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SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Tolerancia a la Sal/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Intercambiadores de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/metabolismoRESUMEN
STAT6 plays a prominent role in adaptive immunity by transducing signals from extracellular cytokines. We now show that STAT6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger STING (also named MITA/ERIS) to recruit STAT6 to the endoplasmic reticulum, leading to STAT6 phosphorylation on Ser(407) by TBK1 and Tyr(641), independent of JAKs. Phosphorylated STAT6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing. Virus-induced STAT6 activation is detected in all cell-types tested, in contrast to the cell-type specific role of STAT6 in cytokine signaling, and Stat6(-/-) mice are susceptible to virus infection. Thus, STAT6 mediates immune signaling in response to both cytokines at the plasma membrane, and virus infection at the endoplasmic reticulum.
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Inmunidad Innata , Proteínas de la Membrana/metabolismo , Infecciones por Virus ARN/inmunología , Virus ARN , Factor de Transcripción STAT6/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Secuencia de Bases , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Datos de Secuencia Molecular , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Factor de Transcripción STAT6/genéticaRESUMEN
The COVID-19 pandemic represents an unparalleled global public health crisis. Despite concerted research endeavours, the repertoire of effective treatment options remains limited. However, neutralising-antibody-based therapies hold promise across an array of practices, encompassing the prophylaxis and management of acute infectious diseases. Presently, numerous investigations into COVID-19-neutralising antibodies are underway around the world, with some studies reaching clinical application stages. The advent of COVID-19-neutralising antibodies signifies the dawn of an innovative and promising strategy for treatment against SARS-CoV-2 variants. Comprehensively, our objective is to amalgamate contemporary understanding concerning antibodies targeting various regions, including receptor-binding domain (RBD), non-RBD, host cell targets, and cross-neutralising antibodies. Furthermore, we critically examine the prevailing scientific literature supporting neutralising antibody-based interventions, and also delve into the functional evaluation of antibodies, with a particular focus on in vitro (vivo) assays. Lastly, we identify and consider several pertinent challenges inherent to the realm of COVID-19-neutralising antibody-based treatments, offering insights into potential future directions for research and development.
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COVID-19 , SARS-CoV-2 , Humanos , Anticuerpos Neutralizantes/uso terapéutico , COVID-19/terapia , Pandemias , Anticuerpos Antivirales/uso terapéuticoRESUMEN
BACKGROUND: The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. METHODS: Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. RESULTS: Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P < 0.05). CONCLUSIONS: Our study contributes to the understanding of the species diversity of Nocardia isolates in Henan, China, and the clinical characteristics of patients with pulmonary nocardiosis infections. Clinical and microbiologic differences between patients with and without bronchiectasis. These findings will contribute to the early diagnosis and treatment of patients.
