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Auxin regulates plant growth and development through downstream signaling pathways, including the best-known SCFTIR1/AFB-Aux/IAA-ARF pathway and several other less characterized "noncanonical" pathways. Recently, one SCFTIR1/AFB-independent noncanonical pathway, mediated by Transmembrane Kinase 1 (TMK1), was discovered through the analyses of its functions in Arabidopsis apical hook development. Asymmetric accumulation of auxin on the concave side of the apical hook triggers DAR1-catalyzed release of the C-terminal of TMK1, which migrates into the nucleus, where it phosphorylates and stabilizes IAA32/34 to inhibit cell elongation, which is essential for full apical hook formation. However, the molecular factors mediating IAA32/34 degradation have not been identified. Here, we show that proteins in the CYTOKININ INDUCED ROOT WAVING 1 (CKRW1)/WAVY GROWTH 3 (WAV3) subfamily act as E3 ubiquitin ligases to target IAA32/34 for ubiquitination and degradation, which is inhibited by TMK1c-mediated phosphorylation. This antagonistic interaction between TMK1c and CKRW1/WAV3 subfamily E3 ubiquitin ligases regulates IAA32/34 levels to control differential cell elongation along opposite sides of the apical hook.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas F-Box , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Transducción de Señal , Ubiquitinas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas F-Box/genética , Proteínas F-Box/metabolismoRESUMEN
Poxvirus genomes consist of a linear duplex DNA that ends in short inverted and complementary hairpin structures. These elements also encode loops and mismatches that likely serve a role in genome packaging and perhaps replication. We constructed mutant vaccinia viruses (VACV) where the native hairpins were replaced by altered forms and tested effects on replication, assembly, and virulence. Our studies showed that structure, not sequence, likely determines function as one can replace an Orthopoxvirus (VACV) hairpin with one copied from a Leporipoxvirus with no effect on growth. Some loops can be deleted from VACV hairpins with little effect, but VACV bearing too few mismatches grew poorly and we couldn't recover viruses lacking all mismatches. Further studies were conducted using a mutant bearing only one of six mismatches found in wild-type hairpins (SΔ1Δ3-6). This virus grew to ~20-fold lower titers, but neither DNA synthesis nor telomere resolution was affected. However, the mutant exhibited a particle-to-PFU ratio 10-20-fold higher than wild-type viruses and p4b/4b core protein processing was compromised, indicating an assembly defect. Electron microscopy showed that SΔ1Δ3-6 mutant development was blocked at the immature virus (IV) stage, which phenocopies known effects of I1L mutants. Competitive DNA binding assays showed that recombinant I1 protein had less affinity for the SΔ1Δ3-6 hairpin than the wild-type hairpin. The SΔ1Δ3-6 mutant was also attenuated when administered to SCID-NCR mice by tail scarification. Mice inoculated with viruses bearing wild-type hairpins exhibited a median survival of 30-37 days, while mice infected with SΔ1Δ3-6 virus survived >70 days. Persistent infections favor genetic reversion and genome sequencing detected one example where a small duplication near the hairpin tip likely created a new loop. These observations show that mismatches serve a critical role in genome packaging and provide new insights into how VACV "flip and flop" telomeres are arranged.
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Nucleótidos , Virus Vaccinia , Animales , ADN , Ratones , Ratones SCID , Telómero , Virus Vaccinia/genética , Virión/genética , Replicación Viral/genéticaRESUMEN
The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.
