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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124970, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39153349

RESUMEN

Due to their exceptional optical properties and adjustable functional characteristics, hydrogen-bonded organic frameworks (HOFs) demonstrate significant potential in applications such as sensing, information encryption. However, studies on the synthesis of HOFs designed to construct multifunctional platforms are scant. In this work, we report the synthesis of a new fluorescent HOF by assembling melem and isophthalic acid (IPA), designated as HOF-IPA. HOF-IPA exhibited good selectivity and sensitivity towards Fe3+, making it suitable as a fluorescent sensor for Fe3+ detection. The sensor achieved satisfactory recoveries ranging from 97.79 % to106.42 % for Fe3+ sensing, with a low relative standard deviation (RSD) of less than 3.33 %, indicating significant application potential for HOF-IPA. Due to the ability of F- to mask the electrostatic action on the surface of Fe3+ and inhibit the photoelectron transfer (PET) of HOF-IPA, the HOF-IPA - Fe3+ system can be utilized as a fluorescent "off-on" sensor for F- detection. Additionally, owing to the colorless, transparent property of HOF-IPA in aqueous solution under sunlight and its blue fluorescence property under UV light (color) or microplate reader (fluorescence intensity), HOF-IPA based ink can be used for various types of information encryption, and all yielding favorable outcomes.

2.
Cytotherapy ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39283287

RESUMEN

BACKGROUND: Many studies have demonstrated the effectiveness of chimeric antigen receptor-T (CAR-T) cell therapy for relapsed or refractory multiple myeloma (RRMM), but the hematologic toxicity has not been well characterized. METHODS: A total of 111 adults with RRMM who received BCMA CAR-T cells, BCMA + CD19 CAR-T cells or tandem BCMA/CD19 dual-target (BC19) CAR-T cells infusion were enrolled. We characterized cytopenia and hematologic recovery at different time points after CAR-T-cell therapy, analyzed the effect of cytopenia on prognosis and identified the risk factors. RESULTS: Patients had a high probability of cytopenia, with anemia, neutropenia and thrombocytopenia occurring in 92%, 95% and 73%, respectively. There were 60 (54%) patients had prolonged hematologic toxicity (PHT) after D28. The median hemoglobin and platelet count were significantly lower at D28 post-CAR-T cell therapy than at baseline. Hemoglobin increased to above baseline at D90. The median absolute neutrophil count was lower than baseline at D0 and D28, and it recovered to baseline at D180. The baseline level of lactate dehydrogenase was associated with thrombocytopenia. Extramedullary involvement was associated with hemoglobin recovery, while the baseline level of albumin and types of CAR-T were related to platelet recovery. Patients with anemia at baseline and at D0, D180 and D360 had shorter progression-free survival (PFS), while anemia at D0, D60, D180 and D360 was associated with shorter overall survival (OS). Neutropenia at D0 was associated with shorter PFS and patients with neutropenia at D90 or D180 had shorter OS. Patients with thrombocytopenia at any time had shorter PFS and OS. Compared to patients without PHT, patients with PHT had shorter PFS and OS. CONCLUSIONS: The majority of RRMM patients treated with CAR-T cells experienced cytopenia. Cytopenia occurred at specific time points was associated with a poorer prognosis.

3.
Plant J ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39283988

RESUMEN

The formation and development of storage roots is the most important physiological process in sweetpotato production. Sucrose transporters (SUTs) regulate sucrose transport from source to sink organs and play important roles in growth and development of plants. However, whether SUTs involved in sweetpotato storage roots formation is so far unknown. In this study, we show that IbSUT1, a SUT, is localized to the plasma membrane. Overexpression of IbSUT1 in sweetpotato promotes the sucrose efflux rate from leaves, leading to increased sucrose levels in roots, thus induces lignin deposition in the stele, which inhibits the storage roots formation and compromises the yield. Heterologous expression of IbSUT1 in Arabidopsis significantly increases the sucrose accumulation and promotes lignification in the inflorescence stems. RNA-seq and biochemical analysis further demonstrated that IbMYB1 negatively regulates the expression of IbSUT1. Overexpression of IbMYB1 in Arabidopsis reduces the sucrose accumulation and lignification degree in the inflorescence stems. Moreover, co-overexpression of IbMYB1 and IbSUT1 restores the phenotype of lignin over-deposition in Arabidopsis. Collectively, our results reveal that IbSUT1 regulates source-sink sucrose transport and participates in the formation of sweetpotato storage roots and highlight the potential application of IbSUT1 in improving sweetpotato yield in the future.

