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BACKGROUND: Epstein-Barr virus (EBV) can be reactivated and proliferated with fatal outcome in immuno-compromised people, but the clinical consequences of EBV infection in patients with severe fever with thrombocytopenia syndrome (SFTS) remain uncertain. In this study, we investigated the infection rate, the influence and the early predictors of EBV infection in SFTS patients. METHODS: In this retrospective study, SFTS patients who were treated in the First Affiliated Hospital of Nanjing Medical University from May 2011 to August 2021 were enrolled and divided into infected and non-infected groups. We compared the demographic characteristics, clinical manifestations and signs, laboratory tests and prognosis, and explored the risk factors of EBV infection by receiver operating characteristic (ROC) curve and logistic regression. RESULTS: A total of 120 hospitalized SFTS patients with EBV-DNA testing were enrolled in this study. Patients with EBV infection had statistically significant higher mortality rate (32.0% vs. 11.43%, P = 0.005). Compared with the non-infected group, the EBV-infected group had higher levels of C-reactive protein (CRP), creatine-kinase (CK), fasting blood glucose (FBG), blood urea nitrogen (BUN), D-dimer, and CD56+ cell counts, lower levels of immunoglobulin G (IgG), IgM, complement 3 (C3), and C4. The proportion of patients with age ≥ 60 years and ferritin > 1500.0 ng/ml in the EBV-infected group was significantly higher than that in the non-infected group. The results of ROC analysis showed that the cut-off values of CRP, IgG, C3, C4, and CD56+ cell counts to predict EBV infection were 13.2 mg/l, 12.5 g/l, 1.1 g/l, 0.6 g/l, 0.3 g/l, and 94.0 cells/µl. Multivariable logistic analysis showed that age ≥ 60 years old, CRP > 13.2 mg/l, BUN > 5.4 mmol/l, ferritin > 1500.0 ng/ml, IgG < 12.5 g/l, IgM < 1.1 g/l, C4 < 0.3 g/l, and CD56+ cell counts > 94.0 cells/µl were the independent risk factors of EBV infection in SFTS patients. CONCLUSIONS: SFTS combined with EBV infection is associated with high morbidity and mortality. It is necessary to strengthen screening for EBV infection and its early predictive markers after admission in SFTS patients.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Síndrome de Trombocitopenia Febril Grave , Humanos , Masculino , Femenino , Persona de Mediana Edad , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/virología , Estudios Retrospectivos , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/sangre , Síndrome de Trombocitopenia Febril Grave/diagnóstico , Anciano , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Factores de Riesgo , Pronóstico , Adulto , Curva ROC , China/epidemiología , Anticuerpos Antivirales/sangre , ADN Viral/sangreRESUMEN
A. Baumannii is an opportunistic nosocomial pathogen which has severe antibiotic resistance. However, the epidemiology is less clearly understood in Jilin province and China. Thus, 89 A. baumannii isolates from a single hospital in Jilin province between 2013-2017 were performed by MLST. In order to better understanding of the epidemiology of Jilin isolates, Chinese strains originated from other domestic regions and worldwide isolates in MLST database were analyzed by silico phylogenetic tools together. A total of 22 STs in Jilin were identified, and 10 STs were found to be novel. The top three predominant sequence types are ST195 (n = 34, 38.2%), ST208 (n = 14, 15.7%) and ST540 (n = 13, 14.6%). ST369 is predicted to be group founder and ST195, ST540 are subgroup founders of the majority STs in Jilin Province. Some newly discovered singletons showed close relationship with strains from other countries, which suggest that nation-cross transmission is one of important origin of Jilin strains. The majority of Jilin STs showed clonality and close relationship with the majorities from other regions of China. But occupation of individual STs in Jilin were different from that of other domestic regions. The aggregation trend and genetic relationship proved that predominant Jilin STs continue to mutate during transmission. Drug resistance facilitated transmission of Jilin A.baumannii isolates because more than 94% of isolates are resistant to at least one carbapenem and the STs with strong resistance to carbapenems usually has more isolates. In conclusion, high diversity and different occupation of STs, and occupation of novel STs proved that epidemiology of A. baumannii in Jilin has special regional characteristics, and drug resistance facilitated transmission of domestic strains and foreign strains.
