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BACKGROUND: The consistency of pancreatic apparent diffusion coefficient (ADC) values and intravoxel incoherent motion (IVIM) parameter values across different magnetic resonance imaging (MRI) devices significantly impacts the patient's diagnosis and treatment. AIM: To explore consistency in image quality, ADC values, and IVIM parameter values among different MRI devices in pancreatic examinations. METHODS: This retrospective study was approved by the local ethics committee, and informed consent was obtained from all participants. In total, 22 healthy volunteers (10 males and 12 females) aged 24-61 years (mean, 28.9 ± 2.3 years) underwent pancreatic diffusion-weighted imaging using 3.0T MRI equipment from three vendors. Two independent observers subjectively scored image quality and measured the pancreas's overall ADC values and signal-to-noise ratios (SNRs). Subsequently, regions of interest (ROIs) were delineated for the IVIM parameters (true diffusion coefficient, pseudo-diffusion coefficient, and perfusion fraction) using post-processing software. These ROIs were on the head, body, and tail of the pancrease. The subjective image ratings were assessed using the kappa consistency test. Intraclass correlation coefficients (ICCs) and mixed linear models were used to evaluate each device's quantitative parameter values. Finally, a pairwise analysis of IVIM parameter values across each device was performed using Bland-Altman plots. RESULTS: The Kappa value for the subjective ratings of the different observers was 0.776 (P < 0.05). The ICC values for inter-observer and intra-observer agreements for the quantitative parameters were 0.803 [95% confidence interval (CI): 0.684-0.880] and 0.883 (95%CI: 0.760-0.945), respectively (P < 0.05). The ICCs for the SNR between different devices was comparable (P > 0.05), and the ICCs for the ADC values from different devices were 0.870, 0.707, and 0.808, respectively (P < 0.05). Notably, only a few statistically significant inter-device agreements were observed for different IVIM parameters, and among those, the ICC values were generally low. The mixed linear model results indicated differences (P < 0.05) in the f-value for the pancreas head, D-value for the pancreas body, and D-value for the pancreas tail obtained using different MRI machines. The Bland-Altman plots showed significant variability at some data points. CONCLUSION: ADC values are consistent among different devices, but the IVIM parameters' repeatability is moderate. Therefore, the variability in the IVIM parameter values may be associated with using different MRI machines. Thus, caution should be exercised when using IVIM parameter values to assess the pancreas.
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Acute appendicitis is a common surgical emergency. It is commonly caused by obstruction of the appendiceal lumen due to fecaliths, tumors, or lymphoid hyperplasia. For over a century, appendectomy has been the primary treatment for acute appendicitis. Abraham Groves performed the first open appendectomy in 1883. In 1983, Kurt Semm completed the first laparoscopic appendectomy, heralding a new era in appendectomy. However, appendectomy is associated with certain complications and a rate of negative appendectomies. Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson's disease, but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer, gallstones, and cardiovascular disease. With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic te-chnology, Liu proposed the endoscopic retrograde appendicitis therapy. It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis. Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis. This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.
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Apendicectomía , Apendicitis , Humanos , Apendicitis/cirugía , Apendicectomía/efectos adversos , Apendicectomía/métodos , Apendicectomía/historia , Resultado del Tratamiento , Apéndice/cirugía , Apéndice/patología , Apéndice/diagnóstico por imagen , Colonoscopios , Enfermedad Aguda , Diseño de EquipoRESUMEN
We investigate interfacial instability in a lifting Hele-Shaw cell by experiments and theory. We characterize the unexplored transition from stable to unstable patterns under a wide range of controlling parameters. Surprisingly, we find that the perturbation growth rate-based criterion for the onset of instability from linear stability theory is too strict by over 3 orders of magnitude. To reconcile this striking discrepancy, we propose a new criterion based on perturbation amplitude, which is in excellent agreement with the experimental results. We further show that the fingering pattern evolves to produce a hierarchical fluid structure and derive a theoretical equation to predict the fingering evolution.
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In Singapore, an ageing population with increasing chronic disease burden and complex social circumstances have strained the healthcare system. For the health system to run more efficiently, patients should be appropriately sited according to their medical needs. In Singapore, community hospitals serve as an intermediate inpatient facility managing patients with sub-acute and rehabilitation care needs. Our policy brief uncovers the gaps in transforming community hospital care models and offers actionable steps to unlock the community hospital chokepoints in Singapore's health system. The future community hospitals can accommodate higher acuity but medically stable patients, while patients who do not require inpatient rehabilitation care can be appropriately sited to community partners, if policy, resourcing and technology factors are addressed. An evidence-based, stepwise approach involving all stakeholders will be required to pilot and evaluate new models before large-scale change.
