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1.
Nanotechnology ; 35(5)2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37965950

RESUMEN

Nanoparticles embedded within a crystalline solid serve as impurity phonon scattering centers that reduce lattice thermal conductivity, a desirable result for thermoelectric applications. Most studies of thermal transport in nanoparticle-laden composite materials have assumed the nanoparticles to possess a single size. If there is a distribution of nanoparticle sizes, how is thermal conductivity affected? Moreover, is there a best nanoparticle size distribution to minimize thermal conductivity? In this work, we study the thermal conductivity of nanoparticle-laden composites through a molecular dynamics approach which naturally captures phonon scattering processes more rigorously than previously used analytical theories. From thermal transport simulations of a systematic variety of nanoparticle configurations, we empirically formulate how nanoparticle size distribution, particle number density, and volume fraction affect the lattice thermal conductivity. We find at volume fractions below 10%, the particle number density is by far the most impactful factor on thermal conductivity and at fractions above 10%, the effect of the size distribution and number density is minimal compared to the volume fraction. In fact, upon comparisons of configurations with the same particle number density and volume fractions, the lattice thermal conductivity of a single nanoparticle size can be lower than that of a size distribution which contradicts intuitions that a single size would attenuate phonon transport less than a spectrum of sizes. The random alloy, which can be considered as a single size configuration of maximum particle number density where the nanoparticle size is equal to the lattice constant, is the most performant in thermal conductivity reduction at volume fractions below 10%. We conclude that nanoparticle size distribution only plays a minor role in affecting lattice thermal conductivity with the particle number density and volume fraction being the more significant factors that should be considered in fabrication of nanoparticle-laden composites for potential improved thermoelectric performance.

2.
J Environ Sci (China) ; 132: 56-70, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37336610

RESUMEN

Road silt loading (sL) is an important parameter in the fugitive road dust (FRD) emissions. In this study, the improved Testing Re-entrained Aerosol Kinetic Emissions from Roads (TRAKER) combined with the AP-42 method was firstly developed to quickly measure and estimate the sLs of paved roads in Beijing, China. The annual average sLs in Beijing was 0.59±0.31 g/m2 in 2020, and decreased by 22.4% compared with that in 2019. The seasonal variations of sLs followed the order of spring > winter > summer > autumn in the two years. The seasonal mean road sLs on the same type road in the four seasons presented a decline trend from 2019 to 2020, especially on the Express way, decreasing 47.4%-72.7%. The road sLs on the different type roads in the same season followed the order of Major arterial ∼ Minor arterial ∼ Branch road > Express road, and Township road ∼ Country highway > Provincial highway ∼ National highway. The emission intensities of PM10 and PM2.5 from FRD in Beijing in 2020 were lower than those in 2019. The PM10 and PM2.5 emission intensities at the four planning areas in the two years all presented the order of the capital functional core area > the urban functional expansion area > the urban development new area > the ecological conservation and development area. The annual emissions of PM10 and PM2.5 from FRD in Beijing in 2020 were 74,886 ton and 18,118 ton, respectively, decreasing by ∼33.3% compared with those in 2019.


Asunto(s)
Contaminantes Atmosféricos , Polvo , Polvo/análisis , Beijing , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , China , Estaciones del Año , Emisiones de Vehículos/análisis
3.
J Med Virol ; 94(6): 2519-2527, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35075669

RESUMEN

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus affecting human health globally. G-quadruplex secondary structures attract great attention as potential targets for antiviral strategy. In this study, we show that the CHIKV genome possesses several conserved potential G-quadruplex sequences. G-quadruplex ligands BRACO-19 and TMPyP4 could stabilize the CHIKV G-quadruplex and inhibit the transcription of constructs containing CHIKV G-quadruplex sequences. Importantly, BRACO-19 and TMPyP4 suppress CHIKV replication. Our study not only reinforces the presence of viral G-quadruplex sequences but also suggests that targeting G-quadruplex structure could represent a novel strategy to inhibit CHIKV.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Animales , Antivirales/farmacología , Virus Chikungunya/genética , Humanos , Ligandos , Replicación Viral
4.
Ophthalmic Res ; 64(6): 1037-1047, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34510043