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Bronquiectasia , Diabetes Mellitus , Nocardiosis , Nocardia , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Nocardia/genética , ARN Ribosómico 16S/genética , Combinación Trimetoprim y Sulfametoxazol , Nocardiosis/tratamiento farmacológico , China , Bronquiectasia/tratamiento farmacológico , Resistencia a MedicamentosRESUMEN
INTRODUCTION AND OBJECTIVES: Type 2 Diabetes Mellitus (T2DM), a prevalent metabolic disorder, often coexists with a range of complications, with retinopathy being particularly common. Recent studies have shed light on a potential connection between diabetic retinopathy (DR) and hepatic fibrosis, indicating a possible shared pathophysiological foundation in T2DM. This study investigates the correlation between retinopathy and hepatic fibrosis among individuals with T2DM, as well as evaluates the diagnostic value of DR for significant hepatic fibrosis. MATERIALS AND METHODS: Our cross-sectional analysis incorporated 5413 participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2008. The Fibrosis-4 score (FIB-4) classified hepatic fibrosis into different grades (F0-F4), with significant hepatic fibrosis marked as F2 or higher. Retinopathy severity was determined using retinal imaging and categorized into four levels. The analysis of variance or Chi-square tests facilitated group comparisons. Additionally, the receiver operating characteristic (ROC) analysis appraised the predictive accuracy of retinopathy for significant hepatic fibrosis in the T2DM population. RESULTS: Among 5413 participants, the mean age was 59.56 ± 12.41, with 50.2% male. And 20.6% were diagnosed with T2DM. Hepatic fibrosis grading was positively associated with retinopathy severity (OR [odds ratio]: 1.521, 95%CI [confidence interval]: 1.152-2.008, P = 0.003) across the entire population. The association was amplified in the T2DM population according to Pearson's analysis results. The ROC curve demonstrated retinopathy's diagnostic capacity for significant hepatic fibrosis in the T2DM population (AUC [area under curve] = 0.72, 95%CI: 0.651-0.793, P < 0.001). CONCLUSIONS: Retinopathy could serve as an independent predictor of significant hepatic fibrosis in T2DM population. Ophthalmologists are advised to closely monitor T2DM patients with retinopathy.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Cirrosis Hepática , Encuestas Nutricionales , Valor Predictivo de las Pruebas , Curva ROC , Índice de Severidad de la Enfermedad , Humanos , Masculino , Estudios Transversales , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/complicaciones , Femenino , Persona de Mediana Edad , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Estados Unidos/epidemiología , Factores de Riesgo , Adulto , Área Bajo la Curva , Distribución de Chi-Cuadrado , PrevalenciaRESUMEN
STUDY OBJECTIVE: To establish a prediction model to help doctors determine which patients with cesarean scar defect are more suitable for transvaginal repair. DESIGN: Retrospective analysis. SETTING: Xinhua Hospital and Shanghai First Maternity & Infant Hospital between June 2014 and May 2021. PATIENTS: 1015 women who underwent transvaginal repair of cesarean scar defect (CSD). INTERVENTIONS: All enrolled patients underwent CSD repair performed by the same gynecologist and his team. And followed up a clinic visit at 6 months to record their menstruation and measure multiple parameters of the CSD by Magnetic Resonance Imaging. MAIN OUTCOMES AND MEASURES: CSD patients are categorized as optimal healing group when the menstruation duration is no more than 7 days, meanwhile the thickness of residual myometrium is no less than 5.39 mm after vaginal repair. The final nomogram is constructed to predict surgical outcomes based on preoperative variables. RESULTS: The key factors that determine optimal healing are the timing of cesarean section (elective or emergency), menstrual cycle, CSD length, width, depth, and the thickness of the lower uterine segment. With the prediction model, scores are given to each parameter according to the statistics. Total scores range from 0 to 25 points, with a cutoff point of 16.5. When a score is greater than 16.5, the transvaginal repair can achieve optimal healing. Uterine position (anteflexion or retroflexion) and preoperative thickness of residual myometrium are the key factors affecting postoperative thickness of residual myometrium. The width of the CSD and the thickness of the lower uterine segment are the key factors affecting abnormal uterine bleeding symptoms (p < 0.01). CONCLUSIONS: For the first time, we established a prediction model system that may predict the repair effect of CSD and can potentially be useful in future clinical trials to determine which patients are more suitable for surgery or other treatment options.