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Corydalis , Filogenia , Himalayas , Biodiversidad , Ecosistema , PlantasRESUMEN
Metabolites are important indicators of cancer and mutations in genes involved in amino acid metabolism may influence tumorigenesis. Immunotherapy is an effective cancer treatment option; however, its relationship with amino acid metabolism has not been reported. In this study, RNA-seq data for 371 liver cancer patients were acquired from TCGA and used as the training set. Data for 231 liver cancer patients were obtained from ICGC and used as the validation set to establish a gene signature for predicting liver cancer overall survival outcomes and immunotherapeutic responses. Four reliable groups based on 132 amino acid metabolism-related DEGs were obtained by consistent clustering of 371 HCC patients and a four-gene signature for prediction of liver cancer survival outcomes was developed. Our data show that in different clinical groups, the overall survival outcomes in the high-risk group were markedly low relative to the low-risk group. Univariate and multivariate analyses revealed that the characteristics of the 4-gene signature were independent prognostic factors for liver cancer. The ROC curve revealed that the risk characteristic is an efficient predictor for 1-, 2-, and 3-year HCC survival outcomes. The GSVA and KEGG pathway analyses revealed that high-risk score tumors were associated with all aspects of the degree of malignancy in liver cancer. There were more mutant genes and greater immune infiltrations in the high-risk groups. Assessment of the three immunotherapeutic cohorts established that low-risk score patients significantly benefited from immunotherapy. Then, we established a prognostic nomogram based on the TCGA cohort. In conclusion, the 4-gene signature is a reliable diagnostic marker and predictor for immunotherapeutic efficacy.
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Aflatoxin is the most common type of mycotoxins in contaminated corn, peanuts and rice, which affects the livestock and ultimately endangers human health. Aflatoxin is reported to have carcinogenicity, mutation, growth retardation, immunosuppression and reproductive toxicity. In present study we reported the causes for the declined porcine oocyte quality under aflatoxin exposure. We set up an in vitro exposure model and showed that aflatoxin B1 disturbed cumulus cell expansion and oocyte polar body extrusion. We found that aflatoxin B1 exposure disrupted ER distribution and elevated the expression of GRP78, indicating the occurrence of ER stress, and the increased calcium storage also confirmed this. Besides, the structure of cis-Golgi apparatus, another intracellular membrane system was also affected, showing with decreased GM130 expression. The oocytes under aflatoxin B1 exposure showed aberrant lysosome accumulation and higher LAMP2 expression, a marker for lysosome membrane protection, and this might be due to the aberrant mitochondria function with low ATP production and the increase of apoptosis, since we found that BAX expression increased, and ribosomal protein which is also an apoptosis-related factor RPS3 decreased. Taken together, our study revealed that aflatoxin B1 impairs intracellular membrane system ER, Golgi apparatus, lysosome and mitochondria function to affect porcine oocyte maturation quality.
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Aflatoxina B1 , Oocitos , Humanos , Animales , Porcinos , Aflatoxina B1/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Oocitos/metabolismo , Apoptosis , Membranas Intracelulares , Adenosina Trifosfato/metabolismoRESUMEN
Deoxynivalenol is a mycotoxin, produced by Fusarium from contaminated corn, wheat, and other grains, that induces multiple effects in humans and animals, including cytotoxic, genotoxic, immunotoxic, and carcinogenic effects. Recent studies show that deoxynivalenol also affects the reproductive system of mammals, including oocyte quality. However, the effects of deoxynivalenol on early embryonic development have not been reported. In this study, fluorescence intensity analysis was used to show that deoxynivalenol disrupted the first cleavage of the zygote. The high deoxynivalenol dose disturbed the movement of the pronucleus after fertilization, while the low deoxynivalenol dose caused aberrant spindle morphology during the metaphase of the first cleavage. Further analysis showed that the reactive oxygen species level increased in the deoxynivalenol-exposed two-cell embryos, indicating oxidative stress. Moreover, deoxynivalenol caused DNA damage in the embryos, as positive γH2A.X signals were detected in the nucleus. These events led to the early apoptosis of mouse embryos, which was confirmed by autophagy. Taken together, our study provides evidence for the toxicity of deoxynivalenol during early embryonic development in the mouse model.
