RESUMEN

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) contributes to the cardiometabolic diseases through multiple mechanisms. Fatty liver index (FLI) has been formulated as a non-invasive, convenient, and cost-effective approach to estimate the degree of MASLD. The current study aims to evaluate the correlation between FLI and the prevalent cardiometabolic multimorbidity (CMM), and to assess the usefulness of FLI to improve the detection of the prevalent CMM in the general population. Methods: 26,269 subjects were enrolled from the National Health and Nutrition Examination Survey 1999-2018. FLI was formulated based on triglycerides, body mass index, γ -glutamyltransferase, and waist circumference. CMM was defined as a history of 2 or more of diabetes mellitus, stroke, myocardial infarction. Results: The prevalence of CMM was 10.84%. With adjustment of demographic, anthropometric, laboratory, and medical history covariates, each standard deviation of FLI leaded to a 58.8% risk increase for the prevalent CMM. The fourth quartile of FLI had a 2.424 times risk for the prevalent CMM than the first quartile, and a trend towards higher risk was observed. Smooth curve fitting showed that the risk for prevalent CMM increased proportionally along with the elevation of FLI. Subgroup analysis demonstrated that the correlation was robust in several conventional subpopulations. Receiver-operating characteristic curve analysis revealed an incremental value of FLI for detecting prevalent CMM when adding it to conventional cardiometabolic risk factors (Area under the curve: 0.920 vs. 0.983, P < 0.001). Results from reclassification analysis confirmed the improvement from FLI. Conclusion: Our study demonstrated a positive, linear, and robust correlation between FLI and the prevalent CMM, and our findings implicate the potential usefulness of FLI to improve the detection of prevalent CMM in the general population.

RESUMEN

BACKGROUND: The number of spikelets per spike is a key trait that affects the yield of bread wheat (Triticum aestivum L.). Identification of the QTL for spikelets per spike and its genetic effects that could be used in molecular assistant breeding in the future. RESULTS: In this study, four recombinant inbred line (RIL) populations were generated and used, having YuPi branching wheat (YP), with Supernumerary Spikelets (SS) phenotype, as a common parent. QTL (QSS.sicau-2 A and QSS.sicau-2D) related to SS trait were mapped on chromosomes 2 A and 2D through bulked segregant exome sequencing (BSE-Seq). Fourteen molecular markers were further developed within the localization interval, and QSS.sicau-2 A was narrowed to 3.0 cM covering 7.6 Mb physical region of the reference genome, explaining 13.7 - 15.9% the phenotypic variance. Similarly, the QSS.sicau-2D was narrowed to 1.8 cM covering 2.4 Mb physical region of the reference genome, and it explained 27.4 - 32.9% the phenotypic variance. These two QTL were validated in three different genetic backgrounds using the linked markers. QSS.sicau-2 A was identified as WFZP-A, and QSS.sicau-2D was identified a novel locus, different to the previously identified WFZP-D. Based on the gene expression patterns, gene annotation and sequence analysis, TraesCS2D03G0260700 was predicted to be a potential candidate gene for QSS.sicau-2D. CONCLUSION: Two significant QTL for SS, namely QSS.sicau-2 A and QSS.sicau-2D were identified in multiple environments were identified and their effect in diverse genetic populations was assessed. QSS.sicau-2D is a novel QTL associated with the SS trait, with TraesCS2D03G0260700 predicted as its candidate gene.

Asunto(s)

Mapeo Cromosómico , Fenotipo , Sitios de Carácter Cuantitativo , Triticum , Triticum/genética , Cromosomas de las Plantas/genética , Estudios de Asociación Genética , Genes de Plantas

