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1.
Mol Cell ; 81(14): 2960-2974.e7, 2021 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-34111398

RESUMEN

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1-/- phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.


Asunto(s)
5-Metilcitosina/análogos & derivados , Regulación Alostérica/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitinación/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , 5-Metilcitosina/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Desmetilación del ADN , Metilación de ADN/genética , Reparación del ADN/genética , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Células HEK293 , Humanos , Células MCF-7 , Ratones , Ratones Noqueados , Regiones Promotoras Genéticas/genética , Unión Proteica/genética
2.
Plant Physiol ; 194(2): 1104-1119, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-37647540

RESUMEN

Cold affects the growth and development of plants. MYB transcription factors and histone H3K4me3 transferase ARABIDOPSIS TRITHORAXs (ATXs) play important regulatory functions in the process of plant resistance to low-temperature stress. In this study, DgMYB expression was responsive to low temperature, and overexpression of DgMYB led to increased tolerance, whereas the dgmyb mutant resulted in decreased tolerance of Chrysanthemum morifolium (Dendranthema grandiflorum var. Jinba) to cold stresses. Interestingly, we found that only peroxidase (POD) activity differed substantially between wild type (WT), overexpression lines, and the mutant line. A DgATX H3K4me3 methylase that interacts with DgMYB was isolated by further experiments. DgATX expression was also responsive to low temperature. Overexpression of DgATX led to increased tolerance, whereas the dgatx mutant resulted in decreased tolerance of chrysanthemum to cold stresses. Moreover, the dgmyb, dgatx, and dgmyb dgatx double mutants all led to reduced H3K4me3 levels at DgPOD, thus reducing DgPOD expression. Together, our results show that DgMYB interacts with DgATX, allowing DgATX to specifically target DgPOD, altering H3K4me3 levels, increasing DgPOD expression, and thereby reducing the accumulation of reactive oxygen species (ROS) in chrysanthemum.


Asunto(s)
Arabidopsis , Chrysanthemum , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Histonas/metabolismo , Chrysanthemum/genética , Chrysanthemum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las Plantas , Frío , Arabidopsis/genética , Arabidopsis/metabolismo
3.
Small ; 20(27): e2309661, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38268235

RESUMEN

Soft robots based on flexible materials have attracted the attention due to high flexibility and great environmental adaptability. Among the common driving modes, electricity, light, and magnetism have the limitations of wiring, poor penetration capability, and sophisticated equipment, respectively. Here, an emerging wireless driving mode is proposed for the soft crawling robot based on wireless power transfer (WPT) technology. The receiving coil at the robot's tail, as an energy transfer station, receives energy from the transmitting coil and supplies the electrothermal responsiveness to drive the robot's crawling. By regulating the WPT's duration to control the friction between the robot and the ground, bidirectional crawling is realized. Furthermore, the receiving coil is also employed as a sensory organ to equip the robot with localization, ID recognition, and sensing capabilities based on electromagnetic coupling. This work provides an innovative and promising strategy for the design and integration of soft crawling robots, exhibiting great potential in the field of intelligent robots.

4.
Plant Physiol ; 194(1): 243-257, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37399189

RESUMEN

Plant lignocellulosic biomass, i.e. secondary cell walls of plants, is a vital alternative source for bioenergy. However, the acetylation of xylan in secondary cell walls impedes the conversion of biomass to biofuels. Previous studies have shown that REDUCED WALL ACETYLATION (RWA) proteins are directly involved in the acetylation of xylan but the regulatory mechanism of RWAs is not fully understood. In this study, we demonstrate that overexpression of a Populus trichocarpa PtRWA-C gene increases the level of xylan acetylation and increases the lignin content and S/G ratio, ultimately yielding poplar woody biomass with reduced saccharification efficiency. Furthermore, through gene coexpression network and expression quantitative trait loci (eQTL) analysis, we found that PtRWA-C was regulated not only by the secondary cell wall hierarchical regulatory network but also by an AP2 family transcription factor HARDY (HRD). Specifically, HRD activates PtRWA-C expression by directly binding to the PtRWA-C promoter, which is also the cis-eQTL for PtRWA-C. Taken together, our findings provide insights into the functional roles of PtRWA-C in xylan acetylation and consequently saccharification and shed light on synthetic biology approaches to manipulate this gene and alter cell wall properties. These findings have substantial implications for genetic engineering of woody species, which could be used as a sustainable source of biofuels, valuable biochemicals, and biomaterials.