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Apoptosis , Micotoxinas , Femenino , Embarazo , Humanos , Animales , Ratones , Autofagia , Núcleo Celular , Micotoxinas/toxicidad , MamíferosRESUMEN
The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high-risk human papilloma virus (HR-HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR-HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51-0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50-0.95; C vs. T: OR = 0.78, 95% CI = 0.63-0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR-HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51-0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51-0.94; A vs. G: OR = 0.75, 95% CI = 0.58-0.96). Patients with CC and HR-HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T-C-A decreased the risk of HR-HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR-HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.
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Proteína Forkhead Box O3/genética , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Estudios de Casos y Controles , China , Femenino , Factores de Transcripción Forkhead/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Intrones/genética , Mutación , Infecciones por Papillomavirus/genética , Polimorfismo de Nucleótido Simple/genética , Neoplasias del Cuello Uterino/genéticaRESUMEN
Nonylphenol (NP) is an environmental endocrine disruptor, which is mainly used in the production of surfactants, lubricants, additives, pesticides, and emulsifiers. NP is widely found in sewage and sludge, which has neurotoxicity, immunotoxicity, metabolic toxicity and reproductive toxicity. In this study, we investigated the effects of NP exposure on mammalian oocyte quality from organelle aspects with mouse in vivo model. The results showed that the ovarian weight of mice exposed to 500 µg/L NP for 4 weeks increased and the development ability of oocytes decreased, showing with lower rate of polar body extrusion. Further analysis indicated that exposure to NP caused the abnormal distribution of mitochondria, following with altered membrane potential drop. NP exposure disrupted the spindle periphery localization of ER, and affected the expression of GRP78 for the induction of ER stress. Moreover, Golgi apparatus fragment in the oocytes was observed, and Rab11-based vesicle transport was disturbed. We also found that the protein degradation might be affected since LAMP2 expression increased and LC3 decreased, indicating the lysosome and autophagy dysfunction. Taken together, our findings suggested that the exposure of NP to mice in vivo affected oocyte quality through its effects on the distribution and function of organelles.
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BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.
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Neoplasias Nasofaríngeas , ARN Largo no Codificante , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Regulación Neoplásica de la Expresión Génica , Histona Metiltransferasas/genética , Histona Metiltransferasas/metabolismo , Humanos , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
C/EBP-homologous protein (CHOP) and histone H3 lysine 4 (H3K4) methylation have been verified to be correlated with apoptosis, whereas their biological function in arsenic-induced hepatocyte apoptosis through the mitochondrial pathway is still unclear. This study aimed to explore the specific regulatory mechanism of CHOP and H3K4me1/2 in arsenic-induced mitochondrial apoptosis in hepatocytes. Apoptosis and proliferation results showed arsenic promoted apoptosis and inhibited cell growth in BRL-3A cells. Meanwhile, arsenic treatment significantly upregulated the 78-kDa glucose-regulated protein (GRP78), CHOP, su(var)-3-9,enhancer-of-zeste,trithorax (SET) domain containing 7/9 (SET7/9), H3K4me1/2, BIM and BAX expression, while markedly downregulated lysine-specific histone demethylase 1 (LSD1) and BCL2 expression. After down-regulating CHOP, LSD1, and (su(var)-3-9,enhancer-of-zeste,trithorax) domain-containing protein 7/9 (SET7/9) in BRL-3A cells by siRNA, silencing CHOP and SET7/9 notably attenuated the pro-apoptotic and anti-proliferative effects of arsenic treatment on BRL-3A cells, which was reversed after inhibiting LSD1. In addition, our results suggested that knockdown of CHOP altered the expression of mitochondrial-associated proteins BCL2 and BIM, whereas knockdown of LSD1 and SET7/8 regulated the level of H3K4me1/2 modification and BAX protein. Coupled with chromatin immunoprecipitation results, we found that the level of CHOP in the promoter regions of BCL2 and BIM was significantly increased in BRL-3A cells exposed to 30 µmol/L NaAsO2 for 24 h, whereas the levels of H3K4me1/2 in the promoter regions of BAX were unchanged. Collectively, these data indicated that arsenic triggered the mitochondrial pathway to induce hepatocyte apoptosis by up-regulating the levels of CHOP and H3K4me1/2.
