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1.
Chem Sci ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39290592

RESUMEN

In this work, we designed and synthesized three spirobifluorene (SBF)-based hole-transporting materials (HTMs) by incorporating the di-4-tolylamino group at different positions of the SBF skeleton. These materials demonstrate excellent thermal stability with thermal decomposition temperatures (T d) up to 506 °C and outstanding morphological stability with a glass transition temperature (T g) exceeding 145 °C. The meta-linkage mode between the conjugated skeleton and functional groups in the molecular structure results in electronic decoupling, giving these 3,6-substituted SBFs higher triplet energies (E T) compared to 2,7-substituted SBFs. This makes the 3,6-substituted SBFs suitable as universal HTMs for red, green, and blue (RGB) organic light emitting diodes (OLEDs). Among the three HTMs, 3,3',6,6'-tetra(N,N-ditolylamino)-9,9'-spirobifluorene (3,3',6,6'-TDTA-SBF) exhibits the best device performance, achieving maximum external quantum efficiencies (EQEmax) of 26.1%, 26.4%, and 25.4% for RGB phosphorescent OLEDs, with extremely low efficiency roll-off in both green and blue devices. Utilizing 3,3',6,6'-TDTA-SBF as the HTM, we have also fabricated narrowband blue OLEDs based on the widely used multiple resonance emitter BCz-BN, which exhibits a EQEmax of 29.8% and low efficiency roll-off.

2.
Food Chem Toxicol ; 192: 114928, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142553

RESUMEN

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) and Helicobacter pylori might synergistically promote the malignant transformation of human esophageal epithelial cells (HEECs) through inducing DNA double-strand breaks (DSBs) and inhibition of PAXX protein expression. The long noncoding RNA (lncRNA) TUG1 is associated with multiple cancers, and its overexpression can promote cancer by interfering with the functions of oncogenes. LncRNA TUG1 is also associated with DNA methyltransferase 1 (DNMT1) and the epithelial signaling pathway of H. pylori infection. To explore the role of LncRNA TUG1 in the malignant transformation of HEECs induced by H.pylori + MNNG, a stable strain of HEECs with LncRNA TUG1 knockdown (LncRNA TUG1-KD) was constructed using RNA interference technology with lentivirus as a vector. Set up negative controls LncRNA TUG1-NC (null carrier lentivirus was selected to transfect HEECs) and block controls (normal HEECs without exposure). H. pylori + MNNG were added to the LncRNA TUG1-KD and LncRNA TUG1-NC groups for 6 h and then passaged until their malignant transformation. From each group, cells in the early, intermediate, and late stages of malignant transformation were used for the alkaline comet assay and determination of protein expression, including γ-H2AX and PAXX, by western blotting assay to assess DNA damage and repair processes. Clone formation assay in soft agar and nude mouse xenograft model was used to assess malignancy. This study suggests that H. pylori + MNNG promotes the malignant transformation of HEECs by inducing DNA DSBs and inhibiting PAXX expression, and this effect may be alleviated by LncRNA TUG1 knockdown. It elucidates the pathogenesis of EC from the perspective of the combined effect of epigenetic and environmental carcinogens, offering new insights for the comprehensive prevention and treatment of EC.


Asunto(s)
Transformación Celular Neoplásica , Daño del ADN , Células Epiteliales , Helicobacter pylori , Metilnitronitrosoguanidina , ARN Largo no Codificante , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Metilnitronitrosoguanidina/toxicidad , Humanos , Transformación Celular Neoplásica/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Animales , Neoplasias Esofágicas/genética , Ratones , Esófago/patología , Esófago/efectos de los fármacos , Infecciones por Helicobacter , Ratones Desnudos
3.
Adv Sci (Weinh) ; : e2402693, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136057

RESUMEN

Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium-activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type-specific TMEM16F-deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell-expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.

