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Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens. Although a number of chemokines were able to amplify specific CD8 + T-cell or humoral response alone or simultaneously. CCL11 was identified as the most potent chemokine in improving immunogenicity, promoting specific CD8 + T-cell stemness and generating tumor rejection. Fusing CCL11 with E6/E7 antigen as a therapeutic DNA vaccine significantly improved treatment effectiveness and caused eradication of established large tumors in 92% tumor-bearing mice (n = 25). Fusion antigens with CCL11 expanded the TCR diversity of specific T cells and induced the infiltration of activated specific T cells, neutrophils, macrophages and dendritic cells (DCs) into the tumor, which created a comprehensive immune microenvironment lethal to tumor. Combination of the DNA vaccine with anti-CTLA4 treatment further enhanced the therapeutic effect. In addition, CCL11 could also be used for mRNA vaccine design. To summarize, CCL11 might be a potent T cell enhancer against cancer.
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Vacunas contra el Cáncer , Neoplasias , Proteínas Oncogénicas Virales , Vacunas contra Papillomavirus , Vacunas de ADN , Animales , Ratones , Vacunación Basada en Ácidos Nucleicos , Vacunas de ADN/genética , Vacunas contra Papillomavirus/genética , Neoplasias/genética , Neoplasias/terapia , Linfocitos T CD8-positivos , Proteínas E7 de Papillomavirus/genética , Proteínas Oncogénicas Virales/genética , Ratones Endogámicos C57BL , Microambiente TumoralRESUMEN
Sonodynamic antimicrobial chemotherapy (SACT), as a novel anti-infective program, has received tremendous attention due to its good tissue penetration depth and low invasion. Ultrasound (US) frequency was one of the important parameters for SACT. To investigate the influence of different US frequencies on sonodynamic antimicrobial activity of ciprofloxacin-capped gold nanoparticles (CIP:GNPs). C. albicans and E. coli were chosen as the action objects. The bacterial survival rate was used in the assessment index and measured by plate colony-counting methods. The reactive oxygen species (ROS) produced under US irradiation were detected by ROS fluorescence probe and used to analyze the sonodynamic antibacterial mechanism of CIP:GNPs following different US frequencies. High-frequency US combined with CIP:GNPs had a good synergistic antimicrobial impact on C. albicans, while medium-frequency US showed a strong effect on E. coli. Moreover, the mechanism research experiment proved that intracellular ROS levels were closely related to changes in US frequency, and significantly affected the synergistic activity of CIP:GNPs. The injury of E. coli appearance showed more sensitivity to the change of US frequency than that of C. albicans, but its action laws were relatively complicated and needed to be further studied.
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A single-photon lidar based on multi-repetition-rate pulse train correlation and accumulation is proposed, and a ranging experiment is conducted on a 32â m target. By accumulating the correlation ranging results of pulse trains with internal spacings of 80, 100, and 125â ns, the signal-to-noise ratio of the cross correlation function is improved by about three-fold, which enables our method to improve the ranging precisions by more than 20% compared with the single repetition-rate method, and the shorter the acquisition time, the more obvious the advantage will be. Experimental results show that at an acquisition time of 0.01â s, our method can still achieve a ranging precision of 2.59â cm, while the single repetition-rate method can no longer obtain effective ranging results at this time. This method will be of great significance for realizing high-speed, large-scale unambiguous single-photon lidar ranging.
