RESUMEN
Sepsis is a life-threatening multiple-organ injury caused by disordered host immune response to microbial infection. However, the correlation between gut microbiota dysbiosis and immune indicators remains unexplored. To address this gap in knowledge, we carried out 16 S rDNA sequencing, analyzed clinical fecal samples from children with sepsis (n = 30) and control children (n = 25), and obtained immune indicators, including T cell subtypes (CD3+, CD3+CD4+, CD3+CD8+, and CD4/CD8), NK cells, cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ), and immunoglobulin indices (IgA, IgE, IgM and IgG). In addition, we analyzed the correlation between gut microbiota dysbiosis and immune indicators, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. We found that children with sepsis exhibited gut bacterial dysbiosis and low alpha diversity. The Spearman's rank correlation coefficient suggested that Rhodococcus erythropolis had a significantly positive correlation with IFN-γ and CD3+ T cells. Klebsiella pneumoniae and Streptococcus mitis were significantly correlated with NK cells. Bacteroides uniformis was significantly positively correlated with IgM and erythrocyte sedimentation rate, and Eubacterium eligens was significantly positively correlated with IL-4 and CD3+CD8+ T cells. The biomarkers discovered in this study had strong discriminatory power. These changes in the gut microbiome may be closely related to immunologic dysfunction and to the development or exacerbation of sepsis. However, a large sample size is required for verification.
Asunto(s)
Microbioma Gastrointestinal , Sepsis , Humanos , Niño , Microbioma Gastrointestinal/fisiología , Linfocitos T CD8-positivos , Disbiosis , Interleucina-4 , Bacterias/genética , Biomarcadores , Inmunoglobulina MRESUMEN
Logistics is a crucial part of every business. The logistics sector not only contributes significantly to Asian economies but also has far-reaching effects on ecological and social concerns. Therefore, it is important to examine the factors that can affect the logistics performance of the country. Hence, the primary objective of the study is to estimate the impact of CO2 emissions, ICT, and human capital on the logistics performance of the 20 Asian economies. In order to investigate the relationship between the variables, we have employed the OLS, 2SLS, GMM, and panel quantile regression. The estimates of CO2 emissions and GHG emissions are significantly negative in 2SLS and GMM methods, implying that environmental pollution hurt logistic performance. The estimates of ICT and education are positively significant, suggesting that increased use of internet and higher education rate are crucial in improving logistics performance. In the panel quantile regression model, the estimates of CO2, internet, and education are insignificant at most quantiles except at a few higher quantiles. Thus, governments should invest in the development of efficient logistics infrastructure to achieve sustainable development.
Asunto(s)
Dióxido de Carbono , Carbono , Humanos , Desarrollo Sostenible , Desarrollo Económico , PolíticasRESUMEN
Eco-innovations are widely considered the best possible solution to fight the menace of environmental degradation. Therefore, in this analysis, we try to examine the impact of eco-innovations and environmental entrepreneurship on SME performance in China from 1998 to 2020. In order to get the short- and long-run estimates, we have employed the QARDL model that can estimate across various quantiles. The findings of the QARDL model confirm the positive impact of eco-innovations in increasing the number of SMEs in the long run, as the estimates attached to eco-innovations are positive and significant across most quantiles. Similarly, the estimates attached to financial development and institutional quality are positively significant across most quantiles. However, in the short run, the results are inconclusive for almost all variables. As far as the asymmetric impact of eco-innovations on SMEs is concerned, it is confirmed both in the short and long run. However, the asymmetric impacts of financial development and institutional quality on SMEs are only confirmed in the long run. Based on the results, important policy suggestions are discussed.
Asunto(s)
Comercio , Emprendimiento , China , Instituciones de Salud , Políticas , Desarrollo Económico , Dióxido de CarbonoRESUMEN
Posttranslational modifications by ubiquitin and ubiquitin-like proteins are important in regulating cellular protein functions. UFM1 (ubiquitin-fold modifier 1), first identified almost two decades ago, is a member of the ubiquitin-like protein family. UFM1 is covalently conjugated to the target proteins in an enzymatic cascade consisting of E1 (activating), E2 (conjugating), and E3 (ligating) enzymes. At the molecular level, modification by UFM1 (UFMylation) is an important mediator of the protein function. Dysregulation of the UFM1 system, e.g., the knockout of UFMylation components, disturbs proteome homeostasis and triggers endoplasmic reticulum stress. Such changes are linked to developmental disorders, tumorigenesis, tissue injury, inflammation, and several hereditary neurological syndromes. This review will focus on the role of the UFMylation in animal development and associated congenital disorders. We will cover the hematopoietic system, liver, central nervous system, intestine, heart, kidney, immune, and skeletal system to provide insight into disease pathogenesis and shed light on possible novel therapeutic methods.