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Acinetobacter baumannii , Antibacterianos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , beta-Lactamasas/genética , Tipificación de Secuencias Multilocus , Filogenia , Epidemiología Molecular , Carbapenémicos/farmacología , China/epidemiología , Pruebas de Sensibilidad MicrobianaRESUMEN
Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.
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Neoplasias de la Mama , Humanos , Ratones , Animales , Femenino , Distribución Tisular , Membrana Celular/metabolismo , Línea Celular Tumoral , Liposomas , Neoplasias de la Mama/metabolismoRESUMEN
BACKGROUND: Digital cognitive behavior therapy for insomnia (dCBT-I) is an effective treatment in alleviating insomnia. This study examined the effect of dCBT-I for improving sleep quality in patients with insomnia complaints from a clinical population in a real-world setting. METHODS: The study included 6,002 patients aged 18 years and above with primary complaints of dissatisfying sleep from a sleep clinic in a psychiatric hospital from November 2016 to April 2021. Patients were diagnosed with insomnia, anxiety disorders, or anxiety comorbid with insomnia or depression according to ICD-10. A mobile app was developed for self-reported assessment and delivering dCBT-I interventions and treatment prescriptions to participants. The primary outcome was change in global sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). At 8- and 12-week follow-up, 509 patients were reassessed. Data were analyzed with non-parametric tests for repeated measures. RESULTS: Patients treated with dCBT-I monotherapy were younger, with a more frequent family history of insomnia compared to those with medication monotherapy and those with combined dCBT-I and medication therapy. Improvements of sleep quality from baseline to 8-week follow-up were significant in each treatment type. Compared to 8-week follow-up, PSQI scores at 12-week were significantly decreased in the depression group receiving combined therapy and in the anxiety group treated with dCBT-I monotherapy and with combined therapy. A time-by-treatment interaction was detected in anxiety patients indicating differential reduction in PSQI scores over time between different treatment options. CONCLUSION: The current findings suggest dCBT-I is a practical and effective approach for lessening insomnia symptoms, especially for patients with anxiety symptoms suggesting with a more extended intervention period (i.e., 12 weeks). TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900022699).
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Terapia Cognitivo-Conductual , Calidad del Sueño , HumanosAsunto(s)
Infecciones por Coronavirus/epidemiología , Internet , Trastornos Mentales/terapia , Servicios de Salud Mental , Aplicaciones Móviles , Neumonía Viral/epidemiología , Estrés Psicológico/terapia , Telemedicina , Betacoronavirus , COVID-19 , China/epidemiología , Brotes de Enfermedades , Humanos , Pandemias , SARS-CoV-2RESUMEN
Plant proteins have the advantages of low cost and high yield, but they are still not comparable to animal proteins in processing due to factors such as gelation and solubility. How to enhance the processing performance of plant proteins by simple and green modification means has become a hot research topic nowadays. Based on the above problems, we studied the effect of gel induction on its properties. In this study, a pea protein-zein complex was prepared by the pH cycle method, and the effects of different induced gel methods on the gel properties of the complex protein were studied. The conclusions are as follows: All three gel induction methods can make the complex protein form a gel system, among which the gel strength of heat treatment and the TG enzyme-inducted group is the highest (372.84 g). Through the observation of the gel microstructure, the gel double network structure disappears and the structure becomes denser, which leads to a stronger water-binding state of the gel sample in the collaborative treatment group. In the simulated digestion experiment, heat treatment and enzyme-induced samples showed the best slow-release effect. This study provides a new method for the preparation of multi-vegetable protein gels and lays a theoretical foundation for their application in food processing.
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In this study, we investigated the impact of fluctuating water levels on the distribution of lead (Pb) and zinc (Zn) in soil and sediments at a historical Pb-Zn smelting site along the Xiangjiang River. Despite the high pH levels (7 to 11) in the study area, which generally inhibits heavy metal solubility, we found that regular changes in water levels still affect Pb-Zn movement. Soil analysis revealed distinct redox zones within the unconfined aquifer, as shown by the variable Fe/Mn and Ce/Ce* ratios. Advanced techniques such as Mn K-edge XAFS, Mössbauer spectroscopy, and TOF-SIMS indicated persistent Fe-Mn redox cycling and highlighted the presence of Pb and Zn-rich manganese oxides near sulfur-bearing minerals. These findings suggest that acidic microzones produced by the oxidation of sulfur-bearing minerals become "refuges" for microbial and heavy metal activity. Considering that sulfur-containing minerals are widespread waste types in nonferrous metal smelting sites, these findings are instructive for a better understanding of the transformation mechanisms of heavy metal ions in nonferrous metal smelting-polluted environments and for guiding pollution remediation strategies.