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Arsénico , Histonas , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Metilación , Histonas/metabolismo , Lisina/metabolismo , Arsénico/toxicidad , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Apoptosis , Hepatocitos/metabolismo , Histona Demetilasas/genética , Histona Demetilasas/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: To assess the general and nutritional health of children with attention deficit/ hyperactivity disorder (ADHD). METHODS AND STUDY DESIGN: The National Multicenter Sleep Research Database for 23791 school-age children in grades 1-6 from 9 cities in China was accessed. Children with a specialist diagnosis of ADHD or not (non-ADHD) in 2005 were studied. National anthropometric growth standards for children aged 2-18 years classified children as underweight, wasted, stunted (short stature presumed nutritional), or overweight/obesity. Independent variables were preterm birth, sleep quality and prior disease and ADHD was the dependent variable. Binary logistic regression models were developed along with interaction analyses for associated disorder or disease on overweight/obesity, and stunted. RESULTS: Some 18731 records were analyzed for 808 children with ADHD. The comparative prevalences for ADHD with non-ADHD children were stunted 9.8% vs 5.9% (p<0.001) and overweight/ obesity (32.6% vs 29.6%, p=0.002) respectively. ADHD boys were more often underweight (7.5% vs 5.3%, p=0.027), but not in girls. ADHD likelihood Odds Ratios, ORs (with 95%CI) were for premature birth 1.838, (1.393-2.423), allergic diseases 1.915 (1.526-2.399), otitis media 1.54 (1.118- 2.146), tonsillar or adenoid hypertrophy1.662 (1.348-2.050), gastroesophageal reflux 3.008(1.792-1.792-5.049), and sleep disorder 2.201(1.847-2.623) were ADHD risk factors. Only poor sleep quality and ADHD exhibited an interaction for stunted with OR=0.409 (0.233-0.719). CONCLUSIONS: Compromised and complex nutritional health in ADHD children challenges clinical nutrition with a range of health problems, albeit coherent with the needed nutritional emphasis in the 'first 1000 days'.
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Trastorno por Déficit de Atención con Hiperactividad , Nacimiento Prematuro , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Niño , Preescolar , China/epidemiología , Estudios Transversales , Femenino , Humanos , Recién Nacido , Masculino , PrevalenciaRESUMEN
During mouse oocyte meiotic maturation, actin filaments play multiple roles in meiosis such as spindle migration and cytokinesis. FASCIN is shown to be an actin-binding and bundling protein, making actin filaments tightly packed and parallel-aligned, and FASCIN is involved in several cellular processes like adhesion and migration. FASCIN is also a potential prognostic biomarker and therapeutic target for the treatment of metastatic disease. However, little is known about the functions of FASCIN in oocyte meiosis. In the present study, we knocked down the expression of FASCIN, and our results showed that FASCIN was essential for oocyte maturation. FASCIN was all expressed in the different stages of oocyte meiosis, and it mainly localized at the cortex of oocytes from the GV stage to the MII stage and showed a similar localization pattern with actin and DAAM1. Depletion of FASCIN affected the extrusion of the first polar body, and we also observed that some oocytes extruded from the large polar bodies. This might have resulted from the defects of actin assembly, which further affected the meiotic spindle positioning. In addition, we showed that inhibition of PKC activity decreased FASCIN expression, indicating that FASCIN might be regulated by PKC. Taken together, our results provided evidence for the important role of FASCIN on actin filaments for spindle migration and polar body extrusion in mouse oocyte meiosis.
