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The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.
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Agamaglobulinemia , Cromossomos Humanos Par 19 , Fluoxetina , Dissomia Uniparental , Humanos , Fluoxetina/uso terapêutico , Cromossomos Humanos Par 19/genética , Agamaglobulinemia/genética , Agamaglobulinemia/tratamento farmacológico , Antígenos CD79/genética , Masculino , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/genética , Mutação/genética , Imunoglobulinas Intravenosas/uso terapêutico , FemininoRESUMO
ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9 %â ee, >99 : 1â dr, and >99 % conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74 % yield, >99.9 %â ee, and 98 : 2â dr at a challenging substrate loading of 110â g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.
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The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which has a close relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) plays an important role not only in regulating the fibrosis process but also in maintaining the mitochondrial function of pancreatic ß-cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG up-regulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose-cultured HK-2 cells and 8-weeks-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF.
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Biofuels developed from biomass crops have the potential to supply a significant portion of our transportation fuel needs. To achieve this potential, however, it will be necessary to develop improved plant germplasm specifically tailored to serve as energy crops. Liquid transportation fuel can be created from the sugars locked inside plant cell walls. Unfortunately, these sugars are inherently resistant to hydrolytic release because they are contained in polysaccharides embedded in lignin. Overcoming this obstacle is a major objective toward developing sustainable bioenergy crop plants. The maize Corngrass1 (Cg1) gene encodes a microRNA that promotes juvenile cell wall identities and morphology. To test the hypothesis that juvenile biomass has superior qualities as a potential biofuel feedstock, the Cg1 gene was transferred into several other plants, including the bioenergy crop Panicum virgatum (switchgrass). Such plants were found to have up to 250% more starch, resulting in higher glucose release from saccharification assays with or without biomass pretreatment. In addition, a complete inhibition of flowering was observed in both greenhouse and field grown plants. These results point to the potential utility of this approach, both for the domestication of new biofuel crops, and for the limitation of transgene flow into native plant species.
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MicroRNAs/genética , Panicum/genética , RNA de Plantas/genética , Zea mays/genética , Sequência de Bases , Biocombustíveis , Biomarcadores , Flores/crescimento & desenvolvimento , Expressão Gênica , Genes de Plantas , Panicum/crescimento & desenvolvimento , Panicum/metabolismo , Plantas Geneticamente Modificadas , Amido/metabolismoRESUMO
Aim: To investigate the correlation of the triglyceride-glucose (TyG) index and its combined obesity indicators with chest pain and cardiovascular disease (CVD) in the pre-diabetes and diabetes population. Methods: This cross-sectional investigation encompassed 6488 participants with diabetes and pre-diabetes who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. The association of the TyG and combined obesity index with chest pain and CVD was investigated using weighted logistic regression models and restricted cubic spline (RCS) analysis. The receiver operating characteristic (ROC) curve analysis was performed to compare different indicators. Results: In multivariate logistic regression fully adjusted for confounding variables, our analyses revealed significant associations between TyG, TyG-BMI, TyG-WC, and TyG-WHtR and chest pain, with adjusted ORs (95% CI) of 1.21 (1.05, 1.39), 1.06 (1.01, 1.11), 1.08 (1.04, 1.14), and 1.27 (1.08, 1.48), respectively. For total-CVD, the adjusted ORs (95% CI) were 1.32 (1.08, 1.61), 1.10 (1.03, 1.17), 1.13 (1.06, 1.19), and 1.63 (1.35, 1.97), respectively, among which TyG, TyG-WC, and TyG-WHtR present curvilinear associations in RCS analysis (all P-nonlinear < 0.05). Furthermore, the ROC curve showed that TyG-WC had the most robust predictive efficacy for total-CVD, coronary heart disease (CHD), and myocardial infarction (MI), while TyG-WHtR had the best predictive ability for angina and heart failure. Conclusion: There are significant associations of TyG and its related indicators with chest pain and total-CVD among the pathoglycemia population. TyG-WC and TyG-WHtR demonstrated superior predictive capability for the incidence of cardiovascular events.