RESUMEN

Sepsis is a life­threatening multiple organ failure disease caused by an uncontrolled inflammatory response and can progress to acute lung injury (ALI). Heat­shock protein B8 (HSPB8) serves a cytoprotective role in multiple types of diseases; however, to the best of our knowledge, the regulatory role of HSPB8 in sepsis­induced ALI remains unclear. A549 human alveolar type II epithelial cells were treated with lipopolysaccharide (LPS) for 24 h to simulate a sepsis­induced ALI model. Cell transfection was performed to overexpress HSPB8, and cells were treated with mitochondrial division inhibitor­1 (Mdivi­1) for 2 h before LPS induction to assess the underlying mechanism. Protein expression was evaluated using western blotting and an immunofluorescence assay. Cytokines were examined using ELISA assay kits and antioxidant enzymes were examined using their detection kits. Cell apoptosis was detected using flow cytometry. The mitochondrial membrane potential was detected by JC­1 staining. HSPB8 was upregulated in A549 cells treated with LPS and HSPB8 overexpression attenuated LPS­induced inflammatory cytokine levels, oxidative stress and apoptosis in A549 cells. LPS inhibited mitophagy and reduced the mitochondrial membrane potential in A549 cells, which was partly inhibited by HSPB8 overexpression. Furthermore, Mdivi­1 decreased the inhibitory effect of HSPB8 on the inflammatory response, oxidative stress and apoptosis in LPS­treated A549 cells. In conclusion, HSPB8 overexpression attenuated the LPS­mediated inflammatory response, oxidative stress and apoptosis in A549 cells by promoting mitophagy, indicating HSPB8 as a potential therapeutic target in sepsis­induced ALI.

Asunto(s)

Lesión Pulmonar Aguda , Apoptosis , Citocinas , Proteínas de Choque Térmico , Lipopolisacáridos , Potencial de la Membrana Mitocondrial , Mitofagia , Chaperonas Moleculares , Estrés Oxidativo , Humanos , Mitofagia/efectos de los fármacos , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Lesión Pulmonar Aguda/inducido químicamente , Lipopolisacáridos/efectos adversos , Células A549 , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Citocinas/metabolismo , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/genética

RESUMEN

This research intends to evaluate the asymmetric relationship between pandemic uncertainty and public health expenditures in selected European Union nations (Germany, France, Sweden, Belgium, Austria, Netherlands, Denmark, Spain, Finland, and Portugal). Earlier studies used panel data methodologies to get consistent results about the pandemic-health expenditures nexus, irrespective of the reality that numerous economies did not identify such a link independently. By contrast, the present research utilizes a unique technique, quantile-on-quantile, that explores time-series dependency in every nation by offering worldwide yet country-related insight into the linkage between the variables. Estimations reveal that pandemic uncertainty increases public health expenditures in most of the selected economies at specified quantiles of data. Additionally, the data indicate that the level of asymmetries among our variables varies by country, stressing the significance of policymakers paying special attention while executing policies concerning health expenditures and pandemic uncertainty.

Asunto(s)

Gastos en Salud , Pandemias , Humanos , Unión Europea , Incertidumbre , Países Bajos

RESUMEN

Objective: To examine the clinical significance of the blood lactate (Lac)/serum albumin (Alb) ratio and the Lac/Alb × age score for assessing the severity and prognosis of patients with sepsis. Methods: A total of 8,029 patients with sepsis, aged >18 years were enrolled between June 2001 to October 2012 from the latest version of the Medical Information Mart for Intensive Care III (MIMIC-III v.1.4). The general data of the patients were obtained from hospital records and included gender, age, body mass index (BMI), laboratory indices, the sequential organ failure assessment (SOFA) score, and simplified acute physiology score II (SAPS II). The patients were graded and scored according to their age and then divided into a survival or death group based on their prognosis. The Lac/Alb ratio after ICU admission was calculated and compared between the two groups. The risk factors for death in patients with sepsis were determined using multivariate logistic regression analysis, while mortality was examined using receiver operating characteristic (ROC) curve and survival curve plots. Finally, the values of the Lac/Alb ratio and Lac/Alb × age score for assessing prognosis of patients with sepsis were analyzed and compared. Results: After items with default values were excluded, a total of 4,555 patients with sepsis were enrolled (2,526 males and 2,029 females). 2,843 cases were classified as the death group and 1,712 cases in the survival group. (1) The mean age, BMI, SOFA and SAPS II scores were higher in the death group than those in the survival group. Significant differences in baseline data between the two groups were also observed. (2) The patients in the death group were divided further into four subgroups according to the quartile of the Lac/Alb ratio from low to high. Comparison of the four subgroups showed that the death rate rose with an increase in the Lac/Alb ratio, while analysis of the survival curve revealed that patients with a higher Lac/Alb ratio had a worse prognosis. (3) Multivariate logistic regression analysis showed that age ≥ 60 years, overweight (BMI ≥ 24 kg/m2), Lac/Alb ratio ≥ 0.16, SOFA score ≥ 2 points, and SAPS II ≥ 40 points were independent risk factors for death in patients with septic. (4) ROC curve analysis indicated that the SAPS II, Lac/Alb x age score, SOFA, and Lac/Alb ratio were the best predictors of death in patients with sepsis. The Lac/Alb × age score was characterized by its simple acquisition and ability to quickly analyze the prognosis of patients. Conclusion: (1)A high Lac/Alb ratio is an independent risk factor for death in patients with sepsis. (2) Although the prognosis of sepsis can be accurately and comprehensively assessed by multi-dimensional analysis of multiple indices, the Lac/Alb × age score is more accurate and convenient for providing a general assessment of prognosis, so is worthy of further clinical recognition.