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BACKGROUND: Few studies have examined long-term outcomes following oral immunotherapy (OIT); none have examined long-term risks and benefits associated with distinct clinical outcomes (desensitization, remission). METHODS: Participants completing the probiotic and peanut oral immunotherapy (PPOIT) -003 randomized trial were enrolled in a follow-on study, PPOIT-003LT. Peanut ingestion, reactions, and health-related quality of life (HRQOL) were monitored prospectively. Outcomes at 1-year and 2-years post-treatment were examined by treatment group and by post-OIT clinical outcome (remission, desensitization without remission [DWR], allergic). RESULTS: 86% (151/176) of eligible children enrolled. Post-treatment peanut ingestion at 2-years post-treatment were similar for PPOIT (86.7%) and OIT (78.7%) groups, both higher than placebo (10.3%). Reactions reduced over time for all treatment and clinical outcome groups (PPOIT 31.7% to 23.3%, OIT 37.7% to 19.7%, placebo 13.8% to 6.9%; remission 27.5% to 15.9%; DWR 57.9% to 36.8%; allergic 11.6% to 7%). At 2-years post-treatment, similar proportions of remission and allergic participants reported reactions (RD 0.09 (95%CI -0.03, 0.20), p = .127), whereas more DWR participants reported reactions than remission (remission vs DWR: RD -0.21 (95%CI -0.39; -0.03), p = .02) and allergic (DWR vs allergic: RD 0.30 (95%CI 0.13, 0.47), p = .001) participants. At 2-years post-treatment, 0% remission versus 5.3% DWR versus 2.3% allergic participants reported adrenaline injector usage. Remission participants had significantly greater HRQOL improvement (adjusted for baseline) compared with both DWR (MD -0.54 (95%CI -0.99, -0.10), p = .017) and allergic (MD -0.82 (95%CI -1.25, -0.38), p < .001). CONCLUSION: By 2-years post-treatment, remission participants reported fewer reactions, less severe reactions and greater HRQOL improvement compared with DWR and allergic participants, indicating that remission is the patient-preferred treatment outcome over desensitization or remaining allergic.
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BACKGROUND: The predictive importance of IKZF1del in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has shown variability across different studies. Thus, the optimal treatment approach for children with IKZF1del BCP-ALL remains contentious, with the ongoing debate surrounding the use of IKZF1del-based high-risk stratification versus a minimal residual disease (MRD)-guided protocol. METHODS: IKZF1 status was reliably determined in 804 patients using multiplex ligation-dependent probe amplification (MLPA) data obtained from four hospitals in Fujian, a province of China. In the Chinese Children Leukemia Group (CCLG)-ALL 2008 cohort, IKZF1 status was included in the risk assignment, with all IKZF1del patients receiving a high-risk regimen. Conversely, in the Chinese Children's Cancer Group (CCCG)-ALL 2015 cohort, IKZF1del was not incorporated into the risk assignment, and patients were treated based on an MRD-guided risk stratification protocol. RESULTS: IKZF1del was found in 86 patients (86/804, 10.7%) overall and in 30 (30/46, 65.2%) BCR::ABL1-positive patients. Overall, IKZF1del was a poor prognostic predictor for patients, though the significance diminished upon age adjustment, white blood cell (WBC) count at diagnosis, treatment group, and MRD status. In the CCLG-ALL 2008 cohort, IKZF1del conferred a notably lower 5-year overall survival (OS) and event-free survival (EFS) and a significantly higher 5-year cumulative incidence of relapse (CIR) than IKZF1wt. In the CCLG-ALL 2015 cohort, IKZF1del conferred a lower 5-year OS and EFS and a higher 5-year CIR than IKZF1wt, but the differences were insignificant. The IKZF1del patients treated with higher intensity chemotherapy (CCLG-ALL 2008 high-risk regimen) had a markedly lower 5-year OS and EFS compared with those treated with the MRD-guided protocol (CCCG-ALL 2015 protocol). Furthermore, patients treated with the CCLG-ALL 2008 high-risk regimen experienced a higher frequency of serious adverse events (SAEs), especially infection-related SAEs, compared with those treated with the CCCG-ALL 2015 MRD-guided protocol. CONCLUSIONS: The prognostic effect of IKZF1del may vary in different protocols. Compared with higher intensity chemotherapy, the MRD-guided protocol may be a more effective approach to treating BCP-ALL with IKZF1del in children.
