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OBJECTIVE: Growing research suggests that food insecurity is associated with worse cognitive functioning; however, prospective studies are needed to examine food insecurity and dementia risk. Using longitudinal and nationally representative data, we examined the effects of food insecurity on dementia risk among older adults. METHODS: Data came from 3,232 adults (≥65 years) from the Panel Study of Income Dynamics. Food insecurity was assessed biennially using the US Household Food Security Survey Module from 2015-2019. Probable dementia risk was assessed biennially using the Eight Item Interview to Differentiate Aging and Dementia (AD8) from 2017-2021. Inverse probability weighting and marginal structural models were used to account for the time-varying nature of food insecurity and sociodemographic and health confounders. RESULTS: After accounting for baseline and time-varying sociodemographic and health covariates, there was a two-fold higher association between food insecurity and probable dementia risk (OR 2.11, 95% CI 1.12, 3.98). Results were robust to expanding the exposure to include marginal food security, and the outcome to include informant-reported memory loss. Furthermore, there was no evidence of heterogeneity in the association of food insecurity and probable dementia risk by sex, race and ethnicity, or participation in the Supplemental Nutrition Assistance program. DISCUSSION: Food insecurity is a modifiable social determinant of health. Interventions and policies are needed to reduce food insecurity and promote healthy aging for older adults.

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Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.

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The risk of ulcerative colitis (UC) is increasing worldwide with limited success using classical drugs, which has underscored the development of novel agents. Recently, carrier-free molecular assembly has been proven to be an effective drug delivery system, but it has yet to be examined for UC drug development using phytochemicals. Based on traditional Chinese medicine compatibility and potential medicinal uses, a pair of natural compounds, berberine (BBR) and magnolol (MAG), were found to self-assemble into nanostructures in aqueous solutions. Spectral analysis revealed that the assembly mechanisms of BBR and MAG were mediated through charge interactions and π-π stacking. Pharmacokinetic studies and animal imaging showed that BBR-MAG self-assembly (BM) effectively promoted the oral bioavailability and biodistribution of BBR in the colon. BM exhibited superior effects in regulating inflammatory factors, maintaining colon barrier integrity, and regulating gut microbiota in a dextran sulfate sodium salt-induced colitis mouse model. Additionally, no apparent signs of toxicity were observed, suggesting that BM has a favorable safety profile. This study presents a new strategy for UC management and highlights the cooperative effects of combined phytochemicals.

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Berberina , Compuestos de Bifenilo , Colitis Ulcerosa , Lignanos , Nanoestructuras , Animales , Colitis Ulcerosa/tratamiento farmacológico , Berberina/química , Berberina/farmacología , Berberina/uso terapéutico , Lignanos/química , Lignanos/farmacología , Lignanos/uso terapéutico , Ratones , Compuestos de Bifenilo/química , Nanoestructuras/química , Masculino , Sulfato de Dextran/química , Colon/efectos de los fármacos , Colon/patología , Modelos Animales de Enfermedad , Distribución Tisular , Ratones Endogámicos C57BL , Microbioma Gastrointestinal/efectos de los fármacos , Disponibilidad Biológica

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Advances in whole-slide imaging and artificial intelligence present opportunities for improvement in Pap test screening. To date, there have been limited studies published regarding how best to validate newer AI-based digital systems for screening Pap tests in clinical practice. In this study, we validated the Genius™ Digital Diagnostics System (Hologic) by comparing the performance to traditional manual light microscopic diagnosis of ThinPrep® Pap test slides. A total of 319 ThinPrep® Pap test cases were prospectively assessed by six cytologists and three cytopathologists by light microscopy and digital evaluation and the results compared to the original ground truth Pap test diagnosis. Concordance with the original diagnosis was significantly different by digital and manual light microscopy review when comparing across: (i) exact Bethesda System diagnostic categories (62.1% vs 55.8%, respectively, p = 0.014), (ii) condensed diagnostic categories (76.8% vs 71.5%, respectively, p = 0.027), and (iii) condensed diagnoses based on clinical management (71.5% vs 65.2%, respectively, p = 0.017). Time to evaluate cases was shorter for digital (M = 3.2 min, SD = 2.2) compared to manual (M = 5.9 min, SD = 3.1) review (t(352) = 19.44, p < 0.001, Cohen's d = 1.035, 95% CI [0.905, 1.164]). Not only did our validation study demonstrate that AI-based digital Pap test evaluation had improved diagnostic accuracy and reduced screening time compared to light microscopy, but that participants reported a positive experience using this system.

