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1.
Eur J Pharmacol ; 982: 176953, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39216743

RESUMEN

Chronic-healing skin wounds are a common complication in diabetic individuals. To alleviate patient suffering, there is a pressing demand for more effective strategies to expedite the repair of diabetic wounds. Fibroblast growth factor 21(FGF21) has been proven to accelerate wound healing, but its stability and ability to assist in the healing of diabetic ulcers have not met expectations. Therefore, we have fused FGF21 with an elastin-like peptide (ELP) to create a recombinant fusion protein (abbreviated as "ELF") to increase the bioactivity and stability in vitro or in vivo. Our results demonstrated that ELF significantly improved the efficiency of FGF21 purification due to the inverse temperature responsive phase transition property of ELP. Meanwhile, the fusion strategy did not impair the structure of FGF21 or diminish its activity, as demonstrated by the highly similar secondary structure of ELF and FGF21, and their considerable inhibitory activity in the glucose consumption experiment of Huh-7 cells. An in vitro migration assay revealed that ELF promoted healing more effectively than either free FGF21 or ELP. Further in vivo study revealed the ability of ELF to improve skin wound healing quality, manifested by lower levels of inflammatory factors, more collagen formation and deposition, and the formation of robust vascular networks, though there was no significant difference in healing rate among the ELF, FGF21, and ELP groups. In conclusion, our study indicated that FGF21 and ELP fusion molecules could be developed as more efficient and cost-effective therapeutic strategies for diabetic wound healing.


Asunto(s)
Colágeno , Diabetes Mellitus Experimental , Elastina , Factores de Crecimiento de Fibroblastos , Proteínas Recombinantes de Fusión , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Elastina/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Factores de Crecimiento de Fibroblastos/uso terapéutico , Factores de Crecimiento de Fibroblastos/genética , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratones , Colágeno/metabolismo , Colágeno/biosíntesis , Masculino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Péptidos/farmacología , Péptidos/uso terapéutico , Piel/patología , Piel/efectos de los fármacos , Piel/metabolismo , Neovascularización Fisiológica/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones Endogámicos C57BL
2.
Telemed J E Health ; 30(9): 2502-2512, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38938217

RESUMEN

Purpose: With the rapid advancement of technology, online health care services are becoming increasingly prominent. This study aims to investigate medical students' perceptions, attitudes, and readiness to adopt online health care services. Methods: Based on a literature review, this study constructed a conceptual model describing the relationships among medical students' perception, personality traits, and usage intention, grounded in the Technology Acceptance Model and Technology Readiness Index (TRI). The data for this study were collected from January to February 2023 through a questionnaire survey at Wenzhou Medical University, China. The proposed hypotheses were tested using structural equation modeling through AMOS software. Results: Out of the 340 respondents, 281 (82.6%) validly responded. Among these, 58.4% of medical students agreed and strongly agreed with the intention to become an online doctor. Within the TRI's motivational factors, optimism positively and significantly affected perceived usefulness (PU) and perceived ease of use (PEOU). Innovativeness also significantly enhanced PEOU. Among the inhibitory factors, insecurity was found to have a negative and statistically significant influence on PU. The rest of the dimensions did not have a significant effect on either PU or PEOU. Importantly, both PU and PEOU demonstrated a direct and substantial effect on usage intention. Conclusions: This study emphasizes the significance of comprehending medical students' readiness to adopt the role of online doctors in shaping the future of health care. By equipping medical students with the necessary skills and competencies, health care institutions can effectively leverage the full potential of online health care services while ensuring the provision of high-quality, accessible, and patient-centered care in the digital era.


