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1.
Neural Regen Res ; 20(1): 277-290, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38767492

RESUMEN

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

2.
J Environ Sci (China) ; 148: 116-125, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095150

RESUMEN

Perfluoroalkyl substances (PFASs) are typical persistent organic pollutants, and their removal is urgently required but challenging. Photocatalysis has shown potential in PFASs degradation due to the redox capabilities of photoinduced charge carriers in photocatalysts. Herein, hexagonal ZnIn2S4 (ZIS) nanosheets were synthesized by a one-pot oil bath method and were well characterized by a series of techniques. In the degradation of sodium p-perfluorous nonenoxybenzenesulfonate (OBS), one kind of representative PFASs, the as-synthesized ZIS showed activity superior to P25 TiO2 under both simulated sunlight and visible-light irradiation. The good photocatalytic performance was attributed to the enhanced light absorption and facilitated charge separation. The pH conditions were found crucial in the photocatalytic process by influencing the OBS adsorption on the ZIS surface. Photogenerated e- and h+ were the main active species involved in OBS degradation in the ZIS system. This work confirmed the feasibility and could provide mechanistic insights into the degradation and defluorination of PFASs by visible-light photocatalysis.


Asunto(s)
Fluorocarburos , Luz , Fotólisis , Fluorocarburos/química , Nanoestructuras/química , Catálisis , Contaminantes Químicos del Agua/química , Zinc/química , Indio/química , Modelos Químicos
3.
Am J Ophthalmol ; 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39218388

RESUMEN

BACKGROUND: Keratoconus (KC) is a corneal ectasia disease in which the vision of some patients cannot achieve satisfaction by spectacle corrections. However, not everyone can embrace contact lenses to achieve better vision. Perceptual learning (PL) is a potential treatment for vision improvement in such patients. PURPOSE: To investigate the effectiveness and maintenance of PL on vision improvement in KC patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Thirty-five non-progressive KC patients aged 9 years or older with unsatisfied spectacle-corrected vision were enrolled. METHODS: Non-progressive KC patients with best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life questionnaires were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat (ITT) principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs. 0.02 ± 0.06 logMAR; P = 0.0006). Eight out of seventeen (47.06 %) patients in the PL group reached CDVA improvement ≥ 2 lines (P=0.0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs. 0.01 ± 0.07 logMAR; P = 0.0011). The increase of CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = 0.009). No side effects were observed and no subjects quit because of training difficulties. CONCLUSION: Three-month perceptual learning improved vision in KC patients and the improvement maintained after 3 months of treatment cessation. The results indicate that perceptual learning may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

4.
Anal Chim Acta ; 1324: 343116, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39218569

RESUMEN

BACKGROUND: Salmonella Typhimurium poses a serious threat to human health worldwide, necessitating the development of a rapid, sensitive, and convenient method for S. Typhimurium detection. Nanozymes are considered ideal signal report elements, which are extensively used for developing colorimetric methods. However, single-component nanozymes display low catalytic activity, and colorimetric methods are susceptible to environmental interference, reducing the sensitivity and accuracy of detection results. To address these drawbacks, this study constructed a dual-mode composite nanozyme-based cascade colorimetric-fluorescence aptasensor for S. Typhimurium detection in food. RESULTS: In this study, the composite Fe3O4@MIL-100(Fe) nanozymes were successful synthesized and demonstrated substantial peroxide-like activity, with 4.76-fold higher specificity activity (SA) than that of Fe3O4 nanozymes. Then, a glucose oxidase (GOx)-Fe3O4@MIL-100(Fe) cascade reaction was developed for colorimetric detection via an aptamer to facilitate the formation of Fe3O4@MIL-100(Fe)/S. Typhimurium/carboxylated g-C3N4 (CCN)-GOx sandwich complexes. Meanwhile, the fluorescence mode was achieved by measuring the fluorescence intensity of the sandwich complexes. In optimum conditions, the dual-mode detection limits (LOD) were 1.8 CFU/mL (colorimetric mode) and 1.2 CFU/mL (fluorescence mode), respectively, with the S. Typhimurium concentration ranging from 10 CFU/mL to 107 CFU/mL. Finally, the feasibility of the dual-mode colorimetric-fluorescence method was validated via three actual samples, yielding recovery rates of 77.32 % to91.17 % and 82.17 % to 103.7 %, respectively. SIGNIFICANCE AND NOVELTY: This study successfully develops a composite nanozyme-based cascade colorimetric and fluorescence dual-mode aptasensor for S. Typhimurium detection. It presents several distinct benefits, such as a broader linear range (10-107 CFU/mL), a lower LOD value (1.2 CFU/mL), and more accurate results. More importantly, the proposed dual-mode method displays a low LOD in colorimetric mode, demonstrating considerable potential for S. Typhimurium on-site detection in food.