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Cesárea , Cicatriz , Humanos , Femenino , Embarazo , Cicatriz/etiología , Cicatriz/cirugía , Estudios Retrospectivos , Cesárea/efectos adversos , Selección de Paciente , ChinaRESUMEN
STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomised to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (nâ¯=â¯63) or VRâ¯+â¯GnRHa (nâ¯=â¯61). Menstruation and TRM in patients pre. vs. post comparisons either with VR or VRâ¯+â¯GnRHa are significant improved (P < .05). Significant differences in menstruation duration and TRM occurred in patients treated with VRâ¯+â¯GnRHa compared with those treated with VR (P < .05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VRâ¯+â¯GnRHa group (Pâ¯=â¯.033), and CSD patients in the VRâ¯+â¯GnRHa group achieved better therapeutic effects than those in the VR group (Pâ¯=â¯.017). Patients who received VRâ¯+â¯GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than did patients treated with VR alone (Pâ¯=â¯.021; Pâ¯=â¯.002, respectively). CONCLUSION: VRâ¯+â¯GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD. PRéCIS: Vaginal Repair Combined with GnRHa Creates Better Therapeutic Effects of CSD. TRIAL REGISTRATION: Date of registration: October 13, 2016, Date of initial participant enrollment: December 20, 2016, Clinical trial identification number: NCT02932761, URL of the registration site: ClinicalTrials.gov, Figshare DOI: 10.6084/m9.figshare.24117114 LINK TO THE CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02932761.
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Isoniazid and streptomycin are vital drugs for treating tuberculosis, which are utilized as efficient anti-tuberculosis agents. This paper presents a novel visible-light-driven composite photocatalyst Ti3C2/Bi/BiOI, which was built from Ti3C2 nanosheets and Bi/BiOI microspheres. Photoelectrochemical (PEC) sensors based on Ti3C2/Bi/BiOI were synthesized for isoniazid identification, which showed a linear concentration range of 0.1-125 µM with a detection limit of 0.05 µM (S/N = 3). Moreover, we designed a PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI to detect streptomycin in 0.1 M PBS covering the electron donor isoniazid, because the isoniazid consumes photogenerated holes thus increasing the photocurrent effectively and preventing photogenerated electron-hole pairs from being recombined. Furthermore, PEC aptasensors based on aptamer/Ti3C2/Bi/BiOI were synthesized for streptomycin identification, which exhibited a linear concentration range of 0.01-1000 nM with a detection limit of 2.3 × 10-3 nM (S/N = 3), and are well stable in streptomycin sensing.
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Isoniazida , Estreptomicina , Microesferas , Titanio , Libros , Metales , OligonucleótidosRESUMEN
Seven new lanthanide coordination polymers, namely [Ln(cpt)3H2O)]n(Ln = La (1), Pr (2), Sm (3), Eu (4), Gd (5), Dy (6), and Er (7)), which were synthesized under hydrothermal conditions using 4'-(4-(4-carboxyphenyloxy)phenyl)-4,2':6',4'-tripyridine (Hcpt) as the ligand. The crystal structures of these seven complexes were determined using single-crystal X-ray diffraction, and they were found to be isostructural, crystallizing in the triclinic P1- space group. The Ln(III) ions were nine-coordinated with tricapped trigonal prism coordination geometry. The Ln(III) cations were coordinated by carboxylic and pyridine groups from (cpt)- ligands, forming one-dimensional ring-chain structures. Furthermore, the luminescent properties of complexes 1-7 were investigated using fluorescent spectra in the solid state. The fluorescence sensing experiments demonstrated that complex 4 exhibits high selectivity and sensitivity for detecting Co2+, Cu2+ ions, and nitrobenzene. Moreover, complex 3 shows good capability for detecting Cu2+ ions and nitrobenzene. Additionally, the sensing mechanism was also thoroughly examined through theoretical calculations.
