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Due to its high efficiency, Fe(II)-based catalytic oxidation has been one of the most popular types of technology for treating growing organic pollutants. A lot of chemical Fe sludge along with various refractory pollutants was concomitantly produced, which may cause secondary environmental problems without proper disposal. We here innovatively proposed an effective method of achieving zero Fe sludge, reusing Fe resources (Fe recovery = 100%) and advancing organics removal (final TOC removal > 70%) simultaneously, based on the in situ formation of magnetic Ca-Fe layered double hydroxide (Fe3O4@CaFe-LDH) nano-material. Cations (Ca2+ and Fe3+) concentration (≥ 30 mmol/L) and their molar ratio (Ca:Fe ≥ 1.75) were crucial to the success of the method. Extrinsic nano Fe3O4 was designed to be involved in the Fe(II)-catalytic wastewater treatment process, and was modified by oxidation intermediates/products (especially those with COO- structure), which promoted the co-precipitation of Ca2+ (originated from Ca(OH)2 added after oxidation process) and by-produced Fe3+ cations on its surface to in situ generate core-shell Fe3O4@CaFe-LDH. The oxidation products were further removed during Fe3O4@CaFe-LDH material formation via intercalation and adsorption. This method was applicable to many kinds of organic wastewater, such as bisphenol A, methyl orange, humics, and biogas slurry. The prepared magnetic and hierarchical CaFe-LDH nanocomposite material showed comparable application performance to the recently reported CaFe-LDHs. This work provides a new strategy for efficiently enhancing the efficiency and economy of Fe(II)-catalyzed oxidative wastewater treatment by producing high value-added LDHs materials.
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Oxidación-Reducción , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Catálisis , Hierro/químicaRESUMEN
Objective: To examine the association of overweight/obesity and serum vitamin C (serum VC) with serum uric acid (SUA) and to assess causality using Mendelian randomization (MR). Methods: 4,772 participants from the National Health and Nutrition Examination Survey (NHANES), 2017-2018 were included in this study. Multivariate linear regression, variance inflation factor and quantile regression were used to analyze the relationships between overweight/obesity and serum VC and SUA levels. Secondly, Mendelian randomization (MR) was utilized to mitigate bias and prevent reverse causality in the observational study. Genetic variants associated with obesity (N = 13,848), vitamin C levels (N = 64,979) and serum uric acid levels (N = 343,836) were sourced from the most extensive genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighted (IVW). Results: Based on the observational study, BMI was positively associated with SUA (ß = 0.06, 95% CI: 0.05 to 0.07, p < 0.001) and serum VC was negatively associated with SUA (ß = -0.14, 95% CI: -0.23 to -0.04, p = 0.005). In individuals with overweight/obesity (BMI > =25), the negative effects of serum VC on SUA enhanced with increasing serum VC. High serum VC level (Q4 level, above 1.19 mg/dL) reduced SUA (ß = -0.30, 95% CI: -0.47 to -0.14, p < 0.001) in individuals with overweight/obesity compared to low serum VC level (Q1 level, below 0.54 mg/dL). IVW-MR analysis revealed a significant association between SUA levels and genetically elevated levels of VC (ß = -0.03, 95% CI: -0.06 to -0.00, p = 0.029) and obesity (ß = 0.06, 95% CI: 0.04 to 0.07, p < 0.001). Conclusion: Cross-sectional observational analysis revealed that BMI exhibited a positive correlation with SUA levels and that serum VC was negatively correlated with SUA levels; moreover, moderate serum VC can reduce SUA, especially in individuals with overweight/obesity. There was evidence indicating a causal effect of VC and obesity on SUA. It highlights the importance of VC in the management of SUA levels, particularly in overweight/obese individuals. The findings might be helpful for the management of high SUA levels.