Asunto(s)
Aptámeros de Nucleótidos , Colorimetría , Salmonella typhimurium , Salmonella typhimurium/aislamiento & purificación , Colorimetría/métodos , Aptámeros de Nucleótidos/química , Técnicas Biosensibles/métodos , Límite de Detección , Fluorescencia , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Estructuras Metalorgánicas/química , Espectrometría de Fluorescencia
5.
RNA Biol ; 21(1): 1-7, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39219231

RESUMEN

Argonaute proteins (Agos) represent a highly conserved family of proteins prevalent in all domains of life and have been implicated in various biological processes. Based on the domain architecture, Agos can be divided into long Agos and short Agos. While long Agos have been extensively studied over the past two decades, short Agos, found exclusively in prokaryotes, have recently gained attention for their roles in prokaryotic immune defence against mobile genetic elements, such as plasmids and phages. Notable functional and structural studies provide invaluable insights into the underlying molecular mechanisms of representative short Ago systems. Despite the diverse domain arrangements, short Agos generally form heterodimeric complexes with their associated effector proteins, activating the effector's enzymatic activities upon target detection. The activation of effector proteins in the short Ago systems leads to bacterial cell death, a mechanism of sacrificing individuals to protect the community.


Asunto(s)
Proteínas Argonautas , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/química , Bacterias/metabolismo , Bacterias/genética , Relación Estructura-Actividad , Conformación Proteica , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Humanos , Modelos Moleculares
6.
Expert Opin Ther Pat ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223788

RESUMEN

INTRODUCTION: c-Jun N-terminal kinase (JNK) regulates various biological processes through the phosphorylation cascade, and is closely associated with numerous diseases, including inflammation, cardiovascular diseases and neurological disorders. Therefore, JNKs have been emerged as potential targets for diseases treatment. AREAS COVERED: This review compiles the patents and literatures concerning JNK inhibitors through retrieving relevant information from the SciFinder, Google Patents databases and PubMed from 2015 to the present. It summarizes the structure-activity relationship (SAR) and biological activity profiles of JNK inhibitors, offering valuable perspectives on their potential therapeutic applications. EXPERT OPINION: The JNK kinase serves as a novel target for the treatment of neurodegenerative disorders, pulmonary fibrosis, and other illnesses. A variety of small molecule inhibitors targeting JNKs have demonstrated promising therapeutic potential in preclinical studies, which act upon the JNK kinases via distinct mechanisms, encompassing traditional ATP competitive inhibition, covalent inhibition, and bidentate inhibition. Among them, several JNK inhibitors from PregLem SA, Celegene SA, and Xigen SA have accomplished the early stage of clinical trials, and their results will guide the development and indications of future JNK inhibitors.

7.
Food Funct ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39224078

RESUMEN

Reproductive aging in female mammals is characterized by ovarian senescence, leading to a significant fertility decline. Lycium barbarum berry, or goji berry, is a food and medicine that appears in various formulas for treating infertility in traditional Chinese medicine. We investigated the function of an aqueous extract of Lycium barbarum berry (LB extract) to improve health status, fertility, and offspring development during female aging. Aged female mice were supplemented with LB extract, and its effects on fertility, locomotor activity, and offspring development were assessed. The results demonstrated that LB extract significantly increased pregnancy and live birth rates in naturally aged female mice. It also effectively improved aged animals' locomotor activity. Moreover, LB extract promoted the growth and development of offspring delivered from the aged animals and reduced the offspring's anxiety. During aging, fertility-related hormones gradually decline. However, the decline of anti-Müllerian hormone (AMH) and estradiol (E2) in the serum of aged mice was restored by LB extract supplementation. Immunohistochemical analysis revealed that the levels of oxidation and the inflammatory IL-6 in intra-ovarian cells were reduced by LB extract, while the antioxidant-associated proteins peroxiredoxin 4 (PRDX4) and nuclear factor erythroid 2-related factor 2 (NRF2) were increased. Bioinformatics analysis revealed a decline in egg PRDX4 expression with age across various species. This suggests that the antioxidant function protected by LB extract through PRDX4 may consistently promote fertility enhancement by improving ovarian function across different species. Importantly, LB extract did not induce significant adverse effects on aged female mice and their offspring. These findings highlight the potential of LB as a protective agent against ovarian oxidative stress, which preserves ovarian function and improves fertility rates in naturally senescent females.