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OBJECTIVE: To understand the recommended dose distribution of prebiotic-containing health food in China. METHODS: The overall recommended dose of prebiotic health food was available from the label information of approved prebiotic health food from 1996 to 2022; the recommended dose distribution of prebiotic-containing health food was analyzed from different healthy functions and different ways of addition. RESULTS: There were 174 prebiotic-containing health food products with clear dose information, respectively, involving 5 prebiotics including Fructooligosaccharides, Galactooligosaccharides, Isomaltooligosaccharides, Xylo-oligosaccharides and Polydextrose, and the majority of prebiotics were added in combination, with 159 products. The recommended dose range of prebiotic-containing health food products was wide, and in general, the dose of prebiotic-containing health food products used alone was higher than the dose used in combination. The recommended daily intake range of health food containing Fructooligosaccharides was 5.28-17 500 mg/d, the recommended daily intake range of health food containing Isomaltooligosaccharides was 220-28 000 mg/d, the dose range of health food containing Xylo-oligosaccharides was 8.4-2 800 mg/d, the dose range of health food containing Polydextrose was 4-12 120 mg/d, the number of Galacto-Oligosaccharides products Only two kinds of products were included, with doses of 259.8 mg/d and 3500 mg/d, respectively. The claimed functions of prebiotic health food products were focused on laxative function, immunity enhancement, and regulation of intestinal flora. The application dose of prebiotic health food with different functional compounding additions was close to the overall dose. CONCLUSION: The recommended dosage range of prebiotics in health food containing prebiotics in China is large, and prebiotics in products are mainly added by compounding.
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Microbioma Gastrointestinal , Prebióticos , Oligosacáridos , ChinaRESUMEN
Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in the plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter roots and less Pi content than wild-type plants under LP conditions. Moreover, a mutant of ABI5, which encodes a central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP conditions. ABI5 facilitated Pi acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpression of PHT1;1 completely rescued its Pi content under LP conditions. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in the Arabidopsis response to phosphate deficiency.
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Proteínas de Arabidopsis , Arabidopsis , Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Regulación de la Expresión Génica de las Plantas , Fosfatos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.
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Proteínas de Arabidopsis , Arabidopsis , Germinación , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Regulación de la Expresión Génica de las Plantas , Semillas/metabolismo , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Arabidopsis/metabolismoRESUMEN
As a key link between top-down regulators and bottom-up factors, zooplankton responds sensitively to environmental variations and provides information on the ecological state of freshwater systems. Although the response of zooplankton to anthropogenic pressures and fluctuating natural conditions, such as nutrient loading and climate change, has been extensively examined, findings have varied markedly. The mechanistic basis for the correlation between environmental variability and the zooplankton community is still debated, particularly for subtropical eutrophic lakes. We used two methods to analyze physicochemical and selected biological variables derived from long-term monitoring of Lake Taihu, a subtropical shallow lake in China. We first applied random forest regression to examine how changes in zooplankton were related to a set of environmental variables on interannual time scales. Then we used the results to guide the construction of a conceptual model for piecewise structural equation modeling (pSEM) to quantify more precisely the zooplankton-environment relationship. Zooplanktivorous fish and nutrient concentrations were the most important predictors of long-term trends in zooplankton in RF regression. Intensification of planktivorous fish predation led to a lower zooplankton biomass and smaller individuals through the removal of larger crustaceans. Moreover, suppression of zooplankton can in part be explained by increases in inedible algae, triggered by a combination of reduced nutrient concentrations and weakened grazer control. These results were also confirmed in the pSEM, which further indicated that top-down regulators might be more important than bottom-up factors for the zooplankton community in Lake Taihu. Our results suggest that stocking of filter-feeding fish in the lake did not meet the expectation that they would control algae, but that the use of biomanipulation measures considering both water quality and fishery management seems promising. This study offers insights into how indicator metrics of zooplankton can improve our understanding of the associations between plankton communities and ecosystem alterations.