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Citoesqueleto de Actina/metabolismo , Proteínas Portadoras/metabolismo , Meiosis , Proteínas de Microfilamentos/metabolismo , Oocitos/metabolismo , Cuerpos Polares/metabolismo , Huso Acromático/metabolismo , Citoesqueleto de Actina/genética , Animales , Proteínas Portadoras/genética , Células Cultivadas , Femenino , Ratones Endogámicos ICR , Proteínas de Microfilamentos/genética , Proteína Quinasa C/metabolismo , Huso Acromático/genética , Proteínas de Unión al GTP rho/metabolismoRESUMEN
BACKGROUND: Thrombospondin-related adhesive protein (TRAP) is a transmembrane protein that plays a crucial role during the invasion of Plasmodium falciparum into liver cells. As a potential malaria vaccine candidate, the genetic diversity and natural selection of PfTRAP was assessed and the global PfTRAP polymorphism pattern was described. METHODS: 153 blood spot samples from Bioko malaria patients were collected during 2016-2018 and the target TRAP gene was amplified. Together with the sequences from database, nucleotide diversity and natural selection analysis, and the structural prediction were preformed using bioinformatical tools. RESULTS: A total of 119 Bioko PfTRAP sequences were amplified successfully. On Bioko Island, PfTRAP shows its high degree of genetic diversity and heterogeneity, with π value for 0.01046 and Hd for 0.99. The value of dN-dS (6.2231, p < 0.05) hinted at natural selection of PfTRAP on Bioko Island. Globally, the African PfTRAPs showed more diverse than the Asian ones, and significant genetic differentiation was discovered by the fixation index between African and Asian countries (Fst > 0.15, p < 0.05). 667 Asian isolates clustered in 136 haplotypes and 739 African isolates clustered in 528 haplotypes by network analysis. The mutations I116T, L221I, Y128F, G228V and P299S were predicted as probably damaging by PolyPhen online service, while mutations L49V, R285G, R285S, P299S and K421N would lead to a significant increase of free energy difference (ΔΔG > 1) indicated a destabilization of protein structure. CONCLUSIONS: Evidences in the present investigation supported that PfTRAP gene from Bioko Island and other malaria endemic countries is highly polymorphic (especially at T cell epitopes), which provided the genetic information background for developing an PfTRAP-based universal effective vaccine. Moreover, some mutations have been shown to be detrimental to the protein structure or function and deserve further study and continuous monitoring.
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Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Epítopos , Guinea Ecuatorial/epidemiología , Frecuencia de los Genes , Variación Genética , Haplotipos , Humanos , Vacunas contra la Malaria , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Plasmodium falciparum/inmunología , Polimorfismo Genético , Proteínas Protozoarias/química , Proteínas Protozoarias/inmunología , Selección GenéticaRESUMEN
BACKGROUND: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB). METHODS: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results. RESULTS: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB. CONCLUSION: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.
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Adenosina Desaminasa/análisis , Mycobacterium tuberculosis/aislamiento & purificación , Tuberculosis Pleural/diagnóstico , Adolescente , Nitrógeno de la Urea Sanguínea , Estudios de Casos y Controles , Dolor en el Pecho , Niño , Femenino , Humanos , L-Lactato Deshidrogenasa/análisis , Modelos Logísticos , Masculino , Análisis Multivariante , Derrame Pleural/microbiología , Estudios Retrospectivos , Factores de Riesgo , Esputo/microbiología , Tuberculosis Pleural/microbiología , Tuberculosis Pleural/patologíaRESUMEN
The prognostic factor for in-hospital mortality in tuberculosis (TB) patients requiring intensive care unit (ICU) care remains unclear. Therefore, a retrospective study was conducted aiming to estimate the in-hospital mortality rate and the risk factors for mortality in a high-burden setting. All patients with culture-confirmed TB that were admitted to the ICU of the hospital between March 2012 and April 2019 were identified retrospectively. Data, such as demographic characteristics, comorbidities, laboratory measures and mortality, were obtained from medical records. The Cox proportional hazards regression model was used to identify prognostic factors that influence in-hospital mortality. A total of 82 ICU patients with confirmed TB were included in the analysis, and 22 deaths were observed during the hospital stay, 21 patients died in the ICU. In the multivariable model adjusted for sex and age, the levels of serum albumin and white blood cell (WBC) count were significantly associated with mortality in TB patients requiring ICU care (all P < 0.01), the hazard ratios were 0.8 (95% confidence interval (CI): 0.7-0.9) per 1 g/l and 1.1 (95% CI: 1.0-1.2) per 1 × 109/l, respectively. In conclusion, in-hospital mortality remains high in TB patients requiring ICU care. Low serum albumin level and high WBC count significantly impact the risk of mortality in these TB patients in China.