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The effects of postharvest ripening of corn on the mechanisms of starch and protein interactions were investigated using molecular dynamics and several chemical substances. Sodium dodecyl sulfate (SDS) treatment all significantly affected the starch content, molecular weight of proteins, relative crystallinity, pasting characteristics and dynamic viscoelasticity in samples before and after postharvest ripening. In the corn that had not undergone postharvest ripening, there were also significant electrostatic interactions and hydrogen bonds between starch and protein. In addition, molecular dynamics had demonstrated that the forces between starch and protein in corn were mainly hydrophobic interactions, electrostatic interaction, and hydrogen bonds. Compared with zein, corn glutelin was more tightly bound to starch. The binding energy of starch to both proteins was reduced in after postharvest-ripened corn. This study laid a rationale for investigating the change mechanism of corn postharvest ripening quality and improving processing property and edible quality of corn.
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Proteínas de Plantas , Almidón , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/química , Zea mays/metabolismo , Almidón/química , Almidón/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Zeína/química , Zeína/metabolismo , Manipulación de Alimentos , Peso Molecular , Viscosidad , Enlace de Hidrógeno , Simulación de Dinámica Molecular , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
The impact of pesticides on reproductive health has been increasingly recognized. ß-cypermethrin (ß-CYP) and emamectin benzoate (EMB) are commonly used with agricultural workers. There are few published studies on the effects of combined poisoning of these two pesticides on the reproductive system. This study investigated the toxic effects and mechanism of ß-CYP and EMB on the reproductive system of female rats based on the hypothalamic-pituitary-ovarian (HPO) axis. The hypothalamic GnRH content tended to decrease, and Kiss-1 and GPR-54 mRNA and protein expression tended to increase in exposed rats. FSH content was elevated for the pituitary gland, and Kiss-1 and GPR-54 mRNA and protein expression were enhanced in all experimental groups compared with the control group. E2 content in rat ovaries and ERα mRNA and protein expression were reduced by ß-CYP and EMB. Furthermore, there were interactive effects of ß-CYP and EMB on FSH and E2 release, pituitary GPR-54 mRNA and protein, and ovarian ERα mRNA expression. To investigate causes of damage, oxidative damage indicators were tested and showed that exposure to ß-CYP and EMB decreased GSH-Px and SOD activities in the HPO axis, increased MDA levels in the hypothalamus and ovary together with LDH activities in the HPO axis, with an interaction effect on GSH-Px and SOD activities in the hypothalamus and pituitary gland as well as on MDA in the ovary. The above results support the screening of sensitive molecular biomarkers and evaluation of the adverse effects of pesticide exposure in greenhouse operations on reproductive health.
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Ivermectina/análogos & derivados , Ovario , Plaguicidas , Piretrinas , Ratas , Femenino , Animales , Ovario/metabolismo , Receptor alfa de Estrógeno/metabolismo , Kisspeptinas/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Folículo Estimulante , Estrés Oxidativo , Homeostasis , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Chemoimmunotherapy has emerged as a promising strategy for improving the efficacy of cancer treatment. Herein, we present PD-1 receptor-presenting membrane-coated paclitaxel dimers nanoparticles (PD-1@PTX2 NPs) for enhanced treatment efficacy. PD-1 cell membrane-cloaked PTX dimer exhibited effective cellular uptake and increased cytotoxicity against cancer cells. PD-1@PTX2 NPs could selectively bind with PD-L1 ligands expressed on breast cancer cells. Our nanoparticles exhibit a remarkable tumor growth inhibition rate of 71.3% in mice bearing 4T1 xenografts and significantly prolong survival in mouse models of breast cancer. Additionally, our nanoparticles promoted a significant 3.2-fold increase in CD8+ T cell infiltration and 73.7% regulatory T cell (Treg) depletion within tumors, boosting a robust antitumor immune response. These findings underscore the potential of utilizing immune checkpoint receptor-presented PTX nanoparticles to enhance the efficacy of chemoimmunotherapy, providing an alternative approach for improving cancer treatment.