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Ecosistema , Zooplancton , Animales , Lagos/química , Conducta Predatoria , Peces , BiomasaRESUMEN
OBJECTIVES: This study aimed to analyze the possible causes of changes in cardiac function and investigate the feasibility of clinical assessment of gastrointestinal cancer in patients with or without acute kidney injury (AKI) assessed using a non-invasive impedance cardiography (ICG, Bioz. Cardio Dynamics, USA) to identify independent risk factors. METHODS: Patients admitted to the Fourth Hospital of Hebei Medical University, China, between May 1, 2019, and February 15, 2022, were included in this study. A total of 51 patients with gastrointestinal cancer (31 men and 20 women, mean age 61.1 ± 10.9 years) with or without AKI were evaluated for ICG. A total of 19 patients underwent ultrasound cardiography (UCG) and ICG evaluations. RESULT: There was a significant positive correlation between cardiac output (CO), cardiac index (CI), stroke volume (SV), left cardiac work index (LCWI), and ejection fraction (EF) measured using UCG and ICG. The relationship was observed between COICG and COUCG (r = 0.707, P = 0.001), CIICG and CIUCG (r = 0.718, P = 0.001), SVICG and SVUCG (r = 0.837, P < 0.001), and LCWIICG and EFUCG (r = 0.540, P = 0.017). Cardiac function parameters measured using ICG were statistically different between patients with gastrointestinal cancer with or without AKI (P ≤ 0.05). Multivariate analysis revealed that AKI independently affects cardiac function in patients with gastrointestinal cancer. CONCLUSIONS: UCG and ICG methods are significantly associated with cardiac function in patients with or without AKI, and patients with gastrointestinal cancer with AKI are worse than those without AKI. AKI is an independent risk factor for cardiac function in patients with gastrointestinal cancer.
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Lesión Renal Aguda , Neoplasias , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Cardiografía de Impedancia/métodos , Estudios de Casos y Controles , Gasto Cardíaco , Volumen Sistólico , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiologíaRESUMEN
Purpose: Acute liver failure (ALF) is a clinically fatal disease that leads to the rapid loss of normal liver function. Acetaminophen (APAP) is a leading cause of drug-induced ALF. Ferroptosis, defined as iron-dependent cell death associated with lipid peroxide accumulation, has been shown to be strongly associated with APAP-induced liver injury. Growth arrest-specific 1 (GAS1) is a growth arrest-specific gene, which is closely related to the inhibition of cell growth and promotion of apoptosis. However, the functional role and underlying mechanism of GAS1 in APAP-induced ferroptosis remain unknown. Methods: We established liver-specific overexpression of GAS1 (GAS1AAV8-OE) mice and the control (GAS1AAV8-vector) mice by tail vein injection of male mice with adeno-associated virus. APAP at 500 mg/kg was intraperitoneally injected into these two groups of mice to induce acute liver failure. The shRNA packaged by the lentivirus inhibits GAS1 gene expression in human hepatoma cell line HepaRG (HepaRG-shNC and HepaRG-shGAS1-2) and primary hepatocytes of mice with liver-specific overexpression of GAS1 were isolated and induced by APAP in vitro to further investigate the regulatory role of GAS1 in APAP-induced acute liver failure. Results: APAP-induced upregulation of ferroptosis, levels of lipid peroxides and reactive oxygen species, and depletion of glutathione were effectively alleviated by the ferroptosis inhibitor, ferrostatin-1, and downregulation of GAS1 expression. GAS1 overexpression promoted ferroptosis-induced lipid peroxide accumulation via p53, inhibiting its downstream target, solute carrier family 7 member 11. Conclusion: Collectively, our findings suggest that GAS1 overexpression plays a key role in aggravating APAP-induced acute liver injury by promoting ferroptosis-induced accumulation of lipid peroxides.
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Ferroptosis , Fallo Hepático Agudo , Animales , Humanos , Masculino , Ratones , Acetaminofén/toxicidad , Proteínas de Ciclo Celular/metabolismo , Ferroptosis/genética , Proteínas Ligadas a GPI/metabolismo , Hepatocitos/metabolismo , Peróxidos Lipídicos/metabolismo , Hígado , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/metabolismo , Ratones Endogámicos C57BLRESUMEN
Blood concentration monitoring plays an important role in the rational use of norvancomycin. However, the reference interval for the norvancomycin plasma concentration in the treatment of infections in hemodialysis patients with end stage kidney disease is undefined. To determine the safe and effective interval for the norvancomycin plasma trough concentration, 39 patients treated with hemodialysis and norvancomycin were analyzed retrospectively. The norvancomycin plasma concentration before hemodialysis was tested as the trough concentration. The associations of the norvancomycin trough concentration with efficacy and adverse reactions were evaluated. No norvancomycin concentration above 20 µg/mL was detected. The trough concentration, but not the dose, had a significant effect on the anti-infectious efficacy. Compared with the low norvancomycin trough concentration group (<9.30 µg/mL), the high concentration group (9.30-20.0 µg/mL) had improved efficacy (OR = 15.45, p < 0.01) with similar side effects (OR = 0.5417, p = 0.4069). It is beneficial to maintain the norvancomycin trough concentration at 9.30-20.0 µg/mL to achieve a good anti-infectious effect in hemodialysis patients with end stage kidney disease. Plasma concentration monitoring provides a data basis for the individual treatment of infections with norvancomycin in hemodialysis patients.