4.
Methods Mol Biol ; 2841: 1-17, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39115761

RESUMEN

Protein secretion mediated by the secretory transport pathway is a sophisticated and highly regulated cellular process in eukaryotic cells. In the conventional secretory transport pathway, newly synthesized proteins pass through several endomembrane compartments to reach their destinations. This transport occurs via small, membrane-enclosed vesicles. To ensure the fidelity of trafficking, eukaryotic cells employ elaborate molecular machinery to accurately sort newly synthesized proteins into specific transport vesicles and precisely deliver them to respective acceptor compartments. Leaderless cargo proteins, lacking a signal peptide, follow an unconventional secretory pathway. This review encompasses the molecular machinery regulating both conventional and unconventional protein secretion in yeast and animal cells.


Asunto(s)
Transporte de Proteínas , Vías Secretoras , Animales , Saccharomyces cerevisiae/metabolismo , Humanos , Levaduras/metabolismo , Proteínas/metabolismo
5.
Chem Sci ; 15(27): 10547-10555, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38994415

RESUMEN

In this work, we present a design concept of introducing linear structures into the orthogonal configuration of 9,9'-spirobifluorene (SBF), aiming to enhance carrier mobilities while maintaining high triplet energies (E T), which are two critical parameters for optimizing host materials in organic light-emitting diodes (OLEDs). To validate our proposed design, four pivotal model molecules of 1,4-diaryl SBFs were synthesized via interannular C-H arylation of bi(hetero)aryl-2-formaldehydes, a task challenging to accomplish using previous synthetic methodologies. The orthogonal configuration and the steric hindrance of SBF lead to high E T through the conjugation breaking at C1 and C4 positions, rendering 1,4-diaryl SBFs suitable as universal pure hydrocarbon (PHC) hosts for red, green, and blue (RGB) phosphorescent OLEDs (PhOLEDs). Meanwhile, the linearity and relatively good planarity of the para-quaterphenyl structure promote high carrier mobilities through orderly intermolecular packing. The synergistic effects of linearity and orthogonality in 1-(para-biphenyl)-4-phenyl-SBF result in exceptional device performance with external quantum efficiencies (EQEs) of 26.0%, 26.1%, and 22.5% for RGB PhOLEDs, respectively. Notably, the green PhOLED exhibits minimal efficiency roll-off, positioning its device performances among the state-of-the-art in PHC hosts.

6.
Opt Express ; 32(10): 18017-18032, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38858968

RESUMEN

Augmented reality head-mounted displays (AR-HMDs) utilizing diffractive waveguides have emerged as a popular research focus. However, the illuminance uniformity over the fields of view (FOV) is often unsatisfactory in volume holographic grating (VHG) based waveguide displays. This paper proposes a high uniformity AR waveguide display system. Firstly, the angular uniformity of the VHG-based waveguide displays is analyzed. Subsequently, diffractive optical elements (DOEs) are seamlessly integrated onto the outer coupling surface of the waveguide substrate to improve the angular uniformity through phase compensation. To design the DOE phase, the multi-objective stochastic gradient descent (MO-SGD) algorithm is proposed. A single DOE is used to compensating various images form the image source. A hybrid loss, which includes the learned perceptual image patch similarity (LPIPS) metric, is applied to enhance the algorithm performance. Simulation results show that the proposed method effectively suppresses illumination degradation at the edge FOV in exit pupil images of the waveguide display system. In the results, the peak signal-to-noise ratio (PSNR) is improved by 5.54 dB. Optical experiments validate the effectiveness of the proposed method. The measured nonuniformity (NU) against FOVs is improved by 53.05% from 0.3749 to 0.1760.

