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1.
Angew Chem Int Ed Engl ; : e202413417, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352449

RESUMEN

The substantial promotion of hydrogen evolution reaction (HER) catalytic performance relies on the breakup of the Sabatier principle, which can be achieved by the alternation of the support and electronic metal support interaction (EMSI) is noticed. Due to the utilization of tungsten disulfides as support for platinum (Pt@WS2), surprisingly, Pt@WS2 demands only 31 mV overpotential to attain 10 mA cm-2 in acidic HER test, corresponding to a 2.5-fold higher mass activity than benchmarked Pt/C. The pH dependent electrochemical measurements associated with H2-TPD and in-situ Raman spectroscopy indicate a hydrogen spillover involved HER mechanism is confirmed. The WS2 support triggers a higher hydrogen binding strength for Pt leading to the increment in hydrogen concentration at Pt sites proved by upshifted d band center as well as lower Gibbs free energy of hydrogen, favourable for hydrogen spillover. Besides, the WS2 shows a comparably lower effect on Gibbs free energy for different Pt layers (-0.50 eV layer-1) than carbon black (-0.88 eV layer-1) contributing to a better Pt utilization. Also, the theoretical calculation suggests the hydrogen spillover occurs on the 3rd Pt layer in Pt@WS2; moreover, the energy barrier is lowered with increment in hydrogen coverage on Pt.

2.
J Nanobiotechnology ; 21(1): 177, 2023 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-37268942

RESUMEN

Long-term chronic inflammation after Achilles tendon injury is critical for tendinopathy. Platelet-rich plasma (PRP) injection, which is a common method for treating tendinopathy, has positive effects on tendon repair. In addition, tendon-derived stem cells (TDSCs), which are stem cells located in tendons, play a major role in maintaining tissue homeostasis and postinjury repair. In this study, injectable gelatine methacryloyl (GelMA) microparticles containing PRP laden with TDSCs (PRP-TDSC-GM) were prepared by a projection-based 3D bioprinting technique. Our results showed that PRP-TDSC-GM could promote tendon differentiation in TDSCs and reduce the inflammatory response by downregulating the PI3K-AKT pathway, thus promoting the structural and functional repair of tendons in vivo.


Asunto(s)
Plasma Rico en Plaquetas , Tendinopatía , Ratas , Animales , Hidrogeles/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Tendones , Tendinopatía/terapia , Tendinopatía/metabolismo , Células Madre , Plasma Rico en Plaquetas/metabolismo , Impresión Tridimensional
3.
Proc Natl Acad Sci U S A ; 117(23): 12763-12771, 2020 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-32461369

RESUMEN

Aphids are sap-feeding insects that colonize a broad range of plant species and often cause feeding damage and transmit plant pathogens, including bacteria, viruses, and viroids. These insects feed from the plant vascular tissue, predominantly the phloem. However, it remains largely unknown how aphids, and other sap-feeding insects, establish intimate long-term interactions with plants. To identify aphid virulence factors, we took advantage of the ability of the green peach aphid Myzus persicae to colonize divergent plant species. We found that a M. persicae clone of near-identical females established stable colonies on nine plant species of five representative plant eudicot and monocot families that span the angiosperm phylogeny. Members of the novel aphid gene family Ya are differentially expressed in aphids on the nine plant species and are coregulated and organized as tandem repeats in aphid genomes. Aphids translocate Ya transcripts into plants, and some transcripts migrate to distal leaves within several plant species. RNAi-mediated knockdown of Ya genes reduces M. persicae fecundity, and M. persicae produces more progeny on transgenic plants that heterologously produce one of the systemically migrating Ya transcripts as a long noncoding (lnc) RNA. Taken together, our findings show that beyond a range of pathogens, M. persicae aphids translocate their own transcripts into plants, including a Ya lncRNA that migrates to distal locations within plants, promotes aphid fecundity, and is a member of a previously undescribed host-responsive aphid gene family that operate as virulence factors.