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Antibacterianos , Fallo Renal Crónico , Humanos , Estudios Retrospectivos , Diálisis RenalRESUMEN
The design and fabrication of nanomaterials with controllable morphology and size is of critical importance to achieve excellent catalytic performance in heterogeneous catalysis. In this work, cobalt oxide (Co3O4) nanostructures with different morphologies (nanoplates, microflowers, nanorods and nanocubes) were successfully constructed in order to establish the morphology-property-performance relationship of the catalysts. The morphology and structure of the nanostructured Co3O4 were characterized by various techniques, and the catalytic performance of the as-prepared nanostructures was studied by monitoring the reduction of p-nitrophenol to p-aminophenol in the presence of excess NaBH4. The catalytic performance was found to be strongly dependent on their morphologies. The experimental results show that the pseudo-first-order reaction rate constants for Co3O4 nanostructures with various shapes are, respectively, 1.49 min-1 (nanoplates), 1.40 min-1 (microflowers), 0.78 min-1 (nanorods) and 0.23 min-1 (nanocubes). The Co3O4 nanoplates exhibited the highest catalytic activity among the four nanostructures, due to their largest specific surface area, relatively high total pore volume, best redox properties and abundance of defect sites. The established correlation between morphology, property and catalytic performance in this work will offer valuable insight into the design and application of nanostructured Co3O4 as a potential non-noble metal catalyst for p-nitrophenol reduction.
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OBJECTIVE: To investigate the addition of dietary fiber in infant formula approved in recent 5 years. METHODS: A total of 1438 infant formula milk powder approved in China from January 2017 to June 2022 were collected and the addition rate, content and mixture of dietary fiber components such as galactooligosaccharide(FOS), fructooligosaccharide(GOS), polyfructose, polyglucose, raffinose and yeast ß-dextran were statistically analyzed. RESULTS: Among the 1438 infant formulas, 84.07%(1209) were added with dietary fiber, and the addition rate increased yearly. Among them, the addition rate of GOS(79.82%) and FOS(79.74%) was the highest, and the median amount of dietary fiber components was 3.00 g/100 g. Among the products added with various dietary fiber components, there were 762 products added with GOS and FOS, The addition ratios of GOS and FOS were mainly concentrated at 1â¶1. CONCLUSION: The addition rate of dietary fiber in infant formula milk powder in China is constantly increasing, however there are large differences in the addition amount, dietary fiber combination and proportion of different products.