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Factor de Transcripción Ikaros , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Factor de Transcripción Ikaros/genética , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Femenino , Niño , Pronóstico , Preescolar , Neoplasia Residual/genética , Lactante , Adolescente , China/epidemiología , Eliminación de GenRESUMEN
BACKGROUND: Supraclavicular nodal (SCL) irradiation is commonly used for patients with high-risk breast cancer after breast surgery. The Radiation Therapy Oncology Group (RTOG) and European Society for Radiotherapy and Oncology (ESTRO) breast contouring atlases delineate the medial part of the SCL region, while excluding the posterolateral part. However, recent studies have found that a substantial proportion of SCL failures are located in the posterolateral SCL region, outside of the RTOG/ESTRO-defined SCL target volumes. Consequently, many radiation oncologists advocate for enlarging the SCL irradiation target volume to include both the medial and posterolateral SCL regions. Nevertheless, it remains uncertain whether adding the posterolateral SCL irradiation improves survival outcomes for high-risk breast cancer patients. METHODS: The SUCLANODE trial is an open-label, multicenter, randomized, phase 3 trial comparing the efficacy and adverse events of medial SCL irradiation (M-SCLI group) and medial plus posterolateral SCL irradiation (entire SCL irradiation, E-SCLI group) in high-risk breast cancer patients who underwent breast conserving-surgery or mastectomy. Patients with pathological N2-3b disease following initial surgery, or clinical stage III or pathological N1-3b if receiving neoadjuvant systemic therapy, are eligible and randomly assigned (1:1) to M-SCLI group and E-SCLI group. Stratification is by chemotherapy sequence (neoadjuvant vs. adjuvant), T stage (T3-4 vs. T1-2), N stage (N1-2 vs. N3), and ER status (positive vs. negative). Other radiation volumes are identical in the two arms, including breast/chest wall, undissected axillary lymph node, and internal mammary node. Advanced intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), or tomotherapy techniques are recommended. Both hypofractionated and conventional fractionation schedules are permitted. The primary end point is invasive disease-free survival, and secondary end points included overall survival, SCL recurrence, local-regional recurrence, distance recurrence, safety outcome, and patient-reported outcomes. The target sample size is 1650 participants. DISCUSSION: The results of the SUCLANODE trial will provide high-level evidence regarding whether adding posterolateral SCL irradiation to medial SCL target volume provides survival benefit in patients with high-risk breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05059379. Registered 28 September 2021, https://www. CLINICALTRIALS: gov/ct2/show/NCT05059379 .
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía , Adyuvantes Inmunológicos , Ganglios Linfáticos , Mama , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.
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Enfermedad de Alzheimer , Apoptosis , Barrera Hematorretinal , Ratones Transgénicos , Retina , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Apoptosis/efectos de los fármacos , Barrera Hematorretinal/efectos de los fármacos , Barrera Hematorretinal/metabolismo , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología , Ratones , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Ratones Endogámicos C57BL , Humanos , Péptidos beta-Amiloides/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Vía de Señalización Wnt/fisiología , MasculinoRESUMEN
BACKGROUND: The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. METHODS: This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups. RESULTS: There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae. CONCLUSIONS: These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory decline and cognitive impairment, which is related to hallmark protein aggregates, amyloid-ß (Ðß) plaques and neurofibrillary tangles; the latter are accumulated with hyperphosphorylated Tau protein. Immune cells play an important role in AD pathogenesis. Although the role of T cells in AD remains controversial, studies have shown that T cell deficiency is associated with increased AD pathology. In contrast, transplantation of T cells reduces AD pathology. T cells can help B cells generate anti-Ðß antibody to neutralize the toxin of Ðß and hyperphosphorylated Tau. T cells also activate macrophages to phagocytose misfolded proteins including Ðß and Tau. Recent data have also shown that AD animals have a damaged thymic microenvironment, especially thymic epithelial cells (TECs), resulting in decreased T cell numbers, which contribute to AD pathology. Therefore, regulation of T cell regeneration, for example by rejuvenating the thymic microenvironment, has the potential to be used in the treatment of AD.