RESUMEN

Brucellosis is a highly contagious zoonotic disease caused by bacteria that belong to the genus Brucella. It is a major endemic disease in northern China. We reported a rare case of central nervous system (CNS) infection caused by Brucella melitensis in a patient living in non-endemic areas. The medical history of the patient included chronic headache and trunk numbness. Based on the presented clinical symptoms and medical examinations, a clinical diagnosis of binocular uveo-encephalitis was made in the local hospital. The patient's symptoms were unrelieved after being treated with empiric therapy. Soon after, the patient was admitted to our hospital because of the obnubilation and coma in the trip. We ran a few examinations and sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately. The Magnetic resonance imaging (MRI) examination was unremarkable, and bilateral mastoid inflammation was attached. Metagenomic next-generation sequencing suggested a CNS infection caused by Brucella melitensis. Then, the results of the serum agglutination test and quantitative polymerase chain reaction assay also confirmed that. After being treated with doxycycline, rifampin, and cefatriaxone, consciousness of the patient was restored and headache diminished. Two months later, a lumbar puncture was used to check the pressure of the CSF, and the total course of treatment was more than 6 months. This case highlighted the potential value of mNGS in early clinal diagnosis. We believe that mNGS may be a complementary method for rapid identification of infection of CNS caused by the pathogen.

RESUMEN

BACKGROUND: Raoultella ornithinolytica is a Gram-negative bacillus that resembles Klebsiella. This bacterium is present in many soil and aquatic environments and is a major causative agent of healthcare-associated infections (HAIs) in medical staff. Clinically, it has been reported to contribute to nosocomial infections in patients that include but are not limited to gastrointestinal, skin, and genitourinary tract infections. These complications are most common in hospitalized patients with underlying immunodeficiency, multiple comorbidities, or those receiving invasive surgery. CASE PRESENTATION: We present a case of a 25-year-old patient with a R. ornithinolytica infection. The patient had no history of any disease. Her main complaints were high fever, a scattered maculopapular rash, and superficial lymph node enlargement (SLNE). Peripheral blood samples were collected for high-throughput sequencing analysis to identify pathogenic microorganisms. The results confirmed a R. ornithinolytica infection, which was treated successfully using meropenem. Loratadine was also administered to treat the patient's compromised skin condition caused by an allergic reaction. CONCLUSIONS: To our knowledge, this is the first case of a systemic maculopapular rash and superficial lymphadenopathy caused by a R. ornithinolytica infection acquired at the community level. Based on this case, we recommend a combination of antibiotic and antiallergic drugs to treat a R. ornithinolytica infection and associated allergic reaction to the bacteria.

Asunto(s)

Infecciones Comunitarias Adquiridas , Infecciones por Enterobacteriaceae , Infecciones Urinarias , Adulto , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Enterobacteriaceae , Infecciones por Enterobacteriaceae/diagnóstico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Femenino , Humanos , Klebsiella , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico

RESUMEN

High glucose­induced endothelial Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling is associated with the development and progression of the vascular complications of diabetes. The present study aimed to investigate whether formononetin, a biologically active compound isolated from Astragalus membranaceus (Fisch.) Bge, was able to regulate the JAK/STAT signaling pathway, improving endothelial function. In the present study, formononetin was identified to act as a JAK2 inhibitor, similarly to tyrphostin AG 490 (AG490), by significantly inhibiting the phosphorylation and the mRNA expression levels of JAK2 and STAT in HUVECs exposed to high glucose levels. In addition, formononetin and AG490 improved the viability of HUVECs and inhibited the protein expression levels of caspase­3. Furthermore, formononetin and AG490 attenuated the inflammatory response in HUVECs by downregulating the protein and mRNA expression levels of interleukin (IL)­1ß and intercellular adhesion molecule 1 (ICAM­1). Formononetin and AG490 also restored nitric oxide (NO) synthesis in HUVECs. Notably, formononetin was able to reverse the abnormal levels of phosphorylated (p)­JAK2, p­STAT3, IL­1ß, ICAM­1 and NO induced by cotreatment with high glucose and IL­6, an agonist of the JAK/STAT signaling pathway. Additionally, the present results suggested that formononetin restored phenylephrine­mediated contraction and acetylcholine­induced relaxation in aortic tissues of rats fed a high­glucose diet, in a dose­dependent manner. Collectively, formononetin could improve endothelial function under glucose stress in vivo and in vitro, suggesting that formononetin may represent a novel potential therapeutic compound to treat diabetic vascular complications.

