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BACKGROUND: Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity. RESULTS: We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs. CONCLUSIONS: Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.
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Cardiotoxicidad , Doxorrubicina , Exosomas , Momordica charantia , Factor 2 Relacionado con NF-E2 , Animales , Cardiotoxicidad/prevención & control , Cardiotoxicidad/metabolismo , Momordica charantia/química , Exosomas/metabolismo , Ratas , Factor 2 Relacionado con NF-E2/metabolismo , Línea Celular , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Supervivencia Celular/efectos de los fármacos , Ratas Sprague-Dawley , Proteína Sequestosoma-1/metabolismoRESUMEN
Environmental factors like COVID-19 can have significant impact on technical efficiency (TE) and total factor productivity (TFP) of health services provided. In this study, focusing on Maternal and Child Health (MCH) hospitals in Hubei Province of China in 2019 to 2021, we aimed to measure their TE and TFP, identify some influential environmental factors, and propose some policy recommendations. Altogether 62 secondary MCH hospitals were selected as the study sample. Four input indicators, 3 output indicators, and 4 environmental indicators were selected to analyze the panel data from 2019 to 2021. Three-stage Data Envelopment Analysis (DEA) and Malmquist Productivity Index (MPI) model were employed to estimate the TE and TFP of these hospitals. During 2019 to 2021, the inputs of the sample hospitals had increased, while the outputs had decreased. The inputs redundancy was negatively associated with birth rate, number of residents, and GDP per capita (P < .05). It was positively associated with number of COVID-19 infections (P < .05). The adjusted TE scores in 2019 to 2021 were 0.822, 0.784, and 0.803, respectively. The TFP declined in 2020 and 2021 compared to 2019, with scores being 0.845 and 0.762. The technical efficiency change (TEC) scores from 2019 to 2021 were 0.926 and 1.063. The technological change (TC) scores from 2019 to 2021 were 0.912 and 0.716. During 2019 to 2021, the operation of sample hospitals had been significantly influenced by environmental factors like COVID-19 pandemic, low birth rate, number of residents, and GDP per capita. The inputs had increased but outputs had decreased, leading to an increase in inputs redundancy and a decline in TE. The TFP showed a downward trend, with TC and SEC being the priority directions for improvement. Some recommendations are made for both hospitals and government to continuously improve the TE and TFP.
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COVID-19 , Eficiencia Organizacional , Humanos , China , COVID-19/epidemiología , SARS-CoV-2 , Femenino , Servicios de Salud Materno-Infantil/estadística & datos numéricos , Servicios de Salud Materno-Infantil/organización & administración , NiñoRESUMEN
Objective:To investigate the characteristics and prognosis of two anastomosis techniques in repairing facial nerve defects. Methods:A retrospective analysis was conducted on 30 patients who underwent facial nerve anastomosisï¼direct or reroutingï¼ for facial nerve defects in our department from January 2012 to December 2021. Among them, 21 were male and 9 were female, with an average age ofï¼37.53±11.33ï¼ years, all with unilateral onset. Preoperative House-Brackmannï¼H-Bï¼ facial nerve function grades were â £ in 2 cases, â ¤ in 9 cases, and â ¥in 19 cases. The duration of facial paralysis before surgery was within 6 months in 21 cases, 6-12 months in 6 cases, and over 1 year in 3 cases. The causes of facial paralysis included 14 cases of cholesteatoma, 6 cases of facial neurioma, 6 cases of trauma, and 4 cases of middle ear surgery injury. Surgical approaches included 9 cases of the middle cranial fossa approach, 8 cases of labyrinthine-otic approach, 7 cases of mastoid-epitympanum approach, and 6 cases of retroauricular lateral neck approach. Results:All patients were followed up for more than 2 years. The direct anastomosis was performed in 10 cases: 6 cases with defects located in the extratemporal segment and 4 cases in the tympanic segment. Rerouting anastomosis was performed in 20 cases: 11 cases with defects located in the labyrinthine-geniculate ganglion, 4 cases from the internal auditory canal to the geniculate ganglion, 3 cases in the internal auditory canal, and 2 cases in the horizontal-pyramid segment. Postoperative H-B facial nerve grades were â ¡ in 2 cases, â ¢ in 20 cases, and â £ in 8 cases, with 73.3%ï¼22/30ï¼ of patients achieving H-B grade â ¢ or better. Conclusion:Both direct and rerouting anastomosis techniques can effectively repair facial nerve defects, with no significant difference in efficacy between the two techniques. Most patients can achieve H-B grade â ¢ or better facial nerve function recovery. Preoperative facial nerve function and duration of facial paralysis are the main prognostic factors affecting the outcome of facial nerve anastomosis.
