Secuencia de Aminoácidos , Regulación de la Expresión Génica de las Plantas , Datos de Secuencia Molecular , Mutación , Fotoperiodo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Saccharomyces cerevisiae/genética , Nicotiana/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación , Dedos de ZincRESUMEN
BACKGROUND: Knee osteoarthritis (KOA) is one form of degenerative arthritis that results from the breakdown of cartilage and underlying bone. The prevalence of KOA is considerably higher in women than in men; however, the reason for this difference has not been thoroughly elucidated to date. The aim of the present study was to estimate the effects of reproductive and hormone factors and obesity on KOA prevalence among Chinese women. METHODS: The cross-sectional study included 7510 women with a mean age of 62.6 ± 8.6 years. Knee pain was defined as pain or aching stiffness on most days for at least 1 month during the past 12 months or persistent pain or aching stiffness within the past week. Clinical KOA was diagnosed based on both pain complaints and a Kellgren-Lawrence grade ≥ 2 X-ray radiograph of at least one knee. RESULTS: Oral contraceptives use (OR 1.18, 1.05-1.34), ≥3 pregnancies (1.38, 1.20-1.60), and postmenopausal hormone replacement therapy (HT) (1.59, 1.23-2.06) were positively associated with knee pain, while oral contraceptives use (1.28, 1.04-1.57), and HT (1.79, 1.21-2.65) were positively associated with clinical KOA. Obesity and oral contraceptives use showed additive and multiplicative effects on knee pain. The OR for knee pain among women with a BMI ≥24 kg/m2 and oral contraceptives use was 2.00 (1.68-2.38) compared with women with a BMI < 24 kg/m2 and no oral contraceptives use. CONCLUSIONS: A high number of pregnancies, oral contraceptives use, and HT are independent risk factors for KOA, and the effects of reproductive and hormone factors on KOA may be increased by obesity.
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Artralgia/epidemiología , Anticonceptivos Hormonales Orales/efectos adversos , Terapia de Reemplazo de Hormonas/efectos adversos , Articulación de la Rodilla , Obesidad/complicaciones , Osteoartritis de la Rodilla/epidemiología , Historia Reproductiva , Anciano , China/epidemiología , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Replication protein A (RPA) is a conserved heterotrimeric protein complex comprising RPA1, RPA2, and RPA3 subunits involved in multiple DNA metabolism pathways attributable to its single-stranded DNA binding property. Unlike other species possessing a single RPA2 gene, rice (Oryza sativa) possesses three RPA2 paralogs, but their functions remain unclear. In this study, we identified RPA2c, a rice gene preferentially expressed during meiosis. A T-DNA insertional mutant (rpa2c) exhibited reduced bivalent formation, leading to chromosome nondisjunction. In rpa2c, chiasma frequency is reduced by ~78% compared with the wild type and is accompanied by loss of the obligate chiasma. The residual ~22% chiasmata fit a Poisson distribution, suggesting loss of crossover control. RPA2c colocalized with the meiotic cohesion subunit REC8 and the axis-associated protein PAIR2. Localization of REC8 was necessary for loading of RPA2c to the chromosomes. In addition, RPA2c partially colocalized with MER3 during late leptotene, thus indicating that RPA2c is required for class I crossover formation at a late stage of homologous recombination. Furthermore, we identified RPA1c, an RPA1 subunit with nearly overlapping distribution to RPA2c, required for ~79% of chiasmata formation. Our results demonstrate that an RPA complex comprising RPA2c and RPA1c is required to promote meiotic crossovers in rice.