8.
Adv Sci (Weinh) ; : e2405367, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207041

RESUMEN

Peritendinous adhesion that forms after tendon injury substantially limits daily life. The pathology of adhesion involves inflammation and the associated proliferation. However, the current studies on this condition are lacking, previous studies reveal that cyclooxygenase-2 (COX2) gene inhibitors have anti-adhesion effects through reducing prostaglandin E2 (PGE2) and the proliferation of fibroblasts, are contrary to the failure in anti-adhesion through deletion of EP4 (prostaglandin E receptor 4) gene in fibroblasts in mice of another study. In this study, single-cell RNA sequencing analysis of human and mouse specimens are combined with eight types of conditional knockout mice and further reveal that deletion of COX2 in myeloid cells and deletion of EP4 gene in sensory nerves decrease adhesion and impair the biomechanical properties of repaired tendons. Furthermore, the COX2 inhibitor parecoxib reduces PGE2 but impairs the biomechanical properties of repaired tendons. Interestingly, PGE2 local treatment improves the biomechanical properties of the repaired tendons. These findings clarify the complex role of PGE2 in peritendinous adhesion formation (PAF) and tendon repair.

9.
Sci Rep ; 14(1): 20083, 2024 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-39209895

RESUMEN

Colorectal cancer (CRC) is one of most common tumors worldwide, causing a prominent global health burden. Cell senescence is a complex physiological state, characterized by proliferation arrest. Here, we investigated the role of cellular senescence in the heterogeneity of CRC. Based on senescence-associated genes, CRC samples were classified into different senescence patterns with different survival, cancer-related biological processes and immune cell infiltrations. A senescence-related model was then developed to calculate the senescence-related score to comprehensively explore the heterogeneity of each CRC sample such as stromal activities, immunoreactivities and drug sensitivity. Single-cell analysis revealed there were different immune cell infiltrations between low and high senescence-related model genes enrichment groups, which was confirmed by multiplex immunofluorescence staining. Pseudotime analysis indicated model genes play a pivotal role in the evolution of B cells. Besides, intercellular communication modeled by NicheNet showed tumor cells with higher enrichment of senescence-related model genes highly expressed CXCL2/3 and CCL3/4, which attracted immunosuppressive cell infiltration and promoted tumor metastasis. Finally, top 6 hub genes were identified from senescence-related model genes by PPI analysis. And RT-qPCR revealed the expression differences of hub genes between normal and CRC cell lines, indicating to some extent the clinical practicability of senescence-related model. To sum up, our study explores the impact of cellular senescence on the prognosis, TME and treatment of CRC based on senescence patterns. This provides a new perspective for CRC treatment.


Asunto(s)
Biomarcadores de Tumor , Senescencia Celular , Neoplasias Colorrectales , Análisis de la Célula Individual , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Humanos , Senescencia Celular/genética , Análisis de la Célula Individual/métodos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Análisis de Secuencia de ARN , Línea Celular Tumoral , Heterogeneidad Genética , Perfilación de la Expresión Génica , Microambiente Tumoral/genética
10.
Int J Biol Macromol ; : 134840, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39217040

RESUMEN

Hen egg low-density lipoprotein (heLDL), as alternative of serum-derived LDL, was used as drug delivery system of ceftiofur (CEF). The CEF-loaded hen egg low-density lipoprotein (CEF-heLDL) with complete apolipoprotein structure and high drug loading rate was synthesized, possesses suitable particle size. CEF-heLDL undergoes cellular uptake and colocalizes with lysosomes in vitro. An intracellular infection model of the bovine endometrial epithelial cells and a coeliac-induced inflammation model of mice by Staphylococcus aureus (S. aureus) were established, and significantly lower intracellular S. aureus levels of CEF-heLDL group than CEF-free group (P < 0.001) was observed. The antibacterial efficacy was sustained for 24 h. Up to 400 mg/kg of CEF-heLDL, 20 times the clinical practice, were intraperitoneally administrated, and no significant toxicity signs on mice were observed. HeLDLs is an effective, safe, and cheap drug carrier, and could also be used for transmembrane delivering other antibiotics.

11.
Clin Nucl Med ; 49(10): 959-961, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39192512

RESUMEN

ABSTRACT: A 23-year-old man with papillary thyroid cancer underwent radioiodine ( 131 I) treatment following total thyroidectomy and node dissection. Posttreatment 131 I SPECT/CT images revealed an additional focus of increased 131 I activity in the left adrenal gland, raising suspicion for possible adrenal metastasis. Ultimately, pathological examination confirmed the diagnosis of an adrenal cyst.


