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1.
Heliyon ; 10(16): e35066, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39220958

RESUMEN

Xixia amber from Henan Province in China has undergone a thorough examination utilizing microscopic observation, infrared spectroscopy, and three-dimensional (3D) fluorescence spectroscopy. This systematic analysis has revealed that there are primarily two varieties of Xixia amber: a light-colored type and a dark-colored type. These can be differentiated based on their coloration, infrared spectra, and distinctive fluorescence attributes. Notably, the infrared spectral profile of Xixia amber features a prominent peak at 1023 cm-1, accompanied by less pronounced peaks at 1088 and 974 cm-1. These spectral characteristics set it apart from amber originating from the Baltic regions, Myanmar, and Fushun. Further distinction is achieved through 3D fluorescence spectra, where Xixia amber exhibits similarities to Burmese and Fushun ambers. Chemical classification via pyrolysis gas chromatography-mass spectrometry (Py-GC-MS) identifies Xixia amber as belonging to Class Ib, characterized by its ordered structure and the absence of succinic acid. This comprehensive study delineates the coloration, infrared spectral properties, photoluminescent behavior, and chemical compositions of Xixia amber, clearly differentiating it from ambers sourced from other geographical locations.

2.
Chem Sci ; 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39165727

RESUMEN

Sialylation, a critical post-translational modification, regulates glycoprotein structure and function by tuning their molecular heterogeneity. However, characterizing its subtle and dynamic conformational effects at the intact glycoprotein level remains challenging. We introduce a glycoform-resolved unfolding approach based on a high-throughput ion mobility-mass spectrometry (IM-MS) platform. This method integrates high-throughput unfolding with parallel fragmentation, enabling simultaneous analysis of sialylation patterns, stoichiometries, and their impact on conformational stability. Applying this approach to fetuin, we identified distinct sialylation patterns and their differential influence on protein conformation, namely sialylation-induced stabilization during early unfolding and increased flexibility in later unfolding stages. IM-MS-guided molecular dynamics simulations revealed that increased sialylation enhances the initial conformational stability, likely through enhanced electrostatic interactions and hydrogen bonding. These findings highlight the complex interplay between sialylation and protein dynamics and establish glycoform-resolved unfolding IM-MS as a powerful tool for characterizing glycoprotein conformational landscapes.

3.
ACS Appl Mater Interfaces ; 16(31): 41400-41408, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39069698

RESUMEN

A photo/electrothermal surface can convert sunlight and electricity into heat to solve icing problems. The combination of active photo/electrothermal surfaces with passive slippery surfaces provides a highly efficient strategy for all-day anti/deicing. However, the lack of transparency remains a primary impediment to the widespread application of these anti-icing measures in photovoltaics, windshields, and other fields. Herein, we report a bilayer transparent photo/electrothermal coating with a liquid-like slippery property for all-day anti/deicing. The prepared coating exhibits ultraslippery, low ice adhesion, and enhanced stability properties through covalent grafting of polydimethylsiloxane (PDMS) brushes in a cross-linked skeleton of epoxy. Moreover, the coating demonstrates a visible transmittance of up to 77% and effectively absorbs ultraviolet and near-infrared light due to the addition of ultraviolet and infrared absorbers, resulting in a temperature increase under sun illumination. The bottom indium tin oxide layer is fabricated to provide the composite coating with electrothermal capability, so that it can achieve all-weather deicing. The coupling of photo/electrothermal and slippery properties can promote the rapid removal of grown ice in a short time. The slippery properties and their exceptional durability under mechanical, optical, and thermal conditions render the composite coatings highly promising for engineering applications.