Asunto(s)
Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Femenino , Masculino , China , Adulto Joven , Adulto , Encuestas y Cuestionarios , Actitud del Personal de Salud , Telemedicina , Motivación , Intención
3.
Int J Biol Macromol ; 273(Pt 1): 132896, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851619

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease with an unclear pathogenesis and no available specific drug treatment. The principal etiological factors are lung inflammation caused by environmental factors, damage to alveolar epithelial cells, leading to epithelial-mesenchymal transition (EMT), and the abnormal proliferation of fibroblasts. Here, we have demonstrated that fibroblast growth factor 21 (FGF21) ameliorates IPF via the autophagy pathway. We administered FGF21 to bleomycin (BLM)-treated mice, which ameliorated their defects in lung function, reduced the accumulation of collagen, restored tissue structure, reduced the deposition of hydroxyproline, reduced the expression of collagen I and α-SMA and increased the expression of E-cadherin. The expression of LC3BII and the number of autophagosomes were significantly higher in the lungs. The expression of AKT and mTOR was significantly reduced by FGF21 treatment. We also determined the effects of FGF21 in A549 cells treated with TGF-ß, and found that FGF21 significantly inhibits activation of the AKT signaling pathway, thereby reducing TGF-ß-induced EMT and preventing the uncontrolled proliferation of fibroblasts. We conclude that FGF21 ameliorates IPF by inhibiting the PI3K-AKT-mTOR signaling pathway and activating autophagy, which provides a theoretical basis for FGF21 to be used for the treatment of IPF.


Asunto(s)
Autofagia , Bleomicina , Transición Epitelial-Mesenquimal , Factores de Crecimiento de Fibroblastos , Fibrosis Pulmonar Idiopática , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Serina-Treonina Quinasas TOR/metabolismo , Autofagia/efectos de los fármacos , Animales , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Ratones , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Bleomicina/efectos adversos , Células A549 , Masculino , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones Endogámicos C57BL , Factor de Crecimiento Transformador beta/metabolismo
4.
Small ; 20(34): e2400288, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38593337

RESUMEN

Capacitive deionization for selective separation of ions is rarely reported since it relies on the electrostatic attraction of oppositely charged ions with no capability to distinguish ions of different valent states. Using molecular dynamic simulation, a screening process identified a hybrid material known as AC/PTh, which consists of activated carbon with a thin layer of polythiophene (PTh) coating. By utilizing AC/PTh as electrode material implementing the short-circuit cycle (SCC) mode in flow-electrode capacitive deionization (FCDI), selective separation of mono-/divalent ions can be realized via precise control of dynamic adsorption and desorption of mono-/divalent ions at a particular surface. Specifically, AC/PTh shows strong interaction with divalent ions but weak interaction with monovalent ions, the distribution of divalent ions can be enriched in the electric double layer after a couple of adsorption-desorption cycles. At Cu2+/Na+ molar ratio of 1:40, selectivity toward divalent ions can reach up to 110.3 in FCDI SCC mode at 1.0 V. This work presents a promising strategy for separating ions of different valence states in a continuously operated FCDI device.

5.
Sensors (Basel) ; 24(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38474944

RESUMEN

In this paper, we introduce a novel panoptic segmentation method called the Mask-Pyramid Network. Existing Mask RCNN-based methods first generate a large number of box proposals and then filter them at each feature level, which requires a lot of computational resources, while most of the box proposals are suppressed and discarded in the Non-Maximum Suppression process. Additionally, for panoptic segmentation, it is a problem to properly fuse the semantic segmentation results with the Mask RCNN-produced instance segmentation results. To address these issues, we propose a new mask pyramid mechanism to distinguish objects and generate much fewer proposals by referring to existing segmented masks, so as to reduce computing resource consumption. The Mask-Pyramid Network generates object proposals and predicts masks from larger to smaller sizes. It records the pixel area occupied by the larger object masks, and then only generates proposals on the unoccupied areas. Each object mask is represented as a H × W × 1 logit, which fits well in format with the semantic segmentation logits. By applying SoftMax to the concatenated semantic and instance segmentation logits, it is easy and natural to fuse both segmentation results. We empirically demonstrate that the proposed Mask-Pyramid Network achieves comparable accuracy performance on the Cityscapes and COCO datasets. Furthermore, we demonstrate the computational efficiency of the proposed method and obtain competitive results.