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Intercambio Genético , Meiosis , Oryza/genética , Proteínas de Plantas/metabolismo , Proteína de Replicación A/metabolismo , ADN Bacteriano , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Mutagénesis Insercional , No Disyunción Genética , Oryza/citología , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente/citología , Plantas Modificadas Genéticamente/genética , Proteína de Replicación A/genéticaRESUMEN
Automatic classification of different types of cough plays an important role in clinical.In the previous research of cough classification or cough recognition,traditional Mel frequency cepstrum coefficients(MFCC)which extracts feature mainly from low frequency band is usually used as feature expression.In this paper,by analyzing the distributions of spectral energy of dry/wet cough,it is found that spectral difference of two types of cough exits mainly in middle frequency band and high frequency band.To better reflect the spectral difference of dry cough and wet cough,an improved method of extracting reverse MFCC is proposed.In this method,reverse Mel filter-bank in which filters are allocated in reverse Mel scale is adopted and is improved by placing filters only in the frequency band with high spectral energy.As a result,features are mainly extracted from the frequency band where two types of cough show both high spectral energy and distinguished difference.Detailed process of accessing improved reverse MFCC was introduced and hidden Markov models trained by 60 dry cough and 60 wet cough were used as cough classification model.Classification experiment results for 120 dry cough and 85 wet cough showed that,compared to traditional MFCC,better classification performance was achieved by the proposed method and the total classification accuracy was raised from 89.76%to 93.66%.
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Tos/diagnóstico , Algoritmos , Tos/clasificación , Humanos , Cadenas de MarkovRESUMEN
Background: Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are the major contributors to mortality and morbidity in preterm infants. This updated meta-analysis was aimed to assess the effects of mother's milk on the incidence of NEC, LOS, and other clinical outcomes in preterm infants. Methods: PubMed, Embase, and the Cochrane library were searched for papers published up to October 2022. Results: A total of 13 RCTs with 1330 infants were included in the final analysis. Significant difference in NEC (stage 2 or 3) was found between the intervention group and the control group (RR = 0.508, 95% CI: 0.314-0.822, and P=0.008). The incidence of proven LOS (RR = 0.809, 95% CI: 0.610-1.071, and P=0.139) and death (RR = 0.800, 95% CI: 0.571-1.122, and P=0.196) was comparable between the two groups. Statistical differences in the incidence of proven or probable LOS (RR = 0.705, 95% CI: 0.577-0.862, and P=0.001) and length of hospitalization (WMD = -4.868, 95% CI: -6.608 to -3.128, and P < 0.001) between the intervention group and the control group were observed. Conclusions: The results of this updated meta-analysis showed that compared to the placebo, mother's milk provides better effects in reducing the incidences of NEC, proven or probable LOS, and the length of stay, whereas no significant benefit of mother's milk was observed in reducing the incidence of proven LOS and death.
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The catalytic conversion of biomass-derived glycerol into high-value-added products, such as glyceric acid (GLYA), using catalyst-supported Au nanoparticles (Au NPs) at room temperature presents a significant challenge. In this study, we constructed a series of supported Au catalysts, including Au/ZrO2@C, Au/C, Au/ZrO2, and Au/ZrO2-C, and investigated their effectiveness in selectively catalytic oxidizing glycerol to GLYA at room temperature. Among these catalysts, the Au/ZrO2@C catalyst exhibited the best catalytic performance, achieving a glycerol conversion rate of 73% and a GLYA selectivity of 79% under the optimized reaction conditions (reaction conditions: 30 mL 0.1 M glycerol, glycerol/Au = 750 mol mol-1, T = 25 °C, p(O2) = 10 bar, stirring speed = 600 rpm, time = 6 h). Physical adsorption, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and other characterization methods were employed to analyze the texture properties of the catalyst. The findings indicated that the support structure, the strong metal-support interactions between Au NPs and the support, and the presence of small metallic Au NPs were the primary factors contributing to the catalyst's high activity and selectivity. Moreover, the reusability of the Au/ZrO2@C catalyst was investigated, and a probable reaction mechanism for the oxidation of glycerol was proposed.