Asunto(s)
Populus , Populus/genética , Populus/metabolismo , Xilanos/metabolismo , Acetilación , Biomasa , Biocombustibles/análisis , Plantas/metabolismo , Pared Celular/metabolismo , Lignina/metabolismo
5.
Plant Physiol ; 191(3): 1492-1504, 2023 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-36546733

RESUMEN

Deciduous woody plants like poplar (Populus spp.) have seasonal bud dormancy. It has been challenging to simultaneously delay the onset of bud dormancy in the fall and advance bud break in the spring, as bud dormancy, and bud break were thought to be controlled by different genetic factors. Here, we demonstrate that heterologous expression of the REVEILLE1 gene (named AaRVE1) from Agave (Agave americana) not only delays the onset of bud dormancy but also accelerates bud break in poplar in field trials. AaRVE1 heterologous expression increases poplar biomass yield by 166% in the greenhouse. Furthermore, we reveal that heterologous expression of AaRVE1 increases cytokinin contents, represses multiple dormancy-related genes, and up-regulates bud break-related genes, and that AaRVE1 functions as a transcriptional repressor and regulates the activity of the DORMANCY-ASSOCIATED PROTEIN 1 (DRM1) promoter. Our findings demonstrate that AaRVE1 appears to function as a regulator of bud dormancy and bud break, which has important implications for extending the growing season of deciduous trees in frost-free temperate and subtropical regions to increase crop yield.


Asunto(s)
Agave , Populus , Proteínas de Plantas/metabolismo , Populus/metabolismo , Estaciones del Año , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
6.
Brain Behav Immun ; 123: 123-142, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243987

RESUMEN

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) mediated by CD4+ T helper (Th) cells, and characterized by immune cell infiltration, demyelination and neurodegeneration, with no definitive cure available. Thus, it is pivotal and imperative to acquire more profound comprehension of the underlying mechanisms implicated in MS. Dysregulated immune responses are widely believed to play a primary role in the pathogenesis of MS. Recently, a plethora of studies have demonstrated the involvement of T follicular helper (Tfh) cells and tertiary lymphoid-like structures (TLSs) in the pathogenesis and progression of MS. Cathepsin C (CatC) is a cysteine exopeptidase which is crucial for the activation of immune-cell-associated serine proteinases in many inflammatory diseases in peripheral system, such as rheumatoid arthritis and septicemia. We have previously demonstrated that CatC is involved in neuroinflammation and exacerbates demyelination in both cuprizone-induced and experimental autoimmune encephalomyelitis (EAE) mouse models. However, the underlying immunopathological mechanism remains elusive. In the present study, we established a recombinant myelin oligodendrocyte glycoprotein 35-55 peptide-induced EAE model using conditional CatC overexpression mice to investigate the effects of CatC on the alteration of CD4+ Th subsets, including Th1, Th2, Th17, Tfh and T regulatory cells. Our findings demonstrated that CatC particularly enhanced the population of Tfh cell in the brain, resulting in the earlier onset and more severe chronic syndrome of EAE. Furthermore, CatC promoted the formation of TLSs in the brain, leading to persistent neuroinflammation and exacerbating the severity of EAE in the chronic phase. Conversely, treatment with AZD7986, a specific inhibitor of CatC, effectively attenuated the syndrome of EAE and its effects caused by CatC both in vivo and in vitro. These findings provide a novel insight into the critical role of CatC in innate and adaptive immunity in EAE, and specific inhibitor of CatC, AZD7986, may contribute to potential therapeutic strategies for MS.

