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Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/- control mice treated with normal saline, those in the ApoE-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg-1 d-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm2vs. (0.032±0.0062) mm2, P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.
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The rumen ciliates are a diverse group of protozoa residing in the rumen of ruminant animals. They are primarily found in the orders Entodiniomorphida and Vestibuliferida, playing crucial roles in the digestion and breakdown of feed within the host's rumen, closely intertwined with the host's nutrient absorption. In vitro monocultures of representatives of rumen ciliates are important to better study them. So far, Entodinium caudatum and Epidinium caudatum, representatives of the order Entodiniomorphida, have been successfully cultivated as a monoculture in vitro. However, for the order Vestibuliferida, no representative species has been established a stable monoculture in vitro up to date, which hampers to study their physiology and metabolism. Therefore, we have developed a simple method for the in vitro cultivation of Dasytricha ruminantium, a representative rumen ciliate in the order Vestibuliferida. Utilizing an optimized culture medium with easily obtainable components, and the cultivation process is simple. This will facilitate further research in metabolism and other studies requiring large pure live materials.1.Filtration and separation for enriching D. ruminantium.2.A culture medium (DRM) suitable for the growth of D. ruminantium, with easily obtainable components.3.Simple cultivation process, facilitating the obtainment of a large number of monocultured D. ruminantium.
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Spliceosome dysfunction and aberrant RNA splicing underline unresolved inflammation and immunopathogenesis. Here, we revealed the misregulation of mRNA splicing via the spliceosome in the pathogenesis of rheumatoid arthritis (RA). Among them, decreased expression of RNA binding motif protein 25 (RBM25) was identified as a major pathogenic factor in RA patients and experimental arthritis mice through increased proinflammatory mediator production and increased hyperinflammation in macrophages. Multiomics analyses of macrophages from RBM25-deficient mice revealed that the transcriptional enhancement of proinflammatory genes (including Il1b, Il6, and Cxcl10) was coupled with histone 3 lysine 9 acetylation (H3K9ac) and H3K27ac modifications as well as hypoxia inducible factor-1α (HIF-1α) activity. Furthermore, RBM25 directly bound to and mediated the 14th exon skipping of ATP citrate lyase (Acly) pre-mRNA, resulting in two distinct Acly isoforms, Acly Long (Acly L) and Acly Short (Acly S). In proinflammatory macrophages, Acly L was subjected to protein lactylation on lysine 918/995, whereas Acly S did not, which influenced its affinity for metabolic substrates and subsequent metabolic activity. RBM25 deficiency overwhelmingly increased the expression of the Acly S isoform, enhancing glycolysis and acetyl-CoA production for epigenetic remodeling, macrophage overactivation and tissue inflammatory injury. Finally, macrophage-specific deletion of RBM25 led to inflammaging, including spontaneous arthritis in various joints of mice and inflammation in multiple organs, which could be relieved by pharmacological inhibition of Acly. Overall, targeting the RBM25-Acly splicing axis represents a potential strategy for modulating macrophage responses in autoimmune arthritis and aging-associated inflammation.
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Purpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM. Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD. Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD. Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.
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Antiferroelectric materials have shown great potential in electronic devices benefiting from the reversible phase transition between ferroelectric and antiferroelectric phases. Understanding the dipole arrangements and clear phase transition pathways is crucial for design of antiferroelectric materials-based energy storage and conversion devices. However, the specific phase transition details remain largely unclear and even controversial to date. Here, we have grown a series of PbZrO3 on SrTiO3 substrates and elucidated the fine atom structures and phase transition pathways using atomic-resolution transmission electron microscopy. Specifically, a roadmap for ferroelectric to antiferroelectric phase transitions, here with increasing film thickness, is determined as ferroelectric rhombohedral (R3c)-ferroelectric monoclinic (Pc)-ferrielectric orthorhombic (Ima2)-antiferroelectric orthorhombic (Pbam), where Pc and Ima2 phases act as structural bridges. Moreover, the phase transition pathway is strongly related to the synergistic effect of oxygen octahedral tilting and cation displacement. These findings provide an insightful understanding for the theories and related properties of antiferroelectrics.