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The long-term physiological consequences of respiratory viral infections, particularly in the aftermath of the COVID-19 pandemic-termed post-acute sequelae of SARS-CoV-2 (PASC)-are rapidly evolving into a major public health concern1-3. While the cellular and molecular aetiologies of these sequelae are poorly defined, increasing evidence implicates abnormal immune responses3-6 and/or impaired organ recovery7-9 after infection. However, the precise mechanisms that link these processes in the context of PASC remain unclear. Here, with insights from three cohorts of patients with respiratory PASC, we established a mouse model of post-viral lung disease and identified an aberrant immune-epithelial progenitor niche unique to fibroproliferation in respiratory PASC. Using spatial transcriptomics and imaging, we found a central role for lung-resident CD8+ T cell-macrophage interactions in impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia. Specifically, IFNγ and TNF derived from CD8+ T cells stimulated local macrophages to chronically release IL-1ß, resulting in the long-term maintenance of dysplastic epithelial progenitors and lung fibrosis. Notably, therapeutic neutralization of IFNγ + TNF or IL-1ß markedly improved alveolar regeneration and pulmonary function. In contrast to other approaches, which require early intervention10, we highlight therapeutic strategies to rescue fibrotic disease after the resolution of acute disease, addressing a current unmet need in the clinical management of PASC and post-viral disease.
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Autophagy is a cellular homeostatic mechanism characterized by cyclic degradation. It plays an essential role in maintaining cellular quality and survival by eliminating dysfunctional cellular components. This process is pivotal in various pathophysiological processes. Benign prostatic hyperplasia (BPH) is a common urological disorder in middle-aged and elderly men. It frequently presents as lower urinary tract symptoms due to an increase in epithelial and stromal cells surrounding the prostatic urethra. The precise pathogenesis of BPH is complex. In recent years, research on autophagy in BPH has gained significant momentum, with accumulating evidence indicating its crucial role in the onset and progression of the disease. This review aims to outline the various roles of autophagy in BPH and elucidate potential therapeutic strategies targeting autophagy for managing BPH.
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Autofagia , Hiperplasia Prostática , Hiperplasia Prostática/terapia , Humanos , Masculino , Autofagia/fisiologíaRESUMEN
The therapeutic efficacy of drugs is determined, to a certain extent, by the efficiency of drug delivery. The low efficiency of drug delivery systems (DDSs) is frequently associated with serious toxic side effects and can even prove fatal in certain cases. With the rapid development of technology, drug delivery has evolved from using traditional frameworks to using nano DDSs (NDDSs), endogenous biomaterials DDSs (EBDDSs), and living cell DDSs (LCDDSs). LCDDSs are receiving widespread attention from researchers at present owing to the unique advantages of living cells in targeted drug delivery, including their excellent biocompatibility properties, low immunogenicity, unique biological properties and functions, and role in the treatment of diseases. However, the theoretical basis and techniques involved in the application of LCDDSs have not been extensively summarized to date. Therefore, this review comprehensively summarizes the properties and applications of living cells, elaborates the various drug loading approaches and controlled drug release, and discusses the results of clinical trials. The review also discusses the current shortcomings and prospects for the future development of LCDDSs, which will serve as highly valuable insights for the development and clinical transformation of LCDDSs in the future.
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Sistemas de Liberación de Medicamentos , Humanos , Sistemas de Liberación de Medicamentos/métodos , Animales , Materiales Biocompatibles , Nanopartículas , Portadores de Fármacos/químicaRESUMEN
Background: Effective glycemic control is crucial for hospitalized patients, leading to benefits such as shorter hospital stays and reduced postoperative infection rates. While previous studies have emphasized the effectiveness of multidisciplinary collaborative stewardship for hospital-wide hyperglycemia management, patient perspectives and preferences have not been adequately considered. Objective: To identify factors influencing treatment preferences of Chinese hospitalized diabetes patients using discrete choice experiments (DCEs) and provide practical insights for the construction of a hospital-wide glycemic control programme. Methods: A face-to-face survey was conducted among diabetes patients admitted to nonendocrine departments in a tertiary hospital in Nanjing, China. The attributes and levels were determined based on DCE principles, and a conditional logit model was used to quantify patients' preferences. Results: A total of 157 respondents were analyzed. Antihyperglycemic effectiveness, healthcare providers, treatment regimen, monitoring frequency, and adverse reactions were the five attributes that significantly influenced patient preference (p < 0.05). Notably, an 80% glycemic control rate (ß = 2.009) and a multidisciplinary management team involving clinical pharmacists (ß = 1.346) had the greatest impact. Negative effects were observed for hypoglycemia (ß = -1.008), insulin pump use (ß = -0.746), and frequent glucose monitoring (ß = -0.523). Female patients exhibited higher concern for healthcare providers (ß = 1.172) compared to males. Younger and shorter-course patients prioritized antihyperglycemic effectiveness (ß = 3.330, ß = 1.510), while older patients preferred multidisciplinary management (ß = 1.186) and opposed increased monitoring frequency (ß = -0.703). Patients with higher educational backgrounds showed greater acceptance of continuous glucose monitoring (ß = 1.983), and those with higher annual income placed more emphasis on glycemic control rate. Conclusion: Treatment preferences of hospitalized diabetes patients are mainly influenced by antihyperglycemic effectiveness, adverse reactions, healthcare providers, and individual characteristics. Comprehensive consideration and an individualized therapy strategy should be given when constructing a hospital-wide glycemic control programme.