7.
Sci Rep ; 14(1): 13323, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858385

RESUMEN

Quantitative real-time PCR (qRT-PCR) has been widely employed for the study of gene expression in fish, and accurate normalization is crucial. In this study, we aimed to identify the most stably expressed genes in various tissues, different developmental stages, and within astaxanthin treatment groups in Lutjanus erythropterus. Twelve candidate genes (EEF1A, CYB5R3, DLD, IDH3A, MRPL17, MRPL43, NDUFS7, PABPC1, PAGR1, PFDN2, PSMC3, and RAB10) were examined via qRT-PCR. We employed geNorm and NormFinder to assess their stability. The results revealed that RAB10 and PFDN2 exhibited relatively stable expression patterns across different tissue and astaxanthin treatment groups, while NDUFS7 and MRPL17 proved to be the most reliable reference gene combinations across various developmental stages. The stability of these selected genes was further validated by assessing the expression of two target genes, CRADD and CAPNS1, across developmental stages, reinforcing the reliability of NDUFS7 as it closely aligned with transcriptome-wide expression patterns at these stages. The present results will help researchers to obtain more accurate results in future qRT-PCR analysis in L. erythropterus.


Asunto(s)
Perfilación de la Expresión Génica , Reacción en Cadena en Tiempo Real de la Polimerasa , Animales , Reacción en Cadena en Tiempo Real de la Polimerasa/normas , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Perfilación de la Expresión Génica/métodos , Perfilación de la Expresión Génica/normas , Estándares de Referencia , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Transcriptoma , Cyprinidae/genética
8.
J Biol Chem ; 300(6): 107390, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38777146

RESUMEN

SARS-CoV-2 entry into host cells is facilitated by the interaction between the receptor-binding domain of its spike protein (CoV2-RBD) and host cell receptor, ACE2, promoting viral membrane fusion. The virus also uses endocytic pathways for entry, but the mediating host factors remain largely unknown. It is also unknown whether mutations in the RBD of SARS-CoV-2 variants promote interactions with additional host factors to promote viral entry. Here, we used the GST pull-down approach to identify novel surface-located host factors that bind to CoV2-RBD. One of these factors, SH3BP4, regulates internalization of CoV2-RBD in an ACE2-independent but integrin- and clathrin-dependent manner and mediates SARS-CoV-2 pseudovirus entry, suggesting that SH3BP4 promotes viral entry via the endocytic route. Many of the identified factors, including SH3BP4, ADAM9, and TMEM2, show stronger affinity to CoV2-RBD than to RBD of the less infective SARS-CoV, suggesting SARS-CoV-2-specific utilization. We also found factors preferentially binding to the RBD of the SARS-CoV-2 Delta variant, potentially enhancing its entry. These data identify the repertoire of host cell surface factors that function in the events leading to the entry of SARS-CoV-2.


Asunto(s)
Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Internalización del Virus , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Humanos , SARS-CoV-2/metabolismo , SARS-CoV-2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , Enzima Convertidora de Angiotensina 2/genética , Dominios Proteicos , Células HEK293 , COVID-19/metabolismo , COVID-19/virología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/química , Interacciones Huésped-Patógeno
9.
Appl Opt ; 63(8): 2070-2077, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38568649

RESUMEN

Most of the current holographic waveguide display systems are designed based on the center beam. When the incident beam consists of rays with different angles, the field of view and optical efficiency would greatly reduce. The heavy angular dependence of the volume holographic grating (VHG) and the back-coupling loss are two main reasons. This paper proposes a design method of the waveguide display system with multiplexed VHG, which is based on a genetic algorithm to optimize and calculate the parameters both of the VHG and the waveguide. The simulation results show that the diagonal field of view of the holographic waveguide system is increased to 28°, and its optical efficiency is improved by 30%. The design method of the waveguide system with the multiplexed grating proposed in this paper can effectively expand the field of view and improve the optical efficiency.