RESUMEN

INTRODUCTION: Photodynamic therapy with verteporfin (vPDT) has been shown to be effective against central serous chorioretinopathy (CSC) and was the preferred therapeutic for CSC treatment. However, alterations in choroidal structure after PDT were reported, and these effects were dose-dependent. This study aimed to compare the changes in choroidal structure after PDT with different doses of verteporfin in rabbits and may provide individualized therapeutic guidance for patients who failed to respond to initial half-dose vPDT. METHODS: The full dose of verteporfin used in CSC was 6 mg/m2, which was used in patients with neovascular age-related macular degeneration. Laser fluence was 50 J/cm2 (irradiance, 600 mW/cm2, 83 s). There were 4 different dose groups in this study (100%, 70%, 50%, and 30%). The alterations were examined at 1 day, 1 week, and 1 month after vPDT using color fundus imaging, indocyanine green angiography, and histopathology analysis. RESULTS: Various degrees of choroidal alterations were demonstrated at different dose groups. Examinations on day 1 showed that gradually reduced verteporfin dose tended to decrease photochemical reactions to the choroid in terms of the number of occlusion vessels and area of the lesion. After 1 month, choroid vessel alteration persisted in high-dose groups (100% and 70%); nevertheless, alterations of low-dose groups (50% and 30%) returned to normal. CONCLUSIONS: vPDT can induce photochemical reactions of the choroid, high dose causes permanent change, and low dose causes recoverable change. The dose-dependent alterations need to be considered for the individual therapeutic plan according to the situation of a patient with CSC.


Asunto(s)
Neovascularización Coroidal , Fotoquimioterapia , Animales , Coroides , Neovascularización Coroidal/tratamiento farmacológico , Angiografía con Fluoresceína , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas , Conejos , Verteporfina/uso terapéutico
5.
Exp Cell Res ; 370(2): 551-560, 2018 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-30009791

RESUMEN

Leukemia is a malignance with complex pathogenesis and poor prognosis. Discovery of noval regulators amenable to leukemia could be of value to gain insight into the pathogenesis, diagnosis and prognosis of leukemia. Here, we conducted a large-scale shRNA library screening for functional regulators in the development of myeloid cells in primary cells. We identified eighteen candidate regulators in the primary screening. Those genes cover a wide range of cellular functions, including gene expression regulation, intracellular signaling transduction, nucleotide excision repair, cell cycle control and transcription regulation. In both primary screening and validation, shRNAs targeting Tcea1, encoding the transcription elongation factor A (SII) 1, exhibited the greatest influence on the proliferative potential of cells. Knocking down the expression of Tcea1 in the 32Dcl3 myeloid cell line led to enhanced proliferation of myeloid cells and blockage of myeloid differentiation induced by G-CSF. In addition, silence of Tcea1 inhibited apoptosis of myeloid cells. Thus, Tcea1 was identified as a gene which can influence the proliferative potential, survival and differentiation of myeloid cells. These findings have implications for how transcriptional elongation influences myeloid cell development and leukemic transformation.


Asunto(s)
Diferenciación Celular/genética , Regulación de la Expresión Génica/genética , Células Mieloides/citología , Factores de Elongación Transcripcional/genética , Animales , Línea Celular , Proteínas de Unión al ADN/metabolismo , Factor Estimulante de Colonias de Granulocitos/genética , Hematopoyesis/genética , Ratones , Transducción de Señal/genética , Factores de Transcripción/metabolismo
6.
Opt Lett ; 42(16): 3093-3096, 2017 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-28809881

RESUMEN

Polarization control of light waves is an important technique in optical communication and signal processing. On-chip polarization rotation from the fundamental transverse-electric (TE00) mode to the fundamental transverse-magnetic (TM00) mode is usually difficult because of their large effective refractive index difference. Here, we demonstrate an on-chip wideband polarization rotator designed with a genetic algorithm to convert the TE00 mode into the TM00 mode within a footprint of 0.96 µm ×4.2 µm. In simulation, the optimized structure achieves polarization rotation with a minimum conversion loss of 0.7 dB and the 1-dB bandwidth of 157 nm. Experimentally, our fabricated devices have demonstrated the expected polarization rotation with a conversion loss of ∼2.5 dB in the measured wavelength range of 1440-1580 nm, where the smallest value reaches ∼2 dB. The devices can serve as a generic approach and standard module for controlling light polarization in integrated photonic circuitry.