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BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Male 8-week-old C57BL/6J mice were randomly allocated into three groups: control group (n = 5), adenine and high-phosphate (HP) diet group (n = 20), and the optimized adenine-containing diet group (n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 (Acer1), alkaline ceramidase 2 (Acer2), prosaposin-like 1 (Psapl1), adenosine A1 receptor (Adora1), and sphingosine-1-phosphate receptor 5 (S1pr5) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS: Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
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Lattice metamaterials have demonstrated remarkable mechanical properties at low densities. As these architected materials advance toward real-world applications, their tolerance for damage and defects becomes a limiting factor. However, a thorough understanding of the fracture resistance and fracture mechanisms in lattice metamaterials, particularly for the emerging shell-based lattices, has remained elusive. Here, using a combination of in situ fracture experiments and finite element simulations, we show that shell-based lattice metamaterials with Schwarz P minimal surface topology exhibit superior fracture resistance compared to conventional octet truss lattices, with average improvements in initiation toughness up to 150%. This superiority is attributed to the unique shell-based architecture that enables more efficient load transfer and higher energy dissipation through material damage, structural plasticity, and material plasticity. Our study reveals a topology-induced intrinsic toughening mechanism in shell-based lattices and highlights these architectures as a superior design route for creating lightweight and high-performance mechanical metamaterials.
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BACKGROUND AND OBJECTIVES: Identification of individuals at high risk of developing Parkinson disease (PD) several years before diagnosis is crucial for developing treatments to prevent or delay neurodegeneration. This study aimed to develop predictive models for PD risk that combine plasma proteins and easily accessible clinical-demographic variables. METHODS: Using data from the UK Biobank (UKB), which recruited participants across the United Kingdom, we conducted a longitudinal study to identify predictors for incident PD. Participants with baseline plasma proteins and no PD were included. Through machine learning, we narrowed down predictors from a pool of 1,463 plasma proteins and 93 clinical-demographic. These predictors were then externally validated using the Parkinson's Progression Marker Initiative (PPMI) cohort. To further investigate the temporal trends of predictors, a nested case-control study was conducted within the UKB. RESULTS: A total of 52,503 participants without PD (median age 58, 54% female) were included. Over a median follow-up duration of 14.0 years, 751 individuals were diagnosed with PD (median age 65, 37% female). Using a forward selection approach, we selected a panel of 22 plasma proteins for optimal prediction. Using an ensemble tree-based Light Gradient Boosting Machine (LightGBM) algorithm, the model achieved an area under the receiver operating characteristic curve (AUC) of 0.800 (95% CI 0.785-0.815). The LightGBM prediction model integrating both plasma proteins and clinical-demographic variables demonstrated enhanced predictive accuracy, with an AUC of 0.832 (95% CI 0.815-0.849). Key predictors identified included age, years of education, history of traumatic brain injury, and serum creatinine. The incorporation of 11 plasma proteins (neurofilament light, integrin subunit alpha V, hematopoietic PGD synthase, histamine N-methyltransferase, tubulin polymerization promoting protein family member 3, ectodysplasin A2 receptor, Latexin, interleukin-13 receptor subunit alpha-1, BAG family molecular chaperone regulator 3, tryptophanyl-TRNA synthetase, and secretogranin-2) augmented the model's predictive accuracy. External validation in the PPMI cohort confirmed the model's reliability, producing an AUC of 0.810 (95% CI 0.740-0.873). Notably, alterations in these predictors were detectable several years before the diagnosis of PD. DISCUSSION: Our findings support the potential utility of a machine learning-based model integrating clinical-demographic variables with plasma proteins to identify individuals at high risk for PD within the general population. Although these predictors have been validated by PPMI, additional validation in a more diverse population reflective of the general community is essential.