6.
Adv Mater ; : e2312182, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38335933

RESUMEN

People have been looking for an energy-efficient and sustainable method to produce future chemicals for decades. Heterogeneous single-atom catalysts (SACs) with atomic dispersion of robust, well-characterized active centers are highly desirable. In particular, correlated SACs with cooperative interaction between adjacent single atoms allow the switching of the single-site pathway to the dual or multisite pathway, thus promoting bimolecular or more complex reactions for the synthesis of fine chemicals. Herein, the structural uniqueness of correlated SACs, including the intermetal distance and electronic interaction in homo/heteronuclear metal sites is featured. Recent advances in the production methods of correlated SACs, showcasing the research status and challenges in traditional methods (such as pyrolysis, wet impregnation, and confined synthesis) for building a comprehensive multimetallic SAC library, are summarized. Emerging strategies such as process automation and continuous-flow synthesis are highlighted, minimizing the inconsistency in laboratory batch production and allowing high throughput screening and upscaling toward the next-stage chemical production by correlated SACs.

7.
Int J Biol Macromol ; 261(Pt 1): 129797, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38290625

RESUMEN

FGF21 plays an active role in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). However, the short half-life and poor stability of wild-type FGF21 limit its clinical application. Previous studies found that PEGylation can significantly increase the stability of FGF21. However, the uneven distribution of PEGylation sites in FGF21 makes it difficult to purify PEG-FGF21, thereby affecting its yield, purity, and activity. To obtain long-acting FGF21 with controlled site-specific modification, we mutated lysine residues in FGF21, resulting in PEGylation only at the N-terminus of FGF21 (mFGF21). In addition, we modified mFGF21 molecules with different PEG molecules and selected the PEG-mFGF21 moiety with the highest activity. The yield of PEG-mFGF21 in this study reached 1 g/L (purity >99 %), and the purification process was simple and efficient with strong quality controllability. The half-life of PEG-mFGF21 in rats reached 40.5-67.4 h. Pharmacodynamic evaluation in mice with high-fat, high-cholesterol- and methionine and choline deficiency-induced NASH illustrated that PEG-mFGF21 exhibited long-term efficacy in improving liver steatosis and reducing liver cell damage, inflammation, and fibrosis. Taken together, PEG-mFGF21 could represent a potential therapeutic drug for the treatment of NASH.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Ratones , Ratas , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factores de Crecimiento de Fibroblastos/genética , Factores de Crecimiento de Fibroblastos/uso terapéutico , Factores de Crecimiento de Fibroblastos/farmacología , Obesidad/tratamiento farmacológico , Hígado
8.
Heliyon ; 9(10): e20971, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37886746

RESUMEN

Robustness is a significant research direction in manipulator control owing to their complicated and uncertain external environment, abrasion, and other factors. The ability to implement multitasking is also necessary for manipulator control because of the physical limitations and complex requirements. However, the existing research has mainly focused on the control of a single task and robustness analysis of single-task control. Although some research on multi-task control has been conducted recently, its robustness has not yet been studied. Because of the excellent performance of the integrated-enhanced zeroing neural network in terms of robustness for time-varying problem solving, it was employed in this study to solve robust multi-task control. First, the multi-task control was formulated as a two-layered time-varying problem, including nonlinear and hybrid linear equations describing the tracking task and additional tasks, respectively. Second, an integrated-enhanced zeroing neural network was employed for the multilayered time-varying problem solving and a robust multi-task control algorithm was obtained, which can suppress different types of noises. Theoretical analyses demonstrated its effectiveness in multitasking and superior robustness compared with conventional algorithms. Finally, simulation results verified the theoretical results.