7.
Mol Genet Genomics ; 291(2): 635-46, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26510744

RESUMEN

The ubiquitin-protein ligases (E3s) directly participate in ubiquitin (Ub) transferring to the target proteins in the ubiquitination pathway. The HECT ubiquitin-protein ligase (UPL), one type of E3s, is characterized as containing a conserved HECT domain of approximately 350 amino acids in the C terminus. Some UPLs were found to be involved in trichome development and leaf senescence in Arabidopsis. However, studies on plant UPLs, such as characteristics of the protein structure, predicted functional motifs of the HECT domain, and the regulatory expression of UPLs have all been limited. Here, we present genome-wide identification of the genes encoding UPLs (HECT gene) in apple. The 13 genes (named as MdUPL1-MdUPL13) from ten different chromosomes were divided into four groups by phylogenetic analysis. Among these groups, the encoding genes in the intron-exon structure and the included additional functional domains were quite different. Notably, the F-box domain was first found in MdUPL7 in plant UPLs. The HECT domain in different MdUPL groups also presented different spatial features and three types of conservative motifs were identified. The promoters of each MdUPL member carried multiple stress-response related elements by cis-acting element analysis. Experimental results demonstrated that the expressions of several MdUPLs were quite sensitive to cold-, drought-, and salt-stresses by qRT-PCR assay. The results of this study helped to elucidate the functions of HECT proteins, especially in Rosaceae plants.


Asunto(s)
Malus/genética , Filogenia , Estrés Fisiológico/genética , Ubiquitina-Proteína Ligasas/genética , Arabidopsis/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Malus/crecimiento & desarrollo , Familia de Multigenes/genética , Ubiquitina/genética , Ubiquitina-Proteína Ligasas/biosíntesis
8.
Biochem J ; 465(1): 163-73, 2015 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-25279554

RESUMEN

Human cathepsin K (CatK) is a major drug target for the treatment of osteoporosis. Although its collagenase activity is unique, CatK also exerts a potent elastolytic activity that is shared with human cathepsins V and S. Other members of the cysteine cathepsin family, which are structurally similar, do not exhibit significant collagen and elastin degrading activities. This raises the question of the presence of specific structural elements, exosites, that are required for these activities. CatK has two exosites that control its collagenolytic and elastolytic activity. Modifications of exosites 1 and 2 block the elastase activity of CatK, whereas only exosite-1 alterations prevent collagenolysis. Neither exosite affects the catalytic activity, protease stability, subsite specificity of CatK or the degradation of other biological substrates by this protease. A low-molecular-mass inhibitor that docks into exosite-1 inhibits the elastase and collagenase activity of CatK without interfering with the degradation of other protein substrates. The identification of CatK exosites opens up the prospect of designing highly potent inhibitors that selectively inhibit the degradation of therapeutically relevant substrates by this multifunctional protease.


Asunto(s)
Catepsina K/antagonistas & inhibidores , Catepsina K/química , Colagenasas/metabolismo , Elastasa Pancreática/metabolismo , Inhibidores de Proteasas/farmacología , Secuencia de Aminoácidos , Animales , Dominio Catalítico , Catepsina K/metabolismo , Bovinos , Colágeno/metabolismo , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Humanos , Cinética , Modelos Moleculares , Datos de Secuencia Molecular , Proteínas Mutantes/metabolismo , Elastasa Pancreática/antagonistas & inhibidores , Unión Proteica/efectos de los fármacos , Proteolisis/efectos de los fármacos , Relación Estructura-Actividad , Especificidad por Sustrato/efectos de los fármacos
9.
Mol Genet Genomics ; 290(4): 1435-46, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25855485