4.
Cancer Med ; 13(14): e70016, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39030882

RESUMEN

BACKGROUND: Gliomas are recognized as the most frequent type of malignancies in the central nervous system, and efficacious prognostic indicators are essential to treat patients with gliomas and improve their clinical outcomes. The chemokine (C-C motif) ligand 2 (CCL2) is a promising predictor for glioma malignancy and progression. However, at present, the methods to evaluate CCL2 expression level are invasive and operator-dependent. OBJECTIVE: It was expected to noninvasively predict CCL2 expression levels in malignant glioma tissues by magnetic resonance imaging (MRI)-based radiomics and assess the association between the developed radiomics model and prognostic indicators and related genes. METHODS: MRI-based radiomics was used to predict CCL2 expression level using data obtained from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) databases. A support vector machine (SVM)-based radiomics model and a logistic regression (LR)-based radiomics model were used to predict the radiomics score, and its correlation with CCL2 expression level was analyzed. RESULTS: The results revealed that there was an association between CCL2 expression level and the overall survival of cases with gliomas, and bioinformatics correlation analysis showed that CCL2 expression level was highly correlated with disease-related pathways, such as mTOR signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Both SVM- and LR-based radiomics data robustly predicted CCL2 expression level, and radiomics scores could also be used to predict the overall survival of patients. Moreover, the high/low radiomics scores were highly correlated with the known glioma-related genes, including CD70, CD27, and PDCD1. CONCLUSION: An MRI-based radiomics model was successfully developed, and its clinical benefits were confirmed, including the prediction of CCL2 expression level and patients' prognosis.


Asunto(s)
Neoplasias Encefálicas , Quimiocina CCL2 , Glioma , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Regulación Neoplásica de la Expresión Génica , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/metabolismo , Glioma/patología , Imagen por Resonancia Magnética/métodos , Clasificación del Tumor , Pronóstico , Máquina de Vectores de Soporte
5.
J Colloid Interface Sci ; 674: 852-861, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38955016

RESUMEN

Lithium-selenium (Li-Se) batteries are considered promising alternatives to lithium-ion batteries due to their higher volumetric capacity and energy density. However, they still face limitations in efficiently utilizing the active selenium. Here, we develop surface-functionalized mesoporous hollow carbon nanospheres as the selenium host. By using KOH activation, the surface of the carbon nanospheres is functionalized with hydroxyl groups, which greatly improve the utilization of selenium and facilitate the conversion of lithium selenides, leading to much higher capacities compared to ZnCl2 activation and untreated carbon nanospheres. Theory and experimental evidence suggest that surface hydroxyl groups can enhance the reduction conversion of polyselenides to selenides and facilitate the oxidation reaction of selenides to elemental selenium. In-situ and ex-situ characterization techniques provided additional confirmation of the hydroxyl groups electrochemical durability in catalyzing selenium conversion. The meticulously engineered Se cathode demonstrates a high specific capacity of 594 mA h g-1 at 0.5C, excellent rate capability of 464 mA h g-1 at 2C, and a stable cycling performance of 500 cycles at 2C with a capacity retention of 84.8 %, corresponding to an ultra-low-capacity decay rate of 0.0144 % per cycle, surpassing many reported lithium-selenium battery technologies.

6.
Carbohydr Polym ; 342: 122388, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39048196

RESUMEN

Chitosan (CS) has physicochemical properties including solubility, crystallinity, swellability, viscosity, and cohesion, along with biological properties like biocompatibility, biodegradation, antioxidant, antibacterial, and antitumor effects. However, these characteristics of CS are greatly affected by its degree of deacetylation, molecular weight, pH and other factors, which limits the application of CS in biomedicine. The modification of CS with catechol-containing substances inspired by mussels can not only improve these properties of CS, but also endow it with self-healing property, providing an environmentally friendly and sustainable way to promote the application of CS in biomedicine. In this paper, the properties of CS and its limitation in the biomedical filed are introduced in detail. Then, the modification methods and properties of substances with catechol groups inspired by mussels on CS are reviewed. Finally, the applications of modified CS in the biomedical field of wound healing, drug delivery, anticancer therapy, biosensor and 3D printing are further discussed. This review can provide valuable information for the design and exploitation of mussel-inspired CS in the biomedical field.


