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Purpose: The purpose of this study is to summarize the design and methodology of a large-scale trial in northern China, the Beijing Angle Closure Progression Study (BAPS). This trial is designed to explore the 5-year incidence of primary angle-closure suspect (PACS) progressing to primary angle-closure (PAC) or primary angle-closure glaucoma (PACG) and to determine the possible risk factors of disease progression. Methods/design: The BAPS is a clinic-based, multicenter, noninterventional trial conducted on a sample of urban Chinese adults. Consecutive eligible patients who meet PACS diagnostic criteria will be recruited from eight participating centers, with the trial commencing on August 4, 2022. The target sample size is set at 825 subjects, with follow up planned for a minimum period of 5 years. Baseline examination will include presenting visual acuity, best corrected visual acuity, intraocular pressure (IOP), undilated slit-lamp biomicroscopy, stereoscopic evaluation of the optic disc, visual field test, optical coherence tomography evaluation of retinal nerve fiber layer, ultrasound biomicroscopy and IOLMaster. Questionnaires will also be used to collect detailed personal history. Patients are scheduled to visit the glaucoma clinic every 12 months and may visit the emergency room in case of acute attack of angle closure. Study endpoints include acute PAC episodes, elevated IOP, peripheral anterior synechiae, glaucomatous visual field defect, or glaucomatous abnormality of optic nerve. Discussion: The BAPS will provide data on the 5-year incidence of PACS progressing to PAC or PACG and determine the risk factors for disease progression. This study will also help redefine high-risk patients with PACS.
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The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
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Epithelial cells play a crucial role in asthma, contributing to chronic inflammation and airway hyperresponsiveness. m6A modification, which involves key proteins such as the demethylase fat mass and obesity-associated protein (FTO), is crucial in the regulation of various diseases, including asthma. However, the role of FTO in epithelial cells and the development of asthma remains unclear. In this study, we investigated the demethylase activity of FTO using a small-molecule inhibitor FB23 in epithelial cells and allergic inflammation in vivo and in vitro. We examined the FTO-regulated transcriptome-wide m6A profiling by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq under FB23 treatment and allergic inflammation conditions. Immunofluorescence staining was performed to assess the tissue-specific expression of FTO in asthmatic bronchial mucosa. We demonstrated that FB23 alleviated allergic inflammation in IL-4/IL-13-treated epithelial cells and house dust mite (HDM)-induced allergic airway inflammation mouse model. The demethylase activity of FTO contributed to the regulation of TNF-α signaling via NF-κB and epithelial-mesenchymal transition-related pathways under allergic inflammation conditions in epithelial cells. FTO was expressed in epithelial, submucosal gland, and smooth muscle cells in human bronchial mucosa. In conclusion, FB23-induced inhibition of FTO alleviates allergic inflammation in epithelial cells and HDM-induced mice, potentially through diverse cellular processes and epithelial-mesenchymal transition signaling pathways, suggesting that FTO is a potential therapeutic target in asthma management.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Asma , Inflamación , Animales , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Ratones , Asma/metabolismo , Asma/genética , Inflamación/metabolismo , Humanos , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/patología , Células Epiteliales/metabolismo , Ratones Endogámicos BALB C , Femenino , Hipersensibilidad/metabolismo , Hipersensibilidad/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Plant-derived natural compounds are significant resources for the discovery of potential anticancer drugs. While research in the plant-based anticancer field has surged in recent years, systematic bibliometric analyses covering a longer period and containing up-to-date publications remain scarce. Here, we conducted a bibliometric analysis of literature on the anticancer properties of plant natural compounds over the past three decades, leveraging the bibliometric framework and open-access platform, KNIME. Our findings showed that the number of plant anticancer-related publications underwent an accelerating growth from 1992 to 2023. The country and institution analyses revealed that countries with traditional medical systems contributed a large portion of publications in the plant anticancer field, such as India, China, and South Korea. This study also highlighted the top ten eminent researchers and publications, assisting researchers in identifying pivotal literature. The primary publications were domains of chemistry and biology-related fields, such as Pharmacology & Pharmacy, Plant Sciences, and Biochemistry & Molecular Biology. Additionally, we noted that flavonoids have been focal plant compounds in anticancer, with strong anticancer potential. Our study provides new insights into the progress and trends in the plant anticancer field and will assist researchers in grasping the future research direction.