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Glicemia , Doenças Cardiovasculares , Dor no Peito , Inquéritos Nutricionais , Obesidade , Estado Pré-Diabético , Triglicerídeos , Humanos , Feminino , Masculino , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/diagnóstico , Pessoa de Meia-Idade , Estudos Transversais , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/complicações , Triglicerídeos/sangue , Dor no Peito/sangue , Dor no Peito/epidemiologia , Dor no Peito/diagnóstico , Glicemia/análise , Obesidade/complicações , Obesidade/sangue , Obesidade/epidemiologia , Adulto , Estados Unidos/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Idoso , Fatores de RiscoRESUMO
The aim of this study was to evaluate the clinical efficacy of alcohol-based therapy for patients with large odontogenic keratocysts (OKCs). The study was implemented as a retrospective, single-center study. Patients treated with ethanol-based therapy for odontogenic keratocyst were retrospectively evaluated for baseline and postoperative data. The pre- and postoperative clinical situation and the extent of radiographic shrinkage were compared. The event is defined as the achievement of >50% reduction in cyst volume. The cyst reduction rate calculated on panoramic radiographs ranged from 7.4% to 99.9% (mean [standard deviation] 55.3% [27.9%]) and was statistically significant (P < 0.05). Specifically, it has been found that, radiographically, 47.6% of patients achieved >50% reduction in cyst volume within 12 months. The continuous cortical bone was rebuilt, and the cyst cavity was filled with regenerated trabecular bone. The 22 included patients presented with nonclinical problems, had no need for further intervention, and exhibited persistent impaction of the teeth. The results of this study demonstrated that ethanol-based therapy triggered marked radiographic reductions of large OKC, indicating that using this technique is efficient.
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Cistos Odontogênicos , Tumores Odontogênicos , Humanos , Estudos Retrospectivos , Cistos Odontogênicos/diagnóstico por imagem , Cistos Odontogênicos/cirurgia , Etanol/uso terapêutico , Resultado do TratamentoRESUMO
AIMS: Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination. METHODS AND RESULTS: We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts. CONCLUSIONS: TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.
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Vacinas contra COVID-19 , COVID-19 , Cardiomiopatia de Takotsubo , Humanos , COVID-19/complicações , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Ecocardiografia , Cardiomiopatia de Takotsubo/induzido quimicamente , Cardiomiopatia de Takotsubo/etiologia , Vacinação/efeitos adversosRESUMO
BACKGROUND: Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. METHODS: A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. RESULTS: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non-takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non-takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001). CONCLUSION: Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.
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COVID-19 , Mortalidade Hospitalar , Hospitalização , Cardiomiopatia de Takotsubo , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Cardiomiopatia de Takotsubo/epidemiologia , Cardiomiopatia de Takotsubo/diagnóstico , Feminino , Masculino , Incidência , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Estados Unidos/epidemiologia , SARS-CoV-2 , Comorbidade , Fatores de RiscoRESUMO
Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF-α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc-α, PPAR-γ, and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively.
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Background Acute pericarditis (AP) is considered a cardiovascular complication in patients with COVID-19. We aimed to ass-ess the incidence, associated complications, and clinical impact of AP on hospitalized patients with COVID-19. Methods and Results In this retrospective cohort study, International Classification of Diseases, Tenthth Revision, Clinical Modification (ICD-10) codes were used to identify patients with COVID-19 with or without AP in the National Inpatient Sample 2020 database. We compared outcomes between AP and non-AP groups before and after propensity-score matching for patient and hospital demographics and relevant comorbidities. A total of 211 619 patients with a primary diagnosis of COVID-19 were identified, including 983 (0.46%) patients who had a secondary diagnosis of AP. Before matching, patients with COVID-19 with AP were younger (59.93±19.24 years old versus 64.29±16.82 years old) and more likely to have anemia (40.5% versus 19.9%), cancer (6.7% versus 3.6%), and chronic kidney disease (29.3% versus 19.6%) (all P<0.05). After matching, patients with COVID-19 with AP (n=980), when compared with the matched non-AP group (n=2936), had higher rates of mortality (21.3% versus 11.1%, P<0.001), cardiac arrest (5.0% versus 2.6%, P<0.001), cardiogenic shock (4.2% versus 0.5%, P<0.001), ventricular arrhythmia (4.7% versus 1.9%, P<0.001), acute kidney injury (38.3% versus 28.9%, P<0.001), acute congestive heart failure (14.3% versus 4.8%, P<0.001), and longer length of stay (7.00±10.00 days versus 5.00±7.00 days, P<0.001) and higher total charges ($75066.5±$130831.3 versus $44824.0±$63660.5, P<0.001). Conclusions In hospitalized patients with COVID-19, AP is a rare but severe in-hospital complication and is associated with worse in-hospital outcomes.