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Glucemia , Diabetes Mellitus , Control Glucémico , Hospitalización , Hipoglucemiantes , Prioridad del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipoglucemiantes/uso terapéutico , China , Diabetes Mellitus/terapia , Diabetes Mellitus/sangre , Glucemia/metabolismo , Adulto , Conducta de Elección , Encuestas y Cuestionarios , HiperglucemiaRESUMEN
BACKGROUND: Postoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown. METHODS: The perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH2O (or 40 cmH2O for patients with body mass index > 35 kg/m2) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6-8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO2/FiO2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7. DISCUSSION: The E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications. TRIAL REGISTRATION: ClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024.
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Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Hipoxia , Respiración con Presión Positiva , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Hipoxia/etiología , Hipoxia/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Respiración con Presión Positiva/métodos , Puente Cardiopulmonar/efectos adversos , Resultado del Tratamiento , Atelectasia Pulmonar/etiología , Atelectasia Pulmonar/prevención & control , Factores de Tiempo , Atención Perioperativa/métodos , Persona de Mediana Edad , Femenino , Masculino , Adulto , Pulmón/fisiopatología , Pulmón/cirugía , Anciano , Respiración Artificial/efectos adversos , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/prevención & control , Enfermedades Pulmonares/diagnósticoRESUMEN
Seven fatty acids were detected by GC-MS in Xanthoceras sorbifolium Bunge seed oil extracted at different temperatures, including Palmitic acid C16:0, Stearic acid C18:0, Oleic acid C18:1, Eicosenoic acid C20:1, Docosenoic acid C22:1, Tetracosenoic acid C24:1, and Linoleic acid C18:2. The highest content of nervonic acid (NA) was found in Xanthoceras sorbifolium Bunge seed oil extracted at 70 °C. Three methods were selected to analyze the extraction rate of nervonic acid in Xanthoceras sorbifolium Bunge seed oil, including urea complexation, low-temperature solvent crystallization, and a combined treatment using these two methods. The final content of nervonic acid obtained was 14.07%, 19.66%, and 40.17%, respectively. The combined treatment method increased the purity of nervonic acid in Xanthoceras sorbifolium Bunge seed oil by 12.62 times. Meanwhile, thermogravimetric behavior analysis of samples extracted using different methods was conducted by thermogravimetric analyzer, which suggested that the thermal stability of the samples extracted by the combined treatment was enhanced. These results can provide a new process parameter and scientific basis for the extraction of NA. At the same time, FTIR and NMR were also used to characterize the combined extraction sample, and the structure of the samples was proved.