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The magneto-optical response of chiral materials holds significant potential for applications in physics, chemistry, and biology. However, exploration of the near-infrared (NIR) magneto-optical response remains limited. Herein, we report the synthesis and strong NIR-II magneto-optical activity of three pairs of chiral 3d-4f clusters of R/S-Ln15Cu54 (Ln = Sm, Gd, and Dy). Structural analysis reveals that R/S-Ln15Cu54 features a triangular prism cage with C3 symmetry. Interestingly, magnetic circular dichroism (MCD) spectra exhibit remarkable magneto-optical response in the NIR-II region, driven by the f-f transition. The maximum g-factor of R/S-Sm15Cu54 reaches 5.5 × 10-3 T-1 around 1300-1450 nm, surpassing values associated with DyIII and CuII ions. This remarkable NIR-II magneto-optical activity may be attributed to strong magnetic-dipole-allowed f-f transitions and helix chirality of the structure. This work not only presents the largest Ln-Cu clusters to date but also demonstrate the key role of magnetic-dipole-allowed transitions on magneto-optical activity.
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In order to investigate the mechanism of plant growth promoting (PGP) effects of strain Bacillus velezensis WSW007, its PGP traits and production of volatile organic compounds (VOCs) were tested. The effects of VOCs produced by strain WSW007 on plant growth were observed by co-culturing this strain with tobacco seedlings in I-plates. Meanwhile, the effects of VOCs on tobacco gene expression were analysed by a transcriptome analysis and VOCs were identified by solid phase micro extraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS) analysis. As results, strains WSW007 produced acetic acid and siderophore, and could solubilize phosphate; while it also significantly increased the fresh weight of tobacco seedlings via production of VOCs. In transcriptome analysis, plants co-cultured with strain WSW007 presented the highest up-regulated expression for the genes involved in plant growth and development processes, implying that the bacterial VOCs played a role as regulator of plant gene expression. Conclusively, the up-regulation in expression of growth- and development-related genes via VOCs production is an important PGP mechanism in strain B. velezensis WSW007.
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Bacillus , Regulación de la Expresión Génica de las Plantas , Nicotiana , Regulación hacia Arriba , Compuestos Orgánicos Volátiles , Bacillus/metabolismo , Bacillus/genética , Compuestos Orgánicos Volátiles/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crecimiento & desarrollo , Nicotiana/microbiología , Perfilación de la Expresión Génica , Cromatografía de Gases y Espectrometría de Masas , Plantones/crecimiento & desarrollo , Plantones/metabolismoRESUMEN
OBJECTIVE: Previous research has primarily focused on the incidence and mortality rates of Merkel cell carcinoma (MCC), neglecting the examination of cardiovascular mortality (CVM) risk among survivors, particularly older patients. This study aims to assess the risk of CVM in older individuals diagnosed with MCC. METHODS: Data pertaining to older MCC patients were obtained from the Surveillance, Epidemiology, and End Results database (SEER). CVM risk was measured using standardized mortality ratio (SMR) and cumulative mortality. Multivariate Fine-Gray's competing risk model was utilized to evaluate the risk factors contributing to CVM. RESULTS: Among the study population of 2,899 MCC patients, 465 (16.0%) experienced CVM during the follow-up period. With the prolongation of the follow-up duration, the cumulative mortality rate for CVM reached 27.36%, indicating that cardiovascular disease (CVD) became the second most common cause of death. MCC patients exhibited a higher CVM risk compared to the general population (SMR: 1.69; 95% CI: 1.54-1.86, p < 0.05). Notably, the SMR for other diseases of arteries, arterioles, and capillaries displayed the most significant elevation (SMR: 2.69; 95% CI: 1.16-5.29, p < 0.05). Furthermore, age at diagnosis and disease stage were identified as primary risk factors for CVM, whereas undergoing chemotherapy or radiation demonstrated a protective effect. CONCLUSION: This study emphasizes the significance of CVM as a competing cause of death in older individuals with MCC. MCC patients face a heightened risk of CVM compared to the general population. It is crucial to prioritize cardiovascular health starting from the time of diagnosis and implement personalized CVD monitoring and supportive interventions for MCC patients at high risk. These measures are essential for enhancing survival outcomes.