Asunto(s)
Áfidos/patogenicidad , Magnoliopsida/parasitología , Transporte de ARN , ARN Largo no Codificante/metabolismo , Factores de Virulencia/metabolismo , Animales , Áfidos/genética , Proteínas de Insectos/genética , ARN Largo no Codificante/genética , Factores de Virulencia/genética
4.
J Nanobiotechnology ; 20(1): 499, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36424661

RESUMEN

Gene transfection was supposed to be the most promising technology to overcome the vast majority of diseases and it has been popularly reported in clinical applications of gene therapy. In spite of the rapid development of novel transfection materials and methods, the influence of morphology-dependent nanomechanics of malignant osteosarcoma on gene transfection is still unsettled. In this study, cell spreading and adhesion area was adjusted by the prepared micropatterns to regulate focal adhesion (FA) formation and cytoskeletal organization in osteosarcoma cells. The micropattern-dependent FA and cytoskeleton could induce different cellular nanomechanics to affect cell functions. Our results indicated that transfection efficiency was improved with enlarging FA area and cell nanomechanics in micropatterned osteosarcoma. The difference of gene transfection in micropatterned cells was vigorously supported by cellular internalization capacity, Ki67 proliferation ability and YAP mechanotranduction through the regulation of focal adhesion and cytoskeletal mechanics. This study is an attempt to disclose the relationship of cell nanomechanics and gene transfection for efficient gene delivery and develop multifunctional nanomedicine biomaterials for accurate gene therapy in osteosarcoma cells.


Asunto(s)
Neoplasias Óseas , Osteosarcoma , Humanos , Adhesiones Focales , Citoesqueleto/metabolismo , Osteosarcoma/genética , Osteosarcoma/terapia , Osteosarcoma/metabolismo , Transfección , Neoplasias Óseas/genética , Neoplasias Óseas/terapia , Neoplasias Óseas/metabolismo
5.
Sensors (Basel) ; 21(23)2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-34884141

RESUMEN

The detection of an electromagnetic pulse (EMP) field is of great significance in determining the field environment of tested equipment in small spaces. Finger-shaped miniature optical fiber sensors for electromagnetic pulse field measurement were designed. The antenna of a weak field sensor was integrated with a shielding shell, and the wire welded at the direct electro-optic converting circuit connected to an optical fiber through special structure and circuit design was taken as the antenna of a strong field sensor. Measurements in the time domain and frequency domain had been carried out for the two sensors. Experiment results demonstrate that the weak field sensor and the strong field sensor have flat responses from 100 kHz to 1 GHz with a variation of 2.3 dB and 2.9 dB, respectively, and the EMP waveform detected by the sensors agrees well with the applied standard square wave. Moreover, the strong field sensor exhibits linear responses from 645 V/m to 83 kV/m. The resolution of the weak field sensor is as low as 13 V/m. The result indicated that the designed sensors had good performance.

6.
Angew Chem Int Ed Engl ; 60(14): 7597-7601, 2021 03 29.
Artículo en Inglés | MEDLINE | ID: mdl-33448553

RESUMEN

Live cell imaging of lysosome positioning and motility is critical to studying lysosome status and function for pharmacological interventions. To create a super stable lysosomal probe for long-term live cell imaging, we have designed and synthesized an aromatic-peptide-conjugated cyclometalated iridium(III) complex that emits light via π-π stacking oriented self-assembly in water at extremely low concentration. Through endocytic trafficking, self-assemblies are transformed from nanoparticles into sturdily packed networks that are stabilized in lysosomal acidic environment. Upon short time/low dose treatment of the iridium complex at passage 0, live cell lysosomal tracking is applicable beyond the 14th passage of cells with high labelling rate and a mild decline in luminescence intensity. The illuminated lysosomes are trackable using super-resolution imaging to study their response to cellular processes.


Asunto(s)
Complejos de Coordinación/química , Colorantes Fluorescentes/química , Iridio/química , Lisosomas/metabolismo , Rastreo Celular , Dimerización , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Conformación Molecular , Nanopartículas/química , Imagen Óptica , Péptidos/química , Espectrometría de Fluorescencia
7.
J Cell Mol Med ; 24(18): 10444-10457, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32681612