4.
Nat Commun ; 15(1): 7989, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39284811

RESUMEN

There is a growing interest in the creation of engineered condensates formed via liquid-liquid phase separation (LLPS) to exert precise cellular control in prokaryotes. However, de novo design of cellular condensates to control metabolic flux or protein translation remains a challenge. Here, we present a synthetic condensate platform, generated through the incorporation of artificial, disordered proteins to realize specific functions in Bacillus subtilis. To achieve this, the "stacking blocks" strategy is developed to rationally design a series of LLPS-promoting proteins for programming condensates. Through the targeted recruitment of biomolecules, our investigation demonstrates that cellular condensates effectively sequester biosynthetic pathways. We successfully harness this capability to enhance the biosynthesis of 2'-fucosyllactose by 123.3%. Furthermore, we find that condensates can enhance the translation specificity of tailored enzyme fourfold, and can increase N-acetylmannosamine titer by 75.0%. Collectively, these results lay the foundation for the design of engineered condensates endowed with multifunctional capacities.


Asunto(s)
Bacillus subtilis , Proteínas Bacterianas , Hexosaminas , Ingeniería Metabólica , Bacillus subtilis/metabolismo , Bacillus subtilis/genética , Ingeniería Metabólica/métodos , Hexosaminas/biosíntesis , Hexosaminas/metabolismo , Hexosaminas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Vías Biosintéticas , Ingeniería de Proteínas/métodos , Biosíntesis de Proteínas , Trisacáridos/metabolismo , Trisacáridos/biosíntesis , Trisacáridos/química , Extracción Líquido-Líquido/métodos
5.
Plant Sci ; 349: 112261, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270825

RESUMEN

Soil salinization leads to reduced crop yields and waste of land resources, thereby impacting global food security. To meet the increasing demand for food and simultaneously alleviate pressure on soil resources, the development of sustainable agriculture is imperative. In contrast to physical and chemical methods, bioremediation represents an efficient and environmentally friendly approach. Fungal symbionts have been found to be associated with most plants in natural ecosystems, colonizing and residing within the internal tissues of host plants. Moreover, the potential of fungal symbionts in improving saline-alkaline soil has been widely recognized and confirmed. Numerous reports have documented the effectiveness of arbuscular mycorrhizal fungi in alleviating salt stress in plants. Meanwhile, research on other endophytic fungi for mitigating plant salt stress has emerged in recent years, which contributes to refining mechanisms for enhancing plant salt tolerance. In this review, we summarized various mechanisms by which endophytic fungi enhance plant salt tolerance. We also provided an overview of the challenges and development directions in the field of fungal symbiosis, with the aim of offering a viable strategy for the bioremediation of saline-alkali soils.