Asunto(s)
Proteínas , Ubiquitina , Animales , Proteínas/genética , Procesamiento Proteico-Postraduccional , Ubiquitinas/metabolismo , Estrés del Retículo Endoplásmico , Mamíferos/metabolismoRESUMEN
The intensive and long-term use of atrazine (ATZ) has led to the contamination of agricultural soils and non-target organisms, posing a series of threats to human health through the transmission of the food chain. In this study, a 60-day greenhouse pot experiment was carried out to explore the phytoremediation by Chrysopogon zizanioides L. (vetiver). The uptake, accumulation, distribution, and removal of ATZ were investigated, and the degradation mechanisms were elucidated. The results showed that the growth of vetiver was inhibited in the first 10 days of the incubation; subsequently, the plant recovered rapidly with time going. Vetiver grass was capable of taking up ATZ from the soil, with root concentration factor ranging from 2.36 to 15.55, and translocating to the shoots, with shoot concentration factor ranging from 7.51 to 17.52. The dissipation of ATZ in the rhizosphere soil (97.51%) was significantly higher than that in the vetiver-unplanted soil (85.14%) at day 60. Metabolites were identified as hydroxyatrazine (HA), deethylatrazine (DEA), deisopropylatrazine (DIA), and didealkylatrazine (DDA) in the samples of the shoots and roots of vetiver as well as the soils treated with ATZ. HA, DEA, DIA, and DDA were reported first time as metabolites of ATZ in shoots and roots of vetiver grown in soil. The presence of vetiver changed the formation and distribution of the dealkylated products in the rhizosphere soil, which remarkably enhanced the occurrence of DEA, DIA, and DDA. Arthrobacter, Bradyrhizobium, Nocardioides, and Rhodococcus were the major atrazine-degrading bacterial genera, which might be responsible for ATZ degradation in the rhizosphere soil. Our findings suggested that vetiver grass can significantly promote ATZ degradation in the soil, and it could be a strategy for remediation of the atrazine-contaminated agricultural soil.
Asunto(s)
Atrazina , Chrysopogon , Contaminantes del Suelo , Humanos , Atrazina/metabolismo , Biodegradación Ambiental , Contaminantes del Suelo/análisis , Suelo , Bacterias/metabolismoRESUMEN
OBJECTIVE: Advanced practice nurses (APNs) can best support physicians in improving the quality of truth-telling. However, the effectiveness of communication skill training (CST), based on the Japanese SHARE model exclusive to APNs, has not been tested from APNs' and recipients' viewpoints, motivating the author to conduct the present study. METHODS: A two-group before-after model design was adopted, and 61 APNs from two hospitals were randomly assigned to either an experimental group (EG; N = 28) or an control group (CG; N = 33). APNs in the EG received 6 h of CST under the guidance of qualified facilitators and simulated patients. This study used APNs' subjective assessment (N = 61) (self-confidence and perceptions on truth-telling) and recipients' opinions (N = 480) (cancer patients' and their caregivers' satisfaction with truth-telling and emotional status) to assess the effectiveness of the SHARE CST. Data were collected before CST (baseline, T0), immediately after (T1), and 2 weeks after (T2). RESULTS: APNs in the EG had more confidence (p < 0.05) and better perceptions of cancer truth-telling (p < 0.01) than APNs in the CG at both T1 and T2. No group differences were found in patients' or their caregivers' satisfaction with truth-telling, emotional distress, and anxiety (p > 0.05). In addition, patients in the EG had higher depression than patients in the CG (ß = 1.65, p = 0.01). CONCLUSIONS: SHARE CST can improve APNs' confidence and perceptions of cancer truth-telling. However, more rigorous studies are required to test the effectiveness of CST from recipients' viewpoint.