RESUMEN

Over-activated osteoclastogenesis, which is initiated by inflammation, has been implicated in osteoporosis. Corilagin, a natural compound extracted from various medicinal herbaceous plants, such as Cinnamomum cassia, has antioxidant and anti-inflammatory activities. We found that Corilagin suppressed osteoclast differentiation in a dose-dependent manner, significantly decreased osteoclast-related gene expression and impaired bone resorption by osteoclasts. Moreover, phosphorylation of members of the nuclear factor-kappaB (NF-κB) and PI3K/AKT signalling pathways was reduced by Corilagin. In a murine model of osteoporosis, Corilagin inhibited osteoclast functions in vivo and restored oestrogen deficiency-induced bone loss. In conclusion, our findings suggested that Corilagin inhibited osteoclastogenesis by down-regulating the NF-κB and PI3K/AKT signalling pathways, thus showing its potential possibility for the treatment of osteoporosis.


Asunto(s)
Resorción Ósea/patología , Estrógenos/deficiencia , Glucósidos/farmacología , Taninos Hidrolizables/farmacología , FN-kappa B/metabolismo , Osteogénesis/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ligando RANK/farmacología , Actinas/metabolismo , Animales , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Glucósidos/química , Taninos Hidrolizables/química , Ratones , Ratones Endogámicos C57BL , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoprotegerina/metabolismo , Ovariectomía , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos
8.
Mol Ecol ; 28(18): 4228-4241, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31472081

RESUMEN

Aphids present an ideal system to study epigenetics as they can produce diverse, but genetically identical, morphs in response to environmental stimuli. Here, using whole genome bisulphite sequencing and transcriptome sequencing of the green peach aphid (Myzus persicae), we present the first detailed analysis of cytosine methylation in an aphid and investigate differences in the methylation and transcriptional landscapes of male and asexual female morphs. We found that methylation primarily occurs in a CG dinucleotide (CpG) context and that exons are highly enriched for methylated CpGs, particularly at the 3' end of genes. Methylation is positively associated with gene expression, and methylated genes are more stably expressed than unmethylated genes. Male and asexual female morphs have distinct methylation profiles. Strikingly, these profiles are divergent between the sex chromosome and the autosomes; autosomal genes are hypomethylated in males compared to asexual females, whereas genes belonging to the sex chromosome, which is haploid in males, are hypermethylated. Overall, we found correlated changes in methylation and gene expression between males and asexual females, and this correlation was particularly strong for genes located on the sex chromosome. Our results suggest that differential methylation of sex-biased genes plays a role in aphid sexual differentiation.


Asunto(s)
Áfidos/genética , Metilación de ADN/genética , Caracteres Sexuales , Animales , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Genoma de los Insectos , Masculino , Cromosoma X/genética
9.
Protein Expr Purif ; 115: 76-82, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26196501

RESUMEN

The potent and broad activity of Canis interferon α (CaIFNα) makes it an attractive candidate for the treatment of many viral diseases of dogs. Here, we fused CaIFNα to three different protein tags: thioredoxin (Trx), glutathione S-transferase (GST), and NusA (Nus), to facilitate its expression and purification in Escherichia coli. The Trx-CaIFNα and GST-CaIFNα fusion proteins formed inclusion bodies, while the Nus-CaIFNα protein was soluble when expressed at low temperatures. Trx-CaIFNα was purified from inclusion bodies and refolded, while Nus-CaIFNα was purified under native conditions. The purity of Trx-CaIFNα and Nus-CaIFNα was greater than 90%, and their yields were 74.8% and 6.5%, respectively. Both Trx-CaIFNα and Nus-CaIFNα had antiviral activity in vitro. Their anti-viral activity was 1.09±0.47×10(14) and 2.25±0.87×10(12) U/mol, respectively, on Madin-Darby canine kidney cells. Both purification methods had advantages and disadvantages. A greater amount of Trx-CaIFNα was obtained, but refolding was required to obtain active protein. In contrast, soluble Nus-CaIFNα did not require refolding, which saved time and materials. However, Nus-CaIFNα, which contained a larger tag, had lower activity than Trx-CaIFNα. In general, we provided two protocols to obtain large amounts of CaIFNα with high antiviral activity. These protocols may promote the clinical development of CaIFNα in treating viral diseases in dog.