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BACKGROUND: Chronic Myeloid Leukemia (CML) is a blood cancer that remains challenging to cure due to drug resistance and side effects from current BCR-ABL inhibitors. There is an urgent need for novel and more effective BCR-ABL targeting inhibitors and therapeutic strategies to combat this deadly disease. METHOD: We disclose an "OH-implant" strategy to improve a noncovalent BCR-ABL inhibitor, PPY-A, by adding a hydroxyl group to its scaffold. By taking advantage of this OH "hot spot", we designed a panel of irreversible covalent kinase inhibitors and hypoxia-responsive pro-/dual-drugs, and their biological activities were studied in vitro, in cellulo and in vivo. RESULT: The resulting compound B1 showed enhanced solubility and biological activity. B4 achieved sustained BCR-ABL inhibition by forming a stable covalent bond with ABL kinase. Hypoxia-responsive prodrug P1 and dual-drugs D1/D2/D3 demonstrated significant anti-tumor effects under hypoxic conditions. The in vivo studies using K562-xenografted mice showed that B1 displayed superior antitumor activity than PPY-A, while P1 and D3 offered better safety profiles alongside significant tumor control. CONCLUSION: We have successfully developed a chemical biology approach to convert a known noncovalent BCR-ABL inhibitor into more potent and safer inhibitors through covalent and pro-/dual-drug targeting strategies. Our "OH-implant" approach and the resulting drug design strategies have general applicability and hold promise for improvement the performance of various other reported drugs/drug candidates, thereby providing advanced medicines for disease treatment.
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Background: Falls frequently occur among the older adult population. In this study, we examined the variations in fall incidence across different regions over time, focusing on the disparities between urban and rural areas among older adult Chinese individuals, Healthy aging is comprised of five dimensions: (1) absence of chronic diseases, (2) good physical functioning, (3) normal cognitive function, (4) active social participation, and (5) absence of depression. Additionally, we explored the relationship between healthy aging and the occurrence of falls in middle-aged and older adults. Falls are defined as events that occurred within the past two years. Results: Among 9,918 participants, 33.8% lived in urban areas and 23.0% achieved healthy aging. In contrast, 66.2% resided in rural areas with 16.5% achieving healthy aging. In 2011, rural residents had a higher fall incidence rate (17% in rural vs. 13.5% in urban); by 2020, the fall rate remained higher in rural areas (19.5% in rural vs. 17.3% in urban). Unhealthy aging (HR = 1.08, 95%CI: 1.00-1.16) were risk factors for falls. Subgroup analysis revealed that in rural areas, unhealthy aging increased the risk of falls. In urban areas, the increased risk of falls associated with unhealthy aging was not significant (Rural HR = 1.11, 95%CI:1.01-1.22; Urban HR = 1.05, 95%CI: 0.93-1.18). Conclusion: Healthy aging may be more strongly associated with a lower risk of falls in rural areas, while this association might be less pronounced in urban areas due to different environmental and social factors. This highlights the need for environment-specific fall prevention strategies and targeted measures for the older adult.
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Accidentes por Caídas , Envejecimiento Saludable , Población Rural , Población Urbana , Humanos , Accidentes por Caídas/estadística & datos numéricos , China/epidemiología , Masculino , Anciano , Femenino , Incidencia , Estudios Longitudinales , Población Rural/estadística & datos numéricos , Persona de Mediana Edad , Población Urbana/estadística & datos numéricos , Factores de Riesgo , Anciano de 80 o más AñosRESUMEN
Increasing efforts have been made to develop proteins in circulating extracellular vesicles (EVs) as potential disease markers. It is in particular intriguing to measure post-translational modifications (PTMs) such as phosphorylation, preserved and stable in EVs. To facilitate the quantitative measurement of EV protein phosphorylation for potential clinical use, a label-free (LF) multiple reaction monitoring (MRM) strategy is introduced by utilizing a synthetic phosphopeptide set (phos-iRT) as the internal standards and a local normalization method. The quantitation method was investigated in terms of its linear dynamic range, sensitivity, accuracy, precision, and matrix effect, with a dynamic range spanning from 10 to 1000 ng/mL and an accuracy ranging from 82.4 to 116.8% for EV samples. Then, the LF-MRM-based local normalization method was utilized to evaluate and optimize our recently developed EVTOP method for the enrichment of phosphopeptides from EVs. Finally, we applied the optimized EV enrichment approach and the LF-MRM-based local normalization method to quantify phosphopeptides in urine EVs from patients with prostate cancer (PCa) and healthy individuals, showcasing the strategy's superiority in quantifying phosphopeptides without isotopic internal standards and validating that the method is generally applicable in MRM-based EV phosphopeptide quantification.