7.
Environ Sci Technol ; 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39031076

RESUMEN

Ice can serve as a significant temporary repository and conveyance mechanism for microplastics (MPs). MPs present in the water column can become entrapped within developing ice formations, subsequently being sequestered and transported by ice floes. With changing temperatures, MPs stored in ice can be released back into the environment, while freezing conditions can alter the properties of MPs, ultimately affecting the fate of MPs in the environment. Freezing of MPs in freshwater ice results in the aggregation of MP particles due to physical compression, leading to an increase in particle size once the MPs are released from the ice. The freezing-induced aggregation enhances buoyancy effects, accelerating the settling/rising velocity of MPs in water. Additionally, freezing can lead to enhanced surface wetting alterations, thus improving the dispersion of hydrophobic MPs. The presence of salt in the water can mitigate the effect of freezing on MPs due to the formation of a brine network within the ice structure, which reduces the pressure on MPs entrapped by ice. In cold regions, numerous MPs undergo freezing and thawing, re-entering the water column.

8.
Environ Sci Technol ; 58(6): 2944-2955, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38306690

RESUMEN

The estuary is an energetic area connecting the inland, river, and ocean. The migration of microplastics (MPs) in this highly complex area is tied to the entire ecosystem. In this study, the effects of cohesive SPM (clay) and noncohesive SPM (sand) on the vertical migration of positively buoyant MPs, polyethylene (PE), and negatively buoyant MPs, polytetrafluoroethylene (PTFE), in the estuarine environment under hydrodynamic disturbances were investigated. The settling of positively buoyant MPs was more reliant on the cohesive SPM compared to the settling of negatively buoyant MPs. Moreover, MPs interacting with the SPM mixture at a clay-to-sand ratio of 1:9 settled more efficiently than those interacting with clay alone. A significant positive correlation was observed between MP settling percentage and the salinity level. MP settling percentage was significantly negatively correlated with fluid shear stress for both types of MPs, meanwhile, negatively buoyant MPs were able to resist greater hydraulic disturbances. In the low-energy mixing state, for both types of MPs, the settling percentage reached about 50% in only 10 min. The resuspension process of MPs under hydrodynamic disturbances was also uncovered. Additionally, the migration and potential sites of MPs were described in the context of prevalent environmental phenomena in estuaries.


Asunto(s)
Material Particulado , Contaminantes Químicos del Agua , Material Particulado/análisis , Microplásticos , Plásticos , Salinidad , Arena , Hidrodinámica , Arcilla , Ecosistema , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Estuarios
9.
Cell ; 138(4): 660-72, 2009 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-19703393

RESUMEN

Lysine-specific demethylase 1 (LSD1) exerts pathway-specific activity in animal development and has been linked to several high-risk cancers. Here, we report that LSD1 is an integral component of the Mi-2/nucleosome remodeling and deacetylase (NuRD) complex. Transcriptional target analysis revealed that the LSD1/NuRD complexes regulate several cellular signaling pathways including TGFbeta1 signaling pathway that are critically involved in cell proliferation, survival, and epithelial-to-mesenchymal transition. We demonstrated that LSD1 inhibits the invasion of breast cancer cells in vitro and suppresses breast cancer metastatic potential in vivo. We found that LSD1 is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of TGFbeta1. Our data provide a molecular basis for the interplay of histone demethylation and deacetylation in chromatin remodeling. By enlisting LSD1, the NuRD complex expands its chromatin remodeling capacity to include ATPase, histone deacetylase, and histone demethylase.