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Anastomosis Quirúrgica , Nervio Facial , Parálisis Facial , Humanos , Masculino , Femenino , Adulto , Nervio Facial/cirugía , Estudios Retrospectivos , Anastomosis Quirúrgica/métodos , Pronóstico , Parálisis Facial/cirugía , Persona de Mediana Edad , Traumatismos del Nervio Facial/cirugía , Resultado del TratamientoRESUMEN
Graphdiyne (GDY)-based materials, owing to their unique structure and tunable electronic properties, exhibit great potential in the fields of catalysis, energy, environmental science, and beyond. In particular, GDY/metal oxide hybrid materials (GDY/MOs) have attracted extensive attention in energy and environmental catalysis. The interaction between GDY and metal oxides can increase the number of intrinsic active sites, facilitate charge transfer, and regulate the adsorption and desorption of intermediate species. In this review, we summarize the structure, synthesis, advanced characterization, small molecule activation mechanism and applications of GDY/MOs in energy conversion and environmental remediation. The intrinsic structure-activity relationship and corresponding reaction mechanism are highlighted. In particular, the activation mechanisms of reactant molecules (H2O, O2, N2, etc.) on GDY/MOs are systemically discussed. Finally, we outline some new perspectives of opportunities and challenges in developing GDY/MOs for efficient energy and environmental catalysis.
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Objective:To investigate the technique of personalized flap making under otoscopy and its clinical application. Methods:The clinical data of patients who underwent 301 Military Hospital myringoplasty in the Department of otoendoscopic surgery, Department of Otorhinolaryngology, head and neck surgery, Department of Otorhinolaryngology, from October 2022 to 2023 August were analyzed retrospectively, all enrolled patients were performed independently by the same skilled otoendoscopic surgeon. The patients' general condition, medical history, tympanic membrane perforation scope, perforation size, need for tympanic cavity exploration, thickness of skin flap, tympanic cavity lesion scope, skin flap making method and postoperative rehabilitation were collected. Results:Many factors such as the location of tympanic membrane perforation, the thickness of the skin flap, the degree of curvature or stricture of the ear canal and the extent of the lesion in the tympanic cavity should be considered in the manufacture of the individualized tympanic membrane skin flap, the way of skin flap making does not affect the long-term postoperative rehabilitation, but it can effectively avoid unnecessary ear canal skin flap injury and improve the operation efficiency. Conclusion:Scientific flap fabrication is important for improving surgical efficiency and enhancing surgical confidence.