6.
Acta Pharmacol Sin ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294445

RESUMEN

Sodium-glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i) is a novel class of anti-diabetic drug, which has displayed a promising benefit for non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effects of SGLT2i against NAFLD and the underlying mechanisms. The db/db mice and western diet-induced NAFLD mice were treated with dapagliflozin (1 mg·kg-1·d-1, i.g.) or canagliflozin (10 mg·kg-1·d-1, i.g.) for 8 weeks. We showed that the SGLT2i significantly improved NAFLD-associated metabolic indexes, and attenuated hepatic steatosis and fibrosis. Notably, SGLT2i reduced the levels of pro-inflammatory cytokines and chemokines, downregulated M1 macrophage marker expression and upregulated M2 macrophage marker expression in liver tissues. In cultured mouse bone marrow-derived macrophages and human peripheral blood mononuclear cell-derived macrophages, the SGLT2i (10, 20 and 40 µmol/L) significantly promoted macrophage polarization from M1 to M2 phenotype. RNA sequencing, Seahorse analysis and liquid chromatography-tandem mass spectrometry analysis revealed that the SGLT2i suppressed glycolysis and triggered metabolic reprogramming in macrophages. By using genetic manipulation and pharmacological inhibition, we identified that the SGLT2i targeted PFKFB3, a key enzyme of glycolysis, to modulate the macrophage polarization of M1 to M2 phenotype. Using a co-culture of macrophages with hepatocytes, we demonstrated that the SGLT2i inhibited lipogenesis in hepatocytes via crosstalk with macrophages. In conclusion, this study highlights a potential therapeutic application for repurposing SGLT2i and identifying a potential target PFKFB3 for NAFLD treatment.

7.
BMC Genomics ; 25(1): 864, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285286

RESUMEN

BACKGROUND: Greater yam is a key staple crop grown in tropical and subtropical regions, while its asexual propagation mode had led to non-flowering mutations. How transposable elements contribute to its genetic variations is rarely analyzed. We used transcriptome and whole genome sequencing data to identify active transposable elements (TEs) and genetic variation caused by these active TEs. Our aim was to shed light on which TEs would lead to its intraspecies variation. RESULTS: Annotation of de novo assembly transcripts indicated that 0.8 - 0.9% of transcripts were TE related, with LTR retrotransposons (LTR-RTs) accounted for 65% TE transcripts. A large portion of these transcripts were non-autonomous TEs, which had incomplete functional domains. The majority of mapped transcripts were distributed in genic deficient regions, with 9% of TEs overlapping with genic regions. Moreover, over 90% TE transcripts exhibited low expression levels and insufficient reads coverage to support full-length structure assembly. Subfamily analysis of Copia and Gypsy, the two LTR-RTs revealed that a small number of subfamilies contained a significantly larger number of members, which play a key role in generating TE transcript. Based on resequencing data, 15,002 L-RT insertion loci were detected for active LTR-RT members. The insertion loci of LTR-RTs were highly divergent among greater yam accessions. CONCLUSIONS: This study showed the ongoing transcription and transpositions of TEs in greater yam, despite low transcription levels and incomplete proteins insufficient for autonomous transposition. While our research did not directly link these TEs to specific yam traits such as tuber yield and propagation mode, it lays a crucial foundation for further research on how these TE insertion polymorphisms (TIPs) might be related to variations in greater yam traits and its tuber propagation mode. Future research may explore the potential roles of TEs in trait variations, such as tuber yield and stress resistance, in greater yam.


Asunto(s)
Elementos Transponibles de ADN , Dioscorea , Dioscorea/genética , Dioscorea/crecimiento & desarrollo , Elementos Transponibles de ADN/genética , Retroelementos , Tubérculos de la Planta/genética , Tubérculos de la Planta/crecimiento & desarrollo , Genoma de Planta , Transcriptoma , Variación Genética , Secuencias Repetidas Terminales/genética
8.
Front Cell Dev Biol ; 12: 1459040, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258228