RESUMEN

The F-box protein family is a large family that is characterized by conserved F-box domains of approximately 40-50 amino acids in the N-terminus. F-box proteins participate in diverse cellular processes, such as development of floral organs, signal transduction and response to stress, primarily as a component of the Skp1-cullin-F-box (SCF) complex. In this study, using a global search of the apple genome, 517 F-box protein-encoding genes (F-box genes for short) were identified and further subdivided into 12 groups according to the characterization of known functional domains, which suggests the different potential functions or processes that they were involved in. Among these domains, the galactose oxidase domain was analyzed for the first time in plants, and this domain was present with or without the Kelch domain. The F-box genes were distributed in all 17 apple chromosomes with various densities and tended to form gene clusters. Spatial expression profile analysis revealed that F-box genes have organ-specific expression and are widely expressed in all organs. Proteins that contained the galactose oxidase domain were highly expressed in leaves, flowers and seeds. From a fruit ripening expression profile, 166 F-box genes were identified. The expressions of most of these genes changed little during maturation, but five of them increased significantly. Using qRT-PCR to examine the expression of F-box genes encoding proteins with domains related to stress, the results revealed that F-box proteins were up- or down-regulated, which suggests that F-box genes were involved in abiotic stress. The results of this study helped to elucidate the functions of F-box proteins, especially in Rosaceae plants.


Asunto(s)
Proteínas F-Box/genética , Genoma de Planta/genética , Malus/genética , Familia de Multigenes , Proteínas de Plantas/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas de las Plantas/genética , Análisis por Conglomerados , Proteínas F-Box/clasificación , Frutas/genética , Frutas/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Malus/crecimiento & desarrollo , Datos de Secuencia Molecular , Proteínas de Plantas/clasificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido
10.
Int J Biol Macromol ; 255: 127952, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37951437

RESUMEN

Wound infection control is a primary clinical concern nowadays. Various innovative solutions have been developed to fabricate adaptable wound dressings with better control of infected wound healing. This work presents a facile approach by leveraging 3D printing to fabricate chitosan/glycerol into composite dressings with tailored micropatterns to improve wound healing. The bioinks of chitosan/glycerol were investigated as suitable for 3D printing. Then, three tailored micropatterns (i.e., sheet, strip, and mesh) with precise geometry control were 3D printed onto a commercial dressing to fabricate the micropatterned composite dressings. In vitro and in vivo studies indicate that these micropatterned dressings could speed up wound healing due to their increased water uptake capacity (up to ca. 16-fold@2 min), benign cytotoxicity (76.7 % to 90.4 % of cell viability), minor hemolytic activity (<1 %), faster blood coagulation effects (within 76.3 s), low blood coagulation index (14.5 % to 18.7 % @ 6 min), enhanced antibacterial properties (81.0 % to 86.1 % against S. aureus, 83.7 % to 96.5 % against E. coli), and effective inhibition of wound inflammation factors of IL-1ß and TNF-α. Such tailored micropatterned composite dressing is facile to obtain, highly reproducible, and cost-efficient, making it a promising implication for improved and personalized contaminated wound healing.


Asunto(s)
Quitosano , Quitosano/farmacología , Glicerol/farmacología , Escherichia coli , Staphylococcus aureus , Cicatrización de Heridas , Antibacterianos/farmacología , Vendajes/microbiología , Impresión Tridimensional
11.
Carbohydr Polym ; 332: 121931, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38431421

RESUMEN

Lumpectomy plus radiation is a treatment option offering better survival than conventional mastectomy for patients with early-stage breast cancer. However, successive radioactive therapy remains tedious and unsafe with severe adverse reactions and secondary injury. Herein, a composite hydrogel with pH- and photothermal double-sensitive activity is developed via physical crosslinking. The composite hydrogel incorporated with tempo-oxidized cellulose nanofiber (TOCN), polyvinyl alcohol (PVA) and a polydopamine (PDA) coating for photothermal therapy (PTT) triggered in situ release of doxorubicin (DOX) drug was utilized to optimize postoperative strategies of malignant tumors inhibition. The incorporation of TOCN significantly affects the performance of composite hydrogels. The best-performing TOCN/PVA7 was selected for drug loading and polydopamine coating by rational design. In vitro studies have demonstrated that the composite hydrogel exhibited high NIR photothermal conversion efficiency, benign cytotoxicity to L929 cells, pH-dependent release profiles, and strong MCF-7 cell inhibitory effects. Then the TOCN/PVA7-PDA@DOX hydrogel is implanted into the tumor resection cavity for local in vivo chemo-photothermal synergistical therapy to ablate residue tumor tissues. Overall, this work suggests that such a chemo-photothermal hydrogel delivery system has great potential as a promising tool for the postsurgical management of breast cancer.