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Uveal melanoma (UM) is an aggressive intraocular malignancy derived from melanocytes in the uvea tract of the eye. Up to 50% of patients with UM develop distant metastases which is usually fatal within one year; preventing metastases is therefore essential. Metabolic reprogramming plays a critical role in UM progression and metastasis. However, the metabolic phenotype of UM cells in the hypoxic tumor is not well understood. Here, we report that hypoxia-induced BNIP3 reprograms tumor cell metabolism, promoting their survival and metastasis. In response to hypoxia, BNIP3-mediated mitophagy alleviates mitochondrial dysfunction and enhances mitochondrial oxidative phosphorylation (OXPHOS) while simultaneously reducing mitochondrial reactive oxygen species (mtROS) production. This, in turn, impairs HIF1A/HIF-1α protein stability and inhibits glycolysis. Inhibition of mitophagy significantly suppresses BNIP3-induced UM progression and metastasis in vitro and in vivo. Collectively, these observations demonstrate a novel mechanism whereby BNIP3 promotes UM metabolic reprogramming and malignant progression by mediating hypoxia-induced mitophagy and suggest that BNIP3 could be an important therapeutic target to prevent metastasis in patients with UM.Abbreviations: AOD: average optical density; BNIP3: BCL2/adenovirus E1B interacting protein 3; CQ: chloroquine; CoCl2: cobalt chloride; GEPIA: Gene Expression Profiling Interactive Analysis; HIF1A: hypoxia inducible factor 1, alpha subunit; IHC: immunohistochemistry; mtROS: mitochondrial reactive oxygen species; NAC: N-acetylcysteine; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; ROS: reactive oxygen species; TCGA: The Cancer Genome Atlas; UM: uveal melanoma.
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OBJECTIVES: We explored the value of contrast-enhanced ultrasound (CEUS) in evaluating femoral head (FH) perfusion, guiding interventions and follow-up for infants with developmental dysplasia of the hip (DDH) and septic arthritis of the hip (SAH). The aim was to provide robust evidence for clinical assessment. METHODS: Ten infants, including 7 with DDH and 3 with SAH, were prospectively enrolled, with their bilateral hips alternately scanned during the CEUS exams. Twenty hips were classified into the case group (n = 11) and the control group (n = 9). Pre- and post-interventional studies were performed in DDH infants requiring interventions. FH perfusion was assessed by the perfusion area ratio (PAR) and quadrant location of microbubble-defect regions. RESULTS: In the case group, 25 CEUS studies were conducted, including 11 baseline, 7 follow-up and 7 post-intervention studies. The PAR significantly decreased in the case group (49.79% vs. 100.00%, p < 0.05). The microbubble-defect regions averagely affected 2 quadrants, primarily quadrat No. 3 (30%) and No. 4 (32%). Seven hip abduction angle adjustments were made based on pre-interventional studies, resulting in a significant increase in PAR in post-interventional studies (37.63% vs. 60.24%, p < 0.05). PAR increased in follow-up studies compared to baseline values (45.61% vs. 76.07%, p < 0.05). The inter- and intra-observer reproducibility of PAR measurements were excellent (intraclass correlation coefficient, both 0.97). CONCLUSION: CEUS proves to be a promising technique for quantitatively detecting FH perfusion in DDH and SAH infants with high reproducibility. It is valuable for baseline, intra-intervention and follow-up studies, aiming in clinical conditions and therapeutic effect evaluation.
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BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).
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The NLRP3 inflammasome promotes inflammation in disease, yet the full repertoire of mechanisms regulating its activity is not well delineated. Among established regulatory mechanisms, covalent modification of NLRP3 has emerged as a common route for the pharmacological inactivation of this protein. Here, we show that inhibition of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) results in the accumulation of methylglyoxal, a reactive metabolite whose increased levels decrease NLRP3 assembly and inflammatory signaling in cells. We find that methylglyoxal inactivates NLRP3 via a non-enzymatic, covalent-crosslinking-based mechanism, promoting inter- and intraprotein MICA (methyl imidazole crosslink between cysteine and arginine) posttranslational linkages within NLRP3. This work establishes NLRP3 as capable of sensing a host of electrophilic chemicals, both exogenous small molecules and endogenous reactive metabolites, and suggests a mechanism by which glycolytic flux can moderate the activation status of a central inflammatory signaling pathway.
