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Background: Elevated red blood cell distribution width (RDW) levels are strongly associated with an increased risk of mortality in patients with congestive heart failure (CHF). Additionally, heart failure has been closely linked to diabetes. Nevertheless, the relationship between RDW and in-hospital mortality in the intensive care unit (ICU) among patients with both congestive heart failure (CHF) and diabetes mellitus (DM) remains uncertain. Methods: This retrospective study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, a comprehensive critical care repository. RDW was assessed as both continuous and categorical variables. The primary outcome of the study was in-hospital mortality at the time of hospital discharge. We examined the association between RDW on ICU admission and in-hospital mortality using multivariable logistic regression models, restricted cubic spline analysis, and subgroup analysis. Results: The cohort consisted of 7,063 patients with both DM and CHF (3,135 females and 3,928 males). After adjusting for potential confounders, we found an association between a 9% increase in mortality rate and a 1 g/L increase in RDW level (OR = 1.09; 95% CI, 1.05â¼1.13), which was associated with 11 and 58% increases in mortality rates in Q2 (OR = 1.11, 95% CI: 0.87â¼1.43) and Q3 (OR = 1.58, 95% CI: 1.22â¼2.04), respectively, compared with that in Q1. Moreover, we observed a significant linear association between RDW and in-hospital mortality, along with strong stratified analyses to support the findings. Conclusions: Our findings establish a positive association between RDW and in-hospital mortality in patients with DM and CHF.
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Satellite nodules is a key clinical characteristic which has prognostic value of hepatocellular carcinoma (HCC). Currently, there is no gene-level predictive model for Satellite nodules in liver cancer. For the 377 HCC cases collected from the dataset of Cancer Genome Atlas (TCGA), their original pathological data were analyzed to extract information regarding satellite nodules status as well as other relevant pathological data. Then, this study employed statistical modeling for prognostic model establishment in TCGA, and validation in International Cancer Genome Consortium (ICGC) cohorts and GSE76427. Through rigorous statistical analyses, 253 differential satellite nodules-related genes (SNRGs) were identified, and four key genes related to satellite nodules and prognosis were selected to construct a prognostic model. The high-risk group predicted by our model exhibited an unfavorable overall survival (OS) outlook and demonstrated an association with adverse worse clinical characteristics such as larger tumor size, higher alpha-fetoprotein, microvascular invasion and advanced stage. Moreover, the validation of the model's prognostic value in the ICGC and GSE76427 cohorts mirrored that of the TCGA cohort. Besides, the high-risk group also showed higher levels of resting Dendritic cells, M0 macrophages infiltration, alongside decreased levels of CD8+ T cells and γδT cells infiltration. The prognostic model based on SNRGs can reliability predict the OS of HCC and is likely to have predictive value of immunotherapy for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Pronóstico , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , AncianoRESUMEN
Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.
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Calcio , Diabetes Mellitus , Insuficiencia Cardíaca , Mortalidad Hospitalaria , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/sangre , Femenino , Masculino , Anciano , Calcio/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Diabetes Mellitus/sangre , Diabetes Mellitus/mortalidad , Anciano de 80 o más AñosRESUMEN
Current studies on facial growth and development have been largely based on European populations. Less studied are African populations, who because of their distinct genetic makeup and environmental conditions, provide deeper insights into patterns of facial development. Patterns of facial shape development in African populations remain largely uncharacterised. Our study aimed to establish facial growth and development trajectories based on a cohort of 2874 Bantu Africans from Tanzania aged 6-18 years, with particular focus on identifying morphogenetic processes that lead to observed developmental shape changes. Procrustes ANCOVA suggested sexually dimorphic patterns of facial shape development (p = 0.0036). The forehead was relatively contracted during development in both sexes. The glabella region was more anteriorly displaced in females due to expansion in the region laterosuperior to the eyes. Nasal protrusion increased with development, which was found to arise from local expansion in the nasal alae and columella. Local expansion in the upper and lower labial regions resulted in forward displaced lips in both sexes, with the effect more pronounced in males. The mentum was displaced more anteriorly in females due to comparatively more expanded mental regions with development. The lateral facial region corresponding to the underlying body of the mandible were developmentally expanded but were posteriorly positioned due to protrusive growth of surrounding structures. Generalised additive modelling of Procrustes variance suggested that facial variation decreased non-linearly with age (p < 0.05). Relative principal component analysis suggested that variations in facial outline shape were developmentally constrained, whereas nasolabial and mental regions, where developmental changes were significant, became morphologically diversified with development. In contrast to simple descriptive illustration of facial shape development, we gained transformative insights into patterns of facial shape development by analysing morphogenetic processes and variational properties. Our analytical framework is broadly applicable to morphometric studies on ontogenetic shape changes.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.