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Carcinoma de Células de Merkel , Enfermedades Cardiovasculares , Neoplasias Cutáneas , Humanos , Carcinoma de Células de Merkel/mortalidad , Carcinoma de Células de Merkel/epidemiología , Masculino , Anciano , Femenino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/epidemiología , Anciano de 80 o más Años , Factores de Riesgo , Programa de VERF/tendencias , Estados Unidos/epidemiología , Medición de Riesgo/métodosRESUMEN
Cyclic peptides (CPs) are emerging as promising drug candidates. Numerous natural CPs and their analogs are effective therapeutics against various diseases. Notably, many of them contain peptidyl cis-prolyl bonds. Due to the high rotational barrier of peptide bonds, conventional molecular dynamics simulations struggle to effectively sample the cis/trans-isomerization of peptide bonds. Previous studies have highlighted the high accuracy of the residue-specific force field (RSFF) and the high sampling efficiency of high-temperature molecular dynamics (high-T MD). Herein, we propose a protocol that combines high-T MD with RSFF2C and a recently developed reweighting method based on probability densities for accurate structure prediction of proline-containing CPs. Our method successfully predicted 19 out of 23 CPs with the backbone rmsd < 1.0 Å compared to X-ray structures. Furthermore, we performed high-T MD and density reweighting on the sunflower trypsin inhibitor (SFTI-1)/trypsin complex to demonstrate its applicability in studying CP-complexes containing cis-prolines. Our results show that the conformation of SFTI-1 in aqueous solution is consistent with its bound conformation, potentially facilitating its binding.
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Simulación de Dinámica Molecular , Péptidos Cíclicos , Prolina , Péptidos Cíclicos/química , Prolina/química , Tripsina/química , Tripsina/metabolismo , Temperatura , Conformación ProteicaRESUMEN
In this work, iron-containing sludge is used to prepare iron-based catalysts for efficient H2S selective catalytic oxidation. First, the effect of calcination temperatures on the catalytic activities of H2S selective oxidation is carried out and it can be found that S-500 calcined at 500 °C performs excellent catalytic activity. Then, the catalytic performance of the S-500 catalyst is further optimized using alkaline treatment with different concentrations of NaOH solution. The results indicate that S-500(2.0) treated with 2 M NaOH solution has the highest catalytic activity of H2S selective oxidation. Next, various characterization methods are used to analyze the structure and physical-chemical of the sludge-based catalysts. N2-Brunauer-Emmett-Teller (N2-BET) and X-ray photoelectron spectroscopy analyses show that the S-500(2.0) catalyst has the smallest average particle (11.17 nm), the biggest ratio of S ext/S micro(17.98) with bigger external specific surface area (49.09 m2·g-1), a higher proportion of Fe3+ species (50.88%), and surface adsorbed oxygen species (48.07%). Meanwhile, O2-TPD and CO2-TPD analysis indicates that the S-500(2.0) catalyst has a bigger value of the Oads/OTotal ratio (50.56%) and (CO2)(weak+moderate) /(CO2)Total ratio of (31.41%), indicating that there are much more oxygen vacancies and weak alkaline sites. As a result, the excellent catalytic performance of H2S selective oxidation can be attributed to its outstanding physical-chemical properties.
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Disentangling the limitations of O-O bond activation and OH* site-blocking effects on Pt sites is key to improving the intrinsic activity and stability of low-Pt catalysts for the oxygen reduction reaction (ORR). Herein, we integrate of PtFe alloy nanocrystals on a single-atom Fe-N-C substrate (PtFe@FeSAs-N-C) and further construct a ferromagnetic platform to investigate the regulation behavior of the spin occupancy state of the Pt d-orbital in the ORR. PtFe@FeSAs-N-C delivers a mass activity of 0.75 A mgPt-1 at 0.9 V and a peak power density of 1240 mW cm-2 in the fuel-cell, outperforming the commercial Pt/C catalyst, and a mass activity retention of 97%, with no noticeable current drop at 0.6 V for more than 220 h, is attained. Operando spectroelectrochemistry decodes the orbital interaction mechanism between the active center and reaction intermediates. The Pt dz2 orbital occupation state is regulated to t2g6eg3 by spin-charge injection, suppressing the OH* site-blocking effect and effectively inhibiting H2O2 production. This work provides valuable insights into designing high-performance and low-Pt catalysts via spintronics-level engineering.
