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Obeticholic acid (OCA), a semisynthetic bile acid derivative, was approved for its therapeutic use in primary biliary cirrhosis. OCA has a enterohepatic circulation and host-gut microbiota metabolic interaction, which produce various metabolites. Such metabolites, especially structural isomers of OCA, together with the need to achieve idea lower limit of quantitation (LLOQ) with minimum matrix interference, bring about significant difficulties to the bioanalysis of OCA. Herein, by applying a combination of solid-phase extraction (SPE) and ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), we introduced an approach for the bioanalysis of OCA along with its two major metabolites-glyco-OCA (GOA) and tauro-OCA (TOA) in human plasma, the full validation results of which showed excellent performance. The quantitative range is 0.2506 â¼ 100.2 ng/mL for OCA, 0.2500 â¼ 100.0 ng/mL for GOA, as well as 0.1250 â¼ 50.00 ng/mL for TOA, respectively. This method was successfully applied to the pharmacokinetic studies in healthy subjects following administration of OCA tablets.
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Ácido Quenodesoxicólico , Límite de Detección , Comprimidos , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/sangre , Ácido Quenodesoxicólico/farmacocinética , Ácido Quenodesoxicólico/química , Reproducibilidad de los Resultados , Modelos Lineales , Extracción en Fase Sólida/métodos , MasculinoRESUMEN
Background: Colorectal cancer (CRC) is an aggressive primary intestinal malignancy with the third-highest incidence and second-highest mortality among all cancer types worldwide. Transcription factors (TFs) regulate cell development and differentiation owing to their ability to recognize specific DNA sequences upstream of genes. Numerous studies have demonstrated a strong correlation between TFs, the etiology of tumors, and therapeutic approaches. Here, we aimed to explore prognosis-related TFs and comprehend their carcinogenic mechanisms, thereby offering novel insights into the diagnosis and management of CRC. Materials and Methods: Differentially expressed TFs between CRC and normal tissues were identified leveraging The Cancer Genome Atlas database, Weighted correlation network analysis and Cox regression analysis were performed to identify prognosis-related TFs. The cellular functions of hub TF zinc finger E-box binding homeobox 1 (ZEB1) were determined using by 5-ethynyl-2'-deoxyuridine and cell invasion assays in CRC cells. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment, and gene set enrichment analyses were used to identify the cellular processes in which ZEB1 participates. Immunoaffinity purification, silver staining mass spectrometry, and a chromatin immunoprecipitation assay were conducted to search for proteins that might interact with ZEB1 and the target genes they jointly regulate. Results: Thirteen central TFs related to prognosis were identified through bioinformatics analysis techniques. Among these TFs, ZEB1 emerged as the TF most closely associated with CRC, as determined through a combination of regulatory network diagrams, survival curves, and phenotype analyses. ZEB1 promotes CRC cell growth by recruiting the NuRD(MTA1) complex, and the ZEB1/NuRD(MTA1) complex transcriptionally represses glycolysis-associated tumor suppressor genes. Conclusion: Our study not only identified a hub biomarker related to CRC prognosis but also revealed the specific molecular mechanisms through which ZEB1 affects cancer progression. These insights provide crucial evidence for the diagnosis of CRC and potential treatment opportunities.
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The metastasis-associated protein (MTA) family plays a crucial role in the development of breast cancer, a common malignancy with a high incidence rate among women. However, the mechanism by which each member of the MTA family contributes to breast cancer progression is poorly understood. In this study, we aimed to investigate the roles of MTA1, MTA3, and tripartite motif-containing 21 (TRIM21) in the proliferation, invasion, epithelial-mesenchymal transition (EMT), and stem cell-like properties of breast cancer cells in vivo and in vitro. The molecular mechanisms of the feedback loop between MTA1 and MTA3/TRIM21 regulated by estrogen were explored using Chromatin immunoprecipitation (ChIP), luciferase reporter, immunoprecipitation (IP), and ubiquitination assays. These findings demonstrated that MTA1 acts as a driver to promote the progression of breast cancer by repressing the transcription of tumor suppressor genes, including TRIM21 and MTA3. Conversely, MTA3 inhibited MTA1 transcription and TRIM21 regulated MTA1 protein stability in breast cancer. Estrogen disrupted the balance between MTA1 and MTA3, as well as between MTA1 and TRIM21, thereby affecting stemness and the EMT processes in breast cancer. These findings suggest that MTA1 plays a vital role in stem cell fate and the hierarchical regulatory network of EMT through negative feedback loops with MTA3 or TRIM21 in response to estrogen, supporting MTA1, MTA3, and TRIM21 as potential prognostic biomarkers and MTA1 as a treatment target for future breast cancer therapies.