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Mercury (Hg), as a global pollutant, is persistent, migratory, insidious, highly biotoxic and highly enriched, and is widely distributed in the atmosphere, hydrosphere, biosphere and lithosphere. Wetland ecosystems, as active mercury reservoirs, have become the most important sources and sinks of heavy metal mercury. Distinguished from natural wetlands, artificial wetlands located in urban sections of rivers face problems such as diverse urban pollution sources and complex spatial and temporal changes. Therefore, in this study, five intermittently distributed artificial wetlands were selected from the upstream to the downstream of the Changchun section of the Yitong River, a tributary of the Songhua River basin in the old industrial base of Northeast China. The mercury levels in the water bodies, sediments and plants of the artificial wetlands were collected and tested in four quarters from April 2023 to analyse the spatial and temporal distribution characteristics of total mercury. The results showed that the mercury levels in the water bodies, sediments and plants of the five wetlands showed a fluctuating trend with the river flow direction and had certain spatial and temporal distribution characteristics. This phenomenon was attributed to the sinking of external mercury pollution sources. In general, the wetland ecosystems showed a decreasing trend in the total Hg output of the downstream watershed. This may be due to the retention of particulate matter by aquatic plants in artificial wetlands to regular salvage of dead aquatic plants. At the same time urbanization and industrialization affect mercury levels in aquatic environments, so the risk of residential exposure needs to be looked at.
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BACKGROUND: Prior studies have established a connection between folate intake and cardiovascular disease (CVD). Abdominal aortic calcification (AAC) has been introduced as a good predictor of CVD events, but no previous study has investigated the relationship between dietary folate intake and severe AAC. Therefore, the study aims to explore the association between dietary folate intake and severe AAC in the United States (US) middle-aged and elderly population. METHODS: This study employed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between dietary folate intake and severe AAC. Two 24-h dietary recall interviews were conducted to assess dietary folate intake and its sources, while a DXA scan was used to determine the AAC score. To analyze the association between dietary folate intake and severe AAC, a multivariable logistic regression model was applied, and a subgroup analysis was performed. RESULTS: Our analysis utilized data from 2640 participants aged 40 years and above, including 288 individuals diagnosed with severe AAC. After adjusting for confounding factors, we observed an inverted L-shaped association between folate intake and severe AAC. Upon further adjustment for specific confounding factors and covariates, the multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the second, third, and fourth quartiles of folate intake, using the first quartile as the reference, were as follows: 1.24 (0.86-1.79), 0.86 (0.58-1.27), and 0.63 (0.41-0.97), respectively. Subgroup analysis results were consistent with the logistic regression models, indicating concordant findings. Moreover, no significant interaction was observed in the subgroup analyses. CONCLUSIONS: The study findings suggest an inverted L-shaped association between dietary folate intake and severe AAC. However, additional prospective investigations are necessary to explore the impact of dietary folate intake on severe AAC in patients.
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Enfermedades Cardiovasculares , Calcificación Vascular , Adulto , Persona de Mediana Edad , Humanos , Anciano , Estados Unidos/epidemiología , Encuestas Nutricionales , Ácido Fólico , Estudios Transversales , Estudios Prospectivos , Aorta Abdominal/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/epidemiología , Factores de RiesgoRESUMEN
The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)-immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P = .022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities.