Asunto(s)
Neoplasias de la Mama/metabolismo , Histona Desacetilasas/metabolismo , Metástasis de la Neoplasia/genética , Oxidorreductasas N-Desmetilantes/metabolismo , Animales , Línea Celular Tumoral , Ensamble y Desensamble de Cromatina , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Células HeLa , Histona Demetilasas , Humanos , Complejo Desacetilasa y Remodelación del Nucleosoma Mi-2 , Ratones , Ratones SCID , Trasplante de Neoplasias , Nucleosomas/metabolismo , Oxidorreductasas N-Desmetilantes/química , Fragmentos de Péptidos/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
10.
Macromol Rapid Commun ; 45(14): e2400105, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38623606

RESUMEN

Intelligent materials derived from green and renewable bio-based materials garner widespread attention recently. Herein, shape memory polyurethane composite (PUTA/Fe) with fast response to near-infrared (NIR) light is successfully prepared by introducing Fe3+ into the tannic acid-based polyurethane (PUTA) matrix through coordination between Fe3+ and tannic acid. The results show that the excellent NIR light response ability is due to the even distribution of Fe3+ filler with good photo-thermal conversion ability. With the increase of Fe3+ content, the NIR light response shape recovery rate of PUTA/Fe composite films is significantly improved, and the shape recovery time is reduced from over 60 s to 40 s. In addition, the mechanical properties of PUTA/Fe composite film are also improved. Importantly, owing to the dynamic phenol-carbamate network within the polymer matrix, the PUTA/Fe composite film can reshape its permanent shape through topological rearrangement and show its good NIR light response shape memory performance. Therefore, PUTA/Fe composites with high content of bio-based material (TA content of 15.1-19.4%) demonstrate the shape memory characteristics of fast response to NIR light; so, it will have great potential in the application of new intelligent materials including efficient and environmentally friendly smart photothermal responder.


Asunto(s)
Carbamatos , Rayos Infrarrojos , Hierro , Poliuretanos , Taninos , Taninos/química , Poliuretanos/química , Hierro/química , Carbamatos/química , Fenoles/química , Fenol/química , Materiales Inteligentes/química , Polifenoles
11.
Environ Res ; 250: 118506, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38387496

RESUMEN

Polystyrene nanoplastics (PS-NPs), a group of ubiquitous pollutants, may injure the central nervous system through the blood‒brain barrier (BBB). However, whether exposure to PS-NPs contributes to BBB disruption and the underlying mechanisms are still unclear. In vivo, we found that PS-NPs (25 mg/kg BW) could significantly increase BBB permeability in mice and downregulate the distribution of the tight junction-associated protein zona occludens 1 (ZO-1) in brain microvascular endothelial cells (BMECs). Using an in vitro BBB model, exposure to PS-NPs significantly reduced the transendothelial electrical resistance and altered ZO-1 expression and distribution in a dose-dependent manner. RNA-seq analysis and functional investigations were used to investigate the molecular pathways involved in the response to PS-NPs. The results revealed that the ferroptosis and glutathione metabolism signaling pathways were related to the disruption of the BBB model caused by the PS-NPs. PS-NPs treatment promoted ferroptosis in bEnd.3 cells by inducing disordered glutathione metabolism in addition to Fe2+ and lipid peroxide accumulation, while suppressing ferroptosis with ferrostatin-1 (Fer-1) suppressed ferroptosis-related changes in bEnd.3 cells subjected to PS-NPs. Importantly, Fer-1 alleviated the decrease in ZO-1 expression in bEnd.3 cells and the exacerbation of BBB damage induced by PS-NPs. Collectively, our findings suggest that inhibiting ferroptosis in BMECs may serve as a potential therapeutic target against BBB disruption induced by PS-NPs exposure.