Asunto(s)
Escherichia coli/genética , Interferón-alfa/genética , Interferón-alfa/aislamiento & purificación , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Animales , Perros , Glutatión Transferasa/genética , Cuerpos de Inclusión , Interferón-alfa/química , Interferón-alfa/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Solubilidad , Tiorredoxinas/genética
10.
J Proteome Res ; 13(12): 5751-66, 2014 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-25311705

RESUMEN

Jasmonates (JAs) are important phytohormones that regulate a wide range of plant processes including growth, development, senescence, and defense. Jasmonate ZIM-domain (JAZ) proteins are repressors in JA signaling. In Arabidopsis thaliana, 12 JAZ encoding genes were identified, but only a few have been studied in detail. In this study, we focused on characterizing the molecular networks involving JAZ2 and JAZ7. To understand the phenotypes and elucidate the regulatory functions of JAZ2 and JAZ7, shoot and root tissues from wild type (WT), jaz2, and jaz7 were harvested for RNA sequencing and metabolomics. Distinct changes of transcripts and metabolites in JA biosynthesis, primary and specialized metabolism, and oxidative stress were observed among the three genotypes. In particular, many defense or stress-associated metabolites and specialized metabolites were increased in response to methyl jasmonate (MeJA) treatment. Most importantly, these changes were subjected to quantitative modulation by the JAZ proteins at both transcriptional and metabolic levels, the degree of which may control resource allocation between growth and defense. This study not only reveals MeJA-induced molecular reprogramming but also demonstrates the functions of JAZ proteins as key regulators in fine-tuning JA signal transduction.


Asunto(s)
Acetatos/farmacología , Arabidopsis/efectos de los fármacos , Ciclopentanos/farmacología , Perfilación de la Expresión Génica/métodos , Metabolómica/métodos , Oxilipinas/farmacología , Secuencia de Aminoácidos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Cromatografía Liquida , Ciclopentanos/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Glucosa/metabolismo , Espectrometría de Masas , Metaboloma/efectos de los fármacos , Datos de Secuencia Molecular , Mutación , Oxilipinas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/genética , Brotes de la Planta/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Homología de Secuencia de Aminoácido , Transducción de Señal/efectos de los fármacos , Transcriptoma/efectos de los fármacos
11.
Arch Insect Biochem Physiol ; 85(3): 127-36, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24478036

RESUMEN

The PAR-domain protein 1 (PDP1) is essential for locomotor activity of insects. However, its functions in insect growth and development have not been studied extensively, which prompted our hypothesis that PDP1 acts in energy metabolism. Here we report identification of TcPDP1 in the red flour beetle, Tribolium castaneum, and its functional analysis by RNAi. Treating larvae with dsTcPDP1 induced pupae developmental arrestment, accompanied by accelerated fat body degradation. dsTcPDP1 treatments in adults resulted in reduced female fecundity. Disruption of TcPDP1 expression affected the transcription of genes involved in insulin signaling transduction and mechanistic target of rapamycin (mTOR) pathway. These results support our hypothesis that TcPDP1 acts in energy metabolism in T. castaneum.


Asunto(s)
Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Metabolismo Energético/fisiología , Proteínas de Insectos/metabolismo , Insulina/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Tribolium/metabolismo , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos/genética , Insulina/genética , Larva/genética , Larva/metabolismo , Masculino , Pupa/genética , Pupa/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Tribolium/genética , Tribolium/crecimiento & desarrollo
12.
ACS Appl Mater Interfaces ; 16(39): 52364-52372, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39295081

RESUMEN

The realization of a rechargeable zinc-air battery (ZAB) is hindered by the low intrinsic oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) activities. In this work, an abundant built-in electric field is noticed in a 1D/2D CoO/CoS2 heterostructure, triggering electron transfer from CoO to CoS2 associated with a downshifted d band center of the Co atom mitigating the strong electrochemical adsorption of *OH species on active sites; thereby, boosted OER and ORR performance are achieved. Namely, the OER specific activity of CoO/CoS2 is enhanced by 3.8- and 2.2-fold compared to the counterpart of CoO and CoS2, respectively. Furthermore, the kinetic current density of CoO/CoS2, a fingerprint of intrinsic ORR activity, is promoted by 46 and 6.6 times relative to CoO and CoS2. The rechargeable ZAB performance attains 215.6 mW cm-2, 1.6-times better than Pt/C-IrO2. Moreover, the superior performance remained for 600 h. Besides, the battery performance of the all-solid-state ZAB reaches 83.8 mW cm-2, revealing its promising application in wearable device.