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OBJECTIVE: Bladder cancer (BC), as the most common malignant tumor of the urinary tract, has a complex biological behavior. Currently, there are still some limitations in the diagnosis and treatment of BC. Despite the great progress made in immunotherapy, there is still a lack of key genes for the diagnosis of BC. Therefore, it is particularly important to explore the differentially expressed genes (DEGs) and their effectiveness on prognosis of BC with different tumor microenvironment scores. METHODS: The gene expression dataset of BC was downloaded from the Cancer Genome Atlas (TCGA) database. The correlation between clinicopathological characteristics of patients and scores of immune and stromal components was analyzed. Patients were divided into high and low score groups according to their tumor microenvironment score (Immune score, Stromal score, ESTIMATE score). DEGs between high and low score groups were identified using R software and then subjected to enrichment analyses to assess their potential biological functions and signaling pathways. The protein-protein interaction (PPI) network was constructed using the STRING database to further identify hub genes. The expression levels of hub genes in BC were verified by TCGA database. Subsequently, the hub genes were evaluated for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS), and corresponding forest plots were created. RESULTS: A total of 2346 DEGs were obtained, including 1120 up-regulated genes and 1226 down-regulated genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses found DEGs were mainly enriched in cell migration and immune-related pathways. Meanwhile, The PPI network finally yielded top 10 hub genes with predictive value, which included actin beta (ACTB), interleukin 6 (IL-6), Jun proto-oncogene (JUN), CD4 molecule (CD4), heat shock protein 90 alpha family class A member 1 (HSP90AA1), protein tyrosine phosphatase receptor type C (PTPRC), tumor protein p53 (TP53), SRC proto-oncogene (SRC), fibronectin 1 (FN1), and tumor necrosis factor (TNF). Among them, CD4, PTPRC, and SRC were potential protective factors for BC. CONCLUSION: The top 10 hub genes (ACTB, IL-6, JUN, CD4, HSP90AA1, PTPRC, TP53, SRC, FN1, TNF) obtained based on tumor microenvironment scores all had potential predictive value. Elevated expression of protective factors (CD4, PTPRC, and SRC) indicates better survival outcome of BC subjects. Further exploration of the molecular developmental mechanisms of these hub genes will help to develop novel personalized therapies and improve BC prognosis.
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Biomarcadores de Tumor , Bases de Datos Genéticas , Regulación Neoplásica de la Expresión Génica , Mapas de Interacción de Proteínas , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , Mapas de Interacción de Proteínas/genética , Regulación Neoplásica de la Expresión Génica/genética , Biomarcadores de Tumor/genética , Femenino , Perfilación de la Expresión Génica/métodos , Masculino , Redes Reguladoras de Genes , Proto-Oncogenes Mas , Biología Computacional/métodosRESUMEN
Tetrahydropyridazines constitute an important structural motif found in numerous natural products and pharmaceutical compounds. Herein, we report an aminoacylation reaction of alkenes that enables the synthesis of 1,4,5,6-tetrahydropyridazines through cooperative N-heterocyclic carbene (NHC) and photoredox catalysis. This approach involves the 6-endo-trig cyclization of N-centered hydrazonyl radicals, generated via single-electron oxidation of hydrazones, followed by a radical-radical coupling step. The mild process tolerates a wide range of common functional groups and affords a variety of tetrahydropyridazines in moderate to high yields. Preliminary investigations using chiral NHC catalysts demonstrate the potential of this protocol for asymmetric radical reactions.
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A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (hMAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards hMAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against hMAO-B with an IC50 value of 1.58 µM and potent iron-chelating ability (pFe3+ = 18.79) comparable to that of deferiprone (pFe3+ = 17.90). Molecular modeling and kinetic studies showed that 25c functions as a non-competitive hMAO-B inhibitor. According to the predicted results, compound 25c can penetrate the blood-brain barrier (BBB). Additionally, it has been proved to display significant antioxidant activity and the ability to inhibit neuronal ferroptosis. More importantly, compound 25c reduced the cognitive impairment induced by scopolamine and showed significant non-toxicity in short-term toxicity assays. In summary, compound 25c was identified as a potential anti-AD agent with hMAO-B inhibitory, iron-chelating and anti-ferroptosis activities.