Asunto(s)
Barrera Hematoencefálica , Células Endoteliales , Ferroptosis , Poliestirenos , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Ferroptosis/efectos de los fármacos , Poliestirenos/toxicidad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Ratones , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/irrigación sanguínea , Nanopartículas/toxicidad , Masculino
12.
Retina ; 44(3): 429-437, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37883595

RESUMEN

PURPOSE: To investigate the predictive factors for postsurgical visual prognosis in patients with vitreomacular traction (VMT). METHODS: This retrospective study enrolled 31 eyes from 29 patients who underwent vitrectomy for idiopathic VMT with a follow-up period of ≥3 months. The VMT was divided into three grades based on optical coherence tomography images: Grade 1 denoted partial vitreomacular separation with foveal attachment; Grade 2 exhibited intraretinal cysts or cleft with grade 1 findings; and Grade 3 was Grade 2 plus the subretinal fluid. RESULTS: Three eyes developed a full-thickness macular hole after surgery, all of which were Grade 3 patients. In the rest 28 eyes, the mean postoperative follow-up period was 23.3 ± 25.8 months. The postoperative central foveal thickness ( P = 0.001) and final best-corrected visual acuity (BCVA; P < 0.001) were both significantly improved from baseline. Fifteen eyes (53.8%) gained ≥ two Snellen lines. Multilinear regression analysis showed that the worse the baseline BCVA ( P = 0.004), or the more advanced the VMT grade ( P = 0.049), the worse the final BCVA. Baseline BCVA was negatively associated with the postoperative visual improvement ( P < 0.001). Those Grade 3 patients with baseline Snellen BCVA of ≥20/40 were more likely to achieve a final Snellen BCVA of ≥20/25 ( P = 0.035). CONCLUSION: The VMT grade is an important predictive factor for the postsurgical visual prognosis. Surgical intervention should be performed as early as possible for Grade 3 patients to prevent further disease progression and maximize the postsurgical visual benefit.


Asunto(s)
Tracción , Desprendimiento del Vítreo , Humanos , Estudios Retrospectivos , Desprendimiento del Vítreo/diagnóstico , Desprendimiento del Vítreo/cirugía , Retina/diagnóstico por imagen , Vitrectomía/métodos , Trastornos de la Visión/cirugía , Pronóstico , Tomografía de Coherencia Óptica
13.
Ophthalmic Res ; 67(1): 137-144, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38246146

RESUMEN

INTRODUCTION: The aim of this study was to evaluate the clinical characteristics and surgical outcomes of the epiretinal membrane foveoschisis (ERM-FS) with different morphological types. METHODS: This retrospective observational study reviewed 44 consecutive ERM-FS patients who underwent ERM surgery. According to the optical coherence tomography images, ERM-FS was classified into three groups: group A, FS crossed the fovea with the foveola elevated; group B, FS located at the foveal edges with a near-normal central foveal point thickness; and group C, FS with undermined foveal edges with a near-normal central foveal point thickness. RESULTS: There were 10 eyes in group A, 20 eyes in group B, and 14 eyes in group C. Preoperatively, eyes in group A had the best best-corrected visual acuity (BCVA), the thickest central foveal point thickness, and the highest ellipsoid zone (EZ) intact rate among the three groups. After surgery, a resolution of foveoschisis was observed in 40.0%, 45.0%, and 50.0% of the eyes in group A, group B, and group C (p = 0.928), respectively. BCVA was significantly improved postoperatively. Although there was no significant difference in BCVA among the three groups at 1 month postoperatively, BCVA of group A was the best at 4 and 10 months. Correlation analysis indicated that the type of ERM-FS, baseline BCVA, central foveal point thickness, and postoperative EZ continuity (all p < 0.05) were important factors for the final BCVA. CONCLUSIONS: The damage to the retinal structure and visual function was milder in group A ERM-FS. Our study emphasized the necessity of OCT-based subtyping in patients with ERM-FS.