10.
Aquat Toxicol ; 271: 106927, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643640

RESUMEN

As awareness of BPA's health risks has increased, many countries and regions have implemented strict controls on its use. Consequently, bisphenol analogues like BPF and BPAF are being increasingly used as substitutes. However, these compounds are also becoming increasingly prevalent in the environment due to production, use and disposal processes. The oceans act as a repository for various pollutants, and recent studies have revealed the extensive presence of bisphenols (BPs, including BPA, BPF, BPAF, etc.) in the marine environment, posing numerous health hazards to marine wildlife. Nevertheless, the reproductive toxicity of these chemicals on marine fish is not comprehensively comprehended yet. Thus, the histological features of the gonads and the gene expression profiles of HPG (Hypothalamic-Pituitary-Gonadal) axis-related genes in marine medaka (Oryzias melastigma) were studied after exposure to single and combined BPs for 70 days. The effects of each exposure group on spawning, embryo fertilization, and hatching in marine medaka were also assessed. Furthermore, the impacts of each exposure group on the genes related to methylation in the F2 and F3 generations were consistently investigated. BPs exposure was found to cause follicular atresia, irregular oocytes, and empty follicles in the ovary; but no significant lesions in the testis were observed. The expression of several HPG axis genes, including cyp19b, 17ßhsd, 3ßhsd, and fshr, resulted in significant changes compared to the control group. The quantity of eggs laid and fertilization rate decreased in all groups treated with BPs, with the BPAF-treated group showing a notable reduction in the number of eggs laid. Additionally, the hatching rate showed a more significant decline in the BPF-treated group. The analysis of methylated genes in the offspring of bisphenol-treated groups revealed significant changes in the expression of genes including amh, dnmt1, dnmt3ab, mbd2, and mecp2, indicating a potential transgenerational impact of bisphenols on phenotype through epigenetic modifications. Overall, the potential detrimental impact of bisphenol on the reproduction of marine medaka emphasizes the need for caution in considering the use of BPAF and BPF as substitutes.


Asunto(s)
Compuestos de Bencidrilo , Oryzias , Fenoles , Reproducción , Contaminantes Químicos del Agua , Animales , Oryzias/genética , Oryzias/fisiología , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Masculino , Reproducción/efectos de los fármacos , Femenino , Gónadas/efectos de los fármacos
11.
Chemosphere ; 357: 142103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653400

RESUMEN

Salinity is an important environmental factor influencing the toxicity of chemicals. Bisphenol A (BPA) is an environmental endocrine disruptor with adverse effects on aquatic organisms, such as fish. However, the influence of salinity on the biotoxicity of BPA and the underlying mechanism are unclear. In this study, we exposed marine medaka (Oryzias melastigma) to BPA at different salinities (0 psµ, 15 psµ, and 30 psµ) for 70days to investigate the toxic effects. At 0 psµ salinity, BPA had an inhibitory effect on the swimming behavior of female medaka. At 15 psµ salinity, exposure to BPA resulted in necrotic cells in the ovaries but not on the spermatozoa. In addition, BPA exposure changed the transcript levels of genes related to the nervous system (gap43, elavl3, gfap, mbpa, and α-tubulin) and the hypothalamic-pituitary-gonadal (HPG) axis (fshr, lhr, star, arα, cyp11a, cyp17a1, cyp19a, and erα); the expression changes differed among salinity levels. These results suggest that salinity influences the adverse effects of BPA on the nervous system and reproductive system of medaka. These results emphasize the importance of considering the impact of environmental factors when carrying out ecological risk assessment of pollutants.


Asunto(s)
Compuestos de Bencidrilo , Disruptores Endocrinos , Oryzias , Fenoles , Reproducción , Salinidad , Contaminantes Químicos del Agua , Animales , Oryzias/fisiología , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Contaminantes Químicos del Agua/toxicidad , Femenino , Reproducción/efectos de los fármacos , Masculino , Disruptores Endocrinos/toxicidad , Conducta Animal/efectos de los fármacos , Ovario/efectos de los fármacos , Espermatozoides/efectos de los fármacos
12.
Dev Cell ; 59(11): 1396-1409.e5, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38569547

RESUMEN

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.