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Enfermedad de Alzheimer , Cromonas , Deferiprona , Quelantes del Hierro , Inhibidores de la Monoaminooxidasa , Monoaminooxidasa , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/síntesis química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Quelantes del Hierro/farmacología , Quelantes del Hierro/química , Quelantes del Hierro/síntesis química , Deferiprona/farmacología , Deferiprona/química , Monoaminooxidasa/metabolismo , Humanos , Cromonas/química , Cromonas/farmacología , Cromonas/síntesis química , Relación Estructura-Actividad , Animales , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Ferroptosis/efectos de los fármacos , Estructura Molecular , Simulación del Acoplamiento Molecular , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Relación Dosis-Respuesta a DrogaRESUMEN
BACKGROUND: Despite the rarity of appendiceal tumors, research in this field has intensified, resulting in a growing number of studies and published papers. Surprisingly, no comprehensive bibliometric analysis has specifically addressed appendiceal tumors. AIM: To offer a thorough analysis of the current landscape and future trends in appendiceal tumor research. METHODS: In our bibliometric analysis studies, we explored the Web of Science Core Collection database. The bibliographic details of the chosen publications were automatically converted and analyzed using the bibliometric package in the R environment. Additionally, we employed VoSviewer to create cooperation network maps for countries, institutions, and authors, as well as clustering maps for keywords. Furthermore, CiteSpace, another software tool, was utilized to build dual-map overlays of journals and analyze references with citation bursts. RESULTS: Our study included 780 English-language articles published after 2010. The number of related publications and citations has increased in the past decade. The United States leads in this area, but there is a need to improve cooperation and communication among countries and institutions. Co-occurrence analysis also revealed close collaboration among different authors. Annals of Surgical Oncology was the most influential journal in this field. Analysis of references with high co-citations and references with citation bursts, consistent with analysis of keywords and hotspots, indicated that current research primarily centers on the classification and management of appendiceal mucinous neoplasms and consequent pseudomyxoma peritonei. Despite the abundance of clinical studies, a greater number of in-depth basic research studies should be conducted. CONCLUSION: Current research on appendiceal tumors focuses on classification and management of appendiceal mucinous neoplasms and pseudomyxoma peritonei. Enhanced collaboration and basic research are vital for further advancement.
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Genetic variants in genes encoding subunits of the γ-aminobutyric acid-A receptor (GABAAR) have been found to cause neurodevelopmental disorders and epileptic encephalopathy. In a patient with epilepsy and developmental delay, a de novo heterozygous missense mutation c.671 T > C (p.F224S) was discovered in the GABRB2 gene, which encodes the ß2 subunit of GABAAR. Based on previous studies on GABRB2 variants, this new GABRB2 variant (F224S) would be pathogenic. To confirm and investigate the effects of this GABRB2 mutation on GABAAR channel function, we conducted transient expression experiments using GABAAR subunits in HEK293T cells. The GABAARs containing mutant ß2 (F224S) subunit showed poor trafficking to the cell membrane, while the expression and distribution of the normal α1 and γ2 subunits were unaffected. Furthermore, the peak current amplitude of the GABAAR containing the ß2 (F224S) subunit was significantly smaller compared to the wild type GABAAR. We propose that GABRB2 variant F224S is pathogenic and GABAARs containing this ß2 mutant reduce response to GABA under physiological conditions, which could potentially disrupt the excitation/inhibition balance in the brain, leading to epilepsy.
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Discapacidades del Desarrollo , Epilepsia , Mutación Missense , Receptores de GABA-A , Humanos , Receptores de GABA-A/genética , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/fisiopatología , Células HEK293 , Epilepsia/genética , Epilepsia/fisiopatología , Masculino , FemeninoRESUMEN
Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.
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Fibrosis , Cadenas Pesadas de Miosina , Insuficiencia Renal Crónica , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/genética , Animales , Humanos , Cadenas Pesadas de Miosina/metabolismo , Cadenas Pesadas de Miosina/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Riñón/patología , Riñón/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/complicaciones , Unión Proteica , Línea Celular , Proteínas Motoras Moleculares/metabolismo , Proteínas Motoras Moleculares/genética , Modelos Animales de EnfermedadRESUMEN
Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes. Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD. Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA). Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set. Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition.