Asunto(s)
Quistes , Radioisótopos de Yodo , Neoplasias de la Tiroides , Humanos , Masculino , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/patología , Adulto Joven , Quistes/diagnóstico por imagen , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Cáncer Papilar Tiroideo/diagnóstico por imagen
13.
Nanoscale ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158040

RESUMEN

The electrochemical reduction of carbon dioxide (CO2RR) to carbon monoxide represents a cost-effective pathway towards realizing carbon neutrality. To suppress the hydrogen evolution reaction (HER), the presence of alkali cations is critical, which can however lead to precipitate formation on the electrode, adversely impacting the device stability. Employing pure water as the electrolyte in zero-gap CO2 electrolyzers can address this challenge, albeit at the cost of diminished catalyst performance due to the absence of alkali cations. In this study, we introduce a novel approach by implementing amino modifications on the catalyst surface to mimic the function of alkali metal cations, while simultaneously working in pure water. This modification enhances the adsorption of carbon dioxide and protons, thereby facilitating the CO2RR while concurrently suppressing the HER. Utilizing this strategy in a zero-gap CO2 electrolyzer with pure water as the anolyte resulted in an impressive carbon monoxide faradaic efficiency (FECO) of 95.5% at a current density of 250 mA cm-2, while maintaining stability for over 180 hours without any maintenance.

14.
Comput Biol Chem ; 112: 108143, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39142146

RESUMEN

Breast cancer, one common malignant tumor all over the world, has a considerably high rate of recurrence, which endangers the health and life of patients. While more and more data have been available, how to leverage the gene expression data to predict the survival risk of cancer patients and identify key genes has become a hot topic for cancer research. Therefore, in this work, we investigate the gene expression and clinical data of breast cancer patients, specifically a novel framework is proposed focusing on the survival risk classification and key gene identification task. We firstly combine the differential expression and univariate Cox regression analysis to achieve dimensional reduction of gene expression data. The median survival time is subsequently proposed as the risk classification threshold and a learning model based on neural network is trained to classify the survival risk of patients. Innovatively, in this work, the activation region visualization technology is selected as the identification tool, which identify 20 key genes related to the survival risk of breast cancer patients. We further analyze the gene function of these 20 key genes based on STRING database. It is critical to learn that, the genetic biomarkers identified in this paper may possess value for the following clinical treatment of breast cancer according to the literature findings. Importantly, the genetic biomarkers identified in this paper may possess value for the following clinical treatment of breast cancer according to the literature findings. Our work accomplishes the objective of proposing a targeted approach to enhancing the survival analysis and therapeutic strategies in breast cancer through advanced computational techniques and gene analysis.

15.
Anal Chim Acta ; 1320: 343033, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39142765

RESUMEN

BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.


Asunto(s)
Colorantes Fluorescentes , Oro , Ácido Hipocloroso , Levonorgestrel , Pez Cebra , Humanos , Oro/química , Células HeLa , Ácido Hipocloroso/análisis , Animales , Células Hep G2 , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Levonorgestrel/química , Imagen Óptica , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Nanopartículas del Metal/química
16.
Artículo en Inglés | MEDLINE | ID: mdl-39136510

RESUMEN

OBJECTIVE: Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid disease. In recent decades, its incidence and prevalence have sharply increased. Yiqi Huatan Huoxue recipe is a traditional Chinese medicine formula we use to treat AIT. Its clinical efficacy is clear, but the specific mechanism remains unclear. This study aims to explore whether pyroptosis mediated by the SIRT1/NF-κB/NLRP3 signaling pathway is one of the therapeutic mechanisms of Yiqi Huatan Huoxue recipe. METHODS: Forty 8-week-old female NOD.H-2h4 mice were randomly divided into four groups: the normal group (NG), model group (MG), Yiqi Huatan Huoxue recipe group (YG), and western medicine group (selenium yeast tablet, SeG). The normal group was gavaged with distilled water, while the remaining groups were gavaged with 0.05% sodium iodide (NaI) solution for 8 weeks. After the AIT animal model formed naturally, the mice were euthanized by gavage after 8 weeks. Hematoxylin-eosin staining was used to observe thyroid tissue changes, and enzymelinked immunosorbent assay (ELISA) was used to detect serum anti-thyroglobulin antibodies (TGAb) and mouse anti-thyroid peroxidase antibodies (TPOAb). Real-time quantitative PCR (qRT-PCR), Western blot, and immunohistochemistry were used to detect the expression of sirtuin 1 (SIRT1), nuclear factor κB p65 (NF-κB p65), nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase- 1, gasdermin D (GSDMD), and interleukin (IL)-1ß in thyroid tissue. RESULTS: Compared with the NG group, the thyroid structure of rats in the MG group was severely damaged, with significant lymphocyte infiltration, significantly increased serum TGAb and TPOAb levels, and significantly increased expression levels of SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1ß mRNA, and protein. Compared with the MG group, the thyroid structure damage and lymphocyte infiltration in rats of each treatment group were improved, and the serum TGAb, TPOAb, SRIT1, NF-κB p65, NLRP3, ASC, Caspase-1, GSDMD, IL-1ß mRNA, and protein expression levels were significantly reduced. CONCLUSION: Yiqi Huatan Huoxue recipe can alleviate thyroid structural damage in AIT mice, and its mechanism may be related to the upregulation of SIRT1, NF-κB deacetylation, and inhibition of NLRP3-mediated pyroptosis.