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Biomarcadores , Proteínas Sanguíneas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Proteínas Sanguíneas/análisis , Anciano , Estudios Longitudinales , Estudios de Casos y Controles , Biomarcadores/sangre , Reino Unido/epidemiología , Aprendizaje Automático , Progresión de la Enfermedad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Exploring the molecular mechanisms of primordial germ cell (PGC) migration and the involvement of gonadal somatic cells in gonad development is valuable for comprehending the origins and potential treatments of reproductive-related diseases. METHODS: Diaphanous related formin 1 (Diaph1, also known as mDia1) was screened by analyzing publicly available datasets (ATAC-seq, DNase-seq, and RNA-seq). Subsequently, the CRISPR-Cas9 technology was used to construct Diaph1 knockout mice to investigate the role of Diaph1 in gonad development. RESULTS: Based on data from public databases, a differentially expressed gene Diaph1, was identified in the migration of mouse PGC. Additionally, the number of PGCs was significantly reduced in Diaph1 knockout mice compared to wild type mice, and the expression levels of genes related to proliferation (Dicer1, Mcm9), adhesion (E-cadherin, Cdh1), and migration (Cxcr4, Hmgcr, Dazl) were significantly decreased. Diaph1 knockout also inhibited Leydig cell proliferation and induced apoptosis in the testis, as well as granulosa cell apoptosis in the ovary. Moreover, the sperm count in the epididymal region and the count of ovarian follicles were significantly reduced in Diaph1 knockout mice, resulting in decreased fertility, concomitant with lowered levels of serum testosterone and estradiol. Further research found that in Diaph1 knockout mice, the key enzymes involved in testosterone synthesis (CYP11A1, 3ß-HSD) were decreased in Leydig cells, and the estradiol-associated factor (FSH receptor, AMH) in granulosa cells were also downregulated. CONCLUSIONS: Overall, our findings indicate that the knockout of Diaph1 can disrupt the expression of factors that regulate sex hormone production, leading to impaired secretion of sex hormones, ultimately resulting in damage to reproductive function. These results provide a new perspective on the molecular mechanisms underlying PGC migration and gonadal development, and offer valuable insights for further research on the causes, diagnosis, and treatment of related diseases.
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Proliferación Celular , Forminas , Células Germinativas , Gónadas , Ratones Noqueados , Animales , Ratones , Femenino , Masculino , Forminas/genética , Forminas/metabolismo , Proliferación Celular/genética , Gónadas/metabolismo , Células Germinativas/metabolismo , Apoptosis/genética , Testículo/metabolismo , Testículo/crecimiento & desarrollo , Testículo/citología , Movimiento Celular/genética , Ovario/metabolismo , Ovario/crecimiento & desarrollo , Ratones Endogámicos C57BLRESUMEN
Microstructures have been proved as crucial factors for the sensing performance of flexible pressure sensors. In this study, polypyrrole (PPy)/sunflower pollen (SFP) (P/SFP) was prepared via the in situ growth of PPy on the surface of degreased SFP with a sea urchin-like microstructure; then, these P/SFP microspheres were sprayed onto a flat silk cocoon (FSC) to prepare a sensing layer P/SFP-FSC. PPy-FSC (P-FSC) was prepared as an electrode layer through the in situ polymerization of PPy on the FSC surface. The sensing layer P/SFP-FSC was placed between two P-FSC electrode layers to assemble a P/SFP-FSC pressure sensor together with a fork finger electrode. With 6 mg/cm2 of optimized sprayed P/SFP microspheres, the prepared flexible pressure sensor has a sensitivity of up to 0.128 KPa-1 in the range of 0-13.18 KPa and up to 0.13 KPa-1 in the range of 13.18-30.65 KPa, a fast response/recovery time (90 ms/80 ms), and a minimum detection limit as low as 40 Pa. This fabricated flexible P/SFP-FSC sensor can monitor human motion and can also be used for the encrypted transmission of important information via Morse code. In conclusion, the developed flexible P/SFP-FSC pressure sensor based on microstructure modification in this study shows good application prospects in the field of human-computer interaction and wearable electronic devices.
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Polen , Presión , Seda , Dispositivos Electrónicos Vestibles , Seda/química , Polen/química , Animales , Humanos , Polímeros/química , Técnicas Biosensibles/instrumentación , Técnicas Biosensibles/métodos , Pirroles/química , ElectrodosRESUMEN
Introduction: Sarcopenia, an age-related disease, has become a major public health concern, threatening muscle health and daily functioning in older adults around the world. Changes in the gut microbiota can affect skeletal muscle metabolism, but the exact association is unclear. The richness of gut microbiota refers to the number of different species in a sample, while diversity not only considers the number of species but also the evenness of their abundances. Alpha diversity is a comprehensive metric that measures both the number of different species (richness) and the evenness of their abundances, thereby providing a thorough understanding of the species composition and structure of a community. Methods: This meta-analysis explored the differences in intestinal microbiota diversity and richness between populations with sarcopenia and non-sarcopenia based on 16 s rRNA gene sequencing and identified new targets for the prevention and treatment of sarcopenia. PubMed, Embase, Web of Science, and Google Scholar databases were searched for cross-sectional studies on the differences in gut microbiota between sarcopenia and non-sarcopenia published from 1995 to September 2023 scale and funnel plot analysis assessed the risk of bias, and performed a meta-analysis with State v.15. 1. Results: A total of 17 randomized controlled studies were included, involving 4,307 participants aged 43 to 87 years. The alpha diversity of intestinal flora in the sarcopenia group was significantly reduced compared to the non-sarcopenia group: At the richness level, the proportion of Actinobacteria and Fusobacteria decreased, although there was no significant change in other phyla. At the genus level, the abundance of f-Ruminococcaceae; g-Faecalibacterium, g-Prevotella, Lachnoclostridium, and other genera decreased, whereas the abundance of g-Bacteroides, Parabacteroides, and Shigella increased. Discussion: This study showed that the richness of the gut microbiota decreased with age in patients with sarcopenia. Furthermore, the relative abundance of different microbiota changed related to age, comorbidity, participation in protein metabolism, and other factors. This study provides new ideas for targeting the gut microbiota for the prevention and treatment of sarcopenia. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=475887, CRD475887.