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COVID-19 , Pericardite , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tempo de Internação , Estudos Retrospectivos , Incidência , COVID-19/complicações , COVID-19/epidemiologia , Pericardite/epidemiologiaRESUMO
Biophysical factors are essential in cell survival and behaviors, but constructing a suitable 3D microenvironment for the recruitment of stem cells and exerting their physiological functions remain a daunting challenge. Here, we present a novel silk fibroin (SF)-based fabrication strategy to develop hierarchical microchannel scaffolds for biomimetic nerve microenvironments in vitro. We first modulated the formation of SF nanofibers (SFNFs) that mimic the nanostructures of the native extracellular matrix (ECM) by using graphene oxide (GO) nanosheets as templates. Then, SFNF-GO systems were shaped into 3D porous scaffolds with aligned micro-lamellar structures by freeze-casting. The interconnected microchannels successfully induced cell infiltration and migration to the SFNF-GO scaffolds' interior. Meanwhile, the nano-fibrillar structures and the GO component significantly induced neural stem cells (NSCs) to differentiate into neurons within a short timeframe of 14 d. Importantly, these 3D hierarchical scaffolds induced a mild inflammatory response, extensive cell recruitment, and effective stimulation of NSC neuronal differentiation when implanted in vivo. Therefore, these SFNF-GO lamellar scaffolds with distinctive nano-/micro-topographies hold promise in the fields of nerve injury repair and regenerative medicine.
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Fibroínas , Células-Tronco Neurais , Alicerces Teciduais/química , Células-Tronco Neurais/metabolismo , Fibroínas/química , Neurônios , Diferenciação Celular , Engenharia TecidualRESUMO
Background: Acute kidney injury (AKI) is a prevalent complication of acute aortic dissection (AAD) and is associated with poor outcomes. The onset of AAD may result in endothelial injury due to the formation of the false lumen, which can activate the coagulation pathway and lead to coagulation dysfunction. It serves as a valuable diagnostic and prognostic marker for AAD, but also plays a role in the pathological mechanisms underlying AKI. We aimed to investigate the potential value of coagulation indicators at admission for assessing in-hospital AKI and malignant events after AAD. Methods: We identified patients with AAD admitted to the First Affiliated Hospital of Shantou University Medical College from January 2015 to October 2020 and divided them into two groups according to coagulation function. Univariable and multivariable analyses were used to analyze the association between coagulation indicators and AKI and malignant events in patients with AAD. Chi-squared or Fisher exact test and receiver operating characteristic (ROC) curve analysis was conducted to assess the value of coagulation indicators in predicting in-hospital AKI and malignant events. Results: A total of 487 patients were enrolled in this study, including 309 cases with normal coagulation. After the multivariable adjustment, the incidence of in-hospital AKI in the abnormal coagulation group was significantly higher [model 1: 2.061 (1.214-3.501), P=0.007; model 2: 1.833 (1.058-3.177), P=0.031; model 3: 1.836 (1.048-3.216), P=0.034]. The incidence of malignant events was higher in the abnormal prothrombin time (PT) group [model 1: 4.283 (0.983-18.665), P=0.053; model 2: 7.342 (1.467-36.749), P=0.015; model 3: 6.996 (1.377-35.537), P=0.019]. Chi-squared and Fisher exact test showed that PT and abnormal coagulation score (ACS) were statistically different among the AKI groups and malignant event groups. Under ROC analysis, coagulation indicators were helpful to predict AKI (AUC =0.668; P<0.001). Conclusions: Our study confirmed the presence of coagulation dysfunction is associated with an increased risk of AKI and malignant events. It suggested the severity of coagulation dysfunction is positively correlated with the incidence of in-hospital AKI in AAD patients. These results highlight the importance of considering coagulation dysfunction as a potential mechanism underlying AKI and malignant events after AAD.