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Enfermedad de Alzheimer , Humanos , Animales , Enfermedad de Alzheimer/etiología , Linfocitos T , Timo , Linfocitos B , Células EpitelialesRESUMEN
The IL-36 family, including IL-36α, IL-36ß, IL-36γ, and IL-36R antagonist, belong to the IL-1 superfamily. It was reported that IL-36 plays a role in immune diseases. However, it remains unclear how IL-36 regulates inflammation. To determine the role of IL-36/IL-36R signaling pathways, we established an acute hepatitis mouse model (C57BL/6) by i.v. injection of the plant lectin Con A. We found that the levels of IL-36 were increased in the liver after Con A injection. Our results demonstrated the infiltrated neutrophils, but not the hepatocytes, were the main source of IL-36 in the liver. Using the IL-36R-/- mouse model (H-2b), we surprisingly found that the absence of IL-36 signals led to aggravated liver injury, as evidenced by increased mortality, elevated serum alanine aminotransferase and aspartate aminotransferase levels, and severe liver pathological changes. Further investigations demonstrated that a lack of IL-36 signaling induced intrahepatic activation of CD4+ and CD8+ T lymphocytes and increased the production of inflammatory cytokines. In addition, IL-36R-/- mice had reduced T regulatory cell numbers and chemokines in the liver. Together, our results from the mouse model suggested a vital role of IL-36 in regulating T cell function and homeostasis during liver inflammation.
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Concanavalina A/efectos adversos , Hepatitis/etiología , Hepatitis/metabolismo , Interleucina-1/metabolismo , Receptores de Interleucina-1/metabolismo , Transducción de Señal , Animales , Biomarcadores , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Hepatitis/diagnóstico , Inmunofenotipificación , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Noqueados , Infiltración Neutrófila/genética , Infiltración Neutrófila/inmunología , Receptores de Interleucina-1/genética , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismoRESUMEN
The sluggish oxygen evolution reaction (OER) in overall electrocatalytic water splitting poses a significant challenge in hydrogen production. A series of transition metal phosphides are emerging as promising electrocatalysts, effectively modulating the charge distribution of surrounding atoms for OER. In this study, a highly efficient OER electrocatalyst (CoP-CNR-CNT) was successfully synthesized through the pyrolysis and phosphatization of a Co-doped In-based coordination polymer, specifically InOF-25. This process resulted in evenly dispersed CoP nanoparticles encapsulated in coordination polymer-derived carbon nanoribbons. The synthesized CoP-CNR-CNT demonstrated a competitive OER activity with a smaller overpotential (η10) of 295.7 mV at 10 mA cm-2 and a satisfactory long-term stability compared to the state-of-the-art RuO2 (η10 = 353.7 mV). The high OER activity and stability can be attributed to the high conductivity of the carbon network, the abundance of CoP particles, and the intricate nanostructure of nanoribbons/nanotubes. This work provides valuable insights into the rational design and facile preparation of efficient non-precious metal-based OER electrocatalysts from inorganic-organic coordination polymers, with potential applications in various energy conversion and storage systems.