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Objective: Preoperative obstructive sleep apnea (OSA) is supposed to be the abnormally high occurrence of OSA the night before surgery under general anesthesia. This study aimed to evaluate the prevalence preoperative OSA using cardiopulmonary coupling (CPC) and its correlation with imbalance of sympathetic/parasympathetic nervous system. Methods: A total of 550 patients with plans to receive surgery under general anesthesia were enrolled. All patients were assigned to wear CPC on the night before surgery until the next day. Sleep quality characteristics, heart rate variation parameters, and apnea-hypopnea index were acquired. The diagnosis of pre-existing OSA was not considered in the current study. Results: According to apnea-hypopnea index, 28.4%, 32.2%, 26.2%, and 13.3% patients were assessed as no, mild, moderate, and severe operative OSA, respectively. Multivariate logistic regression model revealed that higher age [p < 0.001, odds ratio (OR) = 1.043] was independently and positively associated with preoperative OSA; heart rate variation parameters representing the imbalance of sympathetic/parasympathetic nervous system, such as higher low-frequency (p < 0.001, OR = 1.004), higher low-frequency/high-frequency ratio (p = 0.028, OR = 1.738), lower NN20 count divided by the total number of all NN intervals (pNN20; p < 0.001, OR = 0.950), and lower high-frequency (p < 0.001, OR = 0.998), showed independent relationships with a higher probability of preoperative OSA. Higher age (p = 0.005, OR = 1.024), higher very-low-frequency (p < 0.001, OR = 1.001), and higher low-frequency/high-frequency ratio (p = 0.003, OR = 1.655) were associated with a higher probability of moderate-to-severe preoperative OSA, but higher pNN10 (p < 0.001, OR = 0.951) was associated with a lower probability of moderate-to-severe preoperative OSA. Conclusion: Preoperative OSA is prevalent. Higher age and imbalance of sympathetic/parasympathetic nervous system are independently and positively associated with a higher occurrence of preoperative OSA. CPC screening may promote the management of preoperative OSA.

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Additive engineering, with its excellent ability to passivate bulk or surface perovskite defects, has become a common strategy to improve the performance and stability of perovskite solar cells (PVSCs). Among the various additives reported so far, ammonium salts are considered an important branch. It is worth noting that although both ammonium-based additives (R-NH3 +) and amine-based additives (R-NH2) are derivatives of ammonia (NH3), the functions of the two can be easily confused due to their structural similarities. Moreover, there is no comprehensive comparative analysis of them in the literature. Here, the differences between phenethylammonium iodide (PEA+) and phenethylamine (PEA) additives are revealed experimentally and theoretically. The results clearly show that PEA outperforms PEA+ in terms of device performance and stability based on the following three factors: i) PEA's defect passivation capability is superior to that of PEA+; ii) PEA has better hydrophobicity to hinder water ingress; and iii) PEA completely improves the stability of PVSCs by enhancing thermal stability and inhibiting iodide migration in perovskite more effectively than PEA+. As a result, the power conversion efficiency (PCE) of the inverted methylammonium triiodide (MAPbI3) device using PEA increases by ≈15% to over 21%. More importantly, this device exhibits greater ability to prevent water invasion, thermal-induce degradation, and inhibit iodide ion migration, resulting in better long-term stability.

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ABSTRACT: Aneurysms are localized dilations of blood vessels, which can expand to 50% of the original diameter. They are more common in cardiovascular and cerebrovascular vessels. Rupture is one of the most dangerous complications. The pathophysiology of aneurysms is complex and diverse, often associated with progressive vessel wall dysfunction resulting from vascular smooth muscle cell death and abnormal extracellular matrix synthesis and degradation. Multiple studies have shown that long noncoding RNAs (lncRNAs) play a significant role in the progression of cardiovascular and cerebrovascular diseases. Therefore, it is necessary to find and summarize them. LncRNAs control gene expression and disease progression by regulating target mRNA or miRNA and are biomarkers for the diagnosis and prognosis of aneurysmal cardiovascular and cerebrovascular diseases. This review explores the role, mechanism, and clinical value of lncRNAs in aneurysms, providing new insights for a deeper understanding of the pathogenesis of cardiovascular and cerebrovascular aneurysms.