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Transcranial direct current stimulation (tDCS) has been used to explore the causal relationship between specific brain regions and task switching. However, most studies have focused on the frontal cortex, and only few have examined other related cortices, e.g., the parietal cortex. So far, no prior study has systematically explored the tDCS-induced effect of the parietal cortex in different task switching types. Therefore, the current study mainly used the unilateral anodal-tDCS (a-tDCS) stimulation setting to investigate the possible involvement of the parietal cortex in predictable and unpredictable task switching. It was noted that compared with sham group, significantly higher switch cost reaction time of right anode tDCS (RA) group was found in predictable task but not unpredictable task. No interaction effect was observed between congruence and tDCS groups in predictable task. These findings suggested that a-tDCS over right parietal cortex could markedly decrease the predictable task-switching performance in both congruent and incongruent trials, and indicated that parietal cortex is more likely to be involved in the proactive cognitive processes, such as endogenous preparation.
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Estimulação Transcraniana por Corrente Contínua , Eletrodos , Lobo Frontal , Lobo Parietal/fisiologia , Tempo de Reação/fisiologiaRESUMO
Brassinosteriod (BR) plays important roles in regulation of plant growth, development and environmental responses. BR signaling regulates multiple biological processes through controlling the activity of BES1/BZR1 regulators. Apart from the roles in the promotion of plant growth, BR is also involved in regulation of the root foraging response under low nitrogen, however how BR signaling regulate this process remains unclear. Here we show that BES1 and LBD37 antagonistically regulate root foraging response under low nitrogen conditions. Both the transcriptional level and dephosphorylated level of BES1, is significant induced by low nitrogen, predominantly in root. Phenotypic analysis showed that BES1 gain-of-function mutant or BES1 overexpression transgenic plants exhibits progressive outgrowth of lateral root in response to low nitrogen and BES1 negatively regulates repressors of nitrate signaling pathway and positively regulates several key genes required for NO3 - uptake and signaling. In contrast, BES1 knock-down mutant BES1-RNAi exhibited a dramatical reduction of lateral root elongation in response to low N. Furthermore, we identified a BES1 interacting protein, LBD37, which is a negative repressor of N availability signals. Our results showed that BES1 can inhibit LBD37 transcriptional repression on N-responsive genes. Our results thus demonstrated that BES1-LBD37 module acts critical nodes to integrate BR signaling and nitrogen signaling to modulate the root forging response at LN condition.
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OBJECTIVE: This study assesses the effect of malnutrition on the in-hospital outcomes of patients with takotsubo cardiomyopathy (TCM). METHODS: We performed a retrospective cohort analysis using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for a primary diagnosis of TCM from the National Inpatient Sample database (2016-2018). A concurrent diagnosis of malnutrition was then identified, and these patients were divided into the malnutrition group and non-malnutrition group. To adjust for underlying risk factors, a multivariable logistic regression model was employed followed by a propensity score matching analysis for the malnutrition and the non-malnutrition group. We then compared the in-hospital outcomes between these two groups. RESULTS: Among 4733 patients with a primary diagnosis of TCM, 221 (4.7%) patients with TCM were found to be malnourished. After propensity score matching, patients with TCM with malnutrition were found to have a higher mortality rate (8.3% versus 2.0%, P < 0.001), a higher rate of complications including cardiogenic shock (16.1% versus 7.0%, P < 0.001), ventricular arrhythmia (8.8% versus 3.9%, P = 0.01), acute kidney injury (24.9% versus 10.6%, P < 0.001), and acute respiratory failure (32.7% versus 17.8%, P < 0.001). There was no statistically significant difference in the incidence of cardiac arrest between the two groups. Malnutrition of severe degree was associated with a sevenfold (odds ratio 6.8, 95% confidence interval, 3.2-13.4) increased risk of in-hospital mortality compared with those without malnutrition. CONCLUSION: Patients with malnutrition who were admitted with TCM were associated with higher rates of in-hospital mortality and complications compared with those without malnutrition.