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BACKGROUND: Evidence remains limited and inconsistent for assessing cognitive function in Chinese older adults (CFCOA) and inequalities in cognitive function in Chinese older adults (ICFCOA) and exploring their influencing factors and gender differences. This study aimed to identify influencing factors and inequality in CFCOA to empirically explore the existence and sources of gender differences in such inequality and analyse their heterogeneous effects. METHODS: Based on data from the China Health and Retirement Longitudinal Study (CHARLS) for three periods from 2011 to 2015, recentered influence function unconditional quantile regression (RIF-UQR) and recentered influence function ordinary least squares (RIF-OLS) regression were applied to assess influencing factors of CFCOA, while grouped treatment effect estimation, Oaxaca-Blinder decomposition, and propensity score matching (PSM) methods were conducted to identify gender differences in ICFCOA and influencing factors, respectively. RESULTS: The results showed heterogeneous effects of gender, age, low BMI, subjective health, smoking, education, social interactions, physical activity, and household registration on CFCOA. Additionally, on average, ICFCOA was about 19.2-36.0% higher among elderly females than among elderly males, mainly due to differences in characteristic effects and coefficient effects of factors such as marital status and education. CONCLUSIONS: Different factors have heterogeneous and gender-differenced effects on CFCOA and ICFCOA, while the formation and exacerbation of ICFCOA were allied to marital status and education. Considering the severe ageing and the increasing incidence of cognitive decline, there is an urgent need for the government and society to adopt a comprehensive approach to practically work for promoting CFCOA and reducing ICFCOA.
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Cognición , Humanos , Masculino , Femenino , Anciano , China/epidemiología , Cognición/fisiología , Estudios Longitudinales , Factores Sexuales , Estudios de Cohortes , Persona de Mediana Edad , Anciano de 80 o más Años , Disparidades en el Estado de Salud , Factores Socioeconómicos , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Pueblos del Este de AsiaRESUMEN
BACKGROUND: We recently encountered a Rhnull phenotype proband within one family in the Chinese population. Rhnull is a rare autosomal recessive disorder characterized by the absence of the Rh antigens on the erythrocyte membrane, resulting in chronic hemolytic anemia. This study described the serological and molecular analysis of a Chinese Rhnull proband and his immediate family. METHODS: Red blood cells antigen phenotyping and antibody screening/identification were conducted. RHD, RHCE, and RHAG were analyzed using genomic DNA by polymerase chain reaction and sequence analysis. RESULTS: Serologic tests showed a D-C-E-c-e- phenotype in the proband associated with the suspicion of anti-Rh29 (titer 16). Molecular analyses showed a new mutation (c.406dupA) in exon 3 of RHAG. This duplication introduced a reading frameshift (p.Thr136AsnfsTer21). The RHAG mutation was found in the homozygous state for the proband and heterozygous state for his parents. CONCLUSION: We identified a novel RHAG mutation resulting in the Rhnull phenotype of the regulator type. Inheritance of the novel allele was shown by family study.
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Mutación del Sistema de Lectura , Fenotipo , Sistema del Grupo Sanguíneo Rh-Hr , Femenino , Humanos , Masculino , Proteínas Sanguíneas , Pueblos del Este de Asia , Glicoproteínas de Membrana/genética , Linaje , Sistema del Grupo Sanguíneo Rh-Hr/genéticaRESUMEN
Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.