Asunto(s)
Bivalvos , Quitosano , Cicatrización de Heridas , Quitosano/química , Animales , Bivalvos/química , Humanos , Cicatrización de Heridas/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Técnicas Biosensibles/métodos , Sistemas de Liberación de Medicamentos/métodos , Antineoplásicos/química , Antineoplásicos/farmacología , Impresión Tridimensional
7.
Medicine (Baltimore) ; 103(23): e38244, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847676

RESUMEN

BACKGROUND: Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data. METHODS: Relevant case-control studies were collected from PubMed, Embase, Web of Science and Cochrane databases up to January 7, 2024. Subsequently, odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of correlations. A sensitivity analysis was performed to evaluate the robustness and reliability of these included studies. RESULTS: A total of 25 articles including 44 studies, were included in this meta-analysis, including 26 studies on rs16260, 6 studies on rs3743674, 7 studies on rs5030625, and 5 studies on rs1801552. The pooled results showed that rs16260 was remarkably associated with an increased GC risk of GC among Caucasians. Moreover, the rs5030625 variation dramatically enhanced GC predisposition in the Asian population. However, no evident correlations between CDH1 rs3743674 and rs1801552 polymorphisms and GC risk were observed. CONCLUSIONS: Our findings suggested that CDH1 gene polymorphisms were significantly correlated with GC risk, especially in rs16260 and rs5030625 polymorphisms.


Asunto(s)
Antígenos CD , Cadherinas , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas , Humanos , Antígenos CD/genética , Pueblo Asiatico/genética , Cadherinas/genética , Estudios de Casos y Controles , Factores de Riesgo , Neoplasias Gástricas/genética , Población Blanca/genética
8.
J Bone Joint Surg Am ; 106(13): 1162-1170, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38691582

RESUMEN

BACKGROUND: Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. METHODS: This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. RESULTS: Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. CONCLUSIONS: Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Absorciometría de Fotón , Artroplastia de Reemplazo de Cadera , Conservadores de la Densidad Ósea , Densidad Ósea , Fémur , Osteoporosis Posmenopáusica , Proteína Relacionada con la Hormona Paratiroidea , Humanos , Femenino , Proteína Relacionada con la Hormona Paratiroidea/farmacología , Proteína Relacionada con la Hormona Paratiroidea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/farmacología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Fémur/efectos de los fármacos , Fémur/diagnóstico por imagen , Fémur/cirugía
9.
Plant Dis ; 108(8): 2550-2557, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38587804

RESUMEN

'Lantian 26', a leading elite winter wheat cultivar in Gansu Province since its release in 2010, exhibits high resistance or immunization to stripe rust in the adult-plant stage under a high disease pressure in Longnan (southeastern Gansu). Identifying the resistance genes in 'Lantian 26' could provide a basis for enhanced durability and high levels of resistance in wheat cultivars. Here, a segregating population was developed from a cross between a highly susceptible wheat cultivar Mingxian 169 and the highly stripe rust-resistant 'Lantian 26'. The F2 and F2:3 progenies of the cross were inoculated with multiple prevalent virulent races of stripe rust for adult-plant-stage-resistance evaluation in two different environments. Exon sequence alignment analysis revealed that a stripe rust resistance gene on the 718.4- to 721.2-Mb region of chromosome 7BL, tentatively named as YrLT26, and a cosegregation sequence-tagged site (STS) marker GY17 was developed and validated using the F2:3 population and 103 wheat cultivars. The other two resistance genes, Yr9 and Yr30, were also identified in 'Lantian 26' using molecular markers. Therefore, the key to high and durable resistance to stripe rust at the adult stage is the combination of Yr9, Yr30, and YrLT26 genes in 'Lantian 26'. This could be a considerable strategy for improving the wheat cultivars with effective and durable resistance in the high-pressure region for stripe rust.


Asunto(s)
Basidiomycota , Resistencia a la Enfermedad , Genes de Plantas , Enfermedades de las Plantas , Triticum , Triticum/microbiología , Triticum/genética , Triticum/inmunología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Resistencia a la Enfermedad/genética , Basidiomycota/fisiología , Genes de Plantas/genética
10.
Osteoporos Int ; 35(8): 1407-1415, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38653862

