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1.
Proc Natl Acad Sci U S A ; 121(21): e2312519121, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38739799

RESUMEN

Drawing on a harmonized longitudinal dataset covering more than 55,000 smallholder farms in six African countries, we analyze changes in crop productivity from 2008 to 2019. Because smallholder farmers represent a significant fraction of the world's poorest people, agricultural productivity in this context matters for poverty reduction and for the broader achievement of the UN Sustainable Development Goals. Our analysis measures productivity trends for nationally representative samples of smallholder crop farmers, using detailed data on agricultural inputs and outputs which we integrate with detailed data on local weather and environmental conditions. In spite of government commitments and international efforts to strengthen African agriculture, we find no evidence that smallholder crop productivity improved over this 12-y period. Our preferred statistical specification of total factor productivity (TFP) suggests an overall decline in productivity of -3.5% per year. Various other models we test also find declining productivity in the overall sample, and none of them finds productivity growth. However, the different countries in our sample experienced varying trends, with some instances of growth in some regions. The results suggest that major challenges remain for agricultural development in sub-Saharan Africa. They complement previous analyses that relied primarily on aggregate national statistics to measure agricultural productivity, rather than detailed microdata.


Asunto(s)
Agricultura , Productos Agrícolas , África del Sur del Sahara , Productos Agrícolas/crecimiento & desarrollo , Agricultura/métodos , Agricultura/tendencias , Humanos , Producción de Cultivos/estadística & datos numéricos , Producción de Cultivos/tendencias , Agricultores/estadística & datos numéricos , Granjas , Desarrollo Sostenible/tendencias
2.
PLoS Pathog ; 20(7): e1012352, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39024388

RESUMEN

CD4+ T cells are central mediators of protective immunity to blood-stage malaria, particularly for their capacity in orchestrating germinal center reaction and generating parasite-specific high-affinity antibodies. T follicular helper (Tfh) cells are predominant CD4+ effector T cell subset implicated in these processes, yet the factors and detailed mechanisms that assist Tfh cell development and function during Plasmodium infection are largely undefined. Here we provide evidence that receptor for activated C kinase 1 (RACK1), an adaptor protein of various intracellular signals, is not only important for CD4+ T cell expansion as previously implied but also plays a prominent role in Tfh cell differentiation and function during blood-stage Plasmodium yoelii 17XNL infection. Consequently, RACK1 in CD4+ T cells contributes significantly to germinal center formation, parasite-specific IgG production, and host resistance to the infection. Mechanistic exploration detects specific interaction of RACK1 with STAT3 in P. yoelii 17XNL-responsive CD4+ T cells, ablation of RACK1 leads to defective STAT3 phosphorylation, accompanied by substantially lower amount of STAT3 protein in CD4+ T cells, whereas retroviral overexpression of RACK1 or STAT3 in RACK1-deficient CD4+ T cells greatly restores STAT3 activity and Bcl-6 expression under the Tfh polarization condition. Further analyses suggest RACK1 positively regulates STAT3 stability by inhibiting the ubiquitin-proteasomal degradation process, thus promoting optimal STAT3 activity and Bcl-6 induction during Tfh cell differentiation. These findings uncover a novel mechanism by which RACK1 participates in posttranslational regulation of STAT3, Tfh cell differentiation, and subsequent development of anti-Plasmodium humoral immunity.


Asunto(s)
Diferenciación Celular , Malaria , Plasmodium yoelii , Receptores de Cinasa C Activada , Factor de Transcripción STAT3 , Células T Auxiliares Foliculares , Animales , Receptores de Cinasa C Activada/metabolismo , Factor de Transcripción STAT3/metabolismo , Malaria/inmunología , Malaria/parasitología , Ratones , Plasmodium yoelii/inmunología , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismo , Ratones Endogámicos C57BL , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Ratones Noqueados , Centro Germinal/inmunología
3.
Molecules ; 29(13)2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38998939