Asunto(s)
Calcio , Retículo Endoplásmico , Mecanotransducción Celular , Optogenética , Canales Catiónicos TRPP , Animales , Retículo Endoplásmico/metabolismo , Chlorocebus aethiops , Células COS , Optogenética/métodos , Calcio/metabolismo , Canales Catiónicos TRPP/metabolismo , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Aparato de Golgi/metabolismo , Estrés del Retículo Endoplásmico/fisiología , Chaperón BiP del Retículo Endoplásmico/metabolismo
13.
Sci Data ; 11(1): 322, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548787

RESUMEN

Oryzias sinensis, also known as Chinese medaka or Chinese ricefish, is a commonly used animal model for aquatic environmental assessment in the wild as well as gene function validation or toxicology research in the lab. Here, a high-quality chromosome-level genome assembly of O. sinensis was generated using single-tube long fragment read (stLFR) reads, Nanopore long-reads, and Hi-C sequencing data. The genome is 796.58 Mb, and a total of 712.17 Mb of the assembled sequences were anchored to 23 pseudo-chromosomes. A final set of 22,461 genes were annotated, with 98.67% being functionally annotated. The Benchmarking Universal Single-Copy Orthologs (BUSCO) benchmark of genome assembly and gene annotation reached 95.1% (93.3% single-copy) and 94.6% (91.7% single-copy), respectively. Furthermore, we also use ATAC-seq to uncover chromosome transposase-accessibility as well as related genome area function enrichment for Oryzias sinensis. This study offers a new improved foundation for future genomics research in Chinese medaka.


Asunto(s)
Oryzias , Animales , Cromosomas/genética , Genoma , Genómica , Anotación de Secuencia Molecular , Oryzias/genética , Filogenia
14.
Artículo en Inglés | MEDLINE | ID: mdl-38508354

RESUMEN

Bisphenol AF (BPAF) is a novel environmental endocrine disruptor, and is widely detected in the aquatic environment, which is a potential threat to the health of fish. In this study, male Oryzias curvinotus were exposed to environmental concentrations (0.93 and 9.33 µg/L) of BPAF for 21 days. The effects of BPAF on survival, growth, reproduction, liver and testis histology, and gene transcriptional profiles of O. curvinotus were investigated. The results showed that the survival rate of male O. curvinotus slight decrease with increasing BPAF concentration, and there was no significant effect on body length, body weight, and K-factor. BPAF (9.33 µg/L) caused significant changes in testicular structure and reduced spermatid count in O. curvinotus. Changes in transcript levels of some antioxidant-related genes in gills and liver following BPAF exposure, imply an effect of BPAF on the immune system. After BPAF exposure, chgs and vtgs were up-regulated, validating the estrogenic effect of BPAF. In the hypothalamic - pituitary - gonadal axis (HPG) results, erα, erγ and cyp19a1b were all up-regulated in the brain, and the 0.93 µg/L BPAF group was more up-regulated than the 9.33 µg/L BPAF group. In testis, BPAF significantly up-regulated the mRNA expression level of cyp17a1 and cyp11b, while significantly down-regulated mRNA expression level of cyp11a, and cyp19a1 was significantly down-regulated only in the 0.93 µg/L BPAF group. In conclusion, environmental levels of BPAF have adverse effects on the survival and reproduction of O. curvinotus, and the potential toxic effects of environmental levels of BPAF cannot be ignored.


Asunto(s)
Fluorocarburos , Oryzias , Animales , Masculino , Reproducción , Testículo , Compuestos de Bencidrilo/toxicidad , Compuestos de Bencidrilo/metabolismo , ARN Mensajero/metabolismo
15.
Anal Chem ; 96(8): 3508-3516, 2024 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-38364051

RESUMEN

Extracellular vesicles (EVs) are cell-derived particles that exhibit diverse sizes, molecular contents, and clinical implications for various diseases depending on their specific subpopulations. However, fractionation of EV subpopulations with high resolution, efficiency, purity, and yield remains an elusive goal due to their diminutive sizes. In this study, we introduce a novel strategy that effectively separates EV subpopulations in a gel-free and label-free manner, using two-dimensional (2D) electrophoresis in a microfluidic artificial sieve. The microfabricated artificial sieve consists of periodically arranged micro-slit-well structures in a 2D array and generates an anisotropic electric field pattern to size fractionate EVs into discrete streams and steer the subpopulations into designated outlets for collection within a minute. Along with fractionating EV subpopulations, contaminants such as free proteins and short nucleic acids can be simultaneously directed to waste outlets, thus accomplishing both size fractionation and purification of EVs with high performance. Our platform offers a simple, rapid, and versatile solution for EV subpopulation isolation, which can potentially facilitate the discovery of biomarkers for specific EV subtypes and the development of EV-based therapeutics.