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Desnitrificación , Electrodos , Grafito , Polímeros , Pirroles , Grafito/química , Polímeros/química , Pirroles/química , Técnicas Electroquímicas/métodos , Fuentes de Energía Bioeléctrica , Nitratos/química , Carbono/química , Fibra de Carbono/químicaRESUMEN
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses have caused large outbreaks within avian populations on five continents, with concurrent spillover into a variety of mammalian species. Mutations associated with mammalian adaptation have been sporadically identified in avian isolates, and more frequently among mammalian isolates following infection. Reports of human infection with A(H5N1) viruses following contact with infected wildlife have been reported on multiple continents, highlighting the need for pandemic risk assessment of these viruses. In this study, the pathogenicity and transmissibility of A/Chile/25945/2023 HPAI A(H5N1) virus, a novel reassortant with four gene segments (PB1, PB2, NP, MP) from North American lineage, isolated from a severe human case in Chile, was evaluated in vitro and using the ferret model. This virus possessed a high capacity to cause fatal disease, characterized by high morbidity and extrapulmonary spread in virus-inoculated ferrets. The virus was capable of transmission to naïve contacts in a direct contact setting, with contact animals similarly exhibiting severe disease, but did not exhibit productive transmission in respiratory droplet or fomite transmission models. Our results indicate that the virus would need to acquire an airborne transmissible phenotype in mammals to potentially cause a pandemic. Nonetheless, this work warrants continuous monitoring of mammalian adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts.
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Hurones , Subtipo H5N1 del Virus de la Influenza A , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Hurones/virología , Humanos , Chile , Gripe Humana/virología , Gripe Humana/transmisión , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/transmisión , Infecciones por Orthomyxoviridae/veterinaria , Subtipo H5N1 del Virus de la Influenza A/genética , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H5N1 del Virus de la Influenza A/clasificación , Subtipo H5N1 del Virus de la Influenza A/fisiología , Virus Reordenados/genética , Virus Reordenados/aislamiento & purificación , Virus Reordenados/patogenicidad , Virus Reordenados/clasificación , Filogenia , Gripe Aviar/virología , Gripe Aviar/transmisiónRESUMEN
BACKGROUND: Corticosteroids have beneficial effects in improving outcomes in hospitalized patients with severe COVID-19 by suppressing excessive immune responses. However, the effect of corticosteroids on the humoral and T-cell responses of survivors of COVID-19 1 year after infection remains uncertain, as it relates to the extent of immediate, antigen-specific defense provided by protective memory. RESEARCH QUESTION: What is the effect of corticosteroids on long-term humoral and T-cell immune responses? STUDY DESIGN AND METHODS: In this retrospective cohort study conducted at a single center, we analyzed data from a cohort who had survived COVID-19 to compare the 1-year seropositivity and titer changes in neutralizing antibodies (NAbs) and SARS-CoV-2-specific antibodies. Additionally, we evaluated the magnitude and rate of SARS-CoV-2-specific T-cell response in individuals who received corticosteroids during hospitalization and those who did not. RESULTS: Our findings indicated that corticosteroids do not statistically influence the kinetics or seropositive rate of NAbs against the Wuhan strain of SARS-CoV-2 from 6 months to 1 year. However, subgroup analysis revealed a numerical increase of NAbs titers, from 20.0 to 28.2, in categories where long-term (> 15 days) and high-dose (> 560 mg) corticosteroids were administered. Similarly, corticosteroids showed no significant effect on nucleoprotein and receptor-binding domain IgG at 1 year, except for spike protein IgG (ß, 0.08; 95% CI, 0.04-0.12), which demonstrated a delayed decline of titers. Regarding T-cell immunity, corticosteroids did not affect the rate or magnitude of T-cell responses significantly. However, functional assessment of memory T cells revealed higher interferon-γ responses in CD4 (ß, 0.61; 95% CI, 0.10-1.12) and CD8 (ß, 0.63; 95% CI, 0.11-1.15) memory T cells in the corticosteroids group at 1 year. INTERPRETATION: Based on our findings, short-term and low-dose corticosteroid therapy during hospitalization does not appear to have a significant effect on long-term humoral kinetics or the magnitude and rate of memory T-cell responses to SARS-CoV-2 antigens. However, the potential harmful effects of long-term and high-dose corticosteroid use on memory immune responses require further investigation.