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Perforación de la Membrana Timpánica , Membrana Timpánica , Humanos , Membrana Timpánica/lesiones , Perforación de la Membrana Timpánica/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Miringoplastia/métodos , Endoscopía/métodos , Timpanoplastia/métodosRESUMEN
Objective:To compare the application of endoscope and microscope in all kinds of stapes surgeries. Methods:Fifty-nine stapes surgeries have been collected from April 2020 to May 2023 in Senior Department of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, Chinese PLA Medical School. Hearing level, hospital stay post-operation, times of hospital visit post-operation, etc. have been compared between the endoscopic group and microscopic group. Patients who were failed to place the stapes prosthesis because of the poor exposure of the oval window have been analyzed. Results:Otosclerosis was the most common diagnosis in both groups. There was 1ï¼1/23ï¼ middle ear malformation in the endoscopic group and 5ï¼5/36ï¼ middle ear malformations in the microscopic group. There were 2 Van Der Hover syndromes and 4 Treacher Collins syndromes in the microscopic group. In the endoscopic group ABG of 10 earsï¼43.5%ï¼ ≤ 10 dB, and ABG of 21 earsï¼91.3%ï¼ ≤20 dB.In the microscopic group ABG of 13 earsï¼41.9%ï¼ ≤ 10 dB, and ABG of 28 earsï¼90.3%ï¼ ≤ 20 dB. There was no statistic difference between 2 groups. Times of hospital visit post-operation in the endoscopic group was less than in the microscopic groupï¼P<0.01ï¼. There was no facial palsy, tympanic perforation or profound sensorineural hearing loss in both groups. Conclusion:Endoscope is more suitable for patients who are evaluated with no severe stapes malformation, or less manipulation of drilling the bone. It could also reduce the hospital visit post-operation. Patients with narrow ear canal or severe middle ear malformation are recommended to perform the surgery with microscope, because it provides the chance of manipulation with 2-hands of surgeons.
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Otosclerosis , Cirugía del Estribo , Humanos , Estribo , Oído Medio/cirugía , Oído Medio/anomalías , Otosclerosis/diagnóstico , Endoscopios , Poliésteres , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Rabbit coccidiosis is a parasitism caused by either one or multiple co-infections of Eimeria species. Among them, Eimeria intestinalis is the primary pathogen responsible for diarrhea, growth retardation, and potential mortality in rabbits. Concerns regarding drug resistance and drug residues have led to the development of recombinant subunit vaccines targeting Eimeria species as a promising preventive measure. The aim of this study was to assess the immunoprotective efficacy of recombinant subunit vaccines comprising EiROP25 and EiROP30 (rhoptry proteins (ROPs)) against E. intestinalis infection in rabbits. METHODS: Cloning, prokaryotic expression, and protein purification were performed to obtain EiROP25 and EiROP30. Five groups of fifty 35-day-old Eimeria-free rabbits were created (unchallenged control group, challenged control group, vector protein control group, rEiROP25 group, and rEiROP30 group), with 10 rabbits in each group. Rabbits in the rEiROP25 and rEiROP30 groups were immunized with the recombinant proteins (100 µg per rabbit) for primary and booster immunization (100 µg per rabbit) at a two-week intervals, and challenged with 7 × 104 oocysts per rabbit after an additional two-week interval. Two weeks after the challenge, the rabbits were euthanized for analysis. Weekly collections of rabbit sera were made to measure changes in specific IgG and cytokine level. Clinical symptoms and pathological changes after challenge were observed and recorded. At the conclusion of the animal experiment, lesion scores, the relative weight increase ratio, the oocyst reduction rate, and the anticoccidial index were computed. RESULTS: Rabbits immunized with rEiROP25 and rEiROP30 exhibited relative weight gain ratios of 56.57% and 72.36%, respectively. Oocysts decreased by 78.14% and 84.06% for the rEiROP25 and rEiROP30 groups, respectively. The anticoccidial indexes were 140 and 155. Furthermore, there was a noticeable drop in intestinal lesions. After the primary immunization with rEiROP25 and rEiROP30, a week later, there was a notable rise in specific IgG levels, which remained elevated for two weeks following challenge (P < 0.05). Interleukin (IL)-2 levels increased markedly in the rEiROP25 group, whereas IL-2, interferon gamma (IFN-γ), and IL-4 levels increased substantially in the rEiROP30 group (P < 0.05). CONCLUSION: Immunization of rabbits indicated that both rEiROP25 and rEiROP30 are capable of inducing an increase in specific antibody levels. rEiROP25 triggered a Th1-type immune protection response, while rEiROP30 elicited a Th1/Th2 mixed response. EiROP25 and EiROP30 can generate a moderate level of immune protection, with better efficacy observed for EiROP30. This study provides valuable insights for the promotion of recombinant subunit vaccines targeting rabbit E. intestinalis infection.