Asunto(s)
Neoplasias , Enfermeras y Enfermeros , Comunicación , Humanos , Proyectos Piloto , Taiwán , Revelación de la VerdadRESUMEN
The regulatory circuitry underlying embryonic stem (ES) cell self-renewal is well defined, but how this circuitry is disintegrated to enable lineage specification is unclear. RNA-binding proteins (RBPs) have essential roles in RNA-mediated gene regulation, and preliminary data suggest that they might regulate ES cell fate. By combining bioinformatic analyses with functional screening, we identified seven RBPs played important roles for the exit from pluripotency of ES cells. We characterized hnRNPLL, which mainly functions as a global regulator of alternative splicing in ES cells. Specifically, hnRNPLL promotes multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation. hnRNPLL depletion thus leads to sustained expression of ES cell-preferred isoforms, resulting in a differentiation deficiency that causes developmental defects and growth impairment in hnRNPLL-KO mice. In particular, hnRNPLL-mediated alternative splicing of two transcription factors, Bptf and Tbx3, is important for pluripotency exit. These data uncover the critical role of RBPs in pluripotency exit and suggest the application of targeting RBPs in controlling ES cell fate.
Asunto(s)
Empalme Alternativo , Antígenos Nucleares/metabolismo , Diferenciación Celular , Células Madre Embrionarias/citología , Ribonucleoproteínas Nucleares Heterogéneas/fisiología , Proteínas del Tejido Nervioso/metabolismo , Células Madre Pluripotentes/citología , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/metabolismo , Animales , Antígenos Nucleares/genética , Células Madre Embrionarias/metabolismo , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Células Madre Pluripotentes/metabolismo , Isoformas de Proteínas , Proteínas de Dominio T Box/genética , Factores de Transcripción/genéticaRESUMEN
CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) plays a crucial role in mammalian liver development and hepatic function by controlling hepatocyte proliferation and differentiation, glucose and lipid metabolism, UFMylation, and endoplasmic reticulum homeostasis. However, the role of CDK5RAP3 in liver regeneration remains unknown. A liver-specific Cdk5rap3 knockout (CKO) mouse model was used to study the function of CDK5RAP3 during liver regeneration induced by standard two-thirds partial hepatectomy (PHx). Twenty-four hours after PHx, the liver-to-body weight ratio was markedly higher in CKO mice than in wild-type mice. However, this ratio did not increase significantly and gradually over time after PHx in CKO mice. Hepatocyte proliferation was significantly delayed in CKO mice compared with wild-type mice. Meanwhile, CDK5RAP3 deficiency increased lipid accumulation, impaired glycogen synthesis, and lowered blood glucose levels after PHx. Critically, the absence of CDK5RAP3 seemed to promote an inflammatory response and induce apoptosis at a late stage of liver regeneration. In addition, CDK5RAP3 deficiency disrupted UFMylation homeostasis and aggravated endoplasmic reticulum stress in hepatocytes after PHx. Taken together, these data suggest that CDK5RAP3 enhances liver regeneration, at least partially via controlling cell cycle and glucose and lipid metabolism.
Asunto(s)
Proteínas de Ciclo Celular/deficiencia , Estrés del Retículo Endoplásmico/fisiología , Hepatocitos/metabolismo , Metabolismo de los Lípidos/fisiología , Regeneración Hepática/fisiología , Proteínas Supresoras de Tumor/deficiencia , Animales , Ciclo Celular/fisiología , Diferenciación Celular/fisiología , Proliferación Celular/fisiología , Hígado/metabolismo , Ratones NoqueadosRESUMEN
Protein modification by ubiquitin and ubiquitin-like proteins (UBLs) regulates numerous biological functions. The UFM1 system, a novel UBL conjugation system, is implicated in mouse development and hematopoiesis. However, its broad biological functions and working mechanisms remain largely elusive. CDK5RAP3, a possible ufmylation substrate, is essential for epiboly and gastrulation in zebrafish. Herein, we report a crucial role of CDK5RAP3 in liver development and hepatic functions. Cdk5rap3 knockout mice displayed prenatal lethality with severe liver hypoplasia, as characterized by delayed proliferation and compromised differentiation. Hepatocyte-specific Cdk5rap3 knockout mice suffered post-weaning lethality, owing to serious hypoglycemia and impaired lipid metabolism. Depletion of CDK5RAP3 triggered endoplasmic reticulum stress and activated unfolded protein responses in hepatocytes. We detected the in vivo interaction of CDK5RAP3 with UFL1, the defined E3 ligase in ufmylation. Notably, loss of CDK5RAP3 altered the ufmylation profile in liver cells, suggesting that CDK5RAP3 serves as a novel substrate adaptor for this UBL modification. Collectively, our study identifies CDK5RAP3 as an important regulator of ufmylation and suggests the involvement of ufmylation in mammalian development.