Asunto(s)
Neoplasias de la Mama , Celulosa Oxidada , Hipertermia Inducida , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Terapia Fototérmica , Hidrogeles/química , Fototerapia , Mastectomía , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Concentración de Iones de Hidrógeno
12.
Micromachines (Basel) ; 15(5)2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38793158

RESUMEN

As a cutting-edge technology, animal robots based on living organisms are being extensively studied, with potential for diverse applications in the fields of neuroscience, national security, and civil rescue. However, it remains a significant challenge to reliably control the animal robots with the objective of protecting their long-term survival, and this has seriously hindered their practical implementation. To address this issue, this work explored the use of a bio-friendly neurostimulation system that includes integrated stimulation electrodes together with a remote wireless stimulation circuit to control the moving behavior of rat robots. The integrated electrodes were implanted simultaneously in four stimulation sites, including the medial forebrain bundle (MFB) and primary somatosensory cortex, barrel field (S1BF). The control system was able to provide flexibility in adjusting the following four stimulation parameters: waveform, amplitude, frequency, and duration time. The optimized parameters facilitated the successful control of the rat's locomotion, including forward movement and left and right turns. After training for a few cycles, the rat robots could be guided along a designated route to complete the given mission in a maze. Moreover, it was found that the rat robots could survive for more than 20 days with the control system implanted. These findings will ensure the sustained and reliable operation of the rat robots, laying a robust foundation for advances in animal robot regulation technology.

13.
Brain Res ; 1841: 149085, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38876320

RESUMEN

As a cutting-edge technology of connecting biological brain and external devices, brain-computer interface (BCI) exhibits promising applications on extensive fields such as medical and military. As for the disable individuals with four limbs losing the motor functions, it is a potential treatment way to drive mechanical equipments by the means of non-invasive BCI, which is badly depended on the accuracy of the decoded electroencephalogram (EEG) singles. In this study, an explanatory convolutional neural network namely EEGNet based on SimAM attention module was proposed to enhance the accuracy of decoding the EEG singles of index and thumb fingers for both left and right hand using sensory motor rhythm (SMR). An average classification accuracy of 72.91% the data of eight healthy subjects was obtained, which were captured from the one second before finger movement to two seconds after action. Furthermore, the character of event-related desynchronization (ERD) and event related synchronization (ERS) of index and thumb fingers was also studied in this study. These findings have significant importance for controlling external devices or other rehabilitation equipment using BCI in a fine way.

14.
Plant Cell Rep ; 32(9): 1427-40, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23689258

RESUMEN

KEY MESSAGE: The role of LTO1/ At VKOR-DsbA in ROS homeostasis and in redox regulation of cysteine-containing proteins in chloroplast was studied in lto1 - 2 mutant, and a potential target of LTO1 was captured. A chloroplast membrane protein LTO1/AtVKOR-DsbA encoded by the gene At4g35760 was recently found to be an oxidoreductase and involved in assembly of PSII. Here, the growth of a mutant lto1-2 line of Arabidopsis was found to be severely stunted and transgenic complementation ultimately demonstrated the phenotype changes were due to this gene. A proteomic experiment identified 23 proteins presenting a differential abundance in lto1-2 compared with wild-type plants, including components in PSII and proteins scavenging active oxygen. Three scavengers of active oxygen, L-ascorbate peroxidase 1, peroxisomal catalase 2, dehydroascorbate reductase 1, are reduced in lto1-2 plants, corresponding to high levels of accumulation of reactive oxygen species (ROS). The photosynthetic activities of PSII and the quantity of core protein D1 decreased significantly in lto1-2. Further investigation showed the synthesis of D1 was not affected in mutants both at transcription and translation levels. The soluble DsbA-like domain of LTO1 was found to have reduction, oxidation and isomerization activities, and could promote the formation of disulfide bonds in a lumenal protein, FKBP13. A potential target of LTO1 was captured which was involving in chlorophyll degradation and photooxidative stress response. Experimental results imply that LTO1 plays important roles in redox regulation, ROS homeostasis and maintenance of PSII.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Proteínas de Cloroplastos/metabolismo , Proteínas de la Membrana/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Clorofila/metabolismo , Proteínas de Cloroplastos/genética , Clonación Molecular , Regulación de la Expresión Génica de las Plantas , Técnicas de Inactivación de Genes , Prueba de Complementación Genética , Homeostasis , Proteínas de la Membrana/genética , Oxidación-Reducción , Estrés Oxidativo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Complejo de Proteína del Fotosistema II/fisiología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/fisiología , Proteoma/metabolismo
15.
Protein Pept Lett ; 30(7): 531-540, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37231716