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AIMS: To explore the application and long-term clinical effects of modified Yamane technique in intrascleral intraocular lens (IOL) fixation combined with or without iris reconstruction. SETTINGS AND DESIGN: The data of patients receiving IOL fixation with modified Yamane technique in an ophthalmology department between December 2021 and August 2023 were analyzed retrospectively. The longest follow-up duration was > 12 months. METHODS AND MATERIAL: The trailing haptic was fixed with the needle before the leading haptic. The silicone haptic stoppers were used to stabilize the IOL when iris reconstruction was combined. Preoperative and postoperative best-corrected visual acuity (BCVA), corneal endothelial cells (CECs), postoperative intraocular pressure (IOP), surgical indications and methods, and postoperative complications were recorded. Anterior segment optical coherence tomography (OCT) was used to evaluate IOL decentration and tilt. The paired sample t-test or Wilcoxon rank sum test were used to compare the results of the same index before and after the operation. RESULTS: Twelve patients (12 eyes) were included in this cohort. There were 1 case of IOL dislocation, eight cases of lens dislocation or subluxation, and three cases of aphakia. Traumatic lens dislocation was the main cause of aphakia. Primary lens extraction was performed in previous surgeries, and all three were combined with pars plana vitrectomy (PPV). Four of 12 patients underwent IOL fixation and iris reconstruction. The mean age of participants was 63 ± 10.61 years. The mean BCVA increased from 0.89 ± 0.72 logMAR to 0.39 ± 0.56 logMAR at the last visit (p < 0.05). The postoperative relative refractive error was - 0.13 ± 0.42 D (-0.60 D to + 0.57 D). The OCT showed that the IOLs were well centered, with a mean decentration of 0.20 ± 0.13 mm and a mean tilt of 2.31°±0.93°. Ten patients did not experience any complications. CONCLUSIONS: The modified Yamane technique in IOL fixation surgery, especially combined with iris reconstruction, reduces operation difficulty, increases operational stability and safety, and improves postoperative visual acuity without serious intra- or postoperative complications. The long-term improvement effect was remarkable.
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Iris , Implantación de Lentes Intraoculares , Lentes Intraoculares , Esclerótica , Agudeza Visual , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Implantación de Lentes Intraoculares/métodos , Iris/cirugía , Anciano , Agudeza Visual/fisiología , Esclerótica/cirugía , Procedimientos de Cirugía Plástica/métodos , Tomografía de Coherencia Óptica/métodos , Estudios de SeguimientoRESUMEN
Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3ß at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3ß pathway.
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Atrofia , Berberina , Encéfalo , Disfunción Cognitiva , Imagen por Resonancia Magnética , Sustancia Blanca , Animales , Berberina/farmacología , Berberina/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/diagnóstico por imagen , Atrofia/tratamiento farmacológico , Ratones , Masculino , Sustancia Blanca/efectos de los fármacos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Imagen de Difusión Tensora , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/metabolismoRESUMEN
As an efficient triazole fungicide, prothioconazole (PTC) is widely used for the prevention and control of plant fungal pathogens. It was reported that the residues of PTC and prothioconazole-desthio (PTC-d) have been detected in the environment and crops, and the effects of PTC-d may be higher than that of PTC. Currently, PTC and PTC-d have been proven to induce hepatic metabolic disorders. However, their toxic effects on cellular bile acid (BA) and glucolipid metabolism remain unknown. In this study, HepG2 cells were exposed to 1-500 µM of PTC or PTC-d. High concentrations of PTC and PTC-d were found to induce cytotoxicity; thus, subsequent experimental exposure was conducted at concentrations of 10-50 µM. The expression levels of CYP7A1 and TG synthesis-related genes and levels of TG and total BA were observed to increase in HepG2 cells. Molecular docking analysis revealed direct interactions between PTC or PTC-d and CYP7A1 protein. To further investigate the underlying mechanisms, PTC and PTC-d were treated to HepG2 cells in which CYP7A1 expression was knocked down using siCYP7A1. It was observed that PTC and PTC-d affected the BA metabolism process and regulated the glycolipid metabolism process by promoting the expression of CYP7A1. In summary, we comprehensively analyzed the effects and mechanisms of PTC and PTC-d on cellular metabolism in HepG2 cells, providing theoretical data for evaluating the safety and potential risks associated with these substances.