9.
Molecules ; 28(19)2023 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-37836616

RESUMEN

In the healing of wounds, human-like collagen (hCol) is essential. However, collagen-based composite dressings have poor stability in vivo, which severely limits their current therapeutic potential. Based on the above, we have developed a recombinant fusion protein named hCol-ELP, which consists of hCol and an elastin-like peptide (ELP). Then, we examined the physicochemical and biological properties of hCol-ELP. The results indicated that the stability of the hCol-ELP fusion protein exhibited a more compact and homogeneous lamellar microstructure along with collagen properties, it was found to be significantly superior to the stability of free hCol. The compound hCol-ELP demonstrated a remarkable capacity to induce the proliferation and migration of mouse embryo fibroblast cells (NIH/3T3), as well as enhance collagen synthesis in human skin fibroblasts (HSF) when tested in vitro. In vivo, hCol-ELP demonstrated significant enhancements in healing rate and a reduction in the time required for scab removal, thereby exhibiting a scar-free healing effect. The findings provide a crucial theoretical foundation for the implementation of an hCol-ELP protein dressing in fields associated with the healing of traumatic injuries.


Asunto(s)
Elastina , Péptidos , Ratones , Animales , Humanos , Elastina/química , Péptidos/farmacología , Péptidos/química , Colágeno/química , Cicatrización de Heridas , Proteínas Recombinantes de Fusión/metabolismo
10.
EMBO J ; 42(20): e113743, 2023 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-37661833

RESUMEN

Mitochondria play essential roles in cancer cell adaptation to hypoxia, but the underlying mechanisms remain elusive. Through mitochondrial proteomic profiling, we here find that the prolyl hydroxylase EglN1 (PHD2) accumulates on mitochondria under hypoxia. EglN1 substrate-binding region in the ß2ß3 loop is responsible for its mitochondrial translocation and contributes to breast tumor growth. Furthermore, we identify AMP-activated protein kinase alpha (AMPKα) as an EglN1 substrate on mitochondria. The EglN1-AMPKα interaction is essential for their mutual mitochondrial translocation. After EglN1 prolyl-hydroxylates AMPKα under normoxia, they rapidly dissociate following prolyl-hydroxylation, leading to their immediate release from mitochondria. In contrast, hypoxia results in constant EglN1-AMPKα interaction and their accumulation on mitochondria, leading to the formation of a Ca2+ /calmodulin-dependent protein kinase 2 (CaMKK2)-EglN1-AMPKα complex to activate AMPKα phosphorylation, ensuring metabolic homeostasis and breast tumor growth. Our findings identify EglN1 as an oxygen-sensitive metabolic checkpoint signaling hypoxic stress to mitochondria through its ß2ß3 loop region, suggesting a potential therapeutic target for breast cancer.


Asunto(s)
Proteínas Quinasas Activadas por AMP , Neoplasias de la Mama , Femenino , Humanos , Proteínas Quinasas Activadas por AMP/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Hipoxia , Prolina Dioxigenasas del Factor Inducible por Hipoxia/genética , Prolina Dioxigenasas del Factor Inducible por Hipoxia/metabolismo , Mitocondrias/metabolismo , Proteómica
11.
Sci Total Environ ; 904: 166824, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37673241

RESUMEN

Irrational use of fipronil for rice pest control often occurred, resulting in high concentrations of fipronil and its transformation products (TPs) (collectively termed fiproles) in aquatic sediment, calling for a better understanding of the migration and transformation of fipronil in surface water as well as efficient methods for source identification. Herein, the fate and transport of fiproles from a paddy field to receiving rivers were assessed in Poyang Lake basin, Jiangxi, China using polar organic chemical integrative samplers with mixed-mode adsorbents (POCIS-MMA). Average concentrations of fiproles in water were 6.16 ± 6.32 ng/L, with median, minimum, and maximum values being 2.99 ± 0.67, 0.40 ± 0.08, and 18.6 ± 3.1 ng/L, respectively. In all samples, over half of fiproles (55.9 %-90.8 %) presented in the form of TPs and fipronil desulfinyl was the dominant TP. Two approaches were applied for source identification, including the change of molar concentration ratios of fipronil to its TPs and the relative attenuation values of fiproles normalized to a reference compound (acetamiprid) that was stable in aquatic environment. While the paddy field upstream was the main source of waterborne fiproles, additional input sources in the downstream region were identified. The present study indicated that the combination of attenuation of molar concentration ratios of micro-pollutants to their respective TPs and relative attenuation values of micro-pollutants' concentrations normalized to a reference compound measured by POCIS is an effective means to study the migration and transformation of micro-pollutants in field.