Asunto(s)
Vesículas Extracelulares , Microfluídica , Vesículas Extracelulares/química , Proteínas/análisis , Electroforesis , Biomarcadores/análisis
16.
Animals (Basel) ; 14(2)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38254391

RESUMEN

In recent years, bisphenol AF (BPAF) in aquatic environments has drawn attention to its ecological risks. This study aims to investigate the toxic effects of BPAF (188.33 µg/L) exposure for 30 days on female marine medaka (Oryzias melastigma). On the 10th and 30th day of exposure, the toxicity was evaluated using histological analysis of the liver and ovaries and the transcription levels of genes related to the antioxidant system, immune system, and hypothalamic-pituitary-gonadal (HPG) axis. Findings revealed that (1) BPAF exposure caused vacuolation, karyopyknosis and karyolysis in the liver of marine medaka, and the toxic impact augmented with duration; (2) exposure to BPAF for 10 days facilitated the growth and maturation of primary ova, and this exposure had a comparatively inhibitory effect after 30 days; (3) exposure to BPAF resulted in a biphasic regulation of the transcriptional abundance of genes involved in antioxidant and inflammatory response (e.g., il-8, cat), with an initial up-regulation followed by down-regulation. Additionally, it disrupted the transcriptional pattern of HPG axis-related genes (e.g., 3ßhsd, arα). In conclusion, 188.33 µg/L BPAF can alter the expression levels of functionally related genes, impair the structural integrity of marine organisms, and pose a threat to their overall health.

17.
J Cell Biol ; 223(2)2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-38019180

RESUMEN

Multiple physiology-pertinent transmembrane proteins reach the cell surface via the Golgi-bypassing unconventional protein secretion (UcPS) pathway. By employing C. elegans-polarized intestine epithelia, we recently have revealed that the small GTPase RAB-8/Rab8 serves as an important player in the process. Nonetheless, its function and the relevant UcPS itinerary remain poorly understood. Here, we show that deregulated RAB-8 activity resulted in impaired apical UcPS, which increased sensitivity to infection and environmental stress. We also identified the SNARE VTI-1/Vti1a/b as a new RAB-8-interacting factor involved in the apical UcPS. Besides, RAB-11/Rab11 was capable of recruiting RABI-8/Rabin8 to reduce the guanine nucleotide exchange activity of SMGL-1/GEF toward RAB-8, indicating the necessity of a finely tuned RAB-8/RAB-11 network. Populations of RAB-8- and RAB-11-positive endosomal structures containing the apical UcPS cargo moved toward the apical side. In the absence of RAB-11 or its effectors, the cargo was retained in RAB-8- and RAB-11-positive endosomes, respectively, suggesting that these endosomes are utilized as intermediate carriers for the UcPS.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proteínas de Unión al GTP rab , Animales , Caenorhabditis elegans/genética , Membrana Celular , Transporte de Proteínas , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Unión al GTP rab/metabolismo , Endosomas
18.
Proc Natl Acad Sci U S A ; 120(46): e2215285120, 2023 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-37931110