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Background: The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy (LLLS). The purpose of this study was to assess the effects of indocyanine green (ICG) fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients. The optimal dose and injection time of ICG were also investigated. Methods: This is a retrospective cohort study. From October 2016 to December 2022, the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed. According to whether ICG fluorescence cholangiography was used, they were divided into a non-ICG group (n=46) and an ICG group (n=57). Biliary complications were observed and the optimal dose and injection time of ICG were explored. Results: Three donors in the non-ICG group suffered from bile leakage. Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group. Two recipients had bile leakage, and the other two had biliary stenosis. There was no biliary complications both in donors and recipients in the ICG group. The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection, significantly weaker than that at 0.05 mg/kg 30 minutes (200.3±17.6, P=0.001) and 90 minutes after injection (140.2±15.4, P=0.001). The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg, both measured 90 minutes after injection (0.098±0.032 vs. 0.078±0.022, P=0.021). Conclusions: ICG fluorescence cholangiography is safe and feasible in LLLS. It reduces biliary complications in both donors and recipients. The optimal ICG dose was 0.004 mg/kg, and 90 minutes after injection was the best observation time. ICG fluorescence cholangiography is recommended for routine use in LLLS.
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OBJECTIVE: To investigate the effects of selinexor, a inhibitor of nuclear export protein 1 (XPO1) on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia (AML). METHODS: MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points. The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry. RESULTS: Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner (r 24 h=0.7592, r 48 h=0.9456, and r 72 h=0.9425). Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner (r =0.9057 in 2.5 µmol/L group, r =0.9897 in 5 µmol/L group and r =0.9994 in 10 µmol/L group). Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner (r =0.9732), and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration. The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor. With the increase of drug concentration, the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased. CONCLUSION: Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation, inducing apoptosis and blocking cell cycle.
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Apoptosis , Proliferación Celular , Hidrazinas , Leucemia Mieloide Aguda , Triazoles , Hidrazinas/farmacología , Triazoles/farmacología , Apoptosis/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Leucemia Mieloide Aguda/tratamiento farmacológico , Línea Celular Tumoral , Ciclo Celular/efectos de los fármacos , Proteína Exportina 1 , CarioferinasRESUMEN
BACKGROUND: Epicoccum sorghinum is a pathogenic fungus that causes leaf spot in a wide range of plants, including maize, and synthesizes the mycotoxin tenuazonic acid (TEA), which is carcinogenic. Despite the relevant economic and yield losses caused by E. sorghinum worldwide, methods for the control of this pathogen are lacking. RESULTS: In this work, the efficacy of Bacillus-produced dipicolinic acid (DPA) for control of E. sorghinum was evaluated using in vitro and in vivo assays, and compared with the efficacy of three commercial fungicides, including carbendazim, prochloraz, and thiram. DPA inhibited E. sorghinum mycelial growth, and conidia germination, and produced important alterations in E. sorghinum hyphae. Interestingly, 10 mM DPA reduced TEA biosynthesis by 86.6%. Although DPA rapidly degraded on maize leaves, 10 mM DPA showed higher preventive (67.4% lesion length inhibition) and inhibitory (89.5% lesion length inhibition) efficacies for the control of E. sorghinum on maize leaves compared to the commercial fungicides. CONCLUSIONS: Collectively, this study presents the first method for the control of E. sorghinum on maize and demonstrates that DPA application is a suitable approach to inhibit E. sorghinum symptoms in plants and TEA biosynthesis. © 2024 Society of Chemical Industry.
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OBJECTIVES: Clarifying the uncertain causal relationship between periodontitis and infective endocarditis using Mendelian randomization analysis, given their historically perceived association and clinical significance. METHODS: Genetic variation data for acute periodontitis, chronic periodontitis, aggressive periodontitis, and infective endocarditis were obtained from published GWAS in individuals of European ancestry. Instrumental variables significantly associated with periodontitis were selected and univariable Mendelian randomization was conducted to infer the causal association between periodontitis and infective endocarditis. Multivariable Mendelian randomization was also performed to adjust for potential confounders including smoking, drinking, diabetes, and education. RESULTS: Our analysis found no evidence of a causal association between periodontitis and infective endocarditis, with odds ratios (ORs) of 0.992 (95% CI: 0.879-1.120), 0.947 (95% CI: 0.738-1.214), and 1.056 (95% CI: 0.916-1.217) for acute periodontitis, chronic periodontitis, aggressive periodontitis, respectively. The robustness of our findings was confirmed by heterogeneity tests, pleiotropy tests, leave-one-out analyses, and MR-PRESSO. In the multivariable MR analysis, adjusting for smoking, drinking, diabetes, and education, the overall patterns between genetic liability to periodontitis and infective endocarditis remained consistent (all P > .05). CONCLUSION: Our findings indicate that there is no genetic causal association between periodontitis and infective endocarditis.
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BACKGROUND: The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. METHODS: We included stage II-IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan-Meier's analysis was performed to calculate survival rates. RESULTS: A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3-4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. CONCLUSIONS: Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.