Asunto(s)
Membrana Epirretinal , Fóvea Central , Retinosquisis , Tomografía de Coherencia Óptica , Agudeza Visual , Vitrectomía , Humanos , Estudios Retrospectivos , Vitrectomía/métodos , Agudeza Visual/fisiología , Membrana Epirretinal/cirugía , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/fisiopatología , Femenino , Masculino , Fóvea Central/patología , Tomografía de Coherencia Óptica/métodos , Anciano , Retinosquisis/cirugía , Retinosquisis/diagnóstico , Retinosquisis/fisiopatología , Persona de Mediana Edad , Estudios de Seguimiento
14.
Nano Lett ; 23(20): 9280-9286, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37811843

RESUMEN

The fabrication of artificial structures using a twisted van der Waals assembly has been a key technique for recent advancements in the research of two-dimensional (2D) materials. To date, various exotic phenomena have been observed thanks to the modified electron correlation or moiré structure controlled by the twist angle. However, the twisted van der Waals assembly has further potential to modulate the physical properties by controlling the symmetry. In this study, we fabricated twisted bilayer WTe2 and demonstrated that the twist angle successfully controls the spatial inversion symmetry and hence the spin splitting in the band structure. Our results reveal the further potential of a twisted van der Waals assembly, suggesting the feasibility of pursuing new physical phenomena in 2D materials based on the control of symmetry.

15.
Chem Senses ; 482023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37586060

RESUMEN

Smell detection depends on nasal airflow, which can make absorption of odors to the olfactory epithelium by diffusion through the mucus layer. The odors then act on the chemo-sensitive epithelium of olfactory sensory neurons (OSNs). Therefore, any pathological changes in the olfactory area, for instance, dry nose caused by Sjögren's Syndrome (SS) may interfere with olfactory function. SS is an autoimmune disease in which aquaporin (AQP) 5 autoantibodies have been detected in the serum. However, the expression of AQP5 in olfactory mucosa and its function in olfaction is still unknown. Based on the study of the expression characteristics of AQP5 protein in the nasal mucosa, the olfaction dysfunction in AQP5 knockout (KO) mice was found by olfactory behavior analysis, which was accompanied by reduced secretion volume of Bowman's gland by using in vitro secretion measure system, and the change of acid mucin in nasal mucus layer was identified. By excluding the possibility that olfactory disturbance was caused by changes in OSNs, the result indicated that AQP5 contributes to olfactory functions by regulating the volume and composition of OE mucus layer, which is the medium for the dissolution of odor molecules. Our results indicate that AQP5 can affect the olfactory functions by regulating the water supply of BGs and the mucus layer upper the OE that can explain the olfactory loss in the patients of SS, and AQP5 KO mice might be used as an ideal model to study the olfactory dysfunction.


Asunto(s)
Trastornos del Olfato , Síndrome de Sjögren , Ratones , Humanos , Animales , Olfato , Mucosa Olfatoria/metabolismo , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Acuaporina 5/genética , Acuaporina 5/metabolismo , Trastornos del Olfato/genética , Trastornos del Olfato/metabolismo
16.
Virol J ; 20(1): 5, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36624466

RESUMEN

BACKGROUND: Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. METHODS: We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0-3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. RESULTS: Clinical findings showed that severe infection was more common in infants aged 0-3 months than in older children (78.0% vs. 35.4%, p < 0.001), with higher morbidity of pneumonia, meningitis, and sepsis (p < 0.01). EV-B types were detected more frequently in infants aged 0-3 months than in older children (88.0% vs. 7.7%, p < 0.001). Echovirus 11 was the most identified EV-B, and it recombined with E6 in P2 and P3 regions. Risk factors for severe EV infection included EV-B types infection, age less than 3 months, elevated alanine aminotransferase level, abnormal platelet count, and abnormal cerebrospinal fluid characteristics. CONCLUSIONS: Our data indicated that EV-B types mainly cause severe infection in infants aged 0-3 months. Therefore, knowledge about EV-B types could have implications in designing effective intervention and prevention strategies for young infants with severe EV infection.