RESUMEN

In this paper, four heteroleptic Ce(III) complexes, including Ce(thd)3-phen (thd = 2,2,6,6-tetramethyl-3,5-heptanedione, phen = 1, 10-phenanthroline (1), Ce(thd)3-MEDA (MEDA = N-Methylethylenediamine (2), Ce(thd)3-MOMA (MOMA = N-(2-Methoxyethyl)methylamine (3), and Ce(thd)3-DMDE (DMDE = N,N″-dimethyl ethanol amine (4), were synthesized and characterized with 1H-NMR, elemental analysis, and X-ray single-crystal diffraction. The thermogravimetric analysis and vapor pressure results indicated that the complexing ability of a nitrogen-containing bidentate ligand with a cerium ion was stronger than that of a mixed oxygen-nitrogen-containing bidentate ligand. Complex 2 was selected as an ALD precursor to deposit a CeO2 film on a SiO2/Si (100) wafer. The self-limited deposition results demonstrated that complex 2 was a potential ALD precursor.

4.
Biochem Biophys Res Commun ; 629: 165-170, 2022 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-36122454

RESUMEN

Hypoxic pulmonary hypertension (HPH) is a respiratory disease characterized by increased pulmonary vascular resistance and pulmonary arterial pressure. Persistent hypoxia alters the metabolic and transport functions of endothelial cells and promotes thrombosis and inflammation. Type 3 inositol-1,4,5-trisphosphate receptor (IP3R3) controls the release of calcium ions from the endoplasmic reticulum to the cytoplasm and mitochondria and is involved in cell proliferation, migration, and protein synthesis. In this study, we investigated the role and function of IP3R3 in HPH. The results showed that the expression level of IP3R3 was increased in pulmonary artery endothelial cells (PAECs) in a rat HPH model. The pulmonary artery pressure indices of IP3R3(-/-) mice with persistent hypoxia were significantly lower than those of HPH mice. The expression level of IP3R3 was significantly increased in hypoxia-treated PAECs. Knockdown of IP3R3 significantly inhibited the proliferation, migration and mesenchymal transition of PAECs induced by hypoxia. In conclusion, knockdown of IP3R3 can inhibit hypoxia-induced dysfunctions in PAECs, thus enabling IP3R3(-/-) mice to avoid HPH development. IP3R3 plays a key role in HPH and can be used as a potential target for the prevention and treatment of HPH.


Asunto(s)
Hipertensión Pulmonar , Animales , Calcio/metabolismo , Proliferación Celular , Células Endoteliales/metabolismo , Hipertensión Pulmonar/metabolismo , Hipoxia/complicaciones , Hipoxia/genética , Hipoxia/metabolismo , Inositol/metabolismo , Ratones , Polifosfatos , Arteria Pulmonar/metabolismo , Ratas
5.
J Neurosci ; 38(15): 3823-3839, 2018 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-29540548

RESUMEN

Itch is an unpleasant sensation that initiates scratching behavior. The itch-scratch reaction is a complex phenomenon that implicates supraspinal structures required for regulation of sensory, emotional, cognitive, and motivational aspects. However, the central mechanisms underlying the processing of itch and the interplay of the supraspinal regions and spinal cord in regulating itch-scratch processes are poorly understood. Here, we have shown that the neural projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a critical circuit element for regulating itch-related behaviors in the brains of male C57BL/6J mice. Moreover, we demonstrate that ACC-DMS projections selectively modulate histaminergic, but not nonhistaminergic, itch-related behavior. Furthermore, photoactivation of ACC-DMS projections has also no significant effects on pain behavior induced by thermal, mechanical, and chemical stimuli except for a relief on inflammatory pain evoked by formalin and complete Freund's adjuvant. We further demonstrate that the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons, which represent a population of spinal inhibitory interneurons that mediate the inhibition of itch. Therefore, this study presents the first evidence that the ACC-DMS projections modulate histaminergic itch-related behavior and reveals an interplay between the supraspinal and spinal levels in histaminergic itch regulation.SIGNIFICANCE STATEMENT This study reveals that the projections from anterior cingulate cortex (ACC) to dorsal medial striatum (DMS) constitute a supraspinal circuit for modulation of histaminergic, but not nonhistaminergic, itch. Manipulation of ACC-DMS projections has no effect on acute pain sensation. Furthermore, the dorsal spinal cord exerts an inhibitory effect on itch signal from ACC-DMS projections through B5-I neurons. Understanding the supraspinal itch circuits is of great significance in the development of new therapies for chronic itch-related intractable diseases.