12.
Elife ; 122023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37589705

RESUMEN

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3-METTL14 heterodimers and Wilms' tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239-580 of METTL3). We find that METTL3a is required for the METTL3-WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3-METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a-mTOR axis as a potential therapeutic target for breast cancer.


Asunto(s)
Neoplasias de la Mama , Proteínas de Ciclo Celular , Metiltransferasas , Factores de Empalme de ARN , Humanos , Proteínas de Ciclo Celular/genética , Transformación Celular Neoplásica , Citoplasma , Metiltransferasas/genética , ARN , Factores de Empalme de ARN/genética , Neoplasias de la Mama/patología , Progresión de la Enfermedad
13.
Inquiry ; 60: 469580231183695, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37357728

RESUMEN

As online health communities (OHCs) continue to proliferate, narrative reviews on doctors have become a vital reference source for patients when choosing online health services. However, the potential value of subjective information reflecting patient experiences in OHCs has not been fully explored. The present study seeks to investigate the impact of narrative reviews on patients' selection of e-doctors and the extent to which such reviews are moderated by doctors' specialties. This paper collected data from 747 doctors and 105 032 reviews from WeDoctor, one of China's most popular OHCs, in 2019. We employed Latent Dirichlet Allocation topic modeling to extract 3 topics and analyzed their effects on patient e-doctor choice using a multiple regression method. Our findings indicate that Topic 1, clinical skills and effects, had a positive impact on patient choice in OHCs (ß1 = .243, P < .001), as did Topic 2, service attitude and trust (ß2 = .130, P < .05). However, the impact of Topic 3, convenience, did not show a significant effect in this study. Moreover, our results suggest that the specialty of Internal Medicine can positively moderate the relationship between Topic 1 (clinical skills and effects) and patient e-doctor choice (ß9 = .087, P < .05). Based on the findings of this study, e-doctors are encouraged to enhance their technical competence to improve treatment effectiveness and adjust their communication methods to increase patient trust and sense of security. OHC platform managers should accurately understand the key factors that influence patient choice and take measures to improve their service quality accordingly.


Asunto(s)
Medicina , Médicos , Telemedicina , Humanos , Competencia Clínica , Relaciones Médico-Paciente , Encuestas y Cuestionarios , Calidad de la Atención de Salud , Conducta de Elección , Participación del Paciente
14.
J Hazard Mater ; 458: 131851, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37369174

RESUMEN

Neonicotinoids (NEOs) and fipronil (FIP) are ubiquitous in aquatic environment, yet the transformation and water-sediment exchange are largely unknown for these systemic insecticides and their transformation products (TPs). Herein, occurrence, field-based partitioning coefficients, and fugacity fractions (ff) of NEOs, FIP, and their TPs were analyzed in the drainage and receiving rivers near a rice paddy field. NEOs and FIPs were frequently detected in the sediments with concentrations of TPs being often higher than the parent compounds. Average ff values of NEOs (0.944-1.00) were larger than those of FIPs (0.399-0.716), indicating NEOs had a greater tendency to diffuse from sediment into water. Similar as well-studied hydrophobic compounds, hydrophobicity was the main factor impacting the water-sediment exchange of moderately hydrophobic FIPs. Alternatively, electrostatic interactions governed the fate of hydrophilic NEOs in water-sediment system. The log Kd values of NEOs were positively correlated with their N/C ratios (p < 0.05), possibly because the negatively charged sediments (zeta potential were from -19.1 ± 0.6 to -5.84 ± 0.57 mV) generated electrostatic attraction with amino functional group. Our study highlighted the ubiquitousness of TPs and distinct water-sediment interaction for moderately hydrophobic and hydrophilic insecticides in an agriculture-dominated watershed.