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Aneurisma Intracraneal , Músculo Liso Vascular , Miocitos del Músculo Liso , Fenotipo , ARN Largo no Codificante , Humanos , Músculo Liso Vascular/patología , Músculo Liso Vascular/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/metabolismo , Aneurisma Intracraneal/fisiopatología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Animales , Regulación de la Expresión Génica , Aneurisma/genética , Aneurisma/patología , Aneurisma/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Transducción de Señal

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Lithium metal batteries (LMBs) with LiNi0.8Co0.1Mn0.1O2 (NCM811) cathodes have garnered significant interest as next-generation energy storage devices due to their high energy density. However, the instability of their electrode/electrolyte interfaces in regular carbonate electrolytes (RCEs) results in a rapid capacity decay. To address this, a colloid electrolyte consisting of Li3P nanoparticles uniformly dispersed in the RCE is developed by a one-step synthesis. This design concurrently creates stable cathode electrolyte interphase (CEI) and solid electrolyte interphase (SEI) on both electrode surfaces. The cathode interface derived from this colloid electrolyte significantly facilitates the decomposition of Li salts (LiPF6 and LiDFOB) on the cathode surface by weakening the P-F and B-F bonds. This in situ formed P/LiF-rich CEI effectively protects the NCM811 cathode from side reactions. Furthermore, the Li3P embedded in the SEI optimizes and homogenizes the Li-ion transport, enabling dendrite-free Li deposition. Compared to the RCE, the designed colloid electrolyte enables robust cathode and anode interfaces in NCM811||Li full cells, minimizing gas and dendrite formation, and delivering a superior capacity retention of 82% over 120 cycles at a 4.7 V cutoff voltage. This approach offers different insights into electrolyte regulation and explores alternative electrolyte shapes and formulations.

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Exosomes are being increasingly explored in biomedical research for wound healing applications. Exosomes can improve blood circulation and endocrine signaling, resulting in enhanced cell regeneration. However, exosome treatments suffer from low retention and bioavailability of exosomes at the wound site. Hydrogels are a popular tool for drug delivery due to their ability to encapsulate drugs in their network and allow for targeted release. Recently, hydrogels have proven to be an effective method to provide increased rates of wound healing when combined with exosomes that can be applied noninvasively. We have designed a series of single-domain protein-based hydrogels capable of physical cross-linking and upper critical solution temperature (UCST) behavior. Hydrogel variant Q5, previously designed with improved UCST behavior and a significantly enhanced gelation rate, is selected as a candidate for encapsulation release of exosomes dubbed Q5Exo. Q5Exo exhibits low critical gelation times and significant decreases in wound healing times in a diabetic mouse wound model showing promise as an exosome-based drug delivery tool and for future hybrid, noninvasive protein-exosome design.

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Materiales Biocompatibles , Exosomas , Hidrogeles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Exosomas/química , Exosomas/metabolismo , Hidrogeles/química , Animales , Ratones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Cinética , Tamaño de la Partícula , Ensayo de Materiales , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico

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A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.

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Productos Biológicos , Productos Biológicos/química , Productos Biológicos/farmacología , Productos Biológicos/aislamiento & purificación , Estructura Molecular , Especies en Peligro de Extinción , Plantas Medicinales/química , Hojas de la Planta/química

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The behavioral sensitization, characterized by escalated behavioral responses triggered by recurrent exposure to psychostimulants, involves neurobiological mechanisms that are brain-region and cell-type specific. Enduring neuroadaptive changes have been observed in response to methamphetamine (METH) within the orbitofrontal cortex (OFC), the cell-type specific transcriptional alterations in response to METH sensitization remain understudied. In this study, we utilized Single-nucleus RNA-sequencing (snRNA-seq) to profile the gene expression changes in the OFC of a rat METH sensitization model. The analyses of differentially expressed genes (DEGs) unveiled cell-type specific transcriptional reactions associated with METH sensitization, with the most significant alterations documented in microglial cells. Bioinformatic investigations revealed that distinct functional and signaling pathways enriched in microglia-specific DEGs majorly involved in macroautophagy processes and the activation of N-methyl-D-aspartate ionotropic glutamate receptors (NMDAR). To validate the translational relevance of our findings, we analyzed our snRNA-seq data in conjunction with a transcriptomic study of individuals with opioid use disorder (OUD) and a large-scale Genome-Wide Association Studies (GWAS) from multiple externalizing phenotypes related to drug addiction. The validation analysis confirmed the consistent expression changes of key microglial DEGs in human METH addiction. Moreover, the integration with GWAS data revealed associations between addiction risk genes and the DEGs observed in specific cell types, particularly microglia and excitatory neurons. Our study highlights the importance of cell-type specific transcriptional alterations in the OFC in the context of METH sensitization and their potential translational relevance to human drug addiction.