Asunto(s)
Cuerpo Estriado/fisiología , Giro del Cíngulo/fisiología , Histamina/metabolismo , Neuronas/fisiología , Prurito/fisiopatología , Animales , Cuerpo Estriado/citología , Giro del Cíngulo/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Nocicepción
6.
J Cell Physiol ; 234(5): 5507-5518, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30317575

RESUMEN

The tumor suppressor protein p53 is a central governor of various cellular signals. It is well accepted that ubiquitination as well as ubiquitin-like (UBL) modifications of p53 protein is critical in the control of its activity. Interferon-stimulated gene 15 (ISG15) is a well-known UBL protein with pleiotropic functions, serving both as a free intracellular molecule and as a modifier by conjugating to target proteins. Initially, attentions have historically focused on the antiviral effects of ISG15 pathway. Remarkably, a significant role in the processes of autophagy, DNA repair, and protein translation provided considerable insight into the new functions of ISG15 pathway. Despite the deterministic revelation of the relation between ISG15 and p53, the functional consequence of p53 ISGylation appears somewhat confused. More important, more recent studies have hinted p53 ubiquitination or other UBL modifications that might interconnect with its ISGylation. Here, we aim to summarize the current knowledge of p53 ISGylation and the differences in other significant modifications, which would be beneficial for the development of p53-based cancer therapy.


Asunto(s)
Citocinas/metabolismo , Neoplasias/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Ubiquitinación , Ubiquitinas/metabolismo , Animales , Antineoplásicos/uso terapéutico , Humanos , Terapia Molecular Dirigida , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Estabilidad Proteica , Proteolisis , Sumoilación , Proteína p53 Supresora de Tumor/genética , Ubiquitinación/efectos de los fármacos
7.
J Cell Physiol ; 234(5): 7587-7599, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30479019

RESUMEN

Activation of quiescent hepatic stellate cells (HSCs) is the major event in liver fibrosis, along with enhancement of cell proliferation and overproduction of extracellular matrix. Recent findings suggest that senescence of activated HSCs might limit the development of liver fibrosis. The p53, a guardian of the genome is associated with liver fibrosis, has been shown to regulate HSCs senescence. In this study, we report that microRNA-145 (miR-145) and p53 were downregulated in vivo and in vitro, concomitant with the enhanced expression of zinc finger E-box binding homeobox 2 (ZEB2). In addition, overexpression of miR-145 and p53 led to upregulation of the number of senescence-associated ß-galactosidase-positive HSCs and the expression of senescence markers p16 and p21, along with the reduced abundance of HSC activation markers α-smooth muscle actin and type I collagen in activated HSCs. Furthermore, silencing of ZEB2 promoted senescence of activated HSCs. Moreover, we also demonstrated that miR-145 specifically targeted the 3'-untranslated regions of ZEB2. In vitro promoter regulation studies show that ZEB2 could bind to the E-box of the p53 promoter as well as inhibit its promoter activity and thus suppress the expression of p53, which in turn repressed activated HSCs senescence. Taken together, our results describe a novel miR-145-ZEB2-p53 regulatory line might participate in the senescence of activated HSCs and might carry potential therapeutic targets for restraining liver fibrosis.