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Corticoesteroides , Anticuerpos Antivirales , COVID-19 , Hospitalización , Inmunidad Humoral , SARS-CoV-2 , Humanos , Masculino , Femenino , Estudios Retrospectivos , COVID-19/inmunología , Persona de Mediana Edad , SARS-CoV-2/inmunología , Inmunidad Humoral/efectos de los fármacos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Hospitalización/estadística & datos numéricos , Corticoesteroides/uso terapéutico , Células T de Memoria/inmunología , Estudios de Seguimiento , Anticuerpos Neutralizantes/inmunología , Anciano , Tratamiento Farmacológico de COVID-19 , Adulto , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Abnormal changes of monocytes have been observed in acute COVID-19, whereas associations of monocyte count with long COVID were not sufficiently elucidated. METHODS: A cohort study was conducted among COVID-19 survivors discharged from hospital. The primary outcomes were core symptoms of long COVID, distance walked in 6 min, and lung function, and the secondary outcomes were health-related quality of life and healthcare use after discharge. Latent variable mixture modeling was used to classify individuals into groups with similar trajectory of monocyte count from discharge to 2-year after symptom onset. Multivariable adjusted generalized linear regression models and logistic regression models were used to estimate the associations of monocyte count trajectories and monocyte count at discharge with outcomes. RESULTS: In total, 1389 study participants were included in this study. Two monocyte count trajectories including high to normal high and normal trajectory were identified. After multivariable adjustment, participants in high to normal high trajectory group had an odds ratio (OR) of 2.52 (95% CI, 1.44-4.42) for smell disorder, 2.27 (1.27-4.04) for 6-min walking distance less than lower limit of normal range, 2.45 (1.08-5.57) for total lung capacity (TLC) < 80% of predicted, 3.37 (1.16-9.76) for personal care problem, and 1.70 (1.12-2.58) for rehospitalization after discharge at 2-year follow-up compared with those in normal trajectory group. Monocyte count at discharge showed similar results, which was associated with smell disorder, TLC < 80% of predicted, diffusion impairment, and rehospitalization. CONCLUSIONS: Monocyte count may serve as an easily accessible marker for long-term management of people recovering from COVID-19.
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COVID-19 , Trastornos del Olfato , Humanos , Estudios de Cohortes , Monocitos , Síndrome Post Agudo de COVID-19 , Calidad de Vida , Tolerancia al Ejercicio , Pulmón , SobrevivientesRESUMEN
Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.
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Chalconas , Sirtuina 2 , Neoplasias de la Mama Triple Negativas , Humanos , Sirtuina 2/farmacología , Línea Celular Tumoral , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Tubulina (Proteína)/farmacología , Tubulina (Proteína)/uso terapéutico , Proliferación Celular , ApoptosisRESUMEN
Developmental changes of facial shape are commonly investigated through geometric morphometrics. A limitation with this approach is the inability to investigate patterns of morphological changes at local scale. This could be addressed through quantifying the deformation required to deform one shape to another. This study aimed to investigate changes in mean, rate and variance of facial shape at local scale using geometric morphometrics through deformation perspective. A total of 2112 Europeans 3 to 40 years old from the three-dimensional Facial Norms project were included. Shape and rate trajectories from partial least-squares regressions revealed that the developmentally protrusive nasal bridge was due to local expansion in surrounding tissues as opposed to shape changes in nasal bridge per se. Local expansion of the supraorbital region, in particular the medial part in males, resulted in the sloping forehead and deep-situated eyes with development. Facial shape variation increased nonlinearly with age (p < 0.05), with features having larger rate of change becoming more developmentally diversified. In summary, our deformation perspective facilitates unravelling morphogenetic processes underlying shape changes. Our extended analytical scope inspires novel measures worthy of consideration while establishing facial growth charts. The analytical framework in this study is broadly applicable for analysis of shape changes in general.