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Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Estrógenos , Histona Desacetilasas , Células Madre Neoplásicas , Proteínas Represoras , Transactivadores , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Femenino , Proteínas Represoras/metabolismo , Proteínas Represoras/genética , Transactivadores/metabolismo , Transactivadores/genética , Estrógenos/farmacología , Estrógenos/metabolismo , Histona Desacetilasas/metabolismo , Histona Desacetilasas/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Animales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Retroalimentación Fisiológica/efectos de los fármacos , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Ratones Desnudos , Células MCF-7 , Ratones Endogámicos BALB C , Proteínas de NeoplasiasRESUMEN
Deregulation of E3 ubiquitin ligases drives the proliferation and metastasis of various cancers; however, the underlying mechanisms remain unknown. This study aimed to investigate the role of tripartite motif-containing 22 (TRIM22), a poorly investigated E3 ubiquitin ligase in the TRIM family, as a tumor suppressor in breast cancer. High expression of TRIM22 in breast cancer correlated with better prognosis. Functional experiments demonstrated that TRIM22 significantly inhibited the proliferation and invasion of breast cancer cells. Label-free proteomics and biochemical analyses revealed that the copper chaperone for superoxide dismutase (CCS), an oncoprotein that is upregulated in breast cancer and promotes the growth and invasion of breast cancer cells, was a target of TRIM22 for degradation via K27-linked ubiquitination. Notably, the ability of the coiled-coil domain-defective mutants of TRIM22 to induce CCS ubiquitination and degradation diminished, with lysine 76 of the CCS serving as the ubiquitination site. Moreover, the TRIM22-mediated inhibition of the proliferation and invasion of breast cancer cells was restored by ectopic CCS expression. RNA-sequencing experiments using Gene Set Enrichment Analysis demonstrated that TRIM22 is involved in the JAK-STAT signaling pathway. TRIM22 overexpression also improved reactive oxygen species levels in breast cancer cells and inhibited STAT3 phosphorylation, which was restored via CCS overexpression or N-acetyl-l-cysteine treatment. Chromatin immunoprecipitation-quantitative polymerase chain reaction results showed that TRIM22 overexpression decreased the enrichment of phosphorylated STAT3 in FN1, VIM and JARID2 promoters. Clinically, low TRIM22 expression correlated with high CCS expression and decreased survival rates in patients with breast cancer. Moreover, TRIM22 upregulation was associated with a better prognosis in patients with breast cancer who received classical therapy. TRIM22 expression was downregulated in many cancer types, including colon, kidney, lung, and prostate cancers. To the best of our knowledge, the E3 ubiquitin ligase TRIM22 was first reported as a tumor suppressor that inhibits the proliferation and invasion of breast cancer cells through CCS ubiquitination and degradation. TRIM22 is a potential prognostic biomarker in patients with breast cancer.
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Neoplasias de la Mama , Proliferación Celular , Antígenos de Histocompatibilidad Menor , Factor de Transcripción STAT3 , Transducción de Señal , Proteínas de Motivos Tripartitos , Ubiquitinación , Femenino , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Células MCF-7 , Antígenos de Histocompatibilidad Menor/genética , Antígenos de Histocompatibilidad Menor/metabolismo , Invasividad Neoplásica , Pronóstico , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteolisis , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Proteínas de Motivos Tripartitos/genética , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Background: Cancers arise from genetic and epigenetic abnormalities that affect oncogenes and tumor suppressor genes, compounded by gene mutations. The N6-methyladenosine (m6A) RNA modification, regulated by methylation regulators, has been implicated in tumor proliferation, differentiation, tumorigenesis, invasion, and metastasis. However, the role of m6A modification patterns in the tumor microenvironment of gastric cancer (GC) remains poorly understood. Materials and methods: In this study, we analyzed m6A modification patterns in 267 GC samples utilizing 31 m6A regulators. Using consensus clustering, we identified two unique subgroups of GC. Patients with GC were segregated into high- and low-infiltration cohorts to evaluate the infiltration proportions of the five prognostically significant immune cell types. Leveraging the differential genes in GC, we identified a "green" module via Weighted Gene Co-expression Network Analysis. A risk prediction model was established using the LASSO regression method. Results: The "green" module was connected to both the m6A RNA methylation cluster and immune infiltration patterns. Based on "Module Membership" and "Gene Significance", 37 hub genes were identified, and a risk prediction model incorporating nine hub genes was established. Furthermore, methylated RNA immunoprecipitation and RNA Immunoprecipitation assays revealed that YTHDF1 elevated the expression of DNMT3B, which synergistically promoted the initiation and development of GC. We elucidated the molecular mechanism underlying the regulation of DNMT3B by YTHDF1 and explored the crosstalk between m6A and 5mC modification. Conclusion: m6A RNA methylation regulators are instrumental in malignant progression and the dynamics of tumor microenvironment infiltration of GC. Assessing m6A modification patterns and tumor microenvironment infiltration characteristics in patients with GC holds promise as a valuable prognostic biomarker.
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Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
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Adyuvantes Inmunológicos , Modelos Animales de Enfermedad , Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Animales , Adyuvantes Inmunológicos/administración & dosificación , Vacunas contra la Tuberculosis/inmunología , Vacunas contra la Tuberculosis/administración & dosificación , Mycobacterium tuberculosis/inmunología , Ratones , Femenino , Antígenos Bacterianos/inmunología , Aciltransferasas/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Proteínas Bacterianas/inmunología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Tuberculosis Latente/inmunología , Ratones Endogámicos BALB C , Administración IntranasalRESUMEN
Surface Plasmon Resonance (SPR) technology, as a powerful analytical tool, plays a crucial role in the preparation, performance evaluation, and biomedical applications of nanoparticles due to its real-time, label-free, and highly sensitive detection capabilities. In the nanoparticle preparation process, SPR technology can monitor synthesis reactions and surface modifications in real-time, optimizing preparation techniques and conditions. SPR enables precise measurement of interactions between nanoparticles and biomolecules, including binding affinities and kinetic parameters, thereby assessing nanoparticle performance. In biomedical applications, SPR technology is extensively used in the study of drug delivery systems, biomarker detection for disease diagnosis, and nanoparticle-biomolecule interactions. This paper reviews the latest advancements in SPR technology for nanoparticle preparation, performance evaluation, and biomedical applications, discussing its advantages and challenges in biomedical applications, and forecasting future development directions.
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Nanopartículas , Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Nanopartículas/química , Humanos , Sistemas de Liberación de Medicamentos/métodosRESUMEN
Antral follicle size is a useful predictive marker of the competency of enclosed oocytes for yielding an embryo following in vitro maturation and fertilization. However, the molecular mechanisms underpinning oocyte developmental potential during bovine antral follicle growth are still unclear. Here, we used a modified single-cell multi-omics approach to analyze the transcriptome, DNA methylome and chromatin accessibility in parallel for oocytes and cumulus cells collected from bovine antral follicles of different sizes. Transcriptome profiling identified three types of oocytes (Small, Medium and Large) that underwent different developmental trajectories, with Large oocytes exhibiting the largest average follicle size and characteristics resembling metaphase-II oocytes. Differential expression analysis and real-time PCR assay showed that most replication-dependent histone genes were highly expressed in Large oocytes. The joint analysis of multi-omics data revealed that the transcription of 20 differentially expressed genes in Large oocytes was associated with both DNA methylation and chromatin accessibility. In addition, oocyte-cumulus interaction analysis showed that inflammation, DNA damage, and p53 signaling pathways were active in Small oocytes, which had the smallest average follicle sizes. We further confirmed that p53 pathway inhibition in in vitro maturation experiments using oocytes obtained from small antral follicles could improve the quality of oocytes and increased the blastocyte rate after in vitro fertilization and culture. Our work provides new insights into the intricate orchestration of bovine oocyte fate determination during antral folliculogenesis, which is instrumental for optimizing in vitro maturation techniques to optimize oocyte quality.
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Honey is not equivalent to sugar and possess a worldwide health promoting effects such as antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. Nevertheless, the potential impacts of honey on high-fat diet induced chronic kidney disease (CKD) and gut microbiota remain to be explored. Herein a high-fat diet was used to induce a mouse CKD model, and analysis was conducted on liver, kidney, spleen indices, tissue morphology, biochemical parameters, CKD related genes, and gut microbial diversity. The results indicated that significant inhibitory effects on renal damage caused by a high-fat diet in mice and improvement in disease symptoms were observed upon honey treatment. Significant changes were also found in serum TC, TG, UA, and BUN as well as the inflammation-related protein TNF-α and IL-6 levels in renal tissues. Gene expression analysis revealed that honey intake closely relates to gut microbiota diversity, which can regulate the composition of gut microbiota, increase microbial diversity, especially Bifidobacteriales and S24_7 and promote the synthesis of short chain fatty acids (SCFAs). In summary, this study suggests that honey has both preventive and therapeutic effects on CKD, which may be associated with its ability to improve microbial composition, increase microbial diversity, and regulate SCFAs levels.
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Dieta Alta en Grasa , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Miel , Ratones Endogámicos C57BL , Polifenoles , Insuficiencia Renal Crónica , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/microbiología , Ratones , Dieta Alta en Grasa/efectos adversos , Masculino , Polifenoles/farmacología , Riñón/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismoRESUMEN
Flexible composite film has gained increasing attention in the fields of wearable devices and portable electronic products. In this work, a novel core-shell structure of cellulose nanofibers/BaTiO3@TiO2 (CNF/BTO@TiO2) was synthesized with the assistant of the biological macromolecule material of cellulose nanofiber (CNF), in which the CNF can improve the stability and dispersibility of BaTiO3 (BTO) in the aqueous phase and elevate the integrity of the core-shell structure. The core-shell structure can reduce the agglomeration of fillers in polyvinylidene fluoride (PVDF) and improve the structural defects of the composite film. Meanwhile, the core-shell structure can promote the polarization of the electric dipole and the formation of ß phase in PVDF due to the generated interface spatial polarization between the shell of TiO2 and the core of BTO. When the content of the core-shell structure was 5 wt%, the ß phase content reaches 61.89 %, and the piezoelectric coefficient of composite film reaches 84.29 pm/V. Thus the maximum output open-circuit voltage (VOC) and short-circuit current (ISC) of the piezoelectric composite film is as high as 13.10 V and 464.3 nA. In addition, its excellent pressure sensing capability allows for its application in various flexible electronic devices.
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Compuestos de Bario , Celulosa , Nanofibras , Polivinilos , Titanio , Titanio/química , Nanofibras/química , Polivinilos/química , Compuestos de Bario/química , Celulosa/química , Electricidad , Polímeros de FluorocarbonoRESUMEN
Spherical movable tensegrity robots, resorting to the intrinsic hallmark of being lightweight and resilient, have exhibited tremendous potential in exploring unpredictable terrains and extreme environments where traditional robots often struggle. The geometry of spherical tensegrities is suitable for rolling locomotion, which guarantees the system to react to changing demands, navigate unexplored terrain, and perform missions even after suffering massive damage. The objective of this article is to enrich the type of spherical movable tensegrity robots with multiple kinematic gait patterns and to gain superior motion paths that are in conformity with the intrinsic features of structural rolling locomotion. Aiming at this purpose, three 12-rod spherical tensegrities with multi-gait patterns are investigated, and the dynamic simulation on independent (or evolutionary) gait patterns is conducted and testified on ADAMS. The routing spaces and the blind zones formed by single kinematic gait are compared to assess the suitability of the assigned kinematic gait pattern. Accordingly, we develop a trajectory planning method with the embedding of the steering control strategy into a modified rapidly exploring random tree (MRRT) algorithm to produce qualified marching routes. In the meantime, two momentous evaluation indictors, applicable to multi-gaits tensegrities, are introduced in searching the corresponding optimal gait patterns that conform to specified needs. The techniques are illustrated and validated in simulation with comparisons on several prototypes of tensegrity robots, indicating that the proposed method is a viable means of attaining marching routes on rolling locomotion of spherical movable tensegrity robots.
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The aim of the present study was to explore the association between N6methyladenosine (m6A) modification regulatory generelated long noncoding (lnc)RNA RP1228H13.5 and cancer prognosis through bioinformatics analysis, as well as the impact of RP1228H13.5 on cell biologyrelated behaviors and specific molecular mechanisms. Bioinformatics analysis was used to construct a risk model consisting of nine genes. This model can reflect the survival time and differentiation degree of cancer. Subsequently, a competing endogenous RNA network consisting of 3 m6Arelated lncRNAs, six microRNAs (miRs) and 201 mRNAs was constructed. A cell assay confirmed that RP1228H13.5 is significantly upregulated in liver cancer cells, which can promote liver cancer cell proliferation, migration and invasion, and inhibit liver cancer cell apoptosis. The specific molecular mechanism may be the regulation of the expression of zinc finger protein interacting with K protein 1 (ZIK1) by targeting the downstream hsamiR205. Further experiments found that the m6A methyltransferase 14, N6adenosinemethyltransferase subunit mediates the regulation of miR2055p expression by RP1228H13.5. m6A methylation regulatory factorrelated lncRNA has an important role in cancer. The targeting of hsamiR205 by RP1228H13.5 to regulate ZIK1 may serve as a potential mechanism in the occurrence and development of liver cancer.
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Adenina/análogos & derivados , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , Neoplasias Hepáticas/genética , Metiltransferasas/genética , ARN Largo no Codificante/genética , Proteínas Asociadas a MicrotúbulosRESUMEN
Caspase-11 detection of intracellular lipopolysaccharide mediates non-canonical pyroptosis, which could result in inflammatory damage and organ lesions in various diseases such as sepsis. Our research found that lactate from the microenvironment of acetaminophen-induced acute liver injury increased Caspase-11 levels, enhanced gasdermin D activation and accelerated macrophage pyroptosis, which lead to exacerbation of liver injury. Further experiments unveiled that lactate inhibits Caspase-11 ubiquitination by reducing its binding to NEDD4, a negative regulator of Caspase-11. We also identified that lactates regulated NEDD4 K33 lactylation, which inhibits protein interactions between Caspase-11 and NEDD4. Moreover, restraining lactylation reduces non-canonical pyroptosis in macrophages and ameliorates liver injury. Our work links lactate to the exquisite regulation of the non-canonical inflammasome, and provides a basis for targeting lactylation signaling to combat Caspase-11-mediated non-canonical pyroptosis and acetaminophen-induced liver injury.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Piroptosis , Humanos , Acetaminofén/toxicidad , Caspasas Iniciadoras/metabolismo , Caspasas/metabolismo , Ácido LácticoRESUMEN
BACKGROUND: Sarcopenia is a senile syndrome of age-related muscle loss. It is thought to affect the development of chronic kidney disease and has a serious impact on the quality of life of the elder adults. Little is known about the association between sarcopenia and new-onset chronic kidney disease in middle-aged and elder adults. Using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted a longitudinal analysis to investigate the association between sarcopenia status and new-onset chronic kidney disease in middle-aged and elder adults in China. METHODS: The study population consisted of 3676 participants aged 45 or older selected from 2011 CHARLS database who had no history of chronic kidney disease at the baseline and completed the follow-up in 2015. A multivariate cox regression model was employed to examine the association between sarcopenia and the incidence of new-onset chronic kidney disease. RESULTS: Followed up for 4 years, a total of 873 (22.5%) new cases of chronic kidney disease occurred. Among them, participants diagnosed with sarcopenia (HR1.45; 95% CI 1.15-1.83) were more likely to develop new-onset chronic kidney disease than those without sarcopenia. Similarly, patients with sarcopenia were more likely to develop new-onset chronic kidney disease than those with possible sarcopenia (HR 1.27; 95%CI 1.00-1.60). Subgroup analysis revealed that elder adults aged between 60 and 75 years old (HR 1.666; 95%CI 1.20-22.28), with hypertension (HR 1.57; 95%CI 1.02-2.40), people with sarcopenia had a significantly higher risk of developing new-onset chronic kidney disease than those without sarcopenia (all P < 0.05). CONCLUSION: Middle-aged and elder adults diagnosed with sarcopenia have a higher risk of developing new-onset chronic kidney disease.
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Insuficiencia Renal Crónica , Sarcopenia , Humanos , Persona de Mediana Edad , Anciano , Jubilación , Estudios Longitudinales , Calidad de Vida , ChinaRESUMEN
Injectable materials have attracted great attention in the manufacture of in situ forming hydrogels for biomedical applications. In this study, a facile method to prepare methacrylic anhydride (MA)-modified sodium carboxymethyl cellulose (CMC) as an injectable material for the fabrication of hydrogels with controllable properties is reported. The chemical structure of the series of MA-grafted CMC (CMCMAs) with different MA contents was confirmed by Fourier transform infrared and nuclear magnetic resonance spectroscopy, and the properties of CMCMAs were characterized. Then, the CMCMAs gel (CMCMAs-G) was fabricated by crosslinking of MA under blue light irradiation. The gelation performances, swelling behaviors, transmittance, surface porous structures and mechanical properties of CMCMAs-G can be controlled by varying the content of MA grafted on the CMC. The compressive strength of CMCMAs-G was measured by mechanical compressibility tests and up to 180 kPa. Furthermore, the in vitro cytocompatibility evaluation results suggest that the obtained CMCMAs-G exhibit good compatibility for cell proliferation. Hence, our strategy provides a facile approach for the preparation of light-sensitive and an injectable CMC-derived polymer to fabricate hydrogels for biomedical applications.
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Carboximetilcelulosa de Sodio , Hidrogeles , Hidrogeles/química , Carboximetilcelulosa de Sodio/química , Metacrilatos , Espectroscopía de Resonancia Magnética , SodioRESUMEN
This study developed an efficient and stable landfill leachate treatment process, which was based on the combination of biochar catalytic ozonation and activated sludge technology for intensive treatment of landfill leachate, aiming to achieve the standard discharge of leachate. The focus is to investigate the effect of manganese loading on the physicochemical properties of biochar and the mechanism of its catalytic ozonation. It was found that more surface functional groups (CO, Mn-O, etc.) and defects (ID/IG = 1.27) were exposed via the change of original carbon structure by loading Mn, which is conducive to the generation of lattice oxygen. Meanwhile, generating different valence states of Mn metal can improve the redox properties and electron migration rate, and encourage the production of reactive oxygen species (ROS) during the reaction process and enhance the catalytic efficiency. The synergistic action of microorganisms, especially denitrifying bacteria, was found to play a key role in the degradation of nitrogenous pollutants during the activated sludge process. The concentration of NH+4-N was reduced from the initial 1087.03 ± 9.56 mg/L to 9.05 ± 1.91 mg/L, while COD was reduced from 2290 ± 14.14 mg/L to 86.5 ± 2.12 mg/L, with corresponding removal rates of 99.17% and 99.20%, respectively. This method offers high efficiency and stability, achieving discharge standards for leachate (GB16889-2008). The synergy between Mn-loaded biochar and microorganisms in the activated sludge is key to effective treatment. This study offers a new approach to solving the challenge of waste leachate treatment.
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Carbón Orgánico , Ozono , Contaminantes Químicos del Agua , Ozono/química , Manganeso , Contaminantes Químicos del Agua/química , Aguas del AlcantarilladoRESUMEN
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.
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Constructed wetlands (CWs) are widely used to treat wastewater, while innovative studies are needed to support resource conservation, enhance multi-functionality, and improve the effectiveness of effluent usage. This study assessed the potential of CW's multiple functions by combining low-rank coal (lignite) and industrial waste (steel slag) in different configurations as CW substrates. The results of scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and metagenomic sequencing showed that the experimental treatment with lignite and steel slag mixtures had the highest multi-functionality, including efficient nutrient removal and carbon sequestration, as well as hydroponic crop production. Lignite and steel slag were mixed to form lignite-steel slag particle clusters, where Ca2+ dissolved on the surface of steel slag was combined with PO43- in wastewater to form Ca3(PO4)2 precipitation for phosphorus removal. A biofilm grew on the surface of lignite in this cluster, and OH- released from steel slag promoted lignite to release fulvic acid, which provided a carbon source for heterotrophic microorganisms and promoted denitrification. Moreover, fulvic acid enhanced carbon sequestration in CWs by increasing the biomass of Phragmites australis. The effluent from lignite-steel slag CW increased cherry tomato yield and quality while saving N and P applications. These results provide new ideas for the "green" and economic development of CW technology.
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Aguas Residuales , Humedales , Acero/química , Carbón Mineral , Eliminación de Residuos Líquidos/métodos , Fósforo/químicaRESUMEN
BACKGROUND: Bone mineral density (BMD) is important for the outcome of cervical spine surgery. As the gold standard of assessing BMD, dual-energy X-ray absorptiometry scans are often not ordered or go unreviewed in patients' charts. As the supplement, MRI-based vertebral bone quality (VBQ) was found to accurately predict osteopenia/osteoporosis and postoperative complications in lumbar spine. However, discussion of the efficiency of VBQ in cervical spine is lacking. And measurement methods of VBQ in cervical spine are diverse and not universally acknowledged like lumbar spine. We aimed to compare the predictive performance of three kinds of different Cervical-VBQ (C-VBQ) scores for bone mineral density assessment in patients undergoing cervical spine surgery. HU value of cervical spine was set as a reference. METHODS: Adult patients receiving cervical spine surgery for degenerative diseases were retrospectively included between Jan 2015 and Dec 2022 in our hospital. The VBQ scores and HU value were measured from preoperative MRI and CT. The correlation between HU value/C-VBQs (named C-VBQ1/2/3 according to different calculating methods) and DEXA T-score was analyzed using univariate linear correlation and Pearson's correlation. We evaluated the predictive performance of those two parameters and achieved the most appropriate cutoff value by comparing the receiver operating characteristic (ROC) curves. RESULTS: 106 patients (34 patients with T ≥ - 1.0 vs 72 patients with T < - 1.0) were included (mean age: 51.95 ± 10.94, 48 men). According to Pearson correlation analysis, C-VBQ1/2/3 and HU value were all significantly correlated to DEXA T-score (Correlation Coefficient (r): C-VBQ1: - 0.393, C-VBQ2: - 0.368, C-VBQ3: - 0.395, HU value: 0.417, p < 0.001). The area under the ROC curve (AUC) was calculated (C-VBQ1: 0.717, C-VBQ2: 0.717, C-VBQ3: 0.727, HU value: 0.746). The AUC of the combination of C-VBQ3 and HU value was 0.786. At last, the most appropriate cutoff value was determined (C-VBQ1: 3.175, C-VBQ2: 3.005, C-VBQ3: 2.99, HU value: 299.85 HU). CONCLUSIONS: Different MRI-based C-VBQ scores could all be potential and alternative tools for opportunistically screening patients with osteopenia and osteoporosis before cervical spine surgery. Among them, C-VBQ calculated in ASIC2-C7/SIT1-CSF performed better. We advised patients with C-VBQ higher than cutoff value to accept further BMD examination.