RESUMEN

Review of medical records from 173 women with osteoporosis who received abaloparatide treatment revealed that 96.0% had at least one visit for osteoporosis management and 55.5% had medication support group access. The most common reasons for discontinuing treatment were financial (31.2%) and tolerability (22.8%). Most patients (64.8%) completed treatment as prescribed. PURPOSE: Abaloparatide is approved for the treatment of women with postmenopausal osteoporosis at high risk for fracture. This study evaluated real-world treatment patterns for patients new to abaloparatide, regardless of osteoporosis treatment history. METHODS: Data for patients with ≥ 1 prescription for abaloparatide were collected retrospectively from six academic and clinical practice settings across the US. RESULTS: A total of 173 patients were enrolled (mean [SD] age, 69.8 [7.4] years). At the time of abaloparatide treatment initiation, 78.6% had received other osteoporosis medications. Mean (SD) time from discontinuation of osteoporosis medications prior to initiation of abaloparatide was 1.7 (3.2) years. Twenty-four months of follow-up data from the initiation date of abaloparatide was collected from 94.0% of patients and 6.0% of patients had 12-24 months of follow-up. During the follow-up period, 96.0% of patients had at least one visit for osteoporosis management and 55.5% had access to a medication support program. The median duration of therapy was 18.6 months and 105/162 (64.8%) completed abaloparatide treatment as prescribed. The most common reasons for treatment discontinuation were financial (31.2%) and tolerability (22.8%). Following completion of a course of treatment with abaloparatide, 82/162 (50.6%) patients transitioned to another osteoporosis medication. The median time between abaloparatide treatment course completion and the initiation of follow-on medication was 21 days. CONCLUSION: Most patients completed treatment with abaloparatide as prescribed, and over half continued with an antiresorptive agent. This favorable conduct may be the result of regular follow-up visits and accessibility to both medication and patient support services.


Asunto(s)
Conservadores de la Densidad Ósea , Osteoporosis Posmenopáusica , Proteína Relacionada con la Hormona Paratiroidea , Humanos , Femenino , Anciano , Osteoporosis Posmenopáusica/tratamiento farmacológico , Proteína Relacionada con la Hormona Paratiroidea/uso terapéutico , Proteína Relacionada con la Hormona Paratiroidea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Fracturas Osteoporóticas/prevención & control , Cumplimiento de la Medicación/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano de 80 o más Años , Costos de los Medicamentos
11.
Angew Chem Int Ed Engl ; 63(28): e202404703, 2024 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-38655625

RESUMEN

Self-assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting-hydrolysis-transformation (THT) assembly of glycosylated peptides in living cells holistically resembling viral infection for efficient cargo delivery and combined tumor therapy. We design a glycosylated peptide via incorporating a ß-galactose-serine residue into bola-amphiphilic sequences. Co-assembling of the glycosylated peptide with two counterparts containing irinotecan (IRI) or ligand TSFAEYWNLLSP (PMI) results in formation of the glycosylated co-assemblies SgVEIP, which target cancer cells via ß-galactose-galectin-1 association and undergo galactosidase-induced morphological transformation. While GSH-reduction causes release of IRI from the co-assemblies, the PMI moieties release p53 and facilitate cell death via binding with protein MDM2. Cellular experiments show membrane targeting, endo-/lysosome-mediated internalization and in situ formation of nanofibers in cytoplasm by SgVEIP. This cascade THT process enables efficient delivery of IRI and PMI into cancer cells secreting Gal-1 and overexpressing ß-galactosidase. In vivo studies illustrate enhanced tumor accumulation and retention of the glycosylated co-assemblies, thereby suppressing tumor growth. Our findings demonstrate an in situ assembly strategy mimicking viral infection, thus providing a new route for drug delivery and cancer therapy in the future.


Asunto(s)
Sistemas de Liberación de Medicamentos , Glicopéptidos , Humanos , Glicopéptidos/química , Glicopéptidos/metabolismo , Animales , Virosis/tratamiento farmacológico , Virosis/metabolismo , Irinotecán/química , Irinotecán/farmacología , Ratones , Línea Celular Tumoral
12.
Biol Reprod ; 111(1): 123-134, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38660750