13.
Adv Sci (Weinh) ; 11(29): e2401478, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38785178

RESUMEN

To ensure compositional consistency while mitigating potential immunogenicity for stem cell therapy, synthetic scaffolds have emerged as compelling alternatives to native extracellular matrix (ECM). Substantial progress has been made in emulating specific natural traits featuring consistent chemical compositions and physical structures. However, recapitulating the dynamic responsiveness of the native ECM involving chemical transitions and physical remodeling during differentiation, remains a challenging endeavor. Here, the creation of adaptive scaffolds is demonstrated through sequential protein-instructed molecular assembly, utilizing stage-specific proteins, and incorporating in situ assembly technique. The procedure is commenced by introducing a dual-targeting peptide at the onset of stem cell differentiation. In response to highly expressed integrins and heparan sulfate proteoglycans (HSPGs) on human mesenchymal stem cell (hMSC), the peptides assembled in situ, creating customized extracellular scaffolds that adhered to hMSCs promoting osteoblast differentiation. As the expression of alkaline phosphatase (ALP) and collagen (COL-1) increased in osteoblasts, an additional peptide is introduced that interacts with ALP, initiating peptide assembly and facilitating calcium phosphate (CaP) deposition. The growth and entanglement of peptide assemblies with collagen fibers efficiently incorporated CaP into the network resulting in an adaptive biphasic scaffold that enhanced healing of bone injuries.


Asunto(s)
Diferenciación Celular , Matriz Extracelular , Células Madre Mesenquimatosas , Péptidos , Andamios del Tejido , Humanos , Células Madre Mesenquimatosas/metabolismo , Andamios del Tejido/química , Péptidos/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Ingeniería de Tejidos/métodos , Osteoblastos/metabolismo , Células Cultivadas , Animales
14.
Chem Commun (Camb) ; 60(44): 5747-5750, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38747111

RESUMEN

CoO/Fe3O4 nanosheets exhibit a superior rechargeable zinc-air battery (ZAB) performance of 276 mW cm-2 and stability over 600 h. The all-solid-state ZAB also affords a high power density of 107 mW cm-2.

15.
Chem Commun (Camb) ; 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39324214

RESUMEN

High entropy alloy nanoparticles encapsulated into nitrogen-doped carbon nanotubes show superior bifunctionality for the ORR and OER, evidenced by a battery performance of 214 mW cm-2, sustained for 200 h.

16.
Chem Commun (Camb) ; 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39344481

RESUMEN

The faradaic efficiency of Bi2WO6 is 62.0% at -0.3 V vs. RHE, an improvement of 1.4- and 1.8-times relative to Bi2O3 and WO3 for the nitrate reduction reaction. In addition, the catalysis occurring on Bi2WO6 follows the pathway: *NO3-*NO2-*NO-*NOH-*HNOH-*H2NOH-*NH3, as verified by operando Raman spectroscopy and theoretical calculations.

17.
Research (Wash D C) ; 7: 0336, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38533181

RESUMEN

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the backsplice junction of circATNX1 was screened and delivered by tetrahedral framework nucleic acids (tFNAs) due to their unique compositional and tetrahedral structural features. Our siRNA delivery system demonstrates superior abilities to transfect aging cells, clear intracellular ROS, and enhanced biological safety. Using siRNA-tFNAs to silence circATXN1, aging NPCs exhibit reduced mislocalization of progerin in the cytoplasm and up-regulation of IGF-1R, thereby demonstrating a rejuvenated cellular phenotype and improved mitochondrial function. In vivo, administering an aging cell-adapted siRNA nucleic acid framework delivery system to progerin pathologically expressed premature aging mice (zmpste24-/-) can ameliorate the cellular matrix in the nucleus pulposus tissue, effectively delaying IVDD. This study not only identified circATXN1 functioning as a cell senescence promoter in IVDD for the first time, but also successfully demonstrated its therapeutic potential via a tFNA-based siRNA delivery strategy.