Asunto(s)

Endotelio/metabolismo , Glucosa/metabolismo , Isoflavonas/farmacología , Quinasas Janus/metabolismo , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Animales , Biomarcadores , Supervivencia Celular , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Ratas

RESUMEN

Proteins containing the FxxxVQxhTG or VQ motif interact with WRKY transcription factors. Although VQ proteins have been reported in several plants, knowledge about their structures, functions and evolution is still very limited. Here, we report structural and functional analysis of the VQ protein family from soybean. Like Arabidopsis homologues, soybean VQ proteins bind only Group I and IIc WRKY proteins and a substantial number of their genes are responsive to stress-associated phytohormones. Overexpression of some soybean VQ genes in Arabidopsis had strong effects on plant growth, development, disease resistance and heat tolerance. Phylogenetic analysis, sequence alignment and site-directed mutagenesis revealed that the region immediately upstream of the FxxxVQxhTG motif also affects binding to WRKY proteins. Consistent with a larger WRKY-binding VQ domain, soybean VQ22 protein from cultivated soybean contains a 4-amino acid deletion in the region preceding its VQ motif that completely abolishes its binding to WRKY proteins. By contrast, the 4-amino acid deletion is absent in the VQ22 protein from wild soybean species (Glycine soja). Overexpression of wild soybean VQ22 in cultivated soybean inhibited growth, particularly after cold treatment. Thus, the mutation of soybean VQ22 is associated with advantageous phenotypes and may have been positively selected during evolution.

Asunto(s)

Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Glycine max/genética , Proteínas de Plantas/química , Transactivadores/química , Factores de Transcripción/química , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Arabidopsis/metabolismo , Sitios de Unión , Botrytis/patogenicidad , Botrytis/fisiología , Resistencia a la Enfermedad/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Glycine max/metabolismo , Glycine max/microbiología , Transactivadores/genética , Transactivadores/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo

RESUMEN

Oxytocin (OXT), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of OXT to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that OXT in the central nervous system rather than the blood circulation plays an important role in rat pain modulation. The communication tried to investigate the interaction between the OXT and pain modulation in Chinese patients with headache to understand the OXT effect on human pain modulation. The results showed that (1) intranasal OXT could relieve the human headache in a dose-dependent manner; (2) OXT concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients in relation with the pain level; and (3) there was a positive relationship between plasma and CSF OXT concentration in headache patients. The data suggested that intranasal OXT, which was delivered to the central nervous system through olfactory region, could treat human headache and OXT might be a potential drug of headache relief by intranasal administration.

Asunto(s)

Cefalea/tratamiento farmacológico , Oxitocina/uso terapéutico , Dolor/tratamiento farmacológico , Administración Intranasal , Adulto , Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Femenino , Cefalea/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Oxitocina/sangre , Oxitocina/líquido cefalorraquídeo , Dolor/fisiopatología , Dimensión del Dolor/efectos de los fármacos , Adulto Joven

RESUMEN

Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of AVP to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that AVP in the brain rather than the spinal cord and blood circulation plays an important role in rat pain modulation. For understanding the role of AVP on pain modulation in human, the communication tried to investigate the effect of intranasal AVP on human headache. The results showed that (1) AVP concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients, who related with the headache level; (2) there was a positive relationship between plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP could relieve the human headache in a dose-dependent manner. The data suggested that intranasal AVP, which was delivered to the brain through olfactory region, could treat human headache and AVP might be a potential drug of pain relief by intranasal administration.