RESUMEN

Purpose: This study aimed to evaluate the optical coherence tomography angiography (OCTA) changes in subzones of peripapillary atrophy (PPA) among type 2 diabetic patients (T2DM) with or without diabetic retinopathy (DR) using well-designed deep learning models. Methods: A multi-task joint deep-learning model was trained and validated on 2,820 images to automate the determination and quantification of the microstructure and corresponding microcirculation of beta zone and gamma zone PPA. This model was then applied in the cross-sectional study encompassing 44 eyes affected by non-proliferative diabetic retinopathy (NPDR) and 46 eyes without DR (NDR). OCTA was utilized to image the peripapillary area in four layers: superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary (CC) and middle-to-large choroidal vessel (MLCV). Results: The patients in both groups were matched for age, sex, BMI, and axial length. The width and area of the gamma zone were significantly smaller in NPDR group compared to the NDR group. Multiple linear regression analysis revealed a negative association between the diagnosis of DR and the width and area of the gamma zone. The gamma zone exhibited higher SCP, DCP and MLCV density than the beta zone, while the beta zone showed higher CC density than the gamma zone. In comparison to the NDR group, the MLCV density of gamma zone was significantly lower in NPDR group, and this density was positively correlated with the width and area of the gamma zone. Discussion: DR-induced peripapillary vascular changes primarily occur in gamma zone PPA. After eliminating the influence of axial length, our study demonstrated a negative correlation between DR and the gamma zone PPA. Longitudinal studies are required to further elucidate the role of the gamma zone in the development and progression of DR.

9.
Ann Rheum Dis ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299725

RESUMEN

OBJECTIVE: We assessed the role of a systemic lupus erythematosus causal hypofunctional variant, neutrophil cytosolic factor 1 (NCF1)-p.Arg90His (p.R90H) substitution, in systemic sclerosis (SSc). METHODS: Association of NCF1-H90 with SSc was performed in case-control cohorts, bleomycin (BLM)-treated Ncf1-R90 C57BL/6 wildtype and Ncf1-H90 knock-in (KI) littermates. Peripheral blood mononuclear cell (PBMC) subsets were analysed by cytometry by time-of-flight. RESULTS: The NCF1-H90 allele is associated with risk for diffuse cutaneous SSc (dcSSc) in Chinese and European Americans, and lung fibrosis in Chinese patients with SSc (OR=2.09, p=7.96E-10). Low copy number of NCF1 associated with lung fibrosis in European Americans (OR=4.33, p=2.60E-2). BLM-treated KI mice demonstrated increased pulmonary fibrosis, exhibiting activated type I interferon signature, elevated Spp1, Ccl2, Arg1, Timp1 and Il6 expression, enriched macrophage scores in lung tissues. In a longitudinal observation cohort, homozygous H90 patients with SSc at baseline had increased anti-nuclear antibody titres, anti-topoisomerase antibody seropositivity and anti-centromere antibody seronegativity, increased incidence of lung fibrosis and Gender-Age-lung Physiology index, elevated modified Rodnan Skin Score (mRSS) and elevated plasma osteopontin (OPN, SPP1), CCL2, ARG1, TIMP-1 and IL-6. These H90 patients with SSc sustained elevated mRSS during follow-up years with decreased survival. The 0, 1 and 2 copies of H90 carriage in SSc PBMCs exhibited dose-dependent increases in profibrotic CD14+CD68+CD11b+Tim3+monocytes. Elevated OPN, CCL2 and ARG1 in CD68+CD11b+monocyte-derived macrophages from H90 patients were decreased after co-culturing with anti-CCL2 antibody. CONCLUSION: Low NCF1 activity increases the risk for the development of dcSSc and lung fibrosis via expanding profibrotic SPP1+MoMs in a CCL2-dependent manner, contributing to the severity of lung fibrosis in both BLM-treated mice and patients with SSc.

10.
Cancer Gene Ther ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300216

RESUMEN

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target.

11.
Inorg Chem ; 63(37): 17116-17126, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39231020

RESUMEN

Precisely tuning how and where a reaction occurs in a one-step selective system is important but challenging owing to the similar electronic environments in multiple active sites. In this work, highly selective and effective reaction sites were obtained by generating copper coordination polymers (Cu-CP) of a range of sizes and morphologies, from bulk solid crystals (1) to uniform nanosphere structures (1a), by controlling the amount of surfactant hexadecyl trimethylammonium bromide (CTAB). The results indicated that the morphology and size of the uniform nanosphere structures were affected by the proportion of CTAB; uniform distribution of nanosphere structures was achieved with a premade building carrier when the content of CTAB was 0.005 mmol, generating a well-established platform. Photocatalytic cadmium sulfide (CdS) was then immobilized on the surface of the premade platform unit 1a through an in situ process to generate CdS@1a composites with well-dispersed catalytic CdS active sites. Furthermore, the well-defined CdS@1a composite platform was utilized as photocatalysts to explore the selective one-step depolymerization reaction under blue-light irradiation. Notably, the CdS0.149@1a composite, which featured a unique structure with evenly dispersed, closely spaced catalytic sites, exhibiting remarkable photoelectrochemical behaviors for selective one-step depolymerization of lignin model substances to aromatic monomer phenol and acetophenone framework products. This work demonstrates the use of an inherently morphological process to construct outstanding photocatalysts that could enable a wide range of photocatalytic reactions.