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Unidades de Cuidados Intensivos , Tuberculosis Pulmonar/mortalidad , Adulto , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tuberculosis Pulmonar/epidemiologíaRESUMEN
The plant root is a dynamic system, which is able to respond promptly to external environmental stimuli by constantly adjusting its growth and development. A key component regulating this growth and development is the finely tuned cross-talk between the auxin and cytokinin phytohormones. The gradient distribution of auxin is not only important for the growth and development of roots, but also for root growth in various response. Recent studies have shed light on the molecular mechanisms of cytokinin-mediated regulation of local auxin biosynthesis/metabolism and redistribution in establishing active auxin gradients, resulting in cell division and differentiation in primary root tips. In this review, we focus our attention on the molecular mechanisms underlying the cytokinin-controlled auxin gradient in root tips.
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Arabidopsis/fisiología , Citocininas/metabolismo , Ácidos Indolacéticos/metabolismo , Desarrollo de la Planta , Raíces de Plantas/metabolismo , Transporte Biológico , Vías Biosintéticas , Diferenciación Celular , Desarrollo de la Planta/genética , Unión Proteica , Proteolisis , Transducción de SeñalRESUMEN
OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS). METHODS: We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS. RESULTS: The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35ï¼0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46ï¼0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34ï¼0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44ï¼0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42ï¼0.88, P = 0.008) . CONCLUSIONS: The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.
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Astenozoospermia/genética , Osteopontina , Polimorfismo de Nucleótido Simple , Humanos , Masculino , Osteopontina/genéticaRESUMEN
The production of photo-switchable molecular nanomagnets with substantial coercivity, which is indispensable for information storage and process applications, is challenging. Introducing photo-responsive spin-crossover units provides a feasible means of controlling the magnetic anisotropy, interactions, and overall nanomagnet properties. Herein, we report a cyanide-bridged chain 1â 12H2 O ({[(Pz Tp)FeIII (CN)3 ]2 FeII (Pmat)2 }n â 12 H2 O) generated by linking the FeII -based spin-crossover unit with the [(Pz Tp)Fe(CN)3 ]- (Pz Tp: tetrakis(pyrazolyl)borate) building block in the presence of asymmetric ditopic ligand Pmat ((4-pyridine-4-yl)methyleneamino-1,2,4-triazole). Structural characterization revealed that the introduction of this asymmetric ligand led to a distorted coordination environment of FeII ions, which were equatorially coordinated by four cyanide N atoms, and apically coordinated by one pyridine N atom and one triazole N atom. Upon 808-nm light irradiation, 1â 12H2 O underwent photoinduced spin-crossover and exhibited single-chain magnet behavior with a coercive field of up to 1.3â T. This represents a 3d-based photoinduced single-chain magnet exhibiting pronounced hysteresis.
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OBJECTIVE: To date, the burden of childhood spinal TB in China has not been estimated, and current treatment is hindered by a lack of evidence. This study aimed to review our experience of childhood spinal TB. METHODS: We reviewed the medical records of paediatric patients (≤15 years) admitted for spinal TB (confirmed or possible) at Shandong Provincial Chest Hospital from January 2006 to December 2019. Demographic, clinical, laboratory and radiological data were collected from medical records and analysed retrospectively. RESULTS: Seventy-two patients were diagnosed with spinal TB. 45 were male (62.5%), and 27 female (37.5%), with a mean age of 8.42 ± 4.47 (SD) years. During this 14-year period, the overall prevalence of spinal TB among childhood TB was 4.5%. T-SPOT.TB, AFB smear, mycobacterial culture, TB RT-PCR and biopsies were positive in 29.6%, 14.3%, 23.3%, 43.8% and 88.5% of assayed patients, respectively. The overall surgical rate of the studied patients was 40.3%. The requirement of surgery in childhood spinal TB was associated with pulmonary TB (OR = 4.000, 95% CI: 1.197, 13.367). CONCLUSION: Spinal TB in children cannot be neglected. It remains a severe problem to public health, and more attention should be paid to initiating treatment early.