Asunto(s)
Senescencia Celular/genética , Células Estrelladas Hepáticas/patología , MicroARNs/genética , Proteína p53 Supresora de Tumor/genética , Caja Homeótica 2 de Unión a E-Box con Dedos de Zinc/genética , Regiones no Traducidas 3'/genética , Animales , Línea Celular , Proliferación Celular/genética , Regulación hacia Abajo/genética , Hígado/patología , Cirrosis Hepática/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas/genética , Transducción de Señal/genética , Regulación hacia Arriba/genética
8.
J Formos Med Assoc ; 117(4): 276-282, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29449065

RESUMEN

BACKGROUND/PURPOSE: Fluoride and epigallocatechin gallate (EGCG) have been proven to prevent dental caries. The purpose of this study was to evaluate the effects of fluoride and EGCG on soft-drink-induced dental erosion in vitro. METHODS: Forty enamel and dentin specimens were prepared from extracted human teeth. The specimens were divided into 4 groups and treated separately with distilled water (as control), 0.5 M sodium fluoride (NF), 400 µM EGCG (EG), and a solution containing 0.5 M NaF and 400 µM EGCG (FG). Cyclic erosive treatment was performed according to the experimental procedures. The specimens were analyzed using laser scanning confocal microscopy, scanning electron microscopy, and a microhardness tester. The data were analyzed using ANOVA and Bonferroni's post hoc test. The significance level was set at 5%. RESULTS: The amount of substance loss was lower in the NF and EG groups than in the control group (p < 0.05). The erosion-caused substance loss was more pronounced in the dentin than in the enamel specimens. Surface microhardness loss was lower in the NF and EG groups than in the control group (p < 0.05). The diameter of the dentinal tubule was wider in the control group than in the NF and EG groups (p < 0.05). No combined effects were observed in the FG group. CONCLUSION: Both fluoride and EGCG are effective in preventing soft-drink-induced erosion compared with the control group. Fluoride and EGCG may interfere with each other. The mechanisms of the anti-erosive effect need to be explored in the future.


Asunto(s)
Bebidas Gaseosas/efectos adversos , Catequina/análogos & derivados , Fluoruro de Sodio/farmacología , Erosión de los Dientes/prevención & control , Catequina/farmacología , Esmalte Dental , Dentina , Humanos , Microscopía Electrónica de Rastreo , Raíz del Diente
9.
Environ Sci Pollut Res Int ; 31(6): 9495-9511, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38191723

RESUMEN

Correctly identifying and handling the relationship between land use carbon emission efficiency (LUCEE) and land ecological security (LES) are important to promote carbon neutrality in the overall layout of ecological civilization construction. This study takes 30 provinces in China as the research unit and measures the level of LUCEE and LES in each province in the period from 2011 to 2020 via a super-efficient slack-based measure model considering undesirable output. The coupling coordination degree (CCD) of LUCEE and LES is calculated, and its spatiotemporal evolution pattern is explored by kernel density estimation and standard deviational ellipse (SDE). The Dagum Gini coefficient is used to study spatial regional differences and the sources of differences. Results show that (1) China's LUCEE exhibited a downward and then an upward trend, as well as a spatial pattern of "high in the west and low in the east" with obvious regional differences. The LES experienced a positive transformation of "less secure → basically secure → more secure" nationwide, with no apparent regional differences. (2) The kernel density curves showed a continuous increase in CCD in general, while interprovincial differences increased, then decreased, and shifted from multipolar to bipolar differentiation. (3) The migration of SDE centers in CCD demonstrated a path of "southeast → southwest → northeast," and the ellipticity increased from 0.167 to 0.173, showing a trend of concentrated distribution. (4) The overall Gini coefficient of the national CCD indicated a decreasing trend, but imbalances remained, with the largest annual average value in the western region (0.120) and the smallest in the northeast (0.044). The main source of regional disparity was the intensity of transvariation. Accordingly, this study proposes targeted regional development strategies to promote low-carbon sustainable land use and improve the ability of land ecosystems to prevent security risks.


Asunto(s)
Carbono , Ecosistema , China , Condiciones Sociales , Análisis Espacial , Desarrollo Económico , Eficiencia
10.
IEEE J Biomed Health Inform ; 28(5): 2891-2903, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38363665

RESUMEN

Spectral CT can provide material characterization ability to offer more precise material information for diagnosis purposes. However, the material decomposition process generally leads to amplification of noise which significantly limits the utility of the material basis images. To mitigate such problem, an image domain noise suppression method was proposed in this work. The method performs basis transformation of the material basis images based on a singular value decomposition. The noise variances of the original spectral CT images were incorporated in the matrix to be decomposed to ensure that the transformed basis images are statistically uncorrelated. Due to the difference in noise amplitudes in the transformed basis images, a selective filtering method was proposed with the low-noise transformed basis image as guidance. The method was evaluated using both numerical simulation and real clinical dual-energy CT data. Results demonstrated that compared with existing methods, the proposed method performs better in preserving the spatial resolution and the soft tissue contrast while suppressing the image noise. The proposed method is also computationally efficient and can realize real-time noise suppression for clinical spectral CT images.