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Background: Janus kinase (JAK) inhibitors have emerged as a progressively utilized therapeutic approach for the management of rheumatoid arthritis (RA). However, the complete determination of their cardiovascular safety remains inconclusive. Hence, the primary objective of this network meta-analysis is to meticulously assess and juxtapose the cardiovascular risks linked to distinct JAK inhibitors employed in RA patients. Methods: A systematic review and network meta-analysis were meticulously conducted, encompassing a collection of randomized controlled trials (RCTs) that focused on investigating the incidence of major adverse cardiovascular events (MACE) and all-cause mortality associated with Janus kinase (JAK) inhibitors administered to patients with rheumatoid arthritis (RA). Extensive exploration was performed across multiple electronic databases, incorporating studies published until March 2023. To be included in this analysis, the RCTs were required to involve adult participants diagnosed with RA who received treatment with JAK inhibitors. To ensure accuracy, two authors independently undertook the selection of eligible RCTs and meticulously extracted aggregate data. In order to examine the outcomes of MACE and all-cause mortality, a frequentist graph theoretical approach within network meta-analyses was employed, utilizing random-effects models. Third study has been registered on PROSPERO under the reference CRD42022384611. Findings: A specific selection encompassing a total of 14 meticulously chosen randomized controlled trials was undertaken, wherein 13,524 patients were assigned randomly to distinct treatment interventions. The analysis revealed no notable disparity in the occurrence of major adverse cardiovascular events (MACE) between the interventions and the placebo group. However, in comparison to adalimumab, the employment of JAK inhibitors exhibited an association with higher rates of all-cause mortality [odds ratio (OR): 1.7, 95% confidence interval (CI): 1.02-2.81]. This observed increase in risk primarily stemmed from the usage of tofacitinib (OR: 1.9, 95% CI: 1.12-3.23). None of the other JAK inhibitors exhibited a statistically significant variance in all-cause mortality when compared to adalimumab. Interpretation: Our study suggests that JAK inhibitors may not increase the risk of MACE in RA patients but may be associated with a higher risk of all-cause mortality compared to adalimumab, primarily due to tofacitinib use. Rheumatologists should carefully consider the cardiovascular risks when prescribing JAK inhibitors, particularly tofacitinib, for RA patients. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=384611, CRD42022384611.
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Grafting the wine grape variety Cabernet Sauvignon onto salinity-tolerant rootstocks can improve salinity tolerance and grape yields in regions with high salinity soils. In this experiment, the effects of different rootstocks and rootstock combinations on the saline-alkaline stress (modified Hoagland nutrient solution + 50 mmol L-1 (NaCl + NaHCO3)) of Cabernet Sauvignon were studied. Correlation and principal component analyses were conducted on several physiological indicators of saline-alkaline stress. Salinity limited biomass accumulation, induced damage to the plant membrane, reduced the chlorophyll content and photosynthetic capacity of plants, and increased the content of malondialdehyde, sodium (Na+)/potassium (K+) ratio, and antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase). Significant differences in several indicators were observed among the experimental groups. The results indicate that the saline-alkaline tolerance of Cabernet Sauvignon after grafting was the same as that of the rootstock, indicating that the increased resistance of Cabernet Sauvignon grapes to saline-alkaline stress stems from the transferability of the saline-alkaline stress resistance of the rootstock to the scion.
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Different rootstocks for grapes can significantly affect fruit color and quality, possibly by affecting hormone contents, related genetic pathways, and fruit coloring mechanisms in skin. 'Cabernet Sauvignon' was grafted to '5BB', 'SO4', '140R', 'CS', '3309M' and 'Vitis riparia' rootstocks, with self-rooting seedlings as the control (CS/CS), and sampled from the early stage of veraison to the ripening stage. The effects of rootstock on the contents of gibberellin (GA3), auxin (IAA), and abscisic acid (ABA) in grape skin were determined alongside the expression levels of eight anthocyanin synthesis related genes using real-time fluorescence quantitative PCR methods. The rootstock cultivars exhibited accelerated fruit color change, and the CS/140R combination resulted in grapes with more color than the control group in the same period. With the development of fruit, the IAA and GA3 contents in the skin of different rootstock combinations showed trends of increasing initially, then decreasing, while the ABA content decreased initially and then increased. During the verasion (28 July), the various 'Cabernet Sauvignon' rootstock combinations exhibited varying degrees of increases in GA3, ABA, and IAA contents; correlation analysis showed that, at the start of veraison, the expression levels of the anthocyanin synthesis-related genes VvCHS, VvDFR, and VvUFGT had strong positive correlations with hormone contents, which indicated they are key genes involved in the endogenous hormone responsive anthocyanin biosynthesis pathway. The results of this study showed that rootstock regulates the fruit coloring process by influencing the metabolism level of peel hormones in the 'Cabernet Sauvignon' grape.