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BACKGROUND: There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. METHODS AND RESULTS: A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. CONCLUSIONS: The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.
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Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Glomeruloesclerosis Focal y Segmentaria , Riñón , Nefrosis Lipoidea , Humanos , China/epidemiología , Masculino , Estudios Retrospectivos , Adulto , Femenino , Persona de Mediana Edad , Biopsia/estadística & datos numéricos , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/epidemiología , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/epidemiología , Glomeruloesclerosis Focal y Segmentaria/patología , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Adulto Joven , Nefrosis Lipoidea/patología , Nefrosis Lipoidea/epidemiología , Riñón/patología , Adolescente , Nefritis Lúpica/patología , Nefritis Lúpica/epidemiología , Anciano , Vasculitis por IgA/patología , Vasculitis por IgA/epidemiología , Vasculitis por IgA/diagnóstico , Glomerulonefritis/patología , Glomerulonefritis/epidemiología , Enfermedades Renales/patología , Enfermedades Renales/epidemiología , Enfermedades Renales/diagnósticoRESUMEN
Periodontitis is an inflammatory disease characterized by the destruction of periodontal tissues, and the promotion of bone tissue regeneration is the key to curing periodontitis. Psoralen is the main component of Psoralea corylifolia Linn, and has multiple biological effects, including anti-osteoporosis and osteogenesis. We constructed a novel hydrogel loaded with psoralen (PSO) and stromal cell-derived factor-1 (SDF-1) for direct endogenous cell homing. This study aimed to evaluate the synergistic effects of PSO/SDF-1 on periodontal bone regeneration in patients with periodontitis. The results of CCK8, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining showed that PSO/SDF-1 combination treatment promoted cell proliferation, chemotaxis ability, and ALP activity of PDLSCs. qRT-PCR and western blotting showed that the expression levels of alkaline phosphatase (ALP), dwarf-associated transcription factor 2 (RUNX2), and osteocalcin (OCN) gene were upregulated. Rat periodontal models were established to observe the effect of local application of the composite hydrogel on bone regeneration. These results proved that the PSO/SDF-1 combination treatment significantly promoted new bone formation. The immunohistochemical (IHC) results confirmed the elevated expression of ALP, RUNX2, and OCN osteogenic genes. PSO/SDF-1 composite hydrogel can synergistically regulate the biological function and promote periodontal bone formation. Thus, this study provides a novel strategy for periodontal bone regeneration.