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Inmunoterapia , Ratones Endogámicos BALB C , Nanopartículas , Paclitaxel , Receptor de Muerte Celular Programada 1 , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Animales , Nanopartículas/química , Receptor de Muerte Celular Programada 1/metabolismo , Femenino , Humanos , Inmunoterapia/métodos , Ratones , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/inmunología , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Ensayos Antitumor por Modelo de Xenoinjerto , Dimerización , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Antígeno B7-H1/metabolismoRESUMEN
Immune checkpoint inhibitors (ICIs) have effectively eradicated advanced tumors by inducing durable and systematic antitumor immune responses. However, when used as a standalone treatment, ICIs typically exhibit a low response rate in many cancers. In this study, we engineered an in situ-formed gel depot using elastin-like polypeptides (ELPs) to efficiently deliver PD-L1 antibodies (aPD-L1) and gemcitabine (GEM) for enhanced immunotherapy in melanoma. Sustainably released chemotherapeutics from gel depots could kill melanoma cells and promote PD-L1 upregulation in tumor cells. Moreover, aPD-L1/GEM-encapsulated ELP hydrogel promoted a 3.0-fold increase of tumor-infiltrated CD8+ T cells and 60% Tregs depletion compared with PBS group, eliciting a robust antitumor immune response for immunotherapy in melanoma mouse models. This research highlights the promising potential of ELP-based hydrogels in delivering ICIs and chemotherapeutic agents for potentiated cancer immunotherapy.
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Linfocitos T CD8-positivos , Melanoma , Animales , Ratones , Antígeno B7-H1 , Hidrogeles/uso terapéutico , Elastina/uso terapéutico , Inmunoterapia , Anticuerpos Monoclonales/uso terapéutico , Melanoma/tratamiento farmacológicoRESUMEN
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with an extensive geographical distribution and high mortality rate. To date, the role of SFTS virus (SFTSV) in urine is still elusive. We aimed to explore the relationship between urinary bunyavirus and acute kidney injury (AKI) and mortality in patients with SFTS. Methods: Urine samples were collected from 102 patients to quantify SFTSV load in urine (U-SFTSV). Patient renal function was evaluated on admission. Receiver operating characteristic (ROC) curve and logistic regression analysis were performed to evaluate the predictive value of U-SFTSV. Viral infectivity assays in Vero cells were performed from 10 urine samples. Results: The U-SFTSV level was positively correlated with SFTSV load in plasma (r = 0.624) and indicators of renal damage. The U-SFTSV level was identified as an independent risk factor for SFTS-associated AKI (odds ratio, 3.631; P = .019). The U-SFTSV showed great value in predicting the fatal outcome of SFTS patients with high area under curve (0.881). The Kaplan-Meier survival comparison showed that patients with U-SFTSV levels greater than 6379 copies/mL were at a higher risk of death within 28â days after onset. In addition, 4 urine samples with high U-SFTSV levels were infectious. Conclusions: Our large cohort study identified that the U-SFTSV level is a novel convenient and noninvasive predictive biomarker for incidence of AKI and poor outcome of patients with SFTS. Urine specimens could be a source of SFTSV infection in humans.
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Objectives: Invasive pulmonary aspergillosis (IPA) is common in immuno-compromised people, and a high incidence of IPA has been found in patients with severe fever with thrombocytopenia syndrome (SFTS). Our study aimed to determine the independent risk factors for IPA and the relationship between smoking status and the risk of IPA in SFTS patients. Methods: A retrospective analysis of SFTS patients in the First Affiliated Hospital of Nanjing Medical University from May 2011 to December 2021 was reviewed. The patients were divided into two groups: IPA and non-IPA groups. We compared demographic characteristics, clinical manifestation, laboratory parameters, treatment, and prognosis, and explored the risk factors of IPA using logistic regression and ROC curve. The dose-dependent effect of smoking on the risk of IPA was further estimated, including the age of smoking initiation, daily smoking amount, smoking duration, and pack-years of smoking. Results: In total, 189 individuals were included. Compared with the non-IPA group, the IPA group had higher levels of smoking, drinking, cough, dyspnea, aCCI scores, Dabie bandavirus (DBV) RNA load, ferritin, PCT, IL-6, APTT, LDH, BUN, creatinine, and lower levels of FT4 and TSH. The incidences of MODS, admission to ICU, ventilation, and broad-spectrum antibiotic treatment were significantly higher in the IPA group than in the non-IPA group. Multivariable logistic analysis showed that smoking history, cough, creatinine, admission to ICU, broad-spectrum, and corticosteroid therapies were the independent risk factors for IPA in SFTS patients. We further confirmed that the age of smoking initiation <30 years, smoking at least one pack per day, smoking for at least 40 years, and having at least 40 pack-years of smoking exposure were the independent risk factors for IPA among smokers. Conclusion: The prognosis of SFTS patients in the IPA group is worse than that of the non-IPA group. Attention should be paid to SFTS patients with a smoking history, cough, creatinine, admission to ICU, and broad-spectrum and corticosteroid therapies. There is a strong dose-dependent association between smoking and IPA development in SFTS patients. Prophylactic antifungal therapy should be considered for SFTS patients with these risk factors, but further studies are necessary to determine if it is beneficial for the prognosis of these patients.