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Quimioradioterapia , Ciclobutanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Compuestos Organoplatinos , Radioterapia de Intensidad Modulada , Humanos , Masculino , Anciano , Femenino , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/mortalidad , Ciclobutanos/uso terapéutico , Ciclobutanos/administración & dosificación , Ciclobutanos/efectos adversos , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/tratamiento farmacológico , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Estimación de Kaplan-MeierRESUMEN
OBJECTIVE: To investigate the impact of response to induction chemotherapy (IC) on survival outcomes in patients with locally advanced nasopharyngeal carcinoma (LANPC) and evaluate the efficacy of adding nimotuzumab to concurrent chemoradiotherapy (CCRT) based on different responses to IC. METHODS: We retrospectively included patients with stage III-IVA NPC who underwent IC with and without nimotuzumab during CCRT. Statistical analysis included the chi-square test, propensity score matching, Kaplan-Meier survival analysis, and Cox proportional hazards model. RESULTS: Among 383 identified patients, 216 (56.4%) received nimotuzumab during CCRT, while 167 (43.6%) did not. Following IC, 269 (70.2%) patients showed a complete response (CR) or partial response (PR), and 114 (29.8%) had stable disease (SD) or progressive disease (PD). The response to IC independently influenced disease-free survival (DFS) and overall survival (OS). Patients achieving CR/PR demonstrated significantly higher 3-year DFS (80.3% vs. 70.6%, P = 0.031) and OS (90.9% vs. 83.2%, P = 0.038) than those with SD/PD. The addition of nimotuzumab during CCRT significantly improved DFS (P = 0.006) and OS (P = 0.037) for CR/PR patients but not for those with SD/PD. CONCLUSIONS: This study emphasizes the importance of IC response in LANPC and highlights the potential benefits of nimotuzumab during CCRT for improving survival outcomes in CR/PR patients. Tailored treatment approaches for SD/PD patients warrant further investigation.
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Anticuerpos Monoclonales Humanizados , Quimioradioterapia , Quimioterapia de Inducción , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Quimioradioterapia/métodos , Quimioterapia de Inducción/métodos , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Adulto , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento , Estimación de Kaplan-Meier , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Adulto JovenRESUMEN
Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5's tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA's regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.
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Neoplasias de la Boca , ARN Circular , Nexinas de Clasificación , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Ratones , Ratones Desnudos , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Femenino , Proteína ADAM10/metabolismo , Proteína ADAM10/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismoRESUMEN
Herein, a practical three-component [2 + 1 + 3] cyclization of various cyclic ketones with α,ß-unsaturated aldehydes/ketones and ammonium iodide (NH4I) to access highly functional fused pyridines has been developed. The features of this transformation include mild reaction conditions, readily available starting materials, and excellent chemoselectivity. This protocol is compatible with various functional groups, and the preliminary studies on the mechanism of the reaction are also provided.
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Photo-assisted Zn-air batteries can accelerate the kinetics of oxygen reduction and oxygen evolution reactions (ORR/OER); however, challenges such as rapid charge carrier recombination and continuous electrolyte evaporation remain. Herein, for the first time, piezoelectric catalysis is introduced in a photo-assisted Zn-air battery to improve carrier separation capability and accelerate the ORR/OER kinetics of the photoelectric cathode. The designed microhelical catalyst exploits simple harmonic vibrations to regenerate the built-in electric field continuously. Specifically, in the presence of the low-frequency kinetic energy that occurs during water flow, the piezoelectric-photocoupling catalyst of poly(vinylidene fluoride-co-trifluoroethylene)@ferric oxide(Fe@P(V-T)) is periodically deformed, generating a constant reconfiguration of the built-in electric field that separates photogenerated electrons and holes continuously. Further, on exposure to microvibrations, the gap between the charge and discharge potentials of the Fe@P(V-T)-based photo-assisted Zn-air battery is reduced by 1.7 times compared to that without piezoelectric assistance, indicating that piezoelectric catalysis is highly effective for enhancing photocatalytic efficiency. This study provides a thorough understanding of coupling piezoelectric polarization and photo-assisted strategy in the field of energy storage and opens a fresh perspective for the investigation of multi-field coupling-assisted Zn-air batteries.