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Coccidiosis , Eimeria , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Conejos , Animales , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Proteínas Recombinantes , Vacunas Sintéticas , Oocistos , Vacunas de Subunidad , Inmunoglobulina G , Pollos , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Typically, SO2 unavoidably deactivates catalysts in most heterogeneous catalytic oxidations. However, for Pt-based catalysts, SO2 exhibits an extraordinary boosting effect in propane catalytic oxidation, but the promotive mechanism remains contentious. In this study, an in situ-formed tactful (Pt-S-O)-Ti structure was concluded to be a key factor for Pt/TiO2 catalysts with a substantial SO2 tolerance ability. The experiments and theoretical calculations confirm that the high degree of hybridization and orbital coupling between Pt 5d and S 3p orbitals enable more charge transfer from Pt to S species, thus forming the (Pt-S-O)-Ti structure with the oxygen atom dissociated from the chemisorbed O2 adsorbed on oxygen vacancies. The active oxygen atom in the (Pt-S-O)-Ti active structure is a robust site for C3H8 adsorption, leading to a better C3H8 combustion performance. This work can provide insights into the rational design of chemical bonds for high SO2 tolerance catalysts, thereby improving economic and environmental benefits.
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Oxígeno , Titanio , Titanio/química , Oxidación-Reducción , Catálisis , AdsorciónRESUMEN
As China's "double carbon" goal continues to advance, logistics as a key area of carbon emissions and low-carbon logistics center site selection are key links in the process. However, existing studies on logistics center location often ignore the impact of demand uncertainty, which leads to a waste of resources in the planning and construction processes. We take logistics cost and carbon emission as the objectives, and the multi-objective site selection model established based on stochastic programming theory takes demand uncertainty as a stochastic constraint. We transform the stochastic constraint model into a 0-1 mixed integer multi-objective planning model by utilizing the idea of equivalence transformation. The Aptenodytes Forsteri Optimization (AFO) algorithm is combined with the Ideal Point Method to solve the model, and the algorithm is compared with the Particle Swarm Optimization (PSO), Differential Evolutionary (DE), Tabu Search (TS), Sparrow Search (SS) algorithms, and the exact solver Linear Interactive and General Optimizer (LINGO). The examples verify the validity of the models and algorithms, with an average reduction of 6.2% and 3.6% in logistics costs and carbon emissions in the case of demand determination, and at the confidence level of 0.9 under demand uncertainty, both logistics costs and carbon emissions are decreased to varying degrees. This study provides a new research idea for the low-carbon logistics location problem under demand uncertainty, which helps to promote the transformation of the logistics industry to low-carbon and high-efficiency.
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Spheniscidae , Animales , Modelos Teóricos , Carbono , Incertidumbre , AlgoritmosRESUMEN
PURPOSE: Determination of isocitrate dehydrogenase (IDH) genotype is crucial in the stratification of diagnosis and prognostication in diffuse gliomas. We sought to build and validate radiomics models and clinical features incorporated nomogram for preoperative prediction of IDH mutation status and WHO grade of diffuse gliomas with L-[methyl-11C] methionine ([11C]MET) PET/CT imaging according to the 2016 WHO classification of tumors of the central nervous system. METHODS: Consecutive 178 preoperative [11C]MET PET/CT images were retrospectively studied for radiomics analysis. One hundred six patients from PET scanner 1 were used as training dataset, and 72 patients from PET scanner 2 were used for validation dataset. [11C]MET PET and integrated CT radiomics features were extracted, respectively; three independent predictive models were built based on PET features, CT features, and combined PET/CT features, respectively. The SelectKBest method, Spearman correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and machine learning algorithms were applied for feature selection and model building. After filtering the satisfactory predictive model, key clinical features were incorporated for the nomogram establishment. RESULTS: The combined [11C]MET PET/CT radiomics model, which consisted of four PET features