Asunto(s)
Algoritmos , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Relación Señal-Ruido
11.
J Vis Exp ; (203)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38345250

RESUMEN

Transplantation of photoreceptor cells and retinal pigment epithelial (RPE) cells provide a potential therapy for retinal degeneration diseases. Subretinal transplantation of therapeutic donor cells into mouse recipients is challenging due to the limited surgical space allowed by the small volume of the mouse eye. We developed a trans-scleral surgical transplantation platform with direct transpupillary vision guidance to facilitate the subretinal delivery of exogenous cells in mouse recipients. The platform was tested using retinal cell suspensions and three-dimensional retinal sheets collected from rod-rich Rho::EGFP mice and cone-rich OPN1LW-EGFP;NRL-/- mice, respectively. Live/dead assay showed low cell mortality for both forms of donor cells. Retinal grafts were successfully delivered into the subretinal space of a mouse model of retinal degeneration, Rd1/NS, with minimum surgical complications as detected by multimodal confocal scanning laser ophthalmoscope (cSLO) imaging. Two months post-transplantation, histological staining demonstrated evidence of advanced maturation of the retinal grafts into 'adult' rods and cones (by robust Rho::EGFP, S-opsin, and OPN1LW:EGFP expression, respectively) in the subretinal space. Here, we provide a surgical platform that can enable highly accurate subretinal delivery with a low rate of complications in mouse recipients. This technique offers precision and relative ease of skill acquisition. Furthermore, the technique could be used not only for studies of subretinal cell transplantation but also for other intraocular therapeutic studies including gene therapies.


Asunto(s)
Degeneración Retiniana , Ratones , Animales , Degeneración Retiniana/cirugía , Degeneración Retiniana/metabolismo , Retina/metabolismo , Células Fotorreceptoras Retinianas Conos/metabolismo , Trasplante de Células/métodos , Visión Ocular
12.
J Virol Methods ; 328: 114954, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38763359

RESUMEN

Porcine circovirus type 2 (PCV2) is intensely prevalent in global pig farms. The PCV2 vaccine is an important means of preventing and controlling PCV2. The quality control of PCV2 vaccines is predominantly based on detection techniques such as animal testing and neutralizing antibody titration. Measuring the content of effective proteins in vaccines to measure vaccine efficacy is an excellent alternative to traditional methods, which can greatly accelerate the development speed and testing time of vaccines. In this study, we screened a monoclonal antibody (mAb) that can effectively recognize not only the exogenous expression of PCV2 Cap protein but also PCV2 virus. The double antibody sandwich ELISA (DAS-ELISA) was developed using this mAb that specifically recognize PCV2 Cap. The minimum protein content detected by this method is 3.5 ng/mL. This method can be used for the quality control of PCV2 inactivated vaccine and subunit vaccine, and the detection results are consistent with the results of mice animal experiments. This method has the advantages of simple operation, good sensitivity, high specificity and wide application. It can detect the effective antigen Cap protein content of various types of PCV2 vaccines, which not only shorten the vaccine inspection time but also save costs.