15.
Endocrinology ; 164(6)2023 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-37207449

RESUMEN

α-Ketoglutarate (αKG)-dependent dioxygenases are a superfamily of enzymes that require oxygen, reduced iron, and αKG for their catalytic functions. Therefore, they have the potential to sense the availabilities of oxygen, iron, and specific metabolites, including αKG and its structurally related metabolites. These enzymes play essential roles in various biological processes, including cellular adaptation to hypoxia, epigenetic and epitranscriptomic regulation of gene expression, and metabolic reprogramming. Many αKG-dependent dioxygenases are dysregulated in cancer pathogenesis. Herein, we review how they are regulated and function in breast cancer, which may offer new therapeutic intervention strategies for targeting this family of enzymes.


Asunto(s)
Neoplasias de la Mama , Dioxigenasas , Humanos , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Ácidos Cetoglutáricos/metabolismo , Hierro , Dioxigenasas/metabolismo , Oxígeno/metabolismo
16.
Eur J Pharmacol ; 952: 175811, 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37245859

RESUMEN

Fibroblast growth factor 21 (FGF21) and glucagon-like peptide-1 (GLP-1) may be useful for the treatment of type 2 diabetes, obesity, and non-alcoholic fatty liver disease (NAFLD). Previous studies have shown that GLP-1 may synergize with FGF21 in the regulation of glucose and lipid metabolism. Currently, no approved drug therapy is available for non-alcoholic steatohepatitis (NASH). Here, we constructed and screened dual-targeting fusion proteins of GLP-1 and FGF21, connected by elastin-like polypeptides (ELPs), to investigate whether a combination of these two hormones would have therapeutic effects in models of NASH. The temperature phase transition and release of the hormones under physiological conditions were studied to identify a bifunctional fusion protein of FGF21 and GLP-1 (GEF) that was highly stable and showed sustained release. We further evaluated the quality and therapeutic efficacy of GEF in three mouse models of NASH. We successfully synthesized a novel recombinant bifunctional fusion protein with high stability and low immunogenicity. The GEF protein synthesized ameliorated hepatic lipid accumulation, hepatocyte damage, and inflammation; prevented the progression of NASH in the three models; reduced glycemia; and caused weight loss. This novel GEF molecule may be suitable for clinical use for the treatment of NAFLD/NASH and related metabolic diseases.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Péptido 1 Similar al Glucagón/genética , Péptido 1 Similar al Glucagón/uso terapéutico , Péptido 1 Similar al Glucagón/metabolismo , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo
17.
Mar Pollut Bull ; 185(Pt A): 114182, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36257243

RESUMEN

Considering the phasing-out of polybrominated diphenyl ethers (PBDEs), environmental concerns of PBDE alternatives and dechlorane plus (DP) are rising. Accordingly, this study investigates occurrence and ecological risks of PBDEs, PBDE alternatives and DPs in sediments of two littoral regions, the Pearl River Estuary (PRE) and Daya Bay (DYB), in southern China. Total PBDEs concentrations in surface sediments of the PRE and DYB were in the range (mean) of 0.30-28.7 (8.71) and 0.29-43.4 (6.05) ng/g dw, respectively. DP levels in surface sediments of the PRE (0.004-0.27 ng/g dw) were significantly higher than those in the DYB (0.005-0.24 ng/g dw) (p < 0.05). BDE 209 was the predominant component, followed by DBDPE, exhibiting regional variations in BFRs usage. Vertical profiles of BFRs and DP in the PRE and DYB sediment cores exhibited clear anthropogenic influences. Risk quotients suggest critical ecological risks of tetra-, penta- and deca-BDE congeners in all the surface sediments.


Asunto(s)
Retardadores de Llama , Éteres Difenilos Halogenados , Éteres Difenilos Halogenados/análisis , Retardadores de Llama/análisis , Ríos , Estuarios , Bahías , Sedimentos Geológicos , Monitoreo del Ambiente , China
18.
Langmuir ; 38(40): 12263-12272, 2022 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-36177722