OBJECTIF: A ce jour, la charge de la tuberculose (TB) vertébrale infantile en Chine n'a pas été estimée et le traitement actuel est entravé par un manque de données. Cette étude visait à passer en revue notre expérience de la TB vertébrale infantile. MÉTHODES: Nous avons examiné les dossiers médicaux des patients pédiatriques (≤15 ans) admis pour une TB vertébrale (confirmés ou possibles) au Shandong Provincial Chest Hospital de janvier 2006 à décembre 2019. Les données démographiques, cliniques, de laboratoire et radiologiques ont été recueillies à partir des dossiers médicaux et analysées rétrospectivement. RÉSULTATS: Soixante-douze patients ont reçu un diagnostic de TB vertébrale. 45 étaient de sexe masculin (62,5%) et 27 de sexe féminin (37,5%), avec un âge moyen de 8,42 ± 4,47 (DS) ans. Au cours de cette période de 14 ans, la prévalence globale de la TB vertébrale dans la TB infantile était de 4,5%. T-SPOT.TB, frottis de BAR, culture mycobactérienne, RT-PCR, TB et biopsies étaient positifs chez 29,6%, 14,3%, 23,3%, 43,8% et 88,5% des patients testés, respectivement. Le taux chirurgical global chez les patients étudiés était de 40,3%. La nécessité d'une intervention chirurgicale dans la TB vertébrale infantile était associée à la TB pulmonaire (OR: 4,000, IC95%: 1,197 - 13,367). CONCLUSION: La TB vertébrale chez l'enfant ne peut pas être négligée. Elle demeure un grave problème de santé publique et il faudrait accorder plus d'attention à l'initiation précoce du traitement.
Asunto(s)
Tuberculosis Pulmonar/complicaciones , Tuberculosis de la Columna Vertebral/diagnóstico , Tuberculosis de la Columna Vertebral/epidemiología , Tuberculosis de la Columna Vertebral/cirugía , Adolescente , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Prevalencia , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances the transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among childhood pleural TB patients in China. METHODS: Between January 2006 and December 2019, consecutive patients aged ≤15 years with definite or possible pleural TB were included for analysis. Treatment delay duration was defined as the time interval from the onset of symptoms to treatment initiation and was stratified into two categories: < 30 days, ≥30 days (median delay day is 30 days). The electronic medical records of children were reviewed to obtain demographic characteristics, clinical characteristics, laboratory examinations, and radiographic findings. Univariate and multivariate logistic regressions were used to explore the factors associated with treatment delay in patients. RESULTS: A total of 154 children with pleural TB were included, with a mean age of 12.4 ± 3.3 years. The median treatment delay was 30 days (interquartile range, 10-60 days) and 51.3% (n = 79) of patients underwent a treatment delay. Multivariate analysis revealed that heart rate (≤92 beats/min, age-adjusted OR = 2.503, 95% CI: 1.215, 5.155) and coefficient of variation of red cell distribution width (RDW-CV, ≥12.9%, age-adjusted OR = 4.705, 95% CI: 2.048, 10.811) were significant risk factors for treatment delays in childhood pleural TB. CONCLUSION: Our findings suggested that a significant treatment delay occurs among children with pleural TB in China. Patients with a low heart rate or a high RDW-CV experienced delays in the initiation of anti-TB therapy. Therefore, well awareness of the associations between clinical characteristics and treatment delay may improve the management of children with pleural TB and enable us to develop preventive strategies to reduce the treatment delay.