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Estimulantes del Sistema Nervioso Central , Metanfetamina , Corteza Prefrontal , Ratas Sprague-Dawley , Metanfetamina/farmacología , Animales , Masculino , Ratas , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Microglía/metabolismo , Microglía/efectos de los fármacos , Análisis de Secuencia de ARN/métodos

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Bovine viral diarrhea virus (BVDV) is an RNA virus associated with severe economic losses in animal production. Effective vaccination and viral surveillance are urgent for the prevention and control of BVDV infection. However, the application of traditional modified live vaccines and inactivated vaccines is faced with tremendous challenges. In the present study, we describe the preclinical efficacy of two BVDV mRNA vaccines tested in mice and guinea pigs, followed by a field trial in goats, where they were compared to a commercial vaccine (formaldehyde inactivated). The two mRNAs were engineered to express the envelope protein E2 of BVDV-1, the most prevalent subtype across the world, through a 5' cap-dependent or independent fashion. Better titers of neutralizing antibodies against BVDV-1 were achieved using the capped RNA in the sera of mice and guinea pigs, with maximum values reaching 9.4 and 13.7 (by -log2), respectively, on the 35th day post-vaccination. At the same time point, the antibody levels in goats were 9.1 and 10.2 for the capped and capless RNAs, respectively, and there were no significant differences compared to the commercial vaccine. The animals remained healthy throughout the experiment, as reflected by their normal leukogram profiles. Collectively, our findings demonstrate that mRNA vaccines have good safety and immunogenicity, and we laid a strong foundation for the further exploitation of efficient and safe BVDV vaccines.

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Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood. Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women. Design, Setting, and Participants: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024. Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages. Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias. Results: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up. Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.

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Consumo de Bebidas Alcohólicas , Bebidas Alcohólicas , Gota , Humanos , Gota/epidemiología , Gota/etiología , Masculino , Femenino , Persona de Mediana Edad , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/efectos adversos , Anciano , Estudios Prospectivos , Adulto , Bebidas Alcohólicas/estadística & datos numéricos , Bebidas Alcohólicas/efectos adversos , Factores de Riesgo , Reino Unido/epidemiología , Modelos de Riesgos Proporcionales , Incidencia , Factores Sexuales

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Lung cancer (LC) is the leading cause of cancer-related mortality worldwide. Radiotherapy is the main component of LC treatment; however, its efficacy is often limited by radioresistance development, resulting in unsatisfactory clinical outcomes. Here, we found that LC radiosensitivity is up-regulated by decreased expression of long-chain acyl-CoA synthase 6 (ACSL6) after irradiation. Deletion of ACSL6 results in significant elevation of Friend leukemia integration 1 transcription factor (FLI1) and a marked decline of collagens (COLs). Blocking of ACSL6 impairs the tumor growth and upregulates FLI1, which reduces the levels of COLs and compromises irradiation-induced autophagy, leading to considerable therapeutic benefits during radiotherapy. Moreover, the direct interaction between ACSL6 and FLI1 and engagement between FLI1 and COLs indicates the involvement of the ACSL6-FLI1-COL axis. Finally, the potently adjusted autophagy flux reduces its otherwise contributive capability in surviving irradiation stress and leads to satisfactory radiosensitization for LC radiotherapy. These results demonstrate that enhanced ACSL6 expression promotes the aggressive performance of irradiated LC through increased FLI1-COL-mediated autophagy flux. Thus, the ACSL6-FLI1-Col-autophagy axis may be targeted to enhance the radiosensitivity of LC and improve the management of LC in radiotherapy.

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BACKGROUND: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients. AIMS: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients. METHODS: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively. RESULTS: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955). CONCLUSIONS: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.