Asunto(s)

Arginina Vasopresina/administración & dosificación , Arginina Vasopresina/uso terapéutico , Cefalea/tratamiento farmacológico , Administración Intranasal , Adulto , Arginina Vasopresina/sangre , Arginina Vasopresina/líquido cefalorraquídeo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven

RESUMEN

An overview is presented of an approach for treating cancer that uses nanoparticles to deliver heat to diseased areas after absorbing energy from a laser of the appropriate wavelength. The implications are discussed of the relationship of parameters necessary to raise the temperature to therapeutically beneficial levels. Tight focusing is required for a continuous-wave laser to sufficiently heat individual nanoparticles because of heat loss to the surrounding fluid during the period of exposure. The natural thermal confinement of pulse lasers minimizes this effect because of the finite thermal diffusion time, which restricts the absorbed energy to a region around the particle, that offers the potential for achieving high temperatures that can promote phase change on the surface of a nanoparticle or even melting of the particle. A discussion of a way to potentially measure temperature on the scale of an individual nanoparticle is included based on using a single-walled nanotube (SWNT) of carbon as a thermistor. The challenges of this undertaking are that SWNTs do not always follow Ohm's law, they may exhibit metallic or semiconductor behavior with an often unpredictable result in manufacturing, and no two SWNTs behave identically, which necessitates calibration for each SWNT. Some results are presented that show the electrical characteristics of SWNTs and their potential for exploitation in this application.

Asunto(s)

Calor , Nanopartículas/uso terapéutico , Neoplasias/terapia , Animales , Humanos , Modelos Biológicos , Nanopartículas/ultraestructura , Neoplasias/patología

RESUMEN

We present a nanoscale color detector based on a single-walled carbon nanotube functionalized with azobenzene chromophores, where the chromophores serve as photoabsorbers and the nanotube as the electronic read-out. By synthesizing chromophores with specific absorption windows in the visible spectrum and anchoring them to the nanotube surface, we demonstrate the controlled detection of visible light of low intensity in narrow ranges of wavelengths. Our measurements suggest that upon photoabsorption, the chromophores isomerize from the ground state trans configuration to the excited state cis configuration, accompanied by a large change in dipole moment, changing the electrostatic environment of the nanotube. All-electron ab initio calculations are used to study the chromophore-nanotube hybrids and show that the chromophores bind strongly to the nanotubes without disturbing the electronic structure of either species. Calculated values of the dipole moments support the notion of dipole changes as the optical detection mechanism.

Asunto(s)

Nanocompuestos/química , Nanotecnología/métodos , Nanotubos de Carbono/química , Nanotubos/química , Absorción , Electrodos , Luz , Modelos Químicos , Modelos Estadísticos , Fotoquímica/métodos , Tensoactivos/química

RESUMEN

Carbon nanotube transistors combine molecular-scale dimensions with excellent electronic properties, offering unique opportunities for chemical and biological sensing. Here, we form supported lipid bilayers over single-walled carbon nanotube transistors. We first study the physical properties of the nanotube/supported lipid bilayer structure using fluorescence techniques. Whereas lipid molecules can diffuse freely across the nanotube, a membrane-bound protein (tetanus toxin) sees the nanotube as a barrier. Moreover, the size of the barrier depends on the diameter of the nanotube--with larger nanotubes presenting bigger obstacles to diffusion. We then demonstrate detection of protein binding (streptavidin) to the supported lipid bilayer using the nanotube transistor as a charge sensor. This system can be used as a platform to examine the interactions of single molecules with carbon nanotubes and has many potential applications for the study of molecular recognition and other biological processes occurring at cell membranes.

Asunto(s)

Materiales Biomiméticos/química , Biotecnología/métodos , Membrana Celular/química , Membrana Dobles de Lípidos/química , Técnicas de Sonda Molecular , Nanotecnología/métodos , Nanotubos de Carbono/química

RESUMEN

We have used single-walled carbon nanotube transistors to measure changes in the chemical potential of a solution due to redox-active transition-metal complexes. The interaction of the molecules with a gold electrolyte-gate wire changes the electrostatic potential sensed by the nanotube, which in turn shifts the gate-voltage dependence of the nanotube conductance. As predicted by the Nernst equation, this shift depends logarithmically on the ratio of oxidized to reduced molecules.

Asunto(s)

Nanotubos de Carbono , Soluciones/química , Algoritmos , Oro/química , Microscopía de Fuerza Atómica , Oxidación-Reducción , Electricidad Estática , Transistores Electrónicos

RESUMEN

Semiconducting single-walled carbon nanotubes are studied in the diffusive transport regime. The peak mobility is found to scale with the square of the nanotube diameter and inversely with temperature. The maximum conductance, corrected for the contacts, is linear in the diameter and inverse temperature. These results are in good agreement with theoretical predictions for acoustic phonon scattering in combination with the unusual band structure of nanotubes. These measurements set the upper bound for the performance of nanotube transistors operating in the diffusive regime.