Asunto(s)
Hígado/embriología , Hígado/metabolismo , Proteínas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Proteínas de Ciclo Celular , Diferenciación Celular , Proliferación Celular , Pérdida del Embrión/patología , Embrión de Mamíferos/metabolismo , Embrión de Mamíferos/patología , Retículo Endoplásmico/metabolismo , Eliminación de Gen , Células Hep G2 , Hepatocitos/citología , Hepatocitos/metabolismo , Homeostasis , Humanos , Hígado/patología , Ratones Noqueados , Unión Proteica , Especificidad por Sustrato , Proteínas Supresoras de TumorRESUMEN
OBJECTIVES: The free anterolateral thigh (ALT) flap is commonly used for the reconstruction of the cervical oesophagus with satisfactory results. Its convenience and popularity make it a popular flap for reconstructive surgeons. The use of intestinal flaps, however, carries a higher level of technical difficulty and is normally performed as a primary reconstructive procedure. This report investigates the feasibility of intestinal flaps for the reconstruction of the cervical oesophagus and strategies to optimize its success when used as a secondary flap after primary ALT flap failure. METHODS: We retrospectively reviewed 22 patients (age 39-72 years) who were men, between April 2013 and January 2015, with intestinal segments (free and pedicled ileocolon, jejunal and colon flaps) that were used secondarily to salvage failed primary free ALT flap reconstructions after hypopharyngeal cancer resection. Ten patients presented with leakage and 2 with tracheo-oesophageal fistulae as complications from the primary flap failure. RESULTS: Oral intake commenced around 1-month postoperatively. One case of flap failure was observed. The majority had no major postoperative complications. Patients were followed up (6-27 months), and 21 cases of a secondary intestinal flap were successful with the restoration of oesophageal continuity and oral intake. CONCLUSIONS: Intestinal flaps, free or pedicled, can be used secondarily after failed ALT flap reconstructions with minimal complications or morbidity. Intestinal flaps successfully allow restoration of gastrointestinal continuity with early commencement of oral intake and swallowing function.
Asunto(s)
Esófago/cirugía , Neoplasias Hipofaríngeas/cirugía , Intestinos/trasplante , Procedimientos de Cirugía Plástica/métodos , Terapia Recuperativa/métodos , Colgajos Quirúrgicos/trasplante , Adulto , Anciano , Anastomosis Quirúrgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
We apply a nanomanipulation technique to assemble pairs of monodispersed octahedral gold nanocrystals (side length, 150 nm) along their major axes with a varying tip-to-tip separation (25-125 nm). These pairs are immobilized onto indium tin oxide coated silica substrates and studied as plasmonic dimers by polarization-selective total internal reflection (TIR) microscopy and spectroscopy. We confirm that the plasmon coupling modes with the scattering polarization along the incident light direction result from the transverse-magnetic-polarized incident light, which induces two near-field-coupled dipole moments oriented normal to the air-substrate interface. In such cases, both in-phase (antibonding) and antiphase (bonding) plasmon coupling modes can be directly observed with the incident light wave vector perpendicular and parallel to the dimer axis, respectively. The observation of antiphase plasmon coupling modes ("dark" plasmons) is made possible by the unique polarization nature of the TIR-generated evanescent field. Furthermore, with decreasing nanocrystal separation, the plasmon coupling modes shift to shorter wavelengths for the incident light perpendicular to the dimer axis, whereas relatively large red shifts of the plasmonic coupling modes are found for the parallel incident light.