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Vitis , Vitis/genética , Antocianinas/metabolismo , Frutas/genética , Ácido Abscísico/metabolismo , Hormonas/metabolismoRESUMEN
Background: Although with the application of etanercept biosimilars in the field of rheumatoid arthritis, the evidences of their efficacy, safety, and immunogenicity are still limited. We conducted this meta-analysis to evaluate the efficacy, safety and immunogenicity of etanercept biosimilars for treating active rheumatoid arthritis compared to reference biologics (Enbrel®). Methods: PubMed, Embase, Central, and ClinicalTrials.gov were searched for randomized controlled trials of etanercept biosimilars treated in adult patients diagnosed with rheumatoid arthritis from their earliest records to 15 August 2022. The outcomes included ACR20, ACR50, and ACR70 response rate at different time points from FAS or PPS, adverse events, and proportion of patients developed anti-drug antibodies. The risk of bias of each included study was assessed using the revised Cochrane Risk of Bias in Randomised Trials tool, and the certainty of evidence was rated according to the Grading of Recommendation Assessment, Development, and Evaluation. Results: Six RCTs with 2432 patients were included in this meta-analysis. Etanercept biosimilars showed more benefits in ACR50 at 24 weeks from PPS [5 RCTs, OR = 1.22 (1.01, 1.47), p = 0.04, I 2 = 49%, high certainty], ACR50 at 1 year from PPS [3 RCTs, OR = 1.43 (1.10, 1.86), p < 0.01, I 2 = 0%, high certainty] or FAS [2 RCTs, OR = 1.36 (1.04, 1.78), p = 0.03, I 2 = 0%, high certainty], and ACR70 at 1 year from PPS [3 RCTs, OR = 1.32 (1.01, 1.71), p = 0.04, I 2 = 0%, high certainty]. In terms of other outcomes about efficacy, safety, and immunogenicity, the results showed that there was no significant difference between etanercept biosimilars and reference biologics, and the certainty of evidences ranged from low to moderate. Conclusion: Etanercept biosimilars showed more benefits in ACR50 response rate at 1 year than reference biologics (Enbrel®), other outcomes for clinical efficacy, safety, and immunogenicity of etanercept biosimilars were comparable with originator in patients with rheumatoid arthritis. Systematic Review Registration: PROSPERO, identifier CRD42022358709.
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INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.
Asunto(s)
Bronquiectasia , Niño , Humanos , Estudios Retrospectivos , Bronquiectasia/diagnóstico por imagen , Bronquiectasia/epidemiología , Pulmón , Tos/etiología , Tos/complicaciones , China/epidemiologíaRESUMEN
A series of nitrogen-doped porous carbon nanosheets (NPCNs) doped with transition-metal-supported Pt catalysts were prepared by colloidal deposition and evaluated for the selective oxidation of glycerol to glyceric acid (GLYA) under nonalkaline conditions. The transition metal contained in the catalyst was found to affect its performance and selectivity for GLYA, with the Pt/Zr@NPCN catalyst showing the highest catalytic activity and selectivity. These materials were characterized using Brunauer-Emmett-Teller surface area analysis, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and CO2 temperature-programmed desorption. The results showed that the small size of the Pt nanoparticles, the interaction between the Pt nanoparticles and the support, and the unique textural properties of the catalyst all promoted glycerol conversion and GLYA selectivity. A Zr concentration of 1.5 wt % and a support preparation temperature of 800 °C were found to provide a catalyst with the optimal performance that exhibited a glycerol conversion and selectivity for GLYA of 68.62 and 77.29%, respectively, at an initial O2 pressure of 10 bar and 60 °C after 6 h. Even after being recycled five times, this material provided a GLYA selectivity of approximately 75%, although the glycerol conversion decreased from 68 to 50%. The insights may provide new suggestions on the design of efficient support for the selective oxidation of polyols.