17.
Orphanet J Rare Dis ; 19(1): 299, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148107

RESUMEN

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.


Asunto(s)
Sirolimus , Humanos , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Niño , Femenino , Adolescente , Preescolar , Adulto , Masculino , Lactante , Adulto Joven , Persona de Mediana Edad , Recién Nacido , Anciano , Esclerosis Tuberosa/tratamiento farmacológico , Linfangioleiomiomatosis/tratamiento farmacológico , Estudios Prospectivos
18.
Chem Sci ; 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39149214

RESUMEN

Phosphor-converted white light-emitting diodes (PC-WLEDs) have attracted considerable attention in solid-state lighting and display. However, urgent issues of thermal quenching and high cost remain formidable challenges. Herein, a novel metal-organic framework (MOF) phosphor [CdCl2(AD)] was facilely prepared using a mixture of CdCl2 and acridine (AD) under solvothermal conditions. It shows intensive green emission with a long lifetime of 31.88 ns and quantum yield of 65% while maintaining 95% and 84% of its initial emission intensity after remaining immersed in water for 60 days and being heated to 150 °C, respectively. The low thermal quenching of this MOF material is comparable to or can even exceed that of commercial inorganic phosphors. The combination of experiments and theoretical calculations reveals that the alternating arrangement of delocalized AD π-conjugated systems and CdCl2 inorganic chains through strong coordination bonds and π⋯π stacking interactions imparts the MOF phosphor with high thermal stability and optoelectronic performance. The successful fabrication of green and white LED devices by coating [CdCl2(AD)] and/or N630 red phosphor on a 365/460 nm commercial diode chip suggests a promising and potential alternative to commercial phosphors.

19.
Bioresour Technol ; 410: 131300, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39153696

RESUMEN

This study investigated the effects of different external circuit loading mode on pollutants removal and power generation in microbial fuel cells (MFC). The results indicated that MFC exhibited distinct characteristics of higher maximum power density (Pmax) (named MFC-HP) and lower Pmax (named MFC-LP). And the capacitive properties of bioanodes may affect anodic electrochemistry. Reducing external load to align with the internal resistance increased Pmax of MFC-LP by 54.47 %, without no obvious effect on MFC-HP. However, intermittent external resistance loading (IER) mitigated the biotoxic effects of sulfamethoxazole (SMX) (a persistent organic pollutant) on chemical oxygen demand (COD) and NH4+-N removal and maintained high Pmax (424.33 mW/m2) in MFC-HP. Meanwhile, IER mode enriched electrochemically active bacteria (EAB) and environmental adaptive bacteria Advenella, which may reduce antibiotic resistance genes (ARGs) accumulation. This study suggested that the external circuit control can be effective means to regulate electrochemical characteristics and pollutants removal performance of MFC.

20.
MedComm (2020) ; 5(9): e673, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39161799

RESUMEN

Saliva biopsy of nasopharyngeal carcinoma (NPC) has been developed in our latest study, indicating the application of oral sampling in NPC detection. Further exploration of the potential for self-sampling from the oral cavity is necessary. A total of 907 various samples from oral cavity, including saliva (n = 262), oropharyngeal swabs (n = 250), oral swabs (n = 210), and mouthwash (n = 185), were collected. Epstein‒Barr virus (EBV) DNA methylation at the 12,420 bp CpG site in EBV genome from the repeat-copy W promoter (Wp) region and at the 11,029 bp CpG site in the single-copy C promoter (Cp) region were simultaneously detected in these samples. A significant increase in EBV methylation, no matter at Wp or Cp region, was found in all types of samples from NPC patients. However, EBV DNA methylation in saliva and oropharyngeal swab showed a better diagnostic performance in detecting NPC. The combination of these two sample types and two markers could help to improve the detection of NPC. Our study further explored the optimal self-sampling methods and detection target in the detection of NPC and may facilitate the application of EBV DNA methylation detection in a home-based large-scale screening of NPC.

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