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Fibras de la Dieta , Fórmulas Infantiles , Humanos , Lactante , Polvos , Estudios de Seguimiento , ChinaRESUMEN
BACKGROUND: The orchid growth and development often associate with microbes. However, the interaction between plant performance and microbial communities within and surrounding plants is less understood. Dendrobium catenatum, which used to be an endangered orchid species, has become a billion dollar industry in China. Simulated natural cultivation modes, such as living tree epiphytic (LT) and cliff epiphytic (CE) cultivations, improve the production or quality of D. catenatum and contribute to the development of D. catenatum industry. In a previous study, morphological characteristics, anatomical structure, and main bioactive components (polysaccharides and ethanol-soluble extractives) of D. catenatum grown under LT and CE significantly differed from a facility cultivation mode, pot (PO) cultivation, were observed. Whether cultivation mode affects bacterial and fungal communities of D. catenatum, thereby affecting the chemical quality of this plant, need to be explored. RESULTS: Both three plant organs (leaf, stem, and root) and cultivating substrates obtained under three cultivation modes: living tree epiphytic (LT), cliff epiphytic (CE), and pot (PO) cultivation were examined by adopting high-throughput sequencing methods. Subsequently, bacterial and fungal correlations with D. catenatum main chemical components, stem polysaccharides and ethanol-soluble extractives and leaf phenols and flavonoids, were elucidated. The results showed that microbial communities of the plants and substrates are both influenced by the cultivation mode. However, the plants and their cultivating substrates exhibited different patterns of bacterial and fungal composition, with clearly distinguished dominant bacterial groups, but shared dominance among fungal groups. Bacteria and fungi differed in abundance, diversity, and community structure, depending on the cultivation environment and plant organ. Both bacterial and fungal communities were affected by cultivation mode and plant organ. In both plants and substrates, PO bacterial and fungal community structure differed significantly from those of LT and CE modes. Bacterial and fungal community structure differed significantly between roots and the other two plant organs examined (stems and leaves). Several bacteria and fungi were positively correlated with main chemical components in D. catenatum. CONCLUSIONS: The findings indicate that microbial communities of the plants and substrates were both influenced by the cultivation mode and plant organ, and some of them were positively correlated with main chemical components in D. catenatum. The research would enhance our understanding of interactions between Dendrobium and the microbial environment, and to provide a theoretical basis for the development of improved D. catenatum cultivation methods.
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Dendrobium , Micobioma , Bacterias/genética , Dendrobium/química , Etanol , Flavonoides , Fenoles , Plantas , Polisacáridos , ÁrbolesRESUMEN
BACKGROUND AND AIMS: NASH is an advanced stage of liver disease accompanied by lipid accumulation, inflammation, and liver fibrosis. Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) is a member of the "inhibitory" class of α-subunits, and recent studies showed that Gnai2 deficiency is known to cause reduced weight in mice. However, the role of GNAI2 in hepatocytes, particularly in the context of liver inflammation and lipid metabolism, remains to be elucidated. Herein, we aim to ascertain the function of GNAI2 in hepatocytes and its impact on the development of NASH. APPROACH AND RESULTS: Human liver tissues were obtained from NASH patients and healthy persons to evaluate the expression and clinical relevance of GNAI2. In addition, hepatocyte-specific Gnai2-deficient mice (Gnai2hep-/- ) were fed either a Western diet supplemented with fructose in drinking water (WDF) for 16 weeks or a methionine/choline-deficient diet (MCD) for 6 weeks to investigate the regulatory role and underlying mechanism of Gnai2 in NASH. GNAI2 was significantly up-regulated in liver tissues of patients with NASH. Following feeding with WDF or MCD diets, livers from Gnai2hep-/- mice had reduced steatohepatitis with suppression of markers of inflammation and an increase in lipophagy compared to Gnai2flox/flox mice. Toll-like receptor 4 signals through nuclear factor kappa B to trigger p65-dependent transcription of Gnai2. Intriguingly, immunoprecipitation, immunofluorescence, and mass spectrometry identified peroxiredoxin 1 (PRDX1) as a binding partner of GNAI2. Moreover, the function of PRDX1 in the suppression of TNF receptor-associated factor 6 ubiquitin-ligase activity and glycerophosphodiester phosphodiesterase domain-containing 5-related phosphatidylcholine metabolism was inhibited by GNAI2. Suppression of GNAI2 combined with overexpression of PRDX1 reversed the development of steatosis and fibrosis in vivo. CONCLUSIONS: GNAI2 is a major regulator that leads to the development of NASH. Thus, inhibition of GNAI2 could be an effective therapeutic target for the treatment of NASH.