12.
Bioorg Chem ; 153: 107779, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39236583

RESUMEN

To facilitate the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we synthesized three series of derivatives by introducing phenyl pyrazole fragments into the structure of pyrazol-4-yl amides. The results of the bioactivity assay showed that most of the target compounds possessed varying degrees of inhibitory activity against the tested fungi. At a concentration of 100 mg/L, the compound B8 exhibited effective protective activity against S. sclerotiorum in vivo. Molecular docking analysis and succinate dehydrogenase (SDH) inhibition assay indicated that B8 was not a potential SDHI. The preliminary antifungal mechanism of studies showed that B8 induced a large amount of reactive oxygen species (ROS) and severe lipid peroxidation damage in S. sclerotiorum mycelium, resulting in mycelial rupture and disruption of the integrity of the cell membrane and leakage of soluble proteins, soluble sugars and nucleic acids. Further transcriptome analysis showed that compound B8 blocked various metabolic pathways by downregulating the differentially expressed genes (DEGs) catalase, disrupting hydrogen peroxide hydrolysis, accelerating membrane oxidative damage, and upregulating neutral ceramidase, accelerating sphingolipid metabolism to disrupt cell membrane structure and cell proliferation and differentiation, potentially accelerating cell death. The above results indicated that the potential target of these dis-pyrazole carboxamide derivatives may be the cell membrane of pathogenic fungi.

13.
PLoS One ; 19(9): e0309976, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39236049

RESUMEN

Sarmentosin (SA) and Quercetin (QC) are two active components of Sedum Sarmentosum Bunge, which is a traditional Chinese herbal medicine. This study aimed to investigate the role and regulatory mechanism of SA and QC in fatty liver of Genetic Improvement of Farmed Tilapia (GIFT) tilapia. GIFT tilapia were randomly divided into two groups with three replicates per treatment (30 fish in each replicate): normal diet group (average weight 3.51±0.31 g) and high-fat diet group (average weight 3.44±0.09 g). After 8 weeks feeding trial, growth index, lipid deposition, and biochemical indexes were measured. Lipid deposition, and lipid and inflammation-related gene expression were detected in a primary hepatocyte model of fatty liver of GIFT tilapia treated with SA or QC. Our results showed that high-fat diet caused lipid deposition and peroxidative damage in the liver of GIFT tilapia. The cell counting kit-8 assay results indicated that 10 µM SA and 10 µM of QC both had the least effect on hepatocyte proliferation. Moreover, both 10 µM of SA and 10 µM of QC showed lipolytic effects and inhibited the expression of lipid-related genes (FAS, Leptin, SREBP-1c, and SREBP2) in fatty liver cells. Interestingly, QC induced autophagosome-like subcellular structure and increased the expression of IL-8 in fatty liver cells. In conclusion, this study confirmed that SA and QC improved fatty liver caused by high-fat diet, providing a novel therapeutic approach for fatty liver of GIFT tilapia.