and eight integrated CT features, was significantly associated with IDH genotype (p < 0.0001 for both training and validation datasets). Nomogram based on the [11C]MET PET/CT radiomics score, patients' age, and dichotomous tumor location status showed satisfactory discrimination capacity, and the AUC was 0.880 (95% CI, 0.726-0.998) in the training dataset and 0.866 (95% CI, 0.777-0.956) in the validation dataset. In IDH stratified WHO grade prediction, the final radiomics model consists of four PET features and two CT features had reasonable and stable differential efficacy of WHO grade II and III patients from grade IV patients in IDH-wildtype patients, and the AUC was 0.820 (95% CI, 0.541-1.000) in the training dataset and 0.766 (95% CI, 0.612-0.921) in the validation dataset. CONCLUSION: [11C]MET PET radiomics features could benefit non-invasive IDH genotype prediction, and integrated CT radiomics features could enhance the efficacy. Radiomics and clinical features incorporation could establish satisfactory nomogram for clinical application. This non-invasive predictive investigation based on our consecutive cohort from two PET scanners could provide the perspective to observe the differential efficacy and the stability of radiomics-based investigation in untreated diffuse gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Isocitrato Deshidrogenasa/genética , Estudios de Cohortes , Metionina , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiómica , Radioisótopos de Carbono , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/patología , Racemetionina , Mutación , Organización Mundial de la SaludRESUMEN
Pluripotent stem cells (PSCs) are a promising source of allogeneic T cells for off-the-shelf immunotherapies. However, the process of differentiating genetically engineered PSCs to generate mature T cells requires that the same molecular elements that are crucial for the selection of these cells be removed to prevent alloreactivity. Here we show that antigen-restricted mature T cells can be generated in vitro from PSCs edited via CRISPR to lack endogenous T cell receptors (TCRs) and class I major histocompatibility complexes. Specifically, we used T cell precursors from RAG1-/-RAG2-/-B2M-/- human PSCs expressing a single TCR, and a murine stromal cell line providing the cognate human major histocompatibility complex molecule and other critical signals for T cell maturation. Possibly owing to the absence of TCR mispairing, the generated T cells showed substantially better tumour control in mice than T cells with an intact endogenous TCR. Introducing the T cell selection components into the stromal microenvironment of the PSCs overcomes inherent biological challenges associated with the development of T cell immunotherapies from allogeneic PSCs.
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Studies on the bench and at bedside have demonstrated that the process of epileptogenesis is involved in neuroinflammatory responses. As the receptor of proinflammatory cytokine IL-1ß, IL-1ß type 1 receptor (IL-1R1) is reported to express abundantly in the endothelial cells in epileptic brains, which is deemed to be implicated in the epileptogenic process. However, whether and how endothelial IL-1R1 modulates neuroinflammatory responses in the pathological process of epileptic seizures and/or status epilepticus (SE) remains obscure. Here, we indicated endothelial IL-1R1 is involved in neuroinflammation, facilitating epilepsy progress via Nrf2/HO-1/NLRP3. In vitro, we observed upregulation of inflammatory cytokines in co-culture model under IL-1ß challenge, as well as in BV2 cells after stimulation with conditional medium (CM) from IL-1ß-stimulated bEnd.3 cells. In vivo, mice with conditional knockout of endothelial IL-1R1 (IL-1R1-CKO) were generated by hybrid IL-1R1flox/flox mice with Tek-Cre mice. IL-1R1-CKO reduced seizure susceptibility in kainic acid (KA)-induced SE model. In addition, IL-1R1-CKO KA mice exhibited lessened hippocampal neuroinflammation, mitigated neuronal damage, and decreased abnormal neurogenesis. In cognitive behavioral tests, IL-1R1-CKO KA mice presented improvement in learning and memory. Furthermore, we also indicated blockage of endothelial IL-1R1 downregulated the expressions of Nrf2/HO-1/NLRP3 pathway-related proteins. Nrf2-siRNA reversed the downregulation of HO-1, NLRP3, caspase-1, and IL-1ß. These results demonstrated CKO of endothelial IL-1R1 reduces seizure susceptibility and attenuates SE-related neurobehavioral damage by suppressing hippocampal neuroinflammation via Nrf2/HO-1/NLRP3.