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Desnutrição , Cardiomiopatia de Takotsubo , Mortalidade Hospitalar , Hospitais , Humanos , Desnutrição/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/epidemiologiaRESUMO
Cellulose is inherently resistant to breakdown, and the native crystalline structure (cellulose I) of cellulose is considered to be one of the major factors limiting its potential in terms of cost-competitive lignocellulosic biofuel production. Here we report the impact of ionic liquid pretreatment on the cellulose crystalline structure in different feedstocks, including microcrystalline cellulose (Avicel), switchgrass (Panicum virgatum), pine ( Pinus radiata ), and eucalyptus ( Eucalyptus globulus ), and its influence on cellulose hydrolysis kinetics of the resultant biomass. These feedstocks were pretreated using 1-ethyl-3-methyl imidazolium acetate ([C2mim][OAc]) at 120 and 160 °C for 1, 3, 6, and 12 h. The influence of the pretreatment conditions on the cellulose crystalline structure was analyzed by X-ray diffraction (XRD). On a larger length scale, the impact of ionic liquid pretreatment on the surface roughness of the biomass was determined by small-angle neutron scattering (SANS). Pretreatment resulted in a loss of native cellulose crystalline structure. However, the transformation processes were distinctly different for Avicel and for the biomass samples. For Avicel, a transformation to cellulose II occurred for all processing conditions. For the biomass samples, the data suggest that pretreatment for most conditions resulted in an expanded cellulose I lattice. For switchgrass, first evidence of cellulose II only occurred after 12 h of pretreatment at 120 °C. For eucalyptus, first evidence of cellulose II required more intense pretreatment (3 h at 160 °C). For pine, no clear evidence of cellulose II content was detected for the most intense pretreatment conditions of this study (12 h at 160 °C). Interestingly, the rate of enzymatic hydrolysis of Avicel was slightly lower for pretreatment at 160 °C compared with pretreatment at 120 °C. For the biomass samples, the hydrolysis rate was much greater for pretreatment at 160 °C compared with pretreatment at 120 °C. The result for Avicel can be explained by more complete conversion to cellulose II upon precipitation after pretreatment at 160 °C. By comparison, the result for the biomass samples suggests that another factor, likely lignin-carbohydrate complexes, also impacts the rate of cellulose hydrolysis in addition to cellulose crystallinity.
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Biomassa , Celulose/química , Enzimas/química , Configuração de Carboidratos , Cristalografia por Raios X , Hidrólise , Propriedades de SuperfícieRESUMO
The aim of the present study was to investigate the effect of tumor necrosis factor-α (TNF-α) on the proliferation and osteogenesis of human periodontal mesenchymal stem cells (hPDLSCs). Antigen expression in hPDLSCs was detected by flow cytometry. hPDLSCs were divided into four groups: A control group with no TNF-α treatment, and three experimental groups treated with 0.1, 1 and 10 ng/ml TNF-α, respectively. The effect of TNF-α on proliferation of hPDLSCs in vitro was detected using a Cell Counting Kit-8 assay. Differentiation into an osteogenic lineage was detected by alkaline phosphatase sand alizarin red staining, and the mRNA and protein expression levels of runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and type I collagen (Col-I) were detected using reverse transcription-quantitative PCR and western blot respectively. Following treatment with 10 ng/ml TNF-α, proliferation was significantly increased compared with an untreated control group (P<0.01). Additionally, there was a significant inhibition of alkaline phosphatase enzyme activity, alizarin red mineralization node size, and in the gene and protein expression levels of osteogenic differentiation markers, including Runx2, OCN and COL-I (all, P<0.05). Taken together, the results indicated that treatment with 10 ng/ml TNF-α promoted the proliferation of hPDLSCs in vitro and inhibited osteogenic differentiation of hPDLSCs, providing an experimental basis for regulation of hPDLSC-mediated periodontal tissue regeneration.