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Triazoles , Humanos , Regulación hacia Arriba , Células Hep G2 , Simulación del Acoplamiento Molecular , Triazoles/toxicidad , Triazoles/químicaRESUMEN
Based on the one strain many compounds strategy, a new brominated isocoumarin, 5-bromo-6,8-dihydroxy-3,7-dimethylisocoumarin (1), along with four new natural products, methyl 3-bromo-2,4-dihydroxy-6-methylbenzoate (2), methyl 2-bromo-4,6-dihydroxybenzoate (3), (E)-3-(3-bromo-4-hydroxyphenyl) acrylic acid (4) and 4-hydroxy-3-methyl-6-phenyl-2H-pyran-2-one (5), and four known compounds, methyl orsellinate (6), 4-hydroxy-3-methyl-6-(1-methyl-1-propenyl)-2H-pyran-2-one (7), pilobolusate (8) and cis-ferulic acid (9), were isolated from the ethyl acetate extract of the fungus Aspergillus sp. WXF1904 under the condition of adding bromine salt to the production medium. The structures of the new compounds were established by analysis of NMR and MS data. Compounds (1-9) were evaluated for inhibitory activity of acetylcholinesterase and pancreatic lipase, the new compound 1, known compounds 6 and 7 displayed weak inhibitory activity against acetylcholinesterase, compounds 2, 5, 7 and 8 showed weak inhibitory activity against pancreatic lipase.
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Acetilcolinesterasa , Isocumarinas , Aspergillus/química , Hongos , Isocumarinas/química , Lipasa , Estructura Molecular , Benzoatos/químicaRESUMEN
Lignin is a crucial substance in the formation of the secondary cell wall in plants. It is widely distributed in various plant tissues and plays a significant role in various biological processes. However, the number of copies, characteristics, and expression patterns of genes involved in lignin biosynthesis in maize are not fully understood. In this study, bioinformatic analysis and gene expression analysis were used to discover the lignin synthetic genes, and two representative maize inbred lines were used for stem strength phenotypic analysis and gene identification. Finally, 10 gene families harboring 117 related genes involved in the lignin synthesis pathway were retrieved in the maize genome. These genes have a high number of copies and are typically clustered on chromosomes. By examining the lignin content of stems and the expression patterns of stem-specific genes in two representative maize inbred lines, we identified three potential stem lodging resistance genes and their interactions with transcription factors. This study provides a foundation for further research on the regulation of lignin biosynthesis and maize lodging resistance genes.
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Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Lignina , Zea mays , Zea mays/genética , Zea mays/metabolismo , Lignina/biosíntesis , Lignina/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Genes de Plantas , Perfilación de la Expresión Génica/métodos , Pared Celular/metabolismo , Pared Celular/genética , Estudio de Asociación del Genoma Completo , FenotipoRESUMEN
Alpine meadows constitute one of the major ecosystems on the Qinghai-Tibetan Plateau, with livestock grazing exerting a considerable impact on their biodiversity. However, the degree to which plant diversity influences community stability under different grazing intensities remains unclear in this region. This study conducted controlled grazing experiments across four levels of grazing intensity (no-, low-, medium-, and high-grazing) based on herbage utilization rate to assess the influence of grazing intensities on plant community structure and diversity-stability relationships. We discovered that high-grazing reduced plant diversity and attenuated the temporal stability and resistance of above-ground biomass. No- and low-grazing could alleviate plant biomass loss, with community resistance being optimal under low-grazing. The direct effects of livestock grazing on temporal stability were found to be negligible. Plant characteristics and diversity accounted for a substantial proportion of livestock grazing effects on community resistance (R2 = 0.46), as revealed by piecewise structural equation model analysis. The presence of plant diversity enhances the resistance of alpine meadows against disturbance and accelerates the recovery after grazing. Our results suggest that low-grazing intensity may represent a judicious option for preserving species diversity and community stability on the Qinghai-Tibetan Plateau.