RESUMEN

Both electrical conductivity and surface wettability are required for the selection of active carbon materials in flow-electrode capacitive deionization, while a trade-off exists between these two properties. In this work, a hybrid material with a thin layer of polyaniline (PANI) coating on activated carbon (AC/PANI) was successfully developed to retain excellent electrical conductivity and acquire good surface wettability. By adjusting the dosage of initiator, AC/PANI composites with different loading fractions of PANI were obtained. The electrochemical testing demonstrated that the AC/PANI composites have higher specific capacitance and lower ion diffusion resistance compared to pure AC, resulting in better desalinization performance. Specifically, with a feed concentration of 1600 mg/L, excellent adsorption capacity and high charge efficiency can be simultaneously achieved at 13.51 mg/g and 92.21%, respectively. Benefiting from the formation of a continuous electrical percolation network and reduced solid/liquid interfacial transport resistance, a 39% enhancement of average salt adsorption rate (from 0.54 to 0.75 µmol/min/cm2) was obtained.

19.
Environ Sci Technol ; 56(17): 12494-12505, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36006007

RESUMEN

Neonicotinoid insecticides have attracted worldwide attention due to their ubiquitous occurrence and detrimental effects on aquatic organisms, yet their impacts on fish reproduction during long-term exposure remain unknown. Here, zebrafish (F0) were exposed to a neonicotinoid, acetamiprid, at 0.19-1637 µg/L for 154 d. Accumulation and biotransformation of acetamiprid were observed in adult fish, and the parent compound and its metabolite (acetamiprid-N-desmethyl) were transferred to their offspring. Acetamiprid caused slight survival reduction and significant feminization in F0 fish even at the lowest concentration. Hormone levels in F0 fish were remarkedly altered, that is, gonad 17ß-estradiol (E2) significantly increased, while androstenedione decreased. The corresponding transcription of steroidogenic genes (ar, cyp19b, fshß, gnrh2, gnrh3, and lhß) were significantly upregulated in the brain and gonad of the females but downregulated in the males. The vtg1 gene expression in the liver of male fish was also upregulated. In addition to F0 fish, parental exposure to acetamiprid decreased hatchability and enhanced malformation of F1 embryos. Chronic exposure to acetamiprid at environmentally relevant concentrations altered hormone production and the related gene expression of the hypothalamic-pituitary-gonad (HPG) axis in a sex-dependent way, caused feminization and reproductive dysfunction in zebrafish, and impaired production and development of their offspring.


Asunto(s)
Insecticidas , Contaminantes Químicos del Agua , Animales , Bioacumulación , Femenino , Feminización/inducido químicamente , Feminización/metabolismo , Gónadas , Humanos , Insecticidas/metabolismo , Insecticidas/toxicidad , Masculino , Neonicotinoides/toxicidad , Reproducción , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/metabolismo
20.
J Hazard Mater ; 437: 129426, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-35897175

RESUMEN

Municipal wastewater contains numerous chemicals and transformation products with highly diverse physiochemical properties and intrinsic toxicity; thus, it is imperative but challenging to identify major toxicants. Herein, toxicity identification evaluation (TIE) was applied to identify major toxicants in a typical municipal wastewater treatment plant (WWTP). Impacts of chemical properties on the removal of contaminants and toxicity at individual treatment stages were also examined. The WWTP influent caused 100% death of Daphnia magna and zebrafish embryos, and toxicity characterization suggested that organics, metals, and volatiles all contributed to the toxicity. Toxicity identification based on 189 target and approximately one-thousand suspect chemicals showed that toxicity contributions of organic contaminants, metals, and ammonia to D. magna were 77%, 4%, and 19%, respectively. Galaxolide, pyrene, phenanthrene, benzo[a]anthracene, fluoranthene, octinoxate, silver, and ammonia were identified as potential toxicants. Comparatively, the detected transformation products elicited lower toxicity than their respective parent contaminants. In contrast, the analyzed contaminants showed negligible contributions to the toxicity of zebrafish embryos. Removal efficiencies of these toxicants in WWTP were highly related to their hydrophobicity. Diverse transformation and removal efficiencies of contaminants in WWTPs may influence the chemical compositions in effluent and ultimately the risk to aquatic organisms in the receiving waterways.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Amoníaco/toxicidad , Animales , Bioensayo , Sustancias Peligrosas , Metales , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/química , Aguas Residuales/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Pez Cebra
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