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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Tomografía de Coherencia Óptica , Humanos , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/cirugía , Anciano , Estudios de Seguimiento , Resultado del Tratamiento , Angiografía Coronaria

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Electrodialysis (ED) is an eco-friendly and feasible method to separate or recover ionic compounds by electric field attraction and configuration of ion exchange membranes. Strain Burkholderia sp. H-2 could biotransform 5-hydroxymethylfurfural (5-HMF) into a green platform compound, 2,5-furandicarboxylic acid (FDCA), using a bioreactor system. In this study, electrodialysis with the bipolar membrane (EDBM) and traditional ED systems were applied to recover and concentrate FDCA. Artificial and real FDCA effluents of the 5-HMF biotransformation bioreactor were used as the feedstock to establish the optimal conditions for FDCA recovery. The optimal FDCA concentration and pH of the artificial FDCA effluent were 2100 mg/L and 5, respectively. The suitable current density of the EDBM was 8.93 mA/cm2. For FDCA recovery and concentration using the ED, the feedstock volume and FDCA concentration in the concentration chamber were 1.5 L and 1000 mg/L, respectively. The FDCA recovery efficiency of the real FDCA effluent was 55.6 %. Suppose the pretreatment procedure of the real bioreactor effluent is further optimized. It is believed to benefit the enhancement of FDCA recovery efficiency and reduce energy consumption.

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Four undescribed polyketides, beshanzones A (1) and B (2) as well as beshanhexanols A (3) and B (4), along with three known ones (5-7) were isolated from the rice fermentation of two endophytic fungi associated with the critically endangered Chinese endemic conifer Abies beshanzuensis. γ-Butyrolactone derivatives 1, 2, and 5 were isolated from Phomopsis sp. BSZ-AZ-2, an interesting strain that drawn our attention this time. The cyclohexanol derivatives 3, 4, 6, and 7 were obtained during a follow-up investigation on Penicillium commune BSZ-P-4-1. The chemical structures including absolute configurations of compounds 1-4 were determined by spectroscopic methods, Mo2(OAc)4 induced electronic circular dichroism (IECD), GIAO NMR calculations and DP4+ probability analyses. In particular, compound 2 contains a novel 5/5 bicyclic ring system, which might be biogenetically derived from the known compound 5 through hydrolysis followed by an Aldol reaction. All isolates were evaluated for their antimicrobial activities against a small panel of bacterial and fungal pathogens. Compounds 6 and 7 showed moderate inhibitory activities against Candida albicans, with MIC values of 16 and 32 µg/mL, respectively.

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Abies , Especies en Peligro de Extinción , Endófitos , Policétidos , Endófitos/química , Policétidos/farmacología , Policétidos/aislamiento & purificación , Policétidos/química , Estructura Molecular , China , Abies/química , Phomopsis/química , Pruebas de Sensibilidad Microbiana , Penicillium/química , Bacterias/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/aislamiento & purificación , 4-Butirolactona/análogos & derivados , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/farmacología , 4-Butirolactona/química

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Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.

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Adyuvantes Inmunológicos , Antígenos de Neoplasias , Vacunas contra el Cáncer , Células Dendríticas , Neoplasias de la Próstata , ARN Mensajero , Animales , Masculino , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/tratamiento farmacológico , Antígenos de Neoplasias/inmunología , Ratones , Células Dendríticas/inmunología , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/administración & dosificación , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Humanos , Ratones Endogámicos C57BL , Línea Celular Tumoral , Vacunas de ARNm , Linfocitos T CD8-positivos/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Inmunoterapia/métodos , Activación de Linfocitos/efectos de los fármacos

RESUMEN

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.

Asunto(s)

Experiencias Adversas de la Infancia , Dolor , Humanos , Masculino , Femenino , China/epidemiología , Estudios Longitudinales , Experiencias Adversas de la Infancia/estadística & datos numéricos , Persona de Mediana Edad , Estudios Transversales , Anciano , Dolor/epidemiología , Ejercicio Físico , Factores Socioeconómicos , Factores de Riesgo

RESUMEN

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.

Asunto(s)

Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Tasa de Filtración Glomerular , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Anciano , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Persona de Mediana Edad , Factores de Riesgo , Estudios de Seguimiento , Anciano de 80 o más Años