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Takotsubo cardiomyopathy (TCM), characterized by reversible ventricular dysfunction, has similar mortality to acute coronary syndrome. With the growing interest in the diagnosis of and interventions for TCM, many risk factors had been found to affect the prognosis of TCM patients, such as age, sex, and pre-existing diseases. Because of the incomplete understanding of the pathophysiologic mechanism in TCM, evidence-based medical therapy for this condition is lacking. Early intervention on risk factors may improve the outcomes of TCM. In this review, we sought to provide up-to-date evidence on risk factors and medical therapies that affect TCM outcome. We found that male sex, physical triggers, and certain comorbidities such as chronic kidney disease, malignant disease, higher body mass index, sepsis, chronic obstructive pulmonary disease, and anaemia were associated with poor TCM prognosis. In contrast, race, hyperlipidaemia, diabetes mellitus, and mood disorders were not clearly associated with TCM prognosis. We also reviewed the effect of medical therapies on TCM outcome, including angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, calcium channel blockers, and statins. The evidence that these medications confer a survival benefit on TCM patients is limited. Understanding these prognostic factors could help develop risk-stratification tools for TCM and establish effective prevention and interventions for this not-so-benign condition. Further multicentre clinical studies with large samples and meta-analyses of findings from previous studies are needed to address the inconsistent findings among the many potential risk factors for TCM.
Assuntos
Cardiomiopatia de Takotsubo , Índice de Massa Corporal , Comorbidade , Humanos , Masculino , Prognóstico , Fatores de Risco , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/epidemiologiaRESUMO
miR-139-5p has a tumor suppressor effect in some cancers and negatively regulates CXCR4. To this end, we examined the expression and mechanism of of action of miR-139-5p and CXCR4 in oral squamous cell carcinoma (OSCC). miRNA-139-5p was down-regulated whereas CXCR4 was increased in tissues and cells of OSCC. Moreover, low expression of miR-139-5p was associated with a low survival. Overexpression of miR-139-5p in OSCC inhibited in vitro and in vivo cell proliferation and in vitro mobility of OSCC and inhibited the expression of WNT responsive c-myc, cyclinD1, and Bcl-2, and such effects were all reversible by an inhibitor of miR-139-5p or over-expression of CXCR4. The inverse relation between expression of miR-139-5p and CXCR4 might be related to the fact that miR-139-5p negatively regulates CXCR4 expression by virtue of direct binding. These findings underscore the importance of miR-139-5p and CXCR4 in regulation of OSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/genética , Receptores CXCR4/genética , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Progressão da Doença , Humanos , Camundongos Nus , Neoplasias Bucais/metabolismo , Neoplasias Bucais/terapia , Interferência de RNA , Receptores CXCR4/metabolismo , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Myositis ossificans (MO) is a rare disease and its major feature is the formation of heterotropic bone involving muscle or any other type of soft tissue (tendons, ligament, fascia and connective tissue). In the present study, a case report of a patient diagnosed with MO is presented. The diagnosis was established by evaluation of the medical history of the patient and the patient's family, as well as clinical data, radiology and post-operative pathology. The patient underwent excision surgery of the calcified lesion. In addition, genomic DNA was examined from blood samples of the patient and the patient's father with their consent. A mutation in the non-coding region was detected but any direct causative effect remains elusive. The present case report provided significant information with regard to the incidence of MO in four members of the same family assessed over three generations. The disease exhibited a unique localization in the maxillofacial region.