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Lung adenocarcinoma (LUAD) is a non-small-cell lung cancer and is the leading cause of cancer-related deaths worldwide. Immunotherapy is a promising candidate for LUAD, and tumor mutation burden (TMB) could be a new biomarker to monitor the response of cancer patients to immunotherapy. It is known that the mucin 16 (MUC16) mutation is the most common and affects the progression and prognosis of several cancers. However, whether MUC16 mutations are associated with TMB and tumor-infiltrating immune cells in LUAD is not fully elucidated. All the data were obtained from the cancer genome atlas database to assess the prognostic value and potential mechanism of MUC16 in LUAD. An immune prognostic model (IPM) was developed based on immune-related genes that could be differentially expressed between MUC16MUT and MUC16WT LUAD patients. Later, the IPM effect on the prognosis and immunotherapy of LUAD was comprehensively evaluated. MUC16 was frequently mutated in LUAD, with a mutational frequency of 43.4%, significantly associated with higher TMB and better clinical prognosis. Based on 436 patients with LUAD, an IPM was established and validated to differentiate patients with a low or high risk of poor survival. The univariate and multivariate Cox regression analyses demonstrated that the IPM was an independent prognostic indicator for LUAD patients. Elevated expressions of PD-L1, LAG3, PDCD1, and SIGLEC15, and most of the T-effector and interferon-γ gene signatures, were depicted in the high-risk group. Moreover, the nomogram using the IPM and clinical prognostic factors also predicted the overall survival and clinical utility. Our project developed a robust risk signature depending on the MUC16 status and provided novel insights for individualized treatment options for LUAD patients.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígeno Ca-125 , Mutación , Inmunoterapia , Pronóstico , Proteínas de la MembranaRESUMEN
Chlorogenic acid (CGA) is a naturally occurring plant component with the purpose of alleviating hepatic lipid deposition biological activities. However, the molecular mechanism behind this ability of CGA remains unelucidated. Consequently, we investigated the effect of CGA on hepatic lipid accumulation and elucidated its underlying mechanism. Our study used a high-fat diet (HFD)-induced mouse nonalcoholic fatty liver disease (NAFLD) model in mice to investigate the impact of CGA on hepatic lipid accumulation. The results revealed that the oral administration of CGA can ameliorate HFD-induced hepatic lipid deposition, reduce the NAFLD activity score (NAS), enhance liver autophagy, mitigate liver cell structural damage, and inhibit the MAPK/ERK signaling pathway. Meanwhile, CGA treatment increased the LC3B:LC3B ratio and decreased P62 expression. Cell experiments demonstrated that autophagy contributes to the ability of CGA to alleviate lipid deposition. Further analysis revealed that CGA specifically binds to ALKBH5 and inhibits its m6A methylase activity. The inhibition of ALKBH5 activity significantly reduces AXL mRNA stability in liver cells. The AXL downregulation resulted in suppressing ERK signaling pathway activation. Overall, this study demonstrates that CGA can alleviate hepatic steatosis by regulating autophagy through the inhibition of ALKBH5 activity inhibition.
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Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ácido Clorogénico/metabolismo , Hígado/metabolismo , Autofagia , Lípidos/farmacología , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Eimeria intestinalis is the most pathogenic species of rabbit coccidiosis, causing weight loss, diarrhea, and even acute death. The currently used anticoccidial drugs against E. intestinalis in rabbits are associated with drug resistance and residues. Immunological control might be a potential alternative. We cloned and expressed the E. intestinalis recombinant EF1α and EFG (rEi-EF1α and rEi-EFG, respectively). Rabbits were immunized subcutaneously every 14 days with 100 µg of rEi-EF1α and rEi-EFG and followed by 5 × 104 E. intestinalis sporulated oocysts orally challenge. Serum samples were collected every 7 days to measure the levels of specific antibodies and cytokines. On post-challenge day 14, rabbits were sacrificed and the anticoccidial index was evaluated. The rabbits of PBS challenged groups exhibited anorexia, diarrhea, marked intestinal wall thickening, and white nodules that formed patches, while rabbits from the rEi-EF1α or rEi-EFG challenged group exhibited milder symptoms. The rEi-EF1α group showed a 75.18% oocyst reduction and 89.01%wt gain; the rEi-EFG group had a 60.58% oocyst reduction and 56.04%wt gain. After vaccination, specific IgG levels increased and stayed high (P < 0.05). The IL-4 and IL-2 levels of rEi-EF1α immunized groups showed a significant increase after immunization (P < 0.05). Both rEi-EF1α and rEi-EFG could induce humoral and cellular immune responses. In contrast, rabbits immunized with rEi-EF1α were better protected from challenge by E. intestinalis than rEi-EFG.