RESUMEN

The insulin-like growth factor 2 (IGF2) plays critical roles in cell proliferation, migration, differentiation, and survival. Despite its importance, the molecular mechanisms mediating the trafficking of IGF2 along the secretory pathway remain unclear. Here, we utilized a Retention Using Selective Hook system to analyze molecular mechanisms that regulate the secretion of IGF2. We found that a type I transmembrane protein, TMED10, is essential for the secretion of IGF2 and for differentiation of mouse myoblast C2C12 cells. Further analyses indicate that the residues 112-140 in IGF2 are important for the secretion of IGF2 and these residues directly interact with the GOLD domain of TMED10. We then reconstituted the release of IGF2 into COPII vesicles. This assay suggests that TMED10 mediates the packaging of IGF2 into COPII vesicles to be efficiently delivered to the Golgi. Moreover, TMED10 also mediates ER export of TGN-localized cargo receptor, sortilin, which subsequently mediates TGN export of IGF2. These analyses indicate that TMED10 is critical for IGF2 secretion by directly regulating ER export and indirectly regulating TGN export of IGF2, providing insights into trafficking of IGF2 for myoblast differentiation.


Asunto(s)
Factor II del Crecimiento Similar a la Insulina , Mioblastos , Vías Secretoras , Proteínas de Transporte Vesicular , Animales , Ratones , Diferenciación Celular , Vesículas Cubiertas por Proteínas de Revestimiento/metabolismo , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Transporte de Proteínas , Proteínas de Transporte Vesicular/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo
19.
Mol Biotechnol ; 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37861953

RESUMEN

Carpal navicular fractures are the most common carpal fractures. This study intends to explore the specific mechanism of Zoledronic Acid (ZA) in carpal navicular fracture healing via long non-coding RNA (lncRNA) growth arrest specificity 5 (GAS5) to mediate microRNA (miR)-29a-3p. A fractured rat model was constructed. Two weeks later, a subcutaneous injection of systemic ZA was implemented, and an injection of plasmid vectors interfered with GAS5 or miR-29a-3p expression was performed on the fracture site. Osteocalcin (OCN) and bone morphogenetic protein-2 (BMP-2) were determined, as well as serum levels of alkaline phosphatase (ALP), osteopontin (OPN) and osteoprotegerin (OPG) and bone mineral density. MC3T3-E1 cells were transfected with plasmid vectors interfering with GAS5 or miR-29a-3p, and cell proliferation and apoptosis were analyzed. GAS5 and miR-29a-3p expression in fractured rats was tested, together with their binding relationship. ZA promoted OCN and BMP-2 expression, increased bone mineral density and serum levels of ALP, OPN and OPG in fractured rats. GAS5 was upregulated and miR-29a-3p was down-regulated in fractured rats. Downregulation of GAS5 or upregulation of miR-29a-3p further promoted bone healing in fractured rats. GAS5 targets miR-29a-3p, and down-regulation of miR-29a-3p can reverse the effect of down-regulation of GAS5 on bone healing in fractured rats. ZA promoted the proliferation of MC3T3-E1 cells and inhibited apoptosis by regulating the GAS5/miR-29a-3p axis. ZA regulates miR-29a-3p expression by down-regulating GAS5 to promote carpal navicular fracture healing, promote MC3T3-E1 cell proliferation, and inhibit cell apoptosis.

20.
Sci Data ; 10(1): 604, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689728

RESUMEN

Eretmochelys imbricata, a critically endangered sea turtle inhabiting tropical oceans and protected across the world, had an unknown genome sequence until now. In this study, we used HiFi reads and Hi-C technology to assemble a high-quality, chromosome-level genome of E. imbricata. The genome size was 2,138.26 Mb, with contig N50 length of 123.49 Mb and scaffold N50 of 137.21 Mb. Approximately 97.52% of the genome sequence was anchored to 28 chromosomes. A total of 20,206 protein-coding genes were predicted. We also analyzed the evolutionary relationships, gene family expansions, and positive selection of E. imbricata. Our results revealed that E. imbricata diverged from Chelonia mydas 38 million years ago and had enriched olfactory receptors and aging-related genes. Our genome will be useful for studying E. imbricata and its conservation.


Asunto(s)
Genoma , Tortugas , Animales , Envejecimiento , Evolución Biológica , Cromosomas/genética , Receptores Odorantes/genética , Tortugas/genética
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