RESUMEN

Cholesterol was first found in gallstones as an animal sterol; hence it is called cholesterol. Cholesterol oxidase is the chief enzyme in the process of cholesterol degradation. Its role is obtained by the coenzyme FAD, which catalyzes the isomerization and oxidation of cholesterol to produce cholesteric 4-ene-3-ketone and hydrogen peroxide at the same time. Recently, a great advance has been made in the discovery of the structure and function of cholesterol oxidase, and it has proven added value in clinical discovery, medical care, food and biopesticides development and other conditions. By recombinant DNA technology, we can insert the gene in the heterologous host. Heterologous expression (HE) is a successful methodology to produce enzymes for function studies and manufacturing applications, where Escherichia coli has been extensively used as a heterologous host because of its economical cultivation, rapid growth, and efficiency in offering exogenous genes. Heterologous expression of cholesterol oxidase has been considered for several microbial sources, such as Rhodococcus equi, Brevibacterium sp., Rhodococcus sp., Streptomyces coelicolor, Burkholderia cepacia ST-200, Chromobacterium, and Streptomyces spp. All related publications of numerous researchers and scholars were searched in ScienceDirect, Scopus, PubMed, and Google Scholar. In this article, the present situation and promotion of heterologous expression of cholesterol oxidase, the role of protease, and the perspective of its possible applications were reviewed.


Asunto(s)
Brevibacterium , Rhodococcus , Animales , Colesterol Oxidasa/genética , Colesterol Oxidasa/química , Colesterol Oxidasa/metabolismo , Colesterol/metabolismo , Brevibacterium/metabolismo , Oxidación-Reducción
16.
Virol Sin ; 38(4): 497-507, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37182691

RESUMEN

Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. To better understand how CHIKV rewires the host cell and usurps host cell functions, we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies. One of these novel interactions, between the viral protein E1 and STIP1 homology and U-box containing protein 1 (STUB1), was found to mediate ubiquitination of E1 and degrade E1 through the proteasome. Capsid associated with G3BP1, G3BP2 and AAA+ â€‹ATPase valosin-containing protein (VCP). Furthermore, VCP inhibitors blocked CHIKV infection, suggesting VCP could serve as a therapeutic target. Further work is required to fully understand the functional consequences of these interactions. Given that CHIKV proteins are conserved across alphaviruses, many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses. Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Virus , Animales , Humanos , Virus Chikungunya/genética , ADN Helicasas , Replicación Viral/fisiología , ARN Helicasas/metabolismo , Proteínas con Motivos de Reconocimiento de ARN , Proteínas de Unión a Poli-ADP-Ribosa , Ubiquitina-Proteína Ligasas/metabolismo
17.
Cell Biosci ; 13(1): 106, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37308953

RESUMEN

Bile acids (BA) are important physiological molecules not only mediating nutrients absorption and metabolism in peripheral tissues, but exerting neuromodulation effect in the central nerve system (CNS). The catabolism of cholesterol to BA occurs predominantly in the liver by the classical and alternative pathways, or in the brain initiated by the neuronal-specific enzyme CYP46A1 mediated pathway. Circulating BA could cross the blood brain barrier (BBB) and reach the CNS through passive diffusion or BA transporters. Brain BA might trigger direct signal through activating membrane and nucleus receptors or affecting activation of neurotransmitter receptors. Peripheral BA may also provide the indirect signal to the CNS via farnesoid X receptor (FXR) dependent fibroblast growth factor 15/19 (FGF15/19) pathway or takeda G protein coupled receptor 5 (TGR5) dependent glucagon-like peptide-1 (GLP-1) pathway. Under pathological conditions, alterations in BA metabolites have been discovered as potential pathogenic contributors in multiple neurological disorders. Attractively, hydrophilic ursodeoxycholic acid (UDCA), especially tauroursodeoxycholic acid (TUDCA) can exert neuroprotective roles by attenuating neuroinflammation, apoptosis, oxidative or endoplasmic reticulum stress, which provides promising therapeutic effects for treatment of neurological diseases. This review summarizes recent findings highlighting the metabolism, crosstalk between brain and periphery, and neurological functions of BA to elucidate the important role of BA signaling in the brain under both physiological and pathological conditions.