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Objective: To investigate the prognostic factors and outcomes in patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN) in Southern China. Methods: A retrospective analysis of medical records of patients with ANCA-GN admitted to Shenzhen Hospital of Southern Medical University and Nanfang Hospital of Southern Medical University between September 2011 and September 2021 was performed. The clinical presentation, biological, and renal pathology were collected. In addition, the risk factors for end-stage renal disease (ESRD) and short-term overall survival in patients with ANCA-GN were analyzed. Results: A total of 93 patients with ANCA-GN were included in the study. Of them, 91.4%, were perinuclear anti-neutrophil cytoplasmic antibodies (MPO-pANCA)-positive. Approximately one-quarter (24.7%) of patients had progressed to ESRD, and 7.5% died within six months. Most patients presented with hematuria (94.6%), proteinuria (78.5%), elevated serum creatinine (86.0%), anemia (90.3%), and increased erythrocyte sedimentation rate (ESR) (44.1%). The majority (94.6%) of patients presented with crescent formations at histopathological examination. Serum creatinine, hemoglobin, and Birmingham vasculitis activity score (BVAS) were all independent factors for ESRD (P<0.05). Moreover, while ANCA renal risk score (ARRS) has an impact on prognosis of nephropathy, it did not influence ESRD independently (P>0.05). The effect of Berden's histopathologic classification on ESRD has not been confirmed. Age at onset, ESR and cardiovascular involvement were all independent factors affecting short-term overall survival of patients with ANCA-GN (P<0.05). Conclusions: Serum creatinine, hemoglobin, and BVAS were all independent risk factors of ESRD, while ARRS and Berden's histopathologic classification were not. Age at onset, ESR, and cardiovascular involvement were independent risk factors for the overall six-month survival rate in patients with ANCA-GN.
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Krypton chloride (KrCl*) excimer lamps (222 nm) are used as a promising irradiation source to drive ultraviolet-based advanced oxidation processes (UV-AOPs) in water treatment. In this study, the UV222/peracetic acid (PAA) process is implemented as a novel UV-AOPs for the degradation of emerging contaminants (ECs) in water. The results demonstrate that UV222/PAA process exhibits excellent degradation performance for carbamazepine (CBZ), with a removal rate of 90.8 % within 45 min. Notably, the degradation of CBZ in the UV222/PAA process (90.8 %) was significantly higher than that in the UV254/PAA process (15.1 %) at the same UV dose. The UV222/PAA process exhibits superior electrical energy per order (EE/O) performance while reducing resource consumption associated with the high-energy UV254/PAA process. Quenching experiments and electron paramagnetic resonance (EPR) detection confirm that HO⢠play a dominant role in the reaction. The contributions of direct photolysis, HOâ¢, and other active species (RO⢠and 1O2) are estimated to be 5 %, 88 %, and 7 %, respectively. In addition, the effects of Cl-, HCO3-, and humic acid (HA) on the degradation of CBZ are evaluated. The presence of relatively low concentrations of Cl-, HCO3-, and HA can inhibit CBZ degradation. The UV222/PAA oxidation process could also effectively degrade several other ECs (i.e., iohexol, sulfamethoxazole, acetochlor, ibuprofen), indicating the potential application of this process in pollutant removal. These findings will propel the development of the UV222/PAA process and provide valuable insights for its application in water treatment.
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Ácido Peracético , Fotólisis , Rayos Ultravioleta , Contaminantes Químicos del Agua , Purificación del Agua , Contaminantes Químicos del Agua/química , Ácido Peracético/química , Purificación del Agua/métodos , Carbamazepina/química , Oxidación-ReducciónRESUMEN
Dysphagia has emerged as a serious health issue facing contemporary society. Consuming thickened liquids is an effective approach for improving the swallowing safety for dysphagia patients. The thickening effect of chia seed gum (CSG), a novel thickener, in different dispersing media (water, orange juice, and skim milk) was investigated. Moreover, the potential application of CSG for dysphagia management was evaluated by comparison with xanthan gum (XG) and guar gum (GG). The thickened liquids prepared with 0.4 %-1.2 % (w/v) CSG, XG, and GG could be classified into levels 1-4, 2-4, and 1-3, respectively, according to the International Dysphagia Diet Standardization Initiative (IDDSI) framework. All the thickened liquids displayed shear-thinning characteristics that facilitated safe swallowing. The viscosities (η50) of CSG dissolved in water (0.202-1.027 Pa·s) were significantly greater than those of CSG dissolved in orange juice (0.070-0.690 Pa·s) and skim milk (0.081-0.739 Pa·s), indicating that CSG had a greater thickening effect in water than in orange juice and skim milk. Compared with those prepared with GG, the thickened liquids prepared with CSG and XG exhibited greater viscoelasticity, better water-holding capacity, and more compact networks. The findings suggested that CSG can be used as a potential thickener for thickening liquid foods to manage dysphagia.