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Coccidiosis , Eimeria , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Animales , Conejos , Coccidiosis/prevención & control , Inmunización , Vacunación , Diarrea , Oocistos , Pollos , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Eimeria intestinalis infects rabbits, causing severe intestinal coccidiosis. Prolonged anticoccidial drug use might lead to coccidia resistance and drug residues in food. Thus, vaccines are required to control rabbit coccidiosis. In this study, recombinant E. intestinalis 14-3-3 and GRA10 proteins (rEi-14-3-3 and rEi-GRA10) were obtained via prokaryotic expression and used as recombinant subunit vaccines. Fifty 30-day-old rabbits were randomly grouped as follows: PBS-uninfected group, PBS-infected group, Trx-His-S control group, and rEi-14-3-3 and rEi-GRA10 immunized groups. The rabbits were subcutaneously immunized twice at 2-week intervals, challenged with 7 × 104 sporulated oocysts, and sacrificed 14 days later. The protective effects were assessed via clinical signs, relative weight gain, oocyst reduction, mean intestinal lesion score, ACI (anticoccidial index), cytokine, and specific antibody levels in sera. The rEi-14-3-3 and rEi-GRA10 groups had higher relative weight gain rates of 81.94% and 73.61% (p < 0.05), and higher oocyst reduction rates of 86.13% and 84.87% (p < 0.05), respectively. The two immunized groups had fewer intestinal lesions (p < 0.05) and higher IgG levels (p < 0.05). Higher levels of IL-2, IL-4, and IFN-γ cytokines in the rEi-14-3-3 group (p < 0.05) and a higher level of IFN-γ in the rEi-GRA10 group (p < 0.05) were observed. The ACI values of the rEi-14-3-3 and rEi-GRA10 groups were 168.24 and 159.91, with good and moderate protective effects, respectively. Both rEi-14-3-3 and rEi-GRA10 induced humoral immunity in the rabbits. In addition, rEi-14-3-3 induced Th1- and Th2-type immune responses. Both recombinant proteins were protective against E. intestinalis infection in rabbits, with rEi-14-3-3 showing a better protective effect.
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Coccidiosis , Eimeria , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Animales , Conejos , Proteínas 14-3-3 , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Citocinas , Oocistos , Vacunas Sintéticas , Aumento de Peso , Pollos , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Objective: The purpose of this study was to obtain the stress-strain of the cervical spine structure during the simulated manipulation of the oblique pulling manipulation and the cervical rotation-traction manipulation in order to compare the mechanical mechanism of the two manipulations. Methods: A motion capture system was used to record the key kinematic parameters of operating the two manipulations. At the same time, a three-dimensional finite element model of the C0-T1 full healthy cervical spine was established, and the key kinematic parameters were loaded onto the finite element model in steps to analyze and simulate the detailed process of the operation of the two manipulations. Results: A detailed finite element model of the whole cervical spine including spinal nerve roots was established, and the validity of this 3D finite element model was verified. During the stepwise simulation of the two cervical spine rotation manipulations to the right, the disc (including the annulus fibrosus and nucleus pulposus) and facet joints stresses and displacements were greater in the oblique pulling manipulation group than in the cervical rotation-traction manipulation group, while the spinal cord and nerve root stresses were greater in the cervical rotation-traction manipulation group than in the oblique pulling manipulation group. The spinal cord and nerve root stresses in the cervical rotation-traction manipulation group were mainly concentrated in the C4/5 and C5/6 segments. Conclusion: The oblique pulling manipulation may be more appropriate for the treatment of cervical spondylotic radiculopathy, while cervical rotation-traction manipulation is more appropriate for the treatment of cervical spondylosis of cervical type. Clinicians should select cervical rotation manipulations for different types of cervical spondylosis according to the patient's symptoms and needs.