18.
Invest Ophthalmol Vis Sci ; 64(13): 41, 2023 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-37883094

RESUMEN

Purpose: Proteopathy is believed to contribute to age-related macular degeneration (AMD). Much research indicates that AMD begins in the retinal pigment epithelium (RPE), which is associated with formation of extracellular drusen, a clinical hallmark of AMD. Human RPE produces a drusen-associated abnormal protein, the exon Ⅵ-skipping splice isoform of retinal G protein-coupled receptor (RGR-d). In this study, we investigate the detrimental effects of RGR-d on cultured cells and mouse retina. Methods: ARPE-19 cells were stably infected by lentivirus overexpressing RGR or RGR-d and were treated with MG132, sometimes combined with or without endoplasmic reticulum (ER) stress inducer, tunicamycin. RGR and RGR-d protein expression, degeneration pathway, and potential cytotoxicity were explored. Homozygous RGR-d mice aged 8 or 14 months were fed with a high-fat diet for 3 months and then subjected to ocular examination and histopathology experiments. Results: We confirm that RGR-d is proteotoxic under various conditions. In ARPE-19 cells, RGR-d is misfolded and almost completely degraded via the ubiquitin-proteasome system. Unlike normal RGR, RGR-d increases ER stress, triggers the unfolded protein response, and exerts potent cytotoxicity. Aged RGR-d mice manifest disrupted RPE cell integrity, apoptotic photoreceptors, choroidal deposition of complement C3, and CD86+CD32+ proinflammatory cell infiltration into retina and RPE-choroid. Furthermore, the AMD-like phenotype of RGR-d mice can be aggravated by a high-fat diet. Conclusions: Our study confirmed the pathogenicity of the RGR splice isoform and corroborated a significant role of proteopathy in AMD. These findings may contribute to greater comprehension of the multifactorial causes of AMD.


Asunto(s)
Proteínas del Ojo , Degeneración Macular , Receptores Acoplados a Proteínas G , Animales , Humanos , Ratones , Exones , Degeneración Macular/genética , Opsinas , Isoformas de Proteínas , Retina , Receptores Acoplados a Proteínas G/genética , Proteínas del Ojo/genética
19.
Nanomaterials (Basel) ; 12(22)2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36432256

RESUMEN

In the present work, a facile one-step methodology was used to synthesize honeycomb-like BiFeO3/g-C3N4 composites, where the well-dispersed BiFeO3 strongly interacted with the hg-C3N4. The 10BiFeO3/hg-C3N4 could completely degrade RhB under visible light illumination within 60 min. The degradation rate constant was remarkably improved and approximately three times and seven times that of pristine hg-C3N4 and BiFeO3, respectively. This is ascribed to the following factors: (1) the unique honeycomb-like morphology facilitates the diffusion of the reactants and effectively improves the utilization of light energy by multiple reflections of light; (2) the charged dye molecules can be tightly bound to the spontaneous polarized BiFeO3 surface to form the Stern layer; (3) the Z-scheme heterojunction and the ferroelectric synergistically promoted the efficient separation and migration of the photogenerated charges. This method can synchronously tune the micro-nano structure, surface property, and internal field construction for g-C3N4-based photocatalysts, exhibiting outstanding potential in environmental purification.

20.
Front Immunol ; 12: 740223, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956175

RESUMEN

Poxviruses have evolved a variety of innate immunity evasion mechanisms, some of which involve poxvirus-encoded E3 ubiquitin ligases and adaptor proteins. Based on their functional domains and ubiquitin transfer mechanisms, these poxvirus-encoded E3 ubiquitin ligases and adaptor proteins can be divided into five categories: PRANC, ANK/BC, BBK, P28/RING, and MARCH proteins. Although the substrates of many poxvirus E3 ubiquitin ligases remain to be discovered, most of the identified substrates are components of the innate immune system. In this review, we discuss the current research progress on poxvirus-encoded E3 ubiquitin ligases and adaptor proteins to provide mechanistic insights into the interplay between these viruses and their hosts.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/inmunología , Poxviridae/enzimología , Ubiquitina-Proteína Ligasas/inmunología , Proteínas Virales/inmunología , Humanos , Poxviridae/inmunología
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