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OBJECTIVE: This study aims to explore the changes in dynamic overlapping communities in the brains of schizophrenia (SZ) patients and further investigate the dynamic restructuring patterns of overlapping communities in SZ patients. MATERIALS AND METHODS: A total of 43 SZ patients and 49 normal controls (NC) were selected for resting-state functional MRI (rs-fMRI) scans. Dynamic functional connectivity analysis was conducted separately on SZ patients and NC using rs-fMRI and Jackknife Correlation techniques to construct dynamic brain network models. Based on these models, a dynamic overlapping community detection method was utilized to explore the abnormal overlapping community structure in SZ patients using evaluation metrics such as the structural stability of overlapping communities, nodes' functional diversity, and activity level of overlapping communities. RESULTS: The stability of communities in SZ patients showed a decreasing trend. The changes in the overlapping community structure of SZ patients may be related to a decrease in the diversity of overlapping node functions. Additionally, compared to the NC group, the activity level of overlapping communities of SZ patients was significantly reduced. CONCLUSION: The structure or organization of the brain functional network in SZ patients is abnormal or disrupted, and the activity of the brain network in information processing and transmission is weakened in SZ patients.
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OBJECTIVE: To evaluate the clinical efficacy of internal limiting membrane (ILM) peeling combined with perimacular hole massage versus ILM flap insertion in the management of patients with idiopathic macular holes was conducted. METHODS: 35 patients (total of 35 eyes) with idiopathic macular holes (with hole diameters ranging from 366 to 1430 µm) were divided into two groups-Group A consisted of 20 eyes that underwent pars plana vitrectomy (PPV) combined with ILM peeling and perimacular hole massage, while Group B comprised 15 eyes that underwent PPV combined with ILM flap insertion. Subsequent follow-up examinations were performed at 1 week, 1 month, and 3 months post-surgery. The study also involved a comparison of best corrected visual acuity (BCVA) and optical coherence tomography (OCT) classifications between both the patient groups. RESULTS: The macular hole closure rates in Group A were 60 %, while in Group B, the closure rate was 93 %. There was significant difference in hiatus healing rate between the two groups (t = 4.843, p = 0.048). The difference in BCVA at 3 months post-operation between the two groups was statistically significant (t = 3.221, p = 0.003). Three months post-operatively, the BCVA in Group B demonstrated improvement compared to the pre-operative BCVA, with a statistically significant difference (p > 0.05). Three months post-operatively, the BCVA in Group A demonstrated improvement compared to the pre-operative BCVA, but this difference was not statistically significant (p > 0.05). CONCLUSION: The combination of PPV with ILM flap insertion demonstrates favorable therapeutic efficacy in the treatment of idiopathic macular holes, leading to improved visual acuity.
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Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.
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Fusarium oxysporum is an asexual filamentous fungus that causes vascular wilt in hundreds of crop plants and poses a threat to public health through Fusariosis. F. oxysporum f. sp. conglutinans strain Fo5176, originally isolated from Brassica oleracea, is pathogenic to Arabidopsis, making it a model pathosystem for dissecting the molecular mechanisms underlying host-pathogen interactions. Assembling the F. oxysporum genome is notoriously challenging due to the presence of repeat-rich accessory chromosomes. Here, we report a gap-free genome assembly of Fo5176 using PacBio HiFi and Hi-C data. The 69.56 Mb assembly contained 18 complete chromosomes, including all centromeres and most telomeres (20/36), representing the first gap-free genome sequence of a pathogenic F. oxysporum strain. In total, 21,460 protein-coding genes were annotated, a 26.3% increase compared to the most recent assembly. This high-quality reference genome for F. oxysporum f. sp. conglutinans Fo5176 provides a valuable resource for further research into fungal pathobiology and evolution.