Asunto(s)
Hígado Graso , Hepatocitos , Metabolismo de los Lípidos , Quercetina , Animales , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Quercetina/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Hígado Graso/metabolismo , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Cíclidos/metabolismo , Dieta Alta en Grasa/efectos adversos , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Tilapia/metabolismo , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos
14.
World J Surg Oncol ; 22(1): 243, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256855

RESUMEN

OBJECTIVE: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. PATIENTS AND METHODS: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. RESULTS: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470-21.569), PR (OR = 7.690, 95%CI: 3.974-16.129, Her-2 (OR = 10.489, 95%CI: 2.779-23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031-0.377 were significant independent risk factors affecting AR expression. CONCLUSIONS: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Recurrencia Local de Neoplasia , Receptor ErbB-2 , Receptores Androgénicos , Receptores de Estrógenos , Receptores de Progesterona , Humanos , Receptores Androgénicos/metabolismo , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Persona de Mediana Edad , Biomarcadores de Tumor/metabolismo , Pronóstico , Adulto , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Receptores de Estrógenos/metabolismo , Estudios de Seguimiento , Anciano , Estudios Retrospectivos , Metástasis Linfática , Estadificación de Neoplasias , Clasificación del Tumor , Anciano de 80 o más Años
15.
Environ Pollut ; 361: 124889, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39236842

RESUMEN

Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 µM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.

16.
J Stomatol Oral Maxillofac Surg ; : 102066, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39245287

RESUMEN

OBJECTIVE: To investigate the effect of different forms of autolyzed antigen-extracted allogeneic(AAA) bone combined with vascular endothelial growth factor (VEGF) on bone reconstruction. METHOD: The AAA bone was made into a block and a granule shape, and mixed with VEGF to prepare VEGF bone. Establishment of rat calvarium defect animal model, it is divided into 5 groups. With block bone, granular bone, block VEGF bone, granular VEGF bone was implanted in the bone defect for repair as the experimental group. The defect area was evaluated by histological and CBCT analysis 4 weeks postoperatively. RESULTS: Postoperative 4 weeks imaging results showed that there was no high-density shadow in the bone defect area of the blank group and the volume of high-density shadow in the bone defect area of the experimental group was different. Histological results showed that no osteoblasts were found in the blank group, and new bone was formed in the experimental group. The effect of bone formation in the granular bone was better than that in the block bone, and the amount of new bone formation in the VEGF bone group was higher than that of the single bone group. CONCLUSION: Granular bone has a better osteogenesis effect than block bone. The effect of allogeneic bone combined with VEGF in promoting new bone formation in the area of the bone defect is better than that of allogeneic bone alone. These results provide a theoretical and practical basis for its further clinical application.

17.
ACS Appl Mater Interfaces ; 16(34): 44341-44349, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39152897

RESUMEN

Oxidase enzyme-based electrochemical bioassays have garnered considerable interest due to their specificity and high efficiency. However, in traditional solid-liquid diphase enzyme electrode systems, the low solubility of oxygen and its slow mass transfer rate limit the oxidase catalytic reaction kinetics, thereby affecting the bioassay performance, including the detection accuracy, sensitivity, and linear dynamic range. ZIF-8 nanoparticles (NPs) possess hydrophobic and high-porosity characteristics, enabling them to serve as oxygen nanocarriers. In this work, we constructed a solid-liquid-air triphase enzyme electrode by encapsulating ZIF-8 NPs within an oxidase network. Hydrophobic ZIF-8 NPs can provide a rapid and sufficient supply of oxygen for the oxidase-catalyzed reactions, which enhances and stabilizes the kinetics of oxidase-catalyzed reactions. This approach eliminates the issue of "oxygen deficiency" at the traditional solid-liquid diphase interface. Consequently, the triphase enzyme electrode exhibits a 12-fold higher linear detection range than the diphase system and possesses good detection accuracy in electrolytes even with fluctuating oxygen levels. This work proposes a novel approach to construct triphase reaction systems for addressing the gas deficiency problem in heterogeneous catalysis.


Asunto(s)
Electrodos , Cinética , Catálisis , Oxígeno/química , Oxidorreductasas/química , Oxidorreductasas/metabolismo , Estructuras Metalorgánicas/química , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Nanopartículas/química , Enzimas Inmovilizadas/química , Enzimas Inmovilizadas/metabolismo , Bioensayo , Imidazoles
18.
BMC Endocr Disord ; 24(1): 166, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215269

RESUMEN

OBJECTIVE: This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis. METHOD: PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis. RESULTS: A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia. CONCLUSION: Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia. PROSPERO REGISTRATION NUMBER: CRD42023472974.