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AIM: To evaluate the impact of non-alcoholic fatty liver disease (NAFLD) presence and fibrosis risk on adverse outcomes in patients with type 2 diabetes and chronic kidney disease. METHODS: Data were sourced from two longitudinal cohorts: 1172 patients from the National Health and Nutrition Examination Survey (NHANES) and 326 patients from the kidney biopsy cohort at the West China Hospital of Sichuan University. Cox regression estimated hazard ratios (HRs) for NAFLD and liver fibrosis concerning adverse clinical outcomes. Subsequently, a two-sample Mendelian randomization study using genome-wide association study statistics explored NAFLD's potential causal link to cardio-cerebrovascular events. RESULTS: In the NHANES cohort, NAFLD stood as an independent risk factor for various outcomes: overall mortality [HR 1.53 (95% confidence interval, CI 1.21-1.95)], mortality because of cardio-cerebrovascular diseases [HR 1.63 (95% CI 1.12-2.37)], heart disease [HR 1.58 (95% CI 1.00-2.49)], and cerebrovascular disease [HR 3.95 (95% CI 1.48-10.55)]. Notably, advanced liver fibrosis, identified by a fibrosis-4 (FIB-4) score >2.67, exhibited associations with overall mortality, cardio-cerebrovascular disease mortality and heart disease mortality. Within the kidney biopsy cohort, NAFLD correlated with future end-stage kidney disease [ESKD; HR 2.17 (95% CI 1.41-3.34)], while elevated FIB-4 or NAFLD Fibrosis Scores predicted future ESKD, following full adjustment. Liver fibrosis was positively correlated with renal interstitial fibrosis and tubular atrophy in biopsies. Further Mendelian randomization analysis supported a causal relationship between NAFLD and cardio-cerebrovascular events. CONCLUSIONS: In patients with type 2 diabetes and chronic kidney disease, the NAFLD presence and elevated FIB-4 scores link to heightened mortality risk and ESKD susceptibility. Moreover, NAFLD shows a causal relationship with cardio-cerebrovascular events.
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Diabetes Mellitus Tipo 2 , Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Longitudinales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Cirrosis Hepática/mortalidad , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , China/epidemiología , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/complicaciones , Factores de Riesgo , Análisis de la Aleatorización Mendeliana , Encuestas Nutricionales , Adulto , Anciano , Estudios de Cohortes , Estudio de Asociación del Genoma CompletoRESUMEN
Titanium silicon molecular zeolite (TS-1) plays an important role in catalytic reactions due to its unique nanostructure. The straight channel on TS-1 was parallel to the orientation of the short b-axis and directly exposed to the aperture of the 10-member ring with a diameter of 0.54 nm × 0.56 nm. This structure could effectively reduce the diffuse restriction of bulk organic compounds during the oxidative desulfurization process. As a kind of cationic polymer electrolyte, polydimethyldiallyl ammonium chloride (PDDA) contains continuous [C8H16N+Cl-] chain segments, in which the Cl- could function as an effective structure-directing agent in the synthesis of nanomaterials. The chain of PDDA could adequately interact with the [0 1 0] plane in the preparation process of zeolite, and then the TS-1 nanosheet with short b-axis thickness (6 nm) could be obtained. The pore structure of the TS-1 nanosheet is controlled by regulating the content of PDDA. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), N2 physical adsorption analysis, infrared absorption spectrum and ultraviolet-visible spectrum were used to determine the TS-1. The thinner nanosheets exhibit excellent catalytic performance in oxidative desulfurization of dibenzothiophene (DBT), in which the removal rate could remain at 100% after three recycles. Here, the TS-1 nanosheet with short b-axis thickness has a promising future in catalytic reactions.
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Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration. Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects. Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.
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Apoptosis , Diosgenina , Ácido Hialurónico , Liposomas , Neoplasias Ováricas , Paclitaxel , Polietilenglicoles , Especies Reactivas de Oxígeno , Femenino , Liposomas/química , Liposomas/farmacocinética , Paclitaxel/farmacología , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Diosgenina/farmacología , Diosgenina/química , Diosgenina/farmacocinética , Diosgenina/administración & dosificación , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Línea Celular Tumoral , Polietilenglicoles/química , Animales , Especies Reactivas de Oxígeno/metabolismo , Humanos , Apoptosis/efectos de los fármacos , Sinergismo Farmacológico , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FosfatidiletanolaminasRESUMEN
BACKGROUND: Postoperative delirium (POD) and cognitive dysfunction (POCD) are common complications following thoracic surgery, particularly in patients aged 65 years and above. These complications can significantly affect recovery and increase healthcare costs. This study investigates the effects of low-dose S-ketamine on reducing POD and POCD in this patient demographic. METHODS: In this retrospective cohort study, medical records of patients aged ≥ 65 years who underwent elective thoracic surgery from January 2019 to August 2023 were reviewed. Patients were categorized into S-ketamine and Control groups based on intraoperative S-ketamine exposure. POD was assessed using the Confusion Assessment Method (CAM), while cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline, 1 week, 1 month, and 6 months post-surgery. Intraoperative and postoperative parameters, including hemodynamic stability, blood loss, pain scores, and ICU stay length, were also recorded. RESULTS: The study comprised 140 participants, with 70 in each group. The S-ketamine group demonstrated a significantly lower incidence of POD at 7 days post-surgery (12.0% vs. 26.7%, P < 0.001), and reduced POCD at 1 month (18.7% vs. 36.0%, P < 0.05) and 6 months (10.7% vs. 21.3%, P < 0.05). The Ketamine group had a significantly higher median MoCA score compared to the Control group both at 1 month (P = 0.021) and 6 months (P = 0.007). Adverse events, such as infection, bleeding, and respiratory failure, showed no significant differences between the groups, suggesting a safe profile for S-ketamine. CONCLUSION: Administering low-dose S-ketamine during thoracic surgery in patients aged 65 years and above significantly reduces the incidence of POD and POCD, highlighting its neuroprotective potential. These findings advocate for the inclusion of S-ketamine in anesthetic protocols to improve postoperative outcomes and reduce healthcare costs in this patient population.