Asunto(s)
Infecciones por Enterovirus , Enterovirus , Parechovirus , Infecciones por Picornaviridae , Humanos , Lactante , Enterovirus/genética , Enterovirus Humano B , Infecciones por Enterovirus/epidemiología , Parechovirus/genética , Estudios Retrospectivos
17.
EMBO Rep ; 22(7): e52036, 2021 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-34114325

RESUMEN

Dysregulation of lipid metabolism could lead to the development of metabolic disorders. We report here that the F-box protein JFK promotes excessive lipid accumulation in adipose tissue and contributes to the development of metabolic syndrome. JFK transgenic mice develop spontaneous obesity, accompanied by dyslipidemia, hyperglycemia, and insulin resistance, phenotypes that are further exacerbated under high-fat diets. In contrast, Jfk knockout mice are lean and resistant to diet-induced metabolic malfunctions. Liver-specific reconstitution of JFK expression in Jfk knockout mice leads to hepatic lipid accumulation resembling human hepatic steatosis and nonalcoholic fatty liver disease. We show that JFK interacts with and destabilizes ING5 through assembly of the SCF complex. Integrative transcriptomic and genomic analysis reveals that the SCFJFK -ING5 axis interferes with AMPK activity and fatty acid ß-oxidation, leading to the suppression of hepatic lipid catabolism. Significantly, JFK is upregulated and AMPKα1 is down-regulated in liver tissues from NAFLD patients. These results reveal that SCFJFK is a bona fide E3 ligase for ING5 and link the SCFJFK -ING5 axis to the development of obesity and metabolic syndrome.


Asunto(s)
Resistencia a la Insulina , Síndrome Metabólico , Enfermedad del Hígado Graso no Alcohólico , Animales , Dieta Alta en Grasa/efectos adversos , Humanos , Metabolismo de los Lípidos/genética , Hígado/metabolismo , Síndrome Metabólico/genética , Síndrome Metabólico/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Obesidad/genética , Obesidad/metabolismo , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismo
18.
Inorg Chem ; 62(34): 14072-14085, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37578854

RESUMEN

The organometallic compounds of lithium ions have garnered continuous interest as indispensable precursors for the syntheses of organometallic complexes of main-group metals, transition metals, lanthanide metals, and actinide metals. In this work, we present a strategy for the preparation of a series of polynuclear lithium complexes. This methodology features the utilization of organolithium reagents both as metal sources to coordinate with the ligands and as nucleophilic reagents to undergo nucleophilic addition to the C═N bonds of the ligands. Reaction of a ligand HL1 [HL1 = 2-(((1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)methylene)amino)phenol] with n-BuLi produced complex [Li8(L1a)4]·1.5Tol (1·1.5Tol) [H2L1a = 2-((1-(1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)pentyl)amino)phenol]. One prominent feature regarding the formation of 1·1.5Tol is the occurrence of nucleophilic addition of n-BuLi to the C═N bond of HL1, leading to the generation of a new [L1a]2- ligand that contains both aminophenol and 1-(2-pyrrolyl)alkylamine scaffolds. The developed protocol can be adapted to a series of organolithium reagents. Compounds [Li8(L1b)4] (2) and [Li8(L1c)4] (3) were afforded by treatment of HL1 with sec-BuLi and LiCH2SiMe3, respectively. Reaction of an analogous ligand HL2 [HL2 = 2-(((1-(2-(dimethylamino)ethyl)-1H-pyrrol-2-yl)methylene)amino)-4-methylphenol] with n-BuLi generated compound [Li8(L2a)4] (4). C═N bond activation was not observed in the reaction of HL1 with NaOtBu, and the complex [Na4(L1)4]·Tol (5·Tol) was obtained. A decanuclear complex [Li10(L3a)2(L3b)2] (6) was also prepared via the reaction of HL3 [HL3 = 2-(2-((((1H-pyrrol-2-yl)methylene)amino)methyl)-1H-pyrrol-1-yl)-N,N-dimethylethan-1-amine] with t-BuLi. A remarkable feature in terms of the synthesis of 6 is the simultaneous occurrence of hydrogen atom abstraction from the C-H bond of the pyrrolyl ring and nucleophilic addition to the C═N bond of the HL3 ligand by t-BuLi. A series of amines containing biologically and physiologically important moieties were achieved by hydrolysis of the crude products from the reactions of the HL1-HL3 ligands and organolithium reagents. This work provides an efficient approach to high-nuclearity lithium compounds as well as a series of amines.