Asunto(s)
Diabetes Gestacional , Hipoglucemia , Humanos , Hipoglucemia/epidemiología , Recién Nacido , Factores de Riesgo , Femenino , Embarazo , Diabetes Gestacional/epidemiología , Cesárea/estadística & datos numéricos , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/etiología , Hipertensión Inducida en el Embarazo/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/epidemiología , Síndrome de Dificultad Respiratoria del Recién Nacido/etiología , Estudios de Casos y Controles
19.
Carbohydr Res ; 544: 109229, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39154417

RESUMEN

Liver cancer is the third leading cause of cancer deaths globally. The use of Hydroxycamptothecin (HCPT) as a first-line chemotherapeutic agent for liver, lung, and gastric cancers is often hampered by its low activity, limited targeting, and poor water solubility. This results in a low accumulation of HCPT in tumor cells, as well as the inability to maintain continuous treatment. Consequently, there is an urgent need to develop an accessory method that can enhance the therapeutic efficacy of HCPT while exhibiting good biocompatibility and targeted delivery ability. To address this critical issue, an enzyme-triggered supramolecular nanocarrier, refer as SCD/LCC SNCs, has been successfully developed, leveraging the aggregation of the negatively charged sulfate-modified ß-CDs and positively charged lauroylcholine chloride (LCC). This nanocarrier demonstrates acetylcholinesterase (LCC) triggered decomposition behavior, making it a promising drug carrier for HCPT. The cellular assays conducted have demonstrated that HCPT loaded into these SCD/LCC SNCs exhibit reduced cytotoxicity towards normal cells while maintaining robust tumor inhibitory activity and inducing apoptosis. Therefore, this study offers a promising strategy for the effective use of HCPT in the treatment of liver cancer.


Asunto(s)
Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Camptotecina/farmacología , Camptotecina/química , Camptotecina/análogos & derivados , Acetilcolinesterasa/metabolismo , Acetilcolinesterasa/química , Apoptosis/efectos de los fármacos , Portadores de Fármacos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Sistemas de Liberación de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Células Hep G2
20.
Langmuir ; 40(36): 19134-19145, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39195164

RESUMEN

Designing nonprecious metal anode catalysts for photoassisted direct methanol fuel cells (PDMFCs) remains a challenge. As a semiconductor catalyst with a spinel structure, NiCo2O4 has good methanol catalytic oxidation activity and photocatalytic activity, making it a highly promising anode non-noble metal catalyst for PDMFCs. However, compared with the noble metal catalyst, the photoelectrocatalytic activity remained to be improved. In this report, an anion regulation strategy was adopted to improve the photoassisted methanol electrocatalytic activity. Using a CoNi-Aspartic (CoNi-Asp) nanorod as the precursor, the anion-regulated NiCo2X4 (X = O, S, Se, Te) was prepared by oxidation, sulfuration, selenization, and telluridation reactions. The regulation of anions and their effects on the electronic structure, intermediate product, and photoelectric catalytic performance of NiCo2X4 (X= O, S, Se, Te) was systematically discussed. Photoelectrochemical characterization and adsorption energy of •OH revealing the volcano-like correlation between the anion in NiCo2X4 (X = O, S, Se, Te) and their photoelectrocatalytic performance. The narrowest band gap (2.239 eV), the highest •OH adsorption energy (-3.32 eV), and the highest ratio of Co3+/Co2+ (2.19) ensure the best photoelectric catalytic performance of NiCo2S4, under the visible light irradiation, the photoresponse current density was 1.9 A g-1, the current density at 0.6 V was up to 21.9 A g-1. After 9 h of stability testing, the current retention rate was 80%. This report sheds an idea for the rational design of non-noble anode catalysts for PDMFCs.

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