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Delirio , Ketamina , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Torácicos , Humanos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Anciano , Femenino , Masculino , Estudios Retrospectivos , Procedimientos Quirúrgicos Torácicos/efectos adversos , Complicaciones Posoperatorias/prevención & control , Delirio/prevención & control , Cognición/efectos de los fármacos , Disfunción Cognitiva/prevención & control , Anciano de 80 o más AñosRESUMEN
A heterostructured crystalline bilayer specimen is known to produce moiré fringes (MFs) in the conventional transmission electron microscopy (TEM). However, the understanding of how these patterns form in scanning transmission electron microscopy (STEM) remains limited. Here, we extended the double-scattering model to establish the imaging theory of MFs in STEM for a bilayer sample and applied this theory to successfully explain both experimental and simulated STEM images of a perovskite PbZrO3/SrTiO3 system. Our findings demonstrated that the wave vectors of electrons exiting from Layer-1 and their relative positions with the atomic columns of Layer-2 should be taken into account. The atomic column misalignment leads to a faster reduction in the intensity of the secondary scattering beam compared to the single scattering beam as the scattering angle increases. Consequently, the intensity distribution of MFs in the bright field (BF)-STEM can be still described as the product of two single atomic images. However, in high angle annular dark field (HAADF)-STEM, it is approximately described as the superposition of the two images. Our work not only fills a knowledge gap of MFs in incoherent imaging, but also emphasizes the importance of the coherent scattering restricted by the real space when analyzing the HAADF-STEM imaging.
RESUMEN
A BF3·OEt2-catalyzed cascade cyclization reaction of vinyloxirane with coumarin is described, affording the benzocoumarin derivatives with moderate to excellent yields (72-92%). The reaction demonstrates exceptional substrate tolerance and has been extensively explored for its potential in drug development, including scale-up experiments, functional group transformations, and screening of the products for anticancer activity. Moreover, the reaction mechanism has been rigorously validated through intermediate trapping and control experiments. Additionally, this reaction represents the uncommon nonmetal catalyzed intermolecular cyclization of vinyloxiranes.
RESUMEN
Background: Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme involved in kidney disease, yet its regulation in diabetic kidney disease (DKD) remains inadequately understood. Objective: Therefore, we investigated the changes of NAD+ levels in DKD and the underlying mechanism. Methods: Alternations of NAD+ levels and its biosynthesis enzymes were detected in kidneys from streptozotocin-induced diabetic mouse model by real-time PCR and immunoblot. The distribution of NAD+ de novo synthetic enzymes was explored via immunohistochemical study. NAD+ de novo synthetic metabolite was measured by LC-MS. Human data from NephroSeq were analyzed to verify our findings. Results: The study showed that NAD+ levels were decreased in diabetic kidneys. Both mRNA and protein levels of kynurenine 3-monooxygenase (KMO) in NAD+ de novo synthesis pathway were decreased, while NAD+ synthetic enzymes in salvage pathway and NAD+ consuming enzymes remained unchanged. Further analysis of human data suggested KMO, primarily expressed in the proximal tubules shown by our immunohistochemical staining, was consistently downregulated in human diabetic kidneys. Conclusion: Our study demonstrated KMO of NAD+ de novo synthesis pathway was decreased in diabetic kidney and might be responsible for NAD+ reduction in diabetic kidneys, offering valuable insights into complex regulatory mechanisms of NAD+ in DKD.