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Pathologic opening of the blood-brain barrier accelerates the progression of various neural diseases. Basigin, as an essential molecule for the opening of the blood-brain barrier, is a highly glycosylated transmembrane molecule specified in barrier-forming endothelial cells. This study analyzed the involvement of basigin in the regulation of the blood-brain barrier focusing on its glycosylation forms. First, basigin was found to be expressed as cell surface molecules with complex-type glycan as well as those with high-mannose-type glycan in barrier-forming endothelial cells. Monolayers of endothelial cells with suppressed expression of basigin with high-mannose-type glycan were then prepared and exposed to pathologic stimuli. These monolayers retained their barrier-forming properties even in the presence of pathologic stimuli, although their expression of basigin with complex-type glycan was maintained. In vivo, the blood-brain barrier in mice pretreated intravenously with endoglycosidase H was protected from opening under pathologic stimuli. Pathologically opened blood-brain barrier in streptozotocin-injected mice was successfully closed by intravenous injection of endoglycosidase H. These results show that high-mannose-type glycan of the basigin molecule is essential for the opening of the blood-brain barrier and therefore a specific target for protection as well as restoration of pathologic opening of the blood-brain barrier.
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Basigina , Barrera Hematoencefálica , Animales , Ratones , Basigina/metabolismo , Barrera Hematoencefálica/metabolismo , Ciclofilina A/metabolismo , Células Endoteliales/metabolismo , Glicósido Hidrolasas/metabolismo , Hipoxia , Manosa , Polisacáridos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Two-dimensional metal-organic frameworks are considered to be promising electrocatalytic materials due to their ultrathin lamellar structure, ultrahigh porosity and large surface area, but there are still many challenges such as the embedding of organic ligands leading to low density of active sites and poor conductivity. Herein, we synthesize two-dimensional ferrocene-based metal-organic frameworks nanosheet electrocatalysts via the one-step hydrothermal hydrogen peroxide etching method. The prepared FcNi-BDC-H2O2/NF exhibits excellent oxygen evolution reaction performance with a current density of 100 mA·cm-2 at only 258 mV and a small driving potential of 1.542 V (10 mA·cm-2) is required to achieve overall water splitting. Significantly, an overall water-cracked cell using a solar cell assembly achieves the solar hydrogen conversion efficiency of 19.5%. The introduction of high electronegativity ferrocene and the etching of H2O2 increase the Ni3+ content of FcNi-BDC-H2O2, and expose more unsaturated active sites, which improve the intrinsic activity of the catalysts and the mass transfer rate during the catalytic process. Moreover, the FcNi-BDC-H2O2/NF demonstrates significant urea oxidation reaction performance, achieving a potential of 1.35 V and producing 10 mA·cm-2. This study presents a viable approach to investigating highly efficient electrocatalysts for oxygen evolution reaction and urea oxidation reaction using MOF-based bifunctional catalysts.
RESUMEN
Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck epidermis. Accumulating long non-coding RNAs (lncRNAs) have been proven to be involved in the occurrence and development of HNSCC. LncRNA long intergenic non-protein coding RNA 491 (LINC00491) has been confirmed to regulate the progression of some cancers. In our study, we aimed to explore the potential biological function of LINC00491 and expound the regulatory mechanism by which LINC00491 affects the progression of HNSCC. RT-qPCR was utilized to analyze the expression of LINC00491 in HNSCC cell lines and the normal cell line. Functionally, we carried out a series of assays to measure cell proliferation, apoptosis, migration and invasion, such as EdU assay, colony formation, wound healing and western blot assays. Also, mechanism assays including RNA pull down and RIP were also implemented to investigate the interaction of LINC00491 and RNAs. As a result, we discovered that LINC00491 was highly expressed in HNSCC cells. In addition, LINC00491 depletion suppressed cell proliferation, migration and EMT process. Furthermore, we discovered that LINC00491 could bind to miR-508-3p. MiR-508-3p overexpression can restrain HNSCC cell growth. Importantly, miR-508-3p can target SATB homeobox 1 (SATB1) in HNSCC cells. Further, Wnt signaling pathway was proved to be activated by LINC00491 through SATB1 in HNSCC cells. In a word, LINC00491 accelerated HNSCC progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway.