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The pathophysiological mechanisms involved in fibrotic interstitial lung diseases (FILDs) are akin to those observed in idiopathic pulmonary fibrosis (IPF), implying the potential for shared therapeutic approaches. Pirfenidone exhibits antifibrotic and anti-inflammatory properties, making it the first small-molecule drug approved for treating IPF. Pirfenidone has been utilized in IPF treatment for more than one decade. However, guidelines for progressive pulmonary fibrosis (PPF) treatment suggest that further research and evidence are needed to fully comprehend its efficacy and safety across various PPF subtypes. In recent years, numerous studies have explored the use of pirfenidone in treating non-IPF FILD. Herein, we provide an overview of the latest research data on application of pirfenidone in occupational-related ILD, connective tissue disease-associated ILD, post-coronavirus disease-2019 pulmonary fibrosis, and other conditions. We summarize the level of evidence and highlight challenges associated with using pirfenidone in different FILDs to offer clinical guidance.
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The microfluidic method primainly utilizes two incompatible liquids as continuous phase and dispersed phase respectively. It controls the formation of droplets by managing the microchannel structure and the flow rate ratio of the two phases. Droplet-based microfluidics is a rapidly expanding interdisciplinary research field encompassing physics, biochemistry, and Microsystems engineering. Droplet microfluidics offer a diverse and practical toolset that enables chemical and biological experiments to be conducted at high speeds and with greater efficiency compared to traditional instruments. The applications of droplet-based microfluidics are vast, including areas such as drug delivery, owing to its compatibility with numerous chemical and biological reagents and its ability to carry out various operations. This technology has been extensively researched due to its promising features. In this review, we delve into the materials used in droplet generation-based microfluidic devices, manufacturing techniques, methods for droplet generation in channels, and, finally, we summarize the applications of droplet generation-based microfluidics in drug delivery vectors, encompassing nanoparticles, microspheres, microcapsules, and hydrogel particles. We also discuss the challenges and future prospects of this technology across a wide array of applications.
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Sistemas de Liberación de Medicamentos , Microfluídica , Sistemas de Liberación de Medicamentos/métodos , Microfluídica/métodos , Humanos , Nanopartículas/química , Dispositivos Laboratorio en un Chip , Hidrogeles/química , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/instrumentaciónRESUMEN
While sodium hypochlorite (NaClO) has long been used to disinfect drinking water, concerns have risen over its use due to causing potentially hazardous byproducts. Catalytic ozonation with metal-free catalysts has attracted increasing attention to eliminate the risk of secondary pollution of byproducts in water treatment. Here, we compared the disinfection efficiency and microbial community of catalytic ozone with a type of metal-free catalyst fluorinated ceramic honeycomb (FCH) and NaClO disinfectants under laboratory- and pilot-scale conditions. Under laboratory conditions, the disinfection rate of catalytic ozonation was 3â¼6-fold that of ozone when the concentration of Escherichia coli was 1 × 106 CFU/ml, and all E. coli were killed within 15 s. However, 0.65 mg/L NaClO retained E. coli after 30 min using the traditional culturable approach. The microorganism inactivation results of raw reservoir water disinfected by catalytic ozonation and ozonation within 15 s were incomparable based on the cultural method. In pilot-scale testing, catalytic ozonation inactivated all environmental bacteria within 4 min, while 0.65 mg/L NaClO could not achieve this success. Both catalytic ozonation and NaClO-disinfected methods significantly reduced the number of microorganisms but did not change the relative abundances of different species, i.e., bacteria, viruses, eukaryotes, and archaea, based on metagenomic analyses. The abundance of virulence factors (VFs) and antimicrobial resistance genes (ARGs) was detected few in catalytic ozonation, as determined by metagenomic sequencing. Some VFs or ARGs, such as virulence gene 'FAS-II' which was hosted by Mycobacterium_tuberculosis, were detected solely by the NaClO-disinfected method. The enriched genes and pathways of cataO3-disinfected methods exhibited an opposite trend, especially in human disease, compared with NaClO disinfection. These results indicated that the disinfection effect of catalytic ozone is superior to NaClO, this finding contributed to the large-scale application of catalytic ozonation with FCH in practical water treatment.
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Cerámica , Desinfectantes , Desinfección , Agua Potable , Ozono , Hipoclorito de Sodio , Purificación del Agua , Ozono/química , Desinfectantes/farmacología , Agua Potable/microbiología , Agua Potable/química , Desinfección/métodos , Cerámica/química , Purificación del Agua/métodos , Hipoclorito de Sodio/farmacología , Hipoclorito de Sodio/química , Catálisis , Halogenación , Escherichia coli/efectos de los fármacos , Proyectos Piloto , Microbiología del Agua , Bacterias/efectos de los fármacosRESUMEN
Elevated levels of superoxide anion radicals (O2·-) have been implicated in the pathogenesis of a variety of diseases, such as cancer, inflammatory diseases and autoimmune diseases. To determine the O2·- concentration for assisting disease detection, a method based on surface-enhanced Raman scattering (SERS) combined with transparent polymer microneedles has been developed. Photocrosslinked NOA61 is used to prepare microneedles with sulfhydryl group, which can contribute to anchor gold nanoparticles (Au NPs) functionalized by p-mercaptobenzoic acid (PATP). This work successfully constructed SERS microneedles for in situ detection. A REDOX reaction occurred between PATP and O2·-, resulting in the formation of dimethylaminoborane (DMAB) and a subsequent change in Raman signal. Based on the quantitative relationship between the change of peak area ratio at 1042 cm-1 and 1077 cm-1 and the concentration change of O2·-, a standard curve with a linear range of 0-480 ng/mL was constructed. The SERS microneedles were effectively employed to track melanoma progression in mice, establishing a fundamental correlation between O2·- concentration and melanoma stage, as confirmed by ELISA. The benefits of this approach, including convenience, in situ applicability, and low cost, are anticipated to offer novel insights for non-invasive in situ detection, potentially enhancing disease monitoring and diagnosis.
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Oro , Nanopartículas del Metal , Agujas , Espectrometría Raman , Superóxidos , Animales , Espectrometría Raman/métodos , Superóxidos/análisis , Oro/química , Nanopartículas del Metal/química , Ratones , Mutación , Melanoma/diagnóstico , Compuestos de Sulfhidrilo/química , Melanoma Experimental/diagnóstico , Melanoma Experimental/patología , Límite de Detección , Ratones Endogámicos C57BLRESUMEN
Background: Although Shen Gui capsules (SGCP) are widely used as an adjuvant treatment for chronic heart failure (CHF), their clinical efficacy and safety remain controversial. Purpose: To assess the efficacy and safety of SGCP in the treatment of CHF through a systematic review and meta-analysis, to provide high-quality evidence for evidence-based medicine. Methods: Seven databases were searched for randomized controlled trials (RCTs) assessing SGCP for CHF, from inception to 9 January 2023. RCT quality of evidence was evaluated using the Cochrane Handbook for the Evaluation of Intervention Systems to assess risk of bias and Grading of Recommendations Assessment, Development, and Evaluation. A meta-analysis with subgroup and sensitivity analyses was performed using Review Manager 5.4 and Stata 12. Results: Nine RCTs representing 888 patients with CHF were included in the review. Meta-analysis revealed that SGCP combined with conventional heart failure therapy is more advantageous for improving left ventricular ejection fraction [LVEF; mean difference (MD) = 5.26, 95% confidence interval (CI) (3.78, 6.74), p < 0.0000] and increasing effective rate [relative risk (RR) = 1.21, 95%CI (1.14, 1.29), p < 0.001] compared with conventional therapy alone. The experimental treatment also reduced brain natriuretic peptide [MD = -100.15, 95%CI (-157.83, -42.47), p = 0.0007], left ventricular end-diastolic diameter [MD = -1.93, 95%CI (-3.22, -0.64), p = 0.003], and hypersensitive C-reactive protein [MD = -2.70, 95%CI (-3.12,-2.28), p < 0.001] compared with the control group. However, there was not a statistically significant difference in tumor necrosis factor-α [MD = -14.16, 95%CI (-34.04, 5.73), p = 0.16] or left ventricular end-systolic diameter [MD = -1.56, 95%CI (-3.13, 0.01), p = 0.05]. Nor was there a statistically significant between-groups difference in incidence of adverse events (p > 0.05). Conclusion: SGCP combined with conventional heart failure therapy can improve LVEF and increase the effective rate to safely treat patients with CHF. However, further high-quality studies are needed to confirm these findings, due to the overall low quality of evidence in this literature.Clinical Trial Registration: https://www.crd.york.ac.uk/PROSPERO/logout.php, PROSPERO [CRD42023390409].
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Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug.
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Ginsenósidos , Daño por Reperfusión Miocárdica , Ratas , Ratones , Animales , Daño por Reperfusión Miocárdica/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Apoptosis , Miocitos Cardíacos/metabolismoRESUMEN
The frequent detection of persistent per- and polyfluoroalkyl substances (PFAS) in organisms and environment coupled with surging evidence for potential detrimental impacts, have attracted widespread attention throughout the world. In order to reveal research hotspots and trends of technologies for PFAS removal, herein, we performed a data-driven analysis of 3975 papers and 436 patents from Web of Science Core Collection and Derwent Innovation Index databases up to 2023. The results showed that China and the USA led the way in the research of PFAS removal with outstanding contributions to publications. The progression generally transitioned from accidental discovery of decomposition, to experimentation with removal effects and mechanisms of existing methods, and finally to enhanced defluorination and mechanism-driven design approaches. The keywords co-occurrence network and technology classification together revealed the main knowledge framework, which was constructed and correlated through contaminants, substrates, materials, processes and properties. Moreover, adsorption was demonstrated to be the dominant removal process among the current studies. Subsequently, we concluded the principles, advances and drawbacks of enrichment and separation, biological methods, advanced oxidation and reduction processes. Further exploration indicated the hotspots such as alternatives and precursors for PFAS ("genx": 1.258, "f-53b": 0.337), degradable mineralization technologies ("photocatalytic degrad": 0.529, "hydrated electron": 0.374), environment-friendly remediation technologies ("phytoremedi": 0.939, "constructed wetland": 0.462) and combination with novel materials ("metal-organic framework": 1.115, "layered double hydroxid": 0.559) as well as computer science ("molecular dynamics simul": 0.559, "machine learn"). Furthermore, the future direction of technological innovation might lie in high-performance processes that minimize secondary pollution, the development of recyclable and renewable treatment agents, and collaborative control strategies for multiple pollutants. Overall, this study offers comprehensive and objective review for researchers and industry professionals in this field, enabling rapid access to knowledge guidance and insights into research frontiers.
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Fluorocarburos , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/análisis , Fluorocarburos/análisis , Fluorocarburos/química , Restauración y Remediación Ambiental/métodos , Restauración y Remediación Ambiental/tendencias , AdsorciónRESUMEN
Background: As a ribosome receptor, LRRC59 was thought to regulate mRNA translation on the ER membrane. Evidence suggests that LRRC59 is overexpressed in a number of human malignancies and is associated with poor prognoses, but its primary biological function in the development of oral squamous cell carcinoma (OSCC) remains obscure. Objective: The purpose of this study is to investigate at the expression changes and functional role of LRRC59 in OSCC. Methods: LRRC59 gene expression and correlation with prognosis of OSCC patients were first examined using the data from The Cancer Genome Atlas (TCGA) databases. Following that, a series of functional experiments, including cell counting kit-8, cell cycle analysis, wound healing assays, and transwell assays, were carried out to analyze the biological roles of LRRC59 in tumor cells. Mechanistically, we employed Tandem Affinity Purification-Mass Spectrometry (TAP-MS) approach to isolate and identify protein complexes of LRRC59. Downstream regulatory proteins of LRRC59 were verified through immunoprecipitation and immunofluorescence experiments. Furthermore, we isolated exosomes from OSCC cell supernatant and conducted co-culture experiments to examine the effect of LRRC59 knockdown on OSCC cells. Results: In samples from OSCC patients, LRRC59 was highly expressed and correlated with poor prognoses. Moreover, the gene sets analysis based on TCGA RNA-seq data indicated that LRRC59 seemed to be strongly related with protein secretory and OSCC migration. Upregulated levels of LRRC59 are more prone to lymph node metastasis in OSCC patients. LRRC59 knockdown impaired the ability of OSCC cell proliferation, migration, and invasion invitro. Mechanistically, our TAP-MS data situate LRRC59 in a functional nexus for mRNA translation regulation via interactions with SRP pathway components, translational initiation factors, CRD-mediated mRNA stabilization factors. More importantly, we found that LRRC59 interacted with cytoskeleton-associated protein 4 (CKAP4) and promoted the formation of CKAP4-containing exosomes. We also revealed that the LRRC59-CKAP4 axis was a crucial regulator of CKAP4-containing exosome secretion in OSCC cells for migration and invasion. Conclusions: Therefore, based on our findings, LRRC59 may serve as a potential biomarker for OSCC patients, and LRRC59-induced exosome secretion via the CKAP4 axis may serve as a potential therapeutic target for OSCC.
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Electrocatalytic methods are valuable tools for addressing water pollution and scarcity, offering effective pollutant removal and resource recovery. To investigate the current status and future trends of electrocatalysis in wastewater treatment, a detailed analysis of 9417 papers and 4061 patents was conducted using scientometric methods. China emerged as the leading contributor to publications, and collaborations between China and the USA have emerged as the most frequent partnerships. Primary article co-citation clusters focused on oxygen evolution reaction and electrochemical oxidation, transitioning towards advanced oxidation processes ("persulfate activation"), and electrocatalytic reduction processes ("nitrate reduction"). Bifunctional catalysts, theoretical calculations, electrocatalytic combination technologies, and emerging contaminants were identified as current research hotspots. Patent analysis revealed seven types of electrochemical technologies, which were compared using SWOT analysis, highlighting electrochemical oxidation as prominent. The technological evolution presented the pathway of electro-Fenton to combined electrocatalytic technologies with biochemical processes, and finally to coupling with electrocoagulation. Standardized evaluation systems, waste resource utilization, and energy conservation were important directions of innovation in electrocatalytic technologies. Overall, this study provided a reference for researchers to understand the framework of electrocatalysis in wastewater treatment and also shed light on potential avenues for further innovation in the field.
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Contaminantes Ambientales , Contaminantes Químicos del Agua , Purificación del Agua , Aguas Residuales , Contaminantes Químicos del Agua/análisis , Electrodos , Contaminantes Ambientales/análisis , Oxidación-Reducción , Purificación del Agua/métodosRESUMEN
Long-acting injectable microspheres have been on the market for more than three decades, but if calculated on the brand name, only 12 products have been approved by the FDA due to numerous challenges in achieving a fully controllable drug release pattern. Recently, more and more researches on the critical factors that determine the release kinetics of microspheres shifted from evaluating the typical physicochemical properties to exploring the microstructure. The microstructure of microspheres mainly includes the spatial distribution and the dispersed state of drug, PLGA and pores, which has been considered as one of the most important characteristics of microspheres, especially when comparative characterization of the microstructure (Q3) has been recommended by the FDA for the bioequivalence assessment. This review extracted the main variables affecting the microstructure formation from microsphere formulation compositions and preparation processes and highlighted the latest advances in microstructure characterization techniques. The further understanding of the microsphere microstructure has significant reference value for the development of long-acting injectable microspheres, particularly for the development of the generic microspheres.
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Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ácido Poliglicólico/química , Ácido Láctico/química , Liberación de Fármacos , Microesferas , Preparaciones de Acción Retardada , Tamaño de la PartículaRESUMEN
The management of patients with acute myeloid leukemia (AML) remains a challenge because of the complexity and heterogeneity of this malignancy. Despite the recent approval of several novel targeted drugs, resistance seems inevitable, and clinical outcomes are still suboptimal. Increasing evidence supports the use of natural plants as an important source of anti-leukemic therapeutics. Licochalcone A (LCA) is an active flavonoid isolated from the roots of licorice, Glycyrrhiza uralensis Fisch., possessing extensive anti-tumor activities. However, its effects on AML and the underlying mechanisms remain unknown. Here, we showed that LCA decreased the viability of established human AML cell lines in a dose- and time-dependent manner. LCA significantly induced mitochondrial apoptotic cell death, accompanied by the downregulation of MCL-1, upregulation of BIM, truncation of BID, and cleavage of PARP. A prominent decline in the phosphorylation of multiple critical molecules, including AKT, glycogen synthase kinase-3ß (GSK3ß), ERK, and P38 was observed upon LCA treatment, indicating PI3K and MAPK signals were suppressed. Both transcription and translation of c-Myc were also inhibited by LCA. In addition, LCA enhanced the cytotoxicity of the BCL-2 inhibitor venetoclax. Furthermore, the anti-survival and pro-apoptotic effects were confirmed in primary blasts from 10 patients with de novo AML. Thus, our results expand the applications of LCA, which can be regarded as a valuable agent in treating AML.
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Chalconas , Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-bcl-2 , Sulfonamidas , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Línea Celular Tumoral , Leucemia Mieloide Aguda/patología , Apoptosis , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , MitocondriasRESUMEN
BACKGROUND: Peripherally inserted central catheters (PICCs) are common vascular access devices inserted for adults undergoing intravenous treatment in the community setting. Individuals with a PICC report challenges understanding information and adapting to the device both practically and psychologically at home. There is a lack of research investigating the supportive care needs of individuals with a PICC to inform nursing assessment and the provision of additional supports they may require to successfully adapt to life with a PICC. The aim of this study was to identify the supportive care needs of adults with cancer or infection living with a PICC at home. METHOD: Qualitative, semi-structured interviews were used to identify supportive care needs of adults living with a PICC at home. Participants were recruited from cancer and infectious diseases outpatient units. Two researchers independently analysed transcripts using content analysis. RESULTS: A total of 15 participants were interviewed (30-87 years old). There were 5 males and 10 females interviewed, 9 participants had a cancer diagnosis and most lived in a metropolitan area. Many participants lived with a partner/spouse at home and three participants had young children. Participants identified supportive care needs in the following eight categories (i (i) Adapting daily life (ii) Physical comfort (iii) Self-management (iv) Emotional impact (v) Information content (vi) Understanding information (vii) Healthcare resources and (viii) Social supports. CONCLUSIONS: Adults living with a PICC at home report a broad range of supportive care needs. In addition to practical and information needs, health consumers may also require support to accept living with a device inside their body and to assume responsibility for the PICC. These findings may provide nurses with a greater understanding of individual needs and guide the provision of appropriate supports.
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OBJECTIVE: Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. METHODS: Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. RESULTS: A total of 13 patients were enrolled, including six males and seven females, aged 55-79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment. CONCLUSIONS: Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Transicionales , Síndrome de Stevens-Johnson , Neoplasias de la Vejiga Urinaria , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/epidemiología , Carcinoma de Células Transicionales/complicaciones , Calidad de Vida , Neoplasias de la Vejiga Urinaria/complicacionesRESUMEN
Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6.
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MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , MicroARNs/metabolismo , Ácido Oléico/metabolismo , Metabolismo de los Lípidos/genética , Hepatocitos/metabolismo , Péptidos/farmacología , Péptidos/metabolismo , ARN Mensajero/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismoRESUMEN
Chromatin modifications play a crucial role in the regulation of gene expression. The repressor element-1 (RE1) silencing transcription factor (REST), also known as neuron-restrictive silencer factor (NRSF) and X2 box repressor (XBR), was found to regulate gene transcription by binding to chromatin and recruiting chromatin-modifying enzymes. Earlier studies revealed that REST plays an important role in the development and disease of the nervous system, mainly by repressing the transcription of neuron-specific genes. Subsequently, REST was found to be critical in other tissues, such as the heart, pancreas, skin, eye, and vascular. Dysregulation of REST was also found in nervous and non-nervous system cancers. In parallel, multiple strategies to target REST have been developed. In this paper, we provide a comprehensive summary of the research progress made over the past 28 years since the discovery of REST, encompassing both physiological and pathological aspects. These insights into the effects and mechanisms of REST contribute to an in-depth understanding of the transcriptional regulatory mechanisms of genes and their roles in the development and progression of disease, with a view to discovering potential therapeutic targets and intervention strategies for various related diseases.
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Proteínas Represoras , Factores de Transcripción , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica , CromatinaRESUMEN
The widely used biofilm process in advanced wastewater treatment is currently challenged by numerous exotic emerging pollutants (EPs), and the underlying principle of the challenge is the adaptive evolution laws of biofilm under EP stress. However, there is still a knowledge gap in exploration of the biofilm adaptive evolution theory. Herein, we comprehensively analyzed the morphological variation, community succession, and assembly mechanism of biofilms to report the mechanism underlying their adaptive evolution under sulfamethoxazole and carbamazepine stress for the first time. The ecological role of the dominant species was driven as a pioneer and assembly hub by EP stress, and the deterministic processes indicated the functional basis of the transformation. In addition, the characteristic responses of dispersal limitation and homogenizing dispersal adequately revealed the assembly pathways in adaptive evolution and the resulting structural variation. Therefore, the "interfacial exposure-structural variation-mass transfer feedback" mechanism was inferred to underly the adaptive evolution process of biofilms. Overall, this study highlighted the internal drivers of the adaptive evolution of the biofilm at the phylogenetic level and deepened our understanding of the mechanism of biofilm development under EP stress in advanced wastewater purification.
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Biopelículas , FilogeniaRESUMEN
Various lung diseases endanger people's health. Side effects and pharmaceutical resistance complicate the treatment of acute lung injury, pulmonary fibrosis, and lung cancer, necessitating the development of novel treatments. Antimicrobial peptides (AMPs) are considered to serve as a viable alternative to conventional antibiotics. These peptides exhibit a broad antibacterial activity spectrum as well as immunomodulatory properties. Previous studies have shown that therapeutic peptides including AMPs had remarkable impacts on animal and cell models of acute lung injury, pulmonary fibrosis, and lung cancer. The purpose of this paper is to outline the potential curative effects and mechanisms of peptides in the three types of lung diseases mentioned above, which may be used as a therapeutic strategy in the future.
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Lesión Pulmonar Aguda , Neoplasias Pulmonares , Fibrosis Pulmonar , Animales , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/química , Fibrosis Pulmonar/tratamiento farmacológico , Antibacterianos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Lesión Pulmonar Aguda/tratamiento farmacológicoRESUMEN
Hydrogenation of naphthalene can effectively reduce the content of aromatics in oil and generate high-value products. A series of Pt-based aluminum-modified core-shell-structured hierarchically periodic mesoporous organosilica@mesoporous silica nanoparticles (Pt/Al-x-PMOs@MSNs) were successfully synthesized and tested for the hydrogenation properties, with preferable mass transfer of macromolecular reactants in the pores and increasing the total acidity of the catalysts. Moreover, the physicochemical properties of the core-shell-structured Pt-based catalysts were systematically analyzed using various characterization techniques. At 300 °C, the naphthalene conversion on the Pt/Al-10-PMOs@MSNs catalyst reached up to 100%, the selectivity of trans-decalin reached 83.9%, and the rate constants (k1, k2) and TOF were 13.2 × 10-6 mol·g-1·s-1, 1.7 × 10-7 mol·g-1·s-1, and 218.8 h-1, respectively. In the presence of sulfur, the naphthalene hydrogenation over the Pt/Al-10-PMOs@MSN catalyst first decreased to around 40% and then recovered to the original level, which originated from the synergistic effect of the texture and chemical properties over the Pt/Al-10-PMOs@MSNs with an excellent performance.
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It is a significant challenge to perform painless invasive detection of inflammation progression in relation to the evolution of pH, redox potential, and reactive oxygen species (ROS) levels in an in situ and real-time manner. In this work, polydopamine-modified, silver nanoparticle-decorated poly (methyl methacrylate) microneedles (AgNPs@PDA@MNs) have been developed as a multiplexed surface enhanced Raman scattering (SERS) diagnostic platform. Using rhodamine 6G as the Raman signal molecule, the AgNPs@PDA@MNs demonstrated a significant enhancement with reasonable linearity in the range of 10-3-10-9 mol/L and the limit of detection is 1.0 × 10-10 mol/L 4-mercaptobenzoic acid, anthraquinone-2-carboxylic acid and para-aminothiophenol were covalently anchored on AgNPs@PDA@MNs SERS substrate. I1143/I1183, I1606/I1667 and I1143/I1077 were used as assay standards for pH, redox potential and ROS level detection, respectively. The SERS multiplexed transparent microneedles (SERS mtMNs) linearly responded to pH in the range of 4.0-8.0, redox potential in the range of 417.0-599.8 mV, and ROS levels in the range of 0-480 ng/mL, demonstrating a significant ability to detect complex inflammation in vivo, in situ and in real-time.
Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanopartículas del Metal/química , Especies Reactivas de Oxígeno , Plata/química , Espectrometría RamanRESUMEN
Biological filtration has been widely used in wastewater treatment around the world, yet achieving satisfactory removal of pollutants remains a challenge due to the complexity of water pollution. In order to reveal the hotspots and trends of biological filtration from the perspective of research innovation, 5454 SCI papers and 14,287 patents collected from the Web of Science Core Collection and Derwent Innovation Index database were analyzed by visualization techniques. The results showed that China ranked first in the number of both papers and patents, while the USA and Japan contributed significantly in papers and patents, respectively. Co-occurrence analysis obtained the mapping knowledge domains and demonstrated distinct associations between contaminants ("nitrogen", "pharmaceuticals", "personal care products"), chemicals ("carbon", "activated carbon", "media"), process ("biodegradation", "adsorption" or "ozonation") and characteristics ("kinetics", "performance", "diversity"). Moreover, this review summarized the recent advances of biological filtration media, microorganism and combined process being applied. It was concluded that environmentally friendly biological filtration ("phytoremedi", "microalga", "recirculating aquaculture system"), bio-enhanced biological filtration ("bioaugment", "fungi", "low augment") and emerging pollutants ("emerging contamin", "antibiotic resistance gen", "organic micropollut", "trace organic chem") were the hotspots through data-driven analyses. Technology evolution path of biological filtration generally indicated the transition from conventional biological filtration for nitrogen and phosphorus removal to Fenton-biofiltration combined technology and finally to ozone-biological filtration. Furthermore, the technical innovation direction of the collaborative control of multi-media pollution, the low-carbon biological filtration and short-process technology was prospected. This work can serve as a quick reference for early-career researchers and industries working in the area of biological filtration.