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Eimeria intestinalis is one of the most pathogenic rabbit coccidia species causing severe intestinal damage and increased risk of secondary infection from opportunistic pathogens, which results in huge economic losses to the rabbit industry. Anticoccidial drugs are currently the main method to control coccidiosis; however, increasing resistance and drug residues have fueled research on anticoccidial vaccines. Apical membrane antigen 1 (AMA1) and immune mapped protein 1 (IMP1), as surface proteins, are associated with host invasion and might have the potential as candidate vaccine antigens. In the present study, recombinant IMP1 (rEiIMP1) and AMA1 (rEiAMA1) from E. intestinalis were expressed using Escherichia coli BL21. The immunoreactivity and immunoprotective effects of rEiIMP1 and rEiAMA1 were then analyzed. Fifty rabbits were grouped randomly (n = 10 per group): The unimmunized-unchallenged control group (sterilized phosphate-buffered saline (PBS)), the unimmunized-challenged control group (sterilized PBS), the vector protein-challenged control group (100 µg of pET-32a vector protein per rabbit), the rEiIMP1 immunized group (100 µg of rEiIMP1 per rabbit), and the rEiAMA1 immunized group (100 µg of rEiAMA1 per rabbit). After two immunizations, the rabbits were challenged with homologous oocysts (except for the unimmunized-unchallenged group). Serum specific antibody levels were assessed weekly throughout the experimental period; and the levels of different cytokines in the serum before the challenge were detected. The clinical symptoms, oocysts output, weight gain, feed conversion ratio (FCR), and lesion scores were recorded after experimental infection, and the anticoccidial indexes (ACIs) were calculated. The results showed that both rEiIMP1 and rEiAMA1 had good immunoreactivity. Rabbits immunized with rEiIMP1 and rEiAMA1 displayed 66.74 % and 63.14 % oocyst reduction, respective land 81.79 % and 78.87 % body weight gain, respectively. The rEiIMP1 and rEiAMA1 groups had lower FCRs (3.77:1 and 4.06:1, respectively) and lesion scores (P = 0.00). The rEiIMP1 and rEiAMA1 showed moderate effects, with an ACI of 152.09 and 147.17, respectively. Immunization induced high levels of anti-rEiIMP1 and -rEiAMA1 antibodies. Rabbits immunized with rEiIMP1 and rEiAMA1 displayed significantly increased interleukin (IL)- 2 (P = 0.00), interferon gamma (IFN)-â¯Î³ (P = 0.00), and IL-â¯4 (P = 0.00) levels. Therefore, this study provided potential candidate vaccine antigens for E. intestinalis.
Asunto(s)
Coccidiosis , Eimeria , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Conejos , Animales , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Inmunización/veterinaria , Vacunación/veterinaria , Proteínas Recombinantes , Aumento de Peso , Interferón gamma , Pollos , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Catalytic ozone (O3 ) decomposition at high relative humidity (RH) remains a great challenge due to the catalysts poison and deactivation under high humidity. Here, we firstly elaborate the role of water activation and the corresponding mechanism of the promoted O3 decomposition over the three-dimensional monolithic molybdenum oxide/graphdiyne (MoO3 /GDY) catalyst. The O3 decomposition over MoO3 /GDY reaches up to 100 % under high humid condition (75 % RH) at room temperature, which is 4.0 times as high as that of dry conditions, significantly surpasses other carbon-based MoO3 materials(≤7.1 %). The sp-hybridized carbon in GDY donates electrons to MoO3 along the C-O-Mo bond, facilitating water activation to form hydroxyl species. As a result, hydroxyl species dissociated from water act as new active sites, promoting the adsorption of O3 and the generation of new intermediate species (hydroxyl â OH and superoxo â O2 - ), which significantly lowers the energy barriers of O3 decomposition (0.57â eV lower than dry conditions).