RESUMEN

In oviparous animals, egg yolk is largely derived from vitellogenin, which is taken up from the maternal circulation by the growing oocytes via the vitellogenin receptor. Recently, a novel member of the lipoprotein receptor superfamily termed low-density lipoprotein receptor-related protein 13 was identified and proposed as a candidate of vitellogenin receptor in oviparous animals. However, the roles of low-density lipoprotein receptor-related protein 13 in vitellogenesis are still poorly defined. Here, we investigated the expression, vitellogenin-binding properties, and function of low-density lipoprotein receptor-related protein 13 in zebrafish. Two different lrp13 genes termed lrp13a and lrp13b were found in zebrafish. Reverse transcription polymerase chain reaction and quantitative polymerase chain reaction revealed both lrp13s to be predominantly expressed in zebrafish ovary, and in situ hybridization detected both lrp13s transcripts in the ooplasm of early stage oocytes. Two yeast hybrid studies showed that among eight vitellogenins of zebrafish, Vtg1, 2, and 3 bind to Lrp13a, while Vtg1, 2, and 5 bind to Lrp13b. We created zebrafish lrp13a and lrp13b mutant lines using CRISPR/Cas9. Knockout of lrp13a leads to a male-biased sex ratio and decreased diameter of embryo yolk, while knockout of lrp13b and double knockout of lrp13a and lrp13b leads to the delay of vitellogenesis, followed by follicular atresia. These phenotypes of mutants can be explained by the disruption of vitellogenesis in the absence of Lrp13s. Taken together, our results indicate that both Lrp13a and Lrp13b can serve as vitellogenin receptors in zebrafish among other vitellogenin receptors that are not yet described.


Asunto(s)
Proteínas del Huevo , Ovario , Vitelogeninas , Proteínas de Pez Cebra , Pez Cebra , Animales , Femenino , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismo , Ovario/metabolismo , Vitelogeninas/metabolismo , Vitelogeninas/genética , Proteínas del Huevo/metabolismo , Proteínas del Huevo/genética , Receptores de Superficie Celular/metabolismo , Receptores de Superficie Celular/genética
13.
BMC Plant Biol ; 24(1): 321, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38654179

RESUMEN

BACKGROUND: pOsNAR2.1:OsNAR2.1 expression could significantly increase nitrogen uptake efficiency and grain yield of rice. RESULT: This study reported the effects of overexpression of OsNAR2.1 by OsNAR2.1 promoter on physiological and agronomic traits associated with drought tolerance. In comparison to the wild-type (WT), the pOsNAR2.1:OsNAR2.1 transgenic lines exhibited a significant improvement in survival rate when subjected to drought stress and then irrigation. Under limited water supply conditions, compared with WT, the photosynthesis and water use efficiency (WUE) of transgenic lines were increased by 39.2% and 28.8%, respectively. Finally, the transgenic lines had 25.5% and 66.4% higher grain yield than the WT under full watering and limited water supply conditions, respectively. Compared with the WT, the agronomic nitrogen use efficiency (NUE) of transgenic lines increased by 25.5% and 66.4% under full watering and limited water supply conditions, and the N recovery efficiency of transgenic lines increased by 29.3% and 50.2%, respectively. The interaction between OsNAR2.1 protein and OsPLDα1 protein was verified by yeast hybrids. After drought treatment, PLDα activity on the plasma membrane of the transgenic line increased 85.0% compared with WT. CONCLUSION: These results indicated that pOsNAR2.1:OsNAR2.1 expression could improve the drought resistance of rice by increasing nitrogen uptake and regulating the expression of OsPLDα1.


Asunto(s)
Sequías , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Regiones Promotoras Genéticas , Resistencia a la Sequía , Nitrógeno/metabolismo , Oryza/genética , Oryza/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente
14.
Appl Environ Microbiol ; 90(4): e0188523, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38451077