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The newly harvested Jidan 66 (JD66) and Liangyu 99 (LY99) varieties of corns were stored for 56 days at constant temperature of 15 and 25 °C with relative humidity of 55%. The postharvest ripening resulted in more disordered secondary structure and less compact tertiary conformation of zein. The emulsifying activity and foaming stability reached maximum after storage of corns at 15 and 25 °C for 14 days, while the emulsifying stability and foaming capacity were the highest at two temperatures of storage for 7 days and 28 days, respectively. Furthermore, zein had the highest viscoelasticity as well as the strongest antioxidant activities after the storage of JD66 at two temperatures for 28 days and the storage of LY99 at 15 °C for 42 days and at 25 °C for 28 days. Therefore, appropriate postharvest ripening of corns changed the structure of zein, improving its antioxidant activities and physicochemical properties.
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OBJECTIVES: To investigate the changes and mechanism of Siglec-9 on NK cells in peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: First, we used single-cell RNA sequencing to analyze the frequency of NK cells in Peripheral Blood Mononuclear Cells (PBMCs) of SFTS patients and healthy controls (HCs), as well as the differences in the genes on NK cells. Secondly, we analyzed the expression of Siglec-9 and other receptors on NK cells by flow cytometry. Thirdly, we analyzed the correlation between Siglec-9 on NK cells and DBV viral load in plasma. RESULTS: Compared with HCs, the frequency of NK cells in peripheral blood of SFTS patients was significantly decreased, and the activating receptors on NK cells were reduced. The expression of Siglec-9 on NK cells and the frequency of Siglec-9+NK cells decreased significantly in SFTS patients. The expression of Siglec-9 on CD16+CD56dim NK cells was negatively correlated with DBV viral load. In addition, Siglec-9+NK cells expressed higher levels of activating receptors and exhibited stronger effector functions than Siglec-9-NK cells. CONCLUSIONS: The decreased expression of Siglec-9 on NK cells predicts NK cell dysfunction in SFTS patients, suggesting that Siglec-9 may be a potential marker for functional NK cell subsets in SFTS patients.
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Leucocitos Mononucleares , Síndrome de Trombocitopenia Febril Grave , Humanos , Leucocitos Mononucleares/metabolismo , Síndrome de Trombocitopenia Febril Grave/metabolismo , Células Asesinas Naturales/metabolismo , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/metabolismo , Citometría de Flujo , Antígeno CD56/metabolismoRESUMEN
Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated. Methods: TRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR-/- SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3-/- mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot. Results: Compared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR-/- SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1ß, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination. Conclusion: TRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.
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Objective: This survey aimed to better comprehend the factors influencing patient response to insomnia treatment. Methods: We conducted an online survey. A total of 1,395 patients completed the questionnaire at baseline. Insomnia, anxiety and depressive symptoms were evaluated using the Pittsburgh Sleep Quality Index (PSQI), 7-item Generalized Anxiety Disorder assessment (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9), respectively. A total of 488 patients completed at least two surveys (baseline and monthly surveys thereafter) and reported that the online CBT was effective at the 1-year follow-up. The 488 patients were divided into three groups: the rapid (treatment effective at 4 weeks), intermediate (4-16 weeks), and delayed-response group (over 16 weeks). Results: Analysis of the demographic characteristics of the 488 patients did not reveal significant sex differences among the three groups (P = 0.111). However, the groups significantly differed in age (P = 0.001) and education (P = 0.006). Compared to the rapid response group, the delayed-response group had a higher mean age (P < 0.01) and a slightly lower level of education. The duration of the disorder was longer in the delayed-response group. Multivariate logistic regression showed that male sex, junior high school education, and higher PSQI were independent risk factors for the delayed response to treatment. Conclusion: Many factors affected the efficiency of insomnia treatment. Male sex, junior school education, and a high PSQI score predicted delayed response to insomnia treatment.