Asunto(s)
Anticuerpos Monoclonales , Anticuerpos Antivirales , Antígenos Virales , Infecciones por Circoviridae , Circovirus , Ensayo de Inmunoadsorción Enzimática , Sensibilidad y Especificidad , Enfermedades de los Porcinos , Vacunas Virales , Circovirus/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática/métodos , Porcinos , Vacunas Virales/inmunología , Anticuerpos Monoclonales/inmunología , Antígenos Virales/inmunología , Antígenos Virales/análisis , Ratones , Anticuerpos Antivirales/sangre , Infecciones por Circoviridae/veterinaria , Infecciones por Circoviridae/diagnóstico , Infecciones por Circoviridae/prevención & control , Enfermedades de los Porcinos/diagnóstico , Enfermedades de los Porcinos/prevención & control , Enfermedades de los Porcinos/virología , Proteínas de la Cápside/inmunología
13.
Org Biomol Chem ; 11(33): 5491-9, 2013 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-23860780

RESUMEN

The copper-catalyzed C-H functionalization/O-H insertion reaction of α-diazophosphonates with alcohols has been developed with iodine as an additive. In order to understand this reaction, we present here a possible mechanism for the combined reaction. This process provides straightforward access to tertiary ß-alkoxy substituted ß-aminophosphonate derivatives with moderate to good yields.


Asunto(s)
Alcoholes , Ácido Aminoetilfosfónico/síntesis química , Compuestos Azo/síntesis química , Cobre/química , Compuestos Organometálicos/química , Organofosfonatos/síntesis química , Alcoholes/química , Ácido Aminoetilfosfónico/química , Compuestos Azo/química , Catálisis , Yodo/química , Estructura Molecular , Organofosfonatos/química
14.
Environ Sci Pollut Res Int ; 30(10): 27013-27029, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36374385

RESUMEN

To achieve the goal of "carbon peak and carbon neutrality", it is crucial for China to effectively control environmental pollution in low-carbon action (LCA). Based on the evidence from 283 cities in China from 2007 to 2019, the difference-in-differences (DID) method is applied to explore the impact of LCA on pollutant emissions represented by the pilot of low-carbon city construction (LCCC) in China. The main findings are as follows. First of all, the LCCC suppresses pollution emissions, and the basic conclusions are still stable after endogenous treatment and robustness testing. Secondly, the mechanism analysis reveals that the main path of LCCC affecting pollution reduction comes from the progress of green technology and the upgrading of industrial structure. Finally, the heterogeneity analysis shows that the pollution reduction effect of the LCCC is better in the eastern region and cities with higher level of green economy development. Based on the policy standpoint of environmental protection, the LCCC has opened up a reasonable exploration path for China and other countries in the world to carry out effective pollution reduction.


Asunto(s)
Contaminantes Ambientales , Contaminación Ambiental , Ciudades , Carbono , China , Desarrollo Económico , Dióxido de Carbono
15.
Acta Biomater ; 167: 16-37, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37331614

RESUMEN

With the advancement of additive manufacturing (AM), customized vascular stents can now be fabricated to fit the curvatures and sizes of a narrowed or blocked blood vessel, thereby reducing the possibility of thrombosis and restenosis. More importantly, AM enables the design and fabrication of complex and functional stent unit cells that would otherwise be impossible to realize with conventional manufacturing techniques. Additionally, AM makes fast design iterations possible while also shortening the development time of vascular stents. This has led to the emergence of a new treatment paradigm in which custom and on-demand-fabricated stents will be used for just-in-time treatments. This review is focused on the recent advances in AM vascular stents aimed at meeting the mechanical and biological requirements. First, the biomaterials suitable for AM vascular stents are listed and briefly described. Second, we review the AM technologies that have been so far used to fabricate vascular stents as well as the performances they have achieved. Subsequently, the design criteria for the clinical application of AM vascular stents are discussed considering the currently encountered limitations in materials and AM techniques. Finally, the remaining challenges are highlighted and some future research directions are proposed to realize clinically-viable AM vascular stents. STATEMENT OF SIGNIFICANCE: Vascular stents have been widely used for the treatment of vascular disease. The recent progress in additive manufacturing (AM) has provided unprecedented opportunities for revolutionizing traditional vascular stents. In this manuscript, we review the applications of AM to the design and fabrication of vascular stents. This is an interdisciplinary subject area that has not been previously covered in the published review articles. Our objective is to not only present the state-of-the-art of AM biomaterials and technologies but to also critically assess the limitations and challenges that need to be overcome to speed up the clinical adoption of AM vascular stents with both anatomical superiority and mechanical and biological functionalities that exceed those of the currently available mass-produced devices.