RESUMEN

Histone acetyltransferase (HAT)-mediated epigenetic modification is essential for diverse cellular processes in eukaryotes. However, the functions of HATs in the human pathogen Aspergillus fumigatus remain poorly understood. In this study, we characterized the functions of MOZ, Ybf2/Sas3, Sas2, and Tip60 (MYST)-family histone acetyltransferase something about silencing (Sas3) in A. fumigatus. Phenotypic analysis revealed that loss of Sas3 results in significant impairments in colony growth, conidiation, and virulence in the Galleria mellonella model. Subcellular localization and Western blot analysis demonstrated that Sas3 localizes to nuclei and is capable of acetylating lysine 9 and 14 of histone H3 in vivo. Importantly, we found that Sas3 is critical for the cell wall integrity (CWI) pathway in A. fumigatus as evidenced by hypersensitivity to cell wall-perturbing agents, altered cell wall thickness, and abnormal phosphorylation levels of CWI protein kinase MpkA. Furthermore, site-directed mutagenesis studies revealed that the conserved glycine residues G641 and G643 and glutamate residue E664 are crucial for the acetylation activity of Sas3. Unexpectedly, only triple mutations of Sas3 (G641A/G643A/E664A) displayed defective phenotypes similar to the Δsas3 mutant, while double or single mutations did not. This result implies that the role of Sas3 may extend beyond histone acetylation. Collectively, our findings demonstrate that MYST-family HAT Sas3 plays an important role in the fungal development, virulence, and cell wall integrity in A. fumigatus. IMPORTANCE: Epigenetic modification governed by HATs is indispensable for various cellular processes in eukaryotes. Nonetheless, the precise functions of HATs in the human pathogen Aspergillus fumigatus remain elusive. In this study, we unveil the roles of MYST-family HAT Sas3 in colony growth, conidiation, virulence, and cell wall stress response in A. fumigatus. Particularly, our findings demonstrate that Sas3 can function through mechanisms unrelated to histone acetylation, as evidenced by site-directed mutagenesis experiments. Overall, this study broadens our understanding of the regulatory mechanism of HATs in fungal pathogens.


Asunto(s)
Aspergillus fumigatus , Histona Acetiltransferasas , Humanos , Aspergillus fumigatus/genética , Aspergillus fumigatus/metabolismo , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/química , Histona Acetiltransferasas/metabolismo , Histonas/genética , Histonas/metabolismo , Virulencia , Pared Celular/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
15.
JBMR Plus ; 8(2): ziae009, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38505522

RESUMEN

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80 µg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12 mo and/or a shift in T-score category (based on LS and TH T-scores) at 12 mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12 mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.

16.
Brain Behav Immun ; 119: 56-83, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38555992

RESUMEN

Decreased hippocampal tropomyosin receptor kinase B (TrkB) level is implicated in the pathophysiology of stress-induced mood disorder and cognitive decline. However, how TrkB is modified and mediates behavioral responses to chronic stress remains largely unknown. Here the effects and mechanisms of TrkB cleavage by asparagine endopeptidase (AEP) were examined on a preclinical murine model of chronic restraint stress (CRS)-induced depression. CRS activated IL-1ß-C/EBPß-AEP pathway in mice hippocampus, accompanied by elevated TrkB 1-486 fragment generated by AEP. Specifi.c overexpression or suppression of AEP-TrkB axis in hippocampal CaMKIIα-positive cells aggravated or relieved depressive-like behaviors, respectively. Mechanistically, in addition to facilitating AMPARs internalization, TrkB 1-486 interacted with peroxisome proliferator-activated receptor-δ (PPAR-δ) and sequestered it in cytoplasm, repressing PPAR-δ-mediated transactivation and mitochondrial function. Moreover, co-administration of 7,8-dihydroxyflavone and a peptide disrupting the binding of TrkB 1-486 with PPAR-δ attenuated depression-like symptoms not only in CRS animals, but also in Alzheimer's disease and aged mice. These findings reveal a novel role for TrkB cleavage in promoting depressive-like phenotype.


Asunto(s)
Depresión , Hipocampo , Estrés Psicológico , Animales , Hipocampo/metabolismo , Ratones , Depresión/metabolismo , Masculino , Estrés Psicológico/metabolismo , Receptor trkB/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Conducta Animal/fisiología , Transducción de Señal/fisiología , Enfermedad de Alzheimer/metabolismo , Glicoproteínas de Membrana/metabolismo
17.
Small ; 20(31): e2311435, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38461533