18.
Polymers (Basel) ; 15(16)2023 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-37631547

RESUMEN

Dendrite growth and parasitic reactions with liquid electrolyte are the two key factors that restrict the practical application of the lithium metal anode. Herein, a bis(benzene sulfonyl)imide based single-ion polymer artificial layer for a lithium metal anode is successfully constructed, which is prepared via blending the as-prepared copolymer of lithiated 4, 4'-dicarboxyl bis(benzene sulfonyl)imide and 4,4'-diaminodiphenyl ether on the surface of lithium foil. This single-ion polymer artificial layer enables compact structure with unique continuous aggregated Li+ clusters, thus reducing the direct contact between lithium metal and electrolyte simultaneously, ensuring Li+ transport is fast and homogeneous. Based on which, the coulombic efficiency of the Li|Cu half-cell is effectively improved, and the cycle stability of the Li|Li symmetric cell can be prolonged from 160 h to 240 h. Surficial morphology and elemental valence analysis confirm that the bis(benzene sulfonyl)imide based single-ion polymer artificial layer effectively facilitates the Li+ uniform deposition and suppresses parasitic reactions between lithium metal anode and liquid electrolyte in the LFP|Li full-cell. This strategy provides a new perspective to achieve a steady lithium metal anode, which can be a promising candidate in practical applications.

19.
Biomater Adv ; 148: 213352, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36867980

RESUMEN

GLP-1 has been clinically exploited for treating type 2 diabetes, while its short circulation half-life requires multiple daily injections to maintain effective glycemic control, thus limiting its widespread application. Here we developed a drug delivery system based on self-assembling polymer-amino acid conjugates (γ-PGA-PAE) to provide sustained release of GLP-1 analog (DLG3312). The DLG3312 loaded γ-PGA based nanoparticles (DLG3312@NPs) exhibited a spherical shape with a good monodispersity under transmission electron microscope (TEM) observation. The DLG3312 encapsulation was optimized, and the loading efficiency was as high as 78.4 ± 2.2 %. The transformation of DLG3312@NPs to network structures was observed upon treatment with the fresh serum, resulting in a sustained drug release. The in vivo long-term hypoglycemic assays indicated that DLG3312@NPs significantly reduced blood glucose and glycosylated hemoglobin level. Furthermore, DLG3312@NPs extended the efficacy of DLG3312, leading to a decrease in the dosing schedule that from once a day to once every other day. This approach combined the molecular and materials engineering strategies that offered a unique solution to maximize the availability of anti-diabetic drug and minimize its burdens to type 2 diabetic patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Preparaciones de Acción Retardada/uso terapéutico , Hipoglucemiantes/uso terapéutico , Polímeros , Péptido 1 Similar al Glucagón/uso terapéutico
20.
Int J Biol Macromol ; 240: 124324, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37023874

RESUMEN

CCL21, a secondary lymphoid tissue chemokine, plays an important role in generating an effective anti-tumor immune response. In this study, a genetically modified CCL21 was developed by inserting a pH low insertion peptide to establish a CCL21-rich microenvironment for tumors. The fusion tag thioredoxin (Trx) was designed and fused at the N-terminal of the recombinant protein to protect it from being irrevocably misfolded in microbial host cells. The prokaryotic expression vector pET32a-CCL21-pHLIP was constructed and successfully expressed in E. coli BL21 (DE3) with a soluble expression form and a molecular weight of ~35 kDa. The induction conditions were optimized to obtain an extremely high yield of 6.7 mg target protein from 31.1 mg total protein. The 6xHis tagged Trx-CCL21-pHLIP was purified using Ni-NTA resin, and it was confirmed using SDS-PAGE and Western blot analyses. Consequently, the Trx-CCL21-pHLIP protein was successfully displayed on the cancer cell surface in a weak acidic microenvironment and showed the same ability as CCL21 in recruiting CCR7-positive cells. Additionally, the CCL21 fusion protein with or without Trx tag showed similar functions. Therefore, the study implies the feasibility of directing a modular genetic method for the development of protein-based drugs.


Asunto(s)
Escherichia coli , Neoplasias , Proteínas Recombinantes de Fusión/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Quimiocina CCL21/genética , Quimiocina CCL21/metabolismo , Proteínas Recombinantes/metabolismo , Membrana Celular , Concentración de Iones de Hidrógeno
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