Asunto(s)
Materiales Biocompatibles , Enfermedades Vasculares , Humanos , Stents , Tecnología
16.
J Pharm Biomed Anal ; 233: 115496, 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37285658

RESUMEN

A study on the polysorbate 80 stability in various formulation buffers commonly used in biopharmaceuticals was performed, to investigate the excipients influence on polysorbate 80 degradation. Polysorbate 80 is a common excipient in biopharmaceutical products. However, its degradation will potentially impact the drug product quality, and may trigger protein aggregation and particles formation. Due to the heterogeneity of the polysorbates and the mutual effects with other formulation compositions, the study of polysorbate degradation is challenging. Herein, a real-time stability study was designed and performed. The polysorbate 80 degradation trend was monitored by fluorescence micelle-based assay (FMA), reversed-phase-ultra-performance liquid chromatography-evaporative light scattering detector (RP-UPLC-ELSD) assay, and LC-MS assay. These assays provide orthogonal results to reveal both the micelle-forming capability and the compositional changes of polysorbate 80 in different buffer systems. The degradation occurred after a period of storage under 25 °C in different trend, which indicates the excipients could impact the degradation kinetics. Upon comparison, the degradation is prone to happen in histidine buffer than in acetate, phosphate or citrate buffers. LC-MS confirms oxidation as an independent degradation pathway with detection of the oxidative aldehyde. Thus, it is necessary to pay more attention to the excipients selection and their potential impact on polysorbate 80 stability to achieve longer shelf life for the biopharmaceuticals. Besides, the protective roles of several additives were figured out, which could be applied as potential industrial solutions to the polysorbate 80 degradation issues.


Asunto(s)
Productos Biológicos , Polisorbatos , Excipientes , Micelas , Cromatografía Líquida de Alta Presión/métodos , Tampones (Química)
17.
J Dent Sci ; 18(2): 822-832, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37021246

RESUMEN

Background/purpose: A challenge that arises with periodontal regeneration surgery has been associated with the future development of periodontal regeneration membrane to prevent gingiva and fibroblasts invade the wound and allow alveolar bone successfully regenerated. Materials and methods: Chitosan (CS) has the advantages of non-toxicity, biodegradation, biocompatibility, and has been widely used in wound dressings. A flexible film was made using polyvinyl alcohol (PVA) blending CS based thermosensitive hydrogel. Results: The proposed 2% PVA/CS hydrogel has the highest swelling ratio about 720% after 60 min incubation and keeps its area after 10 min incubation for surgery suture. The elastic modulus of 0%, 1%, 2%, and 4% PVA/CS hydrogel were 7.75 ± 1.96, 0.91 ± 0.16, 0.75 ± 0.21, and 0.37 ± 0.06 MPa, respectively. The maximum strain of 2% PVA/CS hydrogel was 101.00 ± 28.03 (%). After 8 weeks biodegradation, the remain weight of 2% PVA/CS hydrogel was 71.36 ± 0.79 (%). Conclusion: In vitro cytotoxicity tests were performed and demonstrated PVA/CS hydrogel significantly improving cell proliferation. This study realized a promising flexible film for periodontal regeneration membrane that can prevent the rapid growth of fibroblasts to invade the wound and be used for periodontal regeneration surgery.