19.
Graefes Arch Clin Exp Ophthalmol ; 261(4): 925-933, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36326950

RESUMEN

PURPOSE: To investigate the changes in the external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ) integrity and their relationship with visual outcomes after idiopathic epiretinal membranes peeling. METHODS: Clinical records of 150 eyes from 144 consecutive patients who underwent vitrectomy were reviewed. The status of IZ, EZ, and ELM was assessed by spectral-domain optical coherence tomography at baseline and 1, 4, 10, and 24 months postoperatively. RESULTS: Sixty-one eyes presented with photoreceptor layer disruption preoperatively, and IZ disruption (40.7%) was the primary type. The best-corrected visual acuity (BCVA) in the photoreceptor disruption group was significantly lower than that in the intact group at baseline and the final follow-up. Of them, ELM + EZ + IZ disruption showed the worst BCVA (P = 0.001). After surgery, 62 eyes were observed with disruption aggravated. EZ + IZ disruption (51.0%) was the most frequent type at 1 month postoperatively. The eyes with longer symptom duration, better BCVA, earlier stage, thinner CFT at baseline, and combined cataract surgery more tended to be observed with photoreceptor damage progressed after surgery (P < 0.05). There was no significant difference in the final BCVA between the eyes with and without damage progressed (P = 0.332). Finally, 28.1% of the eyes recovered photoreceptor continuity. The eyes with foveal photoreceptor integrity restored had better BCVA than those remaining discontinuous (P < 0.001). CONCLUSION: ERM-induced photoreceptor disruption mainly manifests as IZ disruption and has a negative effect on BCVA, whereas surgery mainly causes EZ and IZ disruption, which does not have a significant impact on the final BCVA.


Asunto(s)
Extracción de Catarata , Membrana Epirretinal , Humanos , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Agudeza Visual , Fóvea Central , Retina , Tomografía de Coherencia Óptica/métodos , Vitrectomía , Estudios Retrospectivos
20.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3651-3657, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37354268

RESUMEN

PURPOSE: To describe the characteristics and surgical outcomes of idiopathic epiretinal membrane (iERM) in children and to determine the factors associated with postoperative visual acuity (VA). METHODS: We retrospectively reviewed the medical records of 17 patients with iERM (age, < 18 years) who had undergone ERM surgery from 2009 to 2021. Spectral-domain optical coherence tomography features were documented. The eyes with iERMs involving the fovea were assigned to the localized and diffused groups depending on the morphological description of the membrane. Multiple linear regression analysis was used to explore the factors associated with the final VA. RESULTS: The mean age was 9.2 ± 3.8 years. The mean follow-up period was 38.9 ± 45.4 months. After surgery, the central foveal thickness and the best-corrected VA (BCVA) improved significantly (all, P < 0.05). Fourteen eyes with iERMs showed involvement of the foveal area (localized group, six eyes; diffused group, eight eyes). There were no significant differences in the preoperative BCVA between the two groups (P = 0.064). However, the final BCVA was better in the diffused group than in the localized group (P = 0.043). Multiple regression analysis indicated that the localized membrane (P = 0.042) and lower preoperative BCVA (P = 0.043) were factors associated with a worse final VA in pediatric iERMs. CONCLUSIONS: Surgical removal of ERM showed a high anatomical and functional success rate in children. In pediatric patients with iERMs involving the fovea, a good VA was more common when the membrane was diffused than when it was localized.


Asunto(s)
Membrana Epirretinal , Humanos , Niño , Preescolar , Adolescente , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios Retrospectivos , Vitrectomía/métodos , Fóvea Central , Tomografía de Coherencia Óptica/métodos , Agudeza Visual
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