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Soluble dietary fiber (SDF), which is a component of dietary fibers exhibit many physiological functions, biological activity, and good gel forming ability. In this study, extraction of SDF from corn bran was evaluated using twin-screw extrusion and ultrasonic treatment and the combinations of the respective methods with dual enzyme hydrolysis. The monosaccharide compositions, molecular weight, physicochemical properties, and structural and functional characteristics were determined. The results showed that ultrasonic and twin-extrusion treatments significantly increased the SDF content from 2.42 to 4.58 and 6.54%, respectively. Dual enzyme hydrolysis further increased the SDF content. Modification treatment changed the monosaccharide composition, improved physicochemical and functional properties, such as water and oil holding capacity, nitrite adsorption, and antioxidative ability. In conclusion, physical modification combined with enzyme treatment distinctly improved the extraction yield, physicochemical and functional properties of SDF. Therefore, the modified SDF is suitable as a functional food additive.
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The efficient delivery of small interfering RNA (siRNA) for target gene silencing holds great promise for cancer therapy. Protein nanocages have attracted considerable attention as ideal drug delivery systems because of their material-derived advantages and unique structural properties. However, most studies about siRNA delivery have not indicated the real role of protein nanocages in inhibiting tumor growth in vivo. Herein, we fabricated an efficient siRNA delivery system using a small heat shock protein (Hsp) nanocage decorated with Arg-Gly-Asp (RGD) and the transactivator of transcription (Tat) peptide. Hsp-Tat-RGD NC showed good cellular uptake and lysosomal escape in colorectal cancer cells. In addition, the nanocage could efficiently transfect siRNA into the cytoplasmic area of CT26 cells. Hsp-Tat-RGD NC delivering telomerase reverse transcriptase (TERT)-targeting siRNA could significantly downregulate TERT protein expression and trigger tumor cell apoptosis in vitro. More importantly, Hsp-Tat-RGD/siTERT complexes nearly completely inhibited the tumor growth after five times of treatment in mice bearing CT26 xenograft. Our results demonstrate the great potential of the Tat/RGD-decorated Hsp nanocage as a promising siRNA delivery platform for cancer therapy.
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Neoplasias Colorrectales , Proteínas de Choque Térmico Pequeñas , Animales , Neoplasias Colorrectales/genética , Sistemas de Liberación de Medicamentos , Humanos , Ratones , Oligopéptidos , ARN Interferente Pequeño/genéticaRESUMEN
Dysfunctional brain networks have been found in patients with major depressive disorder (MDD). In this study, to verify this in a more straightforward way, we investigated the intrinsic organization of brain networks in MDD by leveraging the resting-state functional near-infrared spectroscopy (rs-fNIRS). Thirty-four MDD patients (24 females, 38.41 ± 13.14 years old) and thirty healthy controls (22 females, 34.43 ± 5.03 years old) underwent a 10 min rest while their brain activity was recorded via fNIRS. The results showed that MDD patients and healthy controls exhibited similar resting-state functional connectivity. Moreover, the depression group showed lower small-world Lambda (1.12 ± 0.04 vs. 1.16 ± 0.10, p = 0.04) but higher global efficiency (0.51 ± 0.03 vs. 0.48 ± 0.05, p = 0.03) than the control group. Importantly, MDD patients, as opposed to healthy controls, showed a significantly lower nodal local efficiency at the left middle occipital gyrus (0.56 ± 0.36 vs. 0.81 ± 0.20, pFDR < 0.05), which predicted the level of depression in MDD (r = 0.45, p = 0.01, R2 = 0.15). In sum, we found a more integrated brain network in MDD patients with a lower nodal local efficiency at the occipital hub, which could predict depressive symptoms.