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Chemically self-recharging zinc ion batteries (ZIBs), which are capable of auto-recharging in ambient air, are promising in self-powered battery systems. Nevertheless, the exclusive reliance on chemical energy from oxygen for ZIBs charging often would bring some obstacles in charging efficiency. Herein, we develop photo-assisted chemically self-recharging aqueous ZIBs with a heterojunction of MoS2/SnO2 cathode, which are favorable to enhancing both the charging and discharging efficiency as well as the chemical self-charging capabilities under illumination. The photo-assisted process promotes the electron transfer from MoS2/SnO2 to oxygen, accelerating the occurrence of the oxidation reaction during chemical self-charging. Furthermore, the electrons within the MoS2/SnO2 cathode exhibit a low transfer impedance under illumination, which is beneficial to reducing the migration barrier of Zn2+ within the cathode and thereby facilitating the uniform inserting of Zn2+ into MoS2/SnO2 cathode during discharging. This photo-assisted chemical self-recharging mechanism enables ZIBs to attain a maximum self-charging potential of 0.95 V within 3 hours, a considerable self-charging capacity of 202.5 mAh g-1 and excellent cycling performance in a self-charging mode. This work not only provides a route for optimizing chemical self-charging energy storage, but also broadens the potential application of aqueous ZIBs.
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Thyroid hormone replacement therapy in NPC.
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The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27-1.60, P < 0.0001). The likelihood of IFG rose steadily as the TyG index quartiles (from Q1 to Q4) increased, with Q4 demonstrating a 62% elevated risk compared to Q1 (adjusted HR = 1.62, 95% CI 1.37-1.90). Additionally, we found the association between TyG index and risk of IFG was a linear. Sensitivity and subgroup analyses confirmed the stability of the results. Our study observed a linear association between the TyG index and the development of IFG in elderly Chinese individuals. Recognizing this association can help clinicians identify high-risk individuals and implement targeted interventions to reduce their risk of progressing to diabetes.
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Glucemia , Ayuno , Triglicéridos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/análisis , China/epidemiología , Pueblos del Este de Asia , Ayuno/sangre , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/epidemiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.
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Ferroptosis , Macrófagos , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2 , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Transducción de Señal , Bazo , Animales , Humanos , Masculino , Ratones , Ferroptosis/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Peroxidación de Lípido/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/genética , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/citología , Bazo/metabolismoRESUMEN
Over 10,000 metric-ton broiler livers are produced annually in Taiwan. Concerning unpleasant odor and healthy issue, broiler livers are not attractive to consumers. Although the patented chicken-liver hydrolysates (CLHs) through pepsin digestion possess several biofunctionalities, there is no study on hepatoprotection of CLH-based formula capsule (GBHP01) against binge drinking (Whiskey, 50% Alc./Vol.). GBHP01 led to an accelerated blood-alcohol clearance in rats, as evidenced by lowering blood-alcohol increment within 0 to 4 h, increasing blood-alcohol decrement within 4 to 8 h, and smaller blood alcohol concentration areas under the curve (BAC AUC) in the 8-h period (p < 0.05). The ameliorative effects of GBHP01 against binge drinking in rats over 6 wk were attributed to accelerated alcohol metabolism by further increasing alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities while downregulating cytochrome P450 2E1 (CYP2E1) protein expression, elevating antioxidant capacity, decreasing zonula occludens-1 (ZO-1) protein decrement and serum endotoxin, and reducing inflammation related protein levels, that is, toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK), and proinflammatory cytokines. The development of CLH supplements could not only enhance the added value of broiler livers through nutraceutical development but also offer a strategy to maximize the utilization of poultry processing residues, as shown in this study.
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Consumo Excesivo de Bebidas Alcohólicas , Pollos , Hígado , Animales , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Hidrolisados de Proteína/química , Hidrolisados de Proteína/administración & dosificaciónRESUMEN
Using a comprehensive molecular epidemiological approach, we characterized the transmission dynamics of HIV-1 among the MSM population in Tianjin, China. Our findings revealed that 38.56% (386/1001) of individuals clustered across 109 molecular transmission clusters (TCs), with MSM aged 50 and below being the group most commonly transmitting HIV-1. Among the identified TCs, CRF01_AE predominated, followed by CRF07_BC. Notably, CRF07_BC demonstrated a higher propensity for forming large clusters compared to CRF01_AE. Birth-death skyline analyses of the two largest clusters indicated that the HIV/AIDS transmission may be at a critical point, nearly all had Re approximately 1 by now. A retrospective analysis revealed that the rapid expansion of these large clusters was primarily driven by the introduction of viruses in 2021, highlighting the crucial importance of continuous molecular surveillance in identifying newly emerging high-risk transmission chains and adapting measures to address evolving epidemic dynamics. Furthermore, we detected the transmission of drug-resistant mutations (DRMs) within the TCs, particularly in the CRF07_BC clusters (K103N, Y181C, and K101E) and CRF01_AE clusters (P225H and K219R), emphasizing the importance of monitoring to support the continued efficacy of first-line therapies and pre-exposure prophylaxis (PrEP). Recombination analyses indicated that complex recombinant patterns, associated with increased amino acid variability, could confer adaptive traits to the viruses, potentially providing a competitive advantage in certain host populations or regions. Our study highlights the potential of integrating molecular epidemiological and phylodynamic approaches to inform targeted interventions.