18.
Sci Total Environ ; 856(Pt 2): 159273, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36209887

RESUMEN

Nitrogenous disinfection byproducts (N-DBPs), such as halocetamides (HAcAms), haloacetonitriles (HANs) and halonitromethanes (HNMs), are emerging DBPs in drinking water. They are more toxic than currently regulated DBPs, attracting more attention to their toxic effects and mechanism. In this study, human embryonic kidney (HEK) 293T cells were employed to explore the cytotoxicity of 29 N-DBPs. The influence of molecular structures and different halogenations on cytotoxicity has been comparatively analyzed. As toxicity is the downstream of chemico-biological interactions, the thiol reactivity of 29 N-DBPs has thus been evaluated by using glutathione (GSH) as a model nucleophile, which is the most prevalent cellular thiol and acts as an antioxidant to protect cells by detoxifying electrophilic compounds. Results show that the cytotoxicity of N-DBPs follows by the order of HAcAms > HANs > HNMs, which is different from their reactivity with GSH (the median of kGSH ranks as HNMs > HAcAms > HANs). However, a significant correlation (p < 0.001) between log kGSH and log IC50 (concentration causing 50% inhibition) has been respectively observed for HAcAms and HANs subset and HNMs subset, indicating such chemical reaction is a probable trigger for these DBPs to result in cytotoxicity. Finally, two separate quantitative structure - activity relationship (QSAR) models based on HANs & HAcAms subset and HNMs subset have been developed for estimating IC50 values. The good statistical performance makes the models possible to quickly and accurately predict IC50 values of other N-DBPs, providing basic data for their health risk assessment and greatly reducing in vivo and in vitro experiments.


Asunto(s)
Desinfectantes , Agua Potable , Contaminantes Químicos del Agua , Purificación del Agua , Humanos , Desinfección/métodos , Purificación del Agua/métodos , Desinfectantes/toxicidad , Desinfectantes/química , Nitrógeno/química , Contaminantes Químicos del Agua/análisis , Agua Potable/análisis , Halogenación , Compuestos de Sulfhidrilo
19.
Phys Med Biol ; 68(7)2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36821861

RESUMEN

Objective.X-ray scatter leads to signal bias and degrades the image quality in Computed Tomography imaging. Conventional real-time scatter estimation and correction methods include the scatter kernel superposition (SKS) methods, which approximate x-ray scatter field as a convolution of the scatter sources and scatter propagation kernels to reflect the spatial spreading of scatter x-ray photons. SKS methods are fast to implement but generally suffer from low accuracy due to the difficulties in determining the scatter kernels.Approach.To address such a problem, this work describes a new scatter estimation and correction method by combining the concept of SKS methods and convolutional neural network. Unlike conventional SKS methods which estimate the scatter amplitude and the scatter kernel based on the value of an individual pixel, the proposed method generates the scatter amplitude maps and the scatter width maps from projection images through a neural network, from which the final estimated scatter field is calculated based on a convolution process.Main Results.By incorporating physics in the network design, the proposed method requires fewer trainable parameters compared with another deep learning-based method (Deep Scatter Estimation). Both numerical simulations and physical experiments demonstrate that the proposed SKS-inspired convolutional neural network outperforms the conventional SKS method and other deep learning-based methods in both qualitative and quantitative aspects.Significance.The proposed method can effectively correct the scatter-related artifacts with a SKS-inspired convolutional neural network design.


Asunto(s)
Artefactos , Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Dispersión de Radiación , Método de Montecarlo , Redes Neurales de la Computación , Tomografía Computarizada de Haz Cónico/métodos , Algoritmos
20.
FEBS Open Bio ; 13(9): 1723-1736, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37400956

RESUMEN

Stress-related illnesses are linked to the onset and progression of renal diseases and depressive disorders. To investigate stress-induced changes in the renal transcriptome associated with the development of depressive behaviors, we generated here a chronic social defeat stress (CSDS) model of C57 BL/6 male mice and then performed RNA sequencing of the kidneys to obtain an inflammation-related transcriptome. Administration of the antidepressant drug fluoxetine (10 mg·kg-1 ·day-1 ) during CSDS induction could partially alleviate renal inflammation and reverse CSDS-induced depression-like behaviors. Moreover, fluoxetine also modulated gene expression of stress-related hormone receptors, including prolactin and melanin-concentrating hormone. These results suggest that CSDS can induce gene expression changes associated with inflammation in the kidney of C57 BL/6 male mice, and this inflammation can be treated effectively by fluoxetine.


Asunto(s)
Antidepresivos , Fluoxetina , Animales , Ratones , Masculino , Fluoxetina/farmacología , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Depresión/metabolismo , Inflamación/tratamiento farmacológico , Riñón
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