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Ecosistema , Ganado , Animales , Pradera , Biodiversidad , Biomasa , PlantasRESUMEN
Sonosensitizers play a crucial role in the efficacy of sonodynamic antitumor therapy (SDT) and sonodynamic antimicrobial chemotherapy (SACT), highlighting the necessity for the development of new compounds with good sonodynamic activity. In this study, three novel 3-substituted ciprofloxacin derivatives (CIPD1, CIPD2, and CIPD3) were designed and synthesized. Their sonodynamic activities were evaluated by assessing the damage to bovine serum albumin (BSA) and Escherichia coli (E. coli). Furthermore, the potential mechanism underlying their sonodynamic damage activities was investigated by detecting reactive oxygen species (ROS) under ultrasound irradiation (US). The results demonstrated that all three derivatives exhibited enhanced sonodynamic damage to BSA and E. coli under US, with CIPD1 and CIPD2 showing superior effectiveness compared to CIP. Both the concentrations of derivatives and the duration of ultrasound irradiation were found to significantly impact their sonodynamic effects. All three CIP derivates could be activated to produce ROS following ultrasound irradiation, primarily consisting of 1O2 and ·OH. The levels of ROS production were positively correlated with their sonodynamic activities, potentially explaining the mechanism underlying their sonodynamic damage activities.
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Ciprofloxacina , Escherichia coli , Especies Reactivas de Oxígeno , Albúmina Sérica Bovina , Ciprofloxacina/farmacología , Ciprofloxacina/química , Especies Reactivas de Oxígeno/metabolismo , Escherichia coli/efectos de los fármacos , Albúmina Sérica Bovina/química , Ondas Ultrasónicas , Animales , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis químicaRESUMEN
BACKGROUND: Optimizing biochar application is vital for enhancing crop production and ensuring sustainable agricultural production. A 3-year field experiment was established to explore the effects of varying the biochar application rate (BAR) on crop growth, quality, productivity and yields. BAR was set at 0, 10, 50 and 100 t ha-1 in 2018; 0, 10, 25, 50 and 100 t ha-1 in 2019; and 0, 10, 25 and 30 t ha-1 in 2020. Crop quality and growth status and production were evaluated using the dynamic technique for order preference by similarity to ideal solution with the entropy weighted method (DTOPSIS-EW), principal component analysis (PCA), membership function analysis (MFA), gray relation analysis (GRA) and the fuzzy Borda combination evaluation method. RESULTS: Low-dose BAR (≤ 25 t ha-1 for cotton; ≤ 50 t ha-1 for sugar beet) effectively increased biomass, plant height, leaf area index (LAI), water and fertility (N, P and K) productivities, and yield. Biochar application increased the salt absorption and sugar content in sugar beet, with the most notable increases being 116.45% and 20.35%, respectively. Conversely, BAR had no significant effect on cotton fiber quality. The GRA method was the most appropriate for assessing crop growth and quality. The most indicative parameters for reflecting cotton and sugarbeet growth and quality status were biomass and LAI. The 10 t ha-1 BAR consistently produced the highest scores and was the most economically viable option, as evaluated by DTOPSIS-EW. CONCLUSION: The optimal biochar application strategy for improving cotton and sugar beet cultivation in Xinjiang, China, is 10 t ha-1 biochar applied continuously. © 2024 Society of Chemical Industry.
Asunto(s)
Beta vulgaris , Carbón Orgánico , Producción de Cultivos , Fertilizantes , Gossypium , Beta vulgaris/química , Beta vulgaris/crecimiento & desarrollo , Carbón Orgánico/química , Gossypium/crecimiento & desarrollo , Gossypium/metabolismo , China , Producción de Cultivos/métodos , Fertilizantes/análisis , BiomasaRESUMEN
Researchers in this study assesses risk behaviors for sexually transmitted infections (STIs) among sexual minority women (SMW) in Beijing, China. A total of 1,631 SMW participated in the study. Compared with women who have sex with women exclusively, women who have sex with both women and men reported more sex partners, more likely sharing sex toys, experiencing STI infections. Digital-genital sex, using sex toys, G-spot stimulation is associated with STI symptoms. SMW in Beijing engaged in high-risk sexual behaviors that may cause substantial risk for STIs. SMW and healthcare providers should be informed and STI testing should be promoted among SMW.