RESUMEN

All weather, high-efficiency, energy-saving anti-icing/de-icing materials are of great importance for solving the problem of ice accumulation on outdoor equipment surfaces. In this study, a composite material with energy storage, active electro-/photo-thermal de-icing and passive super-hydrophobic anti-icing properties is proposed. Fluorinated epoxy resin and MWCNTs/PTFE particles are used to prepare the top multifunctional anti-icing/de-icing layer, which exhibited super-hydrophobicity with water contact angle greater than 155° and conductivity higher than 69 S m-1. The super-hydrophobic durability of the top layer is verified through tape peeling and sandpaper abrasion tests. The surface can be heated by applying on voltage or light illumination, showing efficient electro-/photo-thermal and all-day anti-icing/de-icing performance. The oleogel material at the bottom layer is capable to absorb energy during heating process and release it during cooling process by phase transition, which greatly delayed the freezing time and saved energy. The icing test of single ice droplet, electro-/photo-thermal de-icing and defrosting tests also proved the high efficiency and energy saving of the anti-icing/de-icing strategy. This study provided a new way to manufacture multi-functional materials for practical anti-icing/de-icing applications.

18.
Molecules ; 29(5)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38474525

RESUMEN

Wood is a naturally porous material prone to microbial erosion and degradation in outdoor environments. Therefore, the development of an environmentally friendly wood preservative with excellent antibacterial effects and low toxicity is urgently needed. In this study, nitrogen-doped carbon quantum dots (N-CQDs) with excellent antifungal performance and fluorescent properties were synthesized using a one-step hydrothermal method with chitosan quaternary ammonium salt (HACC) as the raw material. The fluorescence characteristics of N-CQD preservatives can help track their position and distribution in wood. The minimum inhibitory concentration (MIC) of N-CQDs is 1.8 mg/mL, which was nearly 22 times lower than that of HACC (40.0 mg/mL) in the PDA medium. The decay resistance test demonstrated that wood treated with N-CQDs showed a considerably reduced decay degree and its mass loss rate decreased from 46 ± 0.5% to 3.8 ± 0.5%. Biological transmission electron microscopy revealed that N-CQDs effectively destroyed fungal cell structures, thereby hindering the growth of Coriolus versicolor. N-CQDs synthesized using the one-step hydrothermal method can be used as an efficient wood preservative that can effectively improve the utilization and service life of wood.


Asunto(s)
Antifúngicos , Puntos Cuánticos , Madera , Puntos Cuánticos/química , Antibacterianos , Microscopía Electrónica de Transmisión , Carbono/química
19.
Heliyon ; 10(4): e26511, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38420436

RESUMEN

Promoting equal access to public services and improving people's well-being is a key link in building a modern national governance system in China. However, under the Chinese-style fiscal decentralization system, local governments face the "dilemma" of economic growth goals and the improvement of people's livelihoods. China's basic public services still have the problems of insufficient supply quantity, unbalanced structure and low efficiency. This paper aims to explore the impact of fiscal decentralization and local government competition on basic public services, and provide a theoretical and practical basis for deepening the reform of China's fiscal and taxation system, perfecting the transfer payment system, and improving the public service provision at the present stage. Under the premise of theoretical hypothesis, based on the panel data of 178 prefecture-level cities in China from 2008 to 2019, which is obtained from the Statistical Yearbook and the Work report of prefecture-level governments, the fixed effect model and threshold model are used for the empirical test. The results show that: first, the increase of fiscal decentralization has a negative impact on supply of basic public services in prefecture-level cities; second, the local government competition aiming at economic growth will intensify the negative impact, and make the relationship between fiscal decentralization and basic public services show nonlinear characteristics; Third, compared with developed areas, the strengthening regulatory effect of local government competition is more obvious in less-developed areas, such as western and northeastern regions, and third-tier, fourth-tier, and fifth-tier cities. Based on these findings, this paper draws the following policy implications: strengthen the reform of the fiscal and taxation system below the provincial level, promote the construction of a direct transfer payment mechanism, adjust the standards and methods of performance appraisal, and use modern information technology to improve the public service demand and interest expression mechanisms.

20.
EBioMedicine ; 101: 104993, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38324982

RESUMEN

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).


Asunto(s)
Accidente Cerebrovascular Hemorrágico , Peritonitis , Succinatos , Humanos , Ratones , Animales , Proteína 1 Asociada A ECH Tipo Kelch , Accidente Cerebrovascular Hemorrágico/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Macrófagos/metabolismo , Peritonitis/tratamiento farmacológico , Fagocitosis , Pronóstico , Hidroliasas/genética , Hidroliasas/metabolismo , Hidroliasas/farmacología
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